The spread of antimicrobial resistance (AMR) is a global challenge. Close and continuous surveillance for quick detection of AMR can be difficult, especially in remote places. This narrative review focuses on the contributions of pharmacovigilance (PV) as an auxiliary tool for identifying and monitoring the ineffectiveness of, resistance to, and inappropriate use of antibiotics (ABs). The terms “drug ineffective,” “therapeutic failure,” “drug resistance,” “pathogen resistance,” and “multidrug resistance” were found in PV databases and dictionnaires, and denote ineffectiveness. These terms cover a range of problems that should be better investigated because they are useful in warning about possible causes of AMR. “Medication errors,” especially those related to dose and indication, are highlighted in the literature, suggesting inappropriate use of ABs. Hence, the included studies show that the terms of interest related to AMR are not only present but frequent in PV surveillance programs. This review illustrates the feasibility of using PV as a complementary tool for antimicrobial stewardship activities, especially in scenarios where other resources are scarce.

The use of antibiotics in neonatal units worldwide varies significantly. We included data from 2015-2022 from the EpicLatino database, which comprises a network of 32 units in Latin America and the Caribbean with gestational age at birth (GA) of ≤ 32 weeks. A questionnaire was sent to the EpicLatino units, to correlate practice with outcomes. Negative binomial regression with standard errors and confidence intervals computed for incidence-rate ratios (IRRs) was used for comparative statistics on antibiotic days per 1000 patient-days between units. All units that responded had 1-6 differences with the reference unit (Unit 2) with the best results, but there was no clear association with the IRR. Each EpicLatino unit should review its statistics to explore possibilities for reducing antibiotic usage.

Urinary tract infections (UTIs) are highly prevalent in long-term care facilities, constituting the most common infection in this setting. Our research focuses on analyzing clinical characteristics and antimicrobial prescriptions for UTIs in residents across nursing homes (NH) in Spain. This cross-sectional report is part of a before/after intervention study using a multifaceted approach based on the normalization process theory to improve healthcare quality provided by nursing staff in 34 NHs in Spain. In this study we present the results of the first audit including 719 UTI cases, with an average age of 85.5 years and 74.5% being women. Cystitis and pyelonephritis presented distinct symptom patterns. Notably, 6% of asymptomatic bacteriuria cases were treated. The prevalence of dipstick usage was 83%, raising concerns about overreliance, including in the 46 asymptomatic cases, leading to potential overdiagnosis and antibiotic overtreatment. Improved diagnostic criteria and personalized strategies are crucial for UTI management in NHs, emphasizing the need for personalized guidelines on management of UTIs, to mitigate indiscriminate antibiotic use in asymptomatic cases.

This study conducted an extensive analysis of campylobacteriosis surveillance in Portugal from 2009 to 2021, aiming to investigate demographic shifts, seasonal variations, and antimicrobial resistance (AMR) within Campylobacter isolates. Surveillance network and sentinel laboratory-based system data revealed a substantial under-notification of campylobacteriosis cases, suggesting an underestimated disease burden. A paradigm shift was observed in notification rates, with a notable prevalence among the pediatric population, particularly in children aged 1-4 years, diverging from European reports. However, the study also highlighted an emerging trend of Campylobacter infections in younger adults (15-44 years). The study unveiled a unique seasonal distribution of cases, defying typical summer peaks seen elsewhere. AMR analysis revealed extremely to very high-level resistance to ciprofloxacin and tetracycline, both in C. jejuni (93.7% and 79.2%, respectively) and in C. coli (96.5% and 93.2%, respectively), stable throughout the studied period (2013-2021). C. coli also exhibited significantly higher resistance to erythromycin, gentamicin, ampicillin, amoxicillin-clavulanic acid (decreased resistance), and ertapenem compared to C. jejuni (P<0.001). In conclusion, the study highlights the need for enhanced surveillance efforts and emphasizes worrying AMR levels. The implementation of WGS-based surveillance is recommended to attain a more profound comprehension of disease patterns and the evolving landscape of AMR.

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

Antimicrobial resistance (AMR) has a significant global impact on human, animal, and environmental health. Misuse and overuse of antibiotics in clinical and animal production settings are the main drivers behind the emergence of antimicrobial resistant bacteria. However, other compounds with antimicrobial activity may also contribute to this global public health problem. The aim of this comprehensive review is to provide detailed insights into the impact of metals and organic acids on the emergence and spread of AMR in the food chain, for which their role is not fully understood. The review examines the widespread use of organic acids in the food industry as feed additives or disinfectants, the crucial role of copper in animal growth and the harmful effects of mercury and arsenic as pollutants in food-producing environments. Additionally, it explores the antimicrobial mechanisms of metals and organic acids, the tolerance mechanisms developed by bacteria, and the interplay between genes responsible for metal tolerance and AMR. The comprehensive and integrated data presented highlights the need to further explore and understand the role of metals and organic acids as drivers of AMR to develop well-defined strategies effectively mitigating the AMR crisis within the food chain context.

The present study produced and characterised chitosan, chitosan nanoparticle, chitosan n – benzaldehyde Schiff base, chitosan nanoparticle n – benzaldehyde Schiff base, Fe(III) chitosan n – benzaldehyde Schiff base and Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base for biomedical application as antimicrobial agents. The materials were characterized with Fourier Transform Infrared spectroscopy, X-ray Diffractogram and biologically evaluated using disc diffusion method with three gram-positive bacteria. The FTIR absorption peaks were shifted to a lower wave number than the micro materials from which it was modified. These clearly indicate the linkage between phosphate, ammonium ion, Schiff base and Fe(III) metal. The diffracted peaks of Fe(III) chitosan nanoparticle n – benzaldehyde Schiff base were new peaks at 2θ = 24o and 42o when compare to the peak of Fe(III) chitosan n – benzaldehyde Schiff base of 2θ = 22.5o and 34o. The difference in peak shift were attributed to the ionic bonding of the complexation of Fe(III) with the blending of benzaldehyde to chitosan – Tpp backbone structure. Fe(III) chitosan nanoparticle Schiff base has more antimicrobial activity against same bacteria and fungi tested than Fe(III) chitosan n – benzaldehyde Schiff base, chitosan n – benzaldehyde Schiff base and chitosan. The antimicrobial activities of the synthesised six materials shown that the materials have high activities than the above – mentioned standard drugs.

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

Antimicrobial resistance (AMR) is a growing public health concern worldwide, and it poses a significant threat to human, animal, and environmental health. The overuse and misuse of antibiotics have contributed significantly to the emergence and spread of antimicrobial resistance, which may lead to significant economic consequences like reduced productivity and increased healthcare costs. Nanotechnology offers a promising platform for addressing this challenge. Nanoparticles have unique properties that make them highly effective in combating bacterial infections by inhibiting the growth and survival of multidrug-resistant bacteria in three areas of health: human, animal, and environmental. To conduct an economic evaluation of surveillance in this context, it is crucial to have a comprehension of the connections to be addressed by several nations by implementing national action policies based on the One Health strategy. This review provides an overview of the progress made thus far and presents potential future directions to optimize the impact of nanobiotics on AMR.

Community-acquired pneumonia (CAP) is among the most common causes of death and one of the leading healthcare concerns worldwide. It can evolve into sepsis and septic shock, which have a high mortality rate, especially in critical patients and comorbidities. The definitions of sepsis were revised in the last decade as “life-threatening organ dysfunction caused by a dysregulated host response to infection”. Procalcitonin (PCT), C-reactive protein (CRP), and complete blood count including white blood cells are among the most commonly analyzed sepsis-specific biomarkers also used in pneumonia in a broad range of studies. It appears to be a reliable diagnostic tool to expedite care of these patients with severe infections in the acute setting. PCT was found superior to most other acute phase reactants and indicators, including CRP as a predictor of pneumonia, bacteremia, sepsis and poor outcome. In addition, PCT use is beneficial to judge timing for cessation of antibiotic treatment in most severe infectious states. The clinicians should be aware of strengts and weaknesses of known and potential biomarkers in expedient recognition and management of severe infections. This manuscript is intended to present an overview of the definitions, complications and outcomes of CAP and sepsis, with special regard to PCT and other important markers.

Antimicrobial resistance (AMR) is a global health problem threatening safe, effective healthcare delivery in all countries and settings. The ability of microorganisms to become resistant to the effects of antimicrobials is an inevitable evolutionary process. The misuse and overuse of antimicrobial agents has increased the importance of a global focus on antimicrobial stewardship (AMS). This review provides insight into the current AMS landscape and identifies contemporary actors and initiatives related to AMS projects in eight African countries (Ghana, Kenya, Malawi, Nigeria, Sierra Leone, Tanzania, Uganda, and Zambia), which form a network of countries participating in the Commonwealth Partnerships for Antimicrobial Stewardship (CwPAMS) programme. We focus on common themes across the eight countries, including the current status of AMR, infection prevention and control, AMR implementation strategies, AMS, antimicrobial surveillance, antimicrobial use, antimicrobial consumption surveillance, a one health approach, digital health, pre-service and in-service AMR & AMS training, access to and supply of medicines, and the impact of COVID-19. Recommendations suitable for adaptation are presented, including the development of a national AMS strategy and incorporation of AMS in pharmacists’ and other healthcare professionals' curricula for pre-service and in-service training.

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

Objective: The goal of the present study was to evaluate the treatment with Canephron® after the diagnosis of acute cystitis or urinary tract infection (UTI) with regards to the risk of a sporadic recurrent UTI, frequent recurrent UTIs, UTI associated sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis) compared to standard antibiotic treatment. Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 in general practitioner (GP), gynecologist, or urologist practices from which data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI associated sick leave, amount of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson Comorbidity Score (CCI). Results: 2,320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with less sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58–0.72), as well as with less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and with minor additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16) and occurrences of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real world data show that Canephron® is an effective and safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment in particular also to strengthen antimicrobial stewardship strategies.

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

United States is the largest producer and the second largest exporter of broiler meat in the world. In the U.S, broiler production is largely converting to antibiotic-free programs which has caused an increase in morbidity and mortality within broiler farms. Escherichia coli and Clostridium perfringens are two important pathogenic bacteria readily found in the broiler environment and result in annual billion-dollar losses from colibacillosis, gangrenous dermatitis, and necrotic enteritis. Broiler industry is in search of non-antibiotic alternatives including novel vaccines, prebiotics, probiotics, and housing management strategies to mitigate production losses due to these diseases. This review provides an overview of the broiler industry and antibiotic free production, current challenges, and emerging research on antibiotic alternatives to reduce pathogenic microbial presence and improve bird health.

Enterococci are gastrointestinal commensals whose hardiness allowed them to colonize very diverse environments, including soils, water, food and feed. This ability to overcome adverse conditions makes enterococci problematic once they colonize hospital niches. Together with the malleability of their genomes, the capacity to acquire and disseminate determinants of antibiotic resistance have contributed to convert what was once just another opportunistic pathogen into a first-class clinical problem. This review discusses the dimension of the emergence of enterococcal resistance to key antimicrobial agents, the dissemination of this resistance and its significance in terms of public health, with the aim of raising the awareness to the need to devise and implement monitoring programmes and effective antibiotic usage guidelines.

