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The introduction of new technologies in endoscopy has been met with uncertainty, skepticism, and lack of standardization or training parameters, particularly when disruptive devices or techniques are involved. The widespread availability of a novel endoscopic suturing device (OverStitch™) for tissue apposition has enabled the development of applications of endoscopic suturing.The American Gastroenterological Association partnered with Apollo Endosurgery to develop a registry to capture in a pragmatic non-randomized study the safety, effectiveness, and durability of endoscopic suturing in approximating tissue in the setting of bariatric revision and fixation of endoprosthetic devices.We highlight the challenges of the adoption of novel techniques by examining the process of developing and executing this multicenter registry to assess real-world use of this endoscopic suturing device. We also present our preliminary data on the safety and effectiveness of the novel device as it is applied in the treatment of obesity.The Prospective Registry for Trans-Orifice Endoscopic Suturing Applications (ES Registry) was an effective Phase 4, postmarketing registry aimed at capturing pragmatic, real-world use of a novel device. These findings serve to solidify the role of endoscopic suturing in clinical practice.

Background and Aims Direct endoscopic necrosectomy (DEN) of walled-off pancreatic necrosis (WOPN) lacks dedicated instruments and requires repetitive and cumbersome procedures. This study evaluated the safety and efficacy of a new powered endoscopic debridement (PED) system designed to simultaneously resect and remove solid debris within WOPN. Methods This was a single-arm, prospective, multicenter, international device trial conducted from November 2018 to August 2019 at 10 sites. Patients with WOPN ≥6 cm and ≤22 cm and with >30% solid debris were enrolled. The primary endpoint was safety through 21 days after the last DEN procedure. Efficacy outcomes included clearance of necrosis, procedural time, adequacy of debridement, number of procedures until resolution, hospital stay duration, and quality of life. Results Thirty patients (mean age, 55 years; 60% men) underwent DEN with no device-related adverse events. Of 30 patients, 15 (50%) achieved complete debridement in 1 session and 20 (67%) achieved complete debridement within 2 or fewer sessions. A median of 1.5 interventions (range, 1-7) were required. Median hospital stay was 10 days (interquartile range, 22). There was an overall reduction of 91% in percent necrosis within WOPN from baseline to follow-up and 85% in collection volume. Baseline WOPN volume was positively correlated with the total number of interventions (ρ = .363, P = .049). Conclusions The new PED system seems to be a safe and effective treatment tool for WOPN, resulting in fewer interventions and lower hospital duration when compared with published data on using conventional instruments. Randomized controlled trials comparing the PED system with conventional DEN are needed. (Clinical trial registration number: NCT03694210 .)

OBJECTIVE: To examine the effect of a telehealth intervention that used a dietary app, educational website, and weekly dietitian tele-counseling) on sodium intake, diet quality, blood pressure and albuminuria among individuals with diabetes and early stage chronic kidney disease. DESIGN AND METHODS: We examined the effects of a dietary app-supported tele-counseling intervention in a single center, single arm study of 44 participants with type 2 diabetes and stage 1–3a chronic kidney disease. Participants recorded and shared dietary data via MyFitnessPal with registered dietitians, who used motivational interviewing to provide telephone counseling weekly for 8 weeks. After the 8-week intensive intervention, participants were followed at 6 months and 12 months. Outcomes included 24-hour urine sodium (2 collections per timepoint), Healthy Eating Index (HEI) 2015 score (three 24-hour dietary recalls per timepoint), 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), and 24-hour urine albumin excretion. RESULTS: Out of 44 consented participants (mean age 60.3 +/− 11.9 years, 43% female, 89% white, median eGFR was 78.5 ml/min/1.73m(2), median urine albumin excretion 52.9 mg/day, 84% hypertension), 32 (73%) completed 8-week follow-up, 27 (61%) completed 6-month follow up, and 25 (57%) completed 12-month follow up. Among participants who completed 12-month follow up, reported sodium intake decreased by 638 mg/day from baseline of 2919 mg/day (p-value

Medir la vacunación infantil de rutina es crucial para informar las políticas mundiales de vacunación y la implementación de programas, y para hacer un seguimiento del progreso hacia los objetivos establecidos por el Plan de Acción Mundial sobre Vacunas (GVAP) y la Agenda de Inmunización 2030. Se necesitan estimaciones sólidas de la cobertura de vacunación de rutina para identificar los éxitos pasados ​​y persistentes. vulnerabilidades. A partir del Estudio de la carga global de enfermedades, lesiones y factores de riesgo (GBD) 2020, versión 1, realizamos un análisis sistemático de las tendencias de cobertura de vacunas a nivel mundial, regional y nacional utilizando un marco estadístico, por vacuna y a lo largo del tiempo. Métodos Para este análisis recopilamos 55 326 observaciones específicas del país, de la cohorte, del año, de la vacuna y de la dosis de la cobertura de vacunación infantil de rutina entre 1980 y 2019. Utilizando el proceso de regresión gaussiana espaciotemporal, Estimaciones específicas por año de 11 indicadores de cobertura de vacunación infantil de rutina para 204 países y territorios desde 1980 hasta 2019, ajustando los sesgos en los datos informados por los países y reflejando los desabastecimientos informados y las interrupciones en el suministro. Analizamos las tendencias mundiales y regionales en la cobertura y el número de niños con dosis cero (definidos como aquellos que nunca recibieron una dosis de vacuna contra la difteria, el tétanos y la tos ferina [DTP]), el progreso hacia los objetivos del GVAP y la relación entre la cobertura de la vacuna y el desarrollo sociodemográfico. Recomendaciones Para 2019, la cobertura mundial de la tercera dosis de DTP (DTP3; 81,6 % [intervalo de incertidumbre del 95 % 80,4–82,7]) se duplicó con creces con respecto a los niveles estimados en 1980 (39,9 % [37,5–42 ·1]), al igual que la cobertura mundial de la vacuna antisarampionosa de primera dosis (MCV1; del 38,5 % [35,4–41,3] en 1980 al 83,6 % [82,3–84,8 ] en 2019). La cobertura de la vacuna antipoliomielítica de tercera dosis (Pol3) también aumentó, del 42,6 % (41,4–44,1) en 1980 al 79,8 % (78,4–81,1) en 2019, y la cobertura mundial de vacunas más nuevas Las vacunas aumentaron rápidamente entre 2000 y 2019. La cantidad mundial de niños que recibieron dosis cero se redujo en casi un 75 % entre 1980 y 2019, de 56,8 millones (52,6–60,9) a 14,5 millones (13,4– 15·9). Sin embargo, durante la última década, la cobertura mundial de vacunas se estabilizó en general; 94 países y territorios registraron una disminución de la cobertura de DTP3 desde 2010. Se estimó que solo 11 países y territorios alcanzaron el objetivo nacional del GVAP de al menos una cobertura del 90 % para todas las vacunas evaluadas en 2019. Interpretación Después de lograr grandes avances en la cobertura de vacunación infantil en todo el mundo, en gran parte del mundo este progreso se estancó o se revirtió de 2010 a 2019. Estos hallazgos subrayan la importancia de revisar las estrategias de inmunización de rutina y los enfoques programáticos, centrando la prestación de servicios en torno a la equidad y las poblaciones desatendidas. Fortalecer los datos de vacunas y los sistemas de monitoreo es crucial para estas actividades, ahora y hasta 2030, para garantizar que todos los niños tengan acceso y puedan beneficiarse de las vacunas que salvan vidas. Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. Methods For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. Findings By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. Interpretation After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines.

