The present study aimed at investigating the in vitro and in vivo susceptibility of malaria parasites to crude extracts and fractions from Polyalthia suaveolens, Uvaria angolensis, and Monodora tenuifolia. The ethanolic extracts were prepared by maceration, and were further partitioned using water, dichloromethane, hexane, and methanol. The most promising fraction was subjected to column chromatography and the sub-fractions tested for activity in vitro. The antiplasmodial effect of extracts and fractions was tested against the Chloroquine resistant (PfK1) strain in 96 wells microtiter plate format using SYBR green florescence assay. The promising fraction was further assessed for cytotoxicity and acute toxicity in Swiss albino mice and subsequently against the rodent malaria parasite, P. berghei. Qualitative phytochemical screening was also performed on the promising fraction. The methanol fractions exerted the overall better effect with that of the twigs of P. suaveolens (PStw(Ace)) showing the highest potency with a IC50 value of 3.24 µg/mL followed by the fractions of leaf of M. tenuifolia (MoTel(Ace), IC50= 3.84 µg/ml) and stem bark of P. suaveolens (IC50= 4.90 µg/ml). The phytochemical screening showed the presence of alkaloids, lactones, and phenols in the more active fraction of P. suaveolens (PStw(Ace)). The chromatographic fractionation of this fraction led to 12 sub-fractions with PS8 sub-fraction being the most active (IC50= 4.42 µg/mL). In vivo, oral administration of 2000 mg/kg b.w of fraction PStw(Ace) in mice showed no signs of toxicity. Also, fraction PStw(Ace) at 400 mg/kg b.w exerted the highest suppressive effect against P. berghei strain B throughout the 4 days experiment (% parasitaemia below 5.2%). Overall, the results achieved supported the use of the three plants in the traditional treatment of malaria in Cameroon. More interestingly, the methanolic fraction of the twigs extract from P. suaveolens might be of interest in future development of an antimalarial phytodrug.

Forty-eight Pasteurella multocida isolates were recovered from porcine pneumonic lungs collected in Norwestern Spain (2017- 2019). These isolates were characterized for their minimal inhibition concentrations to twelve antimicrobial agents and for the appearance of eight resistance genes: tetA, tetB, blaROB1, blaTEM, ermA, ermC, mphE and msrE. Relevant resistance percentages were shown to teracyclines, sulphamethoxazole/trimethoprim and tiamulin, thus suggesting that P. multocida isolates were mostly susceptible to amoxicillin, ceftiofur, enrofloxacin, florfenicol, marbofloxacin and macrolides. 29.2% of isolates were resistant to more than two antimicrobials. The tetracycline resistance genes (tetA and tetB) were detected in 22.9% of the isolates, but none was positive to both simultaneously; blaROB1 and blaTEM genes were found in one third of isolates but both genes were detected simultaneously in only one isolate. ermC gene was observed in 41.7% of isolates, a percentage that decreased until 22.9% for msrE; finally, ermA was harboured by 16.7% and mphE was not found in any of them. Six clusters were established based on hierarchical clustering analysis on antimicrobial susceptibility for the twelve antimicrobials. Generally, it was unable to foresee the antimicrobial susceptibility pattern for each family and the association of each particular isolate inside the clusters established from the presence or absence of the resistance genes analyzed.

Mannheimia haemolytica is the main pathogen contributing to pneumonic pasteurellosis in sheep. The aim of this study was to investigate the antimicrobial resistance levels in M. haemolytica from the lungs of slaughtered sheep and the genetic resistance mechanisms involved. A total of 256 M. haemolytica isolates, 169 from lungs with pneumonic lesions and 87 without, were analyzed by the disk diffusion method for 12 antimicrobials, and the whole genome of 14 isolates sequenced to identify resistance determinants. Levels of phenotypic resistance ranged from <2 % for 10 antimicrobials (amoxicillin, amoxicillin-clavulanic, ceftiofur, cefquinome, lincomycin/spectinomycin, gentamicin, erythromycin, florfenicol, enrofloxacin, and doxycycline) to 4.3% for tetracycline and 89.1% for tylosin. Six isolates carried tetH genes and four carried, in addition, strA and sul2 genes in putative plasmid sequences. No mutations associated with macrolide resistance were identified in 23 rDNA sequences suggesting that M. haemolytica phenotypic results for tylosin should be interpreted with care in the absence of well-established epidemiological and clinical breakpoints. The identification of strains phenotypically resistant to tetracycline and of several resistance genes, some of which were present in plasmids, highlight the need for continuous monitoring of susceptibility patterns in Pasteurellaceae isolates from livestock

Intrammary infections are a major problem for dairy sheep farms, and Streptococcus uberis is one of the main etiological agents of ovine mastitis. Surveys on antimicrobial resistance are still limited in sheep and characterization of isolates is important for acquiring information on resistance and for optimizing therapy. In this study, a sampling of 124 S. uberis isolates collected in Sardinia (Italy) from sheep milk was analysed by multilocus-sequence typing (MLST) and pulsed field gel electrophoresis (PFGE) for genetic relatedness. All isolates were also subjected to antimicrobial susceptibility analysis by the disk diffusion test using a panel of 14 antimicrobials. Resistance genes were detected by PCR assays. MLST analysis revealed that the isolates were grouped into 86 sequence types (STs), of which 73 were new genotypes, indicating a highly diverse population of S. uberis. The most frequently detected lineage was the clonal complex (CC)143, although representing only 13.7% of all characterized isolates. A high level of heterogeneity was also observed among the SmaI PFGE profiles, with 121 unique patterns. Almost all (96.8%) isolates were resistant to at least one antimicrobial, while all exhibited phenotypic susceptibility to oxacillin, amoxicillin-clavulanic acid and ceftiofur. Of the antimicrobials tested, the highest resistance rate was found against streptomycin (93.5%), kanamycin (79.8%) and gentamicin (64.5%), followed by novobiocin (25%) and tetracycline-TE (19.3%). Seventy-four (59.7%) isolates were simultaneously resistant to all aminoglycosides tested. Seventeen isolates (13.7%) exhibited multidrug resistance. All aminoglycosides-resistant isolates were PCR negative for aad-6 and aphA-3’ genes. Among the TE-resistant isolates, the tetM gene was predominant, indicating that the resistance mechanism is mainly mediated by the protection of ribosomes and not through the efflux pump. Three isolates were resistant to erythromycin, and two of them harboured the ermB gene. This is the first study reporting a detailed characterization of the S. uberis strains circulating in Sardinian sheep. Further investigations will be needed to understand the relationships between S. uberis genotypes, mastitis severity, and intra-mammary infection dynamics in the flock, as well as to monitor the evolution of antimicrobial resistance.

The current study aims to first, isolate H. pylori in cultures from gastric biopsy samples and test their susceptibility. Secondly, we aim to assess the efficacy of the standard triple therapy from patients coming of the western central region of Colombia. Patients with H. pylori positive re-ceived standard triple therapy with PPI [40 mg b.i.d.], clarithromycin [500 mg b.i.d.], amoxicillin [1g b.i.d.] for 14 days. Thereafter, antibiotic susceptibility of the isolates was assessed by E-Test. From 94 patients enrolled, 67 were positive for H. pylori by histology or culture. Resistance to metronidazole, levofloxacin, rifampicin, clarithromycin and amoxicillin was 81, 26.2, 23.9, 19 and 9.5%, respectively. No resistance was found for tetracycline. 54 patients received standard triple therapy, 48 attended follow-ups testing and of them, 30 had resistance test reports. Overall eradication rate was 81.2%, 4 patients underwent second-line management and only one patient remained H. pylori positive by urea breath test during the follow-up [six weeks]. Eradication was significantly higher in patients with clarithromycin susceptible than in resistant strains [95.6% vs. 42.8% p= 0.001]. The updated percentages of resistance to clarithromycin in this geographical area have increased, so this value must be considered when choosing the treatment regimen.

The emergence of multi-drug resistant E. coli is an important matter of increasing considerable concern to global public health. The aim of this study was to investigate the incidence, antibiotic resistance pattern, phylogroups and genetic variation of E. coli isolates from raw milk, vegetable salad and ground meat samples. Methods: Culture-based techniques, Kirby-Bauer disk diffusion susceptibility testing, PCR and RAPD assays were used to determine the incidence rate, antimicrobial resistance pattern, phylogenetic groups and genetic diversity of the E. coli isolates. Results: E. coli isolates were highly resistant to amoxicillin (79.16%), trime-thoprim-sulfamethoxazole (70.83%), amoxicillin-clavulanic acid (62.50%), tetracycline (54.16%), chloramphenicol (54.16%), nitrofurantoin (54.16%), ampicillin (45.83%), streptomycin (45.83%), and kanamycin (33.33%); and completely susceptible to norfloxacin and azithromycin. 70.83% of the isolates were multi-drug resistant. Most E. coli isolates (46%) belonged to phylogroup A. RAPD with UBC245 primer categorized the isolates into 11 clusters. A high level of genetic di-versity was found among the isolates; however, 33.3% of the isolates were grouped in a major cluster (R5). Conclusions: Antibiotic resistance patterns are randomly distributed among the ge-netic clusters. Novel, practical, efficient food safety control and surveillance systems of multi-drug resistant foodborne pathogens are required to control the foodborne pathogen contamina-tion.

Group B Streptococcus (GBS), a commensal in the body, causes a wide range of infectious diseases. The colonisation levels of GBS and its resistance profile to antibiotics provide important information useful for orienting prevention strategies. There is little data available on the subject with determination of resistance phenotypes in Cameroon. We therefore aimed to determine the prevalence of colonization, antibiotic resistance, including patterns of inducible resistance to clindamycin of GBS in Yaounde. To achieve this goal, a prospective cross-sectional study with an analytical component was carried out from the 28th June to the 29th August 2020 at the BIOSANTE laboratory and the Yaounde Gynaeco-Obstetrics and Paediatrics hospital. Vaginal swabs and urine were collected on 163 women. This samples were analysed using 5% defibrinated sheep blood agar and chocolate plus polyvitex agar. The isolates were identified using the morphology of the colony, Gram staining, haemolysis, catalase test and latex grouping test. Antibiotic susceptibility testing was done by disk diffusion method following the recommendations of the ACFSM 2019. The double disk diffusion method was used to identify isolates with clindamycin inducible resistance. Our data was analysed by the software SPSS version 2.1. The results obtained showed that the global prevalence of colonization by GBS was 37% (57/163), 40.35% in non-pregnant women and 59.65% in pregnant women. Pregnancy (P-value = 0.019) and gestational age (P-value = 0.025) constituted the risk factors of maternal colonization by GBS. In addition, the strains of GBS were resistant to all antibiotics tested. A D test showcased that 64.7% of GBS were resistant in a constitutive manner to clindamycin. We also note the presence of M phenotypes. As a whole, our results demonstrate that the rate of GBS colonization in this study was similar or higher than those in the previous report in Cameroon. All this indicates that attention should be paid to this bacterium in the monitoring of antimicrobial resistance and in the care of pregnant women and newborns.

In the present study, we aimed to determine the antimicrobial resistance and genetic structure of a population of S. aureus recovered from transient and persistent intramammary infections and nares/muzzles. We investigated the antimicrobial resistance of 189 S. aureus strains using a broad antimicrobial susceptibility profile. Furthermore, 107 S. aureus isolates were strain-typed using staphylococcal protein-A (spa) typing. Here, a great proportion of strains exhibited multidrug resistance to antimicrobials, including resistance to critically important antimicrobials, although no methicillin-resistant S. aureus strains were found. Our study did not strengthen the idea that extramammary niches (i.e., nares/muzzles) are an important source for S. aureus. A discrepancy in the antimicrobial resistance between S. aureus strains isolated from nasal/muzzles and milk samples was observed. Furthermore, S. aureus isolates from transient and persistent IMIs did not differ by spa typing, suggesting that the persistence of bovine IMIs was determined by cow factors. Thus, the high level of multidrug-resistant S. aureus found in the two herds studied together with the predominance of a well udder-adapted S. aureus strain may contribute to the history of the high prevalence of mastitis caused by S. aureus, leading to great animal and public health concerns.

Infectious keratitis (IK) represents a major cause of corneal blindness. This study aims to investigate the demographics, risk factors, microbiological characteristics and antibiotic susceptibility patterns of IK in Taiwan over the past 15 years. A retrospective population-based study was conducted using the Chang Gung Research Database. Patients with IK were identified by diagnostic codes for corneal ulcer from 2004 to 2019. Of 7807 included subjects, 45.2% of patients had positive corneal cultures. The proportion of contact lens-related IK declined, while that of IK related to systemic diseases grew. The percentage of isolated gram-positive bacteria surpassed that of gram-negative bacteria in the 15-year period. The prevalence of Pseudomonas aeruginosa showed a decreasing trend (p = 0.004), whereas coagulase-negative Staphylococcus (CNS) and Propionibacterium species were increasingly detected (p &lt; 0.001). Overall, the trend of antibiotic susceptibility of both gram-positive and gram-negative bacteria did not change throughout the study period. The susceptibility to the test antibiotics maintained over 90% in gram-negative isolates during 15 years. Vancomycin preserved 100% susceptibility to all gram-positive isolates. Since most tested antibiotics exhibited stable susceptibility over decades, this study reinforced that fluoroquinolones and fortified vancomycin continue to be good empiric therapies for treating bacterial keratitis in Taiwan.

