Buruli ulcer is a chronic ulcerative disease of skin and subcutaneous tissues caused by infection with Mycobacterium ulcerans. Although Australian possums are known to be susceptible to Buruli ulcer, many aspects of the disease in possums, including welfare impacts, remain largely unreported. Severe clinical Buruli ulcer was identified in four common ringtail possums (Pseudocheirus peregrinus) from Melbourne, Victoria. All four possums were euthanised due to welfare concerns and poor prognosis, based on the presence of deep ulcerative lesions to paws, some of which exposed carpal or tarsal bones. These lesions were considered likely to cause partial or complete loss of limb function, which would severely affect the welfare and survival of these wild arboreal animals. Histologically, there was severe ulcerative necrotising pyogranulomatous dermatitis, panniculitis, and myositis, with intralesional acid-fast bacteria. M. ulcerans was detected by real-time PCR in all swabs and biological tissues collected from all four cases. Buruli ulcer may be an important and under-recognised cause of poor possum welfare in endemic areas. In addition to severe cutaneous lesions, infection extends to underlying bones and joints, and the systemic distribution of M. ulcerans throughout all major tissues and internal organs, as observed in these four cases, may further impact the health and fitness of infected possums. Further research is needed to investigate the epidemiology, pathogenesis and impacts of Buruli ulcer in possums, and to inform the design of interventions that may protect the health and welfare of possums and other affected animal species.

Wound infections evidently appeared in times of World War I that accounted a significant mortality and morbidity rate among injured soldiers. Currently, around 11 million people worldwide require medical treatment for wound infections and 300,000 die every year due to untreated wound infection. The extensive use of antibiotics to treat wound infection leads to emerging new microbial strains that are resistant to many antibiotics. There is a growing concern on the emergence and re-emergence of drug-resistant pathogens such as multi-resistant bacterial strains. Hence, the development of new antimicrobial compounds or the modification of those that already exist to improve antibacterial activity is a high priority area of research. During the past few decades, nanotechnology has arisen with new promising technology for synthesis of nanobiomaterials. Metallic nanoparticles (NPs) are considered as new alternative treatment with superior antibacterial activity. In this study, new formulation of titanium oxide (TiO2) NPs with different sizes were synthesized and characterized. Genotoxicity, mutagenicity and antibacterial activities of TiO2 NPs against the causative agents of wound infection were investigated. Antibacterial activity of TiO2 NPs was conducted against three ATCC ® bacterial strains: methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa. The results clearly illustrate a superior antibacterial activity of all newly formulated TiO2 NPs against the most causative agents of wound infection. Most of our TiO2 NPs showed non-genotoxic and non-mutagenic results at the maximum concentrations. Findings of this study will enhance the future of the therapeutic strategies against the resistant pathogenic strains that cause wound infections.

In the course of our ongoing research targeting the identification of potential biocontrol agents from entomopathogenic fungi (EPF), we explored a solid-state rice fungal extract of Blackwellomyces roseostromatus BCC56290 derived from infected lepidopteran larvae. Chemical and biological prospections afforded four unprecedently reported natural products differentiated into one dimeric naphthopyran bioxanthracene ES-242 derivative (1) and three cyclodepsipeptides (2-4) in addition to two known cyclodepsipeptides, cardinalisamides B (5) and C (6). Chemical structures of the isolated compounds were elucidated through comprehensive 1D/2D NMR and HR-ESI-MS data together with comparisons to the reported literature. The absolute configuration of the isolated cyclodepsipeptide was determined using Marfey’s method. All isolated compounds were assessed for their antimicrobial, cytotoxic and nematicidal activities with some compounds revealed significant activities.

Wounds are an increasing global concern, mainly due to a sedentary lifestyle, frequently associated to the occidental way of life. The current prevalence of obesity in western societies, leading to an increase in type II diabetes, and an elderly population, are also a key factor associated to the problem of wounds healing. Therefore, it stands essential to find wound dressing systems allowing reestablishing the skin integrity in the shortest possible time and with the lowest cost, avoiding further damage and promoting patients´ well-being. Wounds can be classified into acute or chronic, depending essentially on the duration of the healing process, which is associated with. It depends on the extent and depth of wound, localization, level of infection and on the patient health status. For each kind of wound and respective healing stage there is a more suitable dressing. The aim of this review was to focus on the possible wound dressing management, aiming the more adequate healing approach for each kind of wound.

Because data on the fungal gut community structure of African children are scarce, we aimed to describe by reanalysing rRNA ITS1 and ITS2metabarcoding data from a study designed to assess the influence of microbiota in malaria susceptibility in Malian children from the Dogon country. More specifically, we aimed to establish the core gut mycobiome and compare the gut fungal community structure of breastfed children, aged 0-2 years, with other age groups. Briefly, DNA was extracted from 296 children’s stool samples. Both rRNA ITS1 and ITS2 genomic barcodes were amplified and subjected to Illumina MiSeq sequencing. The ITS2 barcode generated 1,975,320 reads and 532 operational taxonomic units (OTUs), while the ITS1 barcode generated 647,816 reads and 532 OTUs. The alpha diversity was significantly higher by using the ITS1 compared to the ITS2 barcode (p

French Guiana, located in the Guiana Shield, is a natural reservoir for many zoonotic pathogens that are of considerable medical or veterinary importance. Until now, there are few data available on the description of parasites circulating in this area, especially on protozoan belonging to the phy-lum Apicomplexa; conversely, the neighbouring countries describe a high parasitic prevalence in animals and humans. Epidemiological surveillance is necessary, as new potentially virulent strains may emerge from these forest ecosystems, such as Amazonian toxoplasmosis. However, there is no standard tool for detecting protozoa in wildlife. In this study, we developed Meat-Borne-Parasite, a high-throughput meta-barcoding workflow for detecting Apicomplexa based on Oxford Nanopore Technologies sequencing platform using the 18S gene of fourteen Apicomplexa-positive samples collected in French Guiana. Sequencing reads were then analysed with MetONTIIME pipeline. Thanks to a scoring rule, we were able to classify as Apicom-plexa-positive 10 samples out of 14 and reveal the presence of co-carriages. The same samples were also sequenced with Illumina platform, for validation purposes. On samples identified as Apicomplexa-positive by both platforms, a strong positive correlation at up to genus level was reported. Overall, the presented workflow represents a reliable method for Apicomplexa detec-tion, which may pave the way for more comprehensive biomonitoring of zoonotic pathogens.

Polycyclic polyprenylated acylphloroglucinols (PPAPs) comprise a large group of compounds of mostly plant origin. The best-known compound is hyperforin from St. John's wort with its antidepressant, antitumor and antimicrobial properties. Chemical synthesis of PPAP variants allows the generation of compounds with improved activity and compatibility. Here we studied two synthetic PPAP-derivatives, PPAP 23 and PPAP 53, as to their antimicrobial activity. While PPAP 23 is insoluble in water, PPAP 53, the sodium salt, is water-soluble. In vitro, both compounds exhibited good and comparable activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium. Both compounds had no adverse effects on Galleria mellonella wax moth larvae, even at high concentrations. However, they were unable to protect the larvae from infection with S. aureus because components of the larval coelom neutralized the antimicrobial activity; a similar neutralizing effect was also seen with serum albumin. In a septic arthritis model triggered by S. aureus PPAP23 decreased the formation of abscesses and bacterial load in kidneys, and in a mouse skin abscess model topical treatment with PPAP 53 resulted in an approximately two-fold reduction in S. aureus counts. PPAP 23 and PPAP 53 also showed high growth inhibiting activity against anaerobic Gram-positive pathogenic gut bacteria such as Clostridium perfringens and Clostridium difficile. Based on these results, we envision potential application of PPAP 23 and PPAP 53 in the topical treatment of wound infections with Gram+ pathogens, and their oral use in intestinal infections with C. difficile.

Phyllanthus emblica (P. emblica) has been described in many studies to have multiple therapeutic activities and is considered an important part of Ayurvedic and Unani medicinal systems. This study successfully synthesized P. emblica loaded polyvinylalcohol/gelatin based cryogels (PVA/Gel/P.emblica) to examine their potential in wound dressing applications. Swelling tests, Brunauer-Emmett-Teller (BET) and morphology analysis were conducted within the scope of characterization studies. In vitro cell culture studies were performed using HaCaT cells to illustrate the suitability of the synthesized cryogels as wound dressing material. The swelling tests and BET analysis results showed that swelling and surface area properties of cryogels increased with increasing P. emblica amounts. Morphological results displayed that the cryogels had a dense, interconnected pore morphology and a macroporous structure. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), trypan blue exclusion and live-dead assay results revealed that adding of P. emblica into cryogels led to enhanced cell proliferation, increased cell number, and improved cell viability. Based on the phase contrast microscope, scanning electron microscope (SEM), immunofluorescence and giemsa staining images, it was observed that P. emblica promoted cell attachment, proliferation and penetration. In conclusion, it has been shown that PVA/Gel/P.emblica cryogels are suitable for use as wound dressing materials and can be developed with further studies.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

Oncolytic virotherapy is a promising immunotherapy approach for cancer treatment, utilizing viruses to preferentially infect and eliminate cancer cells while stimulating immune responses. In this review we synthesize current literature on the molecular circuits of immune sensing and response to oncolytic virotherapy; focusing on viral DNA or RNA sensing by infected cells, cytokine and danger-associated signal sensing by neighboring cells, and subsequent downstream activation of immune pathways. The sequential sense-and-response mechanisms involve the triggering of molecular sensors by viruses or infected cells to activate transcription factors and related genes for a breadth of immune responses. We describe how molecular signals induced in the tumor upon virotherapy can trigger diverse immune signaling pathways, activating both antigen-presenting cell-based innate and T cell-based adaptive immune responses. Insights into these complex mechanisms provide valuable knowledge for enhancing oncolytic virotherapy strategies.

Coronavirus disease-19 (COVID-19) has disproportionately affected certain demographics in England, exacerbating existing health disparities. Effective therapeutics are a critical line of defence against COVID-19, particularly for patients at elevated risk for severe disease. Surveillance systems were established to monitor usage of COVID-19 therapeutics in hospital and community settings and inform stewardship. Three antiviral therapies: nirmatrelvir plus ritonavir (Paxlovid®), remdesivir (Veklury®), and molnupiravir (Lagevrio®); and two neutralising monoclonal antibody therapies (nMAbs): sotrovimab (Xevudy®) and casirivimab with imdevimab (Ronapreve®); were in use in England between July 2020 to April 2023. This paper aims to illuminate trends in the utilisation of COVID-19 therapeutics treatment in both hospital and community settings, stratified by the Index of Multiple Deprivation (IMD) in England. Chapter 3 of the English Surveillance Programme for Antimicrobial Utilisation and Resistance (ESPAUR) report 2022 to 2023 also discusses the epidemiological surveillance of these five directly-acting antiviral COVID-19 therapeutics use in England between 2022 to 2023.

