Politicians polarize and experts depolarize public support for COVID-19 management policies across countries.

Political polarization impeded public support for policies to reduce the spread of COVID-19, much as polarization hinders responses to other contemporary challenges. Unlike previous theory and research that focused on the United States, the present research examined the effects of political elite cues and affective polarization on support for policies to manage the COVID-19 pandemic in seven countries (n = 12,955): Brazil, Israel, Italy, South Korea, Sweden, the United Kingdom, and the United States. Across countries, cues from political elites polarized public attitudes toward COVID-19 policies. Liberal and conservative respondents supported policies proposed by ingroup politicians and parties more than the same policies from outgroup politicians and parties. Respondents disliked, distrusted, and felt cold toward outgroup political elites, whereas they liked, trusted, and felt warm toward both ingroup political elites and nonpartisan experts. This affective polarization was correlated with policy support. These findings imply that policies from bipartisan coalitions and nonpartisan experts would be less polarizing, enjoying broader public support. Indeed, across countries, policies from bipartisan coalitions and experts were more widely supported. A follow-up experiment replicated these findings among US respondents considering international vaccine distribution policies. The polarizing effects of partisan elites and affective polarization emerged across nations that vary in cultures, ideologies, and political systems. Contrary to some propositions, the United States was not exceptionally polarized. Rather, these results suggest that polarizing processes emerged simply from categorizing people into political ingroups and outgroups. Political elites drive polarization globally, but nonpartisan experts can help resolve the conflicts that arise from it.

Evaluation of Author Instructions for Inclusive Language Guidance in Highly Cited English Language Medical Journals.

BACKGROUND: Diversity, equity, and inclusion (DEI) are at the core of publication ethics, and language around DEI has been shown to affect patient outcomes. Inclusive language is an important piece of effective communication and is one way to demonstrate and foster a welcoming, respectful, and accessible environment. Non-inclusive terminology in research may represent implicit bias, which is not typically corrected through introspection; thus, a systematic approach is needed in scientific writing. The prevalence of inclusive language guidance in leading medical journals is currently unknown. OBJECTIVE: Investigators assess the prevalence and quality of inclusive language guidelines in author instructions in highly cited English language medical journals. DESIGN: A cross-sectional review of author instructions from a convenience sample of 100 highly cited medical journals was completed in January 2023. SUBJECTS: Each journal's author instructions were reviewed for presence of inclusive language guidelines for manuscript submissions. MAIN MEASURES: Guidelines that included specific examples of inclusive language were defined as "strong." Author instructions were also reviewed for the Sex and Gender Equity in Research (SAGER) checklist, and each journal's publisher and impact factor (IF) were recorded. KEY RESULTS: The 100 journals reviewed had an IF range of 3.0-202.7 with a median IF = 19.5 (IQR 11.95, 38.68), and 28 unique publishers were represented. Inclusive language guidance was provided in 23% of medical journals reviewed. Of those, 20 (86.9%) provided strong guidance. Seven journals also recommended use of the SAGER checklist. CONCLUSION: Significant gaps still exist in ensuring use of inclusive language in medical journals.

CD200 Limits Monopoiesis and Monocyte Recruitment in Atherosclerosis.

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Interferon regulatory factor-5-dependent CD11c+ macrophages contribute to the formation of rupture-prone atherosclerotic plaques.