Background: Commensal Neisseria species are part of the oropharyngeal microbiome and important for health, but also serve as a reservoir for antimicrobial resistance. Little is known about the prevalence of these species in the general population, how this varies by age and how antimicrobial susceptibility varies between species. Methods: We assessed the prevalence and antimicrobial susceptibility of commensal Neisseria species in the parents (n=38) and children (n=50) of 35 families in Belgium.Results: Various commensal Neisseria (n=5) could be isolated from the participants. Most abundant were N. subflava and N. mucosa. N. subflava was detected in 77 of 88 (87.5%) individuals and N. mucosa in 64 of 88 (72.7%). N. mucosa was more prevalent in children (41/50 [82%]) than parents (23/38 [60.5%]; P<0.05), while N. bacilliformis was more prevalent in parents (7/36 [19.4%]) than children (2/50 [4%]; P<0.05). N. bacilliformis showed high ceftriaxone minimum inhibitory concentrations (MICs; median MIC 0.5mg/L; IQR 0.38-0.75) and these high MICs explained the higher ceftriaxone MICs of all Neisseria isolates from the parents than the children. The median azithromycin MIC of all Neisseria isolates per individual was positively correlated with the median family MIC (rho=0.24; P=0.033). The same association was found for the analysis limited to N. subflava (rho=0.36; P=0.004) and N. mucosa (rho=0.30; P=0.027). Interpretation: The most abundant commensal Neisseria species found in this population were N. subflava and N. mucosa, of which the prevalence of N. mucosa varied by age. The prevalence of N. bacilliformis also varied by age and showed concerningly high ceftriaxone MICs which warrant further investigation. We found evidence of clustering of azithromycin, but not ceftriaxone, MIC by family.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Klebsiella pneumoniae is one of the most common causes of clinical and asymptomatic mastitis in dairy cattle, also in milk and dairy products affecting its quality. Mastitis caused by K. pneumoniae is even more serious due to its poor response to antibiotic therapy. This study was conducted to detect and identify the presence of K. pneumoniae in milk and dairy products. A total of 234 samples were randomly collected from various locations in Libya. Samples were examined for the presence of K. pneumoniae by conventional cultural techniques that included cultivation in violet red bile agar plus 4-methylumbelliferyl-ß-D-glucuronide (VRBA + MUG) broth, and CHROM agar followed by identification by PCR and partial sequencing of 16S rRNA. Out of the 234 samples of milk and dairy products collected, 16 (6.8%) of the isolates revealed mucoid colonies on agar media phenotypically suggested to be K. pneumoniae. The isolates identification was confirmed by molecular techniques (16S rRNA). Among examined samples, K. pneumoniae was recovered from she camel’s milk, raw cow’s milk, raw fermented milk, Maasora cheese, Ricotta cheese, soft cheese, full cream milk powder, milk powder infant formula, cereal baby food and growing up formula. From the 16 K. pneumoniae isolates; antibiotic susceptibility testing was performed on 12 isolates, the results showed that K. pneumoniae isolates were resistant to more than 8 antibiotics, interestingly, two isolates revealed MBL production. This study emphasized the relationship between K. pneumoniae and raw milk, cheese, milk powder and infant milk retailed in Libya, which is considered as a risk for human health as many of these products did not comply with microbiological criteria of international and/or Libyan standards. The necessary precautions have to be taken to carry out effective sanitary practices during the production in dairy plants, handling and distribution in the markets particularly at local small manufacture scale.

High rates of resistance to antibiotics are associated with healthcare-related infections, thus appealing for the urgent need for effective antimicrobials against these maladies. The present study aims to determine the chemical composition of essential oil (EO) from Clausena anisata leaves, and evaluate their antibacterial activity against selected nosocomial bacteria. Fresh leaves of Clausena anisata were subjected to a steam distillation using a Clevenger apparatus to afford the essential oil. The phytochemical composition of this oil was analyzed using gas chromatography-mass spectrometry (GC-MS). The essential oil was further tested against selected nosocomial bacteria, including Staphylococcus and Klebsiella species, among others, using a microdilution method. As a result, 0.77% of essential oil was extracted from fresh leaves of Clausena anisata. The GC-MS analysis revealed that the as-prepared essential oil contain E-anethole (70.77%), methyl isoeugenol (13.85%), estragole (4.10%), γ-terpinene (3.33%), myrcene (2.82%) and sabinene (0.77%), with E-anethole being the major constituent. Meanwhile, twenty two compounds were identified in the EO of Clausena anisata leaves through gas chromatography. Upon antibacterial test against selected nosocomial pathogens, the E-anethole-rich essential oil exhibited minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 3.91 to 125 µg/mL and 7.81 to 125 µg/mL, respectively, indicative of a bactericidal orientation of the plant’s essential oil (MIC/MBC ratio: 4). This novel contribution highlights the scientific validation of the use of Clausena anisata leaves in the traditional treatment of various infectious diseases. However, toxicity and pharmacokinetic studies, mechanistic basis of the antibacterial action, and in vivo antibacterial experiments of the E-anethole-rich essential oil of Clausena anisata should be investigated to successfully use this plant in the treatment of infectious diseases.

Streptococcal infection is a main infectious diseases for farmed grey mullet (Mugil cephalus). This study were to identify spreptococcal species in diseased farmed grey mullet and to investigate differences in susceptibility to 13 antibiotics and in genotypes between the stains from the grey mullet and non-grey mullet. 170 samples from diseased farmed grey mullet were collected from three county in 2013 -2016. Multiplex PCR identified L. garviea (146) as the main pathogen, S. agalactia (9), S. dysgalactiae (19), and double infection (5), but no S. iniae. The prevalence changed annually and differed among three counties. Pulsed-field gel electrophoresis (PFGE) analysis demonstrated identical genotype with an ApaI-digested DNA pattern. Disc diffusion results demonstrated differences in antibiotic susceptibility between the strains from grey mullet (146) and non-grey mullet (30). Almost all strains resisted to clindamycin and all strains were susceptible to six antibiotic in grey mullet and 4 antibiotics in non-grey mullet. The reduced susceptible strains was more in non-grey mullet than grey mullet group. The reduced susceptible strains were observed the highest in 2014 and in Chiayi county and decreased from 2014 to 2016. However, the strains with reduced susceptibility to ceftriaxone, cirpofoxacin, moxifloxacin, tetracycline for human treatment were observed.

The geographical environment, food culture, and dietary habits are substantially different between the southern and northern regions in China. We investigated the associations with dietary patterns and metabolic syndrome between Chinese adult from the southern and northern regions (North: 1249; South: 1849) using data from the Chinese Health and Nutrition 2009 survey. Respectively, four dietary patterns were identified by factor analysis in the two regions. Each dietary pattern of factor score was calculated for three groups by tertile (T1<T2<T3). In the northern region, the association between the Alcohol and Western pattern and the risk of abdominal obesity (OR: 1.31; 95%:1.01, 1.68), hypertriglyceridemia (OR: 1.35; 95%:1.05, 1.74), high fasting blood glucose (OR: 1.37; 95%: 1.05, 1.80), and hypertension (OR: 1.55; 95%: 1.45, 1.99) was increased. In the southern region, the Convenience Food pattern was positively associated with hypertriglyceridemia (OR: 1.53; 95%: 1.03, 2.26), low HDL-cholesterol (OR: 1.96; 95%: 1.12, 3.43), and metabolic syndrome (OR: 1.79; 95%: 1.03, 3.11). The Alcohol dietary pattern was positively associated with high fasting blood glucose (OR: 1.83, 95%: 1.13, 2.97). There are some dietary pattern differences in the two regions. It is necessary to consider the factors of food culture and food intake habits in order to provide nutrition education to Chinese individuals from different regions in the future.

In addition to their importance in statistical thermodynamics, probabilistic entropy measurements are crucial for understanding and analyzing complex systems, with diverse applications in time series and one-dimensional profiles. However, extending these methods to two- and three-dimensional data still requires further development. In this study, we present a new method to classify spatiotemporal processes based on entropy measurements. To test and validate the method, we selected four classes of similar processes related to the evolution of random patterns: dynamic colored noises ((i)~white and (ii)~red); (iii)~weak turbulence from reaction-diffusion; (iv)~hydrodynamic fully developed turbulence, and (v)~plasma turbulence from MHD. Considering seven possible ways to measure entropy from a matrix, we present the method as a parameter space composed of the two best separating measures of the five selected classes. The results highlight better combined performance of Shannon Permutation Entropy ($S^p_H$) and a new approach based on Tsallis Spectral Permutation Entropy ($S^s_q$). Notably, our observations reveal the segregation of reaction terms in this $S^p_H \times S^s_q$ space, a result that identifies specific sectors for each class of dynamic process, and can be used to train machine learning models for automatic classification of complex spatiotemporal patterns.

Aims: The lack of information about the inter variability of the test results obtained by CLSI and EUCAST requires further clarifications to interpret antimicrobial susceptibility patterns better. This study aimed to compare the CLSI and EUCAST interpretations of the antimicrobial susceptibility test results of the ESBL–producing uropathogenic Escherichia coli and Klebsiella pneumonia strains. Methods: After obtaining 157 ESBL-producing E. coli and 95, ESBL-producing K. pneumonia isolates from the urine specimens of the patients, Kirby-Bauer’s disc diffusion method was used for conducting antimicrobial susceptibility test. The test procedures and the interpretation of the results were carried out according to the year 2017 versions of both of the two guidelines. For the statistical comparison of concordance between the two guidelines, the Kappa coefficients and the concordance rates were calculated. Results: The results were graded in the range from perfect to poor agreement. For E. coli, interpretations of the AST results revealed a moderate to perfect agreement between both methods. Weighted Kappa agreement scores in the range from 0.42 to 1. The agreement for AMC, TPZ30/6, ceftazidime 10, meropenem, and aztreonam was poor without any inconsistencies. For Klebsiella, the kappa agreement score was in the range from 0.25 to 1. It was incompatible with AMC, TPZ 30/6, ceftazidime 10, aztreonam; there was poor agreement for cefepime, amikacin and ertapenem. Conclusions: Our results showed agreement between the two guidelines for uropathogenic extended-spectrum ß-lactamase producing Escherichia coli and Klebsiella pneumoniae but also showed inconsistencies between two guidelines. Therefore, the results of our study contribute to the comparison of these guidelines for interpreting antibiotic susceptibilities.

Relative to several model bacteria, the ethanologenic bacterium Zymomonas mobilis is shown here to have an elevated resistance to exogenous antimicrobial peptides (AMPs) – both, with regard to peptide bulk concentration in the medium, and the numbers of peptide molecules per cell. By monitoring integration of the AMPs in the bacterial cell membrane and observing the resulting effect on membrane energy-coupling, it is concluded that the membranotropic effects of the tested AMPs in Z. mobilis and in Escherichia coli are comparable. The advantage of Z. mobilis over E. coli apparently results from its uncoupled mode of energy metabolism that, in contrast to E. coli, does not rely on oxidative phosphorylation, and hence, is less vulnerable to disruption of its energy-coupling membrane by AMPs. It is concluded that the high resistance to antimicrobial peptides (AMPs) observed in Z. mobilis not only proves crucial for its survival in its natural environment but also offers a promising platform for AMP production and sheds light on potential strategies for novel resistance development in clinical settings.

This study investigates the land surface temperature (LST) distribution from thermal infrared data for analyzing the characteristics of surface coverage using the Vegetation-Impervious-Soil (VIS) approach. A set of ten images, obtained from Landsat-5 Thematic Mapper, between 2001 and 2010, were used to study the urban environmental conditions of 47 neighborhoods of Porto Alegre city, Brazil. Porto Alegre has had the smallest population growth rate of all 27 state capitals in the last two decades in Brazil, with an increase of 11.55% in inhabitants from 1,263 million in 1991 to 1,409 million in 2010. We applied the environmental Kuznets curve (EKC) theory in order to test the influence of the economically-related scenario on the spatial nature of social-environmental arrangement of the city at neighborhood scale. Our results suggest that the economically-related scenario exerts a non-negligible influence on the physically driven characteristics of the urban environmental conditions as predicted by EKC theory. The linear inverse correlation R2 between household income (HI) and LST is 0.36 and has shown to be comparable to all other studied variables. Future research may investigate the relation between other economically-related indicators to specific land surface characteristics.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Musculoskeletal infections (MIs) are among the most difficult-to-treat staphylococcal diseases. The limited availability of effective antibiotics has encouraged the development of innovative strategies such as combinatory therapy to combat MI. The aim of this study was to investigate the in vitro antistaphylococcal activity of anti-inflammatory and the antimicrobial combinatory effect of celecoxib with oxacillin. The minimum inhibitory concentrations (MICs) of 17 anti-inflammatory drugs were determined for standard strains and clinical isolates of S. aureus strains, counting methicillin-resistant strains (MRSA), by the broth microdilution method. The fractional inhibitory concentration indices (FICIs) were evaluated by the checkerboard assays. Celecoxib produced the most potent antistaphylococcal effect against all the tested strains (MIC ranging from 32 to 64 mg/mL), followed by diacerein against MRSA3 and MRSA ATCC 33592 (MIC 64 mg/mL). Several synergistic effects were observed for tested S. aureus strains, including MRSA (FICI ranging from 0.087 to 0.471). The strongest synergistic interaction (FICI 0.087) was obtained against MRSA ATCC 33592 at a celecoxib concentration of 2 mg/mL with a 19-fold oxacillin MIC reduction (from 512 to 26.888 mg/mL). This is the first report on the antistaphylococcal combinatory effect of celecoxib with oxacillin. Our findings suggest celecoxib and its combination with oxacillin as perspective agents for research focused on the development of novel therapies for MI caused by S. aureus. Thus, this study presents novel findings that celecoxib could, in some cases, resensitise MRSA strains to become susceptible to certain β-lactams (e.g., oxacillin) not previously tested.