Corneal ulcers are a common and potentially vision-threatening condition in horses that can be challenging to treat with conventional therapies alone. This case report describes the successful treatment of a non-healing corneal ulcer in a 28-year-old Hispano-Bretón mare using the secretome derived from adipose tissue-derived mesenchymal stem cells (ASCs). Despite initial treatment with antibiotics, anti-inflammatory drugs, and surgical debridement, the corneal ulcer failed to heal properly, exhibiting persistent epithelial defects and stromal complications. As an alternative regenerative approach, the ASC secretome, a rich source of trophic factors, cytokines, and extracellular vesicles, was topically administered to the affected eye. Remarkably, within one week of secretome treatment, the clinical signs of blepharospasm and epiphora resolved, and the corneal ulcer exhibited complete re-epithelialization, regained transparency, and reduced neovascularization. No recurrence was observed during the 1.5-year follow-up period. This case highlights the potential therapeutic benefits of ASCs secretome in promoting corneal wound healing and suggests its promise as a novel cell-free therapy for treating refractory corneal ulcers in horses.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in rodents (mice, rats, rabbits) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023–31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3, and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

In the early 2000s, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) emerged as a performant and relevant tool for identifying micro-organisms. Since then, it has become practically essential for identifying bacteria in microbiological diagnostic laboratories. In the last decade, it was successfully applied for arthropod identification allowing to distinguish vectors from non-vectors of infectious diseases. However, identification failures are not rare, hampering it widely use. Failure is generally attributed either to the absence of respective counter species MS spectra in the database, or to the insufficient quality of query MS spectra (i.e. lower intensity and diversity of MS peaks detected). To avoid matching errors due to non-compliant spectra, the development of a strategy for detecting and excluding outlier MS profiles became compulsory. To this end, we created MSProfileR, an R package leading to a bioinformatics tool through a simple installation, integrating the control quality system of MS spectra and an analysis pipeline including peak detection and MS spectra comparisons. MSProfileR can also add metadata concerning the sample that the spectra are derived from. MSProfileR has been developed in the R environment and offers a user-friendly web interface using the R Shiny framework. It is available on Microsoft Windows as a web browser application by simply navigation using the link of the package on the Github. MSProfileR is therefore accessible to non-computer specialists and is freely available to the scientific community. We evaluated MSProfileR using two datasets including exclusively MS spectra from arthropods. In addition to coherent sample classification, outlier MS spectra were detected in each dataset confirming the value of MSProfileR.

In tropical developing regions, typhoid fever and malaria often co-occur, posing serious health risks. The two illnesses have similar symptoms, which makes diagnosis and treatment more difficult. Through a thorough analysis of existing literature on typhoid fever, malaria, and co-infection, including research articles, case studies, and review papers, this review seeks to understand the dynamic interactions between typhoid fever and malaria co-infection. The review highlights important problems with co-infection between typhoid and malaria, such as higher morbidity and death, diagnostics-related challenges, and antibiotic resistance. Overlapping symptoms and limitations in current diagnostic tests impede accuracy. Treatment plans are made more difficult by the advent of typhoid strains that are resistant to drugs. The analysis concludes by highlighting the necessity of developing more sensitive and specific diagnostic methods in order to accurately diagnose co-infections. Going forward, the review emphasizes the need for more investigation into the immunological connections between malaria and typhoid illnesses. Essentially, this paper offers a thorough summary of the difficulties and possibilities related to co-infection between typhoid and malaria. It provides a framework for upcoming studies and initiatives that seek to improve public health and patient outcomes in the face of these intricately linked health problems.

Introduction: Chronic wounds caused by diabetes or lower-extremity artery disease are intractable because the wound healing mechanism is no longer effective due to the poor environment of the wound bed. Biosheet obtained using in-body tissue architecture (iBTA) is a collagen-based membranous tissue that is created within the body and autologously contains various growth factors and somatic stem cells including pluripotent stem cells. When applied to a wound, granulation formation can be promoted and even epithelialization may be achieved. Hearin, we report our clinical treatment experience with seven cases of intractable diabetic foot ulcers. Cases: From 46- to 93-year-old 7 patients had large foot ulcers including heel area, which was failed to heal with standard wound treatment. Methods: Two or four Biosheet-forming molds were implanted subcutaneously in the chest or abdomen, and after 3 to 6 weeks, the molds were removed. Biosheets that formed inside the mold were obtained and applied directly to the wound surface. Results: In all cases, there were no problems with the mold embedding and removal procedures, and Biosheets were formed without any infection or inflammation during the implantation period. The Biosheets were simply applied to the wounds, and in all cases, they adhered within one week, did not fall of, and became integrated with the wound surface Complete wound closure was achieved within 8 weeks in two cases and within 5 months in two cases. One patient was lost due to infective endocarditis from septic colitis. One case required lower leg amputation due to the wound recurrence, and one case achieved wound reduction and wound healing in approximately 9 months. Conclusion: Biotube obtained via iBTA promoted wound healing and were extremely useful for intractable diabetic foot ulcers involving heel area.

Background: A Morel–Lavallée lesion (MLL) is a traumatic, internal closed degloving injury that results from shearing of subcutaneous tissue away from underlying fascia, usually associated with high-velocity trauma. Case presentation: A 52-year-old man was transported to hospital for further follow-up of a superficial femoral artery injury. Examination on admission showed bruising seen around the left thigh. Contrast-enhanced computed tomography of the left thigh revealed hematoma with extravasation from a branch of the left superficial femoral artery, but no apparent aneurysms or femoral fractures. The patient was treated with compression bandages and discharged on hospital day 6. He left hospital able to walk unaided. He subsequently complained of left thigh pain with swelling and visited the hospital several times. He was treated at another outpatient clinic and was diagnosed with MLL. Single-use disposable portable negative pressure wound therapy (NPWT) was applied for about 2 months, achieving a stable wound site. Conclusion: We encountered a case of MLL successfully treated with single-use portable NPWT. This report presents the case of a patient with isolated MLL without fracture in the left thigh, in which the diagnosis was missed on initial admission. Finally, the patient received minor interventions including drainage along with tissue debridement and portable NPWT. We reviewed the relevant literature and summarize the pathogenesis, clinical manifestations, and treatment strategies for MLL. Emergency physicians require an increased understanding of MLL to avoid misdiagnosis and missed diagnosis.

Chronic wounds remain a significant clinical challenge, necessitating the exploration of novel therapeutic agents. Sedum telephium L. (syn. Hylotelephium telephium (L.) H. Ohba) leaf juice, known for its traditional medicinal uses, was evaluated for its wound healing properties. This study aimed to chemically characterize the leaf juice and assess its efficacy in promoting wound healing in vitro. Fresh leaves were collected and processed to obtain the juice, which was analyzed for polyphenols, flavonoids, polysaccharides, and proteins. Key bioactive compounds, including flavonols such as kaempferol glycosides and quercetin glycosides, were identified. The juice and its polysaccharidic fraction were tested on human keratinocytes (HaCaT) and fibroblasts (HFF-1) to assess cell viability, wound closure, and the production of growth factors and pro-collagen I. Our results indicated that the whole juice significantly enhanced wound closure in both cell types, with a marked increase in fibroblast growth factor (FGF) and LAP(TGF-β1) production in keratinocytes, highlighting its potential mechanisms of action. The polysaccharidic fraction alone showed limited efficacy, emphasizing the importance of the complete phytocomplex. These findings suggest that Sedum telephium L. represents a promising candidate in the setting of skin regeneration and repair.

Micellar Casein Concentrate (MCC) is manufactured from microfiltration (MF) of skim milk utilizing ceramic or polymeric membrane filtration. While ceramic filtration has higher efficiency, use of polymeric is cost effective and the process is familiar to several US dairy processors. The aim of the present study was to develop an optimized membrane filtration process to produce MCC using spiral wound polymeric membrane filtration (SW MF) system by systematic selection of transmembrane pressure (TMP) and level of diafiltration (DF). Using skim milk as feed material, preliminary lab-scale MF experiments were conducted using 0.5 µm polyvinylidene fluoride (PVDF) membrane. Three TMP (34.5, 62.1, and 103.4 kPa) and three levels of DF (70, 100, and 150%) along with a process without DF as control were used in the study. Effect of TMP and effectiveness of DF on flux rates, SP removal, casein to total protein (CN/TKN) ratio, casein to true protein (CN/TP) ratio, rejection of casein (rej CN) and SP (rej SP) were evaluated. At all TMP values used in the study, the overall flux (O Flux) increased with the level of DF. Highest O Flux of 30.77 liter per meter square per hour (LMH) was obtained with 34.5 kPa pressure and 150% DF. The impact of DF was more pronounced at lower pressures than at the higher pressures used in the study. With controlled DF, instantaneous flux was maintained within 80% of initial flux for the entire process run. For all the experiments, casein has a rejection of 0.97 to 1.0, while serum protein has the lowest rejection of 0.10 at 34.5 kPa pressure and 150% DF level. Use of 34.5 kPa and DF level of 150 % contributed to 81.45% SP removal, and casein to true protein ratio of 0.96. SP removal data from the lab-scale experiments were fitted into a mathematical model using DF and square of TMP as factors. The model predicts SP removal within 90-95% of actual SP removal got from the pilot plant experiments.

Diarrhea is a common occurrence following vascular organ transplantation, including kidney transplants. It can be induced by non-infectious factors, adverse effects of immunosuppressive drugs, or infectious agents such as viruses, bacteria, fungi, or parasites. Intestinal protozoan parasites, include Cryptosporidium spp., are causes of infectious diarrhea particularly in immunocompromised patients. This review aims to summarize reports on epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in adult patients, particularly following kidney transplantation.

Wounds are structural and functional disruptions of the skin that occur because of an accident. Chronic wounds are caused by a breakdown in the finely coordinated cascade of events that occurs during wound healing. Wound healing is a long process that split into at least three continuous and overlapping processes: an inflammatory response, a proliferative phase that leads to tissue repair, and third one is tissue remodeling. Therefore, wound healing studies are extensively studied to develop techniques that can achieve maximum recovery with minimum scar. Several growth hormones and cytokines secreted at the wound site tightly regulate wound healing processes. The traditional approach for wound management has been represented by topical treatments. Metal nanoparticles (e.g., silver, gold, zinc) are increasingly being employed in dermatology due to their favorable effects on wound healing, as well as in treating and preventing bacterial infections. The development of wound dressings materials has now been used to overcome the issues of external environments. The impregnated nanomaterials have provided moist environment that removes the exudates and avoid maceration. This review highlights the mechanism and focus on the current advancement of various nanoparticles impregnation material for wound healing process that can protect wound from infection and maintain the optimum exchange of gases.

