Extended-spectrum ß-lactamase-producing bacteria and their resistance determinants in different wastewaters and rivers in Nepal.

Wastewaters serve as significant reservoirs of antibiotic resistant bacteria. Despite the evidence of antimicrobial resistance in wastewaters and river water in Kathmandu, direct linkage between them is not discussed yet. This study investigated the prevalence of extended-spectrum ß-lactamase (ESBL)-producing bacteria and associated resistance genes in wastewaters and river water. Out of 246 bacteria from wastewaters, 57.72% were ESBL producers and 77.64% of them were multidrug resistant (MDR). ESBL producing E. coli was dominant in municipal and hospital wastewaters (HWW) as well as in river water while K. pneumoniae was common in pharmaceutical wastewater. The blaSHV and blaTEM genes were prevalent and commonly co-occurred with aac(6')-Ib-cr in K. pneumoniae isolated pharmaceutical wastewater. blaCTX-M carrying E. coli from hospital co-harbored aac(6')-Ib-cr while that from municipal influent and river water co-harbored qnrS. Whole genome sequencing data revealed the presence of diverse ARGs in bacterial isolates against multiple antibiotics. In average, an E. coli and a K. pneumoniae isolate contained 55.75 ± 0.96 and 40.2 ± 5.36 ARGs, respectively. Multi-locus sequence typing showed the presence of globally high-risk clones with wider host range such as E. coli ST10, and K. pneumoniae ST15 and ST307 in HWW and river indicating frequent dissemination of antimicrobial resistance in wastewater of Kathmandu. Whole genome sequence data aligned with phenotypic antibiograms and resistance genes detected by PCR in selected isolates. The presence of significant plasmid replicons (IncF, IncY) and mobile genetic elements (IS903, IS26) indicate high frequency of spreading antibiotic resistance. These findings indicate burden and dissemination of antimicrobial resistance in the environment and highlight the need for effective strategies to mitigate the antibiotic resistance.

Emergence of mcr-1 Gene in Colistin-Resistant Escherichia coli Isolates from Chicken in Chitwan, Nepal.

The escalating prevalence of colistin-resistant Escherichia coli in poultry has emerged as a significant concern. This study aimed to assess the occurrence of the mcr-1 gene in colistin-resistant E. coli isolates from poultry samples. A cross-sectional study was conducted at National Avian Disease Investigation Laboratory, Nepal, on 210 chicken meat samples, including liver, heart, and spleen. E. coli was isolated and identified by conventional cultural methods. Antibiotic resistance pattern was assessed by the Kirby-Bauer disc diffusion method. The mcr-1 gene was detected by conventional polymerase chain reaction. The average viable count in chicken meat samples was log 6.01 CFU (colony-forming unit)/g, whereas the average coliform count was log 3.85 CFU/g. Coliforms were detected in at least one sample from 48.01% of total samples. The prevalence of E. coli in all meat samples was 39.52%. Liver accounted for the largest fraction of E. coli isolates (45.45%). Cefepime was the most effective antibiotic. Among all isolates, 45 (54.21%) were multidrug-resistant E. coli, 17 (20.48%) were colistin-resistant E. coli, and 11 (64.70%) harbored the mcr-1 gene. High prevalence of multidrug-resistant E. coli isolates, colistin-resistant isolates, and mcr-1 gene-carrying isolates indicates a serious concern, as it could potentially lead to colistin resistance in human pathogens through horizontal transfer of resistant genes from poultry to humans.

Antibiotic resistance determinants among carbapenemase producing bacteria isolated from wastewaters of Kathmandu, Nepal.