AIMS: Inflammation is a key factor in atherosclerosis. The transcription factor interferon regulatory factor-5 (IRF5) drives macrophages towards a pro-inflammatory state. We investigated the role of IRF5 in human atherosclerosis and plaque stability. METHODS AND RESULTS: Bulk RNA sequencing from the Carotid Plaque Imaging Project biobank were used to mine associations between major macrophage associated genes and transcription factors and human symptomatic carotid disease. Immunohistochemistry, proximity extension assays, and Helios cytometry by time of flight (CyTOF) were used for validation. The effect of IRF5 deficiency on carotid plaque phenotype and rupture in ApoE-/- mice was studied in an inducible model of plaque rupture. Interferon regulatory factor-5 and ITGAX/CD11c were identified as the macrophage associated genes with the strongest associations with symptomatic carotid disease. Expression of IRF5 and ITGAX/CD11c correlated with the vulnerability index, pro-inflammatory plaque cytokine levels, necrotic core area, and with each other. Macrophages were the predominant CD11c-expressing immune cells in the plaque by CyTOF and immunohistochemistry. Interferon regulatory factor-5 immunopositive areas were predominantly found within CD11c+ areas with a predilection for the shoulder region, the area of the human plaque most prone to rupture. Accordingly, an inducible plaque rupture model of ApoE-/-Irf5-/- mice had significantly lower frequencies of carotid plaque ruptures, smaller necrotic cores, and less CD11c+ macrophages than their IRF5-competent counterparts. CONCLUSION: Using complementary evidence from data from human carotid endarterectomies and a murine model of inducible rupture of carotid artery plaque in IRF5-deficient mice, we demonstrate a mechanistic link between the pro-inflammatory transcription factor IRF5, macrophage phenotype, plaque inflammation, and its vulnerability to rupture.

Impact of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) on Food Content During Esophagogastroduodenoscopy (EGD).

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have delayed gastric emptying properties; however, the impact on esophagogastroduodenoscopy (EGD) visualization is unknown. OBJECTIVE: This study examines the impact of GLP-1RA use on EGD visualization and gastric content retention. METHODS: This was a retrospective cohort study with matched controls. The primary endpoint was the odds of retained food documented during EGD. Secondary endpoints included incidence of lavage and need for repeat EGD due to poor visualization and were compared using Fisher exact test. Analyses were performed in R Studio. RESULTS: There were 59 patients in the cohort prescribed a GLP-1RA with 118 matched controls. Food retention was documented with 4 patients (6.8%) in the GLP-1RA cohort versus 2 patients (1.7%) in the control group (odds ratio [OR] 4.22 [95% CI 0.87-20.34]). No difference was observed in the need for lavage during EGD or in the need for repeat EGD attributed to poor visualization. CONCLUSION AND RELEVANCE: This study addresses a previously uninvestigated question in clinical practice. GLP-1RA did not significantly increase odds of retained food on EGD. Although a numerical difference was observed, it did not reach statistical difference. No cases required repeat EGD due to poor visualization, and no change to EGD pre-procedure instructions were warranted at the study facility.

Case report of a phencyclidine false positive due to lamotrigine use with confirmatory testing.

BACKGROUND: Urine toxicology screens are useful in diagnosing patients who present with acute psychosis with a history of substance abuse. Being aware of potential false positive reactants is paramount in diagnostic accuracy. Currently, lamotrigine is not listed among common cross-reactants with phencyclidine (PCP). CASE REPORT: A 49 year old male (98 kg) was brought to the ED by a family member for worsening confusion and agitation. He had a history of Bipolar I, PTSD, schizoaffective disorder, hypertension, and cannabis/opioid abuse. His home medications included paliperidone, duloxetine, lamotrigine, tizanidine, hydroxyzine, and lisinopril. Upon examination, he denied intentional overdose or illicit substances, but largely mumbled incoherently. Blood pressure was 140/90 mmHg, pulse 113. A urine toxicology screen was positive for PCP and cannabinoids. Other labs were unremarkable, co-ingestants negative. By day three, his mental status vacillated but he largely gave unintelligible responses. Given the short half-life of PCP, false positives were investigated. A confirmatory blood test (collected upon admission) for PCP was found to be negative, and a serum lamotrigine level was confirmed to be positive (1.5µg/ml). Once more lucid, the patient admitted to taking large quantities of mirtazapine and tizanidine, making serotonin syndrome the more likely diagnosis. DISCUSSION: There is little in the medical literature describing cross-reactivity of lamotrigine and PCP on urine drug screens. This can be especially difficult to deduce in a known drug abuser who presents psychotic and non-contributory in their work up.

Firearm-related threat exposure and associated factors among men and women entering a supportive housing substance use disorder recovery program.