Background: Schistosome egg deposition in pregnant women may affect the placenta of infected mothers and cause Placental Schistosomiasis (PS). Histopathological examination of placental tissue is an inadequate detection method due to low sensitivity. So far, there has not been any sys-tematic review on PS. Methods: We conducted a systematic literature search on PubMed and in-cluded relevant secondary literature found in the citations of the primarily included publications. Results: We found a total of 8 publications describing PS with a total of 92 cases, describing egg deposition of dead and/or viable eggs and worms of S. haematobium and S. mansoni in placental tissue. One cross-sectional study investigating the prevalence of PS and its association to adverse birth outcomes, found 22% of placentas to be infested using a maceration technique but only < 1% using histologic examination. Additionally, no direct link to deleterious pregnancy outcomes could be shown. Conclusions: PS is a highly unattended and underdiagnosed condition in en-demic populations, due to a lack of awareness as well as low sensitivity of histopathological examinations. However, PS may play an important role in mediating or reinforcing adverse birth outcomes (ABO) such as fetal growth restriction (FGR) in maternal schistosomiasis, possibly by placental inflammation.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

Background: Endovascular treatment of popliteal aneurysms (PA) has increased in the last few years, quickly becoming the main treatment in many vascular centers, based on the acceptable and promising outcomes reported in the literature. However, endograft infections are the most dangerous complication as a serious local compromise and usually require open surgical conversion and device explantation to preserve the affected extremity. Case report: We reported two patients admitted to the emergency room for pain and edema in the lower leg. Both patients have undergone exclusion of ruptured PA a few years before by endovascular graft. CTA showed a significant volume of fluid-corpuscular collection related to perianeurysmal abscess collection in both cases. Blood cultures and drained material cultures were positive for Staphylococcus Capitis in the first case and S. Aureus in the second. The antibiotics prophylaxis was performed for 10 days, then, patients underwent an open surgical conversion with a complete explantation of endovascular material and a femoro-popliteal bypass using an autologous vein in the first case and biological bovine pericardium prosthesis in the other case. Furthermore, we have questioned the literature and found eight more cases described in case report article referred to popliteal graft infections by different microorganisms, mostly presenting acute limb ischemia as the first symptom and suggesting endograft explantation with open conversion and autologous vein bypass as the commonest therapeutic choice. Conclusions: Open surgical conversion of popliteal endograft infection is the best strategy to manage peripheral infection of the popliteal stent.

Blood stream infections (BSI) due to carbapenem-resistant gram-negative bacilli (CR-GNB), especially Klebsiella pneumoniae carbapenemase (KPC) and New-Delhi metallo-β-lactamase (NDM) producers, are a major concern of public health, as they are associated with high morbidity and mortality. We conducted a single-center, retrospective, observational study at a tertiary-care, teaching Greek hospital, to determine the incidence, 30-day and overall, in-hospital, crude mortality, risk factors and efficacy of best available treatment options in patients with BSIs from KPC- or NDM-producing GR-GNB. During the one-year study period, from 1st January to 31st December 2023, we recorded 133 episodes of BSIs in 118 unique patients; 79 episodes were due to KPC-producing and 54 to NDM-producing CR-GNB. Our study showed relatively high incidence of BSIs by both KPC- and NDM-producing CR-GNB (0.49 and 0.31 episodes per 1000 patient-days respectively). We found high 30-day crude mortality rates for patients with BSIs due to KPC- producing CR-GNB (26.4 %), and NDM-producing CR-GNB (37%), while BSIs due to NDM-producing P. aeruginosa had the highest 30-day (47.1%) and overall (70.6%) in-hospital, crude mortality. Beta-lactam/beta-lactamase inhibitors as monotherapy or in combination with other active agents used to treat KPC-producing CR-GNB were associated with improved survival rates (p=0.009).

This review was written with the aim of examining the effects that caused an insult such as a wound to an organ such as the skin. Before examining the cellular mechanisms relating to wound healing, the reader is invited to read the structure of the skin as a necessary basis for understand-ing the final aim of this review. The structure of the skin as a basis for understanding the phe-nomena relating to wound healing is addressed taking into account updated literature that ad-dresses the numerous problems of the skin microenvironment. Starting from this awareness, the paragraph dedicated to wound healing becomes complicated when this phenomenon is not im-plemented and therefore the problems dedicated to chronic wounds, keloids and hypertrophic scars are addressed, pathologies that are still difficult to understand and treat today.

Objective: To explore the hot spots and development trends of community public health research. Methods: The literature related to this topic was searched in CNKI and PubMed databases, and the trend map of the number of articles was drawn according to the obtained data. The included literature were analyzed with Vosviewer software for keyword and author co-occurrence, and CiteSpace 6.3.R1 Basic software was used for mechanism co-occurrence, key emergence and clustering analysis, and timeline distribution map drawing. Results: 189 Chinese literature and 77 English literature were selected. The Chinese literature focused on “community public health service, emergency management, and community governance”, and the research trend was “community public health emergency management and community governance”; English literature focuses on “nursing education, health education, human qualitative research”. Conclusion: Although the Chinese and English literature shows that scholars in this field have different emphases, the primary community health is the key and difficult point to realize the national public health service project, and improving the basic public health service in the primary community is related to the health of all the people, so it is very important.

(1) Background: Several chronic respiratory diseases could be a risk factor for acquiring SARS-CoV-2 infection: among them, Primary Ciliary Dyskinesia (PCD) is a rare (about 1:10.000) inherited ciliopathy (MIM 242650) characterized by recurrent upper and lower respiratory tract infections due to a dysfunctioning of the respiratory cilia; We aimed to investigate if some polymorphisms of the TAS2R38 bitter taste receptor correlate with an increased prevalence of SARS-CoV-2 infection and severity of symptoms in a cohort of PCD subjects; (2) Methods: Patients answered several questions about possible SARS-CoV-2 infection, experienced symptoms and vaccinations; in case of infection, they also filled out a SNOT-22 and ARTIQ questionnaires; (3) Results: Forty PCD adult patients (mean age 36.6 ± 16.7 years, 23 females) participated to the study, out of which 30 % had tested positive for COVID-19 during the last four years; most of them reported a mildly symptomatic disease. We found no differences in age or sex, but a statistic significant difference (p=0.03) was observed in body mass index (BMI), that was higher in the COVID-acquired group (23.2 ± 3.3 vs 20.1 ± 4.1 kg/m2). Genotyping for TAS2R38 polymorphisms showed a prevalence of 28.6% PAV/PAV, 48.6% PAV/AVI and 22.8% AVI/AVI individuals in our cohort. In contrast to our hypothesis, we did not observe a protective role of PAV allele towards SARS-CoV-2 infection; (4) Conclusions: Our findings suggest that subjects with PCD may not be at increased risk of severe outcomes from COVID-19 and the TAS2R38 bitter taste receptor genotype type does not affect SARS-CoV-2 infection.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

Introduction: The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection may cause acute respiratory failure but also remains responsible for many other pathologies, including electrolyte disorders. SARS-CoV-2 infection can cause dysfunction of the renin-angiotensin-aldosterone system and disrupt water hemostasis with thirst and appetite abnormalities. Dysnatremia affects prognosis and may be associated with mortality in patients admitted to SARS-CoV2 intensive care. Patients and Methods: The study included 209 patients admitted to the Intensive Care Unit between April 12, 2021, and March 1, 2022 who were over 18 years old and diagnosed with SARS-CoV-2 infection by clinical and thoracic tomography findings or with a positive reverse transcription polymerase chain reaction (RT-PCR) test result. The laboratory markers, treatment modalities, nutritional, and respiratory support also for outcome evaluation, length of stay in the ICU, total hospitalization duration, and mortality in ICU were recorded.The laboratory marker comparison was made admission with the final assessment performed before the time of mortality in ICU or discharge. Results: Inotropic requirements among patients were high which was reflected in the first-month mortality. Hypernatremia presence was associated with an increase in enteral support and inotropic support requirement and mortality. Hypernatremia was correlated with diabetes mellitus, chronic renal failure, and a longer duration under mechanical ventilation. Discussion: Hypernatremia was an important risk factor in ICU patients hospitalized for SARS-CoV-2 infection, which was also affected by the treatment regimens given itself. This complex relationship underlies the importance of proper electrolyte management, especially in patients who were under severe stress and organ failure.

Abstract Objective: To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Background: Analgesia with local anesthetics following surgery is a critical element of alleviating postoperative pain. However, such strategies in neck surgery has not been a well-established practice. Methods: This prospective double-blind randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration the study participants were randomly allocated into three groups: 1) 100 mg of ropivacaine (Group R), 2) 100mg of ropivacaine plus magnesium sulfate 10mg/kg (Group RMg), and 3) normal saline which served as placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 minutes, as well as 1, 2, 4, 6, 12, and 24 hours postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 minutes before infiltration, 6 hours and 24 hours postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operational, wound or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the group RMg. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery.

Acquired immunodeficiency syndrome (AIDS) has transitioned from a progressive, fatal disease to a chronic, manageable disease thanks to better defining of antiretroviral therapy, hence contributing to increased life expectancy. In parallel, a growing number of subjects without overt clinical signs of disease but living with chronic HIV infection (people living with HIV, PLWH) are experiencing early cardiovascular disease worldwide. However, a progressive increase in the prevalence of multiple comorbid diseases has been reported as these patients age, including cardiovascular disease (CVD). Cardiovascular mortality can be either directly related to the viral infection, a progressive reduction of response to the antiretroviral therapy, chronic inflammation or lifestyle-related. Cardiovascular ageing represents a relevant issue in the management of HIV-infected patients. Although the exact pathophysiological mechanism that leads PLWH to develop cardiovascular disease is not entirely understood, there is substantial evidence that they accumulate age-related conditions earlier than the general population. Furthermore, since the proportion of PLWH growing older than 50 years has progressively increased, this results in a complex interaction between disease-related pathophysiology and the exposition of a growing burden of cardiovascular risk factors. For this reason, we performed a systematic review of the genes most frequently associated with ageing in HIV-infected subjects, followed by a bioinformatic analysis to explore the biological impact of the genes related to ageing.