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

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

Pseudomonas aeruginosa (P. aeruginosa) produces a suite of virulence factors that are coordinated by Quorum Sensing (QS) contributing to its disease-causing ability in aquaculture. The present study is first of its kind to obtain information regarding the presence and distribution of five QS genes, three virulence genes viz: lasI, lasR, rhlI, rhlR, rhlAB, toxA, aprA and plcH and seven of the Extended-spectrum βlactamases (blaVEB, blaPER, blaTEM,, blaSHV, blaCTX-M1, blaCTX-M2 and blaCTX-M3) of Pseudomonas species isolated from fish meat by direct PCR. Bacterial identification was based mainly on conventional biochemical techniques using the Vitek 2, automated system. Phenotypic sensitivity of antibiotics was established by the agar disc diffusion technique through 16 various antimicrobial drugs. Quantification of their in vitro production of numerous virulence genes outside the cell that are QS dependent namely, pyocyanin, elastase, alkaline protease, biofilm and cytotoxicity of Vero cell was as well executed. Fifteen genes demonstrated an enormous variety in their association. The total number of Pseudomonas species isolates were 30/100 to be identified by the API 20NE system as P. aeruginosa 12/30 (40%), P. fluorescens 8/30 (27%), P. putida 6/30 (20%) and P. alkylphenolia 4/30 (13%). The outcomes of this study have great significance for the strategic designation of QS quenching.

Antimicrobial stewardship efforts are an emphasis among many institutions around the world to combat inappropriate antimicrobial utilization, rising healthcare costs and emerging antimicrobial resistance. Implementation of new innovative strategies may be challenging for many institutions with limited or constrained resources. Using proven effective methods as evidenced by other institutions in the peer-reviewed literature may offer an opportunity to evaluate institution-specific practices, which may be implemented locally. A structured examination and survey of the peer-reviewed, stewardship literature by an expert group of clinicians, scholars and educators determined the most influential publications from 2016. Herein, the top thirteen manuscripts are reviewed to aid clinicians identify potential stewardship opportunities and serve as an educational tool for trainees and others.

Drug resistance has become an extremely serious problem worldwide. Antibiotic resistance genes (ARGs) entering the environment with wastewaters promote replenishment of the resistome of natural microbioms. Distribution of several clinically significant ARGs in wastewaters of Rostov-on-Don (Southern Russia), lower reaches of the Don River and natural waters of the neighboring region was investigated. Metagenomic DNA samples isolated from 250 ml of wastewaters or natural waters and 200 mg of surface sediments were used for the study. Identification of the ARGs was carried out with end-point detection PCR. Presence of NDM, OXA-48, CTX-M, VanA, VanB, ErmB, and TetM/TetO genes was detected in urban wastewaters. Samples of wastewater treatment plant (WWTP) sewage were enriched with ARGs in contrast to non-treated wastewaters from the sewage collector. NDM, VanA, ErmB, TetM/TetO genes were found only in wastewaters and were absent in samples of natural waters and surface sediments. Only OXA-48, VanB and CTXM genes were found in natural waters and surface sediments. The described ARGs are quite typical for urban and hospital wastewaters. The target ARGs were detected in the samples connected to the anthropogenous sources of pollution such as Rostov municipal WWTP or livestock enterprise effluents.

Background: Staphylococcus aureus (S. aureus) occasionally threatens the life of the host as a persistent pathogen even though it is normal flora of humans and animals. We characterized drug resistance in S. aureus isolated from animal carcasses and milk samples from the abattoirs and dairy farms in the Eastern Cape Province. Methods: A 1000 meat swab samples and 200 raw milk samples were collected from selected abattoirs and dairy farms in the Eastern Cape Province, South Africa. S. aureus was isolated and positively identified using biochemical tests and confirmed by molecular methods. Antibiotic susceptibility test against 14 different antibiotics was performed against all isolates. Antibiotic resistance genes were also detected. Results: Of the 1200 samples collected, 134 (11.2%) samples were positive for S. aureus. Resistance ranged from 71.6% for penicillin G to 39.2% for tetracycline. Resistance gene (blaZ) was detected in 13 (14.9%), while msrA was found in 31 (52.5%) of S. aureus isolates. Conclusions: The present result shows the potential dissemination of multidrug-resistant S. aureus strains in the dairy farms and abattoirs in the Eastern Cape. Therefore, this implies that the organism may rapidly spread through food and pose serious public health risk

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

This theoretical study presents a novel perspective on the potential anti-inflammatory properties of Bromelain, a natural agent extracted from pineapple stems. The investigation explores the binding capabilities of Bromelain to Apoptosis-associated speck-like containing CARD (ASC), a crucial adapter molecule known for its involvement in inflammatory processes and inflammasome formation. For the first time, these findings suggest that Bromelain exhibits a notable affinity for ASC, indicating its promising role as a natural anti-inflammatory agent. This study sheds light on the molecular interactions that may contribute to Bromelain's therapeutic potential in modulating inflammatory responses.

Background: Human papillomavirus is a common pathogen that infects the skin and mucosal epithelium, is transmitted sexually; causes condylomas or squamous cell carcinomas. Two (16 and 18) of the 150 HPV serotypes are oncogenic types. Studies have been done on the infection by oncogenic human papillomavirus 16/18 and associated factors are found to be very limited in Ethiopia. Objective: This study aimed to assess the prevalence of oncogenic human papillomavirus infection (HPV 16/18) and associated factors among women. Methods: An institutional-based cross-sectional study was conducted among 337 women screened for cervical cancer in two hospitals in East Gojjam Zone from February to April 2021 G.C. Four BSc-qualified nurses who worked in the chosen hospitals collected the data using pretested questionnaire and an HPV test (OncoE6TM Cervical Test) specific to HPV16/18 in cervical swabs. Descriptive analysis was performed to determine the prevalence and a multivariate logistic regression model was used to identify the associated factors of HPV16/18 infection. Finally, statistical significance was declared at P < 0.05.Results: The prevalence of HPV infection was 14.2% (95% CI: 10.7% -18.1%). The mean age of the respondents was 36.7±9.1 years. Women with the age group of 55-65 years (AOR = 7.91, 95% CI: 1.95-32.09), early initiation of sexual intercourse (AOR = 5.36, 95% CI: 1.58-18.13), history of sexually transmitted infection (STI) (AOR = 3.52, 95% CI: 1.27-9.72), human immunodeficiency virus (HIV) positive status (AOR = 6.8, 95% CI: 1.99-23.54), and number of lifetime sexual partners (AOR = 4.37, 95% CI: 1.15-17.3) were important independent factors associated with the presence of oncogenic HPV infection. Conclusion and Recommendation: We found a relatively low prevalence of high-risk HPV infection. Age, early initiation of sexual intercourse at less than 18 years, STI of women, being HIV seropositive, and a number of sexual partners were important factors for high-risk HPV infection. Women aged > 46 years, women with early initiation of sex, a history of STI, being HIV positive, and a history of multiple sexual partners should be encouraged to be screened and vaccinated for HPV infection. Wider-ranging studies are also needed in HPV-infected women in association with the cervical lesion.

Objectives: The term "inflammageing” describes the process of inflammation-induced aging that leads living cells to a state of permanent cell cycle arrest due to chronic antigenic irritation. This in vitro study aimed to shed light on the mechanisms of “inflammageing” on human oral cells. Methods: Primary cultures of human gingival fibroblasts (hGFs) were exposed to variable pro-inflammatory stimuli, including lipopolysaccharide (LPS), Tumor Necrosis Factor-alpha (TNFa), and gingival crevicular fluid (GCF) collected from active periodontal pockets of systemically healthy patients. Inflammageing was studied through two experimental models, employing either late-passage (“aged”) cells (p.10) that were exposed to the pro-inflammatory stimuli or early-passage (“young”) cells (p.1) continuously exposed during a period of several passages (up to p.10) to the above-mentioned stimuli. Cells were evaluated for the expression of beta-galactosidase activity (histochemical staining), senescence-associated genes (qPCR analysis), and biomarkers related to a Senescence Associated Secretory Phenotype (SASP), through proteome profile analysis and bioinformatics. Results: A significant increase (p<0.05) of beta-galactosidase-positive cells was observed after exposure to each pro-inflammatory stimulus. The senescence-associated gene expression included upregulation for CCND1 and downregulation for SUSD6, and STAG1, a profile typical for cellular senescence. Overall, pro-inflammatory priming of late-passage cells caused more pronounced effects in terms of senescence, than long-term exposure of early-passage cells to these stimuli. Proteomic analysis showed induction of SASP, evidenced by upregulation of several pro-inflammatory proteins (IL-6, IL-10, IL-16, IP-10, MCP-1, MCP-2, M-CSF, MIP-1a, MIP-1b, TNFb, sTNF-RI, sTNF-RII, TIMP-2) implicated in cellular aging and immune responses. The least potent impact on the induction of SASP was provoked by LPS and the most pronounced by GCF. Conclusion: This study demonstrates that long-term exposure of hGFs to various pro-inflammatory signals induced or accelerated cellular senescence with the most pronounced impact noted for the late-passage cells. The outcome of this analyses provides insights into oral chronic inflammation, as a potential confounder of age-related diseases.

A retrospective study including 49 women with ovarian clear cell carcinoma between January 2009 and December 2021 at Oxford cancer centre was done. The mean age was 63 years, with 78% post-menopausal. All women underwent cytoreductive surgery with no residual disease (R0) in 39 women. The follow-up time ranged between 12-144 months, with mean of 105.5 months. The 3-year OS was 73.4%, and 3-year PFS was 81.3%, with a mean of 101.7months (95%CI, 84.63-118.93). As expected, women with stage 1 disease had the best outcome. In comparing OS in respect to absence or presence of residual disease, the 3-year OS was 88.6% (95% CI 108.6-141.8), compared to 12.5% (95% CI 4.48-32.11) respectively (P<0.001). In multivariant analysis the variables included were CA 125 (< or >200 IU/ml), Hb (< or >115 g/L), albumin (< or >40 g/L), associated endometriosis, ascites, residual disease, and FIGO staging. FIGO stage was the only independent prognostic indicator of OS with (p<0.05). Surgery to achieve no residual tumour is necessary to improve the prognosis in advanced OCCC. At present, the true challenge is to predict which patients with early-stage disease are at higher risk of recurrence and would most benefit from adjuvant treatments.

Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

In West Africa, research on the hepatitis E virus (HEV) is barely covered despite the recorded outbreaks. The still low level of access to safe water and adequate sanitation is one of the main factors of HEV spread in developing countries. HEV infection induces acute or sub-clinical liver diseases with a mortality rate ranging from 0.5 to 4%. The mortality rate is more alarming (15 to 25%) among pregnant women, especially in the last trimester of pregnancy. Here, we conducted a multicentric socio-demographic and seroepidemiological survey of HEV in Senegal among pregnant women. A total of 1,227 consenting participants attending antenatal clinics responded to our questionnaire. Plasma samples were collected and tested for anti-HEV IgM and IgG by using the WANTAI HEV-IgM and IgG ELISA assay. HEV global seroprevalence was 7.9% with 0.5% and 7.4% for HEV IgM and HEV IgG, respectively. One participant's sample was IgM/IgG positive, while four were declared indeterminate to anti-HEV IgM as per the manufacturer's instructions. From one locality to another, the seroprevalence of HEV antibodies varied from 0 to 1% for HEV IgM and from 1.5 to 10.5% for HEV IgG. The data also showed that seroprevalence varied significantly by marital status (p&lt;0.0001), by the regularity of income (p=0.0043) and by access to sanitation services (p=0.0006). These data could serve as a basis to setup national prevention strategies focused on socio-cultural, environmental and behavioral aspects for a better management of HEV infection in Senegal.