A N-glycan specific lectin from Rhizoctonia bataticola [RBL] was shown to induce growth inhibitory and apoptotic effect in human ovarian, colon and leukemic cells but mitogenic effect on normal PBMCs as reported earlier, revealing its clinical potential. RBL has unique specificity for high mannose tri and tetra antennary N-glycans, expressed in ovarian cancer and also recognizes glycans which are part of CA 125 antigen, a well known ovarian cancer marker. Hence, in the present study diagnostic and therapeutic potential of RBL was investigated using human ovarian epithelial cancer SKOV3 and OVCAR3 cells known for differentially expressing CA 125. RBL binds differentially to human ovarian normal, cyst and cancer tissues. Flow cytometry, western blot analysis of membrane proteins showed the competitive binding of RBL and CA 125 antibody for the same binding sites on SKOV3 and OVCAR3 cells. RBL has strong binding to both SKOV3 and OVCAR3 cells with MFI of 173 and 155 respectively. RBL shows dose and time dependent growth inhibitory effect with IC50 of 2.5 and 8 μg/mL respectively for SKOV3 and OVCAR3 cells. RBL induces reproductive cell death, morphological changes, nuclear degradation and increased release of ROS in SKOV3 and OVCAR3 cells leading to cell death. This is also supported by increase in hypodiploid population, altered MMP leading to apoptosis possibly involving intrinsic pathway. Adhesion, wound healing, invasion and migration assays demonstrated anti-metastasis effect of RBL apart from its growth inhibitory effect. These results show the promising potential of RBL both as a diagnostic and therapeutic agent.

Endoscopic ultrasound (EUS) is one of the significant breakthroughs in the field of advanced endoscopy. In the last two decades, EUS has evolved from a diagnostic tool to a real-time therapeutic modality. The luminal gastrointestinal (GI) tract provides a unique opportunity to access multiple vascular structures, especially in the mediastinum and abdomen, thus permitting a variety of EUS-guided vascular interventions. The addition of the doppler and contrast-enhanced capability to EUS has further helped provide real-time visualization of blood flow in vessels through the GI tract. EUS-guided vascular interventions rely on standard endoscopic accessories and interventional tools such as fine-needle aspiration needles and fine-needle biopsy. EUS allows the visualization of various structures in real-time by differentiating tissue densities and vascularity, thus, avoiding radiation exposure. EUS-guided techniques also allow real-time microscopic examination after target biopsy. Furthermore, many necessary interventions can be done during the same procedure after diagnosis. This article provides an overview of EUS-guided vascular interventions such as variceal, non-variceal bleeding interventions, EUSguided portal vein (PV) access with the formation of an intrahepatic portosystemic shunt, and techniques related to diagnosis of GI malignancies. Furthermore, we discuss current insights and future outlook of therapeutic modalities like PV embolization, PV sampling, angiography, drug administration, and portal pressure measurement.

OBJECTIVE: T-Flex registry was designed to investigate the safety and clinical performance of the ultrathin (60 μm) strut biodegradable polymer-coated sirolimus-eluting stent (SES) with a unique long dual Z (LDZ) link design on a cobalt-chromium stent platform (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) in a real-world all-comer population including high-risk subgroups. METHODS: This was an observational, multicenter, single-arm, and investigator-initiated retrospective registry. A total of 1,203 patients treated with an ultrathin biodegradable polymer-coated SES, irrespective of lesion complexity, comorbidities, and acute presentation were analyzed from May 2016 to January 2017. The primary endpoint was the one-year incidence of target lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction (TV-MI), and clinically-indicated target lesion revascularization (CI-TLR). Stent thrombosis was assessed as an additional safety endpoint. RESULTS: At the one-year follow-up, TLF was observed in 3.8% [95% confidence interval (CI) 2.9–5.1] patients, composed of 0.6% (95% CI: 0.3–1.3) cardiac death, 1.3% (95% CI: 0.8–2.2) TV-MI, and 1.9% (95% CI: 1.3–2.9) CI-TLR. In the high-risk subgroups, TLF at one-year was 6.8% (95% CI: 4.6–9.8) in patients with diabetes, 5.2% (95% CI: 3.4–8) in patients with small-vessel disease, 6.1% (95% CI: 3.9–9.6) in patients with ST-elevation myocardial infarction, and 4.5% (95% CI: 2.4–8.3) in patients with total occlusion. During follow-up, stent thrombosis was reported in 0.8% (95% CI: 0.4–1.5) patients in the overall population. CONCLUSION: Low event rates of TLF and stent thrombosis at one-year follow-up indicate that this ultrathin biodegradable polymer-coated SES has encouraging safety and clinical performance in real-world all-comer populations as well as in high-risk subgroups.

