Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.

The mosquito microbiota reduces the vector competence of Anopheles to Plasmodium and affects host fitness, it is therefore considered as a potential target to reduce malaria transmission. While immune induction, secretion of antimicrobials and metabolic competition are three typical mechanisms of microbiota-mediated protection against invasive pathogens in mammals, the involvement of metabolic competition or mutualism in mosquito-microbiota and microbiota-Plasmodium interactions has not been investigated. Here, we describe a metabolome analysis of the midgut of An. coluzzii provided with a sugar-meal or a blood-meal, under conventional or antibiotic-treated conditions. We observed that the antibiotic treatment affects the tricarboxylic acid cycle and nitrogen metabolism, notably resulting in decreased abundance of free amino acids. Linking our results with published data, we identified candidate pathways which may participate in microbiota/Plasmodium interactions via metabolic interactions or immune modulation.

Epithelial surfaces in humans are home to symbiotic microbes (i.e., microbiota) that influence the defensive function against pathogens depending on the health of the microbiota. Healthy microbiota contribute to the well-being of their host in general (e.g., via the gut-brain-axis), and their respective anatomical site in particular (e.g., oral, urogenital, skin or respiratory microbiota). Despite efforts towards a more responsible use of antibiotics, they are often prescribed for uncomplicated, self-limiting infections and can have a substantial negative impact on the gut microbiota. Treatment alternatives such as non-steroidal anti-inflammatory drugs may also influence the microbiota and thus can have lasting adverse effects. Herbal drugs offer a generally safe treatment option for uncomplicated infections of the urinary or respiratory tract. Additionally, their microbiota preserving properties allow for a more appropriate therapy of uncomplicated infections without contributing to an increase in antibiotic resistance or disturbing the gut microbiota. Here, herbal treatments may be a more appropriate therapy with a generally favorable safety profile.

: Microplastics and nanoplastics (MNPs) are becoming an increasingly severe global problem due to their widespread distribution and complex impact on living organisms. Apart from their environmental impact, the effects of MNPs on living organisms have also continued to attract attention. The harmful impact of MNPs has been extensively documented in marine invertebrates and larger marine vertebrates like fish. However, the research on the toxicity of these particles on mammals is still limited, and their possible effects on humans are poorly understood. Considering that MNPs are commonly found in food or food packaging, humans are primarily exposed to them through ingestion. It would be valuable to investigate the potential harmful effects of these particles on gut health. This review focuses on recent research exploring the toxicological impacts of micro- and nanoplastics on the gut, as observed in human cell lines and mammalian models. Available data from various studies indicate that the accumulation of MNPs in mammalian models and human cells may result in adverse consequences, in terms of epithelial toxicity, immune toxicity, and disruption of gut microbiota. The paper also discusses the current research limitations and prospects in this field, aiming to provide a scientific basis and reference for further studies on the toxic mechanisms of micro- and nanoplastics.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as the Broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml. In contrast, it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. The maximum concentration was 7-8 mcg/ ml at a maximum time of 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the bactericidal antibiotic Myxopyronin A production from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Antibiotics are released into the environment either directly in an unchanged form or in a partially metabolized form. The discharge is usually through untreated waste or industrial treatment effluents. The potential concern is the uptake of these antibiotics by crops irrigated by treated wastewater. This study collected wastewater from eight points at the Pagla, Kadamtali, Dhaka treatment plant. Here we consider three crucial antibiotics, Doxycycline, Ciprofloxacin, and Tetracycline, used mainly during the last two years of the pandemic. A PDA detector was used in high-performance liquid chromatography (HPLC) analysis to determine the raw and processed effluent antibiotics. The most frequently seen antibiotics in natural wastewater were Doxycycline and Ciprofloxacin, with the highest concentration of 0.23µgL-1and 0.20 µgL-1(raw water), respectively. Tetracycline was not detected in natural water. Contrarily, Doxycycline was discovered in the Pagla plant's completed water and had the highest concentration (0.12 gL-1), whereas Ciprofloxacin and Tetracycline were not found in the dead water. The findings of this study showed that Doxycycline was still present in both the raw and processed effluent. Both natural and finished wastewater was subjected to a microbial-resistant test in the presence of all three antibiotics. The results revealed that the samples detected both heterotrophic bacteria and total coliform. The viable aerobic heterotrophic bacteria ranged between 5.421 and 4.754 log cfu/ml. Total bacteria load gradually decreased in the finished wastewater.

Bacterial resistance to antibiotics is a growing global concern, threatening human and environ-mental health, particularly among urban populations. Wastewater treatment plants (WWTPs) are thought to be “hotspots” for antibiotic resistance dissemination. The conditions of WWTPs, in conjunction with the persistence of commonly used antibiotics, may favor the selection and trans-fer of resistance genes among bacterial populations. WWTPs provide an important ecological niche to examine the spread of antibiotic resistance. We used heterotrophic plate count methods to identify phenotypically resistant cultivable portions of these bacterial communities and charac-terized the composition of the culturable subset of these populations. Resistant taxa were more abundant in raw sewage and wastewater before the biological aeration treatment stage. While some antibiotic resistant bacteria (ARB) were detectable downstream of treated wastewater re-lease, these organisms are not enriched relative to effluent-free upstream water, indicating effi-cient removal during treatment. Combined culture-dependent and culture-independent analyses revealed a stark difference in community composition between culturable fractions and the envi-ronmental source material, irrespective of culturing conditions. Higher proportions of the envi-ronmental populations were recovered than predicted by the widely accepted 1% culturability paradigm. These results represent baseline abundance and compositional data for ARB commu-nities for reference in future studies addressing the dissemination of antibiotic resistance associ-ated with urban wastewater treatment ecosystems.

The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC₁₀ and EC₂₅ values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.

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.

The first half of the 20th century was noteworthy for the introduction of a unique group of drugs – antibiotics. It drastically changed concepts of infectious diseases treatment, which for centuries remained a scourge of the human population. With improvement of the antibiotic treatment efficacy, humanity has faced the problem of a dramatic increase in antibiotic resistance in bacteria. The COVID-19 pandemic has only exacerbated the problem and posed a new challenge to the medical community in finding solutions, both clinical and organizational and methodological, to fight antibiotic resistance widespread all over the globe. This publication covers some aspects of evolutionary processes in either pathogens or diseases, including ethical perspective.

Background: Bacteria can survive antibiotic exposure by mechanisms like tolerance without a shift in antimicrobial susceptibility. In this study, we investigated the presence of tolerance to three antimicrobials, ceftriaxone (CRO), azithromycin (AZM), and ciprofloxacin (CIP), in clinical isolates and WHO reference panel of N. gonorrhoeae and explored the prevalence between urogenital and anorectal infection sites. Methods: We examined 66 N. gonorrhoeae clinical isolates, evenly divided between anorectal and urogenital infection sites, using a modified tolerance disk (TD test) for three antibiotics. The isolates underwent a three-step incubation process wherein the isolates were exposed to an antibiotic disc for 20 hours of incubation (Step I), followed by the replacement of the antibiotic disc with a nutrient disc for overnight incubation (Step II) and additional overnight incubation with extra nutrients (Step III). Results: Four isolates were lost due to contamination. Of 62 clinical isolates, 7 exhibited tolerance to AZM, with 6 from anorectal and 1 from urogenital sites (p = 0.0496). Tolerance to CRO was observed in 11 isolates, which was significantly associated with the infection site, with 9 from the anorectum, and 2 from the urogenital site being tolerant (p = 0.02). Tolerance to CIP was found in 11 isolates, but was not significantly associated with the infection site. Tolerance was also detected in 8 (K, M, N, O, P, U, V, W) out of the 14 WHO (World Health Organization) reference strains, with varying patterns of tolerance to CRO (n=8), CIP (n=2) and AZM (n=1). Conclusion: This study identified CRO, AZM, and CIP tolerance in clinical Neisseria gonorrhoeae isolates. Significant variations in tolerance proportions between anorectal and urogenital infection sites, particularly for CRO, were observed. Additionally, tolerance was detected in WHO reference strains.

The over use of pharmaceutical compounds, essentially antibiotics, led to an increase of their concentrations in aquatic ecosystems. In this study, the white-rot fungus Coriolopsis gallica (high-laccase-producing fungus) was investigated for the biodegradation of ampicillin (AMP) under different cultivation conditions. The biotransformation of the antibiotic was confirmed by means of high-performance liquid chromatography (HPLC), and the antibacterial activity was evaluated via the bacterial growth inhibition agar well diffusion method using Escherichia coli as an ampicillin-sensitive test strain. The results showed that AMP (50 mg L-1) was totally removed by C. gallica after 6 days of incubation in a liquid medium. The antibiotic removal rate was maximal with a fungal culture aged 9 days. Such a culture achieved the removal of a higher concentration of up to 500 mg L-1 of ampicillin in 3 days. This higher antibiotic removal rate was concomitant with the maximal laccase production in culture supernatant. In addition, four consecutive doses of 500 mg L-1 of ampicillin were transformed by the same fungal culture in 24 days. After that, the fungus was unable to remove the antibiotic. The measurement of ligninolytic enzyme activity showed that laccase of C. gallica might participate in the biotransformation of AMP.

Methicillin-resistant Staphylococcus aureus (MRSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhancing the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 0.009-0.013 μg/mL and MBIC50 values ranging from 0.008-0.012 μg/mL, in planktonic and biofilm bacteria, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. Obtained data proved the superior therapeutic effectiveness of RFB formulations compared to Control and VCM groups even using a two-fold lower therapeutic dose as demonstrated by significantly reduced bacterial burden and growth index values in major organs. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

Pseudomonas aeruginosa is an antibiotic-resistant priority pathogen as listed by the World Health Organization. P. aeruginosa, a gram-negative, rod-shaped bacterium, is frequently encountered in hospital settings as an opportunistic pathogen in nosocomial infections. P. aeruginosa has shown high antibiotic resistance, which has been attributed to several mechanisms, such as intrinsic, acquired, and adaptive resistance. This study investigates several genes which may be attributed to the acquisition of antibiotic resistance in the bacteria P. aeruginosa, as it transitions from its planktonic form to the more threatening and resistant biofilm form. Subsequently, the study assesses the comparative efficacy of three antibiotics, Ofloxacin (OFX), Tobramycin (TOB), and Ceftazidime (CAZ), in altering the expression levels of the identified multidrug efflux pump genes associated with the ability to extrude antibiotics from the cell when in the biofilm form. Efflux transporter gene expression in P. aeruginosa was conducted via extraction of total RNA in planktonic and biofilm- both untreated and treated - with Tobramycin (TOB), Ofloxacin (OFX), and Ceftazidime (CAZ). Real-time quantitative reverse transcriptase PCR was employed to analyze alterations in expression levels of the Mex A, Mex B, Mex X, Mex Y, OprM, and RPSL genes in the collected samples. In samples where no antibiotics were administered, an increase in expression of the Mex B efflux pump gene was observed compared to all other efflux pump genes in the biofilm form, providing multidrug resistance when active. The gene of interest, Mex B, was assessed for antibiotic resistance by P. aeruginosa culturing in the planktonic and biofilm forms with simultaneous treatment with TOB, OFX, and CAZ. Of the three antibiotics used, OFX showed more effectiveness in preventing biofilm growth by reducing the expression level of the Mex B efflux pump gene in the biofilm form, making P. Aeruginosa more antibiotic sensitive to OFX. TOB has similar results compared to OFX but was slightly less effective in reducing the expression of Mex B. Conversely, CAZ was not effective in reducing expression of the Mex B gene in the biofilm form or the planktonic form and was determined to be ineffective at eradicating the organism.

