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The immune responses and mechanisms limiting symptom progression in asymptomatic cases of SARS‐CoV‐2 infection remain unclear. We comprehensively characterized transcriptomic profiles, cytokine responses, neutralization capacity of antibodies, and cellular immune phenotypes of asymptomatic patients with acute SARS‐CoV‐2 infection to identify potential protective mechanisms. Compared to symptomatic patients, asymptomatic patients had higher counts of mature neutrophils and lower proportion of CD169+ expressing monocytes in the peripheral blood. Systemic levels of pro‐inflammatory cytokines were also lower in asymptomatic patients, accompanied by milder pro‐inflammatory gene signatures. Mechanistically, a more robust systemic Th2 cell signature with a higher level of virus‐specific Th17 cells and a weaker yet sufficient neutralizing antibody profile against SARS‐CoV‐2 was observed in asymptomatic patients. In addition, asymptomatic COVID‐19 patients had higher systemic levels of growth factors that are associated with cellular repair. Together, the data suggest that asymptomatic patients mount less pro‐inflammatory and more protective immune responses against SARS‐CoV‐2 indicative of disease tolerance. Insights from this study highlight key immune pathways that could serve as therapeutic targets to prevent disease progression in COVID‐19., We show that asymptomatic patients elicit a different repertoire of immune responses from symptomatic patients. Our data suggest that asymptomatic patients could limit symptom development with a well‐balanced inflammatory response and more protective immune responses against SARS‐CoV‐2.

Background: The complications and sequelae of coronavirus disease 2019 (COVID-19) and their effect on long-term health are unclear, and the trajectory of associated immune dysregulation is poorly understood. Methods: We conducted a prospective longitudinal multicenter cohort study at 4 public hospitals in Singapore. Patients with COVID-19 were monitored for a median of 6 months after recovery from acute infection. Clinical symptoms and radiologic data were collected, along with plasma samples for quantification of immune mediators. The relationship between clinical symptoms and immune cytokine profiles was investigated. Results: Two hundred eighty-eight participants were recruited, and follow-up data were available for 183, 175, and 120 participants at days 30, 90, and 180 postsymptom onset, respectively. Symptoms related to COVID-19 were present in 31 (16.9%), 13 (7.4%), and 14 (11.7%) at days 30, 90, and 180. In a multivariable model, age >65 years, non-Chinese ethnicity, and the severity of acute infection were associated with increased likelihood of persistent symptoms. Recovered COVID-19 patients had elevated levels of proinflammatory interleukin (IL)-17A, stem cell factor, IL-12p70, and IL-1β and pro-angiogenic macrophage inflammatory protein 1β, brain-derived neurotrophic factor, and vascular endothelial growth factor at day 180 compared with healthy controls. Higher levels of monocyte chemoattractant protein-1 and platelet-derived growth factor-BB were detected in patients with persistent symptoms, versus symptom-free patients. Conclusions: Approximately 10% of recovered patients had persistent symptoms 6 months after initial infection. Immune cytokine signatures of the recovered patients reflected ongoing chronic inflammation and angiogenesis. Patients with COVID-19 should be monitored closely for emerging long-term health consequences. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version Recruitment of study participants and sample collection was funded by the Singapore National Medical Research Council COVID-19 Research Fund (COVID19RF-001, COVID19RF-060) and A*STAR COVID-19 Research funding (H/20/04/g1/006). The SIgN Immunomonitoring Platform is supported by a BMRC IAF 311006 grant and BMRC transition funds (H16/99/b0/011). The SIgN MAP platform was supported by a grant from the National Research Foundation, Immunomonitoring Service Platform (NRF2017_SISFP09) from the National Research Foundation Singapore.

Gender affirmation surgery is paramount in the treatment of gender dysphoria for transgender individuals. For transgender women, vaginoplasty offers the opportunity for removal of masculine-appearing genitalia and replacement with a gender-congruent appearance. While numerous techniques have been described in the past, approaches have standardized considerably. Herein, we describe a technique to penile inversion vaginoplasty and focus on some of the critical steps of the procedure to try to optimize patient outcomes. We also review relevant literature regarding perioperative outcomes.