In this study, we evaluated a detailed molecular mechanism of anti-adipogenic activity of vitexin, apigenin flavone glucoside, present in germinated fenugreek seeds, in differentiating human mesenchymal stem cells (hMSCs). The lipid content of differentiated adipocytes was estimated by ORO staining. Effect on mitotic clonal expansion was checked by cell cycle analysis. Expression of early and terminal adipocyte differentiation markers, anti- and pro-adipogenic transcription factors and signalling intermediates regulating them was evaluated at RNA and protein level. We found vitexin to be non-cytotoxic up to 20 μM at which intracellular lipid accumulation was significantly decreased. Cell cycle analysis suggested that vitexin does not affect mitotic clonal expansion. Expression of early and late differentiation markers, such as CEBPα, CEBPβ, PPARγ, FABP4, perilipin, adiponectin and Glut4 was significantly reduced in the presence of vitexin. Expression of KLF4 and KLF15, positive regulators of PPARγ, was decreased, whereas that of negative regulators, namely KLF2, GATA2, miR20a, miR27a, miR27b, miR128, miR130a, miR130b, miR182 and miR548 increased with vitexin treatment. This effect was mediated by the activation of the AMP-activated protein kinase (AMPK) pathway via the activation of LepR and additionally by inhibiting ROS. Thus, our results showed that vitexin regulates the expression of PPARγ and inhibits adipogenesis of hMSCs at an early stage of differentiation.

Summary Regenerative medicine has great potential. The pace of scientific advance is exciting and the medical opportunities for regeneration and repair may be transformative. However, concerns continue to grow, relating to problems caused both by unscrupulous private clinics offering unregulated therapies based on little or no evidence and by premature regulatory approval on the basis of insufficient scientific rationale and clinical evidence. An initiative by the InterAcademy Partnership convened experts worldwide to identify opportunities and challenges, with a focus on stem cells. This was designed to be inclusive and consensus outputs reflected the diversity of the global research population. Among issues addressed for supporting research and innovation while protecting patients were ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public. The InterAcademy Partnership (IAP) identified options for action for sharing good practice and building collaboration within the scientific community and with other stakeholders worldwide., Highlights • An inclusive IAP study examined global stem cell opportunities and challenges • Great potential leads to concerns for evidence base in unregulated clinics • Also concerns for premature regulatory approval without sufficient evidence • Recommendations for responsible research and innovation and collaborations, In this article, Fears and colleagues describe an inclusive global initiative by the InterAcademy Partnership examining stem cell opportunities and challenges. Great therapeutic potential brings concerns about the inadequate evidence base used by unregulated clinics. Concerns are also expressed about premature regulatory approval without sufficient evidence. Recommendations cover ethical assessment; pre-clinical and clinical research; regulatory authorization and medicines access; and engagement with patients, policy makers, and the public.

Background The European Medicines Agency (EMA) requires enhanced safety surveillance to be conducted for annual seasonal influenza vaccines with the aim of rapidly detecting any potential new safety concerns before the peak immunisation period of the vaccine in any given year. The aim of this study was to detect any clinically significant change in the frequency or severity of expected reactogenicity of the quadrivalent inactivated split-virion influenza vaccine (IIV4) during routine immunisation in Finland for the 2020/21 season. The primary objective was to investigate the frequency of suspected adverse drug reactions (ADRs) occurring within 7 days following vaccination. Methods Enhanced passive safety surveillance of individuals vaccinated with IIV4 was conducted from October 9, 2020 to November 30, 2020 across seven sites in Finland. The vaccinee reporting rate and ADR reporting rate were calculated and compared with known or expected safety data in order to identify any clinically significant changes. Results Data were collected from 1008 individuals with 29 vaccinees reporting 82 suspected ADRs. Of these, 28 people reported 79 suspected ADRs within 7 days following vaccination, corresponding to a vaccinee reporting rate of 2.78% (95% CI: 1.85, 3.99) (ADR reporting rate, 7.84% [95% CI: 6.25, 9.67%]). The most frequently reported ADRs were injection site reactions (vaccination site pain, vaccination site erythema and vaccination site swelling) (n = 46, 2.28%), myalgia (n = 9, 0.89%) and headache (n = 8, 0.79%). No serious suspected adverse events were reported at any point post-vaccination and ADR reporting rates were in general lower compared to those reported for IIV4 in the 2019/20 surveillance study. Conclusion No clinically significant changes in what is known or expected for IIV4 were reported for the 2020/21 season which supports the safety profile of this vaccine and will help maintain public confidence in influenza vaccination.

Neoplasms originating from thymic T-cell progenitors and post-thymic mature T-cell subsets account for a minority of lymphoproliferative neoplasms. These T-cell derived neoplasms, while molecularly and genetically heterogeneous, exploit transcription factors and signaling pathways that are critically important in normal T-cell biology, including those implicated in antigen-, costimulatory-, and cytokine-receptor signaling. The transcription factor GATA-3 regulates the growth and proliferation of both immature and mature T cells and has recently been implicated in T-cell neoplasms, including the most common mature T-cell lymphoma observed in much of the Western world. Here we show that GATA-3 is a proto-oncogene across the spectrum of T-cell neoplasms, including those derived from T-cell progenitors and their mature progeny, and further define the transcriptional programs that are GATA-3 dependent, which include therapeutically targetable gene products. The discovery that p300-dependent acetylation regulates GATA-3 mediated transcription by attenuating DNA binding has novel therapeutic implications. As most patients afflicted with GATA-3 driven T-cell neoplasms will succumb to their disease within a few years of diagnosis, these findings suggest opportunities to improve outcomes for these patients.

Aim: Arterial stiffness, a major marker of vascular impedance, has been identified as a predictor of adverse cardiac outcomes. The present study determined the relationship between blood pressure (BP) and arterial stiffness measured noninvasively using a periscope in hypertensive patients. It has also evaluated the usefulness of indices of arterial stiffness in cardiovascular (CV) risk stratification and the necessity to implement these aortic pressure parameters in clinical practice. Methods: The prospective, observational study involved patients with hypertension between the age of 18 and 80 years. The demographic and anthropometric measurements of all the participants were recorded and various central and peripheral (brachial) arterial pressure parameters were measured using a periscope. The clinical variables were compared separately for different CV risk grades and arterial stiffness index (ASI) using Kruskal–Wallis test for non-normal data and chi-square test for count data. The correlation of different parameters with CV risk grade and ASI were evaluated using Spearmen’s correlation method. The agreement of different ASI indices with CV risk grades was assessed using Kappa method. Results: The study recruited a total of 3,032 patients with hypertension. Classification of the subjects for CV risk grades had demonstrated that major proportion of the patients (n = 713) had moderate and severe CV risks (n = 708). The classification of hypertensive patients for arterial stiffness had shown that 1,037 subjects had severe arterial stiffness. Classification of arterial stiffness based on BP levels had demonstrated that 623 patients with severe arterial stiffness and 315 with borderline arterial stiffness had stage II hypertension, and 480 patients with normal BP had no arterial stiffness. Brachial ASI had a strong correlation with systolic BP (SBP). A very good agreement with K value 0.871 was noted for Kappa agreement of arterial stiffness indices with CV risk. Conclusion: The present study corroborates the use of central BP parameters as indicators of arterial stiffness in hypertensive subjects. Noninvasive measurement of these indices has wider implications in personalized risk assessment of CV risk in subjects with hypertension.