Trace amine-associated receptors (TAARs) are a family of G protein-coupled receptors present in mammals in the brain and in several peripheral organs. Apart from its olfactory role, TAAR5 is expressed in the major limbic brain areas and regulates brain serotonin functions and emotional behaviors. However, most of its functions remain undiscovered. Given the role of serotonin and limbic regions in some aspects of cognition, we used a temporal decision-making task to unveil a possible role of TAAR5 in cognitive processes. We found that TAAR5 knock-out (KO) mice showed a generally better performance due to a reduced number of errors and displayed a greater rate of improvement at the task than WT littermates. However, task-related parameters, such as time accuracy and uncertainty have not changed significantly. Overall, we show that TAAR5 modulates specific domains of cognition, highlighting a new role in brain physiology.

Apomictic plants (reproducing via asexual seeds), unlike sexual individuals, avoid meiosis and egg cell fertilization. Consequently, apomixis is very important for fixing maternal genotypes in the next plant generations. Despite the progress in the study of apomixis, molecular and genetic regulation of the latter remains poorly understood. So far APOLLO (Aspartate Glutamate Aspartate Aspartate histidine exonuclease) is one of the very few described genes associated with apomixis in Boechera species. The centromere-specific histone H3 variant encoded by CENH3 gene is essential for cell division. Mutations in CENH3 disrupt chromosome segregation during mitosis and meiosis since the attachment of spindle microtubules to a mutated form of the CENH3 histone fails. This paper presents in silico characteristic of APOLLO and CENH3 genes, which may affect apomixis. Also, we characterize the structure of CENH3, study expression levels of APOLLO and CENH3 in gynoecium/siliques of the natural diploid apomictic and sexual Boechera species at the stages of before and after fertilization. While CENH3 was a single copy gene in all Boechera species, the APOLLO gene have several polymorphic alleles associated with sexual and apomictic reproduction in the Boechera genera. Expression of the APOLLO apo-allele during meiosis was upregulated in gynoecium of apomict B. divaricarpa downregulating after meiosis until 4th day after pollination (DAP). On the 5th DAP, expression in apomictic siliques increased again. In sexual B. stricta gynoecium and siliques APOLLO apo-allele did not express. Expression of the APOLLO sex-allele during and after meiosis in gynoecium of sexual plants was several times higher than that in apomictic gynoecium. However, after pollination the sex-allele was downregulated in sexual siliques to the level of apomicts and increased sharply on the 5th DAP, while in apomictic siliques it almost did not express. At the meiotic stage, the expression level of CENH3 in the gynoecium of apomicts was two times lower than that of the sexual Boechera, decreasing in both species after meiosis and keep remaining very low in siliques of both species for several days after artificial pollination until the 4th DAP, when the expression level raised in sexual B. stricta siliques exceeding 5 times the level in apomictic B. divaricarpa siliques. We also discuss polymorphism and phylogeny of the APOLLO and CENH3 genes.

The Corona Virus Disease 2019 (COVID-19) outbreak is becoming pandemic with the highest mortality in people with associated comorbidities. These RNA viruses containing four structural proteins usually use spike protein to enter the host cell. It has been demonstrated that Angiotensin Converting Enzyme 2 (ACE2) ,as a part of renin-angiotensin-aldosterone system (RAAS), acts as a host receptor for the virus which is the main target of therapeutic approaches. However, medications acting on RAAS can lead to serious complications especially in people with diabetes and hypertension. To avoid this, other potential treatment modalities should be used in COVID-19 patients with associated comorbidities.

Introduction Our aim was to determine the impact of antimicrobial stewardship tools (AST) and COVID-19 pandemic on antibiotic consumption (AC). Methods We used the national software Consores to determine AC in DDD / 1000 days of hospitalization from 2017 to 2022 in voluntary private hospitals in France. The AST considered were 1/ internal guidelines 2/ list of antibiotics with restricted access 3/ presence of an antibiotic referent or 4/ an ID specialist 5/ proof of annual meeting on antimicrobial resistance. Institutions with dedicated units for COVID-19 patients were specified. Results In 30 institutions total AC varied from (means) 390 to 405 DDD/1000 DH from 2017 to 2022. Fluoroquinolones and amoxicillin / clavulanate consumption decreased from 50 to 36 (p = 0.003) and from 112 to 77 (p = 0.025) respectively, but consumption of piperacillin / tazobactam increased from 9 to 21 (p < 0.001). Over the study period, 10 institutions with ≤ 2 AST had lower AC compared to 20 institutions with ≥ 3 AST (p < 0.01). COVID-19 units opened in 10 institutions were associated with a trend toward higher macrolide consumption from 15 to 25 from 2017 to 2020 (p = 0.065) and with an acceleration of piperacillin / tazobactam consumption from 2020 to 2022 (p ≤ 0.003). Conclusion Antibiotic consumption in 30 private hospitals in France was inversely related to the number of AST. The COVID-19 pandemic was associated with limited impact on AC but special attention should be paid on piperacillin / tazobactam consumption.

The ESKAPE pathogens are public health concerns worldwide, defining the present major antibiotic resistance issues: E. faecium vancomycin-R, S. aureus methicillin-R, Ps. Aeruginosa and A. baumannii carbapenem-R, resistance to 3rd generation cephalosporins of Kl. pneumoniae and Enterobacter spp. Covid-19 pandemic disturbed the health care usual procedures, contributing to the spread of antibiotic-resistant bacteria. The present study retrospectively assessed the prevalence and antimicrobial resistance (AMR) profile of ESKAPE microorganisms during 2020-2022 in a multidisciplinary emergency hospital from Romania, based on microbiological reports. The AMR issues mainly interest the urology department. ESKAPE group accounts for 33.5% of the total bacterial isolated. The specific AMR of ESKAPE pathogens cumulates 30.9%, while antimicrobial multidrug resistance characterizes 21% from all ESKAPE strains. Kl. Pneumoniae, followed by S. aureus, and Ps. aeruginosa are the main hospital problems concerning the ESKAPE surveillance. The directions of the near future antibiotic stewardship program focus to revise the clinical protocols for diagnostic and treatment in each department, to intensify the bacteriological samples collection, to improve the microbiological diagnostic techniques for AMR identification, to continue the epidemiological current actions of surveillance, control, and education.

The presented work studies the processes of synthesis of nitrogen-containing structures of ZnO using atmospheric pressure microwave nitrogen plasma and investigates their photocatalytic activity in the processes of degradation of 2,4-dinitrophenol and the antibiotic ciprofloxacin when irradiated with sunlight. The work proposes an effective method for formation of photosensitive ZnO powders. Due to the features of plasma treatment in the open atmosphere of zinc metal microparticles, ZnO structures are formed with sizes from hundreds of nanometers to several micrometers with various micromorphologies. High photoactivity was demonstrated (rate constants 0.036 min-1 and 0.051 min-1) of synthesized ZnO structures during photo-degradation of 2,4-dinitrophenol and ciprofloxacin, respectively, when exposed to solar radiation. Photo-active structures of ZnO synthesized using microwave nitrogen plasma can find application in processes of mineralization of toxic organic compounds.

Bacterial biofilms can cause widespread infection. In addition to causing urinary tract infections and pulmonary infections in patients with cystic fibrosis, biofilms can help microorganisms adhere to the surfaces of various medical devices, causing biofilm-associated infections on the surfaces of biomaterials such as venous ducts, joint prostheses, mechanical heart valves, and catheters. Biofilms provide a protective barrier for bacteria and provide resistance to antimicrobial agents, which increases the morbidity and mortality of patients. This review introduces the formation process and drug resistance mechanism of biofilms in detail, and further summarizes the main characteristics of clinical persistent infection caused by biofilms and the many methods of treating biomaterial-related biofilm. This provides ideas and directions for the development of new biofilm infection strategies related to therapeutic materials.

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

Background: The AWaRe tool was set up by the World Health Organization (WHO) to promote the rational use of antimicrobials. Indeed, this tool classifies antibiotics into four groups, Access, Watch, Reserve and not-recommended antibiotics. In Republic Democratic of Congo, data on antibiotic dispensing (prescribing) by health professionals according to the AWaRe classification are scarce. In this research work, we aimed to explore antibiotic dispensing pattern from health professionals according to the WHO AWaRe classification to strengthen the national antimicrobial resistance plan. Methods: For this purpose, a survey was conducted from July to December 2022 in the district of Tshangu in Kinshasa. From randomly selected drugstores, drug-sellers were interviewed and randomly selected customers attending those drugstores were included in the study for medical prescriptions collection. The prescribed antibiotics were classified into the Access, Watch, Reserve and not recommended antibiotics group and by antibiotics number by prescription among pharmacies surveyed. Results: Of 400 medical prescriptions collected, 301 (75.25%) contained antibiotics. Of 301 prescriptions containing antibiotics, 164 (164/301; 54.5%) contained one antibiotic, 117 (117/301; 38.9%) two antibiotics, 15 (15/301; 5%) three antibiotics and 5 (5/301; 1.6%) 4 antibiotics. Out of the total of 463 antibiotics prescribed, 169 (169/463; 36.5%) were from the Access group, 200 (200/463; 43.2%) from the Watch group and 94 (94/463; 20.3%) from not recommended antibiotics group, respectively. Based on the anatomical, therapeutic and chemical (ATC) classification, it can be seen that third generation cephalosporins contained 34.33% of the prescribed antibiotics, followed by penicillins 17.17%, macrolides 7.63%, aminoglycosides 7. 36% and Imidazoles 7.36%, thus accounting approximately for 74% of the classes of antibiotics prescribed. Of the 463 antibiotics prescribed, the most frequently prescribed antibiotics were Ceftriaxone (21.38%), Amoxicillin (11.01%), Gentamycin (5.61%), Amoxicillin-clavulanic acid (5 .61%), Azithromycin (4.97%) and Metronidazole (4.75%), thus accounting for approximately 54% of all antibiotics prescribed. Conclusion: These results highlight the importance of strict implementation of the national plan to combat antimicrobial resistance and the need to train health workers in the correct application of the WHO AWaRe classification.

Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.

Antibiotic resistance (ABR) is concerning issue due to its direct and indirect repercusions on public health, since decreased therapeutic effect of certain antibiotic to treatment complications that can cause death. There are several mechanism as to how ABR can be transferred from one microoorganisms to another, and many of them are dependant many environmental factors. The food supply chain is a environment in which ABR gene transfer can occur is multiple pathways, which generate concerns regarding food safety. Here, we summarize relevant mechanisms which are implied in ABR in food supply chain but also we are addressing routes of transmission and prevalence of ABR, implications on public health, and the application of new alternatives to antibiotics such as antimicrobial peptides, mainly bacteriocins, in order to countermeasure ABR.