Background Increased arterial stiffness is reportedly associated with cardiac remodelling, including the left atrium and left ventricle, in middle-aged and older adults. However, little is known about this association in young adults. Methods In total, 73 patients (44 (60%) men) aged 25 to 45 years with suspected coronary artery disease were included in the analysis. The left atrial volume index (LAVI), left ventricular volume index (LVVI), and left ventricular mass index (LVMI) were measured using coronary computed tomography angiography (CCTA). Arterial stiffness was assessed with the cardio-ankle vascular index (CAVI). An abnormally high CAVI was defined as that above the age- and sex-specific cut-off points of the CAVI. Results Compared with patients with a normal CAVI, those with an abnormally high CAVI were older and had a greater prevalence of diabetes mellitus, higher diastolic blood pressure, greater coronary artery calcification score, and a greater LAVI (33.5 ± 10.3 vs. 43.0 ± 10.3 mL/m2, p Conclusions The present study demonstrated that increased arterial stiffness is associated with the LAVI, which reflects the early stages of cardiac remodelling, independent of various comorbidity factors in young adults with suspected coronary artery disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host-pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

Key immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+ monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.

Objectives The emergence of a SARS‐CoV‐2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross‐neutralise against the G614 variant. Methods Antibody profiling against the SARS‐CoV‐2 S protein of the D614 variant by flow cytometry and assessment of neutralising antibody titres using pseudotyped lentiviruses expressing the SARS‐CoV‐2 S protein of either the D614 or G614 variant tagged with a luciferase reporter were performed on plasma samples from COVID‐19 patients with known D614G status (n = 44 infected with D614, n = 6 infected with G614, n = 7 containing all other clades: O, S, L, V, G, GH or GR). Results Profiling of the anti‐SARS‐CoV‐2 humoral immunity reveals similar neutralisation profiles against both S protein variants, albeit waning neutralising antibody capacity at the later phase of infection. Of clinical importance, patients infected with either the D614 or G614 clade elicited a similar degree of neutralisation against both pseudoviruses, suggesting that the D614G mutation does not impact the neutralisation capacity of the elicited antibodies. Conclusions Cross‐reactivity occurs at the functional level of the humoral response on both the S protein variants, which suggests that existing serological assays will be able to detect both D614 and G614 clades of SARS‐CoV‐2. More importantly, there should be negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed., A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS‐CoV‐2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody‐mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine whether humoral immunity acquired from the original SARS‐CoV‐2 isolate is able to induce cross‐detection and cross‐protection against the novel prevailing D614G variant. In this study, we demonstrated an overall equivalent neutralising capacity against both the D614 and G614 pseudoviruses, suggesting negligible impact towards the efficacy of antibody‐based therapies and vaccines that are currently being developed.

Background Dengue and Chikungunya viruses can cause large-scale epidemics, with attack rates of up to 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent in 2018 and 2019, mostly affecting the coastal areas. Despite the importance of these viruses, there is limited knowledge on the epidemiology of dengue (DENV) and Chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero Valley, Tanzania. Methods A cross-sectional study was conducted at Kibaoni Health Center in Kilombero Valley, Southeastern Tanzania, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled from the outpatient department. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time reverse transcription polymerase chain reaction assays. Results Overall, 294 patients were recruited. Most were females (65%), and one-third of patients were aged 14–25 years. DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups during both the dry and rainy seasons. Although all 4 DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections. Conclusions This study reveals the co-circulation of all 4 DENV serotypes and CHIKV in Kilombero. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. The occurrence of all serotypes suggests the possibility of severe clinical outcomes in future DENV epidemics in Tanzania.