The emergence of carbapenem resistant bacteria (CRB) possesses a remarkable threat to the health of humans. CRB and carbapenem resistance genes (CRGs) have frequently been reported in clinical isolates from hospitals, however, their occurrence and distribution in wastewaters from various sources and river water have not been emphasized in Nepal. So, this study aimed to detect carbapenem resistant bacterial isolates and their resistance determinants in river water and different types of wastewaters. River water and both untreated and treated wastewater samples from hospitals, pharmaceutical industries, and municipal sewage were collected in summer and winter seasons. From 68 grab wastewater samples, CRB were detected only in 16 samples, which included eight hospital wastewater, and four each from untreated municipal sewage and river water. A total of 25 CRB isolates were detected with dominance of E. coli (44.0%) and K. pneumoniae (24.0%). The majority of the isolates harbored blaNDM-1 (76.0%), followed by blaOXA (36.0%) and blaKPC (20.0%) genes. Hospital wastewater majorly contributed to the presence of blaNDM-1, blaKPC, and blaOXA along with intI1 genes compared to river water and untreated municipal sewage, especially during the winter season. However, CRB were not detected in treated effluents of hospitals and municipal sewage, and both influents and effluents from pharmaceutical industries. The combined presence of each blaNDM-1 & blaOXA and blaKPC & blaOXA occurred in 16.0% of the bacterial isolates. The increased minimum inhibitory concentration (MIC) of meropenem was significantly associated with the presence of CRGs. The results of this study highlight the significance of carbapenem resistance in bacteria isolated from wastewater and river water, and underscore the necessity for efficient monitoring and control strategies to prevent the dispersion of carbapenem resistance in the environment and its potential consequences on human health.

Preparing for success in final summative medical specialist examinations: The case for RACE.

BACKGROUND: Failure rates on medical specialist final summative examinations in Australia are high, regardless of speciality. Examination failure can have detrimental psycho-social, financial and job security effects on the trainee, while delays in completion of training adversely impacts workforce growth and health outcomes for the community. The study aimed to explore the preparation factors that contribute to ophthalmology trainee success in their final summative examination. METHODS: Semi-structured in-depth interviews were conducted with 29 participants via telephone or Zoom with ophthalmology trainees and Fellows. To be eligible, interviewees had to have sat the Royal Australian and New Zealand College of Ophthalmologists Advanced Clinical Examination (RACE) within the past five years or were providing supervision to trainees preparing for RACE. Interviews were audio-recorded, transcribed and thematically analysed. RESULTS: Examination success was underpinned by six themes relating to preparation: (i) 'Those who fail to plan, plan to fail', which related to development and adherence to a study plan; (ii) 'It takes a village' encompassed trainees establishing and activating personal and professional supports; (iii) 'Get to know your opponent', which encompassed developing an understanding of the examination construct, format and requirements; (iv) 'There is no substitute for hard work', which related to intensive study over a period of 12-18 months; (v) 'Keep pace with the herd', which referred to benchmarking preparation efforts and progress against peers; and (vi) 'Don't jump the gun', which related to ensuring readiness to sit. CONCLUSIONS: Maximising medical specialist examination pass rates is in the best interest of trainees, training Colleges, health care systems and communities. Recognising and facilitating preparation approaches that foster success in final summative examinations are the collective responsibility of trainees, specialist training Colleges, training networks and health systems. Trainees need to plan for examination success, be self-determined to commit to intensive study over an extended time period and be realistic about their readiness to sit.

Distribution of MecA and Erm Genes among Methicillin-resistant Staphylococcus Aureus with Inducible Resistance to Clindamycin.