Background: Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods: We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (U5MR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings: Global U5MR decreased from 71·2 deaths per 1000 livebirths (95% uncertainty interval [UI] 68·3-74·0) in 2000 to 37·1 (33·2-41·7) in 2019 while global NMR correspondingly declined more slowly from 28·0 deaths per 1000 live births (26·8-29·5) in 2000 to 17·9 (16·3-19·8) in 2019. In 2019, 136 (67%) of 204 countries had a U5MR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030, 154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9·65 million (95% UI 9·05-10·30) in 2000 and 5·05 million (4·27-6·02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3·76 million [95% UI 3·53-4·02]) in 2000 to 48% (2·42 million; 2·06-2·86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0·80 (95% UI 0·71-0·86) deaths per 1000 livebirths and U5MR to 1·44 (95% UI 1·27-1·58) deaths per 1000 livebirths, and in 2019, there were as many as 1·87 million (95% UI 1·35-2·58; 37% [95% UI 32-43]) of 5·05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation: Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve U5MR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. This article was supported by the European Research Council, ERC 848325. Alberto Ortiz was supported by FIS/Fondos FEDER (PI18/01366, PI19/00588, PI19/00815, DTS18/00032, ERA-PerMed-JTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009). Daniela Ribeiro acknowledges the financial support from the European Union [FEDER funds through COMPETE, POCI-01-0145-FEDER-029253). Joan B Soriano acknowledges support from the Centro de Investigación en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain Funding: Bill & Melinda Gates Foundation

OBJECTIVE: Evaluate longitudinal changes in brain microstructure and volumes in very preterm during the first year of life with and without intervention. DESIGN: Descriptive pilot study METHODS: Five preterm infants in a three-arm clinical trial, one SPEEDI Early, two SPEEDI Late, and two usual care. Brain structural and diffusion MRI’s were acquired within 72 hours after neonatal intensive care unit discharge (n=5), three months post-baseline (n=5), and six months post-baseline (n=3). Fractional anisotropy (FA), Mean diffusivity (MD), and volume metrics were computed for five brain regions. RESULTS: More than 60% of eligible participants completed 100% of the scheduled MRIs. FA and volume increased from baseline to six months across all brain regions. Rate of white matter volume change from baseline to six months was highest in SPEEDI Early. CONCLUSIONS: Non-sedated longitudinal MRI is feasible in very preterm infants and appears to demonstrate longitudinal changes in brain structure and connectivity.

In March 2020, COVID-19 shuttered access to many healthcare settings offering HIV testing and there is no licensed HIV self-test in Canada.A team of nurses at the University of Ottawa and Ottawa Public Health and staff from the Ontario HIV Treatment Network (OHTN) obtained Health Canada's Special Access approval on April 23, 2020 to distribute bioLytical's INSTI HIV self-test in Ottawa; we received REB approval on May 15, 2020. As of July 20, 2020, eligible participants (≥18 years old, HIV-negative, not on PrEP, not in an HIV vaccine trial, living in Ottawa, no bleeding disorders) could register via www.GetaKit.ca to order kits.In the first 6 weeks, 637 persons completed our eligibility screener; 43.3% (n = 276) were eligible. Of eligible participants, 203 completed a baseline survey and 182 ordered a test. These 203 participants were an average of 31 years old, 72.3% were white, 60.4% were cis-male, and 55% self-identified as gay. Seventy-one percent (n = 144) belonged to a priority group for HIV testing. We have results for 70.9% (n = 129/182) of participants who ordered a kit: none were positive, 104 were negative, 22 were invalid, and 2 "preferred not to say"; 1 participant reported an unreadiness to test.Our results show that HIV self-testing is a pandemic-friendly strategy to help ensure access to sexual health services among persons who are good candidates for HIV testing. It is unsurprising that no one tested positive for HIV thus far, given the 0.08% positivity rate for HIV testing in Ottawa. As such, we advocate for scale-up of HIV self-testing in Canada.RéSUMé: CONTEXTE: En mars 2020, la COVID-19 a empêché l’accès à de nombreux établissements de santé offrant des tests de dépistage du VIH et il n’existe pas d’autotest du VIH autorisé au Canada. INTERVENTION: Une équipe d’infirmières de l’Université d’Ottawa et de Santé publique Ottawa et le personnel du Réseau ontarien de traitement du VIH (OHTN) ont obtenu l’approbation d’accès spécial de Santé Canada le 23 avril 2020 pour distribuer l’autotest VIH INSTI de bioLytical à Ottawa; nous avons reçu l’approbation du Comité d’éthique de la recherche (CER) le 15 mai 2020. À partir du 20 juillet 2020, les participants admissibles (≥18 ans, séronégatifs, ne prenant pas de PPrE, ne participant pas à un essai de vaccin contre le VIH, vivant à Ottawa, ne souffrant pas de troubles de la coagulation) pouvaient s’inscrire via www.GetaKit.ca pour commander une trousse d’autotest. RéSULTATS: Au cours des six premières semaines, 637 personnes ont rempli notre questionnaire d’admissibilité; 43,3 % (n = 276) étaient admissibles. Parmi les participants admissibles, 203 ont répondu à l’enquête de référence et 182 ont commandé un test. Ces 203 participants avaient en moyenne 31 ans, 72,3 % étaient blancs, 60,4 % étaient hommes-cis et 55 % s’identifiaient comme gays. Soixante et onze pour cent (n = 144) appartenaient à un groupe prioritaire pour le dépistage du VIH. Nous avons les résultats pour 70,9 % (n = 129/182) des participants qui ont commandé une trousse : aucun n’était positif, 104 étaient négatifs; 22 étaient invalides; 2 « préféraient ne pas le dire »; et un seul a indiqué qu’il n’était pas prêt à subir le test. CONCLUSION: Nos résultats montrent que l’autodépistage du VIH est une stratégie adaptée à la pandémie pour aider à garantir l’accès aux services de santé sexuelle aux gens qui sont de bons candidats au dépistage du VIH. Il n’est pas surprenant que personne n’ait été testé positif pour le VIH jusqu’à présent, étant donné le taux de positivité de 0,08 % pour le test de dépistage du VIH à Ottawa. C’est ce qui nous incite à préconiser l’intensification du recours à l’autotest du VIH au Canada.

