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Abstract Twin girls born at 30 weeks' gestation with spinal muscular atrophy (SMA) received onsasemnogene‐abeparvovec (OA) at 3.5 weeks of life. They had no treatment‐related adverse events, normal acquisition of motor milestones, and normal neurological examination at 19 months. Genotyping revealed 0 copies of SMN1 and a single, hybrid SMN2 gene containing the positive genetic modifier c.835‐44A>G. This was associated with full‐length SMN2 blood mRNA expression levels similar to a 2 copy SMA infant. The observed favorable outcomes are likely due to the genetic modifier combined with early drug administration enabled by prematurity.

Statement of the Problem: It is essential to address caries risk at an early stage for the prevention of dental caries. Mobile application CaRisk is designed in a particular way to self-assess the dental caries risk by the individual’s themselves.Purpose: The current study aimed to assess the dental caries risk among age groups 5-6 and 35-44 using self-assessment caries risk mobile application CaRisk and compare it with the deft and DMFT values.Materials and Method: This cross-sectional study was conducted in Chennai, India; to evaluate the risk of dental caries in children aged 5 to 6 and adults aged 35 to 44. The scores of the mobile application CaRisk and the decayed- extracted- filled teeth (deft)/ decayed-missing-filled-teeth (DMFT) caries risk assessment were evaluated. Descriptive statistics were performed. The risk category was determined by frequency. Chi-square analysis was done to determine whether the DMFT scores and the CaRisk mobile app were associated. The correlation was performed between the CaRisk mobile application and DMFT scores.Results: Association was found between the caries risk assessment score of the mobile application CaRisk and the DMFT and deft scores of the adults and children for both the age groups 5-6 and 35-44 years respectively and it indicates that it was found to be statistically significant. Pearson’s correlation was performed to assess the strength of association and R-values obtained for the age group 5-6 and 35-44 years respectively, which was statistically significant (0.892 and 0.840).Conclusion: This CaRisk mobile application scores correlate with the deft and DMFT scores and it is an effective self-diagnosis tool for assessing dental caries risk assessment. Further, it is suggested that the mobile application CaRisk should be tested among a huge population.

We hypothesize that in silico structural biology approaches can discover novel drug binding sites for RNA-dependent-RNA-polymerases (RdRp) of positive sense single-strand RNA (ss(+)RNA) virus species. RdRps have a structurally conserved active site with seven motifs (A to G), despite low sequence similarity. We refined this architecture further to describe a conserved structural domain consisting of motifs A, B, C and F. These motifs were used to realign 24 RdRp structures in an innovative manner to search for novel drug binding sites. The aligned motifs from the enzymes were then docked with 833 FDA-approved drugs (Set 1) and 85 FDA-approved antivirals (Set 2) using the Molecular Operating Environment (MOE) docking 2020.09 software. Sirolimus (rapamycin), an immunosuppressant that targets the mammalian mTOR pathway, was one of the top ten drugs for all 24 RdRp proteins. The sirolimus docking site was in the nucleotide triphosphate entry tunnel between motifs A and F but distinct from the active site in motif C. This original finding supports our hypothesis that structural biology approaches based on RdRp motifs that are conserved across evolution can define new drug binding locations and infer potential broad-spectrum inhibitors for SARS-CoV-2 and other ss(+)RNA viruses.

This is a case of locally recurrent invasive secretory carcinoma of the breast during pregnancy, detected as a palpable mass in the reconstructed right breast of a 32-year-old female at 24 weeks gestation. The patient was initially diagnosed with secretory carcinoma 8 years prior, for which she underwent nipple sparing mastectomy followed by adjuvant chemotherapy and endocrine therapy. Due to pregnancy, the recurrence was treated initially with conservative excision alone, followed by definitive management postpartum which included wide local excision, sentinel lymph node biopsy and adjuvant chest wall radiation. Secretory carcinoma of the breast is a rare cancer with a predilection for young age and indolent course. This case report describes an unusual case of recurrent secretory carcinoma, of interest due to both its diagnosis during pregnancy, and its recurrence after nipple sparing mastectomy.