BACKGROUND: The emergence of Methicillin-resistant Staphylococcus aureus and its ability to confer cross-resistance to macrolide-lincosamide-streptogramin B has complicated the treatment against it. Gene-based studies among phenotypic methicillin-resistant isolates with inducible resistance to clindamycin are less available in Nepal. This work was undertaken to detect the mecA and erm genes among such phenotypes isolated from clinical samples. METHODS: S. aureus isolated from different clinical samples was identified by standard microbiological procedures (Gram-staining, colony morphology, and different biochemical tests). Methicillin-resistant and inducible resistant to clindamycin phenotypes were detected by using cefoxitin disc (30 µg) and a double disk diffusion test according to the Clinical and Laboratory Standards Institute guidelines and mecA and erm genes were detected by polymerase chain reaction. RESULTS: Among 120 S. aureus isolates, 51.67% (n=62) were MRSA, and the prevalence of inducibly-resistant, constitutively-resistant and Macrolide-Streptogramin phenotypes were 15.83% (n=19), 28.33% (n=34) and 15.83% (n=19) respectively. While 35.84% (n=43) of isolates showed sensitivity to both antibiotics, erythromycin and clindamycin. Out of 14 inducibly-resistant phenotypes, 57.14% (n=8) were found carrying ermC and 28.57% (n=4) phenotypes contained both ermA and ermC. All phenotypes were positive for the mecA gene. CONCLUSIONS: Macrolides-Lincosamide-Streptogramin B resistance was predominant among methicillin-resistant S. aureus. While all isolates with inducible clindamycin resistance harbored mecA gene, most of them also harbored ermC gene. The higher prevalence of inducible-resistant to clindamycin indicated the need for rational use of antimicrobial agents.

Unilateral proptosis in a patient with thyroid eye disease: A case report.

Unilateral proptosis is an abnormality in which one eye sticks out forward more than the other. Bulging of the eye is commonly seen in Graves' ophthalmopathy, but it's mostly bilateral. Thyroid eye disease presents as the most common extrathyroidal manifestation of Graves' disease, and rarely leads to unilateral proptosis. A 25-year-old female with a history of weight loss, menstrual irregularities, and palpitations presented with progressive right eye bulging, which was further confirmed by magnetic resonance imaging and biochemical investigations. Magnetic resonance imaging of the orbit revealed unilateral extraocular muscle enlargement and enhancement with sparing of the tendons. Timely therapy is crucial for reversing the ocular manifestations of thyroid eye disease.

Triplication of the interferon receptor locus contributes to hallmarks of Down syndrome in a mouse model.

Down syndrome (DS), the genetic condition caused by trisomy 21, is characterized by variable cognitive impairment, immune dysregulation, dysmorphogenesis and increased prevalence of diverse co-occurring conditions. The mechanisms by which trisomy 21 causes these effects remain largely unknown. We demonstrate that triplication of the interferon receptor (IFNR) gene cluster on chromosome 21 is necessary for multiple phenotypes in a mouse model of DS. Whole-blood transcriptome analysis demonstrated that IFNR overexpression associates with chronic interferon hyperactivity and inflammation in people with DS. To define the contribution of this locus to DS phenotypes, we used genome editing to correct its copy number in a mouse model of DS, which normalized antiviral responses, prevented heart malformations, ameliorated developmental delays, improved cognition and attenuated craniofacial anomalies. Triplication of the Ifnr locus modulates hallmarks of DS in mice, suggesting that trisomy 21 elicits an interferonopathy potentially amenable to therapeutic intervention.

The cellular and immunological dynamics of early and transitional human milk.

Human milk is essential for infant nutrition and immunity, providing protection against infections and other immune-mediated diseases during the lactation period and beyond in later childhood. Milk contains a broad range of bioactive factors such as nutrients, hormones, enzymes, immunoglobulins, growth factors, cytokines, and antimicrobial factors, as well as heterogeneous populations of maternal cells. The soluble and cellular components of milk are dynamic over time to meet the needs of the growing infant. In this study, we utilize systems-approaches to define and characterize 62 analytes of the soluble component, including immunoglobulin isotypes, as well as the cellular component of human milk during the first two weeks postpartum from 36 mothers. We identify soluble immune and growth factors that are dynamic over time and could be utilized to classify milk into different phenotypic groups. We identify 24 distinct populations of both epithelial and immune cells by single-cell transcriptome analysis of 128,016 human milk cells. We found that macrophage populations have shifting inflammatory profiles during the first two weeks of lactation. This analysis provides key insights into the soluble and cellular components of human milk and serves as a substantial resource for future studies of human milk.

Beyond the 'big smoke': Enabling supervision of ophthalmology trainees in regional, rural and remote Australia.