Bacteria that have become resistant to antibiotics, also known as superbugs,pose a huge threat to the human population. This is because these developed resistance to antibiotics. Antibiotics are a type of medicine that fights bacteria by either killing it or preventing it from growing. Although antibiotics make the once deadly now easily treatable, they can become ineffective as bacteria develop resistance to the antibiotic, causing diseases to become potentially fatal once more. Thus, scientists are rushing to find solutions in this arms race against evolving bacteria by either evolving current antibiotics or discovering new stands to fight evolving bacteria. In order to discover whether bacteria can develop resistance to household antibiotics, a controlled experiment was conducted. This was done by growing bacteria on agar plates with antibiotic ointments applied (in dilution series) to see if antibiotic resistance could build. Theorizing that by lowering the concentration of over the counter antibiotics, resistant bacteria would be selected and my bacterial population would evolve antibiotic resistance.In conclusion of the experiment antibiotic resistance did appear as a trait, but the level of it was inconsistent across the different bacteria populations.

Tellurium exhibits exceptional intrinsic electronic properties. However, investigations into the modulation of tellurium's electronic properties through physical modification are notably scarce. Here, we present a comprehensive study focused on the evolution of the electronic properties of tellurium crystal flakes under plasma irradiation treatment by employing conductive atomic force microscopy and Raman spectroscopy. The plasma-treated tellurium experienced a process of defect generation through lattice broken. Prior to the degradation of electronic transport performance due to plasma irradiation treatment, a remarkable observation emerged: in the low-energy region of hydrogen plasma-treated tellurium, a notable enhancement in conductivity was unexpectedly detected. The mechanism underlying this enhancement in electronic transport performance was thoroughly elucidated by comparing it with the electronic structure induced by argon plasma irradiation. This study not only fundamentally uncovers the effects of plasma irradiation on tellurium crystal flakes, but also unearths an unprecedented trend of enhanced electronic transport performance at low irradiation energies when utilizing hydrogen plasma. This abnormal trend bears significant implications for guiding the prospective application of tellurium-based 2D materials in the realm of electronic devices.

Developing countries are confronted with general issues of municipal wastewater management and treatment. Untreated faecal sludges and wastewaters from septic tanks and traditional toilet are rejected into rivers and sometimes using for urban agriculture without any treatment to reduce the biorisk. Consequently, there are potential environmental and public health risks. In this study, a wastewater treatment plant prototype coupled with Moringa Oleifera seeds treatment was developed to evaluate their effectiveness for the reduction of faecal indicator bacteria and antibiotics resistant bacteria in domestic wastewater. Results indicate that our performed prototype system presents high capacity to reduce bacteria with abatements up to 99.34%. High reductions of bacteria load were obtained after add of Moringa Oleifera seeds into waters, with reductions varied from 36.6-78.8% for E. coli, 28.3-84.6% for Faecal coliform, 35.3-95.6% for Vibrio cholerae and 32.1-92.4% for total flora. Same effects of Moringa Oleifera seeds were noted for reducing antibiotic resistant bacteria, Extended Spectrum Beta-lactamases and Carbapenem-Resistant Enterobacteriaceae with abatements up to 98% for E. coli and faecal coliform, 100% for Vibrio cholerae and 91.96% for total flora. Our results supported high capacity of Moringa Oleifera seeds as an excellent alternative for pathogens and antibiotics resistant bacteria reduction/purification from domestic wastewater

High hopes were associated with the new anti-angiogenic medicament, bevacizumab, which due to the possibility of binding to isoform A of vascular endothelial growth factor (VEGF), inhibited the creation of new blood vessels. However, not only blood vessels are responsible for the tumor cells' spread. During the process of tumor growth, lymphangiogenesis is mediated by other isoforms of the VEGF family, specifically VEGF-C and VEGF-D, which are independent of the bevacizumab action. Therefore, based on the mechanism of bevacizumab action and the processes of angio- and lymphangiogenesis, we formed three hypotheses: 1) if the lymph nodes in the primary ovarian cancers are metastatic, the outcome of bevacizumab treatment is worsened; 2) concerning the second-line treatment, bevacizumab will act in a weakened manner if the recurrence occurs in lymph nodes compared to local recurrences; 3) patients treated by bevacizumab are more likely to have recurrences in lymph nodes. These hypotheses raise the issue of the existing gap of knowledge, which concerns the effect of bevacizumab on the metastatic lymph nodes.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

The development of computational acoustics allows simulation of sound generation and propagation in complex environment. In particular, meshfree methods are widely used to solve acoustics problems through arbitrarily distributed field points and approximation smoothness flexibility. As a Lagrangian meshfree method, smoothed particle hydrodynamics (SPH) method reduce the difficulty in solving problems with deformable boundaries, complex topologies, or multiphase medium. The traditional SPH method has been applied in acoustic simulation. This study presents the corrective smoothed particle method (CSPM), which is a combination of SPH kernel estimate and Taylor series expansion. The CSPM is introduced as a Lagrangian approach to improve accuracy in solving acoustic wave equations in the time domain. Moreover, a boundary treatment technique based on the hybrid meshfree and finite difference time domain (FDTD) method is proposed to represent different acoustic boundaries with particles. To model sound propagation in pipes with different boundaries, soft, rigid, and absorbing boundary conditions are built with this technique. Numerical results show that the CSPM algorithm is consistent and demonstrates convergence with exact solutions. Main computational parameters are discussed, and different boundary conditions are validated to be effective for benchmark problems in computational acoustics.

Electrochemical methods are used for the treatment of both municipal and industrial wastewater, either independently or in conjunction with biological methods. This conjunction is used for pretreatment or posttreatment of biologically treated wastewater. In our work, we focused on the combination of these processes, where pre-electrolysis was used to produce dissolved iron before the activation process. Electrolysis was also directly introduced into the activation using either iron or carbon electrodes. The surface of one iron electrode was 32.2 cm2, the applied voltage was 21 V, and the supplied current was 270 mA. The surface of one carbon electrode was 7.54 cm2, the supplied current was 82.5 mA, and the applied voltage was 21 V. From laboratory research on the treatment of synthetic municipal wastewater using a combination of electrolysis and activation processes, it resulted that the use of iron electrodes increased the efficiency of phosphorus removal compared to its precipitation with iron salts. The electrolysis had a positive effect on the sedimentation properties of sludge and the destruction of filamentous microorganisms. Electrolysis negatively affected the respiration rates of activated sludge and the efficiency of denitrification. However, it did not have a negative impact on the nitrification activity of the sludge.

In this work, the resistance/susceptibility (R/S) profile of Staphylococcus equorum strains (n=30) from cheese to 16 antibiotics was determined by broth microdilution. The minimum inhibitory concentration (MIC) for all antibiotics was low in most strains, although higher MICs compatible with acquired genes were also noted. Genome analysis of 13 strains showed the S. equorum resistome to be composed of intrinsic mechanisms, acquired mutations, and acquired genes. However, the genetic data did not always correlate with the phenotype. As such, a cat gene providing resistance to chloramphenicol was found on a plasmid in one strain; this was able to provide resistance to Staphylococcus aureus after electroporation. An msr(A) polymorphic gene was identified in five strains. The Mrs(A) variants were associated with variable resistance to erythromycin. All strains harboured a polymorphic fosB/fosD gene, although only one acquired copy was associated with strong resistance to fosfomycin. Similarly, a plasmid-associated blaR1-blaZI operon encoding a penicillinase was identified in five ampicillin- and penicillin G-susceptible strains. Identified genes not associated with resistance further included mph(C) in two strains and norA in all strains. The antibiotic R/S status and gene content of S. equorum strains intended to be employed in food systems should be carefully determined.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

The exponential rise of bacterial resistance poses a threat to antibiotic efficacy, with a great impact on public health. This study aims to analyze the correlation between antibiotic consumption and the emergence of bacterial resistance. Conducted retrospectively at Charles Nicolle Hospital in Tunis, Tunisia from 2010 to 2022, this study was based on STKMED® software for antibiotic consumption data, hospital administrative records for the number of hospitalization days, and SIRSCAN® software for bacteriological data. Data processing was performed using Excel® software, and analysis was conducted using SPSS23®. In 2022, Consumption was almost evenly split between the two major “AWaRe” groups, with 49.33% for "Access" and 46.89% for "Watch", and the consumption of the "Reserve" group also increased, accounting for 3.77% of the total. Bacterial resistances, notably carbapenem-resistant Klebsiella pneumoniae, increased. Seventy-four significant correlations were identified, including those be-tween carbapenem consumption and resistance in Escherichia coli and Klebsiella pneumoniae strains. However, no significant corre-lation was observed with imipenem-resistant Pseudomonas aeruginosa strains. The significant correlations between the emergence of bacterial resistance and antibiotic use, particularly with antibiotics in the "Watch" and "Reserve" groups, underscore the urgent need to continue efforts to combat this threat through rational antibiotic use.

Background: this interventional pilot study aimed to evaluate the short-term (3 years) efficacy of focal laser ablation (FLA) in treating the index lesion of low-intermediate risk prostate cancer, along with assessing the safety of the procedure (ClinicalTrials.gov ID NCT04045756). Methods: forty patients aged between 46 and 86 with histologically proven organ-confined prostate cancer and low to intermediate progression risk were included. FLA was performed under percutaneous fusion magnetic resonance/ultrasound guidance in a Day Hospital setting under local anesthesia. Patients underwent regular clinical assessments, PSA measurements, post-procedure MRI scans, and biopsies at 36 months or if positive findings were detected earlier. Statistical analyses were conducted to assess trends in PSA levels and cavity dimensions over time. Results: forty patients were initially included, with 15 lost to follow-up. At 36 months, a mean PSA reduction of 60% was observed, and 80% of MRI scans showed no signs of in-field clinically significant residual/recurrent cancer. Biopsies at 36 months revealed no malignant findings in 20 patients. No deterioration in sexual function or urinary symptoms was recorded. Conclusions: FLA appears to be safe, feasible and effective in the index lesion treatment of low-intermediate risk prostate cancer, with a high rate of tumor eradication and preservation of quality of life.

The gut microbiota plays a crucial role in maintaining host health and has a significant impact on human health and disease. In this study, we investigated the alpha diversity of gut microbiota in COVID-19 patients and analyzed the impact of COVID-19 variants, antibiotic treatment, type 2 diabetes (T2D), and metformin therapy on gut microbiota composition and diversity. We used a culture-based method to analyze the gut microbiota and calculated alpha-diversity using the Shannon H' and Simpson 1/D indices. We collected clinical data, such as length of hospital stay (LoS), C-reactive protein (CRP) levels, and neutrophil-to-lymphocyte ratio (NLR). We found that patients with T2D had significantly lower alpha-diversity than those without T2D. Antibiotic use was associated with a reduction in alpha-diversity, while metformin therapy was associated with an increase. We did not find significant differences in alpha-diversity between the Delta and Omicron groups. Length of hospital stay, CRP levels, and NLR showed weak to moderate correlations with alpha diversity. Our findings suggest that maintaining a diverse gut microbiota may benefit COVID-19 patients with T2D. Interventions aimed at preserving or restoring gut microbiota diversity, such as avoiding unnecessary antibiotic use and promoting metformin therapy, may improve patient outcomes.