Background: Exposure to firearm victimization has often been overlooked as a sequela of substance use disorders (SUD).Objectives: The overall objective of this study was to explore firearm-related victimization and associated factors among men and women entering a supportive housing SUD recovery program.Methods: This study used program intake information from men (n = 1,758) and women (n = 1,066) clients entering a SUD recovery program.Results: Results found that almost half (49.3%) of the clients entering the program had ever been threatened with a firearm or held at gunpoint, and one-quarter of those clients had experienced firearm-related threats in the 6 months before entering the program. Economic vulnerability, mental health problems, polysubstance use, interpersonal victimization, and early use of drugs and alcohol were associated with firearm-related threat exposure. Many of the factors associated with firearm-related threat exposure were similar for men and women. Multivariate results found that polysubstance use (OR 1.16 men and 1.13 women), number of adverse childhood events (OR 1.13 men and 1.09 women), and interpersonal victimization (OR 3.41 men and 2.05 women) in the 6 months before program entry were significantly associated with ever being threatened with a firearm. Suicidality (OR 1.53 men and 1.80 women) and interpersonal victimization (OR 6.38 men and 6.08 women) were associated with being threatened with a firearm in the 6 months before program entry for both men and women.Conclusion: Results suggest there is a need for firearm-related risk reduction interventions for individuals in SUD recovery programs.

Does a myocardial infarction boost your (B cell) memory?

Graphical abstract Establishment of an autoreactive B cell memory after myocardial infarction: a working hypothesis. The demise of cardiac cells leads to the release of cryptoantigens that induce a humoral immune response that leads to accumulation of immunoglobulins in plaques and eventually amplifies atherogenesis at remote sites.

Translating Violence Prevention Programs from Research to Practice: SafERteens Implementation in an Urban Emergency Department.

BACKGROUND: Youth violence is a leading cause of adolescent mortality, underscoring the need to integrate evidence-based violence prevention programs into routine emergency department (ED) care. OBJECTIVES: To examine the translation of the SafERteens program into clinical care. METHODS: Hospital staff provided input on implementation facilitators/barriers to inform toolkit development. Implementation was piloted in a four-arm effectiveness-implementation trial, with youth (ages 14-18 years) screening positive for past 3-month aggression randomized to either SafERteens (delivered remotely or in-person) or enhanced usual care (EUC; remote or in-person), with follow-up at post-test and 3 months. During maintenance, ED staff continued in-person SafERteens delivery and external facilitation was provided. Outcomes were measured using the RE-AIM implementation framework. RESULTS: SafERteens completion rates were 77.6% (52/67) for remote and 49.1% (27/55) for in-person delivery. In addition to high acceptability ratings (e.g., helpfulness), post-test data demonstrated increased self-efficacy to avoid fighting among patients receiving remote (incidence rate ratio [IRR] 1.22, 95% confidence interval [CI] 1.09-1.36) and in-person (IRR 1.23, 95% CI 1.12-1.36) SafERteens, as well as decreased pro-violence attitudes among patients receiving remote (IRR 0.83, 95% CI 0.75-0.91) and in-person (IRR 0.87, 95% CI 0.77-0.99) SafERteens when compared with their respective EUC groups. At 3 months, youth receiving remote SafERteens reported less non-partner aggression (IRR 0.52, 95% CI 0.31-0.87, Cohen's d -0.39) and violence consequences (IRR 0.47, 95% CI 0.22-1.00, Cohen's d -0.49) compared with remote EUC; no differences were noted for in-person SafERteens delivery. Barriers to implementation maintenance included limited staff availability and a lack of reimbursement codes. CONCLUSIONS: Implementing behavioral interventions such as SafERteens into routine ED care is feasible using remote delivery. Policymakers should consider reimbursement for violence prevention services to sustain long-term implementation.

Implementation of a novel learning experience in scientific writing, publishing, and peer review into a first year pharmacy practice residency.