The L-fucose-specific lectin from Aspergillus niger (ANL), isolated from the corneal smears of a keratitis patient was reported earlier. Here, we examined the interaction of ANL with human hepatocellular and colon cancer cells, evaluated its anti-cancer activity and diagnostic potential to detect aberrantly glycosylated tumour-associated serum glycoproteins such as alpha-fetoprotein (AFP). We observed that ANL strongly bound to both HepG2 and HT-29 cell-lines and this interaction was effectively blocked with L-fucose and mucin in a dose and time-dependent manner with an IC50 of 1.25 and 5 μg/mL for HepG2 and HT-29 cells respectively at 48 hours. ANL treatment increased hypodiploidy and decreased the number of HepG2 cell in G0 -G1 phase at both 24 and 48 hours. Furthermore, ANL increased the level of apoptosis in both HepG2 and HT-29 cells in a time-dependent manner via enhanced production of reactive oxygen species and altered mitochondrial membrane potential, indicative of intrinsic apoptotis pathway activation. Immunoblot analysis confirmed the time-dependent elevation of levels of cytochrome c, initiator caspase-9 and activation of caspase-3. ANL immunohistochemistry on colon cancer tissue and quantification of AFP in HCC patient serum samples by developing an ANL-anti-AFP antibody sandwich enzyme-linked immunosorbent assay confirmed the diagnostic potential of ANL. Here, interaction of ANL with AFP could be effectively blocked in the presence of competing fucose-bearing glycans. We found ANL to be more sensitive than Lens culinaris lectin, a well-known fucose-specific lectin and currently used diagnostic agent. ANL can be further explored as a diagnostic and anti-cancer agent.

Early readmissions of spontaneous bacterial peritonitis (SBP) are often associated with poor outcomes. We compared characteristics and outcomes for index and 30-day readmissions of SBP in the USA.We analyzed the Nationwide Readmissions Database for 2018 to identify all adult (≥ 18 years) 30-day readmissions of SBP in the USA. Hospitalization characteristics and outcomes for index and 30-day readmissions of SBP were compared. Independent predictors of 30-day readmissions were also identified.In 2018, of the 5,797 index admissions for SBP, 30% (1726) were readmitted within 30 day. At the time of readmission, the most common admitting diagnosis was alcoholic cirrhosis of the liver with ascites (11.8%) followed by sepsis due to an unspecified organism (9.2%). SBP as an admitting diagnosis was identified for only 8.3% of these 30-day readmissions. Compared with index admissions, 30-day readmissions of SBP had a lower mean age (56.1 vs 58.6 years, P 0.001) without a statistically significant difference for gender. Furthermore, 30-day readmissions of SBP were associated with significantly higher odds of inpatient mortality (10% vs 4.9%, OR: 2.15, 95% CI: 1.66-2.79, P 0.001), and mean total hospital charge ($85,031 vs $56,000, mean difference: 29,032, 95% CI: 12,867-45,197, P 0.001) compared with index admissions. The presence of chronic pulmonary disease, liver failure, inpatient dialysis, and discharge against medical advice were identified as independent predictors for increased 30-day readmissions of SBP.The 30-day readmission rate of SBP was 30% and these readmissions were associated with higher odds of inpatient mortality compared with index admissions.

Background Cardiovascular disease (CVD) disproportionately affects Black adults in the United States. This is increasingly acknowledged to be due to inequitable distribution of health-promoting resources. One potential contributor is inequities in educational opportunities, although it is unclear what aspects of education are most salient. School racial segregation may affect cardiovascular health by increasing stress, constraining socioeconomic opportunities, and altering health behaviors. We investigated the association between school segregation and Black adults’ CVD risk. Methods and findings We leveraged a natural experiment created by quasi-random (i.e., arbitrary) timing of local court decisions since 1991 that released school districts from court-ordered desegregation. We used the Panel Study of Income Dynamics (PSID) (1991 to 2017), linked with district-level school segregation measures and desegregation court order status. The sample included 1,053 Black participants who ever resided in school districts that were under a court desegregation order in 1991. The exposure was mean school segregation during observed schooling years. Outcomes included several adult CVD risk factors and outcomes. We fitted standard ordinary least squares (OLS) multivariable linear regression models, then conducted instrumental variables (IV) analysis, using the proportion of schooling years spent in districts that had been released from court-ordered desegregation as an instrument. We adjusted for individual- and district-level preexposure confounders, birth year, and state fixed effects. In standard linear models, school segregation was associated with a lower probability of good self-rated health (−0.05 percentage points per SD of the segregation index; 95% CI: −0.08, −0.03; p < 0.001) and a higher probability of binge drinking (0.04 percentage points; 95% CI: 0.002, 0.07; p = 0.04) and heart disease (0.01 percentage points; 95% CI: 0.002, 0.15; p = 0.007). IV analyses also found that school segregation was associated with a lower probability of good self-rated health (−0.09 percentage points; 95% CI: −0.17, −0.02, p = 0.02) and a higher probability of binge drinking (0.17 percentage points; 95% CI: 0.04, 0.30, p = 0.008). For IV estimates, only binge drinking was robust to adjustments for multiple hypothesis testing. Limitations included self-reported outcomes and potential residual confounding and exposure misclassification. Conclusions School segregation exposure in childhood may have longstanding impacts on Black adults’ cardiovascular health. Future research should replicate these analyses in larger samples and explore potential mechanisms. Given the recent rise in school segregation, this study has implications for policies and programs to address racial inequities in CVD.