To enhance the applicability of dual-phase high-entropy alloys (HEAs) like Fe32Cr33Ni29Al3Ti3, fabricated via selective laser melting (SLM), a focus on improving their mechanical properties is essential. As part of this effort, heat treatment was explored. This study compares the microstructure and mechanical properties of the as-printed sample with those cooled in water after undergoing heat treatment at temperatures ranging from 1000 to 1200 ℃ for 1 hour. Both pre- and post-treatment samples reveal a dual-phase microstructure comprising FCC and BCC phases. Although heat treatment led to a reduction in tensile and yield strength, it significantly increased ductility compared to the as-printed sample. This strength-ductility trade-off is related to changes in grain sizes with ultrafine grains enhancing strength and micron grains optimizing ductility, also the influence of the content of FCC/BCC phases and dislocation density. In particular, the sample heat-treated at 1000 °C for 1 hour and then water-cooled exhibited a better combination of strength and ductility, a yield strength of 790 MPa, and an elongation of 13%. This research offers innovative perspectives on crafting dual-phase HEA of Fe32Cr33Ni29Al3Ti3, allowing for tailorable microstructure and mechanical properties through a synergistic approach involving SLM and heat treatment.

The emergence of antimicrobial resistance have represented a serious threats for public health and infections due to multidrug-resistant (MDR) microorganisms represent one of the most important causes of death worldwide. The renew of old antimicrobials, such as colistin, have been proposed as valuable therapeutic alternative to the emergence of the MDR microorganisms. Although colistin is well known to presents several adverse toxic effect, its usage in clinical practice have been reconsidered due to the broad spectrum of activity to gram-negative (GN) bacteria and to the important role of “last resort” agent against MDR-GN. Despite the revolutionary prospective of treatment of this old antimicrobial molecule, many questions remain open regarding the emergence of novel phenotypic traits of resistance and the optimal usage of the colistin in clinical practice. In the last years, several forward steps have been done in the understanding of resistance determinants, clinical usage and pharmacological dosage of this molecule, however, different points regarding the role of colistin in clinical practice and the optimal pharmacokinetic/pharmacodynamic targets are not well defined yet. In this review, we summarize the mode of action, the emerging resistance determinants and its optimal administration in the treatment of difficult-to-treat infections due to MDR Gram-negative bacteria.

The supply chain has incorporated products by putting them into hair scarfs. This study introduces the use of mini chips in health and beauty products and can reduce fatigue through enhanced sleep patterns. The mini chip could be placed in the scarf and used as a prototype. RFID technology provides the supply chain with specific information that is used to identify products and make communication easier. (Muhammad, et. al. 2013) This paper presents a new tool herein referred to as a scarf prototype which is developed to analyse EMG (electromyogram), ECG (electrocardiography), EEG (electroencephalogram), and EOG (electro-oculogram) signals that focuses in the area of sleep disorders. The mini chips used can be used to determine a solution for sleep disruption by using automated analytics. This could lead to improvement in our understanding of sleep disruption and overall sleep physiology. Automated technology allows repeated measurements, evaluation of sleep patterns, and provide suggestions to improve a person’s quality of sleep. This analysis compares the use of polysomnography and the scarf prototype. The analytics provide models and shows correlation between variables, such as EMG, ECG, EEG, and EOG. This study shows that the results from the scarf prototype is just as reliable as the original method, polysomnography.

Medicinal activities carried out within hospitals lead to a high consumption of antibiotics and subsequently result in a high excretion rate of antibiotic residues. These antibiotics consumed in human medicine are not fully absorbed by the body and are often discharged into the environment as biological waste from infected human patients. The significant water consumption in hospitals and the pharmaceutical impact on wastewater from healthcare facilities facilitate the emergence and spread of antibiotic-resistant bacteria and antibiotic-resistant genes in the environment. Hospital effluents could be doubly involved in the dissemination of antibiotic molecules and multidrug-resistant bacteria in various ecosystems. The objective of this study is to characterize hospital effluents by assessing antibiotic concentrations and the diversity of antibiotic-resistant bacteria in these hospital wastewaters and within the environment (aquatic environments; rivers), as well as to inventory the bacteria present and those carrying antibiotic resistance in both hospital wastewater and the environment.

The scratch test consists in pushing a tool across the surface of a material at a given penetration depth or applied load. It has several applications in Science and Engineering including strength testing, damage and quality control of thin films and coatings. Despite numerous attempts in scientific literature, the application of scratch test to characterizations of fracture properties remains a heavily controversial topic. Therefore, this investigation arises as an experimental study in order to assess the fracture toughness using scratch test. A study on the effect of cryogenic treatment, performed after tempering, on fracture toughness, via scratch test experiments, of different tool steels has been made. A laboratory investigation on AISI D2, AISI M2 and X105CrCoMo18 steel confirms the possibility of increasing the fracture toughness by carrying out the cryogenic treatment after the usual heat treatment

Carbapenem-resistant Acinetobacter baumannii (CRAB) infections represent the fourth-leading cause of death attributable to antimicrobial resistance globally, but a standardized therapy is still lacking. In this narrative review we focused the antibiotic treatment of CRAB infections in view of newly β-lactam agents (NBLs) like sulbactam/durlobactam and cefiderocol, discussing the main hot points such as the superiority of combination treatment over monotherapy and the best antibiotic partner to use in combination. Sulbactam/durlobactam seems to be the best candi-date to replace current back-bone agents. Cefiderocol, could play a crucial role in combina-tion-regimen. Due to toxicity and the PK/PD limitations, colistin (or polymyxin B) should be used as an alternative agent (when no other options are available). Tigecycline (or minocycline) and fosfomycin could represent suitable partners for both NBLs. Randomized clinical trials (RCTs) are needed to better evaluate the role of NBLs in CRAB infection treatment and to compare the ef-ficacy of tigecycline and fosfomycin as partner antibiotics. Synergism should be tested between NBLs and “old” drugs (rifampicin and trimethoprim/sulfamethoxazole). Huge efforts should be made to accelerate pre-clinical and clinical studies on safer polymyxin candidates with lung im-proved activity, as well as on the i.v. rifabutin formulation.

The per capita availability of freshwater resources on a global scale is gradually decreasing due to population growth, rapid urbanization, industrialization, and modern lifestyles. In this situation, wastewater management becomes a major concern. Conventional treatment processes used to treat wastewater discharges are not adequate for the advanced removal of pollutants, especially refractory organic pollutants, which are mainly organic compounds that are not easily biodegradable in the environment. The use of photocatalytic membrane reactors (PMRs) for tertiary wastewater treatment has attracted much interest in recent periods, and various configurations have been investigated. The performance of a PMR using an iron doped titanium photo catalyst and Polysulfone-based polymeric membrane for municipal wastewater treatment was evaluated under natural and simulated solar light. Obtained results proved that solar driven PMRs can remove organic loading (COD) with high efficiencies and may represent a suitable alternative for the tertiary treatment step of municipal wastewater.

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.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

This communication explores the transition from Cognitive Behavioural Therapy (CBT) to a more holistic model, named Complex Therapy, developed by Tullio Scrimali for explaining and treating mental disorders. The Author delves into the limitations of traditional CBT and introduces an innovative framework that integrates multiple therapeutic modalities. While CBT is based on the study and modification of behaviour and cognition, Complex Therapy includes, in its focus, the theory of human relationships, the attachment theory, neuroscience, applied neuroscience, complex systems theory and ecology.Complex Therapy addresses the multifaceted nature of mental health issues by combining evidence-based techniques with personalized care strategies. The goal is to enhance patient outcomes through a tailored, comprehensive treatment plan that adapts to the evolving needs of individuals facing mental health challenges.Two innovative and original items which Scrimali has developed, which are a device for Applied Neuroscience MindLAB Set and a new botanical drug, NegEnt, are presented and discussed.The topic also describes, an original and integrated protocol, named Negative Entropy, the author has developed for treating a challenging disorder, such as schizophrenia, he renamed Entropy of Mind.

Background/Objectives: Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods: We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results: The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker, whereas methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions: There is a consensus that clinical symptoms need to receive more attention in establishing a diagnosis. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency and the treatment goals govern decisions regarding the route and dose of B12 therapy.

The current treatment for cervico-facial cancer involves radio and/or chemotherapy. Unfortunately, cancer therapies can lead to local and systemic complications such as mucositis, which is the most common dose-dependent complication in the oral cavity and gastrointestinal tract. Mucositis can cause a considerably reduced quality of life in cancer patients already suffering from physical and psychological exhaustion. However, melatonin, whose role in the treatment of mucositis has recently been investigated, offers an effective alternative therapy in the prevention and/or management of radio and/or chemotherapy-induced mucositis. This review focuses on the pathobiology and management of mucositis in order to improve the quality of cancer patients’ lives.

Antisense technologies consist of the utilization of oligonucleotides or oligonucleotide analogs to interfere with undesirable biological processes, commonly through inhibition of expression of selected genes. This field holds a lot of promise for the treatment of a very diverse group of diseases including viral and bacterial infections, genetic disorders, and cancer. To date, drugs approved for utilization in clinics or in clinical trials target diseases other than bacterial infections. Although several groups and companies are working on different strategies, the application of antisense technologies to prokaryotes still lags with respect to those that target other human diseases. In those cases where the focus is on bacterial pathogens, a subset of the research is dedicated to produce antisense compounds that silence or reduce expression of antibiotic resistance genes. Therefore, these compounds will be adjuvants administered with the antibiotic to which they reduce resistance levels. A varied group of oligonucleotide analogs like phosphorothioate or phosphorodiamidate morpholino residues, as well as peptide nucleic acids, locked nucleic acids and bridge nucleic acids, the latter two in gapmer configuration, have been utilized to reduce resistance levels. The major mechanisms of inhibition include eliciting cleavage of the target mRNA by the host’s RNase H or RNase P, and steric hindrance. The different approaches targeted resistance to β-lactams including carbapenems, aminoglycosides, chloramphenicol, macrolides, and fluoroquinolones.

Obsessive–compulsive disorder (OCD) is believed to follow a waxing and waning course, often according to environmental stressors. During the COVID-19 pandemic, pre-existing OCD symptoms were reported to increase and to change from checking to washing behaviors, while new-onset symptoms were predominantly of the hoarding type. In the present study, we followed the evolution of OCD symptoms, anxiety, depression, and insight of illness in forty-six OCD patients throughout the pandemic. Clinical measures were collected at four different time points before and during the COVID-19 pandemic in Italy. Within-subject comparisons were used to compare clinical scale scores across time, and correlations were examined between patients' baseline characteristics and changes in clinical scores. We found that all clinical measures increased during the first Italian lockdown, with respect to the pre-pandemic values. Anxiety decreased during the temporary elimination of restriction provisions, whereas severity of OCD symptoms and insight returned to pre-pandemic values during the second mandatory lockdown. These results were observed only in two sub-groups of patients: those taking benzodiazepines and those with shorter illness duration. Our findings suggest the need of additional clinical attention to these specific sub-groups of OCD patients in case of particularly distressing circumstances, while pointing to a possible adaptive role of their OCD symptoms when the environment requires a higher care of hygiene and extraordinary supply of essential resources.