OBJECTIVE: Expansion of opportunities for ophthalmology training beyond the 'big smoke' is anticipated to support the future distribution of ophthalmologists in regional, rural and remote areas of Australia. However, little is known about what enables supervision outside of metropolitan tertiary hospital settings that would contribute to positive training experiences for specialist medical trainees and encourage them to leave the 'big smoke' once qualified. The aim of this study was therefore to explore the perceived enablers of ophthalmology trainee supervision in regional, rural and remote health settings across Australia. SETTING: Australia. PARTICIPANTS: Ophthalmologists working in regional, rural or remote health settings with experience and/or interest in supervising ophthalmology trainees (n = 16). DESIGN: Qualitative design involving semistructured interviews. RESULTS: Seven key enablers of ophthalmology trainee supervision in regional, rural and remote health settings were identified: adequate physical infrastructure, resources and funding to host a trainee; availability of online curriculum and teaching resources so as to ensure equity of training opportunities; pre-established training posts, driven by supervision 'champions'; a critical mass of ophthalmologists to help share the supervisory load; relationships and support between training posts, the training network and the Specialist Medical College; alignment of trainee competence and attitude with the needs of the training setting; and the recognition of reciprocal benefits for supervisors through supporting trainees, including workforce support and renewal. CONCLUSION: With training experiences beyond the 'big smoke' anticipated to influence future ophthalmology workforce distribution, implementation of enablers of trainee supervision should occur in regional, rural and remote health settings wherever possible.

FAM193A is a positive regulator of p53 activity.

Inactivation of the p53 tumor suppressor, either by mutations or through hyperactivation of repressors such as MDM2 and MDM4, is a hallmark of cancer. Although many inhibitors of the p53-MDM2/4 interaction have been developed, such as Nutlin, their therapeutic value is limited by highly heterogeneous cellular responses. We report here a multi-omics investigation of the cellular response to MDM2/4 inhibitors, leading to identification of FAM193A as a widespread regulator of p53 function. CRISPR screening identified FAM193A as necessary for the response to Nutlin. FAM193A expression correlates with Nutlin sensitivity across hundreds of cell lines. Furthermore, genetic codependency data highlight FAM193A as a component of the p53 pathway across diverse tumor types. Mechanistically, FAM193A interacts with MDM4, and FAM193A depletion stabilizes MDM4 and inhibits the p53 transcriptional program. Last, FAM193A expression is associated with better prognosis in multiple malignancies. Altogether, these results identify FAM193A as a positive regulator of p53.

Benefits and challenges to ophthalmology training via the Specialist Training Program.

INTRODUCTION: The Specialist Training Program (STP) is a commonwealth funding initiative to support specialist medical training positions in regional, rural and remote areas, and in private settings. The program helps to improve the skills and distribution of the specialist medical workforce by providing trainees experience of a broader range of healthcare settings. OBJECTIVE: To examine the benefits and challenges of ophthalmology training delivered by the STP in regional, rural, remote, and/or private settings across Australia. DESIGN: Qualitative design involving semi-structured in-depth interviews with thirty-two participants experienced in the delivery of ophthalmology training at STP posts including ophthalmology trainees (n = 8), STP supervisors and clinical tutors (n = 16), and other stakeholders (n = 8). FINDINGS: Training delivered at STP posts was reportedly beneficial for ophthalmology trainees, their supervisors and the broader community given it enabled exposure to regional, rural, remote and private settings, access to unique learning opportunities, provided workforce support and renewal, and affordable ophthalmic care. However, all participants also reported challenges including difficulties achieving work/life balance, unmet training expectations, a lack of professional support, and financial and administrative burden. Malalignment between trainee preferences for STP posts, low STP literacy and limited regional, rural and remote training experiences were also seen as missed opportunities to foster future rural ophthalmic workforce development. DISCUSSION: The STP improves access to ophthalmic care in underserved populations while enabling valuable rural and/or private practice exposure for medical specialist trainees and workforce support for supervising ophthalmologists. CONCLUSION: Efforts are needed to improve the quality of training experiences provided at STP posts and post sustainability. Although research is needed to investigate the longer-term benefits of the STP to rural and/or private workforce recruitment and retention, RANZCO should develop further regional, rural and remote STP posts to help realise future rural practice intention amongst ophthalmology trainees.