Background Infectious exacerbations are crucial events that dictate the natural course of COPD patients. Pneumococcal vaccination has been shown to decrease incidence of community-acquired pneumonia in COPD patients. There is a paucity of data on outcomes of hospitalisation in pneumococcal-vaccinated COPD patients in comparison with unvaccinated subjects. The objectives of the present study were to evaluate the difference in hospitalisation outcomes in pneumococcal-vaccinated versus -unvaccinated COPD subjects hospitalised with acute exacerbation. Methods This was a prospective analytical study on 120 subjects hospitalised with acute COPD exacerbation. 60 patients with prior pneumococcal vaccination and 60 unvaccinated patients were recruited. Outcomes of hospitalisation such as mortality rate, need for assisted ventilation, length of hospital stay, need for intensive care unit (ICU) care and length of ICU stay were collected and compared between two groups with appropriate statistical tools. Results 60% of unvaccinated patients (36 out of 60) required assisted ventilation, whereas only 43.3% of vaccinated subjects (26 out of 60) needed assisted ventilation (p-value of 0.04). Most of the secondary outcomes were better in the vaccinated group. The mean±SD length of ICU stay in the vaccinated group was 0.67±1.11 days compared to 1.77±1.89 days in the unvaccinated group. The mean±SD length of hospital stay was 4.50±1.64 days and 5.47±2.03 days in the vaccinated and unvaccinated group, respectively (p-value of 0.005). Conclusions COPD patients who have received prior pneumococcal vaccination have better outcomes when they are hospitalised for an acute exacerbation. Pneumococcal vaccination may be recommended for all patients with COPD who are at risk of hospitalisation with acute exacerbation.

Omental infarction is caused by vascular obstruction with resulting tissue ischemia, representing a rare cause of abdominal pain. It has been described as a rare complication of gastric bypass. It is important to recognize omental infarction and its possible complications as The management is usually conservative with surgery deferred to specific cases. We present the case of a 56-year-old male with a history of gastric adenocarcinoma who underwent esophagogastrectomy with Roux-n-y reconstruction and 3 months later presented with severe persistent abdominal pain, due to a path proven giant omental infarction. Patient later was complicated with a colonic fistula to the omentum.

Background: Coronavirus disease 2019 (COVID-19) has made its presence felt as the worst pandemic witnessed till date in the 21st century. The mortality and morbidity associated with COVID-19 does not end with the acute pneumonia and respiratory failure and consequences extend well into the subsequent weeks to months in a minority. After recovery from severe disease, symptoms, lung function abnormalities and radiological changes are known to persist for varying length of time in a small proportion of patients. Various studies report different incidences of lung function abnormalities post-COVID-19. The present study describes the occurrence, severity, pattern and risk factors for persistent lung function abnormalities post-COVID-19 patients. Aim: The present study was aimed to find out the occurrence of persistent lung function abnormalities in patients hospitalised with COVID-19 at three months of discharge who had normal previous lung function prior to COVID-19. In those with persisting abnormal lung function, the severity, pattern and risk factors for persistent lung function abnormalities were also studied. Methods: The present study was a retrospective study in patients hospitalised with COVID-19 who had radiological evidence of pneumonia at admission. Patients with prior abnormal lung function were excluded from the study. Lung function was analysed with spirometry, 6-min walk test and diffusion capacity between day 85 and 95 of hospital discharge and the occurrence, severity and pattern of impairment was described. Lung function impairment was correlated with baseline characteristics and univariate regression analysis was done to identify risk factors for persisting functional impairment. Results: 39 patients were included in the study. Spirometry at follow up showed a restrictive ventilatory defect in 26 out of 39 patients (64%) and a normal study was noted in 12 patients. One patient had an obstructive ventilatory defect. Diffusion impairment was present in 27 patients and normal transfer factor was seen in 12 patients. The degree of diffusion impairment was mild in 16 patients and moderate in 11 patients. Univariate regression analysis revealed that age, history of systemic hypertension, severe hypoxia at presentation, and extent of lung involvement by CT chest were associated with lung function impairment. Conclusion: Almost two-thirds of patients hospitalised with COVID-19 pneumonia have persistent lung function abnormalities at three months post-discharge. Advanced age, severe disease and medical comorbidities increase the risk of persistent functional abnormalities.