Cardiovascular diseases are a broadly understood concept focusing on vascular and heart dys-function. Lack of physical exercise, type 2 diabetes, obesity, hypertension, dyslipidemia, throm-boembolism, kidney, and lung diseases all contribute to the development of heart and blood vessel dysfunction. Although effective and important, traditional treatment with diuretics, statins, beta–blockers, calcium inhibitors, ACE inhibitors, and anti–platelet drugs remain a second–line treatment after dietary intervention and lifestyle changes. Scientists worldwide are still looking for an herbal product that would be quite effective and free from side effects, either taken together or before the standard pharmacological intervention. Such herbal–originated medication therapy may include Morus alba L. (white mulberry), Elaeagnus rhamnoides (L.) A. Nelson (sea–buckthorn), Allium sativum L. (garlic), Convallaria majalis L. (lily of the valley), Leonurus cardiaca L. (mother-wort), and Crataegus spp. (hawthorn). Valuable herbal raw materials include leaves, fruits, seeds, and even thorns. This short review focuses on six herbs that can constitute an interesting and po-tential therapeutic option in the management of cardiovascular disorders.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

Dysregulation of cartilage homeostasis and the changes in the density and the architecture of the subchondral bone were postulated as a potent mechanically pathological activity contributing to osteoarthritis (OA) pathogenesis. Extracorporeal shockwave therapy (ESWT) is a new, none invasive and effective method in the treatment of animal OA model. In the current study, we demonstrated that shockwave induced the expression of protein-disulfide isomerase-associated 3 (Pdia-3) which is a multifunctional protein hypothesized to be a significant mediator for 1α,25-Dihydroxyvitamin D3 (1α,25(OH)₂D₃) signaling pathway using two-dimensional electrophoresis. Histological analysis and quantitative polymerase chain reaction (qPCR) were verified and observed that the expression of Pdia-3 at 2 weeks was significantly higher than that of any other group at 4 weeks, 8 weeks, and 12 weeks post-shockwave treatment in early OA knee of rat. The other factors of the 1α,25(OH)₂D₃ rapid membrane signaling pathway including extracellular signal-regulated protein kinases 1 (ERK1), osteopontin (OPG), alkaline phosphatase (ALP), and matrix metallopeptidase 13 (MMP13) were measured and significantly increased by qPCR at 2 weeks post-shockwave treatment in early OA knee. Our proteomic data revealed significant Pdia-3 expression in microenvironments of joint tissue that could be actively responded to ESWT, which may potentially regulate biological function of chondrocytes and osteoblasts in the treatment of OA knee.

The main purpose of this work was to tests of form and size of fatigue wear of the top layer of oil gear pump wheel (3PW-BPF-24). The object of tests was operated during a determined number of hours at strictly controlled operational and environmental parameters. A microscope of focal differentiation by Alicona InfiniteFocus G4 (with Focus-Variation optical measuring technology) was used for an identification, measurement and description of noticed superficial defects, which resulted from the fatigue process of the top layer and an earlier thermochemical treatment. The work was finished with an analysis of obtained results (based on the analysis of 3D scans) and conclusions concerning about optimization of the thermal treatment. Taking into consideration the presented results (suggestions) in the technology of improving strength properties of gear wheels (of this type oil pumps) may render it possible to obtain an appropriate fatigue endurance of the top layer, i.e. a minimization of observed superficial defects.

CoCrFeNiMn high-entropy alloy coatings were prepared on compacted graphite iron（CGI） through plasma cladding to strength the CGI substrate. The effects of heat treatment temperatures and times on the microstructure and mechanical properties of the CoCrFeNiMn coatings were investigated. After heat treatment, a single FCC phase was remained in the coating as compared to the deposited one, with smaller dendrites, larger dendritic spacing and more Cr-rich compounds precipitated between dendrites. The coatings’ microhardness was increased after heat treatment. After heat treated at 660°C for 90 minutes, the coating had the highest microhardness of 563±6.9 HV0.2, the lowest frictional coefficient of 0.71 and the smallest wear mass loss of 1.12 mg, and it had the best wear resistance.

Taeniid infections pose a significant threat to both animal and public health, as certain tapeworms within this group can also infect humans, potentially leading to severe health conditions. Therefore, this calls for preventive and control measures, such as regular deworming of dogs. While the efficacy of deworming has been established in developed countries, there is a paucity of reported deworming practices in rural areas of developing countries, such as Tanzania. This study aims to understand determinants for helminth treatment-seeking behavior towards control of cestodial taeniid infections in rural settings in northern Tanzania. A cross-sectional study was undertaken in agropastoral and pastoral areas of northern Tanzania. Comprehensive data from household surveys in selected sub-villages were collected to ascertain dog ownership, dog deworming practices, and the availability of dewormers. Analytical methods were employed to discern how various determinants influenced deworming practices among dog owners in these communities. Awareness of dewormers specifically formulated for dogs emerged as a pivotal factor affecting dog deworming practices. Dog owners who were informed about appropriate dog dewormers were nearly two times more likely to engage in deworming compared to those with limited knowledge (OR = 1.78, 95% CI 1.77 - 4.18, p < 0.001). A majority 32(51.6%, 95% CI: 38.7-64.3) acknowledged accessing dewormers for livestock within their wards. Praziquantel a potent dewormer on cestodes was least known to most dog owners 2(13%, 95% CI: 2.3-41.6). Praziquantel, a potent and common dewormer effective against cestodial taeniid infections, remains relatively unknown in rural areas of northern Tanzania. Therefore, more awareness on appropriate deworming agents against taeniids in dogs should be raised in rural dog-keeping communities.

Around the world, there is no population clear from urinary tract infection (UTI), particularly among women. UTI is considered the most predominant bacterial infection. This study aimed to detect the incidence of the most common major uropathogens in patients severe from urinary tract infection with antibiotic sensitivity tests that assist urologist doctors for appropriate antimicrobial empirical therapy.Methods: This study was carried in a private laboratory in Babil city, Iraq from May 2019 to May 2020. Totally 70 individuals suffering from clear symptoms of UTI, as well as, 20 healthy persons participated in this study as a control group. Then, the standard microbiological methods carried out to isolate and identify bacterial species. Antimicrobial susceptibility tests were performed using different antimicrobial discs by applying the Kirby–Bauer disc diffusion method.Results: Totally, 90 specimens were obtained from them 20 control group, 19 with no growth, and 51 patients with bacterial growth distributed as 43 (83%) females and 8 (17%) males. E. coli were the most common predominant organisms. All isolates were showed a high rate of resistance to evaluated cephalosporins 100% and 82% to cefotaxime and ceftriaxone respectively, while very low resistance recorded in Aminoglycosides 20% and 13% to Gentamicin and amikacin respectively. Most age group infected with UTI was 21-40 years old.Conclusion: The current study showed an increasing burden of urinary tract infection caused by various bacteria implicated in UTI that causes changeable sensitivity to various antimicrobial agents. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopment disorder frequently co-occurring with Attention-Deficit/Hyperactivity Disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage ASD core symptoms, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend neuroleptics to reduce psychomotor agitation in people with ASD. However, since children with ASD are often drug-resistant, alternative treatments are often justified. Reports from literature showed that intra-venous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with lower frequency of adverse events compared to convention-al treatments. However, since findings are occasionally inconsistent, IV-VPA is not an approved option in clinical psychiatry. We aim at improving the knowledge on the IV-VPA treatment option in emergency psychiatry in the pediatric age. Methods: We report the case of a 11-year-old boy suffering from a complex neurodevelopmental condition, who experienced a psychotic episode with severe aggressive and disruptive behaviors, successfully treated with IV-VPA. Besides, we conducted an up-dated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. On the contrary, IV-VPA led to a safe and prompt clinical success, in line with other reports. Based on our literature review, IV-VPA can be highly effective and can reduce the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry.

Alcoholic liver disease (ALD) is a major cause of chronic liver disease. This term covers a broad spectrum of liver lesions, from simple steatosis to alcoholic hepatitis and cirrhosis. The patho-genesis of ALD is multifactorial and not fully elucidated due to complex mechanisms related to direct ethanol toxicity with subsequent hepatic and systemic inflammation. The accumulation of pro-inflammatory cytokines and the reduction of anti-inflammatory cytokines promote the development and progression of ALD. To date, there are no targeted therapies to counteract disease progression and prevent acute liver failure. Corticosteroids reduce mortality by acting on the hepatic-systemic inflammation. On the other hand, several studies analyzed the effect of the inhibition of pro-inflammatory cytokines and the stimulation of anti-inflammatory cytokines as potential therapeutic targets in ALD. This narrative review aims to clarify the role of the cy-tokines in the pathogenesis and treatment of ALD.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

The development of antimicrobial resistance to conventional antibiotics is a major global health challenge. Infections caused by multidrug-resistant gram-negative bacteria have been named one of the most urgent global health threats. Considerable efforts are devoted to developing new antibiotic drugs and investigating the mechanism of antibiotic resistance. Recently, Anti-Microbial Peptides (AMPs) have emerged as a new platform for the target and design of novel drug resistant anti-microbial agents promising a new therapeutic strategy. AMPs are rapid, potent, possess an unusually broad spectrum of activity, and have shown efficacy as topical agents. Unlike traditional therapeutics that interfere with essential bacterial enzymes, AMPs interact with microbial membranes through electrostatic interactions and physically damage cell integrity. However, naturally occurring AMPs have limited selectivity and modest efficacy. Therefore, recent efforts have focused on the development of synthetic AMP analogs as suitable drug targets. This work explores the development of novel antimicrobial agents which mimic the structure of graft-copolymers and mirror the mode of action of an AMP. Chitosan-graft-polypeptide side chains are synthesized by the ring-opening polymerization of N-carboxyanhydrides of L-lysine and L-leucine initiated from the functional groups of chitosan. The derivatives with random- and block-copolymer side chains are explored as drug targets. These graft copolymer systems exhibit activity against clinically significant pathogens and disrupt biofilm formation. This work highlights the potential of chitosan-graft-polypeptide structures in biomedical applications.

The world faces two seemingly unrelated challenges—a shortfall in the STEM workforce and increasing antibiotic resistance among bacterial pathogens. We address these two challenges with Tiny Earth, an undergraduate research course that excites students about science and creates a pipeline for antibiotic discovery.

The antibiotic or antimicrobial resistance is rapidly spreading in microbes relevant to human health. Two visible major contributory factors have been the indiscriminate overuse of antimicrobials for preventing diseases in human and to enhance the productivity in agriculture sector. To mitigate the potential threat posed by post-antibiotic era, the global health stakeholders have been making extra efforts at a war footing to formulate and implement global and national plans of action. In the current article, an endeavour is made to provide a perspective to look beyond the current focus on just use of the antimicrobials. Attention has been drawn towards various obvious and not-so-obvious self-preservation infection-prevention practices in vogue from the pre-antibiotic era whose usage has been on decline in the antibiotic era for various reasons. Particularly, the practices with a clear potential to effectively decrease the spread of pathogens through contact, curtail the evolution and dissemination of the antimicrobial resistance in local environment and its introduction into the global community, should be Identified and strengthened to make them part of comprehensive hygiene and quarantine practices. Broadly, the suggestions pertaining to the personal and community hygiene including bereavement practices, isolation and quarantine of suspected pathogen carriers, and water and environment security have been made to invoke a constructive debate and discussion among various stakeholders for their evaluation and implementation to effectively delay the development of antimicrobial resistance wherever possible and disrupt its spread to pathogens.