Development of combinatorial antibody therapies for diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL), the most common form of lymphoma, is typically treated with chemotherapy combined with the immunotherapy rituximab, an antibody targeting the B cell receptor, CD20. Despite the success of this treatment regimen, approximately a third of DLBCL patients experience either relapse or have refractory disease that is resistant to rituximab, indicating the need for alternative therapeutic strategies. Here, we identified that CD74 and IL4R are expressed on the cell surface of both CD20 positive and CD20 negative B cell populations. Moreover, genes encoding CD74 and IL4R are expressed in lymphoma biopsies isolated from all stages of disease. We engineered bispecific antibodies targeting CD74 or IL4R in combination with rituximab anti-CD20 (anti-CD74/anti-CD20 and anti-IL4R/anti-CD20). Bispecific antibody function was evaluated by measuring direct induction of apoptosis, antibody-dependent cellular phagocytosis (ADCP), and antibody-dependent cellular cytotoxicity in both rituximab-sensitive and rituximab-resistant DLBCL cell lines. Both anti-CD74/anti-CD20 and anti-IL4R/anti-CD20 were able to mediate ADCC and ADCP, but CD74-targeting therapeutic antibodies could also mediate direct cytotoxicity. Overall, this study strongly indicates that development of bispecific antibodies that target multiple B cell receptors expressed by lymphoma could provide improved defense against relapse and rituximab resistance.

Antibiotic Resistance, Biofilm Formation and Sub-Inhibitory Hydrogen Peroxide Stimulation in Uropathogenic Escherichia coli.

Uropathogenic Escherichia coli (UPEC) is the most prevalent cause of urinary tract infections (UTIs). Biofilm formation and antibiotic resistance could be high among the causative agent. The purpose of this study was to determine antibiotic resistance, biofilm production, and biofilm-associated genes, bcsA and csgD, and sub-inhibitory hydrogen peroxide (H2O2) stimulation in UPEC for biofilm formation. A total of 71 UPEC were collected from a tertiary care hospital in Kathmandu and subjected to identify antibiotic susceptibility using Kirby-Bauer disk diffusion. The biofilm formation was assessed using microtiter culture plate method while pellicle formation was tested by a tube method. In representative 15 isolates based on biofilm-forming ability, bcsA and csgD were screened by conventional polymerase chain reaction, and treated with sub-lethal H2O2. The UPEC were found the most susceptible to meropenem (90.2%), and the least to ampicillin (11.3%) in vitro and 90.1% of them were multi-drug resistant (MDR). Most UPEC harbored biofilm-producing ability (97.2%), and could form pellicle at 37°C. Among representative 15 isolates, csgD was detected only among 10 isolates (66.67%) while bcsA gene was present in 13 isolates (86.67%). This study revealed that level of biofilm production elevated after sub-lethal H2O2 treatment (P = .041). These findings suggested that the pathogens are emerging as MDR. The biofilm production is high and the majority of selected strains contained bcsA and csgD genes. Pellicle formation test was suggestive to be an alternative qualitative method to screen biofilm production in UPEC. The sub-inhibitory concentration of H2O2 may contribute in increasing biofilm formation in UPEC.

Acute psychosis unveiling diagnosis of hypothyroidism: A case report.