COVID-19 infection is extremely dangerous for persons with comorbidities such as kidney disease and diabetes. Although many people of all ages and socioeconomic backgrounds have suffered due to this pandemic, those with underlying medical conditions like kidney disease and diabetes are more vulnerable to becoming infected with COVID-19 related to weak immunity. However, the role of vaccination in the co-infection of COVID-19 with diabetics is not available in the literature. Therefore, we examine the unique challenges presented by the co-infection of COVID-19 in individuals with diabetes, focusing on its disease transmission dynamics. A mathematical modelling technique is to be employed in this work to analyse the dynamics of COVID-19 outbreaks with seven compartments, including vaccination with comorbidities such as diabetes. We also investigated analytically by displaying the solutions' existence, boundedness, positivity and sensitivity. After calculating the basic reproduction numbers, the stability analysis of model equilibrium points is also covered. If the reproduction numbers are less than unity, the disease-free equilibrium points of the model appear to be both locally and globally stable. The findings of this study are that as the vaccination rate rises, the incidence of COVID-19 and its co-infections with diabetes decreases. Effective disease treatment strategies may be based partly on the possible impact of vaccination on the co-infection of COVID-19 related to diabetic disease insights.

Viral contamination in the aquaculture industry is a significant challenge that requires further research. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play a role in regulating various biological processes, including immunity. However, most studies have focused on model organisms, and little is known about non-coding RNAs in the immune response to viral hemorrhagic septicemia (VHS) in rainbow trout. In this study, we investigated the listing of non-coding RNAs (ncRNAs) in rainbow trout challenged with VHS virus. We explored their potential role in defense-like responses based on transcriptomic analysis of the virus-treated and control groups. As a result of this research, 4207 lncRNAs were identified, of which 182 lncRNAs were differentially expressed between treated and untreated samples. Among 7753 lncRNA transcripts, 1920 were novel intergenic (class code “u”), and 3748 transcripts were potentially novel isoform of lncRNAs. Gene ontology analysis revealed biological pathways associated with the stress response and immune signaling. Pairs of genes such as TP63-MSTRG.62, IL10-MSTRG.9783, IL10-MSTRG.9784, TK1-MSTRG.22826, and MSTRG.17881-GLI1 showed cis interactions, while DOCK10-MSTRG.30015, MSTRG.36357-LOC101268921, and MSTRG.34190-ENPP2 showed trans interactions. In this study, the role of lncRNAs in regulating the expression of the target genes was clearly identified. This finding is consistent with the regulatory processes of immune system responses mediated by cytokines, as well as the regulation of oxygen levels in response to viral infection. The information presented here highlights the various regulatory mechanisms of lncRNAs in the expression of immune system genes in fish treated with VHS virus.

Autologous platelet-rich plasma (PRP) preparations are prepared at point of care. Centrifugation cellular density separation sequesters a fresh unit of blood into three main fractions: a platelet-poor plasma (PPP) fraction, a stratum rich in platelets (platelet concentrate) and, bioformulation dependent, also leukocyte and erythrocyte fractions. The employment of autologous platelet concentrates facilitates the biological potential to accelerate and support in numerous cellular activities that can lead to tissue repair, tissue regeneration, wound healing, and ultimately functional structural repair. Normally, after PRP preparation the PPP fraction is discarded. One of the less well known, but equally important features of PPP is that particular growth factors (GFs) are not abundantly present in PRP, as they reside outside the platelet alpha granules. Precisely, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF) are mainly present in the PPP fraction. In addition to their roles as angiogenesis activators, these plasma-based GFs are also known to inhibit inflammation, fibrosis, and they promote keratinocyte migration and support in tissue repair and wound healing. Additionally, PPP is known for the presence of exosomes and other macrovesicles, exerting cell-cell communication and cell signaling. Newly developed ultrafiltration technologies incorporate PPP processing methods by eliminating in a fast and efficient manner plasma water, cytokines, molecules, and plasma proteins with a molecular mass (weight) less than the pore size of the fibers. Consequently, a viable and viscous protein concentrate of functional, total proteins, like fibrinogen, albumin, and alpha-2-macroglobulin is created. Consolidating a small volume of high platelet concentrate with a small volume of highly concentrated protein-rich PPP creates a protein rich platelet concentrate (PRPC) biological preparation. After the activation of proteins, mainly fibrinogen, the PRPC matrix retains and facilitates interactions between invading resident cells, like macrophages, fibroblast, and mesenchymal stem cells (MSCs), and the embedded concentrated PRP cells and molecules. The administered PRPC biologic will ultimately undergo fibrinolysis, leading to a sustained release of concentrated cells and molecules that have been retained in the PRPC matrix until the matrix is dissolved. We will discuss the unique biological and tissue reparative and regenerative properties of PRPC matrix.

Abstract: The purpose of this review is to summarize recent knowledge on the main processes that occur during wound healing, including the responses of various cell types and the molecular mechanisms involved. Particular attention is also dedicated to new therapies often involved in the resolution of wounds, whether acute or chronic. Awareness of these dynamics is important for the various professional figures who are confronted with these kinds of problem daily. However, the study of the healing mechanisms has yet to be defined in detail, in fact there are alterations of variously coordinated events which lead to a delayed resolution or, as in the case of keloids, to pathological states consisting in the excessive formation of scars with consequences yet to be seen. to define. Therefore, it is necessary to know the most feasible approaches and the most effective therapies.

Dermal wound healing describes the progressive repair and recalcitrant mechanism of damaged skin and eventually reformatting and reshaping the skin. Many probiotics, nutraceuticals, metal nanoparticles have been associated with improved healing process of intra and inter tissue wounds. Despite the vast nature on material based wound healing mediators, the exact mechanism on material-cellular interaction is still point of repent issue particularly in diabetics and pathological condition. The use of bioengineered alternative agents will likely only continue to dominate the outpatient and perioperative management of chronic, recalcitrant wounds as new additional products continue to cut costs and improve wound healing process. This review article provides an update of the various remedies with confirmed wound healing activities by a diverse group of agents from previous experiments conducted by various researchers

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Infectious diabetic wounds can result in severe injuries or even death. Biocompatible wound dressings offer one of the best ways to treat these wounds, but creating a dressing with suitable hydrophilicity and biodegradation rate can be challenging. To address this issue, we used the electrospinning method to create a wound dressing composed of poly(glycerol sebacate) (PGS) and gelatin (Gel). We dissolved the PGS and Gel in acetic acid (75 v/v%) and added EDC/NHS solution as a crosslinking agent. Our measurements revealed that the scaffolds' fiber diameter ranged from 180.2 to 370.6 nm, and all the scaffolds had porosity percentages above 70%, making them suitable for wound healing applications. Additionally, we observed a significant decrease (p &lt; 0.05) in the contact angle from 110.8° ± 4.3° for PGS to 54.9° ± 2.1° for PGS/Gel scaffolds, indicating an improvement in hydrophilicity of the blend scaffold. Furthermore, our cell viability evaluations demonstrated a significant increase (p &lt; 0.05) in cultured cell growth and proliferation on the scaffolds during the culture time. Our findings suggest that the PGS/Gel scaffold has potential for wound healing applications.

Each year, millions of individuals suffer from a non-healing wound, abnormal scarring, or injuries accompanied by an infection. For these cases, scientists are searching for new therapeutic interventions, from which one of the most promising is the use of extracellular vesicles (EVs). Naturally, EV-based signalling takes part in all four wound healing phases: hemostasis, inflammation, proliferation and remodelling. Such an extensive involvement of EVs suggests exploiting their action to modulate the impaired healing phase. Furthermore, next to their natural wound healing capacity, EVs can be engineered for better defined pharmaceutical purposes, such as carrying specific cargo or targeting specific destinations by labelling them with certain surface proteins. This review aims to promote scientific awareness in basic and translational research of EVs by summarizing the current knowledge about their natural role in each stage of skin repair and the most recent findings in application areas, such as wound healing, skin regeneration and treatment of dermal diseases, including the stem cell-derived, plant-derived and engineered EVs.

Lyme disease, the leading vector-borne ailment in the U.S., annually affects an estimated 476,000 individuals, predominantly in the Northeast and Upper Midwest. Despite its increasing incidence, the evaluation of risk within U.S. cities, including natural public lands, remains inadequate. This study focuses on blacklegged tick occurrences and Borrelia burgdorferi infection prevalence in 24 Staten Island parks, aiming to assess Lyme disease exposure risk. Monthly acarological risk index (ARI) calculations from 2019 to 2022 revealed elevated values (0.16-0.53) in specific parks, notably Wolfe’s Pond Park, High Rock Park, Clay Pit Pond Park, Clove Lake Park, and Fair View Park. June (0.36) and November (0.21) consistently exhibited heightened ARIs, aligning with peak tick collection months. Despite stable yearly infection rates at 28.97%, tick densities varied significantly between parks and years. Identifying a high transmission risk in specific parks in Staten Island, a highly urbanized part of New York City, emphasizes the continuous necessity for Lyme disease risk management, even within the greenspaces of large cities.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Based on its large surface area and covering the whole human body, the skin body’s largest organ and its main function is protection. Injuries and wound healing involving the skin offer valuable lessons shared with and of relevance to other organ systems and the diseases that impact them. Arguably the most complex human body process, wound healing is a multifaceted process that involves multiple cells and the extracellular matrix (ECM), with each component playing a specific role in the different stages of the healing process. Importantly, studies indicate that cells with stem cell-like properties are present within many of the human tissues and play key roles in case of tissue and cellular injury. Cell-to-cell and cell-to-ECM interactions are salient in wound healing subsequent to an injury. Microenvironment related factors and the variations therein including hypoxia or the abundance of oxygen, the presence/absence of growth factors and cytokines add to the complexity of the wound healing process and impact cell function and result in compromised or enhanced wound healing. This expert review critically examines the advances in biochemical and analytical tools that are enable the analysis of numerous cells and molecules within the wound microenvironment, revealing great cellular heterogeneity as well as novel molecular targets of importance to enhance wound healing. In a broader angle, we emphasize the ways in which wound healing is significant in the search for perfect skin after injury and in many common complex human diseases including cancer. In all, wound healing is a centrepiece of integrative biology research and applications in medicine as well as dermatology as discussed in this review.

Both bacteria product flagellin and macrophages are implicated in HIV infection/disease progression. However, the impact of their interaction on HIV infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β, and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV infection and the effectiveness of flagellin adjuvant-based vaccines studies.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.

Dengue infection is caused by the Dengue virus (DENV) and is transmitted to humans by infected female Aedes aegypti and Aedes albopictus mosquitoes. There are nearly 100 million new dengue cases yearly in more than 120 countries with a five-fold increase in incidence over the past four decades. While many patients experience a mild illness, a subset suffer from severe disease which can be fatal. Dysregulated immune responses are central to the pathogenesis of dengue, and haematologic manifestations are a prominent feature of severe disease. While thrombocytopaenia and coagulopathy are major causes of bleeding in severe dengue, leucocyte abnormities are emerging as important markers of prognosis. In this review, we provide our perspective on the clinical aspects and pathophysiology of haematologic manifestations in dengue. We also discuss the key gaps in our current practice and areas to be addressed by future research.