Abstract Background Matching is one commonly utilized method in quasi-experimental designs involving individuals with neurodevelopmental disorders (NDD). This method ensures two or more groups (e.g., individuals with an NDD versus neurotypical individuals) are balanced on pre-existing covariates (e.g., IQ), enabling researchers to interpret performance on outcome measures as being attributed to group membership. While much attention has been paid to the statistical criteria of how to assess whether groups are well-matched, relatively little attention has been given to a crucial prior step: the selection of the individuals that are included in matched groups. The selection of individuals is often an undocumented process, which can invite unintentional, arbitrary, and biased decision-making. Limited documentation can result in findings that have limited reproducibility and replicability and thereby have poor potential for generalization to the broader population. Especially given the heterogeneity of individuals with NDDs, interpretation of research findings depends on minimizing bias at all stages of data collection and analysis. Results In the spirit of open science, this tutorial demonstrates how a workflow can be used to provide a transparent, reproducible, and replicable process to select individuals for matched groups. Our workflow includes the following key steps: Assess data, Select covariates, Conduct matching, and Diagnose matching. Our sample dataset is from children with autism spectrum disorder (ASD; n = 25) and typically developing children (n = 43) but can be adapted to comparisons of any two groups in quasi-experimental designs. We work through this method to conduct and document matching using propensity scores implemented with the R package MatchIt. Data and code are publicly available, and a template for this workflow is provided in the Additional file 1 as well as on a public repository. Conclusions It is important to provide clear documentation regarding the selection process to establish matched groups. This documentation ensures better transparency in participant selection and data analysis in NDD research. We hope the adoption of such a workflow will ultimately advance our ability to replicate findings and help improve the lives of individuals with NDDs.

The COVID-19 pandemic originating in the Wuhan province of China in late 2019 has impacted global health, causing increased mortality among elderly patients and individuals with comorbid conditions. During the passage of the virus through affected populations, it has undergone mutations, some of which have recently been linked with increased viral load and prognostic complexities. Several of these variants are point mutations that are difficult to diagnose using the gold standard quantitative real-time PCR (qRT-PCR) method and necessitates widespread sequencing which is expensive, has long turn-around times, and requires high viral load for calling mutations accurately. Here, we repurpose the high specificity of Francisella novicida Cas9 (FnCas9) to identify mismatches in the target for developing a lateral flow assay that can be successfully adapted for the simultaneous detection of SARS-CoV-2 infection as well as for detecting point mutations in the sequence of the virus obtained from patient samples. We report the detection of the S gene mutation N501Y (present across multiple variant lineages of SARS-CoV-2) within an hour using lateral flow paper strip chemistry. The results were corroborated using deep sequencing on multiple wild-type (n = 37) and mutant (n = 22) virus infected patient samples with a sensitivity of 87% and specificity of 97%. The design principle can be rapidly adapted for other mutations (as shown also for E484K and T716I) highlighting the advantages of quick optimization and roll-out of CRISPR diagnostics (CRISPRDx) for disease surveillance even beyond COVID-19. This study was funded by Council for Scientific and Industrial Research, India.

This paper describes indigenously developed digital Gothic arch tracer for the acquisition of centric jaw relation in patient. The developed tracer eliminates disadvantages of intra-oral tracing and makes it more suitable for recording centric relation in patients. The system also makes real-time monitoring of tracing possible in intraoral tracing. This also opens various avenues for research in removable prosthodontics.

Background. Explantation of native viscera in multivisceral transplant candidates, particularly in those with extensive portomesenteric thrombosis (PMT), carries considerable morbidity due to extensive vascularized adhesions. Preemptive visceral angioembolization has been previously described as a technique to minimize excessive blood loss during mobilization of the native viscera but is not well described specifically in patients with extensive PMT. Methods. In a series of 5 patients who underwent mutivisceral transplant for PMT from June 2015 to November 2018, we performed preoperative superior mesenteric, splenic, and hepatic artery embolization to reduce blood loss during explanation and evaluated the blood loss and blood product utilization, as well as 30-day rates of infectious complications. Results. Following preemptive embolization, median total blood loss was 6000 mL (range 800–7000 mL). The median transfusion requirements were as follows: 16 units packed red blood cells (range 2–47), 14 units fresh frozen plasma (range 0–29), 2 units cryoprecipitate (range 1–14), 4 units platelets (range 2–10), and 500 mL cell saver autotransfusion (range 0–1817). In the first 30 postoperative days, 2 out of 5 patients developed positive blood cultures and 3 out of 5 developed complex intra-abdominal infections. Two patients developed severe graft pancreatitis resulting in mycotic aneurysm of the aortic conduit; bleeding from the aneurysm led to 1 patient mortality. Conclusions. Preoperative embolization is an effective modality to mitigate exsanguinating blood loss during multivisceral transplant in patients with portomesenteric thrombosis; however, it is unclear if the resultant native organ ischemia during explant carries clinically relevant consequences.