Penile inversion vaginoplasty is the most common technique used for gender affirming genital surgery in the treatment of gender dysphoria among transwomen. As vaginoplasty becomes more widely available, the management of associated complications has become its own field. There is a relative dearth of literature on surgery for complications following vaginoplasty. This review illustrates surgical technique and management options for patient reported complaints and complications following vaginoplasty. The goal of this manuscript is 2-fold (1) to introduce community surgeons to common postoperative issues they may encounter and (2) provide a systematic operative approach to complications for reconstructive surgeons who see transgender patients regularly.

Significance Odorant sensing GPCRs are the largest gene family in the human genome. We previously found multiple olfactory receptors and their obligate downstream effectors expressed in the smooth muscle of human bronchi. However, the extent to which odorant-sensing receptors (and the ligands to which they respond) on airway smooth muscle (ASM) are physiologically relevant is not established. Here we show that a monoterpene nerol activates the odorant receptor OR2W3 to relax ASM in both cell and tissue models. Surprisingly, the mechanism of action of OR2W3-mediated ASM relaxation involves paradoxical increases in [Ca2+]i that invoke a cooperative activation of TMEM16A and CFTR to compartmentalize calcium and regulate excitation-contraction coupling in human ASM cells., The recent discovery of sensory (tastant and odorant) G protein-coupled receptors on the smooth muscle of human bronchi suggests unappreciated therapeutic targets in the management of obstructive lung diseases. Here we have characterized the effects of a wide range of volatile odorants on the contractile state of airway smooth muscle (ASM) and uncovered a complex mechanism of odorant-evoked signaling properties that regulate excitation-contraction (E-C) coupling in human ASM cells. Initial studies established multiple odorous molecules capable of increasing intracellular calcium ([Ca2+]i) in ASM cells, some of which were (paradoxically) associated with ASM relaxation. Subsequent studies showed a terpenoid molecule (nerol)-stimulated OR2W3 caused increases in [Ca2+]i and relaxation of ASM cells. Of note, OR2W3-evoked [Ca2+]i mobilization and ASM relaxation required Ca2+ flux through the store-operated calcium entry (SOCE) pathway and accompanied plasma membrane depolarization. This chemosensory odorant receptor response was not mediated by adenylyl cyclase (AC)/cyclic nucleotide-gated (CNG) channels or by protein kinase A (PKA) activity. Instead, ASM olfactory responses to the monoterpene nerol were predominated by the activity of Ca2+-activated chloride channels (TMEM16A), including the cystic fibrosis transmembrane conductance regulator (CFTR) expressed on endo(sarco)plasmic reticulum. These findings demonstrate compartmentalization of Ca2+ signals dictates the odorant receptor OR2W3-induced ASM relaxation and identify a previously unrecognized E-C coupling mechanism that could be exploited in the development of therapeutics to treat obstructive lung diseases.

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients reveals a dramatic increase in the number of immature neutrophils. This increase strongly correlates with disease severity and is associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts is observed for CD8 T-cells and VD2 γδ T-cells, which both exhibit increased differentiation and activation. ROC analysis reveals that the count ratio of immature neutrophils to VD2 (or CD8) T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management., COVID-19 severity is associated with cytokine levels and lymphopenia, but the role of immune cell subsets is not well understood. Here the authors immunophenotype whole blood samples from 54 COVID-19 patients and find that the immature neutrophil-to-VD2 T-cell ratio is associated with severe COVID-19.