An observational cohort study of patients diagnosed with endometrial cancer (EC) stage IA G1, or atypical endometrial hyperplasia (AHE), undergoing organ-preserving treatment, was conducted. Objective of the study: to determine CDO1, PITX2, and CDH13 gene methylation levels in early endometrial cancer and atypical hyperplasia specimens obtained before organ-preserving treatment in the patients with adequate response and with insufficient response to hormonal treatment. Materials and methods: 41 endometrial specimens obtained during diagnostic uterine curettage in women with EC (n=28) and AEH (n=13), willing to preserve reproductive function, were studied; 18 specimens of endometrial cancer IA stage G1 from peri- and early postmenopausal women (comparison group) were included in the study. The control group included 18 endometrial specimens from healthy women obtained by diagnostic curettage for missed abortion and/or intrauterine adhesions. Methylation levels were analyzed using the modified MS-HRM method. Results: All 13 women with AEH had complete response (CR) to medical treatment. In the group undergoing organ-preserving treatment for uterine cancer IA stage G1 (n=28), 14 patients had complete response (EC CR group) and 14 had not (non-CR). It was found that all groups had statistically significant differences in CDO1 gene methylation levels with the control group (p&lt;0.001) except for the EC CR group (p=0.21). The p-value of difference between EC CR and EC non-CR groups was &lt;0.001. The differences in PITX2 gene methylation levels between the control and study groups were also significantly different (p&lt;0.001), except for AEH group (p=0.21). For the difference between EC CR and EC non-CR groups, the p-value was 0.43. For CDH13 gene methylation levels, statistically significant differences were found between the control and EC non-CR groups (p&lt;0.001), and the control and EC comparison groups (p=0.005). When comparing the EC CR group with EC non-CR group, the p-value for this gene was &lt;0.001. Simultaneous assessment of CDO1 and CDH13 genes methylation allowed to accurately distinguish between EC CR and EC non-CR groups (AUC=0.96). Conclusion: Assessment of CDO1 and CDH13 gene methylation in endometrial specimens from patients with endometrial cancer (IA stage G1), planned for medical treatment, can predict the treatment outcome.

We describe an interesting case report about a patient with hemophilia A with severe chronic elbow arthropathy who underwent multiple surgical because of his condition. We collected all the clinical and imaging findings, and we compared the decision-making flow chart and the surgery performed with the most recent indications, treatments and complications reported in the literature. The aim of this case report is to show how usually the hemophilic patient even if young usually comes to our attention from the beginning with complex and advance musculoskeletal disease. Elbow hemophilic arthropathy is a complex disease and the management in these patients could be more difficult than others because of the higher risk of complications rate after all surgical procedures, for this reason it’s very important to treat these patients in hub centers with expertise in well-coordinated multidisciplinary teams. The path from diagnosis to surgical treatment of hemophilic elbow arthropathy can be a risky one, as it happened in this case.

Psoriasis is a lifelong, systemic, immune mediated inflammatory skin condition, affecting 1-3% of the world’s population, with an impact on quality of life similar to diseases like cancer or diabetes. Genetics are the single largest risk factor in psoriasis, with GWAS studies showing that many psoriasis risk genes lie along the IL23/Th17 axis. Potential psoriasis risk genes determined through GWAS can be annotated and characterised using functional genomics, allowing the identification of novel drug targets and the repurposing of existing drugs. The pathogenesis of psoriasis is complex and focusing on the IL23/Th17 axis can provide insight into key cell types, cytokines and intracellular signaling pathways involved. Examination of currently available biological treatments, time to relapse post drug withdrawal and rates of drug primary/secondary drug failure show the need for greater understanding of the underlying genetic mechanisms of psoriasis and how they can impact treatment. This could allow for patient stratification towards the treatment most likely reduce dis-ease burden for the longest period possible.

Research is scarce regarding antimicrobial use and antimicrobial resistance (AMR) for specific localities in Northern Ireland (NI). Additionally, the effects of COVID-19 on antimicrobial pre-scribing patterns and AMR are unknown. Between the European Union (EU) and United States (US), AMR causes approximately 68,000 deaths annually. This study will provide a better understanding of antimicrobial use and prescribing patterns in Belfast and link with AMR. An electronic survey was developed and distributed to eighty-five community pharmacists in Belfast. Yearly and monthly prescription data was gathered from the Business Services Organisation and COVID-19 statistics from Gov.uk. All data was analysed on Microsoft Office Excel® and IBM® SPSS® Statistics 25. Overall response rate was 46%. Most pharmacists (82%) failed to address prescriber non-compliance with guidelines and antimicrobial dosing errors (59%). The most common in-dication for antibiotics was upper respiratory tract infections (URTIs). Overprescribing of anti-biotics was perceived as the leading cause of AMR, therefore 69% of pharmacists indicated in-creased General Practitioner (GP) compliance with guidelines would reduce AMR. Pharmacists’ are in an ideal position to reduce AMR through patient education however, it is demonstrated that pharmacists failed to adequately counsel patients on antibiotic use. All GP practices demonstrated inappropriate antibiotic use, especially for URTIs which suggests antibiotic appropriateness should be reviewed. Many patients avoided contact with GP’s during COVID-19 which may have resulted in reduced antibiotic use. This research established amoxicillin as the most commonly prescribed antibiotic, which is contributing to increased AMR with its broad-spectrum activity and has recognised a decrease in antibiotic prescribing during COVID-19. Based on the results found and a critical review of the literature it is recommended antimicrobial guidelines should be re-viewed and improved, enhanced training should be provided to pharmacists and the antibiotic guardian (AG) campaign should be reenergised.

Antibiotic resistance and accordingly their pollution because of uncontrolled usage has emerged as a serious problem in recent years. Hence, there is an increased demand to develope robust, easy, and sensitive methods for rapid evaluation of antibiotic and their residues. Among different analytical methods, the aptamer-based biosensors (aptasensors) have attracted considerable attention because of good selectivity, specificity, and sensitivity. This review gives an overview about recent developed aptasensors for antibiotic detection. The use of various aptamer assays to determine different groups of antibiotics like β-lactams, Aminoglycosides, Anthracyclines, Chloramphenicol, (Fluoro)Quinolones, Lincosamide, Tetracyclines and Sulfonamides are presented in this paper.

Background: Using the COM-B model as a framework, an EU-wide survey aimed to ascertain multidisciplinary healthcare workers’ (HCWs) knowledge, attitudes and behaviours on antibiotics, antibiotic use and antibiotic resistance. The UK findings are presented. Methods: A 43-item questionnaire was developed through a two-round modified Delphi consensus process. The UK target quota was 1,315 respondents. Results: 2,404 participants responded. The highest proportion were nursing and midwifery professionals (42%), pharmacists (23%) and medical doctors (18%). HCWs correctly answered that antibiotics are not effective against viruses (97%), they have associated side effects (97%), unnecessary use makes antibiotics ineffective (97%) and healthy people can carry antibiotic resistant bacteria (90%). However, fewer than 80% correctly answered that using antibiotics increases a patient’s risk of antimicrobial resistant infection or that resistant bacteria can spread from person to person. Whilst the majority of HCWs (81%) agreed there is a connection between their antibiotic prescribing behaviour and the spread of antibiotic resistant bacteria, only 64% felt that they have a key role in controlling antibiotic resistance. The top three barriers to providing advice or resources were lack of resources (19%), insufficient time (11%) and the patient being uninterested in the information (7%). Approximately 35% of UK respondents who were prescribers prescribed an antibiotic at least once in the last week due to fear of patient deterioration or complications. Conclusion: These findings highlight that a multifaceted approach to tackling the barriers to prudent antibiotic use in the UK is required and provides evidence for guiding targeted policy, intervention development and future research. Education and training should focus on patient communication, information on spreading resistant bacteria and increased risk for individuals.

The paper discusses the mechanism of montmorillonite structure alteration and bentonites properties modification (on the example of samples from clay deposit Taganka, Kazakhstan) due to the thermochemical treatment (treatment with inorganic acid solutions at different temperatures, concentrations and reaction times). With the use of the suit of methods certain processes were distinguished: transformation of montmorillonite structure, which appears in the leaching of interlayer and octahedral cations, protonation of the interlayer and OH groups at octahedral sheets. Changes in the structure of the 2:1 layer of montmorillonite and its interlayer result in significant changes in the properties – reduction of cation exchange capacity and an increase of specific surface area. The results of the work showed that bentonite clays retain a significant portion of its adsorption properties even after the long term and intense thermochemical treatment (6M HNO3, 60°C, 108 hours)

Proteins play a pivotal role in supporting athletes by promoting muscle hypertrophy and minimizing protein catabolism during exercise. They stimulate muscle protein synthesis, aiding in the repair of exercise-induced muscle damage and serving as an energy source, particularly for post-exercise glycogen replenishment. In individuals with phenylketonuria (PKU), for whom protein intake is limited to essential phenylalanine (Phe), supplementation with Phe-free amino acids or glycomacropeptides is necessary. Tailored for macronutrient and micronutrient content, these protein substitutes fulfill most protein requirements, but lack Phe, unlike dietary sources of protein. Protein requirements for athletes with PKU exceed general recommendations due to limited availability in supplements and potential catabolism mitigation. Various factors influence tolerated dietary Phe in PKU, including protein substitute quantity, distribution, pharmacological treatment, age, growth rate, pregnancy, catabolic states, and physical activity. While general protein requirements for PKU surpass those of the general population, adherence to supplement regimens is crucial for athletes and patients with PKU. Strategically timed protein substitutes enhance muscle protein synthesis, body composition, and sports performance within safety limits. Individualized intake is essential for optimal outcomes, as proteins have a multifaceted role in optimizing athletic performance and addressing challenges in PKU.

Exosome-based therapy has emerged as a promising strategy for addressing diverse disorders, indicating the need for further exploration of the potential therapeutic effects of the exosome cargos. This study introduces "enhanced exosomes," a novel type of exosomes developed through a novel cell culture system. These specific exosomes may become potent therapeutic agents for treating ovarian disorders. In this study, we conducted a comparative analysis of the protein and miRNA cargo compositions of enhanced exosomes and naïve exosomes. Our findings revealed distinct cargo compositions in enhanced exosomes, featuring upregulated proteins such as EFEMP1, HTRA1, PAM, RSU1, and SDF4, suggesting their potential for treating ovarian disorders. MicroRNA profiling revealed that miR-1-3p, miR-103a-3p, miR-122-5p, miR-1271-5p, miR-133a-3p, miR-184, miR-203a-3p, and miR-206 are key players in regulating ovarian cancer and chemosensitivity by affecting cell cycle progression, cell proliferation, and cell development. We examined polycystic ovary syndrome and premature ovarian insufficiency and identified altered expression of various miRNAs, such as miR-106a-5p, miR-130b-5p, and miR-130b-3p, for diagnostic insights. This study highlights the potential of enhanced exosomes as new therapeutic agents for women's reproductive health, offering a detailed understanding of the impact of their cargo on ovarian disorders.