Introduction: Hypothyroidism is a common condition in the general population that presents a wide array of medical, neurological and psychiatric symptoms. However, hypothyroidism rarely leads to acute psychosis, termed myxedema psychosis (MP) and is often missed by many physicians. Case presentation: Here we report a case of a 36-years-old female who presented with a one-week history of abnormal behavior, delusions and hallucinations. Investigations revealed a high thyroid-stimulating-hormone (TSH)of 78.60 mlU/mL and low free thyroxine (FT4) of 0.64 pmol/L. Diagnosed with hypothyroidism, she was treated with oral thyroid hormone replacement (l-thyroxine 75 µg/day) with antipsychotics and her symptoms settled within days. She was discharged off antipsychotics and advised to adhere to thyroxine replacement and to follow up for Thyroid function test (TFT). Discussion: Myxedema psychosis is an uncommon manifestation of the common endocrine disease hypothyroidism. The atypical nature of presentations occasionally complicates diagnostics. When approaching a 'first-episode psychosis,' it is essential to perform a complete organic screen consistently. Conclusion: Acute myxedema madness should be considered in the differential diagnosis of acute psychosis in patients with hypothyroidism.

Single-cell analysis of immune cell transcriptome during HIV-1 infection and therapy.

BACKGROUND: Cellular immune responses are phenotypically and functionally perturbed during HIV-1 infection, with the majority of function restored upon antiretroviral therapy (ART). Despite ART, residual inflammation remains that can lead to HIV-related co-morbidities and mortality, indicating that ART does not fully restore normal immune cell function. Thus, understanding the dynamics of the immune cell landscape during HIV-1 infection and ART is critical to defining cellular dysfunction that occurs during HIV-1 infection and imprints during therapy. RESULTS: Here, we have applied single-cell transcriptome sequencing of peripheral blood immune cells from chronic untreated HIV-1 individuals, HIV-1-infected individuals receiving ART and HIV-1 negative individuals. We also applied single-cell transcriptome sequencing to a primary cell model of early HIV-1 infection using CD4+ T cells from healthy donors. We described changes in the transcriptome at high resolution that occurred during HIV-1 infection, and perturbations that remained during ART. We also determined transcriptional differences among T cells expressing HIV-1 transcripts that identified key regulators of HIV-1 infection that may serve as targets for future therapies to block HIV-1 infection. CONCLUSIONS: This work identified key molecular pathways that are altered in immune cells during chronic HIV-1 infection that could remain despite therapy. We also identified key genes that are upregulated during early HIV-1 infection that provide insights on the mechanism of HIV-1 infection and could be targets for future therapy.

Effects of Prior Infection with SARS-CoV-2 on B Cell Receptor Repertoire Response during Vaccination.

Understanding the B cell response to SARS-CoV-2 vaccines is a high priority. High-throughput sequencing of the B cell receptor (BCR) repertoire allows for dynamic characterization of B cell response. Here, we sequenced the BCR repertoire of individuals vaccinated by the Pfizer SARS-CoV-2 mRNA vaccine. We compared BCR repertoires of individuals with previous COVID-19 infection (seropositive) to individuals without previous infection (seronegative). We discovered that vaccine-induced expanded IgG clonotypes had shorter heavy-chain complementarity determining region 3 (HCDR3), and for seropositive individuals, these expanded clonotypes had higher somatic hypermutation (SHM) than seronegative individuals. We uncovered shared clonotypes present in multiple individuals, including 28 clonotypes present across all individuals. These 28 shared clonotypes had higher SHM and shorter HCDR3 lengths compared to the rest of the BCR repertoire. Shared clonotypes were present across both serotypes, indicating convergent evolution due to SARS-CoV-2 vaccination independent of prior viral exposure.

Considerations for Training and Workforce Development to Enhance Rural and Remote Ophthalmology Practise in Australia: A Scoping Review.