BackgroundDengue and Chikungunya viruses can cause large-scale epidemics with attack rates exceeding 80%. In Tanzania, there have been repeated outbreaks of dengue fever, the most recent one in 2018 and 2019 mostly reported in coastal areas. Despite its importance, there is limited knowledge on epidemiology of dengue (DENV) and chikungunya (CHIKV) in Tanzania. This study was conducted to investigate the prevalence of DENV and CHIKV in Kilombero district, South-Eastern Tanzania.MethodsA cross-sectional study was conducted at Kibaoni Health Center, in Kilombero district, in the rainy and dry seasons of 2018. Febrile patients of any age and gender were enrolled. Blood samples were taken and screened for DENV and CHIKV viral RNA by real-time RT-PCR assays.ResultsA total of 294 patients were recruited. Most were females (65%), and aged between 14⍰25 years (33%). DENV and CHIKV were detected in 29 (9.9%) and 3 (1.0%) patients, respectively. DENV was detected across all age groups and during both dry and rainy seasons. Although all four DENV serotypes were detected, serotypes 1 and 3 dominated and were present in 14 patients (42.4%) each. Additionally, the study showed DENV-1 and DENV-3 co-infections.ConclusionThis study reveals the co-circulation of all four DENV serotypes and CHIKV in Kilombero district. Importantly, we report the first occurrence of DENV-4 in Tanzania. Unlike previous DENV outbreaks caused by DENV-2, the 2018 outbreak was dominated by DENV-1 and DENV-3. Occurrence of all serotypes suggests the possibility of having severe clinical outcomes in future DENV epidemics in Tanzania.

Background: Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods: Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. Findings: Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. Interpretation: IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs). Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Published version Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001) and CCGSFPOR20002. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR.

SARS-CoV-2 is the novel coronavirus responsible for the current COVID-19 pandemic. Severe complications are observed only in a small proportion of infected patients but the cellular mechanisms underlying this progression are still unknown. Comprehensive flow cytometry of whole blood samples from 54 COVID-19 patients revealed a dramatic increase in the number of immature neutrophils. This increase strongly correlated with disease severity and was associated with elevated IL-6 and IP-10 levels, two key players in the cytokine storm. The most pronounced decrease in cell counts was observed for CD8 T-cells and VD2 γδ T-cells, which both exhibited increased differentiation and activation. ROC analysis revealed that the count ratio of immature neutrophils to CD8 or VD2 T-cells predicts pneumonia onset (0.9071) as well as hypoxia onset (0.8908) with high sensitivity and specificity. It would thus be a useful prognostic marker for preventive patient management and improved healthcare resource management.

Given the ongoing SARS-CoV-2 pandemic, identification of immunogenic targets against the coronavirus spike glycoprotein will provide crucial advances towards the development of sensitive diagnostic tools and potential vaccine candidate targets. In this study, using pools of overlapping linear B-cell peptides, we report two IgG immunodominant regions on SARS-CoV-2 spike glycoprotein that are recognised by sera from COVID-19 convalescent patients. Notably, one is specific to SARS-CoV-2, which is located in close proximity to the receptor binding domain. The other region, which is localised at the fusion peptide, could potentially function as a pan-SARS target. Functionally, antibody depletion assays demonstrate that antibodies targeting these immunodominant regions significantly alter virus neutralisation capacities. Taken together, identification and validation of these neutralising B-cell epitopes will provide insights towards the design of diagnostics and vaccine candidates against this high priority coronavirus., Characterisation of the human antibody response to SARS-CoV-2 can help the design of serological tests and vaccines. Here, the authors identify two linear epitopes in SARS-CoV-2 spike protein that elicit neutralising antibodies in several patients and could thus be useful for serology and vaccine development.

The Virginia Department of Transportation (VDOT) has identified the West Water Street corridor in downtown Charlottesville as an area of focus for bicyclist safety due to a high rate of pedestrian crashes between 2012 and 2016. Water Street hosts one of the main bicycle routes in the city; however, there is a high level of traffic stress for bicyclists. Therefore, it is critical to determine pedestrian and bicyclist safety countermeasures. Ideally, Water Street would be able to accommodate vehicles, pedestrians, and bicyclists in a safe and efficient manner. The focus of this project is to research, create, and test alternative roadway designs to improve bicyclist and pedestrian safety in the Water Street corridor. The design team analyzes best practices from other bicycle-and pedestrian-friendly cities to inspire design ideas for the specific Water Street corridor. Multi-criteria decision analysis is used to choose the best design concept. This one concept is then extrapolated to other similar designs in which one aspect of the main design alternative is changed. The team tests those designs using a virtual reality (VR) environment and biometric data collection. The team is currently (February 2020) starting to conduct experiments in the VR environment. A user testing plan is being created and reviewed that will then be executed in March 2020 to conduct experiments. User comfort and safety will be evaluated across four different design alternatives. From this evaluation, a recommendation will be proposed to the City of Charlottesville as to what design should be implemented.