BACKGROUND: Pharmacists with competency in writing, publishing, and peer review are essential to continue advancing the pharmacy profession, but structured training of these skills may vary. OBJECTIVE: The authors set out to implement and assess the impact of a structured learning experience into a postgraduate year 1 pharmacy residency training program that provides tangible experience in the processes of scientific writing, publishing, and peer reviewing. METHODS: A quarterly pharmacy newsletter process was augmented to include an editorial board that consisted of residency trained pharmacists with varying levels of experience in scientific writing, publishing, and peer reviewing. The process was designed to provide a structured writing learning experience, to reinforce important concepts and terminology, and to simulate the process of submitting a manuscript to a peer-reviewed publication. Impact of the learning experience on quality of article submissions was assessed by comparing first quarter and last quarter writing submission scores for residents between 2017 and 2020. RESULTS: A statistically significant difference was observed in both raw scores (27 vs. 42.5 points out of 50 points possible, P < 0.05) and the proportion of pass or fail when comparing writing submission scores from the first quarter of the learning experience to submission scores from the last quarter (25% passing rate vs. 83% passing rate, P = 0.007). CONCLUSION: This novel learning experience was successfully integrated into a quarterly pharmacy newsletter and resulted in improved writing scores. This structured writing learning experience can be readily integrated into pharmacy residency training programs, and it provides hands-on training in scientific writing, publishing, and peer review for both residents and preceptors.

Genetic Deficiency of Indoleamine 2,3-dioxygenase Aggravates Vascular but Not Liver Disease in a Nonalcoholic Steatohepatitis and Atherosclerosis Comorbidity Model.

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that increases cardiovascular disease risk. Indoleamine 2,3-dioxygenase-1 (IDO1)-mediated tryptophan (Trp) metabolism has been proposed to play an immunomodulatory role in several diseases. The potential of IDO1 to be a link between NASH and cardiovascular disease has never been investigated. Using Apoe-/-and Apoe-/-Ido1-/- mice that were fed a high-fat, high-cholesterol diet (HFCD) to simultaneously induce NASH and atherosclerosis, we found that Ido1 deficiency significantly accelerated atherosclerosis after 7 weeks. Surprisingly, Apoe-/-Ido1-/- mice did not present a more aggressive NASH phenotype, including hepatic lipid deposition, release of liver enzymes, and histopathological parameters. As expected, a lower L-kynurenine/Trp (Kyn/Trp) ratio was found in the plasma and arteries of Apoe-/-Ido1-/- mice compared to controls. However, no difference in the hepatic Kyn/Trp ratio was found between the groups. Hepatic transcript analyses revealed that HFCD induced a temporal increase in tryptophan 2,3-dioxygenase (Tdo2) mRNA, indicating an alternative manner to maintain Trp degradation during NASH development in both Apoe-/- and Apoe-/-Ido1-/mice-. Using HepG2 hepatoma cell and THP1 macrophage cultures, we found that iron, TDO2, and Trp degradation may act as important mediators of cross-communication between hepatocytes and macrophages regulating liver inflammation. In conclusion, we show that Ido1 deficiency aggravates atherosclerosis, but not liver disease, in a newly established NASH and atherosclerosis comorbidity model. Our data indicate that the overexpression of TDO2 is an important mechanism that helps in balancing the kynurenine pathway and inflammation in the liver, but not in the artery wall, which likely determined disease outcome in these two target tissues.

Solidarity, not charity: Learning the lessons of the COVID-19 pandemic to reconceptualise the radicality of mutual aid.

The COVID-19 pandemic has significantly ruptured our global society. We have seen health care systems, governments and commerce buckle under the strain of disease, lockdowns and unrest, but the rupture has also created space for radical (and anarchist) politics of mutual aid, as societal organising principles, to move into a more prominent position (and offers potential for this shift to remain after the crisis has subsided). However, in the short time since mutual aid has been thrust into the limelight, we have seen a multiplicity and spectrum of geographies, applications and approaches. Indeed, we have also seen its appropriation by government(s) that takes advantage of mutual aid's rallying cry of "solidarity not charity"; absolving the state's responsibilities to sufficiently fund social welfare when good neighbours will do it for free. In this paper we map out how mutual aid has been enacted during the COVID-19 pandemic by charity, contributory and radical groups to address specific and novel forms of vulnerabilities, and the opportunities and challenges this offers for the future. In particular we highlight potential tensions between the enacting of mutual aid practices and the political activism (or not) of the mutual aid actors. Our contribution is to reconceptualise mutual aid to (i) show where the real "mutualism" of mutual aid is, and (ii) create a better understanding of how mutual aid can be mobilised in future emergencies which will inevitably arise in the current climate emergency.

Unhealthy geopolitics: can the response to COVID-19 reform climate change policy?