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

Since streptomycin discovery, actinomycetes were the main source for new antibiotics, but after the Golden age (1950-1960^th) the discovery rate significantly decreased. The high probability to rediscover well-known antibiotics led to a reduction in interest in soil bacteria as a source for new antibiotics. At the same time, actinomycetes remain a very promising reservoir for searching for new active molecules. In this work, we present several reporters containing eye-visible fluorescent protein genes, which can be used to increase the efficiency of determining the mechanism of antibiotics at the very initial stage of screening. Presented reporters and the following pipeline were optimized given the involvement of citizen scientists without specialized skills and equipment in order to utilize the reservoir of soil bacteria in the search for new antibiotic producers. The combination of mechanism-based approaches and civil science has proved its effectiveness in practice revealing a significant increase in the screening rate. Two new strains Streptomyces sp. KB-1 and BV113 were found to produce antibiotics pikromycin and chartreusin, respectively, demonstrating the efficiency of the pipeline.

Antimicrobial resistance (AMR) due to community carriage of antibiotic-resistant bacteria is highly prevalent in the WHO South-East Asia region. One of the major reasons is the misuse of antibiotics in animal farming practices and at community level, which threatens both human and animal health. However, this multifaceted One Health (OH) problem of antibiotic use (ABU) in poultry farms and respective farmers is not well studied in countries like Pakistan. Therefore, we conducted n OH cross-sectional study in rural Punjab to explore the current practices of ABU in poultry and poultry farmers, associated factors, their healthcare-seeking behaviour and biosecurity practices. We found all the participating farmers using antibiotics for poultry, 60% of which were Colistin sulphate and Amoxicillin trihydrate. The significant consumption of antibiotics in poultry farms (60%) and poultry farmers (50%) was without prescription. Most of the farms (85%) had no wastewater drainage system, causing direct shedding of poultry waste and antibiotic residue in the surrounding environment. Lack of farmers’ education, professional farm training and duration of farming experience were the significantly associated factors with ABU and knowledge of AMR. Our study implies the necessity of an integrated OH-AMR policy with the inclusion of farmers’ education, mass awareness, and strict antibiotic usage guidelines.

Multicomponent reactions (MCR) have been used to synthesis a wide range of analogs from several classes of heterocyclic compounds, with multifaceted medicinal uses. The synthesis of highly functionalized molecules in a single pot is a unique property of MCR, allowing researchers to quickly assemble libraries of compounds of biological interest and uncover novel leads as possible therapeutic agents. Isocyanide-based multicomponent reactions have proven to be extremely effective at swiftly specifying members of compound libraries, particularly in discovery of drug . The understanding of structure-activity correlations that drive the development of new goods and technology, requires structural variety in these libraries. In current world, antibiotic resistance is a major ongoing problem which is developing a problematic scenario in public health. The implementation of isocyanide based multicomponent reactions uphold a significant potential in this regard. By utilizing such reactions, new antimicrobial compounds can be discovered and fight against such concerns. This study discusses recent developments in antimicrobial medication discovery using isocyanide-based multicomponent reactions (IMCRs). Furthermore, the article emphasizes the potential of IMCRs in the near future.

Staphylococcus aureus can develop resistance by mutation, tranfection or biofilm formation. Resistance was induced in S. aureus by growth in sub-inhibitory concentrations of ciprofloxacin for 30 days. The ability of the antimicrobials to disrupt biofilms was determined using crystal violet and live/dead staining. Effects on the cell membranes of biofilm cells was evaluated by measuring release of dyes and ATP and nucleic acids. S. aureus did not develop resistance to the AMPs but resistance increased to ciprofloxacin by 128 times after 30 passages. Only peptides reduced biofilms of ciprofloxacin resistant cells. The antibiofilm effect of melimine with ciprofloxacin was more (27%) than with melimine alone at 1X MIC (p < 0.001). Similarly, at 1X MIC the combination of Mel4 and ciprofloxacin produced more (48%) biofilm disruption than Mel4 alone (p < 0.001). Combinations of either of the peptides with ciprofloxacin at 2X MIC released  66 nM ATP, more than either peptide alone (p  0.005). At 2X MIC, only melimine in combination with ciprofloxacin released DNA/RNA which was 3 times more than released by melimine alone (p = 0.043). These results suggest the potential use of melimine and Mel4 with conventional antibiotics for the treatments of S. aureus biofilms.

Increasing attention has been paid to the potential probiotic effects of Latilactobacillus sakei. To explore the genetic diversity of L. sakei, 14 strains isolated from different niches (feces, fermented kimchi and meat products) and 54 published strains were compared and analyzed. The results showed that the average genome size and GC content of L. sakei were 1.98Mb and 41.22%, respectively. Its core genome mainly encodes translation and transcription, amino acid synthesis, glucose metabolism and defense functions. L. sakei has an open pan-genomic characteristics, and its pan-gene curve shows an upward trend. L. sakei has open pan-genome feature, and its pan-genome curve is on the rise. The genetic diversity of L. sakei is mainly reflected in carbohydrate utilization, antibiotic tolerance, and immune/competition-related factors, such as clustering regular interval short palindromic repeat sequence (CRISPR)-Cas. The CRISPR system is mainly IIA type, and a few are IIC types. This work provides a basis for the study of this species.

Treating infections caused by Pseudomonas aeruginosa is increasingly difficult due to high antimicrobial resistance, materialized through the presence of multiple resistance strains, as well as due to rapid development of resistance throughout treatment. The present survey was conducted to investigate the antibiotic susceptibility profile of Pseudomonas aeruginosa pathogens, in two University Veterinary hospitals from different geographical regions of Romania (i.e., south-west - Timisoara county and north-east – Iasi county) involved in canine superficial infections. A total of 142 swab specimens were collected from dogs with superficial infections (superficial skin infections, otitis externa, perianal abscess), with the aim of assessing the presence of Pseudomonas aeruginosa, based on phenotypic and molecular characterization. Fifty-eight samples (40.84%; 58/142) were positive for Pseudomonas aeruginosa (according to their confirmed morphological and molecular features). Susceptibility to usual antibiotics used in the treatment of canine skin conditions was tested for all Pseudomonas strains that were isolated from canine superficial infections, using the Kirby Bauer disc diffusion method. Drug resistance was observed in the case of all tested antibiotics. The susceptibility rate of P. aeruginosa strains that were tested in this study was in the following order: ampicillin sulbactam (55.17%; 32/58), followed by ceftazidime (53.44%; 31/58), aztreonam (51.72%; 30/58), amikacin (44.82%; 26/58), azithromycin (41.37%; 24/58), gentamycin (37.93%; 22/58), cefepime (36.20%; 21/58) meropenem (25.86%; 13/58), piperacillin-tazobactam (25.86%; 13/58) imipenem (22.41%; 13/158), ciprofloxacin (17.24%; 10/58) tobramycin (8.62; 5/58), and polymyxin B (1.72; 1/58) respectively. The results highlight the importance of antibiotic susceptibility testing in Pseudomonas aeruginosa isolates from dogs with superficial infections, in order to use an adequate treatment plan for the management of the skin condition, and other pathology (otitis externa and perianal abscesses).

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

Salmonella, especially invasive non-typhoidal Salmonella (iNTS) are responsible for developing various invasive diseases, and possess higher mortality rate, due to their higher antibiotic resistance profile than the other bacteria. Therefore, the present study was concerned to develop epitope based peptide vaccine against iNTS species as a successive and substitute protective measures. The study considered comprehensive Immunoinformatic approaches, followed by molecular docking and molecular dynamics simulation to predict the efficient vaccine candidate T cell and B cell epitopes, based on the outer membrane proteins. The study identified two best epitopes YGIFAITAL and KVLYGIFAI from total iNTS outer membrane proteins, which showed higher immunity, non-allergenicity, non-toxicity and also showed higher conservancy and population coverage values. Both epitopes showed higher binding affinity and stability towards HLA-C* 03:03. The MM-PBSA binding free energy showed the YGIFAITAL epitope binds more tightly with both MHC-I and MHC-II molecules. The total contact, H-bond analysis and RMSF results also validate the efficiency of these epitopes as vaccine candidate. The projected B cell epitopes AAPVQVGEAAGS, TGGGDGSNT and TGGGDGSNTGTTTT showed higher antigenicity. Overall, the study concluded that these epitopes can be considered as the potential vaccine candidate to make a successive vaccine against iNTS species. However, this result further needs to be validate by wet lab research to make successive vaccine with these projected epitopes.

Background: Antibiotic lock therapy is an interventional modality used for treatment and prevention of central-line associated bloodstream infections. Stability and compatibility data for combinations are lacking, limiting clinical use. Objective: Compatibility and stability of daptomycin lock solutions in combination with azithromycin, gentamicin, and heparin or sodium citrate were evaluated up to 96 hours. Methods: Eight candidate lock solutions were prepared for compatibility and stability testing. All solutions were prepared in glass vials, and included daptomycin 1mg/mL in varying combinations with heparin 100 – 1,000 units/mL, trisodium citrate, azithromycin and/or gentamicin. Lactated Ringer’s solution was added as a diluent in a sufficient quantity to bring the total volume up to 5mL. Drug stability in the admixture was determined by the degradation of the components. The quantification of drugs was performed using Waters Alliance HPLC using Phenomenex Luna C8 (2), 150*2.6mm, 5µ column. A gradient run was executed for 20 minutes with 0.45% ammonium dihydrogen phosphate, pH 3.25 as eluent A and acetonitrile as eluent B at a flow rate of 1.0mL/min. Each solution was visually inspected for particulates and color change. Lock solutions were tested in triplicate. Results: Daptomycin degradation was <10% for all solutions at 48 hours, and for 7 of the 8 solutions at 72 hours. Gentamicin degradation was <5% for solutions in combination with daptomycin and trisodium citrate. No physical incompatibilities were detected. Conclusion: Study data support the stability and compatibility of daptomycin with additives in solution, allowing for fewer exchanges and longer dwell times for a lock solution. The addition of azithromycin or gentamicin may offer synergy and/or extended spectrum of activity. Daptomycin bioactivity with trisodium citrate needs confirmation.

Tuberculosis (TB) is the primary cause of death by a single infectious agent; responsible for around two million deaths in 2016. A major virulence factor of TB is the ability to enter a latent or Non-Replicating Persistent (NRP) state which is presumed untreatable. Approximately, 1.7 billion people are latently infected with TB and on reactivation many of these infections are drug resistant. As the current treatment is ineffective and diagnosis remains poor, millions of people have the potential to reactivate into active TB disease. The immune system seeks to control the TB infection by containing the bacteria in a granuloma, where it is exposed to stressful anaerobic and nutrient deprived conditions. It is thought to be these environmental conditions that trigger the NRP state. A number of in vitro models have been developed that mimic conditions within the granuloma to a lesser or greater extent. These different models have all been utilised for the research of different characteristics of NRP Mycobacterium tuberculosis, however their disparity in approach and physiological relevance often results in inconsistencies and a lack of consensus between studies. This review provides a summation of the different NRP models and a critical analysis of their respective advantages and disadvantages relating to their physiological relevance.

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, which is one of the most common skin diseases. Acne vulgaris often associates with acne-related bacteria such as <i>Propionibacterium acnes</i>, <i>Staphylococcus epidermidis</i>, <i>Staphylococcus aureus</i> and <i>Pseudomonas aeruginosa</i>, some of which exhibit a resistant against commercial antibiotics used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we evaluated <i>in vitro</i> antibacterial activity of chitosan-phytochemical conjugates against acne-related bacteria. Three of chitosan-phytochemical conjugates used in this study showed stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) exhibited the highest antibacterial activity against acne-related bacteria with minimum inhibitory concentration values of 8 μg/mL to 256 μg/mL. In addition, the MICs of antibiotics against antibiotic resistant <i>P. acnes</i> and <i>P. aeruginosa</i> strains were dramatically reduced in the combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration indices clearly revealed a synergistic antibacterial effect between CCA and the antibiotics. Thus, the median ∑FIC values against the antibiotic resistant bacterial strains were ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics.