Background: Streptococcus agalactiae or Group B Streptococcal colonization of the gastrointestinal and genital tracts of pregnant women usually remains asymptomatic; even if it is the critical determinant of infection in neonates and young infants. It causes early and late onset of invasive Group B Streptococcus (GBS) disease manifesting as septicemia, meningitis and pneumonia. Now it is recognized as an important cause of maternal and neonatal morbidity and mortality in many parts of the world including Ethiopia where the magnitude of the problem has been little studied. The aim of this study was to assess the prevalence of GBS colonization, to identify associated risk factors and antimicrobial susceptibility pattern among pregnant women at selected health facilities of Wolaita Sodo Town, Southern Ethiopia. Methodology: A health facility based cross-sectional study design was conducted at WSUCSH & Wolaita Sodo Health Center from June to August, 2022. A total of 279 pregnant women who were in ANC follow up with at 35-37 weeks of gestation were included. For GBS isolation, recto-vaginal swabs were inoculated in 1ml Todd-Hewitt broth medium supplemented with 10μg/ml colistin and 15μg/ml nalidixic acid and followed by identification of isolates based on colonial morphology, gram stains, catalase reaction and CAMP tests. Antimicrobial susceptibility testing was performed using modified Kirby–Bauer disk diffusion method. All collected data were organized in Epi info 4.6.0.2, then transfer tabulated using SPSS version 20. Logistic regression analysis was used to see the association between variables. Finally, the p-value < 0.05 were considered statistically significant. Results: In present study, 279 pregnant mothers included and their age was between 15 to 38 years with a mean of 26.5 ± 4.5 years. Of all participants, the highest 120 (43.01%) were housewives. The overall carriage rate of GBS was 67(24.0%). GBS colonization showed a statistically significant association with college and above levels of maternal education [AOR= 6.610, 95% CI (1.724 - 25.349), P=0.01]. High susceptibility of GBS isolate was seen to Penicillin G & Chloramphenicol (92.5%) for each, Ampicillin, and Ceftriaxone (89.6%) each, following Vancomycin (74.62%), and Erythromycin (77%). Relatively, GBS showed high resistance to Tetracycline (88 %). Conclusion: In this study, the overall prevalence of GBS colonization was 24.0%. College and above educational level was statistically significant with GBS colonization. This study used to give attention to the management of pregnant women by making GBS culture one of the routine diagnoses during ANC follow-up and to prevent infection by early detection.

Motivated by diffraction experiments on the $\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$ reconstructed Si(111) due to deposition of rare earth elements (Dy, Tb) and silicide formation we analyse the splitting and non-splitting of superstructure spots. For this purpose, we model diffraction patterns for one dimensional structures generated by the binary surface technique and use supercell models to keep the analysis simple. Diffraction pattern are calculated in the framework of the kinematical diffraction theory and they are analyzed as a function of the domains and domain boundaries. Basic properties of the diffraction pattern are analyzed for model systems of a two-fold and a three-fold periodicity. The rules derived from these calculations are applied to the "real-world" system of Si(111)-($\left(2\sqrt{3}\times \sqrt{3}\right)\mathrm{R}{30}^{\circ }$)-RESi$2_{}$ (RE = Dy or Tb). Depending on the combination of domains and domain boundaries of different types a plethora of different features are observed in the diffraction patterns. These are analyzed to determine the sizes of both domain boundaries and domains from experimentally observed splitting of specific superstructure spots.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

This study investigated interactions between sugar-related dietary patterns (DP), personality traits, cognitive-behavioural, and emotional functioning. The study involved females aged 18-54. Data were collected between the Winter and Spring of 2020/21. The survey was conducted using anonymized questionnaires. The Ten-Item Personality Inventory (TIPI) was used to examine personality traits based on the Big Five Personality Trait Model. Three-Factor Eating Questionnaire (TFEQ) was used to measure eating behaviours: cogni-tive restraint (CR), uncontrolled eating (UE), and emotional eating (EE). The KomPAN question-naire collected the frequency of intake. Dietary patterns (DPs) were derived by principal component analysis (PCA). A logistic regression (OR) was applied to verify the association between the DPs, personality traits, cognitive-behavioural and emotional functioning. Three DPs were identified: sweet-western (SWDP), pro-healthy (PHDP) and dairy (DDP). Women with high conscientiousness were less likely, by 33%, to adhere to the upper tercile of SWDP and 80% more likely to the upper tercile of PHDP. Elevated CR intensity increased by almost 2-fold (OR: 1.93; p

Quantifying the landscape pattern change can effectively demonstrate the ecological progresses and the consequences of urbanization. Based on remotely sensed land cover data in 1994, 2000, 2006 and a gradient analysis with landscape metrics at landscape- and class- level, we attempted to characterize the individual and entire landscape patterns of Shanghai metropolitan during the rapid urbanization. We highlighted that a roadscape transect approach that combined the buffer zone method and the transect-based approach was introduced to describe the urban-rural patterns of agricultural, residential, green, industrial, and public facilities land along the railway route. Our results of landscape metrics showed significant spatiotemporal patterns and gradient variations along the transect. The urban growth pattern in two time spans conform to the hypothesis for diffusion–coalescence processes, implying that the railway is adaptive as a gradient element to analyze the landscape patterns with urbanization. As the natural landscape was replaced by urban landscape gradually, the urban fringe expanded radically. The results also showed that the desakota region expanded its extent widely. Satellite towns witnessed the continual transformation from the predominantly rural landscape to peri-urban landscape. Furthermore, the gap between urban and rural areas remained large especially in public service. More reasonable urban plans and land use policies should push to make more of an effort to transition from the urban-rural separation to coordinated urban-rural development. This study is a meaningful trial in demonstrating a new form of urban–rural transects to study the landscape change of large cities from a strategic viewpoint. By combining gradient analysis with landscape metrics, we addressed the process of urbanization both spatially and temporally, and provided a more quantitative approach to urban studies.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Medical data flows in streams as the data related to clinical tests and administered drugs by the doctors flows continuously. The doctors must be immediately alerted if negative associations are found among the drugs they prescribe. Data streams are to be processed in single scans as it is not possible to re-scan the data for any iterative processing. To detect negative drug connections, regular and frequent drug patterns must be processed. Negative correlations between disease-curing medications might create adverse responses that kill patients. This paper proposes an algorithm that finds the negative associations among regular and frequent patterns mined from medical data streams. The negative associations mined are the most effective and reduce the negative associations, which are more critical by 50%.

Skin cancer is a prevalent and heterogenous disease with several subtypes, such as melanoma, basal cell carcinoma, and squamous cell carcinoma. Among them, melanoma is the most aggressive subtype, with a higher propensity to spread compared to most solid tumors. The application of OMICS approaches has revolutionized the field of melanoma research by providing comprehensive insights into the molecular alterations and biological processes underlying melanoma development and progression. This review aims to offer an overview of melanoma biology, covering its transition from primary to malignant melanoma, as well as the key genes and pathways involved in the initiation and progression of this disease. Utilizing online databases, we extensively explored the general expression profile of genes, identified the most frequently altered genes, and gene mutations, and examined genetic alterations responsible for drug resistance. Additionally, we studied the mechanisms responsible for immune checkpoint inhibitors resistance in melanoma.

Bovine respiratory disease (BRD) is the leading cause of morbidity and mortality in cattle raised in North America. At the feedlot, cattle are subject to metaphylactic treatment with macrolides to prevent BRD, a practice that may promote antimicrobial resistance and has resulted in an urgent need for novel strategies. Mannheimia haemolytica is one of the major bacterial agents of BRD. The inhibitory effects of two amphipathic, α-helical (PRW4, WRL3) and one β-sheet (WK2) antimicrobial peptides were evaluated against multidrug-resistant (MDR) M. haemolytica isolated from Alberta feedlots. WK2 was not cytotoxic against bovine turbinate (BT) cells by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. All three peptides inhibited M. haemolytica, with WK2, being the most efficacious against multiple isolates. At 8-16 µg/ml, WK2 was bactericidal against Mh 330 in broth and at 32 µg/ml in the presence of BT cells, reduced the population by 3 logs CFU/ml without causing cytotoxic effects. The membrane integrity of Mh 330 was examined using NPN (1-N-phenylnaphthylamine), and ONPG (o-Nitrophenyl β-D-galactopyranoside) with both the inner and outer membranes being compromised. Thus, WK2 may be a viable alternative to the use of macrolides as part of BRD prevention and treatment strategies.

Description of a novel bovine antimicrobial peptide and its antimicrobial spectrum. RNA isolation and RT-PCR were done from various tissues. DCD peptide was synthesized, and antimicrobial activity was analyzed. Bovine dermcidin gene contains five exons intermittent by 4 introns. Bovine DCD-mRNA was 398 bp with ORF 336 bp. Bovine DCD was expressed in skin and blood. Analysis of the amino acid compositions revealed that cysteine was repeated 6 times indicating the presence of 3 disulfide bonds that play role in the peptide stability. Staphylococcus epidermidis, Streptococcus bovis, and Enterococcus faecalis were affected by Bovine DCD peptide. Highest antimicrobial effect was at 50 and 100 µg/ml. The effect on Escherichia coli and Candida albicans was slightly low. In all bacteria, Bovine DCD peptide activity did not affect by varying pH values, but in Staphylococcus aureus, the activity was affected greatly at pH 4.5 and 5.5. The optimum salt concentrations were 100 and 50 mM NaCl with all bacterial strains and E. coli, respectively. In case of C. albicans, the antimicrobial activity of Bovine DCD peptide decreased with increasing the pH value regardless the NaCl concentration. The pH 6.5 of the sweat buffer was the optimum for the Bovine DCD peptide activity.

Background and Objectives: In recent years Electronic scooters (E-Scooters) have gained popularity, whether for private use or as a publicly available transportation method. With introduction of these vehicles, reports of E-Scooter related accidents have surged, sparking a public debate and concern. Aim of this study was to analyse epidemiological data, characteristics and severity of traumatic brain injury (TBI) related to E-Scooter accidents. Materials and Methods: This retrospective case series evaluated 28 patients who were admitted to three largest neurosurgery clinics in Riga, Latvia between time period from April to October in two separate years – 2022 and 2023 after an E-Scooter related accident. Data were collected on patient demographics, time of the accident, alcohol consumption, helmet use, type of TBI, other related injuries, treatment and assessment at discharge. Results: A total of 28 patients were admitted with TBI related to E-Scooter use, with median age 30 years (Q1-Q3, 20.25-37.25), four individuals under age of 18, majority (64%) were male. In 23 cases the injury mechanism was fall, in 5 cases collision. None were wearing a helmet at time of injury. Alcohol intoxication was evident in over half of the patients (51.5%), with severe intoxication (&gt;1.2ppm) in 75% cases among them. Neurological symptoms upon admission were noted in 50% of cases. All patients had intracranial trauma - 50% brain contusions, 43% traumatic subdural hematoma, almost 30% - epidural hematoma. Craniofacial fractures were evident in 71% of cases, fractures in other parts of body in 3 patients. 6 patients required emergency neurosurgical intervention. Neurological complications were noted in 2 patients, 1 patient died. Conclusions: E-Scooter related accidents result in a significant number of brain and other associated injuries, with notable frequency linked to alcohol influence and lack of helmet use. Prevention campaigns to raise awareness of potential risks and implementation of more strict regulations should be done.