: Crohn’s disease (CD) is a multifactorial chronic disorder that involves a combination of factors as genetic, immune response and gut microbiota. Actually, the therapy comprises salicylates, immunosuppressive agents, corticosteroids, biologic drugs. International guidelines don’t recommend the use of antibiotics except for septic complications of CD patients. The increased evidence of the implication of gut bacteria in this chronic disease support the rationale for using antibiotics as primary treatment of active CD. In the last decades several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E.coli) species and Mycobacterium avium paratubercolosis (MAP), aroused the interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment in CD patients but randomized trials of antibiotic treatments against E.coli and MAP did not show prolonged benefits, and only generated conflicting results so much so that several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course and the outcome measures. In this article we attempted to provide an overview and update of the trials on antibiotic treatment in active CD patients taking into account the role of pathogens, the mechanism by which the different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also tried to draw new lines for future studies to use antibiotics to treat active CD patients

Staphylococcus spp. are among the main pathogens responsible for important infections worldwide, both in humans and in domestic or wild animals. Chiropterans, popularly known as bats, inhabit natural environments and human constructions, and have been considered potential disseminators of several pathogens. Studies have shown the expression of the mecA gene in these animals, being a significant threat to One Health. The objective of this study was to determine antibiotic resistance and the presence of the mecA gene in Staphylococcus spp. isolates from bats from forest areas in the municipalities of Paraná, Brazil. A total of 87 frugivorous chiropterans belonging to the family Phyllostomidae were captured. Of these, 87 rectal and 87 oral swabs samples were collected, re-sulting in 32 Staphylococcus spp. isolates. Twenty-four isolates were characterized as coagu-lase-negative, and 8 coagulase-positive Staphylococcus spp. (STACP), which showed notable re-sistance to oxacillin (78.12%), penicillin G (65.62%) and to other antimicrobials as well. One STACP isolate was mecA-positive. Therefore, further studies are needed to elucidate the mechanisms of contamination and dissemination of these pathogens, emphasizing that anthropic actions in na-tural environments, especially those related to the use of antimicrobials, pesticides may be the main reasons for the presence of resistant bacteria in bats.

Lemonomycin (1) was first isolated from the fermentation broth of Streptomyces candidus in 1964. The complete chemical structure was not elucidated until 2000 with extensive spectroscopic analysis. Lemonomycin is currently known as the only glycosylated tetrahydroisoquinoline antibiotic. Its potent antibacterial activity against Staphylococcus aureus and Bacillus subtilis and complex architecture make it an ideal target for total synthesis. In this short review, we summarize the research status of lemonomycin for biological activity, biosynthesis and chemical synthesis. The unique deoxy aminosugar-lemonose was proposed to play a crucial role in biological activity, as shown in other antibiotics, such as arimetamycin A, nocathiacin I, glycothiohexide α, and thiazamycins. Given the self-resistance of the original bacterial host, the integration of biosynthesis and chemical synthesis to pursue efficient synthesis and further derivatization is in high demand for the development of novel antibiotics to combat antibiotic-resistant infections.

Diversity as well as temporal and spatial changes of the proportional abundances of different antibiotics (cycling, mixing or combinations thereof) have been hypothesised to be an effective administrative control strategy in hospitals to reduce the prevalence of antibiotic-resistant pathogens in nosocomial or community-acquired infections. However, a rigorous assessment of the efficacy of these control strategies is lacking. The main purpose here is to present a mathematical framework for the assessment of control stategies from a processual stance. To this end, we adopt diverse measures of heterogeneity and diversity of proportional abundances based on the concept of entropy from other fields and adapt them to the needs in assessing the impact of variations in antibiotic consumption on antibiotic resistance. Thereby, we derive a family of diversity measures whose members exhibit different degrees of complexity. Most important, we extent these measures such that they account for the assessment of temporal changes in heterogeneity including otherwise undetected diversity-invariant permutations of antibiotics consumption and prevalence of resistant pathogens. We apply a correlation analysis for the assessment of associations between changes of heterogeneities on the antibiotics and on the pathogen side. As a showcase, which serves as a proof-of-principle, we apply the derived methods to records of antibiotic consumption and prevalence of antibiotic-resistant germs from University Hospital Dresden. Besides the quantification of heterogeneities of antibiotics consumption and antibiotic resistance, we show that a reduction of prevalence of antibiotic-resistant germs correlates with a temporal change of similarity with respect to the first observation of antibiotics consumption, although heterogeneity remains approximately constant. Although an interventional study is pending, our mathematical framework turns out to be a viable concept for the assessment and optimisation of control strategies intended to reduce antibiotic resistance.

Background: Capsaicinoid are a group of compounds and widely used in the food, medical, and pharmaceutical industries. Capsaicinoid are unique synthesized and accumulated in the pepper fruits. MeJA can enhance the capsaicinoid production. Temporal and spatial expression of capsaicinoid biosynthetic genes are helpful to understand the molecular mechnism of capsaicinoid biosynthesis in the fruits of pepper. Although some of the capsaicinoid biosynthetic genes in pepper have been identified, the expression of these genes at different developing stages of fruit has not been systemically investigated, and little is known about the molecular basis of MeJA inducing capsaicinoid biosynthesis. Results: HPLC study revealed that the capsaicinoid accumulation in the developing fruit of pepper initially appeared at 24 DAP (day after pollination), was actively development at 36 DAP and peaked at 48 DAP. 11 genes that encoded enzymes involved in capsaicinoid biosynthesis were isolated and characterized. Gene expression with quantitative reverse-transcription polymerase chain reaction analysis demonstrated that the CaCS was unique expressed in placenta and the other 10 genes were expressed in all selected tissues and 9 of 11 genes (except CaCa4H and CaCa3H) were strongly expressed in placenta tissue. Spatial expression analysis demostrated that the 11 gene could be collectively grouped into four categories based on the patterns of relative expression of the genes during fruit development. Category I has 2 and they displayed a bell-shaped expression pattern with the peak expression at 24 DAP, Category II contains 5 genes and expression of the 5 genes was constantly increased from 0 to 36 DAP and peaked at 36 DAP. Category III comprises of 2 genes and both genes reached the peak at 48 DAP. Category IV consists of 2 genes and they showed a high expression at 36 and 48 DAF, but unexpressed from 0 to 12 DAP. The gene expressions of the 11 genes were up-regulated by MeJA. 3 genes showed a high expression at 24 h; 4 genes reached the peak at 12 h; the top expression were observed at 18 h; The last one, CaACYase, achieved the highest level at 8 h. Conclusion: The biosynthesis of capsaicinoid in pepper fruit is developmentally regulated. The expression of the majority of capsaicinoid biosynthetic genes is highly consistent with the development accumulation of capsaicinoid in pepper fruit. These results not only provide the initial information on spatial and temporal expression of capsaicinoid biosynthetic genes in pepper developing fruit, but are also valuable to identify the MeJA-induced genes for capsaicinoid biosynthesis and accumulation during pepper fruit development.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and receptor inhibitors remain around 50 percent. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Antibiotic Resistance (ABR) is increasing the mortality and morbidity associated with infectious diseases, besides increasing the cost of healthcare, saturating health-system capacity, and adversely affecting food security. Framing an appropriate narrative and engaging local communities through ‘One Health’ approach is essential to complement the top down measures. However, the absence of objective criteria to measure the performance of ABR interventions at community settings make it difficult to mobilize interest and investment for such interventions. An exercise was therefore done to develop an indicator framework for this purpose. An exhaustive list of indicators was developed from experiences gathered through community engagement work in a local panchayat (small administrative area) in Kerala, India, and a consultative process with health, veterinary, environment, and development experts. A prioritization exercise was done, looking at appropriateness, feasibility and validity, by global experts on ABR. A 15-point indicator framework was designed based on the prioritization process. The final set of indicators covers human health, animal health, environment management and Water Sanitation and hygiene (WASH) domains. The indicator framework was piloted in the panchayat(located in Kerala), which attained a score of 34 (maximum 45). The score increased when interventions were implemented to mitigate the ABR drives, indicating the framework is sensitive to change. Simultaneously, the indicator framework was tested in four sites from three other Indian states with different socioeconomic and health profiles, yielding different scores. Those collecting the field data were able to use it with minimal training. To conclude, this indicator framework can help policymakers broadly understand the factors contributing to ABR and measure the performance of interventions they choose to implement in the community

Background: Although rarely indicated, antibiotics are commonly used for acute diarrhoea in China. We conducted a randomized, double blind exploratory clinical trial of loperamide, berberine and turmeric for treatment of acute diarrhoea. Methods: Adults with acute uncomplicated diarrhoea were randomized to 4 groups: (A) loperamide; (B) loperamide and berberine; (C) loperamide and turmeric; (D) loperamide, berberine and turmeric. All participants were given rescue ciprofloxacin for use after 48 hours if symptoms worsened or were unimproved. Primary endpoints were feasibility and ciprofloxacin use during the 2 week follow-up period. Semi-structured interviews were conducted following recruitment. Results: Only 21.5% (278/1295) of patients screened were deemed eligible, and 49% (136/278) of these consented and entered into the final analysis. Most participants had mild symptoms, because most patients with moderate or severe symptoms wanted to be given antibiotics. Follow-up was good (94% at 2 weeks). Only two participants used rescue antibiotics compared to 65% of acute diarrhoea patients in the hospital during the recruitment period. The median symptom duration was: 14 hours in group B (IQR 10-22), 16 hours in group D (IQR 10-22), 18 hours in group A (IQR 10-33), 20 hours in group C (IQR 16-54). Re-consultation rates were low. There were no serious treatment-related adverse events. Most interviewed participants said the treatment was effective. Conclusion: Although recruitment was challenging because of widespread expectations for antibiotics, patients with mild diarrhoea accepted to try an alternative. This therapy requires further evaluation in a fully powered, randomised controlled trial among a broader sample.

The blood count is crucial for assessing bone marrow's cell production and differentiation during infections, gauging disease severity, and monitoring therapeutic responses. The profile of blood count in chronic form of paracoccidioidomycosis (PCM) has been insufficiently explored. To better understand the changes in hematological cells in different stages of the PCM chronic form, we evaluated the blood count, including immature blood cells in automated equipment, before and during the treatment follow-up of 62 chronic PCM patients. Predominantly male (96.8%) with an average age of 54.3 (SD 6.9) years, participants exhibited pre-treatment conditions such as anemia (45.2%), monocytosis (38.7%), and leukocytosis (17.7%) which became less frequent after clinical cure. Anemia was more prevalent in severe cases. Notably, hemoglobin and reticulocyte hemoglobin content increased, while leukocytes, monocytes, neutrophils, immature granulocytes, and platelets decreased. Chronic PCM induced manageable hematological abnormalities, mainly in the red blood series. Monocytosis, indicating monocytes' role in PCM's immune response, was frequent. Post-treatment, especially after achieving clinical cure, significant improvements were observed in various hematological indices, including immature granulocytes and reticulocyte hemoglobin content, underscoring the impact of infection on these parameters.

Acetic acid bacteria (AAB) are major contributors to the production of fermented vinegar, offering various cultural, culinary, and health benefits. Although the residual unpasteurized AAB after vinegar production are not pathogens, these are necessary the safety evaluations including antibiotic resistance for the use as starters. In this research, we investigated the antibiotics resistance profiles of 26 AAB strains, including various species of Komagataeibacter and Acetobacter, against ten different antibiotics using the E-test method. All strains exhibited resistance to aztreonam and clindamycin. Komagataeibacter species demonstrated a 50% resistance rate to ciprofloxacin, analogous to Acetobacter species, but showed twice the resistance rates to chloramphenicol and erythromycin. Genomic analysis of K. saccharivorans CV1 identified intrinsic resistance mechanisms, such as multidrug efflux pumps, thereby enhancing our understanding of antibiotic resistance in acetic acid-producing bacteria. These findings enhance understanding of antibiotic resistance in AAB for food safety and new antimicrobial strategies, suggesting the need for standardized testing methods and molecular genetic study.