The geopolitics of pandemics and climate change intersect. Both are complex and urgent problems that demand collective action in the light of their global and trans-boundary scope. In this article we use a geopolitical framework to examine some of the tensions and contradictions in global governance and cooperation that are revealed by the pandemic of coronavirus disease 2019 (COVID-19). We argue that the pandemic provides an early warning of the dangers inherent in weakened international cooperation. The world's states, with their distinct national territories, are reacting individually rather than collectively to the COVID-19 pandemic. Many countries have introduced extraordinary measures that have closed, rather than opened up, international partnership and cooperation. Border closures, restrictions on social mixing, domestic purchase of public health supplies and subsidies for local industry and commerce may offer solutions at the national level but they do not address the global strategic issues. For the poorest countries of the world, pandemics join a list of other challenges that are exacerbated by pressures of scarce resources, population density and climate disruption. COVID-19's disproportionate impact on those living with environmental stresses, such as poor air quality, should guide more holistic approaches to the geopolitical intersection of public health and climate change. By discussing unhealthy geopolitics, we highlight the urgent need for a coordinated global response to addressing challenges that cannot be approached unilaterally.

La géopolitique en matière de pandémie partage nombre de similitudes avec celle pratiquée face au changement climatique. Toutes deux sont liées à des problèmes complexes et urgents qui requièrent une action collective en raison de leur portée internationale, qui ne tient compte d'aucune frontière. Dans cet article, nous utilisons un cadre géopolitique pour examiner certaines tensions et contradictions observées dans la gouvernance et la coopération mondiales, et mises en lumière par la pandémie de maladie à coronavirus 2019 (COVID-19). Nous estimons que cette pandémie équivaut à un premier avertissement quant aux dangers inhérents à une faible coopération internationale. Les États de la planète et les territoires nationaux placés sous leur autorité réagissent chacun de leur côté à la pandémie de COVID-19, alors qu'ils devraient adopter une approche commune. De nombreux pays ont instauré des mesures exceptionnelles qui ont entraîné la disparition des partenariats existants au lieu de les renforcer. Fermer les frontières, restreindre la mixité sociale, acheter des fournitures médicales pour les hôpitaux à l'intérieur du pays et subventionner l'industrie et les commerces locaux peuvent certes apporter des solutions à l'échelle nationale, mais ces décisions ne s'attaquent pas aux problèmes stratégiques à l'échelle mondiale. Pour les pays les plus pauvres de la planète, la pandémie s'ajoute à une longue liste de défis exacerbés par la pression qu'exercent la pénurie de ressources, la densité de population et le dérèglement climatique. L'impact disproportionné de la COVID-19 sur celles et ceux qui subissent déjà un stress environnemental, dû par exemple à la mauvaise qualité de l'air, devrait servir de guide à une série d'approches holistiques reflétant le rapport entre santé publique et changement climatique. En abordant le thème d'une géopolitique néfaste, nous attirons l'attention sur l'urgence d'une réponse globale coordonnée qui permettra de relever des défis qui ne peuvent être affrontés unilatéralement.

La geopolítica en materia de pandemias comparte muchas similitudes con la del cambio climático. Ambos son problemas complejos y urgentes que exigen una acción colectiva debido a su alcance global y transfronterizo. En este artículo utilizamos un marco geopolítico para examinar algunas de las tensiones y contradicciones en la gobernanza y la cooperación mundiales que pone de manifiesto la pandemia de la enfermedad del coronavirus de 2019 (COVID-19). Consideramos que la pandemia proporciona una alerta temprana de los peligros inherentes a una cooperación internacional debilitada. Los Estados del mundo, con sus distintos territorios nacionales, están reaccionando individualmente en lugar de colectivamente a la pandemia de la COVID-19. Muchos países han introducido medidas extraordinarias que han cerrado, en lugar de abrir, la asociación y la cooperación internacionales. El cierre de fronteras, las restricciones a la mezcla social, la compra interna de suministros de salud pública y las subvenciones a la industria y el comercio locales pueden ofrecer soluciones a nivel nacional, pero no abordan las cuestiones estratégicas mundiales. En el caso de los países más pobres del mundo, las pandemias se suman a una lista de otros problemas que se ven agravados por las presiones de la escasez de recursos, la densidad demográfica y los trastornos climáticos. El impacto desproporcionado de la COVID-19 en quienes viven con tensiones ambientales, como la mala calidad del aire, debería orientar los enfoques más holísticos de la intersección geopolítica de la salud pública y el cambio climático. Al examinar la geopolítica dañina, ponemos de relieve la urgente necesidad de una respuesta mundial coordinada para hacer frente a los desafíos que no pueden abordarse unilateralmente.