This paper is motivated by spatio-temporal pattern in the occurrence of Leishmaniasis in Afghanistan and the relatively high number of zero counts. We hold the view that correlations that arise from spatial and temporal sources are inherently distinct. Our method decouples these two sources of correlations, there are at least two advantages in taking this approach. First, it circumvents the need to inverting a large correlation matrix, which is a commonly encountered problem in spatio-temporal analyses. Second, it simplifies the modelling of complex relationships such as anisotropy, which would have been extremely difficult or impossible if spatio-temporal correlations were simultaneously considered. We identify three challenges in the modelling of a spatio-temporal process: (1) accommodation of covariances that arise from spatial and temporal sources; (2) choosing the correct covariance structure and (3) extending to situations where a covariance is not the natural measure of association. Moreover, because the data covers a period that overlaps with the US invasion of Afghanistan, the high number of zero counts may be the result of no disease incidence or lapse of data collection. To resolve this issue, a model truncated at zero built on a foundation of the generalized estimating equations was proposed.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

Achieving the dual development of rural revitalization and urbanization is an important strategic goal of China’s current modernization. Rural population and settlements are the main components of the countryside in traditional agricultural areas, and play an important role in the development of the countryside itself in terms of urban and rural land use and in the formation of urban and rural development patterns. This study analyzes the spatial and temporal changes in rural populations and settlements at the township level, as well as the degree and type of coupled development. A framework for urban–rural development relationships based on different types of coupled development is proposed, and a model of urban–rural forces is constructed to derive the spatial pattern of urban–rural development at the township level that may be formed in the future. Our study shows that the rural population and settlements in the study area are characterized by significant spatial and temporal dynamics, indicating that traditional rural areas are in a process of rapid development and change. The results of the township-level coupling measurements present four types of development in terms of the spatial pattern of urban–rural development: A-type is most likely to produce new cities or satellite towns in the Jixi–Harbin–Qiqihar area in the future; B-type is the fastest dying area in the future, located in the Harbin and Qitaihe clusters, with a tendency to merge into Harbin; C-type is the area to be focused on in the future to attract population and strictly control the growth of the rural settlement area to avoid it turning into B-type; D-type may develop regional township centers in the future in the combined area of Jiamusi City, Suihua City and Mudanjiang City. The results of the study provide experience in realizing rural revitalization according to local conditions. The new spatial pattern of urban–rural development provides an important reference for formulating land use policies, optimizing urban–rural land allocation and realizing integrated urban–rural development strategies.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

The Center for Disease Control and Prevention and the World Health Organization issued a practical approach and Global Action Plan to control the threatening emerging antibacterial resistance. One of the main basis of this plan is the Antimicrobial Stewardship Program (ASPs). This study aimed to evaluate community pharmacists’ awareness and perception towards antimicrobial resistance and ASPs in Jordan. Thus, a qualitative study was conducted through in-depth interviews with twenty community pharmacists. Convienience sampling was used in the study. Qualitative analysis of the data yielded four themes and eleven sub-themes. All the respondents showed good understanding about the causes of antimicrobial resistance. The most important causes reported by them was the non-restricted prescription of antimicrobials. Most of the pharmacists believed that they are competent to provide ASPs, however, they believed that there are several barriers against the implementation of ASPs in community pharmacies in Jordan. Barriers demonstrated by the pharmacists, including organizational obstacles, resources obstacles, and personal obstacles. As a conclusion, this study revealed several barriers against the implementation of ASPs in community pharmacies in Jordan. Incorporating ASPs in the community pharmacy settings requires proper pharmacist training, several academic disciplines team efforts, and good pharmacy practice of antimicrobial guidelines.

The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352-372) is highly conserved (>90% in 90% species) in mammalian species. The highest-evolved primates show 58.8% similarity with the lowest-evolved monotremes. CST was initially identified as a physiological brake in catecholamine secretion by inhibiting nicotinic-cholinergic signaling. CST also inhibits desensitization of catecholamine secretion, indicating that CST can act both as a cholinergic antagonist (short-term) and as a cholinergic agonist (long-term). The long-term effect sustains catecholamine secretion during stressful situations. CST is now established as a pleiotropic hormone: it affects the cardiovascular system by lowering blood pressure and cardiac contractility, enhancing baroreflex sensitivity, increasing heart rate variability, and promoting angiogenesis; and it increases insulin sensitivity by reducing inflammation, inhibiting hepatic glucose production, attenuating endoplasmic reticulum stress, and inducing glycogen production. The present review will highlight the important direct and indirect effects of CST, CST1-15 (aka cateslytin), D-CST1-15 (where L-amino acids were changed to D-amino acids), and human variants of CST (Gly364Ser-CST and Pro370Leu-CST) on microbial growth inhibition and their potential as therapy for antibiotic-resistant pathogenic microbes.

The Upper Hunter Valley is a major coal mining area in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. The early part of this study identified two air quality subregions in the valley. This paper aims to provide a holistic summarisation of the relationships between elevated PM10 pollution in two subregions and the local- and synoptic-scale meteorological conditions for spring and summer, when PM10 pollution is relatively high. A catalogue of twelve synoptic types and a set of six local meteorological patterns have been quantitatively derived and linked to each other using the self-organising map (SOM) technique. The complex meteorology-air pollution relationships have been visualised/interpretated on the SOM planes for two representative locations. It was found that the influence of local meteorological patterns differed significantly for mean PM10 levels vs the occurrence of elevated pollution events and between air quality subregions. In contrast, synoptic types showed generally similar relationships with mean vs elevated PM10 pollution in the valley. Two local meteorological patterns, the hot-dry-northwesterly wind conditions and the hot-dry-calm conditions, were found most PM10 pollution conducive in the valley when combined with a set of synoptic counterparts. These synoptic types are featured with the influence of eastward migrating continental high pressure system and westerly troughs, or a ridge extending northwest towards coastal northern NSW or southern Queensland from the Tasman Sea. The method and results can be used in air quality research for other locations of NSW, or similar regions elsewhere.

Background: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV PrEP have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6-months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. Methods: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. Results: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. Conclusions: We conclude that in high antimicrobial consumption populations, the association between antimicrobial consumption and resistance may be attenuated.

Antimicrobial peptides (AMPs) have emerged as a promising solution to tackle bacterial infections and combat antibiotic resistance. However, their clinical application has been hindered by their vulnerability to protease degradation and toxicity towards mammalian cells. To overcome these challenges, our study aims to develop a method to enhance the stability and safety of AMPs, applicable to effective drug-device combination products. KR12 antimicrobial peptide was chosen and in order to further enhance its delivery and efficacy, HIV TAT protein-derived cell-penetrating peptide (CPP) was fused to form CPP-KR12. A new product, CPP-KR12@Si, was developed by forming silica nanoparticles with self-entrapped CPP-KR12 peptide using the biomimetic silica precipitability due to its cationic nature. Peptide delivery from CPP-KR12@Si to bacteria and cells was delivered at a slightly delayed rate with improved stability against trypsin treatment and a reduction in cytotoxicity over CPP-KR12. Finally, the antimicrobial potential of CPP-KR12@Si/bone graft substitute (BGS) combination product was demonstrated, which is coated with CPP-KR12 in the form of nanoparticles on the surface of BGS. Self-entrapped AMP in silica nanoparticles is a safe and effective AMP delivery method that will be useful for developing a drug/device combination product for tissue regeneration.

Antimicrobial Peptides (AMPs), as immune effectors synthesized by a variety of organisms, not only constitute a robust defense mechanism against a broad spectrum of pathogens in the host, but also show promising applications as effective antimicrobial agents. Notably, insects are significant reservoirs of natural AMPs. However, the complex array of variations in types, quantities, antimicrobial activities, production pathways of AMPs, and evolution of AMPs across insect species presents a significant challenge for immunity system understanding and AMP applications. This review covers insect AMP discoveries, classification, common properties, and mechanisms of action. Additionally, we summarize the types, quantities, and activities of im-mune-related AMPs in each model insect. We also conducted the first comprehensive investigation into the diversity, distribution, and evolution of 20 types of AMPs in model insects, employing phylogenetic analysis to describe their evolutionary relationships and shed light on conserved and distinctive AMP families. Furthermore, we summarize the regulatory pathways of AMP production through classical signaling pathways and additional pathways associated with Nitric Oxide, insulin-like signaling, and hormones. This review advances our understanding of AMP as guardians in insect immunity system and also unlocks a gateway to insect AMP resources, facilitating the use of AMPs to address food safety concerns.

Objective: The study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. Methods: In 2022, a total of 4,684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes were determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. Results: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5,47)=18.233, p&lt;0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5,47)=2.037, p=0.091). Conclusion: The study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

Management of urinary tract infection is challenged by increasing antimicrobial re-sistance (AMR) worldwide. In this study we describe the trends in antimicrobial re-sistance of uropathogens isolated from the largest private sector laboratory in Ghana over a five-year period. We reviewed positive urine cultures at the MDS Lancet Laboratories from 2017 to 2021. Proportions of uropathogens with antimicrobial resistance to oral and parenteral antimicrobials recommended by the Ghana standard treatment guidelines were determined. The proportion of multi-drug resistant isolates, ESBL and car-bapenemase-producing phenotypes were determined. Of 94,134 urine specimens submitted for culture, 20,010 (22.1%) were culture positive. Enterobacterales were the commonest group of organisms, E. coli (70.6) being the commonest isolate and Enterococcus spp. the commonest gram positive (1.3%) organisms. Among oral antimicrobials the highest resistance was observed to ciprofloxacin (62.3%) and cefuroxime (60.2) %) and the least resistance to Fosfomycin (1.9%). The least resistance among parenteral antimicrobials was to meropenem ( 0.3%). Highest multi-drug resistance levels were observed among Klebsiella spp. (68.6%) and E. coli (64.0%). ESBL positivity was highest in Klebsiella spp. (58.6%) and E. coli (50.0%). There may be a need to review the Ghana standard treatment guidelines to reflect increased resistance among uropathogens to recom-mended antimicrobials

New antimicrobial approaches are essential to counter antimicrobial resistance. The drug development pipeline is exhausted with emergence of resistance resulting in unsuccessful trials. The lack of an effective drug developed from the conventional drug portfolio has mandated the introspection into the list of potentially effective unconventional alternate antimicrobial molecules. Alternate therapies, that are clinically explicable forms include monoclonal antibodies, antimicrobial peptides, aptamers and phages. Clinical diagnostics optimizes the drug delivery. In the era of diagnostic-based applications, it is logical to draw diagnostic based treatment for infectious diseases. Selection criteria of alternate therapeutics in infectious disease include detection, monitoring of response and resistance mechanism identification. Integrating these diagnostic applications is disruptive to the traditional therapeutic development. The challenges and mitigation methods need to be noted. Applying the goals of clinical pharmacokinetics that include enhancing efficacy and decreasing toxicity of drug therapy this review analyses the strong correlation of alternate antimicrobial therapeutics in infectious diseases. The relationship between drug concentration and the resulting effect defined by the pharmacodynamic parameters are also analyzed. This review analyzes the perspectives of aligning diagnostic initiatives into the use of alternate therapeutics with a particular focus on companion diagnostic applications in infectious diseases.

The gut microbiota has recently been associated with susceptibility/resistance to malaria in animal models and humans, yet the impact of the gut microbiota on the risk of a malaria attack remains to be assessed. This study aims at assessing the influence of the gut microbiota on malaria attacks and Plasmodium parasitæmia in children living in a malaria-endemic area in Mali. Three hundred healthy children were included in a 16-months cohort study in Bandiagara. Their gut bacteria and fungi community structures were characterised via 16S and ITS metabarcoding from stool samples collected at inclusion. Clinician team monitored the occurrence of malaria attacks. Asymptomatic carriage of Plasmodium was assessed by qPCR. Over the 16-month period, 107 (36%) children experienced at least one occurrence of malaria attacks, and 82 (27%) at least one asymptomatic Plasmodium parasitæmia episode. A higher gut bacteria richness was independently associated with susceptibility to asymptomatic parasitæmia episodes and malaria attacks; while the Shannon H diversity and Chao-1 richness index of gut fungi community structure was relatively homogeneous in children who were and were not infected with P. falciparum. Using a linear discriminant effect size analysis of operational taxonomic units assigned to the species level, 17 bacteria, including Clostridiaceae, Eubacteriaceae, Senegalimassilia sp., Atopobiaceae and Lachnosipraceae, and seven fungi, including Dioszegia fristigensis, Ogataea polymorpha and Cutaneotrichosporon cyanovorans, were associated with susceptibility; whereas eight bacteria, including, Bifidobacterium spp., Weissela confusa and Peptostreptococcacea, and 3 fungi, Malassezia sp., Niesslia exosporoides, and Didymocrea leucaenae, were associated with resistance to malaria. Moreover, 15 bacteria, including Coproccus eutactus, Terrisporobacter petrolearius, Klebsiella pneumoniae and Ruminococcaceae, and 13 fungi, including Wallemia mellicola, were associated with susceptibility, whereas 19 bacteria, including Bifidobacterium spp., Bacteroides fragilis, Peptostreptococcacea, and Lactobacillus ruminis, and three fungi, including Cryptococcus neoformans, were associated with resistance to asymptomatic Plasmodium parasitæmia episodes. Further studies are needed to confirm these findings that point the way towards strategies aiming to reduce the risk of malaria by modulating gut microbiota components in at-risk populations.

The assessment of rockfall risks on human activities and infrastructure is of great importance. Rock falls pose a significant risk to a) transportation infrastructure b) inhabited areas and c) Cultural Heritage sites. The paper presents a method to assess rockfall susceptibility at national scale in Greece, using a simple rating approach and GIS techniques. An extensive inventory of rockfalls for the entire country was compiled for the period between 1935 and 2019. The rockfall events that were recorded are those, which have mainly occurred as distinct rockfall episodes in natural slopes and have impacted human activities, such as roads, inhabited areas and archaeological sites. Through a detailed analysis of the recorded data, it was possible to define the factors which determine the occurrence of rockfalls. Based on this analysis, the susceptibility zoning against rockfalls at national scale was prepared, using a simple rating approach and GIS techniques. The rockfall susceptibility zoning takes into account the following parameters: (a) the slope gradient, (b) the lithology, (c) the annual rainfall intensity, (d) the earthquake intensity and (e) the active fault presence. Emphasis was given on the study of the earthquake effect as a triggering mechanism of rockfalls. Finally, the temporal and spatial frequency of the recorded events and the impact of rockfalls on infrastructure assets and human activities in Greece were evaluated.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

Sensors and actuators are fundamental units in Cyber-Physical and Internet of Things systems. Because they are included in a variety of systems, using many technologies, it is very useful to characterize their functions abstractly by describing them as Abstract Entity Patterns (AEPs), that are patterns that describe abstract conceptual entities. For concreteness, we study them here in the context of autonomous cars. An autonomous car is a complex system because, in ad-dition to its own complex design, it interacts with other vehicles and with the surrounding in-frastructure. To handle these functions, it must incorporate various technologies from different sources. An autonomous car is an example of a Cyber-Physical System, where some of its func-tions are performed by Internet of Things units. Sensors are extensively used in autonomous cars to measure physical quantities; actuators are commanded by controllers to perform appro-priate physical actions. From AEPs we can derive concrete patterns, a structure combining re-lated AEPs is an Entity Solution Frame (ESF). Both sensors and actuators are susceptible to mali-cious attacks due to the large attack surface of the system where they are used. Our work is in-tended to make autonomous cars more secure, which also increases their safety. Our final objec-tive is to build a Security Solution Frame for sensors and actuators of autonomous cars that will facilitate their secure design. A Security Solution Frame is a solution structure that groups to-gether and organizes related security patterns. This article is the first stage of a secure unit that can be used to design not only secure autonomous cars but also any system where sensors and actuators are used. This paper concentrates on AEPs and ESFs for sensors and actuators; that is, on the functional aspects of these devices.