BACKGROUND Thyroid dysfunction is associated with cognitive impairment, mood disturbance, and postnatal depression. Sufficient thyroid hormone synthesis requires adequate intake of iodine, selenium, and iron. Iodine deficiency was historically a problem for New Zealand, and initiatives were introduced to overcome the problem: (1) mandatory fortification of all bread (except organic) with iodized salt (2009) and (2) provision of subsidized iodine supplements for pregnant and breastfeeding women (2010). Subsequent to these initiatives, most adults and children have adequate iodine status; however, status among breastfeeding women and their infants remains unclear. This paper outlines the methodology of the Mother and Infant Nutrition Investigation (MINI) study: an observational longitudinal cohort study of breastfeeding women and their infants. OBJECTIVE This study will determine (1) women’s iodine intake and status among supplement users and nonusers; (2) women’s intake and status of iodine, selenium, and iron relating to thyroid function; (3) associations between women’s selenium status, thyroid function, and postnatal depression; (4) infants’ iodine and selenium status relating to first year neurodevelopment. METHODS Breastfeeding women aged over 16 years with a healthy term singleton infant were recruited from Manawatu, New Zealand. Participants attended study visits 3, 6, and 12 months postpartum. Maternal questionnaires investigated supplement use before and after birth, iodine knowledge, and demographic information. Dietary assessment and urine, blood, and breast milk samples were taken to measure iodine, selenium, and iron intake/status. The Edinburgh Postnatal Depression Scale was used repeatedly to screen for postnatal depression. Thyroid hormones (free triiodothyronine, free thyroxine, thyroid stimulating hormone, thyroglobulin, antithyroglobulin antibodies, and antithyroid peroxidase) were measured in blood samples, and thyroid gland volume was measured by ultrasound at 6 months postpartum. Infant iodine and selenium concentrations were determined in urine. The Ages and Stages Questionnaire was used to assess infant development at 4, 8, and 12 months. RESULTS Data collection was completed. Biological samples analysis, excluding nail clippings, is complete. Data analysis and presentation of the results will be available after 2020. CONCLUSIONS This study will provide data on the current iodine status of breastfeeding women. It will also provide a greater understanding of the three essential minerals required for optimal thyroid function among breastfeeding women. The prospective longitudinal design allows opportunities to examine women’s mental health and infant neurodevelopment throughout the first year, a crucial time for both mothers and their infants. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12615001028594; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369324 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/18560

Background: Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Methods: Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 12 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. Findings: Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. Interpretation: IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs). Funding Statement: Biomedical Research Council (BMRC), the A*ccelerate GAP-funded project (ACCL/19-GAP064-R20H-H) from Agency of Science, Technology and Research (A*STAR), and National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001). ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study design and protocols for COVID-19, recovered SARS and seasonal hCoV patient cohorts were evaluated by National Healthcare Group (NHG) Domain Specific Review Board (DSRB) and approved under study numbers 2012/00917, 2020/00091 and 2020/00076, respectively. Healthy donor samples were collected under study numbers 2017/2806 and NUS IRB 04-140. Residual serum sample from National Healthy Survey (NHS) collected in 2010 under study number 006/2010 was used as a positive control in peptide-based ELISA (13). Written informed consent was obtained from participants in accordance with the Declaration of Helsinki for Human Research.

