Appearance and Prevalence of JN.1 SARS-CoV-2 Variant in India and Its Clinical Profile in the State of Maharashtra.

BACKGROUND: In August 2023, the BA.2.86 SARS-CoV-2 variant, with over 30 spike protein mutations, emerged amidst the global dominance of XBB sub-lineages. It evolved into JN.1 by late 2023, spreading across 71 countries. JN.1, distinct for its L455S mutation, significantly dominated global sequences, raising concerns over its transmission and clinical impact. The study investigates JN.1's clinical severity and its effect on hospital admissions in Maharashtra, India. METHODOLOGY: The present study involved 3,150 curated Indian SARS-CoV-2 whole genome sequences with collection dates between 1st August 2023 and 15th January 2024. Lineage and phylogenetic analysis of sequences was performed using Nextclade. Telephonic interviews were conducted to confirm the demographic details and obtain clinical information on the JN.1* (* indicates JN.1 and all its sub-lineages) cases. The obtained data were recorded and analyzed using Microsoft® Excel (Microsoft Corporation, Redmond, WA). RESULTS: Out of 3,150 sequences analyzed, JN.1* was the most common lineage (2377/3150, 75.46%), followed by XBB.2.3* (281/3150, 8.92%) and XBB.1.16* (187/3150, 5.94%). In India, it was first identified on 6th October 2023, in Kerala. The highest proportion of JN.1* sequences originated from Maharashtra (628/2377, 26.42%), followed by West Bengal (320/2377, 13.46%), Andhra Pradesh (293/2377, 12.33%), Kerala (288/2377, 12.12%), and Karnataka (285/2377, 11.99%). In Maharashtra, the JN.1* variant was first identified on 23rd November 2023. A total of 279 JN.1* cases were included in the clinical study. Of these, 95.34% (266/279) had symptomatic disease with mild symptoms; cold (187/279, 67.03%) being the most common symptom, followed by fever (156/279, 55.91%), cough (114/279, 40.86%), and headache (28/279, 15.64%). Of all the cases, 13.26% (37/279) required institutional quarantine or hospitalization, and the rest were isolated at home. Among the hospitalized patients, 54.05% (20/37) cases were given conservative treatment while 45.95% (17/37) cases required supplemental oxygen therapy. Regarding the vaccination status, 94.26% (263/279) of cases received at least one dose of the COVID-19 vaccine, while 5.02% (14/279) were not vaccinated, of which most were children aged zero to nine years (5/14, 35.71%). The overall recovery rate among JN.1* cases was 98.57% (275/279), with 1.43% (4/279) cases succumbing to the disease. CONCLUSION: The JN.1* variant, the dominant variant in India, exhibits clinical features similar to previous circulating variants in Maharashtra without increased severity. Its notable transmissibility underscores the importance of studying the ongoing viral evolution. The pressing necessity for swift identification and the clinical features of new variants is essential for effective public health response.

The Burden and Characteristics of Post-COVID-19 Conditions Among Laboratory-Confirmed Delta and Omicron COVID-19 Cases: A Preliminary Study From Maharashtra, India.

BACKGROUND: Post-COVID-19 conditions (PCC) have emerged as a significant global health concern due to their potential impact on patients' quality of life and healthcare resources. The present study aims to understand the burden and characteristics of PCC in Maharashtra, India, and compares its prevalence among cases infected with Delta and Omicron variants. MATERIAL AND METHODS: A retrospective observational study included 617 laboratory-confirmed Delta and Omicron variant cases. These cases were telephonically followed up to document persistent COVID-19 symptoms using a questionnaire based on the Post-COVID-19 Clinical Form from the Global COVID-19 Clinical Platform of the World Health Organization (WHO), and the results were analyzed. RESULTS: Out of 617 laboratory-confirmed COVID-19 cases, 82.97% and 17.03% were Omicron and Delta cases, respectively. The mean follow-up period for Delta and Omicron cases was 78.05 and 21.56 weeks, respectively. A total of 40 (6.48%) cases reported persistent symptoms at follow-up, with a higher prevalence among those infected with the Delta variant (12.38%) compared to the Omicron variant (5.27%). The most common long COVID symptoms reported were malaise (25%), dyspnea (20%), post-exertional fatigue (17.5%), joint pain (15%), and frequent episodes of cough and cold (15%). Additionally, 1.94% of participants developed a new medical condition following COVID-19 infection, most commonly hypertension (25%), lung fibrosis (16.67%), and asthma (8.33%). Factors such as more than five acute symptoms, a moderate to severe disease, the need for hospitalization, and hospitalization for more than five days were significantly associated with PCC. CONCLUSION: Long COVID results in extended disability and illness. The varying impacts of different COVID-19 variants highlight the complex nature of post-COVID-19 complications. Our findings highlight the need for strategic planning of healthcare resources to ensure optimal response and preparedness to manage the burden of PCC.

Chasing SARS-CoV-2 XBB.1.16 Recombinant Lineage in India and the Clinical Profile of XBB.1.16 Cases in Maharashtra, India.