According to many researchers, Abstraction is the basis of mathematics, computing, counting devices, and computer science and engineering. What is more, all of the above deal with complexity management in some way, and abstraction is the most basic mechanism of complexity management.Generative software development - whether in the sense of empowering humans by machine to create software or in the sense of reusing products - has been and is one of the serious concerns and goals of software engineering. The interesting thing is that in both views of generativity, the main issue is still, in a way, complexity management: whether this complexity management is to achieve diversity and reuse management (Czarnecki’s approach) or to Structuring from existing structures (the approach of Alexander and his followers in an object-oriented society).In this article, we will first look at complexity and its various definitions. The definitions that show, despite the different perspectives on complexity in different disciplines and domains, all point in one direction. We will conclude that complexity is rooted in multiplicity. In the following, we will formally define complexity. In the following discussion, we will look at the generative patterns of software development, and then we will look at the complexity management patterns at seven levels.In this article, the author has tried to maintain a comprehensive approach to complexity and to consider the approaches of different domains to complexity.

Pancreatic cancer stands out as one of the most lethal forms of malignancies, representing 2% of all cancer cases and contributing to 5% of cancer-related fatalities. Therefore, early detection of pancreatic cancer is crucial for enhancing treatment outcomes. Various hereditary cancer syndromes have been linked to an elevated risk of developing pancreatic cancer, suggesting potential benefits from surveillance strategies for individuals at risk. Presently, precision medicine employs PARP inhibitor therapy for pancreatic cancer patients carrying germline variants in Homologous Recombination Repair (HRR) genes. Our objective was to ascertain the occurrence of germline pathogenic/likely pathogenic variants in genes predisposing to cancer among pancreatic cancer patients. Methodologically, we analyzed 184 pancreatic cancer patients referred to our laboratory for genetic examination. Utilizing a Next-Generation Sequencing (NGS) approach, we scrutinized 52 genes implicated in hereditary cancer predisposition. Our findings revealed that 21% of the patients analyzed harbored germline pathogenic/likely pathogenic variants. Within this subset, 48% exhibited positive results in pancreatic cancer susceptibility genes, namely ATM (17%), BRCA1 (12%), BRCA2 (7%), CDKN2A (7%), and PALB2. Significantly, 64.3% of the pathogenic variants were associated with genes involved in the HRR pathway (ATM, BRCA1, BRCA2, BRIP1, CHEK2, FANCL, MRE11, PALB2, RAD50, RAD51B and RAD51C). In conclusion, our study underscores the significance of multigene genetic testing for pancreatic cancer patients, with 21% of individuals yielding findings linked to pancreatic or other cancer predisposition. Moreover, patients carried pathogenic/likely pathogenic variants in HRR genes, potentially benefiting from targeted therapies such as PARP inhibitors or platinum-based treatments.

Pulmonary infections with Mycobacterium avium occur in susceptible individuals following exposure to the bacterium in the environment, where it often persists in biofilms. Many methods have been used to generate biofilms of M. avium, and it is unknown whether different approaches generate similar structures and cell phenotypes. To make a parallel comparison of in vitro biofilm ultrastructure, extracellular matrix (ECM) composition, and drug susceptibility of biofilm resident bacteria, we used two published methods to generate M. avium biofilms: four week incubation in M63 medium or 24 hour exposure to dithiothreitol (DTT). Scanning electron microscopy revealed differences in biofilm ultrastructure between the two methods, including variation in appearance of ECM materials and morphology of resident cells, while light microscopy and staining with calcofluor white indicated that both biofilms contained polysaccharides characteristic of cellulose. Measuring susceptibility of biofilms to degradation by enzymes suggested differences in structurally important ECM molecules, with DTT biofilms having important protein and, to a lesser extent, cellulose components, and M63 biofilms having moderate protein, cellulose, and DNA components. Both biofilms conferred resistance to the bactericidal effects of amikacin and clarithromycin, with resident cells being killed at &gt;10-fold lower rates than planktonic cells at almost all concentrations. Though these comparisons indicate differences in biofilm responses by M. avium under differing conditions, they also suggest common features of biofilm formation including cellulose production and antimicrobial resistance.

Objective: On March 11, 2020 the WHO declared that COVID-19 is pandemic. Among the risk factors for many infectious diseases, a role of the ABO blood group system is reported in the literature. We argue whether it is necessary to investigate the relationship between ABO blood groups and susceptibility to SARS-CoV-2 infection and if we should consider some blood groups as potential risk factors for COVID-19. Results: Based on the scientific evidence reported in this letter, we believe that further studies are needed to investigate how the ABO polymorphism influences the host susceptibility, individual response and clinical risk for SARS-CoV-2 infection.

Globally increasing antibiotic resistance has been connected to the use of antibiotics in medical, veterinary, and agricultural medicine, contributing to the burden of antibiotic resistance in Asia and Europe. The main objective of this study was to correlations of antimicrobial-resistant of various pathogens in three compartments: humans, animals and the environment in India and Germany. A systematic search was carried out in Medline via PubMed, Google Scholar, and science direct, including studies published in 2022. Out of 532 papers, 24 were considered for meta-analysis. This study reveals that in India, β-lactam is highly resistant in animals. Quinolone, on the other hand, was highly resistant in humans. Furthermore, in the environment and integrated studies, aminoglycosides and β-lactams is resistant. While in Germany, a high rate of AMR resistance in all three sectors was reported in β-lactam. However, E. coli was the most frequent pathogen in both countries and is highly resistant to β-lactam, followed by cephalosporin in all the compartments. Monitoring and evaluating antibiotic-sensitivity patterns and developing proper antibiotic regimens may lead to improved outcomes for inhibiting and controlling E. coli infections in various parts of the world.

Bacterial infections have attracted the attention of researchers in recent decades, especially due to the special problems they have faced, such as their increasing diversity and resistance to antibiotic treatment. The emergence and development of the SARS-CoV-2 infection stimulated even more research, to find new structures with antimicrobial and antiviral properties. Among the heterocyclic compounds with remarkable therapeutic properties, benzimidazoles and triazoles stand out, possessing antimicrobial, antiviral, antitumor, anti-Alzheimer, anti-inflammatory, analgesic, antidiabetic, or anti-ulcer activities. In addition, the literature of the last decade reports benzimidazole-triazole hybrids with improved biological properties compared to the properties of simple mono-heterocyclic compounds. This review aims to provide an update on the synthesis methods of these hybrids, along with their antimicrobial and antiviral activities, as well as the structure–activity relationship reported in literature.

Human exposure to antimicrobial resistance (AMR) through food is now very imperfectly understood, creating a significant gap in the design of interventions. The interchange of AMR genes and the transfer of AMR bacteria from animals to humans through the food chain necessitate comprehensive methods to risk reduction. With a focus on AMR in bacterial species isolated from food products, foods (of both animal and non-animal origin), and ambient samples, the current meta-analysis gathered up-to-date information on the epidemiology of AMR in animal-source food chain. As a result, the combined prevalence of AMR across the various food sources was calculated. From the 18,784 food samples obtained as a result of selected publications, 7,676 (40.9%) samples were contaminated, including 4343 (56.6%) and 3363 (43.4%) samples from Taiwan and India, respectively. Meat (chicken, pork, and beef), fish and milk all have moderate to medium potential for AMR exposure to both Gram-positive and Gram-negative foodborne pathogens such S. aureus, Clostridium, E. coli, Salmonella, etc. Antibiotic resistance to β-lactam, fluoroquinolone, carbapenem etc, is present in the majority of food samples. The results of this study emphasize the persistent danger of antimicrobial residue in animal-derived foods in Taiwan, India, and other nations with comparable customs.

As the prevalence of antimicrobial resistance genes is increasing in microbes, we are facing the return of the preantibiotic era. Consecutively, the number of studies concerning antibiotic resistance and its spread in the environment is rapidly growing. Next generation sequencing technologies are widespread used in many areas of biological research and antibiotic resistance is no exception. For the rapid annotation of whole genome sequencing and metagenomic results considering antibiotic resistance, several tools and data resources were developed. These databases, however can differ fundamentally in the number and type of genes and resistance determinants they comprise. Furthermore, the annotation structure and metadata stored in these resources can also contribute to their differences. Several previous reviews were published on the tools and databases of resistance gene annotation, however, to our knowledge, no previous review focused solely and in depth on the differences in the databases. In this review, we compare the most well-known and widely used antibiotic resistance gene databases based on their structure and content. We believe that this knowledge is fundamental for selecting the most appropriate database for a research question and for the development of new tools and resources of resistance gene annotation.

Whether there is any inclination between structures and functions of antimicrobial peptides (AMPs) is a mystery yet to be unraveled. AMPs have various structures associated with many different antimicrobial functions, including antibacterial, anticancer, antifungal, antiparasitic and antiviral activities. However, none has yet reported any antimicrobial functional tendency within a specific category of protein/peptide structures nor any structural tendency of a specific antimicrobial function with respect to AMPs. Here we examine the relationships between structures categorized by three structural classification methods (CATH, SCOP and TM) and seven antimicrobial functions with respect to AMPs using an enrichment analysis. The results show that antifungal activities of AMPs were tightly related to two-layer sandwich structure of CATH, knottin fold of SCOP, and the first structural cluster of TM. The associations with knottin and TM cluster 1 even sustained through the AMPs with a low sequence identity. Besides, another significant mutual enrichment was observed between the third cluster of TM and anti-gram-positive-bacterial/anti-gram-negative-bacterial activities. The findings of the structure-function inclination further our understanding of AMPs and could help us design or discover new therapeutic potential AMPs.

As artificial intelligence continues to advance, researchers are increasingly using machine learning algorithms to study the factors that make people more susceptible to phishing scams. Most studies in this area have taken one of two approaches: either they explore statistical associations between various factors and susceptibility, or they use complex models such as deep neural networks to predict phishing behavior. However, these approaches have limitations in terms of providing practical insights for individuals to avoid future phishing attacks and delivering personalized explanations regarding their susceptibility to phishing. In this paper, we propose a machine learning approach that leverages explainable artificial intelligence techniques to examine the influence of human and demographic factors on susceptibility to phishing attacks. Our analysis reveals that psychological factors such as impulsivity and conscientiousness, as well as appropriate online security habits, significantly affect an individual's susceptibility to phishing attacks. Furthermore, our individualized case-by-case approach offers personalized recommendations on mitigating the risk of falling prey to phishing exploits, considering the specific circumstances of each individual.

In this study, we use descriptive statistics and data visualization techniques to analyze datasets and identify patterns and relationships between bikeshare and other transportation modes. We also use regression analysis to quantify the impact of various factors on bikeshare usage. Our results indicate that bikeshare trips during the pandemic were much longer compared to pre-pandemic times. Moreover, usage of bikeshare differed by user group, with casual users showing a greater increase in usage compared to subscribers. We plotted bivariate choropleth maps to visualize the spatial distribution of changes in bikeshare usage. Our findings suggest that an increase in bikeshare travel was associated with a reduction in travel by ride-hailing and public transit, especially in the northern part of the city, indicating a potential replacement of other modes of transportation. On the western and southern boundary of the city, bikeshare had a complementary effect with other modes. Overall, the data acquired for this study provides a valuable opportunity to understand the behavior of bikeshare users in Chicago, the intercorrelation of bikeshare with other transportation modes, and the impact of infrastructure on bikeshare usage. The findings of this study can inform the design and implementation of bikeshare systems in other cities and contribute to the development of a more sustainable transportation system.

The development of Al-Ni alloys with a controlled microstructure has had a great impact on the field of study of aluminum-based alloys. In the present research, the influence of thermal parameters on the grain structures resulting from the directional solidification process of Al-Ni alloys with different alloy content has been studied. It has also been evaluated how different structures and the distribution of second phases influence the corrosion behavior and microhardness of alloys. The columnar-to-equiaxed transition (CET) was observed to occur when the temperature gradient in the melt decreased to values between 1.3 to 2.9 ° C/cm. In addition, a small increase in the microhardness values was observed as a function of the Ni-content. When the Ni-content increase, the resistance to polarization decreases for samples with equiaxed grain structure, throughout the range of compositions studied. Furthermore, the equiaxed grain structure presents higher resistance to polarization values than the columnar grain zone, for alloys with a composition equal to or lower than the eutectic composition.