An autonomous household robot passed a self-awareness test in 2015, proving that the cognitive capabilities of robots are heading towards those of humans. While this is a milestone in AI, it raises questions about legal implications. If robots are progressively developing cognition, it is important to discuss whether they are entitled to justice pursuant to conventional notions of human rights. This paper offers a comprehensive discussion of this complex question through cross-disciplinary scholarly sources from computer science, ethics, and law. The computer science perspective dissects hardware and software of robots to unveil whether human behavior can be efficiently replicated. The ethics perspective utilizes insights from robot ethics scholars to help decide whether robots can act morally enough to be endowed with human rights. The legal perspective provides an in-depth discussion of human rights with an emphasis on eligibility. The article concludes with recommendations including open research issues.

Background. Donor-derived malignancy is a rare complication in patients who undergo organ transplant. Approaches to treatment have largely been individualized based on clinical circumstances given the lack of evidence-based guidelines, with therapeutic options ranging from discontinuation of immunosuppression and transplantectomy to the addition of chemotherapy or radiotherapy. Case Presentation. Herein, we describe a 60-year-old woman with metastatic donor-derived upper tract urothelial carcinoma (UTUC) discovered nine years postrenal transplant. Molecular diagnostic studies using polymerase chain reaction amplification of short tandem repeat alleles and HLA tissue typing proved that the urothelial carcinoma originated from donor tissue. She achieved sustained complete remission with transplant nephroureterectomy, retroperitoneal lymphadenectomy, immunosuppression withdrawal, and immunotherapy with pembrolizumab. Routine radiologic surveillance has demonstrated 15-month progression-free survival to date off pembrolizumab, and she is now under consideration for retransplantation. Conclusions. Immunotherapy using checkpoint inhibitors can serve as a novel treatment option for patients in the clinical predicament of having a solid organ transplant and simultaneous metastatic malignancy. In this report, we also discuss the oncogenic potential of BK virus, the use of checkpoint inhibitors in urothelial carcinoma, and the feasibility of retransplant for this patient population.

Restrictive dermopathy is a rare entity that is fatal in the neonatal period itself. The rigidity of the skin leads to erosions, contractures, and restriction of respiratory movements. Diagnosis is often made clinically with classical features such as low-set ears, micrognathia, small, and persistently open fixed “o”-shaped mouth, translucent, shiny, rigid skin with prominent superficial blood vessels, and pseudocontractures of limb joints. We report two cases of restrictive dermopathy observed in our center within 2 years period and suggest that this condition may not be as rare as believed.

In industries, components must operate under extreme conditions such as high load, speed, temperature and chemical environment. Materials are selected according to commercial availability, cost and their properties such as strength, hardness, etc. AISI 904L is a high-alloy stainless steel with low carbon content, poor surface hardness and wear characteristics. Many engineering failures are caused by fatigue, corrosion, and poor wear resistance, begins at the surface level. This causes cracks in the surface, reducing the material’s life. The surfaces of the materials were subjected to severe thermal, chemical, and shock loads. The selected AISI 904L materials for this work were subjected to gas nitriding process and processed with 3 different time parameters such as 12 hours, 18 hours and 24 hours respectively and named as GN1, GN2 and GN3. The treatments were done at a constant temperature of 650°C. Gas nitriding, in comparison to other nitriding processes such as plasma and liquid nitriding, provides good dimensional stability, reduced deformation, and uniform case depth regardless of the size and shape of the specimen. To analyze the wear properties, a pin on a disc machine is used. Finally, metallographic studies were performed by scanning electron microscopy.