This study is aimed to assess the prevalence of Coxiella burnetii infection among veterinary medicine students from two Bulgarian Universities, located in Sofia and Stara Zagora. A total of 185 veterinary students blood samples were collected and tested for the detection of C. burnetii phase II antibodies and presence of DNA using an enzyme-linked immunosorbent assay (ELISA) and end-point PCR test, respectively. Out of all samples, 29.7% were positive for at least one C. burnetii phase II antibody marker or by PCR test. Veterinary students from Stara Zagora showed significantly seropositive status of Q fever (33.6%), then those who studied in Sofia (23%). The evidence for recent exposition with detection of anti-C. burnetii IgM (+) antibodies had 14.6%. Seroprevalence among students in Stara Zagora was higher (15.3%). Anti-C. burnetii phase II IgG antibodies were detected in 21.6% examined samples. Our study revealed a higher seropositivity among male students (32.8%) as compared to the female ones (16.0%). End-point PCR assay detected as positive 5.9% blood samples. The relative risk (RR) of Q fever exposure for male students was 40.7%, whereas for female (24.6%). Findings from this study indicated that the C. burnetii infection is widely distributed amongst veterinary students from Bulgaria. The study emphasizes the need for improved safety protocols and infection control measures in veterinary training programs.

Oritavancin is a novel long-acting lipoglycopeptide with in vitro activity against methicillin-resistant (MR) Gram-positive pathogens and a good bactericidal activity even in presence of biofilm forming bacteria. It has been approved for acute bacterial skin and skin structure infections (ABSSSI), but recent reports have demonstrated possible off-label uses, as for prosthetic joint infections (PJI), which, in more than half of cases, are caused by MR Gram positive organisms. We reported a case of a man in his eighties with a late shoulder PJI caused by methicillin resistant Staphyloccus epidermidis (MRSE) with contraindications for surgical replacement and few oral therapeutic options for a long term suppressive antibiotic therapy. The prosthesis was retained, and the patient received ten outpatient sequential doses of 1200 mg of oritavancin during 28 weeks, based on therapeutic drug monitoring (TDM) as a guide for correct timing of administration of each dose. During oritavancin administration, the patient achieved clinical cure, with disappearance of the pain and regaining pre-infection joint mobility, with no side effects reported and no further surgery or hospitalization needed. The treatment is ongoing as a long-lasting suppressive antimicrobial therapy. Oritavancin could represent an excellent solution for treating PJI caused by MR organism, especially in patients who need a long-term suppressive therapy.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

Potato tubers are susceptible to wounding during post-harvest processes, leading to quality decline, perishability and large economic losses. In this study, the potato cultivar, ‘Longshu No.7’, was foliar-sprayed with 3% chitosan (w/v) three times during the pre-harvest period after flowering to evaluate the effect of foliar spraying with chitosan on suberization processing at wounds of harvested potato tubers. Our results demonstrate that foliar-sprayed with chitosan significantly reduced wound-induced fresh weight loss and dry rot disease index by 37.34% and 41.60% on the 28 day after wounding, respectively. Foliar-sprayed with chitosan accelerated the deposition of suberin polyphenolics and lignin at the wound sites of potato tubers with the formation of thicker cell layers. This occurred with increased localized activities of key enzymes in the suberin polyphenolics and lignin pathways, including phenylalanine ammonia lyase, 4-coumaryl-coenzyme A ligase, cinnamyl alcohol dehydrogenase and peroxidase (33.90–64.32%), as well as the contents of cinnamic acid, sinapic acid, flavonoids, lignins and total phenolics (19.70–23.46%) at wound sites of potato tubers on the 7 day after wounding. Our results indicated that foliar application of chitosan accelerated wound-induced suberization of potato tubers and could mitigate post-harvest product damages.

Within the polyurethanes market, only 0.1% are from renewable sources. With the continuing concern about climate change and greenhouse gases in the atmosphere, the substitution of monomers and processes derived from petrochemical sources is crucial for the development of biomaterials. Therefore, polyhydroxyurethanes have propose due to their synthesis route with the incorporation of monomers from renewable sources such as vegetable oils and the substitution of isocyanates known for their high toxicity, carcinogenicity and petrochemical origin, and the use of carbon dioxide. There are few reports on the use of soybean oil and the possible application of these materials in wound healing applications. Based on this, polyhydroxyurethanes were obtained from carbonated soybean oil and two diamines, one aliphatic: 1,4-butadiamine (putrescine), and one cycloaliphatic: 1,3-cyclohexanobis(methylamine), and they were physiochemically, mechanically, and thermally characterized. Four polyhydroxyurethanes were obtained, with stability to hydrolytic and oxidative media, thermal stability above 200 °C, tensile strength between 0.9-1.1 MPa, elongation at break between 81 and 222%. And water absorption up 102% and contact angle between 63,70 and 101,39. Achieving new formulations of biobased NIPHUs that represent a more sustainable process which allow to achieve the physicochemical, mechanical, and thermal properties required for the preparation of wound dressings.

The emergence of SARS-CoV-2 mutations pose significant challenges to diagnostic tests as these mutations can reduce the sensitivity of commonly used RT-PCR assays. Therefore, there is a need to design diagnostic assays with multiple targets to enhance sensitivity. In this study, we identified a novel diagnostic target, nsp10 gene, using nanopore sequencing. Firstly, we determined the analytical sensitivity and specificity of our COVID-19-nsp10 assay. The COVID-19-nsp10 assay had the limit of detection of 74 copies/mL (95% confidence interval: 48-299 copies/mL) and did not show cross-reactivity with other respiratory viruses. Next, we determined the diagnostic performance of the COVID-19-nsp10 assay using 261 respiratory specimens, including 147 SARS-CoV-2-positive specimens belonging to ancestral strain and Alpha, Beta, Gamma, Delta, Mu, Eta, Kappa, Theta and Omicron lineages. Using the LightMix E-gene RT-PCR assay as the reference method, the diagnostic sensitivity and specificity of the COVID-19-nsp10 assay were 100%. The median Cp values for the LightMix E-gene RT-PCR and our COVID-19-nsp10 RT-PCR were 22.48 (range: 12.95-36.60) and 25.94 (range 16.37-36.87), respectively. The Cp values of the COVID-19-nsp10 RT-PCR assay correlated well with those of the LightMix E-gene RT-PCR assay (Spearman’s ρ = 0.968; P&lt;0.0001). In conclusion, nsp10 is a suitable target for SARS-CoV-2 RT-PCR assay.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

The accurate assessment of wound size is a critical step in advanced wound care management. This study aims to introduce and validate a Light Detection and Ranging (LiDAR) technique for measuring wound size. Twenty-eight wounds treated from December 2022 to April 2023 at the Chunganam National University Hospital were analyzed. All wounds were measured using three techniques; conventional ruler methods, the LiDAR technique, and ImageJ analysis. Correlation analysis, linear regression, and Bland-Altman plot analysis were conducted to validate the accuracy of the newly introduced method. The measurement results (Mean ± Standard deviation) obtained using the Ruler method, LiDAR technique, and ImageJ analysis were 112.99 ± 110.07 cm², 73.59 ± 72.97 cm², and 74.29 ± 72.15 cm², respectively. The Pearson correlation coefficient was higher in the LiDAR application (0.995) than the conventional ruler methods (Mean difference; -5.0000 cm2), as was the degree of agreement (Mean difference; 38.6933 cm2). Wound size measurement using LiDAR is a simple and reliable method that allows practitioners to conveniently assess wounds with a flattened and irregular shape. However, non-flattened wounds cannot be assessed owing to the technical limitations of LiDAR.

Chronic wounds are associated with considerable patient morbidity and present a significant economic burden to the healthcare system. Often, chronic wounds are in a state of persistent in-flammation and unable to progress to the next phase of wound healing. Placental-derived bio-materials are recognized for their biocompatibility, biodegradability, angiogenic, an-ti-inflammatory, anti-microbial, anti-fibrotic, immunomodulatory, and immune privileged prop-erties. As such, placental-derived biomaterials have been used in wound management for more than a century. Placental-derived scaffolds are composed of an extracellular matrix (ECM) that can mimic the native tissue, creating a reparative environment to promote ECM remodeling, cell migration, proliferation, and differentiation. Reliable evidence exists throughout the literature to support the safety and effectiveness of placental-derived biomaterials in wound healing. How-ever, differences in source (i.e., anatomical regions of the placenta), preservation techniques, decellularization status, design, and clinical application have not been fully evaluated. This re-view provides an overview of wound healing and placental-derived biomaterials, summarizes the clinical results of placental-derived scaffolds in wound healing, and suggests directions for future work.

In the past decades, regenerative medicine applied on skin lesions has been a field of constant improvement for both human and veterinary medicine. The process of healing cutaneous wound injuries implicates a well-organized cascade of molecular and biological processes. However, sometimes the normal process fails and can result in a chronic lesion. In addition, wounds are considered an increasing clinical impairment, due to the progressive ageing of the population, as well as the prevalence of concomitant diseases, such as diabetes and obesity, that represent risk aggravating factors for the development of chronic skin lesions. Stem cells regenerative potential has been recognized worldwide, including towards skin lesion repair, Tissue engineering techniques have long been successfully associated with stem cell therapies, namely the application of 3D bioprinted scaffolds. With this review we intend to explore several stem cell sources with promising aptitude towards skin regeneration, as well as different techniques used to deliver those cells and provide a supporting extracellular matrix environment, with effective outcomes. Furthermore, different studies are discussed, both in vitro and in vivo, towards their relevance in the skin regeneration field.

Background: Monocyte-derived dendritic cells (mo-DCs) play a vital role in the innate immune response by activating Th17 cells, which in turn release the pro-inflammatory cytokine IL-17. We hypothesised that following repetitive mechanical strain, tenocytes activate monocyte-derived dendritic cells, which in turn, drive the pathogenesis of tendinopathy. Aim: The aim of the study was to determine if monocyte-derived dendritic cells are upregulated in a human tendinopathy model. Method: Torn supraspinatus tendon and matched intact subscapularis tendon samples were collected from 7 patients undergoing arthroscopic shoulder surgery. Healthy control samples of subscapularis tendon were collected from 5 patients undergoing arthroscopic stabilization surgery. Tendon biopsy samples were evaluated immunohistochemically by quantifying the presence of monocyte-derived dendritic cells (CD11C and CD206). Results: Tendinopathic tendon samples exhibited significantly greater (2-3-fold) monocyte-derived dendritic cell expression when compared with healthy control tissue (P &lt; .05). Conclusion: This study provides evidence for a monocyte-derived dendritic cell upregulation in early-stage human tendinopathy.