The objective of the study was to analyse the antimicrobial susceptibility trends of Spanish porcine bacteria to quinolones, cephalosporins and polymyxins. Isolates of Actinobacillus pleuropneumoniae, Pasteurella multocida, and Escherichia coli were isolated from sick pigs from 2019 to 2022. Antimicrobial susceptibility test was determined by minimal inhibitory concentration (MIC) following internationally accepted methodology. MIC categorization was based on distributing the range of MIC values in four categories being category one the most susceptible (lowest MIC value) and four the less susceptible one (highest MIC value). Moreover, clinical susceptibility (susceptible/resistant) was also determined according to CLSI and EUCAST clinical breakpoints. A logistic and multinomial logistic regression model was used to analyze the susceptibility data for dichotomized and categorized MIC data, respectively for any pair of antimicrobial/microorganism. In general terms, the antimicrobial susceptibility of pig bacteria to these antimicrobials remained stable or increased in the last four years in Spain. In the case of A. pleuropneumoniae and quinolones, it was observed a significant temporal trend where isolates from 2020 had significantly increased odds of being more susceptible than isolates from 2019. In the case of E. coli and polymyxins, a significant temporal trend was observed where isolates from 2020 and 2021 had significantly increased odds of being more susceptible than isolates from 2019 and 2020, respectively. Finally, a significant odd of being less susceptible was only observed for cephalosporins and E. coli for 2020 versus 2019, stagnating for the rest of study period. These results provide sound data on critical important antimicrobials in swine medicine.

Genetic, developmental, biochemical, and environmental variables interact intricately to produce sex differences. The significance of sex differences in cancer susceptibility is being clarified by numerous studies. Epidemiological research and cancer registries have revealed over the past few years that there are definite sex variations in cancer incidence, progression, and survival. However, oxidative stress and mitochondrial dysfunction also have a significant impact on the response to treatment of neoplastic diseases. Young women may be more protected from cancer than men because most of the proteins implicated in the regulation of redox state and mitochondrial function are under the control of sexual hormones. In this review, we describe how sexual hormones control the activity of antioxidant enzymes and mitochondria, as well as how they affect several neoplastic diseases. The molecular pathways that underlie the gender-related discrepancies in cancer that have been identified may be better understood, which may lead to more effective precision medicine and vital information on treatment options for both males and females with neoplastic illnesses.

Antimicrobial peptides (AMPs) have emerged as a promising class of bioactive molecules with the potential to combat infections associated with medical implants and biomaterials. This review article aims to provide a comprehensive analysis of the role of antimicrobial peptides in medical implants and biomaterials, along with their diverse clinical applications. The incorporation of AMPs into various medical implants and biomaterials has shown immense potential in mitigating biofilm formation and preventing implant-related infections. We review the latest advancements in biomedical sciences and discuss the AMPs that were immobilized successfully to enhance their efficacy and stability within the implant environment. We also highlight successful examples of AMP coatings for the treatment of surgical site infections (SSIs), Contact lenses, Dental Applications, AMP-Incorporated Bone Grafts, Urinary tract infections (UTIs), Medical Implants, etc. Additionally, we discuss the potential challenges and prospects of AMPs in medical implants, such as effectiveness, instability and implant-related complications. We also discuss strategies that can be employed to overcome the limitations of AMP-coated biomaterials for prolonged longevity in clinical settings.

The antimicrobial peptide LRGG (LLRLLRRGGRRLLRLL-NH2) was designed and chemically synthesized in a study conducted by Jia et al. Gram-negative bacteria were found to be sensitive to LRGG and exhibited a high therapeutic index. Genetic engineering methods were used to create the prokaryotic fusion expression vector pQE-GFP-LRGG, and the resulting corresponding fusion protein GFP-LRGG was subsequently expressed and purified. The precursor GFP was then removed by TEV proteolysis, and pure LRGG was obtained after another round of purification and endotoxin removal. The prokaryotic-expressed antimicrobial peptide LRGG displays a broad-spectrum antibacterial effect on gram-negative bacteria and can eliminate 99.99% of E. coli within 100 minutes at the minimal MIC concentration. Compared to the chemically synthesized LRGG, the prokaryotic-expressed LRGG exhibits similar temperature, pH, salt ion, serum stability, and cell selectivity. Furthermore, prokaryotic-expressed LRGG showed excellent therapeutic effects in both the infection model of cell selectivity and no embryotoxicity in a Galleria mellonella infection model. The mechanism by which LRGG causes bacterial death was found to be disruption of Gram-negative cell membrane.

Since ancient times, various scientists and doctors have utilized different herbs to heal diseases. Due to the rise in drug resistance and the negative effects of chemosynthetic drugs, researchers and the general public around the world have become more interested in medicinal herbs and plant metabolites/extracts. This is due to its non-toxicity and several health benefits when used to treat diseases in clinical and medical settings. Ocimum basilicum is one such plant, possessing a wide range of bioactive phytochemicals including alkaloids, phenolics, flavonoids, tannins, saponins, reducing sugars, cardiac glycosides, steroids and glycosides, as well as complex pharmacological activities including anti-inflammatory, antifungal, antibacterial, antioxidant, wound healing and antiviral properties. The results of many studies on Ocimum basilicum plant extracts are collected and presented in this review. The plant extracts have an excellent potential to be used as medicinal raw materials and exhibit an extensive variety of therapeutic capacities, including antibacterial, antioxidant, wound healing, anti-inflammatory, antifungal, and antiviral properties.

The leaf essential oils from five Eucalyptus spp.: E. astringens, E. camaldulensis, E. lehmanii, E. leucoxylon and E. sideroxylon growing in the same plantation area and conditions (plants with the same age and subjected to the same agronomic practices) were analyzed and evaluated for their antimicrobial activity. The essential oil yields ranged from 0.14 to 0.96% (w/w), and their chromatographic profiles were resolved into 48 compounds; among them, 11 were common to all essential oils. Terpenoids (oxygenated mono, and sesquiterpenes) dominated (55.66-76.67%) the oil profiles. Although 1,8-cineole (21.97-50.93%) was found as the main oxygenated monoterpene in all examined essential oils, principal component analysis observed and confirmed an interspecific chemical variability. Additionally, a set of distinctive chemical markers that could serve as a reliable tool for discrimination of Eucalyptus species and for authentication and quality control purposes (for commercial samples) has been defined for each essential oil. The antimicrobial disc-diffusion assay results revealed that all essential oils were endowed with a strong antimicrobial activity, with those derived from E. camaldulensis, E. lehmanii and E. leucoxylon being the most active.

Pathogenic microorganisms can cause a range of infectious diseases and are often treated with antimicrobial agents. The rise of antimicrobial resistance caused by inappropriate use of these agents in various settings has become a global health threat. There is, therefore, a need to find new and effective agents to combat infections caused by resistant pathogens. Nanotechnology has seen significant growth and development in recent years and has a wide range of applications in various fields, including health, agriculture, and industry. This novel area offers the potential for the synthesis of nanoparticles (NPs) with antimicrobial activity, such as iron oxide nanoparticles (IONPs). The use of IONPs is a promising way to overcome antimicrobial resistance or pathogenicity because of their ability to interact with several biological molecules and to inhibit microbial growth. This review focuses on the most common green synthesis methods for producing IONPs using bacteria, fungi, plants, and organic waste, as well as the most common methods for the characterization of these IONPs. Finally, it summarizes their application as promising antibacterial, antifungal, antiparasitic, and antiviral agents.

The prominent cultivation of lemongrass relies on the pharmacological incentives of its essential oil. The lemongrass essential oil (LEO) has a significant amount of citral (mixture of geranial and neral), isoneral, isogeranial, geraniol, geranyl acetate, citronellal, citronellol, germacrene-D, and elemol in addition to numerous other bioactive compounds. These components confer various medicinal activities to LEO including antifungal, antibacterial, antiviral, anticancer, and antioxidant properties. These attributes are commercially exploited in pharmaceutical, cosmetics, and food preservations industries. Furthermore, the employment of LEO in the treatment of cancer opens a new vista in the field of therapeutics. Although different LEO components have shown promising anticancer activities in vitro, these effects have not been assessed yet in humans. Further studies on the anticancer mechanisms exerted by lemongrass components are required. The present review intends to provide a timely discussion on the relevance of lemongrass extracts in cancer and health treatment, and in food industry applications.

A series of derivatives of trans-3-(2,4,6-trimethoxy phenyl)-4,5-dihydro isoxazolo-4,5-bis(aroylcarbohydrazide) and of trans-3-(2,4,6-trimethoxyphenyl)4,5-dihydroisoxazolo-4,5-bis[carbonyl-(4’phenyl)thiosemi- carbazide (9) were synthesized from trans-3-(2,4,6-trimethoxyphenyl)-4,5-dihydro-4,5-bis(hydrazenocarbonyl) Isoxazole (8). The structures of the Compounds were elucidated by elemental and spectral (IR, NMR, and MS) analysis. The compound 9 show activity against some bacterial species. Whereas, no activity was observed for compounds 10a, 10b and 10c against all bacterial species. The antioxidant activity of new compounds has been screened. Compound 9 showed higher antioxidant activity using the DPPH and ATBS method.

Background: Public misconception and demand for the indication of antibiotics could lead to inappropriate prescribing and consumption. Successful treatment can only be achieved when the public and industrial users have knowledge on antibiotic use and resistance. This survey is aimed to assess antibiotic usage and knowledge regarding antibiotics and antimicrobial resistance (AMR) among undergraduate students of Universiti Brunei Darussalam (UBD), public university located in Brunei Darussalam. Methods: A cross-sectional study was performed using a self-administered questionnaire. The questionnaire was adapted from the World Health Organization (WHO) Antibiotic Resistance, Multi-country public awareness survey distributed online. Students at UBD were invited to participate in the online survey through internal email. The questionnaire consisted of 5 sections: demographic information, antibiotic usage, knowledge on antibiotics, antibiotic resistance (AMR) and use of antibiotics in agriculture. Data were analyzed descriptively and appropriate inferential statistics was used accordingly. Cronbach’s alpha was also done to determine the internal consistency. The section on antibiotic use and knowledge showed good internal consistency of Cronbach’s alpha 0.66 and 0.86 respectively. Research ethics approval was obtained from the PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam (UBD). Results: A total of 145 students returned the complete questionnaire. The result of the study found that 50% of the students had good level of knowledge of antibiotic and antimicrobial resistance with a mean total knowledge score of 11.4 out of 14. Respondents reported the use of antibiotic in the past (69%). Many of the students could identify the use of antibiotics for the treatment of bacterial infection. However, there were also students who incorrectly thought that antibiotics can be used for cold and flu (43%) and fever (41%). Moreover, 76% of the respondents mistakenly believed that antibiotic resistance is the result of the body becoming resistant to antibiotics. Only 12% of the respondents were found to have poor knowledge in the study. Conclusions: Misconceptions in regards to the use of antibiotics for conditions related to viral illnesses was noticed among the respondents in our study. Thus, improving knowledge on antibiotics is crucial to address those beliefs.

Periodic assessment of bacterial contamination is necessary as it allows proper guidance in cases of eye infections through the use of appropriate antibiotics. Due to the extensive use of antibiotic treatment, most of the contamination flora is resistant to the usual ophthalmic antibiotics. The present study shows an updated picture of the susceptibility of Gram-positive and Gram-negative bacteria found on the ocular surface to the most commonly used antibiotic agents in patients undergoing cataract surgery. A total of 993 patients were included in the study with ages between 44 and 98 years old. Conjunctival culture was collected 7 days before cataract surgery. The response of Gram-positive and Gram-negative bacteria to various antibiotic classes like glycopeptides, cephalosporins, carbapenems, fluoroquinolones, aminoglycosides, phenicols, tetracyclines, rifamycins, macrolides and penicillins was assessed. From the tested antibiotics, vancomycin had 97.8% efficacy on Gram-positive bacteria. In the cephalosporin category, we observed an increased resistance of the cefuroxime for both Gram-positive and negative bacteria. Antibiotics that have more than 90% efficacy on Gram-positive bacteria are: meropenem, imipenem, netilmicin, amikacin and rifampicin. On Gram-negative bacteria, we found 100% efficacy of all tested fluoroquinolones, aminoglycosides (except for tobramycin), doxycycline, azithromycin, clarithromycin and chloramphenicol. The current study illustrates patterns of increased resistance of certain bacteria present on ocular surface to some of the commonly used antibiotics in ophthalmological clinical practice. One such revealing example is cefuroxime, which has been highly used as an intracameral antibiotic for the prevention of bacterial endophthalmitis after cataract surgery.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Given that metabolic syndrome, along with obesity as one of its key components, remains one of the leading yet insufficiently addressed public health issues, what contributes to the development and maintenance of the disorder must certainly attract the attention of professionals and scientists. Precisely because of this phenomenon, eating patterns associated with metabolic syndrome should be studied and attempts should be made to uncover patterns in occurrence. The aim of this study is to review the literature and consider the connection between metabolic syndrome and eating patterns such as emotional and compulsive eating, as well as through the lens of food addiction. Furthermore, we have attempted to uncover the role of psychiatry and psychotherapy in the treatment of metabolic syndrome and delve into the complexity of recognizing these patterns and emphasize the importance of a multidisciplinary approach in the treatment of metabolic syndrome.