The Duplex stainless steel AISI 2205 is well known for its corrosion resistance, applicable to high pitting and stress resistance. Cryogenic treatment is chosen to boost the mechanical properties of AISI 2205 Stainless Steel. The specimens undergo cryogenic treatment, one of them being treated to the saturated limit. For comparison purpose, one specimen is kept as untreated. Wear test will be conducted at a constant speed and variable load by a pin on disc wear testing apparatus. Wear test is completed to assess the capability of utilizing a specific surface building innovation to diminish wear for a particular application and to research the impact of treatment conditions on the wear execution, so upgraded surface treatment conditions can be figured it out. Eventually, all specimens were undergone with Scanning Electron Microscope analysis.

Within the context of major medical education curricular reform ongoing in the United States, a subset of schools has re-initiated accelerated (3-year) medical education. It would be helpful for education leaders to pause and consider historical reasons such accelerated medical schools were started, and then abandoned, over the last century to proactively address important issues. As no comprehensive historical review of 3-year medical education exists, we examined all articles published on this topic since 1900. In general, US medical educational curricula began standardizing into 4-year programs in the early 1900s through contributions from William Osler, Abraham Flexner, and establishment of the American Medical Association (AMA) Council of Medical Education (CME). During WWII (1939–1945), accelerated 3-year medical school programs were initiated as a novel approach to address physician shortages; government incentives were used to boost the number of 3-year medical schools along with changed laws aiding licensure for graduates. However, this quick solution generated questions regarding physician competency, resulting in rallying cries for oversight of 3-year programs. Expansion of 3-year MD programs slowed from 1950s to 1960s until federal legislation was passed between the 1960s and the 1970s to support training healthcare workers. With renewed government financial incentives and stated desire to increase physician numbers and reduce student debt, a second rapid expansion of 3-year medical programs occurred in the 1970s. Later that decade, a second decline occurred in these programs, reportedly due to discontinuation of government funding, declining physician shortage, and dissatisfaction expressed by students and faculty. The current wave of 3-year MD programs, beginning in 2010, represents a ‘third wave’ for these programs. In this article, we identify common societal and pedagogical themes from historical experiences with accelerated medical education. These findings should provide today’s medical education leaders a historical context from which to design and optimize accelerated medical education curricula.

Background and Aims: Post-operative nausea and vomiting (PONV) has an 80% incidence in high-risk patients. This is despite the availability of several antiemetic drugs. Selective 5-hydroxytryptamine type 3 (5-HT 3 ) receptor antagonists are considered first-line for prophylaxis, ondansetron being the most commonly used agent. Ramosetron, another selective 5-HT 3 receptor antagonist, is more potent and longer acting than ondansetron. This study was conducted to evaluate the antiemetic efficacy of ramosetron in comparison with ondansetron in patients at a high risk of PONV. Methods: This was a prospective randomised double-blind study carried out over a 6-month period in which 206 patients with at least two risk factors for PONV were randomised to receive ramosetron 0.3 mg or ondansetron 8 mg, 30 min before the end of surgery. The incidence of PONV, severity of nausea and need for rescue antiemetic were recorded over the next 24 h. Primary outcome was the incidence of PONV. Secondary outcomes included severity of nausea and need for rescue. The data were analysed using the Predictive Analytics Software (PASW, version 18: Chicago, IL, USA). Results: The incidence of PONV was found to be 35% in the ramosetron group as opposed to 43.7% in the ondansetron group (P = 0.199). Need for rescue antiemetic was 23.3% in the ramosetron group and 32% in the ondansetron group (P = 0.156) in the 24 h following surgery. Conclusion: Ramosetron 0.3 mg and ondansetron 8 mg were equally effective in reducing the incidence of PONV in high risk patients.