The Maastricht VI/Florence consensus recommends, as one of the measures to enhance the efficacy of Helicobacter pylori (H. pylori) infection eradication, a personalized treatment approach involving the selection of an antimicrobial agent based on the pre-determined resistance of H. pylori. To meet the need to develop test systems for personalized drug selection, we conducted a study of H. pylori molecular resistance in Moscow using a self-developed Sanger sequencing test platform. We validated our test system on 25 pure culture samples of H. pylori with known resistance. Sensitivity and specificity for detecting resistance to clarithromycin was 100%, and to levofloxacin - 93% and 92%, respectively. Then we tested our platform on 112 H. pylori -positive patients who had not previously received proton pump inhibitors (PPI) or antibacterial drugs. Mutations indicating resistance to clarithromycin were found in 27 (24%) samples, and to levofloxacin in 26 (23%) samples. Double resistance was observed in 16 (14%) samples. The most common mutations leading to clarithromycin resistance were 2143G and 2142G, to levofloxacin resistance – 261A and 271A in the gyrA gene, which account for 69% of all identified genetic determinants in levofloxacin-resistant bacteria. Thus, a personalized approach to the selection of H. pylori eradication therapy based on the detection of bacterial resistance before prescribing first-line therapy could help avoid the prescription of ineffective H. pylori eradication therapies and, overall, contribute to the control of antibiotic resistance of H. pylori.

Precision farming is transforming how antibiotics get used on farms. It fights the overuse that creates superbugs and harms nature. Farmers now have high-tech tools to use antibiotics ultra-precisely. Drones, AI, and advanced watering equipment help them pinpoint only sick plants and animals needing treatment. This shields crops while avoiding environmental damage. More careful antibiotic use makes livestock healthier and boosts harvests too. And it prevents resistant germs, where antibiotics stop working altogether. The approach helps farms in multiple ways, using fewer resources for even better results. There are some growing pains, like high costs for small farms. And questions around data privacy also cause concern. But overcoming these hurdles could help precision farming spread far and wide. This technology promises safer, greener, and more productive agriculture. Targeted use of antibiotics protects both crops and people from drug-proof germs. And nature benefits when less medicine spreads into soil and water. The future looks bright for farming with precision.

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.

Antibiotic resistance among bacterial pathogens is recognized as a major threat to human health worldwide. The emergence of multidrug-resistant bacteria can also be found in the community settings, apart from hospital environment, which indicates that reservoirs of antibiotic resistance genes do exist outside the hospital. The growth of antibiotic resistance is a consequence of bacterial adaptations in response to selective pressures. To survive in this hostile environment, bacteria develop defence mechanisms such as chemical modification of antibiotics, enzyme-catalysed antibiotic degradation, altered permeability, antibiotic efflux, mutation of target sites and biofilm formation, resulting in resistance to nearly all currently available antibiotics used in the clinical practice. The present review summarizes insights into the molecular mechanisms underlying the antibiotic resistance which is useful for planning strategies to combat antibiotic resistance and devise innovative therapeutic tools to fight against multidrug-resistant bacterial species.

Antibiotic resistant Pseudomonas aeruginosa infections are the primary cause of mortality in people with cystic fibrosis (CF). Yet it has only recently become appreciated that resistance mutations can also increase P. aeruginosa virulence, even in the absence of antibiotics. Moreover, the mechanisms by which resistance mutations increase virulence are poorly understood. In this study we tested the hypothesis that mutations affecting efflux pumps can directly increase P. aeruginosa virulence. Using genetics, physiological assays, and model infections, we show that efflux pump mutations can increase virulence. Mutations of the mexEF efflux pump system increased swarming, rhamnolipid production, and lethality in a mouse infection model, while mutations in mexR that increased expression of the mexAB-oprM efflux system increased virulence during an acute murine lung infection without affecting swarming or rhamnolipid gene expression. Finally, we show that an efflux pump inhibitor, which represents a proposed novel treatment approach for P. aeruginosa, increased rhamnolipid gene expression in a dose-dependent manner. This finding is important because rhamnolipids are key virulence factors involved in dissemination through epithelial barriers and cause neutrophil necrosis. Together, these data show how current and proposed future anti-Pseudomonal treatments may unintentionally make infections worse by increasing virulence. Therefore, treatments that target efflux should be pursued with caution.

Honey is a complex sweet food stuff with well-established antimicrobial and antioxidant properties. It has been used for millennia in a variety of applications, but those most noteworthy include treatment of surface wounds, burns and inflammation. A variety of substances in honey have been suggested as the key component to its antimicrobial potential; polyphenolic compounds, hydrogen peroxide, methylglyoxal and bee-defensin 1. These components vary greatly across honey samples due to botanical origin, geographical location and the individual bee. The use of medical grade honey, Medihoney and Revamil, in the treatment of surface wounds and burns has been seen to improve the healing process, reduce healing time, reduce scarring and prevent microbial contamination. Therefore, medical grade honeys should be used for these treatments and reduce the demand for antibiotic usage. In this review, we aim to outline the constituents of honey and how they affect the antibiotic potential of honeys in a clinical setting.

Water pollution, intensified by the release of hard-to-degrade pollutants, poses severe threats to ecosystems, human health, and economic development. The existing advanced oxidation processes often involve high operational costs and may result in secondary pollution, highlighting the necessity for innovative and more sustainable solutions. To address these challenges, our study introduces a cost-effective and eco-friendly corona discharge barrier plasma discharger for wastewater treatment. Through the central composite design/response surface methodology, a high decolorization rate of 98% of methylene blue (MB) within 10 minutes was achieved by optimizing parameters such as pH and voltage. Furthermore, the mechanisms of the generation of reactive oxygen species via this device was discussed in detail and the degradation pathways of MB were described. Moreover, this device is also very energy-efficient, with a low energy density and electrical energy per order of 0.15 watt/mL and 5.79 kWh/m³/order, respectively. In conclusion, the plasma discharger developed in this study provides a cost-effective and environmentally sustainable solution for dye wastewater treatment. This research contributes significantly to the advancement of sustainable dye wastewater management practices, offering an innovative method that meets both environmental and economic objectives.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Antibiotic resistance is a major public health issue that requires a multifaceted approach. One potential source of antibiotic-resistant bacteria is wastewater in developing countries, which often lacks proper treatment infrastructure and can release high levels of antibiotics and antibiotic-resistant bacteria into the environment. This review article summarizes current knowledge on strategies to combat antibiotic resistance in wastewater in developing countries. Our review highlights the importance of improving wastewater treatment infrastructure to effectively remove antibiotics and antibiotic-resistant bacteria, implementing measures to reduce the release of antibiotics into the environment, and monitoring and surveillance to track the presence and spread of antibiotic-resistant bacteria in wastewater. We also discuss the potential challenges and barriers to implementing these strategies and the need for further research to determine their effectiveness in real-world settings. Overall, this review highlights the need for a comprehensive approach to address antibiotic resistance in wastewater in developing countries and underscores the importance of addressing this issue to protect public health.

Analyzing the cells in various body fluids can greatly deepen the understanding of the mechanisms governing the cellular physiology. Because of the variability of physiological and metabolic states, it is important to be able to perform such studies on individual cells. Therefore, we developed an optofluidic system in which we precisely manipulated and monitored individual cells of Escherichia coli. We used laser tweezers Raman spectroscopy (LTRS) in a microchamber chip to manipulate and analyze individual E. coli cells. We subjected the cells to antibiotic cefotaxime, and we observed the changes by the time-lapse microscopy and Raman spectroscopy. We found observable changes in the cellular morphology (cell elongation) and in Raman spectra, which were consistent with other recently published observations. We tested the capabilities of the optofluidic system and found it to be a reliable and versatile solution for this class of microbiological experiments.

Multivariate statistical approaches (MSA), such as principal components analysis and multidimensional scaling, seek to uncover meaningful patterns within datasets by considering multiple response variables in a concerted fashion. Although these techniques are readily used by ecologists to visualize and explain differences between study sites, they could theoretically be employed to differentiate organisms within an experimental framework while simultaneously identifying response variables that drive documented experimental differences. Therefore, MSA were used herein to attempt to understand the response of the common, Indo-Pacific reef coral Seriatopora hystrix to temperature changes using data from laboratory-based temperature challenge studies performed in Southern Taiwan. Gene expression and physiological data partitioned experimental specimens by time of sampling, treatment temperature, and site of origin upon employing MSA, signifying that S. hystrix and its dinoflagellate endosymbionts display physiological and molecular signatures that are characteristic of sampling time, site of colony origin, and/or temperature regime. These findings promote the utility of MSA for documenting biologically meaningful shifts in the physiological and/or sub-cellular response of marine invertebrates exposed to environmental change.

Antibiotic resistance has emerged as one of the major concerns to public human health due to issues in treatment and control of major infectious diseases. From discovery of penicillin in 1940, the antibiotic resistance originated and now developed the microorganisms as resistive strains to the major available antibiotics. Furthermore, studies on this captivating activity of the microbes provide insight into the complexities of microbial physiology and may offer some guidance in preventing the onset and consequent development of antibiotic resistance. Despite of initiatives taken in last few decades to overcome the issues, the trends of antibiotic resistance gained much peak. Antibiotic resistance appears to have emerged as a result of various factors including antibiotics being misused and overused in both the medical field and the agricultural sector. Important factors in the development of antibiotic resistance also include bacterial mutation, unplanned evolution, and horizontal gene transfers. In addition, antibiotics resistance imposed the financial consequences to public health and drug development research. Future advancements related to innovative antibiotics and molecular drug designing become challenge for researchers due to intensive multiple antibiotics resistance among human population. Many researches have been conducted on origin, evolutionary aspect of antibiotic resistance and mechanisms of antibiotics resistance, but its effect on future drug development is little understood. Therefore, the recent review will highlight the role of antibiotic resistance in drug designing and impacts of antibiotic resistance on drug development in future.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

The fate of critically sick patients with infections in intensive care units (ICUs) is significantly influenced by antimicrobial resistance, which has become a serious concern in developing nations. This observational study was conducted at the IBN Sina Specialised Hospital in Dhaka, Bangladesh, over a 12-month period from January 2021 to December 2021, in order to track the pattern of antibiotic resistance among the patients admitted to the intensive care unit (ICU). Aspiration pneumonia (29%) and diabetes mellitus (24%), among 200 patients, were the most common main diagnoses. 65 samples (or 26%) of the 250 samples had 85 bacteria identified from them. Urine (14.12%) and tracheal aspirate (64.71%) were the most frequently found sites of infection. In the sample from the tracheal aspirate, Pseudomonas spp. (30.59%), Escherichia coli (24.71%), Acinetobacter spp. (20%), and Klebsiella spp. (14.12) were the most frequently isolated microorganisms. The following antibiotics were shown to have the highest overall patterns of resistance: levofloxacin (68.24), amikacin (64.71), meropenem (49.41), ceftazidime (75.29), ciprofloxacin (78.82), and gentamicin (82.35). The most effective antibiotic against Klebsiella species was meropenem (64.61%), while Acinetobacter species were mostly susceptible to cotrimoxazole (64.67%) and piperacillin + tazobactam (60.50%). Most susceptible to netilmicin (70.48%) and meropenem (49.32%) were Escherichia coli, while Pseudomonas spp. were mostly responsive to colistin (55.14%) and netilmicin (52.25%). Antibiotic resistance is common among intensive care unit (ICU) patients, and most isolated microbes have resistance to traditional medicines.