Cholesterol siRNA conjugates attract attention because they allow the delivery of siRNA into cells without the use of transfection agents. In this study, we compared the efficacy and duration of silencing induced by cholesterol conjugates of selectively and totally modified siRNAs and their heteroduplexes of the same sequence and explored the impact of linker length between the 3' end of the sense strand of siRNA and cholesterol on the silencing activity of “light” and “heavy” modified siRNAs. All 3'-cholesterol conjugates were equally active under transfection, but the conjugate with a C3 linker was less active than those with longer linkers (C8 and C15) in a carrier-free mode. At the same time, they are significantly inferior in activity to the 5'-cholesterol conjugate. Shortening the sense strand carrying cholesterol by 2 nucleotides from the 3'-end did not have a significant effect on the activity of the conjugate. Replacing the antisense strand or both strands with fully modified ones has a significant effect on silencing as well as improving the duration in transfection-mediated and carrier-free modes. A significant 78% suppression of MDR1 gene expression in KB-8-5 xenograft tumors developed in mice promises an advantage from the use of fully modified siRNA cholesterol conjugates in combination chemotherapy.

To harness light-matter interaction at nano-/micro-scale better control tools have to be developed. Here, it is shown that by applying external electric and/or magnetic field, ablation of Si and glass under ultra-short (sub-1~ps) laser pulse irradiation can be controlled via the Lorentz force $\mathbf{F} = e\mathbf{E} + e[\mathbf{v}\times\mathbf{B}]$, where $\mathbf{v}$ is velocity of charge $e$, $\mathbf{E}$ is the applied electrical bias and $\mathbf{B}$ is the magnetic flux density. The external electric E-field was applied during laser ablation using suspended micro-electrodes above glass substrate with an air gap for the incident laser beam. The counter-facing Al-electrodes on Si surface were used to study debris formation patterns on Si. Debris was deposited preferentially towards the negative electrode in the case of glass and Si ablation. Also, an external magnetic field was applied during laser ablation of Si in different geometries and is shown to affect ripple formation. The vectorial nature of the Lorentz force widens application potential of surface modifications and debris formation in external E-/B-fields with potential applications in mass and charge spectroscopes.

Zinc nanoparticles (ZnNPs) open new opportunities for biomedical applications as a strategy against microbes and dye removal in an efficient way. The composite ZnNPs using Rhododendron arboreum (R. arboreum) stem bark were synthesized and characterized for UV-visible spectroscopy (UV-vis), Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDX), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The synthesized nanoparticles showed zones of inhibition of 23±0.09, 18±0.1 and 16±0.05 mm, against the Klebsiella pneumoniae (K. pneumoniae), Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli strains. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values against K. pneumoniae, S. aureus, and E. coli were found to be 34±0.21 and 72.71±0.47, 47±0.11 and 94.86±0.84 and 94±0.18 and 185.43±0.16 µg/mL, respectively. The biosynthesized ZnNPs resulted in significant eradication of the outer and inner membranes of the bacterial cells. Likewise, the synthesized ZnNPs showed time-dependent photocatalytic degradation activity and revealed 65% methyl orange dye degradation with an irradiation period of 6 hours. The findings of this study suggest the suitability of the novel R. arboreum stem bark-based ZnNPs as an effective ameliorant against bactericidal activities and photocatalysts for the removal of hazardous water contaminants.

Nicotinamide riboside (NR) is an NAD+ precursor capable of regulating mammalian cellular metabolism. Phycocyanin oligopeptide (PC), a phytonutrient found in blue-green algae, has antioxidant and anti-inflammatory properties. This study explored the effects of NR, PC, and their combination on telomere length, inflammatory and antioxidant status in rats under chronic stressed conditions (CS). Forty-nine rats were allocated into seven groups: Control, chronic stress (CS), CS with NR (26.44 mg/kg), a low dose of 2.64 mg/kg of PC (PC-LD), or a high dose of 26.44 mg/kg PC (PC-HD), NR+PC-LD and NR+PC-HF. Rats were given daily corticosterone injections (40 mg/kg) to induce stressed conditions, or NR and PC were orally administered for 21 days. NR and PC supplementation, particularly NR plus PC, increased the serum antioxidant enzyme activities, hepatic nicotinamide adenine (NAD+) content, and telomere length (P&lt;0.001 for all) compared with the CS group. The levels of serum malondialdehyde (MDA), liver interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), IL-1β, and IL-8 were reduced under CS condition (P&lt;0.001). In addition, CS decreased the levels of hepatic telomere-related proteins and sirtuin1 (SIRT1-3), while supplementation of NR and PC alone or in combination increased the levels of telomere-related proteins (e.g., POT1b, TRF1, and TRF2), and SIRT3, NAMPT P&lt;0.05. In conclusion, NR and PC, especially their combination, can alleviate metabolic abnormalities by enhancing hepatic cytokines, SIRT3, NAMPT, and NAD+ levels in CS-exposed rats. More research is needed to elucidate further the potential health effects of the combination of NR and PC in humans.

The epidemiology of invasive fungal infections (IFIs) is currently changing, driven by aggressive immunosuppressive therapy, leading to an expanded spectrum of patients at risk of IFIs. Aspergillosis is a leading cause of IFIs, which usually affects immunocompromised patients. There is a limited number of antifungal medications available for treating IFIs and their effectiveness is often hindered by rising resistance rates and practical limitations. Consequently, new antifungals, especially those with novel mechanisms of action, have become increasingly required. This study assessed the activity of four novel antifungal agents with different mechanisms of activity: manogepix, rezafungin, ibrexafungerp, and olorofim against 100 isolates of Aspergillus section Terrei, containing amphotericin B (AmB) wildtypes/non-wildtypes and azole-susceptible/-resistant strains, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) method. In general, all tested agents showed potent and consistent activity against tested isolates, exhibiting a geometric mean (GM) and minimum effective concentration (MEC)/minimum inhibitory concentrations (MIC) range respectively as follows: manogepix (0.048 mg/L, 0.032-0.5 mg/L), rezafungin (0.020 mg/L, 0.016-0.5 mg/L), ibrexafungerp (0.071 mg/L, 0.032-2 mg/L), and olorofim (0.008 mg/L, 0.008-0.032 mg/L). In terms of MIC90/MEC90, olorofim had the lowest values (0.008 mg/L), followed by rezafungin (0.032 mg/L), manogepix (0.125 mg/L), and ibrexafungerp (0.25 mg/L). All antifungals tested demonstrated promising in vitro activity against Aspergillus section Terrei, including A. terreus and cryptic species that were azole-resistant and AmB non-wildtype.

MicroRNAs (miRNAs) play crucial roles in the regulation of the transcriptome and development of diseases including cancer and autoimmune diseases, such as rheumatoid arthritis (RA). Currently, a comprehensive map, illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interaction with terminal cells, such as T cells, fibroblast-like synoviocytes (FLS), osteoblasts, and osteoclasts, is still missing. In this review, we provide a thorough summary of the roles of miRNAs in the susceptibility to pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA, and regulate target genes and pathways including the NF-κB, Fas-FasL, JAK-STAT, IRE1-RIDD, and mTOR pathways. By regulating gene expression, miRNAs affect T cell differentiation to diverse cell types, including Th17 and T-reg cells, and thus constitute promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the novel opportunities to combine these with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) to provide accurate diagnosis and prognosis, especially for seronegative patients. Furthermore, we outline how functional genetic variants of miR-499 and miR-146a partly explain the unmet susceptibility to RA. Additionally, we review the evidence implicating miRNAs as promising biomarkers of efficiency, response, and resistance to disease-modifying anti-rheumatic drugs (DMRDs) and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.

Microalgae are a source of carotenoids, phycocyanin, phenol, amino acids, polyunsaturated fatty acids, sulfated polysaccharides, pigments, and other bioactive molecules with antimicrobial, antioxidant, antiviral, antitumor, anti-inflammatory, and fat-burning properties. The increasing incidence of infectious processes, including tuberculosis, caused by antimicrobial resistant strains of microorganisms necessitates the search for alternative sources of compounds with antimicrobial activity, including microalgae. In this study, the antimicrobial properties of marine and freshwater microalgae extracts were evaluated against Gram-positive (Staphylococcus aureus, Enterococcus faecalis, and Streptococcus pyogenes) and Gram-negative (Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa), Mycobacterium tuberculosis strain H37Rv and Mycobacterium smegmatis. Water, dimethyl sulfoxide, and ethanol were used as extractants. The obtained microalgae extract exhibited cytotoxicity against splenocytes and, to a lesser extent, against peritoneal macrophages of CBA mice. The bacteriostatic effect of the microalgae extracts against bacteria and mycobacteria was demonstrated by MTT test. In addition, activation of bacterial and mycobacterial growth was observed in a number of cases with high levels of microalgae extracts in the medium. In an expression model of tuberculosis in mice, a decrease in mycobacterial load in the lungs and spleen was observed. Thus, microalgae have moderate to weak antimicrobial activity.

Staphylococcus aureus is a microorganism frequently associated with implant-related infections, owing to its ability to produce biofilms. These infections are difficult to treat because antimicrobials must cross the biofilm to effectively inhibit bacterial growth. Although some antibiotics can penetrate the biofilm and reduce the bacterial load, it is important to understand that the results of routine sensitivity tests are not always valid for interpreting the activity of different drugs. In this review, a broad discussion on the genes involved in biofilm formation, quorum sensing, and antimicrobial activity in monotherapy and combination therapy is presented that should benefit researchers engaged in optimizing the treatment of infections associated with S. aureus biofilms.

The global spread of multidrug-resistant (MDR) microbial infections is currently one of the most severe risks to global public health, with 10 million fatalities expected by 2050 unless action is taken. Nanotechnology has revolutionized science and medicine. The reliance on nanotechnology is growing. Nanoparticles have distinct properties that improve biological, chemical, and physical properties studied for various uses. A significant area of attention in the synthesis of nanoscale modulators is the utilization of crude formulations, retro-synthesized, and pure chemicals, mainly from herbal sources, with fewer adverse effects. Green chemistry has devised a tangential technique for synthesizing metals and metal oxides to produce nanoparticles. Plant extracts (leaves, stems, and shoots) and microorganisms (bacteria, fungus, and yeast) are used as reducing intermediates to make nanoparticles. Studies in microbiology have shown that nanoparticles kill bacteria, fungi, viruses, and protozoa. These green nanoparticles contain antibacterial, antifungal, and anti-inflammatory effects. Most nanoparticles have high antibacterial properties, indicating they may be used to combat diseases and biological contaminants. These nanoparticles have antibacterial action against pathogenic microorganisms that cause serious illnesses, including multidrug-resistant pathogens. The current research will pave the way for future applications and improved methods for producing nanoparticles, paving the way for an innovative route in nano-life sciences with widespread recognition.

The members of the Liliaceae family have been regarded as an excellent source of biologically active compounds. However, the work on antimicrobial potential and characterization of the bioactive fractions of Lilium philadelphicum flower is limited and needs to be explored. The present study reports the antimicrobial potential, anti-inflammatory and anticancer potential of the bioactive fraction extracted from the flower of L. philadelphicum (Red Lily) and characterization of these bioactive compounds. The antimicrobial activity was tested against nine different Gram-positive and Gram-negative bacterial strains. The minimum inhibitory concentration (MIC) values of methanolic extract of L. philadelphicum flower against Acinetobacter bouvetii, Achromobacter xylosoxidans, Bacillus subtilis MTCC 121, Candida albicans MTCC 183, Klebsiella pneumoniae MTCC 3384, and Salmonella typhi MTCC 537 were 25, 50, 12.5, 50, 100 and 50 μg mL-1, respectively. The phytochemical analysis of the extract reveals the presence of phenols, flavonoids, tannins, terpenoids, glycosides, coumarins, and quinones. The cytotoxicity of the partially purified compound against the HepG2 cell line in MTT assay demonstrates up to 90% cell viability with a bioactive compound concentration of 50 μg/ml. However, with the increase in bioactive compound concentration up to 1000 μg/ml results into nearly 80% cell viability, just a minor decline in cell viability suggests the importance of bioactive compounds for suitable therapeutic applications. Spectroscopic studies of the bioactive compound by UV-Visible spectroscopy, FT-Infra Red spectroscopy, Gas Chromatography-Mass Spectrometry (GCMS) as well as its phytochemical analysis suggests the presence of terpenoids moiety, responsible for the antimicrobial property of L. philadelphicum flower.

The development of new and effective antimicrobial compounds is an urgent need with the emergence of resistant bacteria. Natural plant flavonoids are known to be effective molecules but their activity and selectivity have to be increased. Based on previous aurone potency, we designed new aurone derivatives bearing acetamido and amino groups at the position 5 of the A ring and managing various monosubstitutions at the B ring. A series of 31 new aurone derivatives were first evaluated for their antimicrobial activity with five derivatives being the most active (compounds 10, 12, 15, 16, and 20). The evaluation of their cytotoxicity on human cells and of their therapeutic index (TI) showed that compounds 10 and 20 have the highest TI. Finally, screening against a large panel of pathogens confirmed that compounds 10 and 20 possess a large spectrum antimicrobial activity, including on bioweapon BSL3 strains, with MIC values as low as 0.78 µM. These results demonstrate that 5-acetamidoaurones are far more active and safest compared with 5-aminoaurones, and that benzyloxy and isopropyl substitutions at the B ring are the most promising strategy in the exploration of new antimicrobial aurones.