To estimate the prevalence of blindness and severe visual impairment (SVI) by using a door-to-door screening and vision center (VC) examination strategy in an urban area in western Maharashtra (Pune), India and repeat the exercise after 4 years to study its impact.Four trained community health workers measured the visual acuity and performed an external ocular examination in patients' homes. People with vision6/18 were requested to visit the VC for a comprehensive eye examination by an optometrist. An ophthalmologist examined people whose vision did not improve to 6/12. A home examination was done for people who did not visit the VC despite two requests. The same population was examined twice in an interval of 4 years.In the study, 44,535 people in 2015-16 and 98.14% (n = 43,708) of them in 2018-19 were examined. Blindness (vision3/60 in better eye), and moderate-to-severe visual impairment (MSVI, vision 6/18-6/60 in better eye) were 0.26% and 1.3%, respectively, in the first cohort, and 0.16% and 1.1%, respectively, in the second cohort (P0.001). When the worse eye was considered, the prevalence of blindness reduced from 0.72% to 0.44%, SVI reduced from 0.1% to 0.07%, and MVI decreased from 1.7% to 1.49% between 2015 and 2019 (P0.001). Females (P0.001) and older individuals (P0.001) were more likely to have blindness or SVI. In the VC, 8211 people were examined in 4 years.The reduction of blindness and MSVI in the urban area of Pune can be partly ascribed to the presence of a VC and attendant screening in this locality.

An L-fucose lectin, ANL from the corneal smears of a mycotic keratitis patient was reported earlier. Interaction of ANL with immortalized Human Corneal Epithelial Cells (HCECs) was studied in order to assign the role of ANL in pathogenesis. ANL showed strong binding to HCECs which could be blocked by L-fucose and mucin. At concentrations below 0.6 μg/mL ANL showed proliferative effect and highest at 0.07 μg/mL leading to expression of proinflammatory cytokines IL-6 and IL-8. ANL induced proinflammatory response is mediated by TLR-2,-4, MyD88, NFkB and C-Jun dependent signaling. In contrast, ANL at concentrations above 0.6 μg/mL showed growth inhibitory effect at 48 h with an IC50 of 2.75 μg/mL. Western blot analysis revealed that HCECs treated with ANL at lower concentration induced the expression of proinflammatory signaling proteins TLR-2, 4, MyD88, NFkB and C-Jun which maintain high cell proliferating state. At higher concentration ANL induced apoptotic effect in HCECs with an increase in early apoptotic population as demonstrated by Annexin V-PI assay. ANL induced the expression of apoptotic proteins FADD, Caspase 8 and -3 mediated by MyD88. These findings demonstrate implication of ANL in pathogenesis and the findings are of clinical significance in developing strategy for controlling the infection leading to mycotic keratitis.

Objective While single-use and detachable-tip duodenoscopes have been recently developed to overcome risks of infection transmission, there are no reliable tools to objectively assess their technical performance. We evaluated the reliability and validity of a newly developed tool to assess the technical performance of reusable duodenoscopes. Methods An assessment tool was developed to measure duodenoscope performance based on three distinct criteria: maneuverability, mechanical/imaging characteristics and ability to perform requisite interventions. The assessment tool was tested prospectively on duodenoscopes used in endoscopic retrograde cholangiopancreatography (ERCP) procedures at nine academic medical centers over a 6-month period. The main outcome was reliability of the duodenoscope assessment tool, which was estimated using Cronbach's coefficient alpha (α). The secondary outcome was validity of the assessment tool. Results The assessment tool evaluated technical performance of reusable duodenoscopes in 1080 ERCP procedures. Indications were biliary in 92.8% and pancreatic in 7.2% procedures. The overall Cronbach's coefficient α for maneuverability was 0.81, assessment of mechanical/imaging characteristics was 0.92, and ability to perform requisite interventions was 0.87. On multiple linear regression analysis, prolonged procedure duration, older patient age and pancreatic interventions were significantly positively associated with higher (worse) scores. Conclusions The newly developed assessment tool appears reliable and valid for evaluating the technical performance of duodenoscopes. Registration: ClinicalTrials.gov Identifier: NCT04004533.

There is increasing evidence of an association between Modic changes (MC) and subclinical infection. However, the association of MC with postoperative surgical site infection (SSI) has not been adequately probed. This study primarily aimed to investigate a probable association between preoperative MC, total endplate damage score (TEPS), and SSI. A retrospective analysis of 1124 patients who underwent surgery in a single institution (2016–2018) was performed, using both univariate and multiple logistic regression analyses to identify independent risk factors for SSI. The prevalence of SSI was 4% (44/1124 patients), with no association with age or sex. The prevalence of MC in the SSI group was significantly higher—79.54% (35/44) compared to 58.79% (635/1080) (p value = 0.006) in the control group with no specific relation to type or location of MC. A higher TEPS was associated with SSI (p value = 0.009). A receiver operating characteristic (ROC) curve for TEPS values to assess predictiveness of SSI showed TEPS ≥ 5.5 to have a better sensitivity of 84% than 72% for a TEPS ≥ 6.5. Univariate analysis showed TEPS > 6 (odds ratio 3.887) to have a stronger association with SSI than the presence of MC (odds ratio 2.725). Among various types of surgeries, discectomy had a higher association with SSI (p value = 0.03) when compared to fusion (p value = 0.071). However, multiple logistic regression analysis revealed only TEPS > 6, presence of MC and hypothyroidism as independent risk factors for SSI. Our data suggest that preoperative MC and TEPS > 6 are independent risk factors for developing surgical site infections. MC could be foci of chronic subclinical infection and not mere markers of degeneration, as initially described.

Background Dysplasia in Barrett’s esophagus (BE) is focal and difficult to locate. The aim of this meta-analysis was to understand the spatial distribution of dysplasia in BE before and after endoscopic ablation therapy. Methods A systematic search was performed of multiple databases to July 2019. The location of dysplasia prior to ablation was determined using a clock-face orientation (right or left half of the esophagus). The location of the dysplasia post-ablation was classified as within the tubular esophagus or at the top of the gastric folds (TGF). Results 13 studies with 2234 patients were analyzed. Pooled analysis from six studies (819 lesions in 802 patients) showed that before ablation, dysplasia was more commonly located in the right half versus the left half (odds ratio [OR] 4.3; 95 % confidence interval [CI] 2.33 – 7.93; P Conclusion Before ablation, dysplasia in BE is found more frequently in the right half of the esophagus versus the left. Post-ablation recurrence is more commonly found in the TGF and is non-visible, compared with the tubular esophagus, which is mainly visible.