The impact of ORF8 382-nucleotide deletion (Δ382) on the cellular host immune response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with wildtype or Δ382 variant of SARS-CoV-2. Interestingly, immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased T cell response, evidenced by enrichment of genes related to T cell functionality that correlated with up-regulation of T cell-associated cytokines, under-expression of neutrophil activation-associated genes, lowered systemic inflammation and effective antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be up-regulated in patients bearing Δ382 and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. These key insights could serve as an important foundation for future human challenge vaccine studies and highlights the prophylactic potential of Δ382 as vaccine candidate. Funding: The study was supported by core and COVID-19 (project number H20/04/g1/006) research grants provided to Singapore Immunology Network by the Biomedical Research Council (BMRC) and A*ccelerate GAP-funded project (ACCL/20-GAP001C20H-E) from the Singapore Ministry of Health’s National Medical Research Council. This study was also funded by the National Medical Research Council (NMRC) COVID-19 Research fund (COVID19RF-001). SIgN Immunomonitoring Platform is supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011. ATR is supported by the Singapore International Graduate Award (SINGA), A*STAR. Conflict of Interest: The authors declare no conflict of interest. Ethical Approval: The study design and protocols for the COVID-19 PROTECT study group were evaluated by National Healthcare Group (NHG) Domain Specific Review Board (DSRB) and approved under study number 2012/00917. Collection of healthy donor samples was approved by SingHealth Centralised Institutional Review Board (CIRB) under study number 2017/2806 and NUS IRB 04-140. Written informed consent was obtained from participants in accordance with the Declaration of Helsinki for Human Research.

Objectives Effects of Zika virus (ZIKV) infection on placental development during pregnancy are unclear. Methods Full‐term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. Results In this study, each woman exhibited a unique immune response with raised IL‐1RA, IP‐10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co‐localised to placental Hofbauer cells, the placentas showed no anatomic defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. Despite these, the babies were delivered without any congenital anomalies. Conclusion These findings should translate to improve clinical prenatal screening procedures for virus‐infected pregnant patients., Zika virus infection during pregnancy is associated with neurologic birth defects, but the effects on placental development are unclear. In this study, each woman exhibited a unique immune response, but they collectively diverged from healthy controls with raised IL‐1RA, IP‐10, EGF and RANTES expression and neutrophil numbers during the acute infection phase. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centred on differential eIF2 signalling, mitochondrial dysfunction and oxidative phosphorylation. These findings should translate to improve clinical prenatal screening procedures for virus‐infected pregnant patients.

Background: Cubital tunnel syndrome is a common compressive neuropathy of the upper extremity. The anconeus epitrochlearis muscle is an unusual but occasional contributor. We review our experience with this anomalous muscle in elbows with cubital tunnel syndrome. Methods: We retrospectively reviewed charts of 13 patients noted to have an anconeus epitrochlearis muscle associated with cubital tunnel syndrome. Results: Ten patients had unilateral ulnar neuropathy supported by nerve conduction studies. Three had bilateral cubital tunnel syndrome symptoms with 1 of those having normal nerve conduction studies for both elbows. Eight elbows were treated with myotomy of the anconeus epitrochlearis muscle and submuscular transposition of the ulnar nerve. The other 8 elbows were treated with myotomy of the anconeus epitrochlearis muscle and in situ decompression of the ulnar nerve only. All but 1 patient had either clinical resolution or improvement of symptoms at follow-up ranging from 2 weeks to 1 year after surgery. The 1 patient who had persistent symptoms had received myotomy and in situ decompression of the ulnar nerve only. Conclusions: An anomalous anconeus epitrochlearis occasionally results in compression of the ulnar nerve but is usually an incidental finding. Its contribution to compression neuropathy can be tested intraoperatively by passively ranging the elbow while observing the change in vector and tension of its muscle fibers over the ulnar nerve. Regardless of findings, we recommend myotomy of the muscle and in situ decompression of the ulnar nerve. Submuscular transposition of the ulnar nerve may be necessary if there is subluxation.