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

Oral squamous cell carcinoma (OSCC) remains an under-studied and significant global cancer killer and dismal survival rates have not changed in decades. A better understanding of the molecular basis of OSCC progression and metastasis is needed to develop new approaches for treating this disease. The supportive network surrounding cancer tumor cells known as the tumor microenvironment (TME) has gained increasing interest lately since it performs essential pro-tumorigenic functions. Cancer-associated fibroblasts (CAFs) are one of the main cell types in the TME and are known to play a key role in influencing the biological behavior of tumors. CAFs present a heterogeneity both in phenotype as well as functions, leading to the suggestion of different CAF subtypes in several cancer forms. The task to subtype CAFs in OSCC has however just begun and there is today no united way of subtyping CAFs in this disease. This review aims to define the features of CAFs and to summarize CAF subtype research in OSCC including aspects as disease prognosis and therapeutic opportunities.

Nowadays, healthcare-associated infections (HAIs) represent a major global public health problem and the burden of these infections is high. In order to reduce the incidence of HAIs and to prevent the spread antibi-otics resistant organisms is mandatory to develop surveillance systems. We undertook a retrospective case-control study of all patients presenting HAIs admitted in Intensive Care Unit (ICU) in order to assess risk factors associated with death among patients with HAIs. Patients admitted to Intensive Care Unit who died were more likely to present an infection with a multidrug resistant bacteria, an infection with Acineto-bacter baumannii, and to suffer from acute myocardial infarction. Among the patients enrolled in the study, a higher probability of death was also observed in association with certain gram-negative pathogens: Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa. The longer the patient remains admitted in ICU, the higher the risk of getting an infection that can often become fatal. Acquiring a noso-comial infection also increases the length of hospitalization which will lead to increased financial damage.

This study investigated clinical nurses’ knowledge and visual differentiation ability of the pressure injury classification system (PICS) and incontinence-associated dermatitis (IAD), additionally analyzing possible influencing factors. A convenience sample of 248 nurses took the PICS and IAD knowledge test (KT) and completed the visual differentiation ability test (VDAT), consisting of 21 photographs with clinical information. The overall mean score for correct answers was 12.65±2.90 points in PICS & IAD KT and 11.43±4.57 points in VDAT. Incorrect responses were most common for statements related to stage Ⅱ, Ⅲ, IAD for PICS & IAD KT, and deep tissue pressure injury (DTPI), unstageable, and stage Ⅲ for VDAT. Significant correlations were found between PICS & IAD KT and VDAT (r=.252, p<.001). Factors affecting scores for VDAT were the scores of PICS & IAD KT, debridement experience in nursing patients with PI, and the management frequency of PI and IAD. Results indicate that nurses have an overall understanding of PICS and IAD, but low visual differentiation ability regarding stage Ⅲ, DTPI, and unstageable PI. Continuing education is needed to further improve knowledge and visual differentiation ability for PICS and IAD.

Head and neck squamous cell carcinoma (HNSCC) takes the sixth place among the most common cancers in the world. Abnormal methylation can be one of the reasons for this cancer. The aim of this study was to investigate the DNA promotor methylation status of cancer-associated genes (ATM, APC, CDO1, RB1, TP53, WIF1) in patients with HNSCC. Bisulfite Conversion and Methylation-Sensitive High-Resolution Melting was used for analysis of the DNA methylation level of normal and tumor tissues in 44 patients. There were significant differences in DNA methylation level between patient’s tumor and normal tissues for CDO1 and WIF1 genes in all subjects and subgroups (p<0.05). In T3 subgroup there was significant correlation between CDO1 gene methylation and age in the normal tissue. The same correlation was detected also for the WIF1 gene methylation in tumor tissue samples in the subgroup with T3 and in normal tissue samples in the subgroup with T4 (p<0,05). In all genes no significant differences were found between the subgroups (T2, T3, T4 stage, primary/recurrent lesion, non-keratinizing/keratinizing SCC, age before/ after 50, smokers/non-smokers) of the patients. Thus, changes in the expression of the CDO1 and WIF1 genes can affect mechanisms of the occurrence and development of HNSCC.

The objective of this study is to examine a nonparametric estimate , using the kernel approach, of the conditional distribution function of a scalar response variable that is given a random variable whose values take place in a separable real Hilbert space. The observations will be dependent on one another in a quasi-associated fashion. The pointwise practically perfect consistencies with rates of this estimator are established by us under some broad conditions. The study’s major objective is to investigate the convergence rate of the proposed estimator and its application in the convergence rate and asymptotic normality of the hazard function. The asymptotic normality of the developed estimator is established precisely. Simulation studies were conducted to investigate the behavior of the asymptotic property in the context of finite sample data.

Secretory and membrane proteins are vital for cell activities, including intra- and intercellular communication. Therefore, protein quality control in the endoplasmic reticulum (ER) is an essential and crucial process for eukaryotic cells. Endoplasmic reticulum-associated degradation (ERAD) targets misfolded proteins during the protein maturation process in the ER and leads to their disposal. This process maintains the ER productive function and prevents misfolded protein stress (i.e., ER stress). The ERAD-stimulating factor ER degradation-enhancing α mannosidase-like 1 protein (EDEM1) acts on misfolded proteins to accelerate ERAD, thereby maintaining the productivity of the ER. However, the detail mechanism underlying the function of EDEM1 in ERAD is not completely understood due to lack of established physiological substrate proteins. In this study, we attempted to identify substrate proteins for EDEM1 using siRNA. The matrix component thrombospondin-1 (TSP1) and epidermal growth factor receptor (EGFR) were identified as candidate targets of EDEM1. Their protein maturation status and cellular localization were markedly affected by knockdown of EDEM1. We also showed that EDEM1 physically associates with EGFR and enhances EGFR degradation via ERAD. Our data highlight the physiological role of EDEM1 in maintaining specific target proteins and provide a potential approach to the regulation of expression of clinically important proteins.

Cells respond to a myriad of stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a senescence-associated-secretory-phenotype (SASP). The heterogeneity of senescent cells (SnCs) and their SASP is vast, yet poorly characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and harmonization of their nomenclature a priority. The Cellular Senescence Network (SenNet), a NIH Common Fund initiative, will leverage emerging single cell and spatial-omics to identify and map SnCs in numerous organs across the lifespan of humans and mice. A common coordinate framework will integrate the data, using validated, standardized methods, creating public 4-dimensional SnC atlases. Key SenNet deliverables include development of innovative tools/technologies to detect SnCs, biomarker discovery, common annotations to describe SnCs and extensive public data sets. The goal is to comprehensively understand and map SnCs for diagnostic and therapeutic purposes to improve human health.

MicroRNAs (miRNAs) are a class of small non-coding RNAs, which function as regulators of gene expression and contribute in numerous physiological processes. However, little is known referring to miRNAs function in insect chemosensation. In the current study, nine small RNA libraries were constructed and sequenced from the antennae of nymphs, adult males and females of Apolygus lucorum. In total, 399 miRNAs were identified including 275 known and 124 novel miRNAs. Known miRNAs were classified into 71 families, amongst which, 23 families were insect-specific. Expression profile analysis showed that miR-7-5p_1 was the most abundant miRNAs in the antennae of A. lucorum. Altogether, 69708 target genes related to biogenesis, membrane and binding activities were predicted for 399 miRNAs. Particularly, 15 miRNAs were found to target 16 olfactory genes. These miRNAs could be involved in regulation of olfactory-associated genes ex-pression. Comparing the antennae of nymphs, adult males and females, 94 miRNAs were found to be differentially expressed. The expression levels of some differentially expressed miRNAs measured by qPCR were consistent with sequencing results. This study provides a global miRNAs transcriptome in the antennae of A. lucorum and valuable information for further investigation on miRNA-mRNA interactions, especially the functions of miRNAs in regulating chemosensation.

Statistical data on officially registered cases of health care-associated infections (HCAIs) in Ukraine in the period 2009-2019 have been analysed. On average, 5089±756 cases of HCAIs were registered annually. Odessa region of Ukraine is the leading country in the number of reported cases. The majority of HCAIs cases involve surgical and therapeutic invasive interventions and perinatal HCAIs. On average, 78.0±5.8 % of HCAIs cases involved adults. The estimated minimum number of HCAIs in Ukraine was expected to be about 1 million per year. Official statistics on registered cases of HCAIs in Ukraine do not reflect reality, so the system of registration and investigation of HCAIs in Ukraine needs to be reformed.

Relationships between the Farey sequence and the Riemann hypothesis other than the Franel-Landau theorem are discussed. Whether a function similar to Chebyshev’s second function is square-root close to a line having a slope different from 1 is discussed. The nontrivial zeros of the Riemann zeta function can be used to approximate many functions in analytic number theory. For example, it could be said that the nontrival zeta function zeros and the Möbius function generate in essence the same function - the Mertens function. A different approach is to start with a sequence that is analogous to the nontrivial zeros of the zeta function and follow the same procedure with both this sequence and the nontrivial zeros of the zeta function to generate in essence the same function. A procedure for generating such a function is given.

Antibacterial bone cements (ABCs), such as antibiotic-loaded bone cements (ALBCs), have been widely utilized in clinical treatments. Currently, bone cements loaded with vancomycin, gentamicin, tobramycin, or clindamycin are approved by the US Food and Drug Administration. However, traditional ALBCs exhibit drawbacks like burst release and bacterial resistance. Therefore, there is a demand for the development of antibacterial bone cements containing novel agents. In this review, we summarize the latest advancements in ABCs. More importantly, we provide an overview and outlook on novel antibacterial agent-loaded bone cements, including metallic antibacterial agents, pH-switchable antibacterial agents, cationic polymers, N-halamines, non-leaching acrylic monomers, antimicrobial peptides, etc. Offering novel perspectives for designing ABCs and treating bone infections.

Enterococci are widely acknowledged as prominent pathogens in hospitals, with the potential to transfer resistance genes, virulence factors, or other characteristics that increase their ability to survive in humans. Healthy cattle, sheep, and goats can be reservoirs for gastrointestinal pathogenic fecal enterococci, some of which could be multidrug-resistant to antimicrobials. The objective of this study was to determine the prevalence and diversity of Enterococcus species in healthy sheep, goat, and cattle carcasses, as well as to analyze the antimicrobial resistance phenotype/genotype and the virulence gene content. During 2019–2020, carcass surface samples of 150 ruminants were collected in a slaughterhouse. A total of 90 enterococci, comprising 5 species, were obtained. The overall prevalence of enterococci was found to be 60%, out of which 37.7% were identified as E. hirae, 33.3% as E. casseliflavus, 15.5% as E. faecium, 12.2% as E. faecalis, and 1.1% as E. gallinarum. Virulence-associated genes of efaA (12.2%) were commonly observed in the Enterococcus isolates, followed by gelE (3.3%), asaI (3.3%), and ace (2.2%). Characteristic resistance genes were identified by PCR with an incidence of 6.6%, 2.2%, 1.1%, 1.1%, 1.1%, and 1.1% for the tetM, ermB, ermA, aac(6’)Ie-aph(2")-la VanC1, and VanC2 genes, respectively. The high resistance to quinupristin-dalfopristin (28.8%), tetracycline (21.1%), ampisilin (20%), and rifampin (15.5%) was distributed among two, four, four, and five of the five species, respectively. The resistance of Enterococcus isolates to 11 antibiotic groups was determined and multidrug-resistant (MDR) strains occupied 18.8% of the Enterococcus isolates. Efflux pump genes causing multidrug resistance were detected in Enterococcus isolates (34.4%). The study's results showed that there were enterococci in the slaughterhouse that were multidrug resistant (MDR) and had a number of genes linked to virulence that could be harmful to human health.