Background Various factors associated with vaccination uptake in children have been identified, but no study has examined their overall immunization status and individual vaccine coverage at 1, 2 and 5 years in the UK. Methods Data from 6977 participants in the Born in Bradford cohort were linked to primary care records. Overall immunization status and individual vaccine uptake of the UK routine childhood vaccination schedule was estimated in White British and Pakistani children born between 2007 and 2011, and factors associated with partial uptake in each ethnic group were identified using Poisson regression. Results Vaccine uptake was greater in Pakistani compared with White British children at all ages and for each year examined in this study. Children of foreign-born White British women were more likely to be partially immunized and those of foreign-born Pakistani women were more likely to be fully immunized. Socio-economic factors were strongly associated with uptake, especially among White British women. Conclusions Vaccination uptake is influenced by social and economic environment, ethnicity and maternal country of birth. This suggests that current health education and service delivery may not be effective for some families, including those from different cultural and ethnic backgrounds, who may require targeted interventions to improve immunization uptake.

Oral mucositis refers to erythematous and ulcerative lesions of oral mucosa during chemo/radiotherapy. Treatment modalities were directed towards reduction in severity of oral mucositis. Zinc plays an important role to retard oxidative processes and is considered as the critical component in wound healing. To compare the efficacy of zinc alone with improvised zinc preparation in reducing the severity of oral mucositis. Improvised zinc was a combination of zinc oxide, amla, tulsi and curcumin at 1% therapeutic concentrations. Seventy-five subjects undergoing chemo/radiotherapy were randomly divided into three groups: Group A (25 subjects) had received topical 5% zinc oxide paste trice daily application after food for entire treatment period, initiated 2 d prior to radiotherapy. Group B (25) received improvised zinc preparations (1%) and instructed to apply same as group A. Group C (25) received standard treatment offered by cancer hospital. All the groups were assessed for oral mucositis using WHO grading system at 7th, 14th, 21st, 28th, 35th day by the oncologist and results were tabulated for statistical analysis. Severity of oral mucositis reduced in zinc and improvised zinc group (p=0.096) when compared with controls with significant p value (0.037). Comparison of improvised zinc preparation (1%) group with only zinc group revealed that severity of overall mucositis though was not significant, was less in improvised zinc group with p value (0.029, 0.013) at 28 and 35 d respectively. Improvised zinc administration during radiation therapy was beneficial in reduction of oral mucositis during cancer treatment.

Sclerotium rolfsii lectin (SRL) exerts apoptotic effect against various cancer cells and an antitumor activity on mice with colon and breast cancer xenografts. The current study aimed to explore its exquisite carbohydrate specificity on human peripheral blood mononuclear cells (PBMCs) and leukemic T-cells. SRL, showed strong binding (>98%) to resting/activated PBMCs, leukemic Molt-4 and Jurkat cell lines. The glycans mediated binding to these cells was effectively blocked by mucin and fetuin, exhibiting 97% and 94% inhibition respectively. SRL showed mitogenic stimulation of PBMCs at 10 μg/ml as determined by thymidine incorporation assay. In contrast, lectin induced a dose dependent growth inhibition of Molt-4 cells with 58% inhibition at 25 μg/ml. Many common membrane receptors in activated PBMCs, Molt 4 and Jurkat cells were identified by lectin blotting. However, membrane receptors that are recognized by SRL in normal resting PBMCs were totally different and are high molecular weight glycoproteins. Treatment of membrane receptors with glycosidases prior to lectin probing, revealed that fucosylated Thomsen–Friedenreich(TF) antigen glycans are increasingly expressed on transformed Molt-4 leukemic cells compared to other cells. The findings highlight the opposite effects of SRL on transformed and normal hematopoietic cells by recognizing different glycan-receptors. SRL has promising potential for diagnostics and therapeutic applications in leukaemia.

Over the last two decades, an exponential growth in technologies and techniques available to biologists has provided mind-boggling quantities of data and led to information overload. Yet, answers to fundamental questions such as “how are we made?” and “what keeps us ticking?” remain incomplete. Developmental biology has provided elegant approaches to address such questions leading to enlightening insights. While several important contributions to developmental biology have come from India over the decades, this area of research remains nascent. Here, we review the journey in India, from the discovery of the ociad gene family to decoding its role in development and stem cells. We compare analysis in silico, in vivo and ex vivo, with developmental models such as Drosophila, mouse and stem cells that gave important insight into how these clinically significant genes function.

The purpose of this systematic review was to identify controlled trials evaluating the efficacy of contingency paradigm-based interventions to improve feeding, motor, or cognitive outcomes during the first year of life.Seventeen studies, including 10 randomized controlled trials, incorporating contingency paradigm-based interventions were identified. Three of 3 trials reported improvements in nutritive sucking using pacifier-activated lullaby in preterm infants before term age. Seven of 12 trials reported improvements in reaching, manual exploration, and kicking behaviors in term and preterm infants; and 6 of 10 trials reported gains in early cognition using sticky mittens and contingent toys.Contingency paradigm-based interventions can improve feeding outcomes in the neonatal intensive care unit in very preterm infants, and increase reaching, and perceptual-cognitive behaviors in term infants. Future research is needed to establish contingency paradigms as an effective early intervention strategy.This review synthesizes a body of literature on contingency paradigm-based interventions and highlights its potential paradigm-based interventions to improve developmental outcomes in infants.

OBJECTIVES Few researchers have evaluated whether school racial segregation, a key manifestation of structural racism, affects child health, despite its potential impacts on school quality, social networks, and stress from discrimination. We investigated whether school racial segregation affects Black children’s health and health behaviors. METHODS We estimated the association of school segregation with child health, leveraging a natural experiment in which school districts in recent years experienced increased school segregation. School segregation was operationalized as the Black-White dissimilarity index. We used ordinary least squares models as well as quasi-experimental instrumental variables analysis, which can reduce bias from unobserved confounders. Data from the Child Development Supplement of the Panel Study of Income Dynamics (1997–2014, n = 1248 Black children) were linked with district-level school segregation measures. Multivariable regressions were adjusted for individual-, neighborhood-, and district-level covariates. We also performed subgroup analyses by child sex and age. RESULTS In instrumental variables models, a one standard deviation increase in school segregation was associated with increased behavioral problems (2.53 points on a 27-point scale; 95% CI, 0.26 to 4.80), probability of having ever drunk alcohol (0.23; 95% CI, 0.049 to 0.42), and drinking at least monthly (0.20; 95% CI, 0.053 to 0.35). School segregation was more strongly associated with drinking behaviors among girls. CONCLUSIONS School segregation was associated with worse outcomes on several measures of well-being among Black children, which may contribute to health inequities across the life span. These results highlight the need to promote school racial integration and support Black youth attending segregated schools.