Background and aimThe association of HIV with coronary atherosclerosis has been established; however, the progression of coronary atherosclerosis over time among participants with HIV is not well known. The Multicenter AIDS Cohort Study Quantitative Coronary Plaque Progression Study is a large prospective multicenter study quantifying progression of coronary plaque assessed by serial coronary computed tomography angiography (CTA).Patients and methodsHIV-infected and uninfected men who were enrolled in the Multicenter AIDS Cohort Study Cardiovascular Substudy were eligible to complete a follow-up contrast coronary CTA 3-6 years after baseline. We measured coronary plaque volume and characteristics (calcified and noncalcified plaque including fibrous, fibrous-fatty, and low attenuation) and vulnerable plaque among HIV-infected and uninfected men using semiautomated plaque software to investigate the progression of coronary atherosclerosis over time.ConclusionWe describe a novel, large prospective multicenter study investigating incidence, transition of characteristics, and progression in coronary atherosclerosis quantitatively assessed by serial coronary CTAs among HIV-infected and uninfected men.

This case report describes eradication of carbapenem-resistant Klebsiella pneumoniae from an ischial pressure injury in a patient who underwent a 3-week course of nontoxic three-part combination local wound therapy. With this therapy, providers prevented systemic spread of this multidrug-resistant pathogen and avoided the nephrotoxicity associated with conventional triple antibiotic therapy.

Zika virus (ZIKV) infection during pregnancy is associated with neurologic birth defects, but the effects on placental development are unclear. Full-term placentas from three women, each infected with ZIKV during specific pregnancy trimesters, were harvested for anatomic, immunologic and transcriptomic analysis. In this study, each woman exhibited a unique immune response, but they collectively diverged from healthy controls with raised IL-1RA, IP-10, EGF and RANTES expression, and neutrophil numbers during the acute infection phase. Although ZIKV NS3 antigens co-localized to placental Hofbauer cells, the placentas showed no anatomical defects. Transcriptomic analysis of samples from the placentas revealed that infection during trimester 1 caused a disparate cellular response centered on differential eIF2 signaling, mitochondrial dysfunction and oxidative phosphorylation. These findings should translate to improve clinical prenatal screening procedures for virus-infected pregnant patients.

Patient perspectives on chaperone use during examinations, especially in surgical subspecialties, are understudied. We aimed to identify specific patient cohorts that desire the presence of chaperones and compare patient and surgeon perspectives, all in an effort to improve quality of care.We prospectively administered a 15-question survey to all patients visiting 2 plastic surgery outpatient clinics between January 2015 and April 2016. Data on demographics, types of procedures (cosmetic or reconstructive), area of examination (sensitive or nonsensitive), views on chaperone use, type of chaperone, and instances of inappropriate behavior by surgeons were collected. Univariate analysis was performed after stratifying patients on their individual desire to have a chaperone. Subsequently, multivariate regression models were constructed to identify individual patient cohorts independently more likely to require a chaperone.A total of 398 participants were surveyed. There were 58.3% female and 41.7% male respondents; of whom 41.8% were 55 years or older and 8.1% were younger than 24 years. Ninety percent of all patients were receiving care for a reconstructive procedure. Most (77%) were being examined over a nonsensitive area. Overall, 82.1% preferred not to have a chaperone present during examinations. Most (72.6%) felt the sex of the examining physician was inconsequential to their need for a chaperone. Most (54.8%) preferred either a family member or a friend to be the chaperone. Only 1.8% (n = 7) experienced inappropriate behavior, of whom 77% (n = 5) noted the absence of a chaperone while being examined. On multivariate analysis, younger patients and examination over a sensitive area were independently associated with a higher odd of requiring a chaperone (odds ratios, 3.4 [95% confidence interval, 1.3-8.9; P = 0.016] and 3.9 [95% confidence interval, 1.9-6.7; P0.001], respectively).Most patients did not want a chaperone during examinations. Younger patients and those having a sensitive area examined were independently more likely to desire a chaperone. Patients preferred having their family member or friend as their chaperone. Given the major differences in perceptions, plastic surgeons should consider selectively using chaperones rather than the carte blanche use of chaperones with every patient.