Ticks transmit a wide variety of pathogens including bacteria, parasites and viruses. Over the last decade, numerous novel viruses have been described in arthropods, including ticks, and their characterization has provided new insights into RNA virus diversity and evolution. However, little is known about their ability to infect vertebrates. As very few studies have described the diversity of viruses present in ticks from the Caribbean, we implemented an RNA-sequencing approach on Amblyomma variegatum and Rhipicephalus microplus ticks collected from cattle in Guadeloupe and Martinique. Among the viral communities infecting Caribbean ticks, we selected four viruses belonging to the Chuviridae, Phenuiviridae and Flaviviridae families for further characterization and designing antibody screening tests. While viral prevalence in individual tick samples revealed high infection rates, suggesting a high level of exposure of Caribbean cattle to these viruses, no seropositive animals were detected. These results suggest that the Chuviridae- and Phenuiviridae-related viruses identified in the present study are more likely tick endosymbionts, raising the question of the epidemiological significance of their occurrence in ticks, especially regarding their possible impact on tick biology and vector capacity. The characterization of these viruses might open the door to new ways of preventing and controlling tick-borne diseases.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

Antibiotics are commonly used to treat infectious diseases. However, massive and inappropriate antibiotics usage cause many problems including the emergence and spread of antibiotic-resistant bacteria. To avoid this issue, in modern countries the interest of using probiotics in feed supplementation to promote health and prevent or treat intestinal infectious diseases in companion animals like dogs has been increasing. We evaluate the probiotic potential of Lactobacilli isolated from healthy dogs faeces. The isolated Lactobacilli were first confirmed by 16SrRNA sequencing, then in vitro tests were conducted to assess survival potential of Lactobacilli under simulated gastrointestinal conditions and adhesion ability to gut epithelia, effects on epithelial barrier function, anti-inflammatory activities, effects on defensin peptides (beta-defensin 3) and inhibitory effects on common pathogens. Lactobacilli showed considerable potential to survive in simulated gastrointestinal environmental conditions, low pH, high bile salt concentrations along with good adhesion properties with MODE-K cells. Pathogenic bacterial growth and their adhesion to MODE-K cells was significantly inhibited by Lactobacilli. Real-time PCR analyses further demonstrated that L. acidophilus strain AR1 and AR3 inhibit Salmonella-induced proinflammatory cytokines (IL-6, IL-8, 1ꞵ) production and reinforce expression of tight junction protein (occludin). None of the strain induce mRNA expression of beta-defensin 3 in MODE-K cells. Based on in vitro results the L. acidophilus strain AR1 has potential to be supplemented in canine feed. However, further in vivo studies investigating health-promoting effects are awaited.

Analyzing urban-rural spatial structures and changes are of great significance for under-standing the urban-rural relationship evolution. While previous studies mostly focused on the urban internal spatial structure evolution, less from the regional scale to explore the urban and rural evolution. Here, taking Dezhou city, a rapidly urbanization city in China as a case study, we employed the local contour tree method and nighttime light data to map urban and active rural regions’ range during 2012-2020, and further explored the respective development processes of them. This study found that different from rural regions, internal structures of urban regions are more complex, and there are often multiple hot spots inside them. The urban-rural regions’ area had increased significantly by 39.3% during 2012-2020 (p&lt;0.05). The urban and rural region rankings of the identified counties are basically consistent with the urban and rural population rankings. Particularly, different from perspectives of earlier land use (i.e., built-up land or impervious surface), this study identified urban and active rural regions in view of the scope of active human activities. This study therefore found populations were greatly responsible for affecting changes of urban and active rural region structures. These findings could be helpful for understanding urban-rural dynamics.

Background and Objectives: The existing recommendations for female pelvic magnetic susceptibility weighted imaging MRI (FP-SWI) have not been optimized to capture the disease characteristics of the female pelvis. Therefore, it is imperative to explore acquisition parameters before conducting larger-scale studies. To establish optimized flip angle (FA) for acquiring FP-SWI to improve the image quality of female pelvic lesion sites. Materials and Methods: To evaluate signal quality and lesion conspicuity, regions of interest (ROIs) were manually drawn within the lesion on SWI sequences. Signal intensity was measured within the ROIs. Additionally, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for SWI sequences acquired at three FA: 10°, 15°, and 20°. Finally, a qualitative assessment of anatomical detail visualization, geometric distortion extent, artifacts, and lesion clarity was performed using a four-point scale. The Wilcoxon rank sum test was employed to compare the qualitative evaluation parameters. The intra-class correlation coefficient (ICC) was calculated to determine the consistency of subjective ratings between two observers. Results: FA=10° showed significantly higher SNR than FA=15° and 20° in most anatomical regions (P&lt;0.05), while the CNR was significantly higher than FA=15° and 20° (P&lt;0.05). Compared with FA=15° and 20°, the image quality of FA=10° was significantly higher, with less distortion and ghosting, and better image contrast (P&lt;0.05). Lesions with FA=10° exhibited higher clarity compared to FA=15° and 20° (P&lt;0.05). Conclusions: The image quality of FP-SWI images at FA=10° exceeds that at FA=15° and 20°. We recommend that when conducting SWI examination of the female pelvic cavity, the FA value should be set at 10° to stabilize the SWI sequence and improve image quality.

Poplars (Populus spp.) are of significant ecological and economic importance. Long-term breeding efforts were aimed mainly at obtaining fast-growing and productive plants and less considered resistance to pests. This study aimed to identify the patterns of susceptibility to Saperda carcharias (Linnaeus, 1758) (Coleoptera: Cerambycidae) among Populus hybrids and pure species, considering crossing combinations and some other traits. In our research, 35 clones of poplar species and hybrids of the Ukrainian and foreign selection from the Aigeiros, Tacamahaca, and Leucoides sections were tested in 2021 and 2023 in the plantation created in 2014 in Eastern Ukraine. S. carcharias preferred infesting clones with earlier foliage development, larger diameters, and height increments. Specifically, hybrids with American maternal lineage showed the highest susceptibility, whereas those with European maternal lineage or Asian origin displayed lower infestation levels or resistance, respectively. This variability suggests a complex relationship between genetic background and pest resistance, underlining the need for a deeper understanding of the factors influencing susceptibility to S. carcharias. Selecting native species clones or creating mixed clone plantations could enhance the resilience of poplar plantations to pest threats.

Diabetes is a major risk factor for tuberculosis (TB). Diabetes increases the risk of progression from latent tuberculosis infection (LTBI) to active pulmonary TB and TB patients with diabetes are at greater risk of more severe disease and adverse TB treatment outcomes compared to TB patients without co-morbidities. Diabetes is a complex disease characterized not only by hyperglycemia but also various forms of dyslipidemia. However, the relative contribution of these underlying metabolic factors to increased susceptibility to TB are poorly understood. This review summarizes our current knowledge on epidemiology and clinical manifestation of TB and diabetes comorbidity. We subsequently dissect the relative contribution of body mass index, hyperglycemia, elevated cholesterol and triglycerides on TB disease severity and treatment outcomes. Lastly, we discuss the impact of selected glucose and cholesterol lowering treatments frequently used in the management of diabetes on TB treatment outcomes.

Fighting against the COVID-19 pandemic caused by the SARS-CoV-2 virus is one of the most critical challenges facing the global health system today. The possibility to identify the group of persons in the cohort of people under 50 years old, who are sensitive to the COVID-disease by non-invasive methods, is a very perspective approach for estimating the epidemiological state of the human population. The study aimed to identify the features of people's faces with COVID-19 that the most correlate with disease severity could serve as one of these approaches. For this aim, 525 photos of patients' faces with different outcomes of COVID-19 disease were analyzed using the Dlib face recognition convolutional neural network pre-trained for face recognition. Face descriptor vectors were obtained using the convolutional neural network. Facial features were found that predict a person's sensitivity to the SARS-CoV-2 virus (disease severity), and the contribution of each of the features to the risk of developing a severe form of COVID in a person was found. The accuracy of the binary classification of the individual severity of the COVID-19 course using the k-nearest neighbors algorithm on the test dataset was accuracy - 84%, AUC - 0.90.

Background: Cigarette smoking (CS) is a global public health problem and a high-risk factor for various diseases. In December 2019, a novel coronavirus (HCoV-19) was identified in Wuhan, China. Because ACE2 has been identified as a receptor for HCoV-19, we hypothesize that CS affects the expression pattern of ACE2 in respiratory tract, causing differences in susceptibility to the virus. Methods: Three datasets (GSE994, GSE17913, and GSE18344), were downloaded from the Gene Expression Omnibus (GEO) database. Correlation and enrichment analysis were used to evaluate the function of ACE2. Also, the different expression of ACE2 in different groups of three datasets were analyzed. Results: Genes associated with ACE2 were enriched in important biological processes such as viral processes and immune response. Elevated ACE2 were found in intrapulmonary airways (GSE994) and oral epithelial cells (GSE17913) of smokers but not those of non-smokers or former smokers. Significant dose- and time-dependent relationships between CS and ACE2 expression were observed in mouse lung tissues, and long periods without smoking were found to significantly reduce ACE2 expression. Conclusions: Both human and rat data confirmed that CS could induce increased ACE2 in the respiratory tract, indicating that smokers have a higher susceptibility to HCoV-19.

Abstract: Objective: The aim of the study was to identify dietary patterns and its association with socio-economic, dietary and lifestyle practices among adolescents in Malaysia. Methods: A validated food frequency questionnaire was used to assess dietary patterns. Results: Multivariate analyses show that age and physical activity (PA) levels were emerged as positive determinants of healthy-based food pattern in Malay (All, p<0.001), whereas higher consumption of eating-out from home (EatOut) and fast food (All, p<0.05) were negative determinants. High weekly breakfast skipping (p<0.001) and EatOut (p<0.01) were positively associated with a western-based pattern, whereas age (p<0.001) and household income (p<0.05) were negative determinants. Higher frequency of daily snacking (p<0.05) was emerged as positive determinant of local-based food pattern. For Chinese adolescents, age (p<0.001), PA levels (p<0.001) and maternal education level (p<0.05) emerged as positive determinants for the healthy-based pattern, whereas high EatOut and fast food intakes (All, p<0.01) were negative determinants. Higher weekly consumption of EatOut (p<0.01), fast food (p<0.05) and carbonated beverages (p<0.05), and daily snacking practice (p<0.01) were positively associated with higher western-based food pattern, whereas age (p<0.01) was inversely associated. Conclusion: These findings suggest that unhealthy dietary and lifestyle practices could increase the risk of adherence to unhealthy western-based food pattern that is high in fat, sugar and salt contents, and consequently increase the risk of developing obesity and metabolic-related disorders during these critical years of growth.

We present a first formal analysis of specific and complete local integration. Complete local integration was previously proposed as a criterion for detecting entities or wholes in distributed dynamical systems. Such entities in turn were conceived to form the basis of a theory of emergence of agents within dynamical systems. Here, we give a more thorough account of the underlying formal measures. The main contribution is the disintegration theorem which reveals a special role of completely locally integrated patterns (what we call ι-entities) within the trajectories they occur in. Apart from proving this theorem we introduce the disintegration hierarchy and its refinement-free version as a way to structure the patterns in a trajectory. Furthermore we construct the least upper bound and provide a candidate for the greatest lower bound of specific local integration. Finally, we calculate the i-entities in small example systems as a first sanity check and find that ι-entities largely fulfil simple expectations.

The goal of this study was to determine the relative susceptibility of four common equine wound pathogens to ten different types of antimicrobial agents based on minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Additionally, to describe the comparison of bactericidal activity of medical grade Manuka honey, local honey, and commercial, food-grade honey to other commonly used wound dressings. The objective is to provide veterinary practitioners with comparative data on the use of a variety of antimicrobial dressings for inhibiting growth of common wound bacteria. MIC and MBC for Manuka, store, and local honeys were comparable to those of sterile gauze, sugar, and hypertonic saline. Across bacterial species, local honey proved to have more bactericidal activity when compared to Manuka and commercial, food-grade honey. The MIC and MBC for PHMB gauze and foam was consistently at a higher dilution compared to the other antimicrobials. The majority of antimicrobials exhibited stronger inhibitory and bactericidal activity against a Streptococcus zooepidemicus isolate obtained from a wound compared to other bacteria that were ATCC lab acclimated. Additional research for in-vivo applications needs to be done to see whether differences exist in effective wound management.

Background: Tuberculosis (TB) manifests itself primarily in the lungs as pulmonary disease (PTB) and sometimes disseminates to other organs to cause extra-pulmonary TB, such as lymph node TB (LNTB). This study aimed to investigate the role of host genetic polymorphism in immunity related genes to find a genetic basis for such differences. Methods: Sixty-three, Single nucleotide polymorphisms (SNPs) in twenty-three, TB-immunity related genes including eleven innate immunity (SLCA11, VDR, TLR2, TLR4, TLR8, IRGM, P2RX7, LTA4H, SP110, DCSIGN and NOS2A) and twelve cytokine (TNFA, IFNG, IL2, Il12, IL18, IL1B, IL10, IL6, IL4, IL1RA, IL8 and TNFB) genes were investigated to find genetic associations in both PTB and LNTB as compared to healthy community controls. The serum cytokine levels were correlated for association with the genotypes. Results: PTB and LNTB showed differential genetic associations. The genetic variants in the cytokine genes (IFNG, IL12, IL4, TNFB and IL1RA and TLR2,4 associated with PTB susceptibility and cytokine levels but not LNTB (p &lt; 0.05). Similarly, genetic variants in LTA4H, P2RX7, DCSIGN and SP110 showed susceptibility to LNTB and not PTB. Pathway analysis showed abundance of cytokine related variants for PTB and apoptosis related variants for LNTB. Conclusions: PTB and LNTB outcomes of TB infection have a genetic component and should be considered for any future susceptibility and functional studies.