Sugarcane mosaic virus (SCMV) and sugarcane streak mosaic virus (SCSMV) are the primary viruses responsible for mosaic diseases in sugarcane. In this study, the mosaic viruses SCMV and SCSMV with the involvement of sorghum mosaic virus (SrMV) were surveyed from eight commercial sugarcane cultivars grown in fields at four locations in East Java, Indonesia. Sugarcane leaves with mosaic symptoms were assessed for disease incidence and severity, and symptomatic leaves were collected for analysis. The incidence and severity of mosaic symptoms were the highest in the PS881 and NX04 cultivars grown in Kediri compared to the other cultivars. RT-PCR analysis showed that SCSMV was present in all sugarcane cultivars and locations. Interestingly, double mixed infections with SCMV were found in PS881, PS882, and Cening, whereas triple mixed infections with SrMV were found in the PS881 cultivar. Phylogenetic analysis grouped SCSMV, SCMV, and SrMV together with isolates from Thailand (KP987832.1), Florida, USA (MT725538.1), and Agentina (EU189037.1). The expression of ascorbate peroxidase gene (Apx) was increased in the virus-infected sugarcane cultivars and prominently elevated in the triple mixed infection of PS881 cultivars. However, the catalase gene (Cat) was slightly upregulated in the mixed infection group. The chlorophyll content was significantly reduced in the leaves of PS58, PS881, PS882, NX04, and HW Merah, in parallel with the expression of the photosystem I gene (PsaA). The expression of photosynthetic genes, such as ribulose-1,5 bisphosphate carboxylase small sub-unit (RbcS), phosphoenolpyruvate carboxylase (Pepc), sucrose-phosphate synthase (Sps1), and PsaA, was significantly reduced and almost depleted in the triple mixed infection of PS881, except for Pepc expression, which remained approximately half of that in the control healthy sugarcane. The decrease in photosynthetic activity was confirmed by the decrease in ribulose-1,5 bisphosphate carboxylase (Rubisco) and PEPC proteins, as detected by immunoblot analysis. The decrease in photosynthetic parameters indicated that the mosaic viral infection substantially reduced the growth and yield of sugarcane.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

Many signaling pathways, molecular and cellular actors which are critical for wound healing have been implicated in cancer metastasis. These two conditions are a complex succession of cellular biological events and accurate regulation of these events is essential. Apart from inflammation, macrophages-released ROS arise as major regulators of these processes. But, whatever the pathology concerned, oxidative stress is a complicated phenomenon to control and requires a finely tuned balance over the different stages and responding cells. This review provides an overview of the pivotal role of oxidative stress in both wound healing and metastasis, encompassing the contribution of macrophages. Indeed, macrophages are major ROS producers but also appear as their targets since ROS interfere with their differentiation and function. Elucidating ROS functions in wound healing and metastatic spread may allow the development of innovative therapeutic strategies involving redox modulators.

Human papillomavirus (HPV), a DNA virus, causes one the most common sexually transmitted infections (STI), spreading through direct sexual contact to the anogenital and oropharyngeal regions. Although most infected individuals may be asymptomatic and naturally undergo viral clearance, in some individuals HPV causes carcinogenesis of the infected epithelia. HPV now accounts for over 70% of oropharyngeal carcinomas (OPC). More than 90% of these OPC are associated with HPV 16, one of the 14 high-risk subtypes. In recent years, HPV positive (HPV+) OPC has been one of the most rapidly rising cancers, by new cancer incidence rates, especially among men. The HPV driven OPCs present some unique infection driven cellular and molecular features, constituting distinct preventive, therapeutic and prognostic strategies, in contrast to HPV negative (HPV-) OPC. In this manuscript, we drive through the role of HPV, from a sexually transmitted infection to malignancy transformation landscape, while parsing through the significant immune response environment. In this comprehensive review we collate key literature around transmission and epidemiology of HPV, while addressing the current state of clinical management, diagnosis, prevention and screening strategies, that can help shed light on this critical area.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

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

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Nanocellulose is cellulose in the form of nanostructures, i.e. features not exceeding 100 nm at least in one dimension. These nanostructures include nanofibrils, e.g. in bacterial cellulose; nanofibers, e.g. in electrospun matrices; nanowhiskers and nanocrystals. These structures can be further assembled into bigger 2D and 3D nano-, micro- and macro-structures, such as nanoplatelets, membranes, films, microparticles and porous macroscopic matrices. There are four main sources of nanocellulose: bacteria (Gluonacetobacter), plants (trees, shrubs, herbs), algae (Cladophora) and animals (Tunicata). Nanocellulose has emerged for a wide range of industrial, technology and biomedical applications, e.g. for adsorption, ultrafiltration, packaging, conservation of historical artifacts, thermal insulation and fire retardation, energy extraction and storage, acoustics, sensorics, controlled drug delivery, and particularly for tissue engineering. Nanocellulose is promising for use in scaffolds for engineering of blood vessels, neural tissue, bone, cartilage, liver, adipose tissue, urethra and dura mater, for repairing connective tissue and congenital heart defects, and for constructing contact lenses and protective barriers. This review is focused on applications of nanocellulose in skin tissue engineering and wound healing as a scaffold for cell growth, for delivering cells into wounds, and as a material for advanced wound dressings coupled with drug delivery, transparency and sensorics. Potential cytotoxicity and immunogenicity of nanocellulose are also discussed.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Wound healing is a complex, dynamic process involving the coordinated interaction of diverse cell types, growth factors, cytokines, and extracellular matrix components. Despite emerging evidence highlighting their importance, dermal sheath cells remain a largely overlooked aspect of wound healing research. This review explores the multifunctional roles of dermal sheath cells in various phases of wound healing, including modulating inflammation, aiding in proliferation, and contributing to extracellular matrix remodeling. Special attention is devoted to the paracrine effects of dermal sheath cells and their role in fibrosis, highlighting their potential in improving healing outcomes, especially in differentiating between hairy and non-hairy skin sites. By drawing connections between dermal sheath cells activity and wound healing outcomes, this work proposes new insights into the mechanisms of tissue regeneration and repair, marking a step forward in our understanding of wound healing processes.

Cutaneous wound healing is a complex multi-stage process involving direct and indirect cell communication events with the aim of efficiently restoring the barrier function of the skin. One key aspect in cutaneous wound healing is associated with cell movement and migration into the physically, chemically and biologically injured area resulting in wound closure. Understanding the conditions under which cell migration is impaired and elucidating the cellular and molecular mechanisms that improve healing dynamics is therefore crucial in devising novel therapeutic strategies to elevate patient suffering, reduce scaring and eliminate chronic wounds. Following the global trend towards automation, miniaturization and integration of cell-based assays into microphysiological systems, conventional wound healing assays such as the scratch assay or cell exclusion assay have recently been translated and improved using microfluidics and lab-on-a-chip technologies. These miniaturized cell analysis systems allow precise spatial and temporal control over a range of dynamic microenvironmental factors including shear stress, biochemical and oxygen gradients to create more reliable in vitro models that resemble the in vivo microenvironment of a wound more closely on a molecular, cellular, and tissue level. The current review provides (a) an overview on the main molecular and cellular processes that take place during wound healing, (b) a brief introduction into conventional in vitro wound healing assays, and (c) a perspective on future cutaneous and vascular wound healing research using microfluidic technology.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Wound infection is a common complication of chronic wounds. It can impair healing, which may not occur without external help. Antimicrobial dressings (AMDs) are a type of external help to infected chronic wounds. In this study, highly porous membranes made of only chitosan and containing the antiseptic polyhexanide (poly(hexamethylene biguanide); PHMB) were prepared by cryogelation, aiming to be used in AMDs. These membranes exhibited high water swelling capacity, fast water absorption and high water vapor transmission. The best drug loading method involved simultaneous loading by soaking in a PHMB solution and sterilization by autoclaving, resulting in sterilized, drug-loaded membranes. The drug release kinetics was comparable to that of a commercial PHMB-releasing AMD assayed under the same conditions. These membranes exhibited high antibacterial activity against Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa, which are bacterial species commonly found in infected wounds, and blood clotting activity. The obtained results suggest that these membranes may be suitable for use in the development of AMDs.

Introduction: Among the many factors that may limit effective wound healing in patients with chronic ulcers, bacterial infection and poor cell recruitment are primary causes that contribute to prolonged healing. Thus, a novel strategy that aims to prevent bacterial infection within the wound, while at the same time providing structural scaffolding that promotes endogenous tissue repair, would be of great interest. Here, we developed a thermo-sensitive silver nanoparticle hydrogel composite as an antibacterial nutritional scaffold for the wound that contains all nutrients required for cell growth while preventing bacterial infection with the ability to fill up all the cavities and void areas in wounds regardless of their geometry. Methods: Silver nanoparticles (AgNPs) were synthesized by chemical reduction. After characterization, silver hydrogel nanocomposite was developed by reconstitution of collagen-based hydrogel powder in a nanoparticle suspension of varying AgNPs concentrations (200, 400, and 600 ppm). The antibacterial activity of the formulations was examined in vitro and in vivo in subcutaneous implant infected model. The wound healing efficacy of the hydrogel nanocomposite was also evaluated using a splinted wound model in rats through comparison of clinical wound measurements and histological assessments. Cytocompatibility assay and biochemical analysis of blood at the end of in vivo wound healing study were performed to evaluate the safety of formulations. Results: The synthesized nanoparticles were spherical and stable. While hydrogel alone did not show any bacterial reduction in vitro, the inhibition of bacterial growth was significant in all silver hydrogel nanocomposites compared to controls (p <0.05) and was dose-dependent, with maximum reduction observed in the 600 ppm group (4.56±0.26 LOG CFU/mL, P<0.001). All concentrations of AgNPs hydrogel composites showed significant antibacterial activity in vivo as well (P<0.0001). Treatment of splinted wounds with AgNPs hydrogel composite resulted in faster wound closure and accelerated wound re-epithelialization. The formulations were non-cytotoxic and did not differ significantly in hematological and biochemical factors from the control group in in vivo study. Conclusions: By presenting promising antibacterial and wound healing activity, silver hydrogel nanocomposite offers a safe therapeutic option that can be used as a functional scaffold for an acceleration of wound healing.

Cold plasma (CP) is an ionised gas containing excited molecules and ions, radicals, free electrons, and emits electric fields and UV radiation. CP is potently antimicrobial and can be applied safely to biological tissue, birthing the field of plasma medicine. Reactive oxygen and nitrogen species (RONS) produced by CP affect biological processes directly or indirectly via the modification of cellular lipids, proteins, DNA, and intracellular signalling pathways. CP can be applied at lower levels for oxidative eustress to activate cell proliferation, motility, migration, and antioxidant production in normal cells, mainly potentiated by the unfolded protein response, Nrf2-activated antioxidant response element and PI3K/Akt pathway, which also activates NFκB. At higher CP exposures, inactivation, apoptosis and autophagy of malignant cells can occur via degradation of PI3K/Akt and MAPK-dependent and -independent activation of the master tumour suppressor p53, leading to caspase-mediated cell death. These opposing responses validate a hormesis approach to plasma medicine. Clinical applications of CP are becoming increasingly realised in wound healing, while clinical effectiveness in tumours is currently coming to light. This review will outline advances in plasma medicine and compare the main redox and intracellular signalling responses to CP in wound healing and cancer.