Complex intercellular interaction is a common theme in plant-pathogen/symbiont relationship. Cellular physiology of both the partners is affected by abiotic stress. However, little is known about the degree of protection each offers to the other from different types of environmental stress. Our current study focused on the changes in response to toxic arsenic in the presence of an endophytic fungus Piriformospora indica that colonizes the paddy roots. The primary impact of arsenic was observed in the form of hyper-colonization of fungus in the host root and resulted in the recovery of its overall biomass, root damage, and chlorophyll due to arsenic toxicity. Further, fungal colonization leads to balance the redox status of the cell by adjusting the antioxidative enzyme system which in turn protects photosynthetic machinery of the plant from arsenic stress. We observed that fungus has ability to immobilize soluble arsenic and interestingly, it was also observed that fungal colonization restricts most of arsenic in the colonized root while a small fraction of it translocated to shoot of colonized plants. Our study suggests that P. indica protects the paddy (Oryza sativa) from arsenic toxicity by three different mechanisms viz. reducing the availability of free arsenic in the plant environment, bio-transformation of the toxic arsenic salts into insoluble particulate matter and modulating the antioxidative system of the host cell.

Background: Dentin hypersensitivity is a recurrent condition causing discomfort and sometimes pain to the patient, which also deters him from maintaining adequate oral hygiene. Home care and office measures are used for treatment of this malady. Aim: To evaluate and compare the efficacy of 2 treatment modalities for dentinal hypersensitivity, iontophoresis with acidulated phosphate gel (APF) gel, and dentin-bonding agent application. Materials and Methods: This split mouth randomized clinical study recruited subjects with a history of hypersensitivity with at least 2 teeth, verified by a light stroke with a dental explorer along the cervical third of the teeth. The patients were subjected to a 1-s air blast and cold water stimuli and their responses were recorded on a verbal rating scale. A total of 30 sites from 15 patients were divided into Group A-1.23% APF gel iontophoresis; and Group B-aqueous solution of hydroxyl-ethyl-methacrylate and glutaraldehyde. The teeth were evaluated immediately after the treatment and at the end of 2 weeks. In case of failure, the tooth was retreated with the same agent as before. Results: The results were statistically analyzed using Kruskal-Wallis analysis of variance and Mann-Whitney U tests. There was no statistically significant difference between the groups at the end of 2 weeks. However, Group A was more effective clinically, with fewer number of failures compared with Group B. Conclusion: Both the agents showed a statistically significant reduction in sensitivity compared with baseline; however, APF gel iontophoresis was more effective in reducing hypersensitivity over a longer time period.

Background: At 60 seconds, 2xED95 dose (0.6mg/kg) of rocuronium is frequently used for intubation. Some studies suggest 3XED95 (0.9mg/kg body weight) dose in achieving excellent intubating conditions. In this context, present study aimed at comparing intubating conditions with these two doses of rocuronium, using clinical criteria by cooper’s score; assisted with adductor pollicis T.O.F response. Materials and Methods: Present prospective randomized comparative clinical study was conducted on 60 patients subjected for general anaesthesia. Induction was done with fentanyl (1mcg/kg body weight) and propofol (2mg/kg body weight) and relaxation achieved with Rocuronium 0.6 mg/kg (Group A-30 cases); 0.9mg/kg (Group B- 30 cases). (n=30) intubation was done at 60 seconds. Intubating conditions were assessed clinically by cooper’s score.T.O.F responses of AP by visual and tactile means. Results: Intubating conditions clinically were excellent in 16 cases (53%), good in 12 cases (40%), and fair in 2 cases (7%) respectively in Group-A. In group-B excellent in 29 cases (97%) and good in 1case (3%). In group A in no case TOF-0 achieved. TOF 1, 2, 3, and 4 were observed in 1 case (3%), 7 cases (23%) 16 cases (54%) and 6 cases (20%) respectively. Whereas in group B, TOF 0, 1, 2, 3 were observed in 18 cases (61%), 4 cases (13%), 7 cases (23%) and 1 case (3%). In no case TOF-4 observed. Chi square test (p

We report a case of a forty-five year old male who was admitted fifteen days prior with biliary pancreatitis. He developed pulmonary thromboembolism (PTE) after uneventful laparoscopic cholecystec-tomy. He was initially treated with intravenous (IV) heparin and inferior vena cava (IVC) filter. Later on he underwent emergency pulmonary embolectomy due to haemodynamic deterioration. There is less incidence of PTE after laparoscopic cholecystectomy, but it becomes high-risk for postoperative thromboembolic complications when it is associated with other risk factors. The purpose of this report is to highlight that preoperative detection of risk factors and thromboprophylaxis in indicated cases can prevent this complication. We also review the incidence of PTE, risk factors and thromboprophylaxis.