Bacteria of the genus Staphylococcus are a significant a challenge for medicine, as many species are resistant to multiple antibiotics and even to all of the antibiotics used. One of the approaches to develop new therapeutics to treat staphylococcal infections is the use of bacteriophages specif-ic to these bacteria or lysins of such bacteriophages capable to hydrolyze the cell walls of these bacteria. In this study, a new bacteriophage St_134 specific to Staphylococcus epedermidis was de-scribed. This small podophage belonging to the Andhravirus genus showed relatively wide host range and was able to infect more than 60 strain of Staphylococcus spp., including a clinical strain from the Staphylococcus aureus complex. Two genes encoding different phage lysins were identi-fied in the Ste134 genome. Both lysins LysSte134_1 and LysSte134_2 were produced in Escherichia coli cells. Endolysin LysSte134_1 was demonstrated catalytic activity against a wide panel of staphylococcal peptidoglycans (4 species, 6 strains), was active against S. aureus and S. epidermidis planktonic cultures and destroyed biofilms formed by clinical strains of S. aureus and S. epider-midis.

Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and is associated with various gastrointestinal disorders. H. pylori is a pervasive pathogen, infecting nearly 50% of the world's population, and presents a substantial concern due to its link with gastric cancer, ranking as the third most common cause of global cancer-related mortality. This review article provides an updated and comprehensive overview of the current understanding of H. pylori infection, focusing on its pathogenesis, diagnosis, and treatment strategies. The intricate mechanisms underlying its pathogenesis, including virulence factors and host interactions, are discussed in detail. Diagnostic methods, ranging from traditional techniques to advanced molecular approaches, are explored, highlighting their strengths and limitations. The evolving landscape of treatment strategies, including antibiotic regimens and emerging therapeutic approaches, is thoroughly examined. Through a critical synthesis of recent research findings, this article offers valuable insights into the contemporary knowledge of Helicobacter pylori infection, guiding both clinicians and researchers toward effective management and future directions in combating this global health challenge.

Leptospirosis is a re-emerging zoonotic disease that has had an unprecedented impact on most health systems in the world. The spectrum of symptoms is variable and usually ranges from asymptomatic cases to severe manifestations involving multiple organ dysfunction accompanied by jaundice, hemorrhage, meningitis, and acute kidney injury that requires the need for intensive care assistance. Although early antibiotic treatment is usually effective, in severe cases it may require renal replacement therapy, invasive mechanical ventilation, vasoactive support, and invasive hemodynamic monitoring, increasing the risk of death. In Latin America, the real burden of acute kidney injury in this condition is unknown and may be underestimated due to the rapid progression of the disease, similar to other vector zoonoses, and the low coverage of diagnostic tests in primary care, especially in rural regions. Therefore, below, we review the clinical aspects and describe the scientific, clinical, and therapeutic evidence of acute kidney injury attributed to Leptospira spp. and its relevance in patients with severe leptospirosis in Latin America.

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

This work demonstrates that microbial fuel cells (MFCs), optimized for energy recovery, can be used as an effective tool to detect the presence of antibiotics in water-based environments. MFCs directly convert chemical energy of organic matter in electrical energy thanks to electroactive biofilms. The efficiency of the conversion process can be significantly affected by the presence of contaminants acting as toxicants for the biofilm. In the present work, we demonstrate that MFCs can successfully detect the presence of antibiotic residues in water and water-based electrolytes associated to the food industry, especially using honey as a new and more complex electron donor. The effectiveness of MFCs to sense antibiotics is here demonstrated for tetracycline that was added to both water and water/honey electrolytes with a minimum concentration close to 3.5 μg⁄kg. MFCs not only efficiently detect the presence of tetracycline in both the electrolytes, but also recover the same performance after each cycle of exposure, showing to a be very robust and reliable technology for both biosensing and energy recovery.

In Pakistan, bats are one of the dominant mammals that play an important role in the ecosystem in terms of pollination, seed dispersal, and control of pest insects. Bats have also played an im-portant role in the emergence and transmission of zoonotic pathogens; however, most current studies focus on viral pathogens, not potential bacterial pathogens. This study was designed to estimate the prevalence and antibiotic profiling of Staphylococcus (S.) aureus in oral and rectal samples from bats captured in northern Pakistan and to determine the factors associated with in-fection. Two hundred individual bats of five species: Pipistrellus javanicus (n = 17), Pipistrellus pipistrellus (n = 10), Rhinopoma microphyllum (n = 48), Rousettus leschenaultii (n = 124), and Scotophilus kuhlii (n = 1) were captured for non-lethal collection of oral and rectal samples to iso-late S. aureus. Bats were sampled from three sites: a natural cave, a man-made castle, and an an-imal shed, in Khyber Pakhtunkhwa and Punjab provinces. Oral (n = 200) and rectal (n = 200) swabs were collected from each individual bat using sterile cotton swabs specifically for use in bacteriological studies. Each isolate of bacteria was identified by using phenotypic tests and con-firmed as S. aureus based on PCR assay. Out of a cumulative four hundred samples, 80 swabs were positive for S. aureus including 47 rectal and 33 oral swabs. Prevalence of S. aureus infection varied significantly among species, with Rousettus leschenaultii exhibiting the highest prevalence (n = 77; 37.90%). In addition to bat species, prevalence varied significantly among habitats but not between sex, age class, or reproductive status. This study confirmed the occurrence of S. aureus in oral and rectal microbiota of bats in Pakistan. Importantly, S. aureus isolates showed resistance to tetracycline, gentamicin, and erythromycin and carried resistant genes such as TetK, TetM, Erma, and aacA-D. In this regard, efforts should be taken to educate the local communities on how to minimize exposure to an antibiotic-resistant bacterial pathogen through contact with bats while simultaneously increasing the awareness of protecting bats as a vital component of our ecosystem.

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

Septic shock substantially alters the pharmacokinetic properties of ß-lactams with a subsequently high risk of insufficiently low serum concentrations and treatment failure. Considering their pharmacokinetic (PK)/pharmacodynamic (PD) index, prolonged infusions (PI) of ß-lactams extend the time that the unbound fraction of the drug remains above the minimal inhibitory concentration MIC (ft >MIC) and may improve patient survival. The present study is a monocentric, retrospective before-and-after analysis of septic shock patients treated with ß-lactams. Patients of the years 2015-2017 received intermittent bolus application whereas patients of 2017-2020 received PI of ß-lactams. The primary outcome was mortality at day 30 and 90 after diagnosis of septic shock. Mortality rates in the PI group were significantly lower on day 30 (PI: 41%, n=119/290 vs. IB: 54.8%, n=68/114; p=0.0097) and day 90 (PI: 47.9%, n=139/290 vs. IB: 62.9%, n=78/124; p=0.005). After propensity-score matching, 30- and 90-day mortality remained lower for the PI group (-10%). PI further reduced duration of invasive ventilation. PI of β-lactam antibiotics led to a stronger decrease in SOFA scores within a 14d-observation period. PI of ß-lactams significantly reduces mortality in patients with septic shock and may have beneficial effects on invasive ventilation and recovery from sepsis-related organ failure.

For polymicrobial infections, AtbFinder utilizes a novel paradigm of the population response to antibiotics, enabling bacterial growth in the form of a mixed microbial community and selecting the antibiotics targeting not only the principal pathogen, but also those bacteria that support their growth. TGV medium allowed culturing a more diverse set of bacteria from polymicrobial biospecimens, compared with that achieved with the standard media and enabled, already within 4h, accurate selection of the antibiotics that completely eliminated all cultivatable bacteria from clinical samples. In conclusion, AtbFinder system may be a valuable tool in improving antibiotic selection, enabling targeted empirical therapy and accurate antibiotic replacement, which is especially important in high-risk patients.

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

Under one-health perspective and the worldwide antimicrobial resistance concern, we investigate extraintestinal pathogenic Escherichia coli (ExPEC), uropathogenic E. coli (UPEC), and multidrug resistant (MDR) E. coli from 197 isolates recovered from healthy dogs in Spain between 2013 and 2017. Ninety-one (46.2%) isolates were classified as ExPEC and/or UPEC including 50 clones, among which (i) four clones were dominant (B2-CH14-180-ST127, B2-CH52-14-ST141, B2-CH103-9-ST372 and F-CH4-58-ST64815) and (ii) 15 had been shown to be displayed by previously published isolates causing extraintestinal infections in humans. Twenty-eight (14.2%) isolates were classified as MDR, associated with B1, D and E phylogroups and included 24 clones, of which eight had also been identified among human isolates causing infections. We selected 23 ST372 strains, 21 healthy dogs faecal isolates and two human clinical isolates for whole genome sequencing and built a SNP-tree with these 23 genomes and 174 genomes (128 from canine strains and 46 from human strains) obtained from public databases. The analysis of these 197 genomes allowed to identify six clusters. Cluster 1 comprised 74.6% of the strain genomes that were mostly composed of canine strain genomes (P &lt; 0.00001). Clusters 4 and 6 also included canine strain genomes, while clusters 2, 3 and 5 were significantly associated with human strain genomes. All these findings suggest that dogs are reservoirs of ExPEC, UPEC and MDR E. coli isolates with zoonotic potential.

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

The global health emergency caused by multi-drug resistant bacteria has led to the search for and development of new antimicrobial agents. Phage therapy is an abandoned antimicrobial therapy that has been resumed in recent years. In this study, we mutated a lysogenic phage from Acinetobacter baumannii into a lytic phage (Ab105-2phiΔCI) showing antimicrobial activity against A.baumannii clinical strains (such as Ab177_GEIH-2000 which showed MICs to meropenem and imipenem of 32 µg/ml and 16 µg/ml, respectively as well as belonging to GEIH-REIPI Spanish Multicenter A. baumannii Study II 2000/2010, Umbrella Genbank Bioproject PRJNA422585). We then enhanced the time kill curves (in vitro) and in Galleria mellonella survival assays (in vivo) antimicrobial activity of the new lytic phage by combining it with carbapenem antibiotics (meropenem and imipenem). We observed in vitro, an antimicrobial synergistic effect (from 4 log to 7 log CFU/ml) with meropenem plus lytic phage in all combinations analysed (0.1, 1 and 10 MOI of Ab105-2phiΔCI mutant as well as 1/4 and 1/8 MIC of meropenem). Moreover, we had a decrease in bacterial growth of 8 log CFU/ml for the combination of imipenem at 1/4 MIC plus lytic phage (Ab105-2phiΔCI mutant) and of 4 log CFU/ml for the combination of imipenem at 1/8 MIC plus lytic phage (Ab105-2phiΔCI mutant) in both MOI 1 and 10. These results were confirmed in in vivo (G. mellonella) obtaining a higher effectiveness in the combination of imipenem and Ab105-2phiΔCI mutant (P<0.05 by Log Rank-Matel Cox test). This approach could help to reduce the emergence of phage resistant bacteria and restore sensitivity to the antibiotics when used to combat multiresistant strains of Acinetobacter baumannii.

Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015-2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24-36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP) (1-2 mg/kg) was administered for mild pneumonia patients, and IVMP (5 -10 mg/kg/day) for severe pneumonia patients. If patients showed persistent fever for 36-48 hours or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Eighty-five patients received only a broad-spectrum antibiotic without macrolide. The mean age and the male:female ratio were 5.6 ± 3.1 years, respectively. Seventy-four percent of patients (190/257) showed immediate defervescence within 24 h, and 95.7% (246/257) of patients showed defervescence within 72 h with improvements in clinical symptoms. Eight patients who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide (n = 172) and without (n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.

Antibiotic residues in aquatic environment have the possibility to induce resistance in environmental bacteria, which ultimately might get transferred to pathogens making treatment of diseases difficultand poses a serious threat to public health. If antibiotic residues in the environment can be eliminated or reduced, it has the possibility to contribute antibiotic resistance. Towards this objective, water containing ciprofloxacin was treated with sunlight assisted photocatalysis using Fe doped ZnOnanoparticles for assessing the degradation potential of this system.Parameters like pH, temperature, catalytic dosage were assessed for the optimum performance of the system. To evaluate degradation of ciprofloxacin,both spectrophotometricas well as microbiological (loss of antibiotic activity)methods were employed. 100 mg/L Fe doped ZnO nanoparticle catalyst and sunlight intensity of 120,000–135,000 lux system gave optimum performance at pH 9 at 30 °C and 40 °C. At these conditions spectrophotometric analysis showed complete degradation of ciprofloxacin (10mg/L) by 210 min. Microbiological studies showed loss of antibacterial activity of the photocatalytically treated ciprofloxacin containingwater against Staphylococcus aureus (10⁸ CFU) in 60 min and for Escherichia coli (10⁸ CFU) in 75 min. Thedeveloped system, thus possess a potential for treatment of antibiotic contaminated waters for eliminating/reducing antibiotic residues from environment.

Healthcare-Associated infections (HAIs) affect more than 100 million patients each year worldwide. These infections are mainly caused by multi-resistant bacterial strains (MDR) such as Acinetobacter Baumanii which is responsible of high mortality rate in immunocompromised individuals. However, the treatment is further aggravated by the abuse of antibiotics, the lack of vaccine and the emergence of resistance posing a huge challenge for the discovery of new therapeutic drugs to overcome this nosocomial infection. In this context, antimicrobial peptides with potential antibacterial proprieties could be an alternative. In this research, we describe the synthesis and the bioactivity of dermaseptins and their derivatives against Acitenobacter baumanii. The cytotoxicity of these DS was investigated on the HEp-2 cell line by the MTT cell viability assay. Thereafter, we studied morphological alterations caused by the action of one of the active peptides on the bacterial membrane using Atomic Force Microscopy (AFM). The cytotoxicity of dermaseptins was concentration-dependent at microgram concentrations. It was observed that all tested analogs exhibit antibacterial activity with MICs ranging from 3.125 to 12.5 μg/mL and MBCs ranging from 6.25 to 25 μg/mL. Microscopic images obtained by AFM revealed morphological changes on the surface of treated bacteria caused by K4S4(1-16), as well as significant surface alterations. Overall, these findings demonstrate that DS might constitute new lead structures for the development of potent antibacterial agents against Acinetobacter infections.

Injured peripheral nerves regenerate their axons in contrast to those in the central nervous system. However, functional recovery after surgical repair is often disappointing. The basis for the poor recovery is the progressive deterioration with time and distance, of the growth capacity of the neurons that lose their contact with targets (chronic axotomy) and the growth support of the chronically denervated Schwann cells (SC) in the distal nerve stumps. This is despite the retained capacity of chronically denervated and atrophic muscle to accept reinnervation. Progressive decline in regeneration associated genes in both axotomized neurons and denervated SCs accounts for the decline in regenerative success in association with silencing of neural activity in sensory neurons due to their disconnection from their sense organs and, in motoneurons due to loss of their synaptic contacts in the spinal cord. Whilst exogenous neurotrophic factors promote nerve regeneration, the profuse axonal outgrowth and difficulties in delivery are avoided by promoting their endogenous expression with brief (1 hour) low frequency (20Hz) electrical stimulation (ES) proximal to the injury site. ES accelerates axon outgrowth and in turn, target reinnervation in both animals and human subjects. Applying ES to intact nerve days prior to nerve injury, conditional ES (CES) increases axonal outgrowth and regeneration rate with the potential for application in nerve transfer surgeries and end-to-side neurorrhaphies. However, the additional surgery for applying CES electrodes may be a hurdle. ES is applicable in all surgeries with excellent outcomes.

Pentagalloyl glucose (PGG) is currently being investigated as a non-surgical treatment for abdominal aortic aneurysms (AAA); however molecular mechanisms of action of PGG on the AAA matrix components and the intra-luminal thrombus (ILT) still need to be better understood. To assess these interactions, we utilized peptide fingerprinting and molecular docking simulations to predict the binding of PGG to vascular proteins in normal and aneurysmal aorta, including matrix metalloproteinases (MMPs), cytokines and fibrin. We performed PGG diffusion studies in pure fibrin gels and human ILT samples. PGG was predicted to bind with high affinity to most vascular proteins, the active sites of MMPs, and several cytokines known to be present in AAA. Finally, despite potential binding to fibrin, PGG was shown to diffuse readily through thrombus at physiologic pressures. In conclusion, PGG can bind to all the normal and aneurysmal aorta protein components with high affinity, potentially protecting the tissue from degradation and exerting anti-inflammatory activities. Diffusion studies showed that thrombus presence in AAA is not a barrier to endovascular treatment. Together, these results provide a deeper understanding of the clinical potential of PGG as a non-surgical treatment of AAA.

Classic Hodgkin lymphoma (cHL) is a lymphoid neoplasm composed of rare neoplastic Hodgkin and Reed-Sternberg (HRS) cells surrounded by a reactive tumor microenvironment (TME) with suppressive properties against anti-tumor immunity. TME is mainly composed of T-cells (CD4 helper, CD8 cytotoxic and regulatory), and tumor-associated macrophages (TAMs) but the impact of these cells on the natural course of the disease is not absolutely understood. TME contributes to the immune evasion of neoplastic HRS cells through production of various cytokines and/or aberrant expression of immune checkpoint molecules, in ways that have not been fully understood yet. Herein, we present a comprehensive review of findings regarding the cellular components and the molecular features of the immune TME in cHL, its correlation with treatment response and prognosis as well as the potential targeting of the TME with novel therapies. Among all cells, macrophages appear to be a most appealing target for immunomodulatory therapies, based on their functional plasticity and antitumor potency.

Kaposi’s sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, is the causative agent of Kaposi’s sarcoma, Castleman’s disease, and primary effusion lymphoma. Although the functions of the viral thymidine kinases (vTK) of herpes simplex virus-1/2 and varicella zoster virus are well understood, that of KSHV ORF21 (an ortholog of vTK) is largely unknown. Here, we investigated the role of ORF21 in lytic replication and infection by generating two ORF21-mutated KSHV BAC clones: ORF21-kinase activity deficient-KSHV (21KD) and stop codon-induced ORF21-deleted-KSHV (21del). The results showed that both ORF21-mutations did not affect viral genome replication, lytic genes transcription, or the production of viral genome-encapsidated particles. ORF21 molecule-dependent function, other than the kinase function of ORF21, was involved in the infectivity of progeny virus. ORF21 was expressed at 36 h after induction of lytic replication, and endogenously expressed ORF21 was localized in the whole cytoplasm and decreased on the cell surface area. Moreover, the effects of ORF21 expression on signaling pathways and proliferation were analyzed. The results showed that ORF21 upregulated the MEK phosphorylation and anchorage-independent cell growth. These findings indicate that ORF21 plays key roles in both infection and oncogenesis of KSHV through the manipulation of cellular function.

Leptospirosis remains an important worldwide zoonotic disease caused by Leptospira spp affecting human and animals. This research aims to study the virulent-associated secreted proteins (protein secretome) of pathogenic Leptospira interrogans serovar Icterohemorrhagiae strain RGA (Leptospira RGA) transition from the environment to mammalian physiological osmolarity, temperature (37 °C) and carbon dioxide concentration (5% CO2) conditions for 24 h. Mass Spectrometry and bioinformatics approaches, we identified 69 potential secreted proteins from the culture supernatant of the Leptospira RGA isolate. We discovered transporters and porins such as phosphate porin, outer membrane efflux, ompA family protein, and polymer-forming cytoskeletal family protein under hyperosmotic condition. Under heat stress, degradation enzymes included zinc metallopeptidase, M23 family (LA3456, LA0709), Rhs family protein (LA1765), thermolysin metallopeptidase; / hydrolase family (LA1345, LA2501). Oxidative stress response proteins induced by osmolarity and temperature shifts included chaperon GrpE, DnaK (LA3705), antioxidants, i.e., thiol-specific redoxin, and peroxiredoxin (LA2809). In response to the in vivo transition, metabolic and other enzymes involved in energy production (COG:C), amino acid metabolism and transport (COG:E), and lipid metabolism and transport (COG:I), as well as moonlighting proteins functionally binding to plasminogen and fibronectin and regulating transcription, were also discovered. An overview of secreted proteins will supplement our understanding of Leptospira biology and pathogenesis during infection and also in response to environmental stimuli and their potential virulent determinants have the potential for developing leptospirosis vaccines and diagnosis.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

Insect herbivores have a wide range of life cycles and feeding habits, making them extremely diverse. With their host plants, they form close relationships and suppress their defense mecha-nisms. Molecular elicitors are the key bio-elements in detection and recognition of attacking enemies in tissue consumption. Insect oral secretion, frass, and fluid of egg deposition contain bio-logical active molecules called herbivore-associated elicitors (HAEs) are recognized by pattern recognition receptors (PRRs). However, in insect herbivores, little is known about the molecular basis of signal transduction and regulation of plant resistance. Many plants distinguish insect feeding from wounding by HAEs presenting in their oral secretions (OS) and induce local and systemic responses against arthropod feeding. PRRs perceive HAEs in the oral secretion of cater-pillars in a species-specific manner to elicit exclusive defense responses. HAEs-PRRs interactions induce plant resistance by reprogramming plant metabolism and transcriptional machinery. Quantitative, timely, and coordinated plant response initiate early signalling events including Ca+2, reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs). We have discussed how early signalling cascades converge into the accumulation of phytohormones that regulate down-stream special metabolites against herbivores. In this review, we have drawn a hypothetical model of PPRs-HAEs mediated induced responses in plants and discussed how PRRs-HAEs interactions based on molecular mechanism that elicit short- and long-term induced defenses in plants. The identification of plant target insect herbivore PRRs-HAEs interactions will help to explore the fundamental molecular mechanisms of host manipulation and may generate prospects to develop novel pest resistance strategies.