Background: Black men are more likely than Non-Hispanic White (NHW) men to be diagnosed with high-risk prostate cancer. We examined the extent to which social factors were associated with differences in prostate cancer risk profiles between Black men and NHW men [using a modification to the original D'Amico risk groups based on prostate specific antigen (PSA), Gleason score (GS), and TNM stage (stage)], based on individual and combined clinicopathologic characteristics. Methods: We conducted a cross-sectional population-based study of 23,555 Black men and 146,889 NHW men diagnosed with prostate cancer in the California Cancer Registry from 2004 to 2017. We conducted multivariable logistic regression to examine the association of year of diagnosis, block group-level neighborhood socioeconomic status (nSES), marital status, and insurance type on differences in prostate cancer risk profiles between Black and NHW men. Results: High PSA (>20 ng/mL), GS, stage, individually and combined prostate cancer risk profiles were more common among Black men versus NHW men. In fully adjusted models, relative to NHW men, we observed a persistent 67% increased odds of high PSA among Black men. nSES was the factor most strongly associated with racial disparity in high PSA, accounting for 25% of the difference. Marital status was the factor that was second most associated with a racial disparity. Conclusions: nSES was the factor most strongly associated with racial disparities in high PSA prostate cancer. Impact: The influence of nSES on racial disparities in PSA, GS, stage, and prostate cancer risk profiles warrants further consideration.

We present a case of a 12-day-old male baby who presented with right elbow deformity and inability to flex the elbow. Radiographs and computed tomography scan of the elbow revealed loss of humeroulnar alignment, superior migration of olecranon, and posteromedial displacement, suggesting an elbow dislocation. The child was successfully managed with open reduction and Kirschner wire fixation of the elbow joint. At 1-year follow-up, the child has a well-reduced and stable elbow joint with a functional range of movements.Congenital dislocation of the ulnohumeral joint can occur because of hypoplasia of the skeletal components or tissue interposition within the joint articulation.

Amongst the most common causes of death globally, stroke is one of top three affecting over 100 million people worldwide annually. There are two classes of stroke, namely ischemic stroke (due to impairment of blood supply, accounting for ~70% of all strokes) and hemorrhagic stroke (due to bleeding), both of which can result, if untreated, in permanently damaged brain tissue. The discovery that the affected brain tissue (i.e., ‘ischemic penumbra’) can be salvaged from permanent damage and the bourgeoning growth in computer aided diagnosis has led to major advances in stroke management. Abiding to the Preferred Reporting Items for Systematic Review and Meta–Analyses (PRISMA) guidelines, we have surveyed a total of 177 research papers published between 2010 and 2021 to highlight the current status and challenges faced by computer aided diagnosis (CAD), machine learning (ML) and deep learning (DL) based techniques for CT and MRI as prime modalities for stroke detection and lesion region segmentation. This work concludes by showcasing the current requirement of this domain, the preferred modality, and prospective research areas.

Coronavirus disease 2019 (COVID-19) patients may have varying degrees of hyperlipasemia. The aim was to compare outcomes among different levels of hyperlipasemia in patients with COVID-19.This is a retrospective study examining outcomes among hospitalized COVID-19 patients with a lipase3× upper limit of normal (ULN), asymptomatic hyperlipasemia (3× ULN), secondary pancreatitis (typical respiratory COVID-19 symptoms and found to have pancreatitis), and primary pancreatitis (presenting with pancreatitis).Of 11,883 patients admitted with COVID-19, 1560 patients were included: 1155 patients had normal serum lipase (control group), 270 had elevated lipase3× ULN, 46 patients had asymptomatic hyperlipasemia with lipase3× ULN, 57 patients had secondary pancreatitis, and 32 patients had primary pancreatitis. On adjusted multivariate analysis, the elevated lipase3× ULN and asymptomatic hyperlipasemia groups had worse outcomes with higher mortality (odds ratio [OR], 1.6 [95% confidence interval [CI], 1.2-2.2) and 1.1 [95% CI, 0.5-2.3], respectively), higher need for mechanical ventilation (OR, 2.8 [95% CI, 1.2-2.1] and 2.8 [95% CI, 1.5-5.2], respectively), and longer length of stay (OR, 1.5 [95% CI, 1.1-2.0] and 3.16 [95% CI, 1.5-6.5], respectively).Patients with COVID-19 with elevated lipase3× ULN and asymptomatic hyperlipasemia have generally worse outcomes than those with pancreatitis.

Drug delivery vehicles have made a great impact on cancer immunotherapies in clinics and pre-clinical research. Notably, the science of delivery of cancer vaccines and immunotherapeutics, modulating immune cell functions has inspired development of several successful companies and clinical products. Interestingly, these drug delivery modalities not only modulate the function of immune cells (often quantified at the mRNA and protein levels), but also modulate the metabolism of these cells. Specifically, cancer immunotherapy often leads to activation of different immune cells such as dendritic cells, macrophages and T cells, which is driven by energy metabolism of these cells. Recently, there has been a great excitement about interventions that can directly modulate the energy metabolism of these immune cells and thus affect their function and in turn lead to a robust cancer immune response. Here we review few strategies that have been tested in clinic and pre-clinical research for generating effective metabolism-associated cancer therapies and immunotherapies.

MINimal fluorescence photon FLUXes (MINFLUX) nanoscopy, providing photon-efficient fluorophore localizations, has brought about three-dimensional resolution at nanometer scales. However, by using an intrinsic on-off switching process for single fluorophore separation, initial MINFLUX implementations have been limited to two color channels. Here we show that MINFLUX can be effectively combined with sequentially multiplexed DNA-based labeling (DNA-PAINT), expanding MINFLUX nanoscopy to multiple molecular targets. Our method is exemplified with three-color recordings of mitochondria in human cells.