Virulence and intermediate resistance to high-end antibiotic (teicoplanin) among coagulase-negative staphylococci sourced from retail market fish.

This study reports the distribution of enterotoxigenic determinants among staphylococci and the susceptibility of staphylococci to various classes of antibiotics. We observed all the isolates as resistant to beta-lactam antibiotics and a few as resistant to non-beta-lactam antibiotics such as clindamycin (47.4%), erythromycin (44.7%), gentamicin (23.7%), norfloxacin (34.2%), tetracycline (26.3%), trimethoprim-sulfamethoxazole (15.8%) etc. The resistance of S. sciuri (n = 1) and S. haemolyticus (n = 1) to rifampicin and intermediate resistance of S. gallinarum (n = 2) to teicoplanin, a high-end antibiotic, are also observed in this study. The multidrug-resistance (≥ 3 classes of antibiotics) was recorded in 23 (60.5%) isolates. The virulomes such as sea, seb, seg and sei were identified predominantly in S. haemolyticus. Surprisingly, certain isolates which were phenotypically confirmed as biofilm-producers by Congo red agar (CRA) test did not harbor biofilm-associated loci. This implies the protein-mediated mechanism of biofilm formation as an alternative to polysaccharide intercellular adhesin (PIA) in staphylococci. However, icaAD locus which encodes PIA was identified in 10 (26.3%) isolates and the eno locus, encoding elastin-binding protein which can accelerate the biofilm production, is identified in all the isolates. The possession of type V SCCmec elements by the S. haemolyticus (15.8%) raised the concern about the rapid dissemination of mecA gene to other species of staphylococci including the virulent S. aureus. In short, this study acknowledges the toxigenicity of coagulase-negative staphylococci (CoNS). Through this study, surveillance of antimicrobial resistance and transference of virulomes in staphylococci is warranted.

Conflict and COVID-19 in Yemen: beyond the humanitarian crisis.

BACKGROUND: Yemen has been left in shambles and almost destroyed by its devastating civil war, and is now having to deal with the spread of coronavirus. The Yemeni people have been are left to fend for themselves and faced many problems such as hunger, the ongoing war, infections, diseases and lack of equipment even before the COVID-19 pandemic. All together it is a humanitarian crisis. Only around 50% of the hospitals and healthcare facilities are in full working condition, and even those that are functioning are operating at nowhere near full potential. Healthcare staff and facilities lack necessary essential equipment and money. CONCLUSION: As, sadly, is common in conflict-affected regions, the violence has brought with it a secondary disaster of infectious disease outbreaks. Yemen is not only battling COVID-19 amid a catastrophic war, but also has to deal with other diseases such as cholera, diphtheria and measles. A number of key measures are needed to support the current efforts against this deadly epidemic and its potential subsequent waves as well as to prevent further epidemics in Yemen.

Deinduction of P-glycoprotein resulting in delayed viral response during hepatitis C treatment.

WHAT IS KNOWN AND OBJECTIVE: Drug-drug interactions can involve inhibition or induction of cell membrane transporters. Deinduction occurs after an inducing agent is stopped. CASE SUMMARY: This case describes suspected P-glycoprotein (P-gp) deinduction by carbamazepine resulting in a slow viral response during treatment of chronic hepatitis C virus (HCV) infection. Evidence of deinduction occurred beyond clearance of carbamazepine and resulted in extension of HCV treatment. WHAT IS NEW: The understanding of the role P-gp transport plays in drug elimination is relatively new and evidence of P-gp deinduction is variable. CONCLUSION: Clinicians should consider deinduction when starting and stopping medications involving strong inducers of P-gp transport proteins.

Molecular assessment of antimicrobial resistance and virulence in multi drug resistant ESBL-producing Escherichia coli and Klebsiella pneumoniae from food fishes, Assam, India.