The cytosolic PNGase (peptide:N-glycanase; Png1 in yeast; NGLY1/Ngly1 in human/mice), also known as peptide-N4-(N-acetyl-beta-glucosaminyl)-asparagine ami-dase, is a well-conserved deglycosylation enzyme (EC 3.5.1.52) which catalyzes the non-lysosomal hydrolysis of an N(4)-(acetyl-β-D-glucosaminyl) asparagine residue into N-acetyl-β-D-glucosaminylamine and a peptide containing an aspartate residue. This enzyme (NGLY1) plays essential roles in clearance of misfolded or unassembled gly-coproteins through a process named ER-associated degradation (ERAD). Accumulating evidence also points out that NGLY1 deficiency can cause an autosomal recessive hu-man genetic disorder associated with abnormal development and congenital disorder of deglycosylation. In addition, the loss of NGLY1 can affect multiple cellular pathways, including but not limited to NFE2L1 pathway, Creb1/Atf1-AQP pathway, BMP path-way, AMPK pathway, and SLC12A2 ion transporter, which might be the underlying reasons for a constellation of clinical phenotypes of NGLY1 deficiency. The current comprehensive review indeed uncovers the detailed NGLY1’s structure and its im-portant roles for participation in ERAD, involvement in CDDG and potential treatment for NGLY1 deficiency.

In the context of the COVID-19 pandemic, thousands of healthcare workers (HCWs) infected with COVID-19 have lost their lives worldwide. At the early stage of the epidemic, when COVID-19 was still not considered as a pandemic, a large number of Chinese HCWs were infected. Officials reported that more than 3,000 HCWs in Hubei contracted the virus at the early stage of the outbreak due to limited knowledge of the virus. Following reports of overloaded local hospitals, more than 42,000 medical staff, including those from the military, were dispatched to Hubei from across the country. At the peak of the fight, one in 10 intensive care medics in China were working in Wuhan. During fighting against COVID-19 in China, although a large number of HCWs were infected by SARS-CoV-2 in the early stages of the epidemic, the timely adoption of measures indicated that, a faster rate of diagnosis could be achieved, patients were isolated in-time, HCWs’ safety was prioritized, training on basic protective knowledge and unified management of HCWs was strengthened, and effective protective measures were implemented. This resulted in the accomplishment of zero SARS-CoV-2 infection among the 42,632 members of the national medical teams sent to Hubei, and the number of COVID-19 cases among HCWs in local hospitals also significantly decreased, thereby indicating that hospital-acquired infections of SARS-CoV-2 among HCWs are fully preventable.

Suboptimal health status (SHS) is a state between health and disease, has several associated factors, although, its underlying mechanism is still unclear. This study aimed to investigate the status of SHS and its associated factors of high school students in three areas of China (Shanxi, Guangzhou, and Tibet). A multidimensional sub-health questionnaire of adolescent (MSQA) is used to evaluate SHS. Among 1461 respondents, females proportion 56.47% was higher than males 43.53% where SHS was higher in Shanxi followed by Tibet and then Guangzhou. The rural area, grade, lack of sleep, home visit in a week, lack of exercise, a heavy burden of study, smoking, drinking, and fewer friends were the risk factors of SHS, while, families living status, seeking help and extroversion were the protective factors. SHS is significantly associated with different influencing factors. For comprehensive prevention and control measures, reduce the risk factors and enhance the protective factors.

Sonoran felids are threatened by drought and habitat fragmentation. Vector range expansion and anthropogenic factors such as habitat encroachment and climate change are altering viral evolutionary dynamics and exposure. However, little is known about the diversity of viruses present in these populations. Small felid populations with lower genetic diversity are likely to be most threatened with extinction by emerging diseases, as with other selective pressures, due to having less adaptive potential. We used a metagenomic approach to identify novel circoviruses, which may have a negative impact on the population viability, from confirmed bobcat (Lynx rufus) and puma (Puma concolor) scats collected in Sonora, Mexico. Given some circoviruses are known to cause disease in their hosts, such as porcine and avian circoviruses, we took a non-invasive approach using scat to identify circoviruses in free-roaming bobcats and puma. Three circovirus genomes were determined, and, based on the current species demarcation, they represent two novel species. Phylogenetic analyses reveal that one circovirus species is more closely related to rodent associated circoviruses and the other to bat associated circoviruses, sharing the highest genome-wide pairwise identity of approximately 70% and 63%, respectively. At this time, it is unknown whether these scat-derived circoviruses infect felids, their prey, or another organism that might have had contact with the scat in the environment. Further studies should be conducted to elucidate the host of these viruses and assess health impacts in felids.

Oral cancer cells (TYS) and the signalling pathways involved in metastasis, in response to cancer-associated fibroblasts (CAFs, COM) and normal oral mucosal fibroblasts (MM1) was studied. Metastatic cell behaviour was observed by cell-scatter, 3D-collagen gel migration and 3D-spheroid invasion assays. Akt, MAPK, EGFR, TGFβRii and CXCR4 inhibitors were used to identify the signalling pathways involved. Signalling pathway protein expression and activation were assessed by SDS-PAGE and Western Blotting. COM-CM (conditioned medium) and MM1-CM stimulated cancer cell scattering, which was blocked only by the Akt inhibitor. COM-CM induced scattered cancer cells showed higher levels of Akt phosphorylation than the negative control and MM1-CM. Migration and invasion of TYS cells into the collagen gels from the spheroids was stimulated by CM from both sources, compared to the negative control. COM cells stimulated TYS, cancer cell invasion into the collagen more than MM1 and the control. Akt and EGFR inhibitors effectively blocked CM and COM cell-induced invasion. Akt-silenced cancer cells were not stimulated to migrate and invade by fibroblast-CM and did not survive addition of the EGFR inhibitor. This suggests that CAFs stimulate oral cancer cell migration and invasion in an Akt- dependent manner. EGFR and Akt are potential therapy targets in metastatic oral cancer.

Since the first description of bisphosphonate-related osteonecrosis of the jaw (BRONJ) numerous research groups have focused on possible pathological mechanisms including the suppression of the bone turnover of the jaw, antiangiogenic effects and soft tissue toxicity. In our review we focused on summarizing the role of the soft tissues in the development and progression of BRONJ. The biological behavior of fibroblasts can be significantly influenced by bisphosphonates (BP) such as a concentration dependent reduction of cell viability. High concentrations of BP can induce apoptosis and necrosis of the cells. Comparable effects could be detected for keratinocytes. Compared to non-nitrogen containing bisphosphonates nitrogen-containing BP have worse effects on cell biology by blocking the mevalonate pathway. Next to this the cell architecture and the expression levels of several genes and proteins are significantly disturbed by BP. These inhibitory effects of BP are in accordance with BP related reduced angiogenesis and neovascularization and could underline the hypothesis that inhibition of fibroblasts and keratinocytes results in delayed wound healing and can induce and trigger BRONJ.

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

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

Fire blight, caused by Erwinia amylovora, is a devastating bacterial disease that threatens world-wide production of apples and pears. In Canada and the US, streptomycin and kasugamycin are commonly used for the control of this pathogen. There is an urgent need for development of biocontrol agents (BCAs) that can be easily incorporated into integrated pest management pro-grams with high efficacy against streptomycin sensitive and resistant strains of E. amylovora. In addition, excessive use of antibiotics in agriculture has increased awareness of the possibility of antibiotic resistance gene transfer to human, animal and environmental microbes. To address this issue, a phage-carrier system (PCS) that combines Pantoea agglomerans as an antagonistic bacterial carrier of Erwinia phages as a double-pronged treatment for fire blight have been de-veloped. The low viability of P. agglomerans cells following spray drying challenged the industrial scale production of this PCS. In the present research, a spray drying protocol was developed for P. agglomerans by modifying the growth medium and the bacterial cell formulation using D(+)-trehalose and maltodextrin. The developed protocol is amenable to industrial scale pro-duction of the BCA/PCS. The P. agglomerans viability was greater than 90% after spray drying, had a prolonged shelf life of 4 months at 4 C, and the reconstituted cells showed an approximate 3 log reduction in E. amylovora counts with a green pear disc challenge assay.

(1) Background: There is a need to assess the availability of essential antimicrobials as the availability of an antimicrobial is a critical element of its rational use. We aimed to assess the availability of antimicrobials listed in National List of Essential Medicines 2015, India (primary list) and a selected (secondary) list comprising of agents indicated for commonly encountered infectious illnesses in various healthcare settings and to identify the reasons for their non-availability. (2) Methods: A cross-sectional survey of 25 public, private, and other sector pharmacies was carried out in Rohtak, a district of North Indian state of Haryana, from April to June 2022. (3) Results: Most of the antimicrobials surveyed were optimally available in various sector pharmacies with the exception of benzathine benzyl penicillin, benzyl penicillin, cloxacillin, cefazolin, cefuroxime, cefadroxil, amphotericin B and antimalarials. Most frequent reasons for limited availability were low demand, no prescriptions and non-listing of drugs in state essential medicine list. (4) Conclusions: Enough evidence needs to be generated with respect to status of availability of essential antimicrobials from different regions of India as well as other lower-middle income countries to devise measures for ascertaining better availability of these agents especially antibiotics at regional, national and global scales.

Antimicrobial resistance (AMR) poses a global public health threat, with rates directly linked with consumption. The World Health Organization (WHO) AWaRе-classification aims to guide antibiotic use, which is influenced by drug availability, affordability, and economic policies. In Jordan, a high proportion of consumed antibiotics belong to the 'Watch' category. Data from the WHO-AWaRе classification, the Essential Medicines List, and the Jordan Food and Drug Administration were analyzed. Antibiotics for adults were classified and their cost per Defined Daily Dose (DDD) was determined, then affordability was assessed. In 2023, 43 injectable and 43 oral antibiotics for adults were registered in Jordan. 'Watch' antibiotics were the most common. 'Access' antibiotics had the lowest cost/DDD. 'Rеsеrvе' antibiotics were the most expensive with few generics. Injectable antibiotics had a negative correlation between cost and the number of alternatives. Affordability was higher for oral antibiotics compared to injectable ones. 'Rеsеrvе' antibiotics were generally unaffordable. This study highlights the need to promote 'Access' antibiotics over other categories by encouraging registration of missing ‘Access’ antibiotics and adjusting 'Watch' and 'Rеsеrvе' antibiotic prices. Competition among generics can lead to lower prices, increasing affordability and accessibility. We emphasize the importance of the AWaRе-classification in guiding antibiotic use in Jordan.

Antibiotics were once called miracle drugs which hit the market with astounding impact as it was considered the ultimate cure for infectious diseases in the mid-20th century. However, today nearly all bacteria that afflict humankind have become resistant to these wonder drugs once developed to stop them, imperilling the foundation of modern medicine. During the COVID pandemic, there was a surge in macrolide use to treat secondary infections and this persistent use of macrolide antibiotics has provoked the emergence of macrolide resistance. In view of the current dearth of new antibiotics in the pipeline, it is essential to find an alternative way to combat drug resistance. Antibiotic potentiators or adjuvants are non-antibacterial active molecules that, when combined with antibiotics, increase their activity. Thus, potentiating the existing antibiotics is one of the promising approaches to tackle and minimize the impact of antimicrobial resistance. Several natural and synthetic compounds have demonstrated effectiveness in potentiating macrolide antibiotics against MDR pathogens. The present review summarizes the different resistance mechanisms adapted by bacteria to resist macrolides and further emphasizes the major macrolide potentiators identified which could serve to revive the antibiotic and can be used for the reversal of macrolide resistance.