Micronutrient homeostasis is a key factor in maintaining a healthy immune system. Zinc is an essential micronutrient that is involved in the regulation of the innate and adaptive immune responses. The main cause of zinc deficiency is malnutrition. Zinc deficiency leads to cell-mediated immune dysfunctions among other manifestations. Consequently, such dysfunctions lead to a worse outcome in the response towards bacterial infection and sepsis. For instance, zinc is an essential component of the pathogen-eliminating signal transduction pathways leading to neutrophil extracellular traps formation, as well as inducing cell-mediated immunity over humoral immunity by regulating specific factors or differentiation. Additionally, zinc deficiency plays a role in inflammation, mainly elevating inflammatory response as well as damage to host tissue. Zinc is involved in the modulation of the proinflammatory response by targeting Nuclear Factor Kappa B, a transcription factor that is the master regulator of proinflammatory responses. It is also involved in controlling oxidative stress and regulating inflammatory cytokines. Zinc plays an intricate function during an immune response and its homeostasis is critical for sustaining proper immune function. This review will summarize the latest findings concerning the role of this micronutrient during the course of infections and inflammatory response and how the immune system modulates zinc depending on different stimuli.

Presenting a case report on the occurrence of IgA nephropathy with hepatitis B infection in a 32-year-old male patient with main complaints of generalized weakness, easy fatigue, and bilateral swelling of the lower extremities. IgA nephropathy (IgAN), or Berger’s disease, is the most common primary glomerulonephritis worldwide. It is characterized by the formation of IgA1-containing circulating immune complexes and their deposition in the glomerular mesangium. Its etiology remains multifactorial and often idiopathic. IgA nephropathy alone does not have an infectious etiology; instead, it usually develops in conjunction with an infectious condition that triggers a dysregulated immune response. There is no proof that any particular infectious agent is the secondary cause of IgA nephropathy. Hepatitis B virus (HBV) infection is an infectious agent associated with renal complications, including IgA nephropathy. Symptoms include gross haematuria and mild proteinuria indicative of renal involvement. Laboratory investigations and serological tests are followed by imaging studies such as ultrasound and renal biopsy to confirm the diagnosis. The challenges encountered during the diagnostic process included overlapping symptoms and limitations of available diagnostic tests, highlighting the need for comprehensive diagnostic evaluation and multidisciplinary management approaches in similar cases. This case underscores the importance of recognizing and managing both conditions simultaneously to prevent long-term complications such as end-stage renal disease.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.

In recent years, photobiomodulation (PBM) has been recognized as a physical therapy in wound management. Despite several published research papers, the mechanism underlying photobiomodulation is still not completely understood. The investigation about application of blue light to improve wound healing is a relatively new research area. Tests in selected patients evidenced a stimulation of the healing process in superficial and chronic wounds treated with a blue LED light emitting at 420 nm; a study in animal model pointed out a faster healing process in superficial wound, with an important role of fibroblasts and myofibroblasts. Here we present a study aiming at evidencing the effects of blue light on the proliferation and metabolism in fibroblasts and keratinocytes. Different light doses were used to treat the cells, evidencing inhibitory and stimulatory effects. Electrophysiology was used to investigate the effects on membrane currents, while Raman spectroscopy revealed the mitochondrial Cytochrome C (Cyt C) oxidase dependence on blue light irradiation. In conclusion, we observed that the blue LED light can be used to modulate the activity of human fibroblasts, and the effects in wound healing are particularly evident when studying the fibroblasts and keratinocytes co-cultures.

Bacterial infections occur when wound healing fails to reach the final stage of healing, usually hindered by the presence of different pathogens. Different topical antimicrobial agents are used to inhibit bacterial growth due to antibiotic failure in reaching the infected site accompanied very often by an increased drug resistance and other side effects. In this review, we focus on antimicrobial peptides (AMPs), especially those with a high potential of efficacy against multidrug-resistant and biofilm-forming bacteria and fungi present in wound infections. Currently, different AMPs undergo preclinical and clinical phase to combat infection-related diseases. AMP dendrimers (AMPDs) have been mentioned as potent microbial agents. Various AMP delivery strategies, such as polymers, scaffolds, films and wound dressings, organic and inorganic nanoparticles, to combat infection and modulate the healing rate have been discussed as well. New technologies such as CRISPR-Cas are taken into consideration as potential future tools for AMP delivery in skin therapy.

Respiratory Syncytial Virus is a common respiratory pathogen known for causing respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and the elderly. This virus is responsible for one-third of pneumonia deaths in the pediatric population, but there are currently only a few effective vaccines and pharmacological treatments. The frac-talkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and a diversity of immune cells. Recent research has highlighted the role of CX3CR1 in the host immune response to RSV infection, and its potential role in the development of an efficient vaccine and novel treatments.

Leishmanial skin lesions are characterized by inflammatory hypoxia alongside the activation of hypoxia inducible factors, HIF-1a and HIF-2a, and subsequent expression of the HIF-a target VEGF-A during Leishmania major infection. However, the factors responsible for HIF-a activation are not known. We hypothesize hypoxia and pro-inflammatory stimuli contribute to HIF-a activation during infection. RNASeq on leishmanial lesions found transcripts associated with HIF-1a signaling are induced. To determine whether hypoxia contributes to HIF-a activation, we followed the fate of myeloid cells infiltrating from the blood and into hypoxic lesions. Recruited myeloid cells experience hypoxia when they enter inflamed lesions, and the length of time in lesions increases their hypoxic signature. To determine whether pro-inflammatory stimuli in the inflamed tissue can also influence HIF-a activation, we subjected macrophages to various pro-inflammatory stimuli and measured VEGF-A. While parasites alone did not induce VEGF-A, and pro-inflammatory stimuli only modestly induce VEGF-A, HIF- stabilization increases VEGF-A during infection. HIF-a stabilization does not impact parasite entry, growth or killing. Alternatively, the absence of ARNT/HIF- signaling enhances parasite internalization. Altogether, these findings suggest HIF-a is active during infection, and while macrophage HIF-a activation promotes lymphatic remodeling through VEGF-A production, HIF-a activation does not impact parasite internalization or control.

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Although the specific etiology is unknown, previous research shows that maternal environment may be a contributing factor. Gestational stress may lead to the development of NEC by interfering with the barrier function of the intestinal epithelial barrier. The migration of cells from the crypts to the tips of the villi is crucial in maintaining the integrity of the epithelial barrier. Previously, the Martin lab found that pups from psychologically stressed pregnant dams were more susceptible to NEC-like injury. We have also shown that investigated how stress signaling and zinc impact intestinal epithelial wound healing. Through a scratch assay, human Caco-2 cell migration was studied over 24 hours, and the percent wound healing was calculated. We found that only hydrocortisone at the 30 ug/ml concentration led to an inhibition of wound healing, and that zinc was unable to rescue hydrocortisone mediated inhibition.

Numerous innovative advancements in dressing technology for wound healing have emerged. Among the various types of wound dressings available, hydrogel dressings, structured with a three-dimensional network and composed of predominantly hydrophilic components, are widely used for wound care due to their remarkable capacity to absorb abundant wound exudate, maintain a moisture environment, provide soothing and cooling effects, and mimic the extracellular matrix. Composite hydrogel dressings, one of the evolved dressings, address the limitations of traditional hydrogel dressings by incorporating additional components, including particles, fibers, fabrics, or foams, within the hydrogels, effectively promoting wound treatment and healing. The added elements enhance the features or add specific functionalities of the dressings, such as sensitivity to external factors, adhesiveness, mechanical strength, control over the release of therapeutic agents, antioxidant and antimicrobial properties, and tissue regeneration behavior. They can be categorized as natural or synthetic based on the origin of the main components of the hydrogel network. This review focuses on recent research on developing natural polysaccharide-based composite hydrogel wound dressings. Their preparation and composition, the reinforcement materials integrated into hydrogels, and therapeutic agents are also explored. Furthermore, their features and the specific types of wounds where applied are discussed as well.

innate and adaptive immune responses lead to wound healing by regulating a complex series of events promoting cellular cross-talk. An inflammatory response is presented with its characteristic clinical symptoms: heat, pain, redness, and swelling. Some smart thermo-responsive polymers like chitosan can be used to create biocompatible and biodegradable scaffolds with 3D architectures similar to human structures, allowing their efficient and safe use as tissue engineering and drug delivery systems in chronic wounds. Locally heated tumors above polymer lower critical solution temperature can induce its conversion into a hydrophobic form, enhancing drug release until the thermal stimulus is gone, where a lower release is due to the swelling of the material. This paper integrates the relevant reported contributions of bioengineered scaffolds for thermo-responsive drug delivery in wound healing. Therefore, we present a comprehensive review that aims to demonstrate the capacity of these systems to provide spatially and temporally controlled release strategies for one or more drugs used in wound healing. In this sense, the novel manufacturing techniques of 3D-printing and electrospinning are explored for the tuning of their physicochemical properties to adjust therapies according to the patient’s convenience, as well as reduce drug toxicity and side effects.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

Multidrug resistant organisms (MDROs) outbreaks have been steadilyincreasing in Intensive care units (ICUs). Still, healthcare institutions and workers (HCW) reached no unanimity on how and when implementing infection prevention and control (IPC) strategies. We aimed to provide a pragmatic, physician practice-oriented, resume of strategies towards different MRDOs outbreaks in ICU. We performed a narrative review on IPC in ICUs, investigating patient-to-staff ratios, education, isolation, decolonization, screening and hygiene practices, outbreak reporting, cost-effectiveness, reproduction-number(R0), and future perspectives. The most effective IPC strategy remains unknown. Most studies focus on a specific pathogen or disease, making the clinician losing the big picture. IPC strategies proved their cost-effectiveness regardless typology, country, or pathogen. A standardized, universal, pragmatic protocol for HCW education should be elaborated. Likewise, a rapid outbreak recognition tool elaboration (i.e., an easy-to-use mathematical model) would improve early diagnosis and spreading prevention. Further studies are needed to express in favor or against MDROs decolonization. New promising strategies are emerging and need to be tested in the field. The lack of IPC strategies application has made, and still makes ICUs a major MDROs reservoir into the community. In a not-too-distant future genetic engineering and phage therapies could represent a plot-twist in MDROs IPC strategies.