Coronary artery disease is the leading cause of morbidity and mortality. Tools have been developed to accurately diagnose and evaluate coronary artery disease. Coronary CT angiography (CCTA) provides detailed imaging to deliver precise analysis and prognostic information. We sought to compare the radiation dose from a 256-detector-row CT scanner with that from a 64-detector-row CT scanner across a similar profile of patients. Methods: Consecutive patients were screened for the Converge Registry study and, after consenting to be included, were enrolled in accordance with an Institutional Review Board-approved protocol. A control group who underwent 64-row CCTA were matched by age, sex, and body mass index (BMI) with a group who underwent 256-row CCTA. Results: We compared 110 patients in each group. We found that mean dose-length product (DLP) was significantly lower in the 256-row group than in the 64-row group (P < 0.05). The radiation dose was reduced by 32% with use of the 256-row scanner for BMIs of 18.5-24.9 (DLP, 111.2 vs. 76.1 mGy-cm [1.56 vs. 1.07 mSv]; P < 0.05). For each BMI subgroup, there was a significant decrease in dose. Regression analysis found that with increasing BMIs, DLP significantly increased for both scanners. Conclusion: The 256-row scanner provided CCTA scans at significantly lower radiation doses than the 64-row scanner in different BMI groups, with all other variables accounted for. Lower radiation exposure along with lower contrast requirements can provide images with high diagnostic accuracy and less risk to the patient.

Intro: Coronary artery disease is the leading cause for morbidity and mortality. Tools have been developed to accurately diagnose and evaluate coronary artery disease. Coronary computed tomographic angiography (CCTA) scans provide detailed imaging along with analysis to in order to deliver precise analysis and prognostic information. We sought to evaluate the radiation doses of the 256 detector CT scanner to a 64 slice scanner across a similar profile of patients. Methods: Consecutive patients were screened, enrolled, and consented for the Converge Registry study, in accordance with the Institutional Review Board (IRB) approved protocol. 110 patients underwent CCTA using the GE Revolution 256 detector CT scanner. We matched patients by age, gender and body mass index (BMI) who underwent 64 slice CT scanning. Results: We compared 110 patients in each group. We found that mean dose length product (DLP, presented also in the tables below in millisieverts (mSv)) was significantly lower in the Revolution 256 detector group compared to the 64 slice control group (p

Malnutrition is a public health problem especially among the Pacific Small Island developing nations. This study assessed malnutrition with dietary intakes in households of South Tarawa, Kiribati, a West Pacific Island Nation State.A cross-sectional community-based study design was used. One hundred and sixty-one households were selected from Betio, Bikenibeu and Teaorereke towns using a systematic random sampling method. About 35% each of the households was selected from Bikenebue and Besio while 30.4% was selected from Teaoraeke. Family (including children) dietary surveys including 24- hour dietary recall were administered to assess adequacy of nutrient intakes and dietary diversity using Household Diet Diversity Scores. A 3-day weighed food record was collected on a sub-sample. Data were analysed using FoodWorks Pro 8 for nutrient intake and Statistical Product for Service Solution (SPSS) version 21 for descriptive statistics.Sixty-one percent of the subjects had the lowest dietary diversity, 36.3% had a medium dietary diversity and only 2.7% had the highest dietary diversity. Based on the weighed food record results (n=29), male subjects of all age groups had adequate intakes of riboflavin, niacin, vitamin C, magnesium, iron and zinc, but had high intakes of protein and sodium; and low intakes of potassium and calcium. Female subjects had adequate intakes of vitamin C, iron, magnesium and zinc, but had high intakes of protein and sodium; and low intakes of potassium and calcium.Across all groups, 61% of the adult Kiribati population studied showed low dietary diversity, and a high prevalence of multiple micronutrient deficiencies.