Seawater has been proposed as a reservoir for antibiotic resistant bacteria and antibiotic resistance genes, thus representing a risk to public health. In this study, we evaluated the presence of antibiotic resistance determinants (bacteria and genes) in 77 seawater samples collected at different points along the coast of the Gulf of Valencia (Spain). Specifically, indicators of fecal contamination bacteria, Escherichia coli and Enterococcus sp. were isolated, and their antibiotic resistance profiles were analyzed by using the Sensititre® system, followed by the detection of main antibiotic resistance genes (blaTEM, qnrS, tetW, sulI, and ermB). The highest frequencies of resistance in E. coli isolates were detected against ampicillin (35.1%) and ciprofloxacin (17.5%), followed by sulfamethoxazole and trimethoprim (15.7%), while 23% of enterococci isolates showed resistance to a single antibiotic, 20% against tetracycline and 3% against daptomycin. By PCR, 93% of the E. coli strains showed the blaTEM and sulI resistance genes. Among the enterococci, the presence of the blaTEM gene was detected in 40% of the isolates, while the rest of the genes were present at very low rates. Among the water samples, 57% were positive for at least one of the tested genes, being blaTEM gene the most commonly found (47%), followed by qnrS (33%) and sulI (23%) genes. These results show that seawater, in addition to having a high rate of fecal contamination, can contribute to the spread of antibiotic resistance.

Salmonella infection is one of major challenges to the poultry industry because of its pressing effects on health of poultry, food safety and human well-being that later may devastate economic losses to the poultry sector. The paper reviews public health implications and the use of antibiotics together with the risk of drug resistance. In recent years, the usage of probiotics in poultry industry has been growing to mitigate an increasing pressure to adopt sustainable farming practices. The mechanisms which probiotics may control Salmonella and important criteria for selecting effective probiotics in poultry are reported. Various studies highlighting the additional benefits of probiotics in poultry production in addition to Salmonella controls are also included. While probiotics offer promise in enhancing poultry health, challenges and limitations in their utilization must also be carefully considered.

Molecular analysis of growing teratoma syndrome has not been extensively studied. Here, we report a 14-year-old boy with a growing mass during treatment for a mixed germ cell tumor of the pineal region. Tumor markers were negative; thus, growing teratoma syndrome was suspected. A radical resection via the occipital transtentorial approach was performed, and histopathological examination revealed a teratoma with malignant features. Methylation classifier analysis confirmed the diagnosis of teratoma, and DMRT1 loss and 12p gain were identified by copy number variation analysis, potentially elucidating the cause of growth and malignant transformation of the teratoma. The patient remains in remission after intense chemoradiation treatment as a high-risk germ cell tumor.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

Background: Antibiotic resistance is an overwhelming serious difficulty globally. This necessitates the exploration of novel sources of antibiotics to overcome this challenge. Aim of the study: Bacterial Myxopyronin A production from various soil environments Egypt; as well as testing its antimicrobial activity in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Different soil environments in Egypt were screened for the growth of bacterial isolates producing Myxopyronin A as an antimicrobial agent. Purification of Myxopyronin A was performed via reversed-phase HPLC. Paper disc diffusion assay, as well as broth dilution technique, were exploited to assess the invitro antimicrobial and minimum inhibitory concentration( MIC) of the test antibiotic. Furthermore, in vivo antimicrobial spectrum, adverse drug reactions, and pharmacokinetics were detected during animal model testing stages and human randomized clinical trials phases 1/2. Results: From the culture supernatant of the Myxobacterium Myxococcus fulvus 124B02 which was the predominant soil bacterial isolate grown on the Casein yeast peptone plate, Myxopyronin A was produced. The test antibiotic blocked the growth of many Gram +ve bacteria with MICs less than 100 mcg/ ml; whereas it inhibited the growth of a few Gram -ve bacteria such as Escherichia coli at MICs greater than 100 mcg/ ml. On the other hand, Eukaryotic cells such as fungal and human cells were not affected. Prokaryotic DNA-dependant-RNA polymerase( RNLP) was noticed to be inhibited via the test antibiotic suggesting its bactericidal action. Cmax was 7-8 mcg/ ml at Tmax 2 hours when 600 mg dose was orally administered in randomized human clinical trials phases 1/2; as well as T1/2 reached 2.5 hours following first-order kinetics of elimination. The duration of its action was nearly 12 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and cholestatic jaundice in less than 5 % of experimental candidates. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin A from Myxococcus fulvus 124B02 isolated from different soil environments in Egypt.

Pseudomonas aeruginosa infections are the focus of new treatment alternatives due to their frequent development of resistance to antibiotics and formation of biofilms. Recently, emphasis has been placed on combinations of antibiotics with drugs used for different indications. In this study the combined effects of metformin with imipenem, ceftazidime, cefepime, ciprofloxacin and levofloxacin has been investigated. 50 P. aeruginosa isolates isolated from patients with cystic fibrosis come to Gaziantep University Microbiology Laboratory were included in the study. The susceptibilities of the isolates to antibiotics were investigated by the liquid microdilution method and the combined effect of metformin and antibiotics by the chequerboard synergy test. In our study, as a result of the chequerboard synergy test; synergy between ceftazidime and metformin 6%, partial synergistic 22% isolates; while no synergistic effect was detected between cefepime and metformin in any isolate, partially synergy 46%; synergy between imipenem and metformin 4%, partial synergy 10%; synergy between ciprofloxacin and metformin 6%, partial synergy 6%, antagonist effect 2%; synergy was detected between levofloxacin and metformin 2% and a partial synergy was detected 12%. This study shows that metformin could be a potential antibiotic in its current form or in different chemical forms to be produced synthetically.

Consumption of milk contaminated with antibiotic residues above the maximum residue limit (MRL) causes direct toxicity to humans and the development of superbugs that leads to the failure of antibiotic therapy and threatens human life. Besides, long-duration exposure might alter the nature of gut microflora results in the enhancement of many diseases. Therefore, we examined 300 raw and processed packet milk samples using thin layer chromatography (TLC) and ultra high performance liquid chromatography (UHPLC) method against five veterinary antibiotics and assessed the risk for consumers in Chattogram, Bangladesh. Risk analysis was calculated by using hazard quotient on the basis of 165 ml per capita milk consumption. We found a total of 7% prevalence of antibiotic residues in raw milk samples which were higher (8%) in individual samples than the pooled samples (4%). However, we did not find any processed packet milk samples as positive. The mean concentration of oxytetracycline residue was detected 61.29 µg/l and amoxicillin was 124 µg/l in individual milk samples. Risk analysis showed the hazard quotient values of 0.0056 for oxytetracycline and 0.0017 for amoxicillin residue which was confirmed that, no significant health risk associated with the consumption of milk produced and marketed in the study area. Our study might fill the gap of knowledge to measure the safety status of milk regarding public health issues.

Education and awareness raising are the primary tools of global health policy to change public behaviour. Considering the limitations of awareness agenda and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages, but also to learn about people’s conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity’s outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1,130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the activity influenced the awareness and understanding of “drug resistance,” while effects on attitudes were minor. Evidence on behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance.

Wastewater treatment plants (WWTPs) are thought to be potential incubators of antibiotic resistance. Persistence of commonly used antibiotics in wastewater may increase the potential for selection of resistance genes transferred between bacterial populations, some of which may pose a threat to human health. In this study, we measured the concentrations of ten antibiotics in wastewater plant influents and effluents, and in surface waters up- and downstream from two Charlotte area treatment facilities. We performed Illumina shotgun sequencing to assay the microbial community and resistome compositions at each site across four time points from late winter to mid-summer of 2016. Antibiotics are present throughout wastewater treatment, and elevated concentrations of multiple antibiotics are maintained in moving stream water downstream of effluent release. While some human gut and activated sludge associated taxa are detectable downstream, these seem to attenuate with distance while the core microbial community of the stream remains fairly consistent. We observe slight suppression of functional pathways in the downstream microbial communities, including amino acid, carbohydrate and nucleic acid metabolism as well as nucleotide and amino acid scavenging. Nearly all antibiotic resistance genes (ARGs) and potentially pathogenic taxa are removed in the treatment process, though a few ARG markers are elevated downstream of effluent release. Taken together, these results represent baseline measurements which future studies can utilize to help to determine which factors control the movement of antibiotics and resistance genes through aquatic urban ecosystems before, during and after wastewater treatment.

Researchers are increasingly concerned about microplastics (MPs) since they have proven to be detrimental to the environment and humans. They not only contribute to the accumulation of plastics in the environment, but they can also help spread micropollutants through absorption. MPs have entered the environment through a variety of channels, including direct discharge through human activities, the textile industry, and wastewater treatment systems. Wastewater treatment plants (WWTPs) are seen as the final line of defense, forming a barrier between MPs and the environment. The most common MPs found in wastewater are polyethylene terephthalate (PET), polyethylene (PE), polypropylene (PP), and polystyrene. The purpose of this study is to investigate and measure the efficacy of conventional and advanced technologies in removing microplastic. The fate of MPs in WWTPs and their impact on various wastewater treatment processes will be thoroughly examined. Both conventional and advanced methods of treatment will be discussed. Conventional methods include coagulation/flocculation, sedimentation, and filtration. Advanced treatment methods that will be discussed include membrane bioreactors, rapid sand filtration, electrocoagulation, and photocatalytic degradation. Despite the high removal of MPs, WWTPs remain an important entry point into aquatic and terrestrial systems due to the large volumes involved and the quantity of sludge reused through land application. Also, the complex interactions between MPs and other environmental pollutants may broaden MPs' effects on wastewater treatment processes, which have yet to be fully researched. Furthermore, potential issues with MP removal from treatment procedures and microplastic remediation techniques in drinking water was discussed.

This study surveyed the variation in Perfluorinated Compounds (PFCs) concentration entering urban wastewater treatment plants and proposed an optimal PFCS treatment method. The PFCS concentration in influent was shown to be affected by the types of industries and operating rate. The concentration of PFCs in the wastewater treatment effluent was slightly lower than that of influent. Thus, PFCs were considered to have barely been removed by the existing biological treatments. The pilot test result showed that about 10% of PFCs were removed by coagulation and precipitation, and the ozone and chlorine test also showed that few PFCs were removed regardless of the amount of injection. The activated carbon adsorption test showed that the removal was significantly increased by the empty bed contact time, with about a 60% removal in five minutes and over a 90% removal in 15 minutes. Therefore it is determined that a more stable and higher PFCs removal would result from the continuous oxidation processes such as ozone and adsorption processes such as activated carbon rather than a single biological treatment.

The emergence of the H3N2 influenza virus in 1968 marked a significant event as it crossed the species barrier. Since then, ongoing mutational dynamics have led to the formation of antigenic clusters, prompting the World Health Organization to advocate for regular updates to H3N2 vaccines. Research in the Western Pacific region underscores the necessity for heightened awareness and effective control strategies. Stemming from avian influenza A, the 1968 H3N2 influenza pandemic resulted in the deaths of one million people globally, with its seasonal variants primarily affecting older individuals and causing severe illness due to antigenic drift. To address the challenge of vaccine efficacy against H3N2 mutations, researchers are exploring innovative strategies such as precise antigenic material administration, controlled release patterns, understanding immune system mechanisms, and glycan engineering. This review comprehensively examines various aspects of the Influenza A (H3N2) virus, encompassing its virological characteristics, evolutionary trends, global epidemiology, vaccination strategies, antiviral interventions, and emerging diagnostic approaches. It underscores the impact of antigenic variation on vaccine design and effectiveness, seasonal outbreak patterns, pandemic potential, and the interplay between viral factors and host immune responses. Moreover, the review evaluates antiviral therapies and the issue of drug resistance, emphasising the necessity for multidisciplinary approaches involving researchers, healthcare professionals, and policymakers to comprehend H3N2 and enhance public health interventions.