The present study investigated the prevalence of Extended-Spectrum Beta Lactamase (ESBL) -producing E. coli and K. pneumoniae from the food fishes in retail markets in Assam, India. A total of 54 ESBL-producing E. coli and 12 K. pneumoniae isolates were recovered from 79 fish samples and were analyzed for antimicrobial resistance genes (ARGs) and virulence genes. E. coli isolates were categorized as multi drug resistant with resistance up to 12 different antibiotics with multiple antibiotic resistances (MAR) index ranging from 0.26 to 0.63. In E. coli, 100% resistance to cefotaxime along with 6% resistance to ceftazidime (third-generation cephalosporins) was observed. Moreover, 85% of the E. coli isolates were resistant to cefepime, a fourth-generation cephalosporin. K. pneumoniae showed resistance to 11 different antibiotics with MAR index value ranging from 0.21 to 0.57. All K. pneumoniae isolates showed 100% resistance to cefotaxime, 67% resistance to ceftazidime and 75% resistance to cefepime. Molecular characterization of ARGs revealed the presence of CTX-M group 1(CTX-M-15) in almost all E. coli isolates (98%, n = 53) and 100% in K. pneumoniae. A combination of uniplex and multiplex PCRs revealed fewer ARGs in E. coli isolates, with each isolate carrying 3 to 5 genes (tetA, dfrA1, sul1, sul2, qnrB, qnrS, aac(6')-Ib-cr). Majority of the E. coli were assigned to low-virulence phylogroup B1 and A while 8% of them belonged to pathogenic phylogroup D. 31 unique genetic profiles were identified for E. coli isolates by Pulsed-Field Gel Electrophoresis (PFGE) typing. K. pneumoniae isolates were highly diverse with 11 unique genetic profiles and a substantial ARG profile (blaTEM, blaSHV, blaOXA-1-like, tetA, strA, strB, dfrA1, sul1, sul2, qnrB, qnrS, aac(6')-Ib-cr, oqxA, oqxB). The frequency of ARGs ranged between 4 and 11. All K. pneumoniae isolates belonged to capsular serotype with wzi gene. Virulence gene iutA was prominent in all isolates while ybtS and kfu were confirmed in two isolates. Our findings raise concerns that fishes bought for consumption may serve as potential reservoirs of AMR genes and pose serious threat to public health. The study emphasizes the need for extensive surveillance of resistant strains in aquaculture and related settings, their in-depth analysis of population structure and transmission dynamics.

Toll-like Receptor 3 Is a Therapeutic Target for Pulmonary Hypertension.

RATIONALE: Pulmonary arterial hypertension (PAH) is characterized by vascular cell proliferation and endothelial cell apoptosis. TLR3 (Toll-like receptor 3) is a receptor for double-stranded RNA and has been recently implicated in vascular protection. OBJECTIVES: To study the expression and role of TLR3 in PAH and to determine whether a TLR3 agonist reduces pulmonary hypertension in preclinical models. METHODS: Lung tissue and endothelial cells from patients with PAH were investigated by polymerase chain reaction, immunofluorescence, and apoptosis assays. TLR3-/- and TLR3+/+ mice were exposed to chronic hypoxia and SU5416. Chronic hypoxia or chronic hypoxia/SU5416 rats were treated with the TLR3 agonist polyinosinic/polycytidylic acid (Poly[I:C]). MEASUREMENTS AND MAIN RESULTS: TLR3 expression was reduced in PAH patient lung tissue and endothelial cells, and TLR3-/- mice exhibited more severe pulmonary hypertension following exposure to chronic hypoxia/SU5416. TLR3 knockdown promoted double-stranded RNA signaling via other intracellular RNA receptors in endothelial cells. This was associated with greater susceptibility to apoptosis, a known driver of pulmonary vascular remodeling. Poly(I:C) increased TLR3 expression via IL-10 in rat endothelial cells. In vivo, high-dose Poly(I:C) reduced pulmonary hypertension in both rat models in proof-of-principle experiments. In addition, Poly(I:C) also reduced right ventricular failure in established pulmonary hypertension. CONCLUSIONS: Our work identifies a novel role for TLR3 in PAH based on the findings that reduced expression of TLR3 contributes to endothelial apoptosis and pulmonary vascular remodeling.