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

The blackening of cut carrots decreases their shelf life and causes severe economic losses but the molecular and metabolic mechanisms that underpin this phenomenon remain poorly characterized. Studies were therefore undertaken to determine the molecular and metabolic causes of the blackening. The susceptibility of blackening was dependent on the period of time that the crop was stored underground prior to harvest. The structure of the cell walls in the black regions was substantially changed compared to the orange regions. The black regions of carrot batons had decreased immunodetection of xyloglucan, HG-pectin, RG-I pectin, galactan and arabinan but had higher levels of lignin and phenolic compounds compared to the orange regions. Transcript profiling analysis revealed that phytohormone signalling processes were activated in the black regions. Transcripts associated with auxin signalling and ethylene-responsive transcription factors were increased in the black regions. In contrast, the levels of transcripts encoding proteins associated with secondary metabolism were decreased in the black regions. These findings implicate ethylene and auxin-related processes in the control of the primary to secondary metabolism shift that results in lignification and cell wall disruption that underpin the blackening process.

The present study aims at valorizing Moroccan Henna (Lawsonia inermis) by developing healing formulations for cosmetic and therapeutic uses. For such a goal, the plant was collected from three locations in Southeastern Morocco (Alnif, Tafraoute Sidi Ali and Tazarine). Phytochemical anal-yses of aqueous extracts of Henna leaves was performed by determining phenolic compounds contents, flavonoids and tannins in the extracts. Then, specific formulations were prepared using aqueous extracts of L. inermis to assess their in vivo wound healing potential in Swiss Albino mice as animal model. Results disclosed that phenolic compound contents (13.48%), flavonoids (9.25%) and tannins (2.57%) are higher in Henna leaf extracts from Alnif, while Tazarine Henna aqueous extract was found to be richer in saponins (0.32%). Exclusion chromatographic analysis on Se-phadex G50 gel corroborates the obtained results and shows that Lawsone levels (Henna coloring agent) are higher in Henna collected from Alnif. Aqueous Henna leaf extracts, at a dose of 10% in petroleum jelly, have been tested for their ability to heal induced burns in mice. Healing moni-toring, carried out with Henna extracts on mice batches and those of two control batches (Mice batch treated with petroleum jelly alone and batch treated with petroleum jelly containing 1% flamazine), showed a great reduction in burnt surface with an accentuated contraction percentage (CP) and complete re-epithelialization duration (CRD) at 21 days in the three studied Henna-based formulations. These findings suggest the interest of potential development of Henna-based for-mulations, as source of phenolic compounds, for further dermatological, cosmetic and therapeutic applications.

Plant extracts have been evaluated to determine their bioactivities and their potential use in wound healing. In this study, a conductive composite material, based on graphene oxide (GO), nanocellulose (CNF) and tannins (TA) from pine bark, reduced using polydopamine (PDA), was developed for wound dressing. The amount of CNF and TA was varied in the composite material and a complete characterization including SEM, FTIR, XRD, XPS, TGA was performed. Also, the conductivity, mechanical properties, cytotoxicity, and in vitro wound healing of the materials were evaluated. The results showed a successful physical interaction between CNF, TA and GO. In-creasing the CNF amount in the composite reduced the thermal properties, surface charge and conductivity of the material, but its strength, cytotoxicity and wound healing performance were improved. The TA incorporation slightly reduced the cell viability and migration, which may be associated with the doses used and the chemical composition of the extracts. However, the in vitro obtained results demonstrated that these composite materials can be suitable for wound healing.

Wounds represents a medical problem that contribute importantly to patient morbidity and to the healthcare costs in several pathologies. In Hidalgo, Mexico, Bacopa procumbens plant has been traditionally used for wound healing care for several generations; in vitro and in vivo experiments were design to evaluate the effects of bioactive compounds obtained from B. procumbens aquoethanolic extract and to determine the key pathways involved in wound regeneration. Bioactive compounds were characterized by HPLC- QTOF-MS and proliferation, migration, adhesion, and differentiation studies were done on NIH/3T3 fibroblasts. Polyphenolic compounds from Bacopa procumbens (PB) regulated proliferation and cell adhesion; enhanced migration reducing the artificial scratch area; and modulated cell differentiation. PB compounds were included in a hydrogel for topical administration on rat excision wound model. Histological, histochemical and mechanical analysis showed that PB treatment accelerates wound closure in at least 48 h; reduce inflammation, increasing cell proliferation and deposition and organization of collagen in earlier times. These changes resulted in the formation of a scar with better tensile properties. Immunohistochemistry and RT-PCR molecular analyses demonstrated that treatment induces: i) overexpression of transforming growth factor beta (TGF-β); and ii) the phosphorylation of Smad 2/3 and ERK1/2, suggesting the central role of some PB to enhance wound healing, modulating TGF-β activation.

Artificial Intelligence (AI) has seen increased application and widespread adoption over the past decade despite, at times, offering a limited understanding of its inner working. AI algorithms are, in large part, built on weights, and these weights are calculated as a result of large matrix multiplications. Computationally intensive processes are typically harder to interpret. Explainable Artificial Intelligence (XAI) aims to solve this black box approach through the use of various techniques and tools. In this study, XAI techniques are applied to chronic wound classification. The proposed model classifies chronic wounds through the use of transfer learning and fully connected layers. Classified chronic wound images serve as input to the XAI model for an explanation. Interpretable results can help shed new perspectives to clinicians during the diagnostic phase. The proposed method successfully provides chronic wound classification and its associated explanation. This hybrid approach is shown to aid with the interpretation and understanding of AI decision-making processes.

Visfatin, a member of the adipokine family, plays an important role in many metabolic and stress responses. The mechanisms underlying the direct therapeutic effects of visfatin on wound healing have not been reported yet. In this study, we examined the effects of visfatin on wound healing in vitro and in vivo. Visfatin enhanced the proliferation and migration of human dermal fibroblasts (HDFs) and keratinocytes, and significantly increased the expression of wound healing-related vascular endothelial growth factor (VEGF) in vitro and in vivo. Treatment of HDFs with visfatin induced activation of both extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal kinases 1 and 2 (JNK1/2) in a time-dependent manner. Inhibition of ERK1/2 and JNK1/2 led to a significant decrease in visfatin-induced proliferation and migration of HDFs. Importantly, blocking VEGF with its neutralizing antibodies suppressed the visfatin-induced proliferation and migration of HDFs and human keratinocytes, indicating that visfatin induces the proliferation and migration of HDFs and human keratinocytes via increased VEGF expression. Moreover, visfatin effectively improved wound repair in vivo, which was comparable to the wound healing activity of epidermal growth factor (EGF). Taken together, we demonstrate that visfatin promotes the proliferation and migration of HDFs and human keratinocytes by inducing VEGF expression and can be used as a potential novel therapeutic agent for wound healing.

Viroids are known the smallest plant pathogens, and although their genome sequences do not encode proteins, they can cause disease in economically important crops. In order to control viroid diseases and mitigate their damage, genetic resources used for breeding of the viroid-resistant crop have been searched, but the practical resistant trait has not been found in almost all viroid-crop combinations, as well as the tolerant trait. Due to the difficulty in exploiting naturally occurring resistance or tolerance, various effective strategies have been devised to control viroid diseases using non-transforming or transforming techniques. Meanwhile, extensive findings related to viroid resistance and tolerance may lead to confer resistance or tolerance to viroid infection by combining with the recently emerged new technologies (e.g., spray-induced gene silencing and genome-editing technologies), which are believed to be more environmentally viable and acceptable to the general public than previously reported approaches. In particular, some genome-modified crops produced by the latter technology are already on the market. In this review, we comprehensively summarize the current status about investigation of naturally occurring genetic traits for viroid resistance and tolerance, accumulating knowledge about host factors involved in viroid pathogenicity, and various basic technologies developed to try to possible viroid disease control strategies. Furthermore, we discuss prospects and challenges for the achievement of more effective, practical, and sustainable disease control of viroid.

Microbiota plays a key role in various body’s functions, physiological, metabolic and immunological processes, through different mechanisms such as the regulation of the development and/or functions of different types of immune cells in the intestines. Several evidences indicate that alteration in the gut microbiota can influence infectious and non-infectious diseases. Bacteria that resides on the mucosal surface or within the mucus layer participate in interactions with the host immune system, and a healthy gut microbiota is essential for the development of mucosal immunity. The immunomodulatory activity of probiotics has been proposed in several bowel disorders or in aging-related dysfunctions. In HIV infected patients, the intestinal immune system is affected and inflammation persists during ART therapy too. Several studies are in progress to investigate the ability of probiotics to modulate epithelial barrier functions, microbiota composition and microbial translocation in HIV infection. This mini-review aims to suggest how the use of probiotics is beneficial not only in maintaining a healthy status but also to improve conditions in HIV subjects.

Previous studies show that women with a history of high-grade CIN have a greater risk of subsequent high-grade anogenital intraepithelial neoplasia or cancer, and the risk is greater for vaginal cancer than for anal and vulvar cancers. It is hypothesized that the laparoscopic hysterectomy procedure may cause a higher incidence of VaIN in hysterectomized women. There are few studies addressing this issue and they show mixed results. This study aimed to investigate the incidence of high-grade or worse VaIN in the population of women undergoing hysterectomy for CIN3 or benign uterine disease, illustrate treatment options and follow-up. Methods: This retrospective study was conducted on 170 women who underwent laparoscopic hysterectomy for high-grade cervical intraepithelial neoplasia (CIN3) or benign gynecological disease. The follow-up strategy included performing a cotest and colposcopy with biopsy if necessary. The median time between primary treatment and diagnosis of high-grade VaIN was 18 months. Results: High grade or worse VaIN was found in 8 patients after hysterectomy (4.7%). All cases of high-grade VaIN occurred in women with persistent HPV infection. The most frequent genotype was 16. Women hysterectomized for CIN3 showed an 8-fold greater risk than women hysterectomized for benign disease of developing high-grade VaIN. The risk of VaIN is low in women hysterectomized for benign disease. The risk of developing VaIN is greater in women with viral persistence Conclusion. All these elements suggest that it is the history of HPV-related disease of the lower genital tract and viral persistence, rather than hysterectomy itself, that should be considered a risk factor for the development of high-grade VaIN. After hysterectomy, patients with a history of CIN should undergo annual screening with vaginal dome cytology and HPV testing.

Verticillium wilt is a soil borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Two V. dahliae isolates were recovered from symptomatic cot-ton plants in Australian cotton fields and were assigned to two distinct vegetative compatibility groups (VCGs). One corresponding to the defoliating (VCG 1A) and the other non-defoliating (VCG 2A) pathotypes of Verticillium, have been transformed with Red and Green Fluorescent protein genes, respectively. The transformants maintained their ability to infect cotton and both strains were observed to colonise the xylem vessels of cotton plants. Moreover, we observed that the cotton V. dahliae strains could also infect some sampled non-Gossypium species found in the Australian landscape. The fluorescently labelled strains of V. dahliae will allow us to gain a thorough understanding of the infection processes of this important pathogen.