Australia has one of the lowest per capita numbers of ophthalmologists among OECD countries, and they predominantly practise in metropolitan centres of the country. Increasing the size and distribution of the ophthalmology workforce is of critical importance. The objective of this review was to investigate the context of rural ophthalmology training and practise in Australia and how they relate to future ophthalmology workforce development. This scoping review was informed by Arksey and O'Malley's framework and the methodology described by Coloqhuon et al. The search yielded 428 articles, of which 261 were screened for eligibility. Following the screening, a total of 75 articles were included in the study. Themes identified relating to rural ophthalmology training and practise included: Indigenous eye health; access and utilisation of ophthalmology-related services; service delivery models for ophthalmic care; ophthalmology workforce demographics; and ophthalmology workforce education and training for rural and remote practise. With an anticipated undersupply and maldistribution of ophthalmologists in the coming decade, efforts to improve training must focus on how to build a sizeable, fit-for-purpose workforce to address eye health needs across Australia. More research focusing on ophthalmology workforce distribution is needed to help identify evidence-based solutions for workforce maldistribution. Several strategies to better prepare the future ophthalmology workforce for rural practise were identified, including incorporating telehealth into ophthalmology training settings; collaborating with other health workers, especially optometrists and specialist nurses in eyecare delivery; and exposing trainees to more patients of Indigenous background.

Evaluation of virtual accreditation of medical specialist training sites for ophthalmology in Australia and New Zealand during the COVID-19 pandemic.

Objective To evaluate the suitability and acceptability of virtual training post accreditation visits conducted online for medical specialist training in ophthalmology in Australia and New Zealand. Methods A two-phase study (pilot and implementation) was conducted. In the pilot phase, an open-ended observation proforma was used by the authors to independently record their observations, which were later compared and discussed until consensus was achieved. All participants were asked to complete an online survey. A document analysis of accreditation documents was conducted. Observation data were broken down into themes and triangulated with online survey and document analysis results. In the implementation phase, the inspections were observed by one of the authors (SK) and the observation notes were discussed with other authors to obtain a contextual and consensual view. A document analysis of all accreditation-related documentation was undertaken. The documents included in the document analysis were planning and scheduling records, interview and inspection notes, training post inspection fact and document notices and accreditation reports. Finally, a post-inspection focus group of all inspectors was conducted. Results The accreditation interviews adequately addressed all relevant issues with high levels of robustness and reliability. Participants found it more difficult to discuss complex issues virtually compared with onsite visits. The virtual accreditation reports were not any different to what would be expected if a face-to-face accreditation visit had been conducted; however, it was not possible using the virtual inspection to determine the appropriateness of facilities and clinic layout to support and facilitate trainee learning and supervision. Conclusions Virtual accreditation of training posts in medical specialist training is viable in limited circumstances where there are no known complex training post-related issues and the site has not made substantial changes to clinic and theatre layout, equipment and facilities since the previous accreditation.

Cross-reactive antibodies elicited to conserved epitopes on SARS-CoV-2 spike protein after infection and vaccination.

SARS-CoV-2 is a novel betacoronavirus that caused coronavirus disease 2019 and has resulted in millions of deaths worldwide. Novel coronavirus infections in humans have steadily become more common. Understanding antibody responses to SARS-CoV-2, and identifying conserved, cross-reactive epitopes among coronavirus strains could inform the design of vaccines and therapeutics with broad application. Here, we determined that individuals with previous SARS-CoV-2 infection or vaccinated with the Pfizer-BioNTech BNT162b2 vaccine produced antibody responses that cross-reacted with related betacoronaviruses. Moreover, we designed a peptide-conjugate vaccine with a conserved SARS-CoV-2 S2 spike epitope, immunized mice and determined cross-reactive antibody binding to SARS-CoV-2 and other related coronaviruses. This conserved spike epitope also shared sequence homology to proteins in commensal gut microbiota and could prime immune responses in humans. Thus, SARS-CoV-2 conserved epitopes elicit cross-reactive immune responses to both related coronaviruses and host bacteria that could serve as future targets for broad coronavirus therapeutics and vaccines.

The Impact of Prior Infection and Age on Antibody Persistence After Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine.

Determining the duration of immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is critical for informing the timing of booster immunization. Many genetic and environmental factors could influence both the magnitude and persistence of the antibody response. Here, we showed that SARS-CoV-2 infection before vaccination and age affected the decay of antibody responses to the SARS-CoV-2 messenger RNA vaccine.