Background SARS-CoV-2 has evolved rapidly, resulting in the emergence of lineages with a competitive advantage over one another. Co-infections with different SARS-CoV-2 lineages can give rise to recombinant lineages. To date, the XBB lineage is the most widespread recombinant lineage worldwide, with the recently named XBB.1.16 lineage causing a surge in the number of COVID-19 cases in India. Methodology The present study involved retrieval of SARS-CoV-2 genome sequences from India (between December 1, 2022 and April 8, 2023) through GISAID; sequences were curated, followed by lineage and phylogenetic analysis. Demographic and clinical data from Maharashtra, India were collected telephonically, recorded in Microsoft® Excel, and analyzed using IBM® SPSS statistics, version 29.0.0.0 (241). Results A total of 2,944 sequences were downloaded from the GISAID database, of which 2,856 were included in the study following data curation. The sequences from India were dominated by the XBB.1.16* lineage (36.17%) followed by XBB.2.3* (12.11%) and XBB.1.5* (10.36%). Of the 2,856 cases, 693 were from Maharashtra; 386 of these were included in the clinical study. The clinical features of COVID-19 cases with XBB.1.16* infection (XBB.1.16* cases, 276 in number) showed that 92% of those had a symptomatic disease, with fever (67%), cough (42%), rhinorrhea (33.7%), body ache (14.5%) and fatigue (14.1%) being the most common symptoms. The presence of comorbidity was found in 17.7% of the XBB.1.16* cases. Among the XBB.1.16* cases, 91.7% were vaccinated with at least one dose of vaccine against COVID-19. While 74.3% of XBB.1.16* cases were home-isolated; 25.7% needed hospitalization/institutional quarantine, of these, 33.8% needed oxygen therapy. Out of 276 XBB.1.16* cases, seven (2.5%) cases succumbed to the disease. The majority of XBB.1.16* cases who died belonged to an elderly age group (60 years and above), had underlying comorbid condition/s, and needed supplemental oxygen therapy. The clinical features of COVID-19 cases infected with other co-circulating Omicron variants were similar to XBB.1.16* cases. Conclusion The study reveals that XBB.1.16* lineage has become the most predominant SARS-CoV-2 lineage in India. The study also shows that the clinical features and outcome of XBB.1.16* cases were similar to those of other co-circulating Omicron lineage infected cases in Maharashtra, India.

Vaxi-DL: An Artificial Intelligence-Enabled Platform for Vaccine Development.

Vaccine development is a complex and long process. It involves several steps, including computational studies, experimental analyses, animal model system studies, and clinical trials. This process can be accelerated by using in silico antigen screening to identify potential vaccine candidates. In this chapter, we describe a deep learning-based technique which utilizes 18 biological and 9154 physicochemical properties of proteins for finding potential vaccine candidates. Using this technique, a new web-based system, named Vaxi-DL, was developed which helped in finding new vaccine candidates from bacteria, protozoa, viruses, and fungi. Vaxi-DL is available at: https://vac.kamalrawal.in/vaxidl/ .

Teledentistry: Evaluation of Instagram posts related to bruxism.

BACKGROUND: Instagram statistic has attracted roughly one billion, monthly active users. In 2021, Instagram belonged to the most popular social networks worldwide. It has been considered an effective tool that contributes to the contemporary sharing of information for raising public awareness while providing educational information. The growing presence of Instagram and frequent user engagement has made it a potentially effective platform for patient communication, seeking educational information, product information for consumers, and advertisements in the form of images and videos. OBJECTIVE: To assess and compare the contents of Instagram posts by healthcare professionals (HP) and non-professional healthcare workers (NPHW) on bruxism and to assess public engagement with this content. METHODS: Twelve "hashtag" terms linked to bruxism were searched. HP and NPHW analyzed the content of relevant posts for the presence of domains. Discourse analysis assessed the post quality for themes. We conducted the descriptive and univariate statistical analysis, whereas inter-rater reliability was tested using Cohen's kappa. RESULTS: A total of 1184 posts were retrieved, with the majority uploaded by NPHW (622 posts). The posts by HPs were in text and image(s) format (53%) with the range of 25-1100 Instagram post "Likes." "Mouthguard" (90) % was the most frequently included domain posted by HP, followed by "treatment plan/pain management", and complaints of clicking or locking of TMJ" (84%). Greater number of domains (p= 0.03) were seen in the posts by NPHWs, compared to HP's having more bruxism-related content. The inter-rater reliability method (0.89) was used for the presence of domains. CONCLUSION: NPHW uses Instagram more frequently to post bruxism-related information than HP. HPs must ascertain that the content posted by NPHW is relevant and the concerns addressed in posts are to the purpose.

Clinical Characteristics and Outcomes of Laboratory-Confirmed SARS-CoV-2 Cases Infected With Omicron Subvariants and the XBB Recombinant Variant.

Background SARS-CoV-2 has evolved to produce new variants causing successive waves of infection. Currently, six variants are being monitored by the World Health Organization that are replacing BA.5. These include BF.7 (BA.5 + R346T in spike), BQ.1 (and BQ.1.1, with BA.5 + R346T, K444T, N460K mutations in spike), BA.2.75 (including BA.2.75.2 and CH.1.1), and XBB (including XBB.1.5). BQ.1 and XBB variants are more immune evasive and have spread quickly throughout the world. Concerning the potential severity of infections caused by these variants, the present study describes the clinical characteristics and outcomes of these major variants in Maharashtra. Methodology A total of 1,141 reverse transcriptase-polymerase chain reaction (RT-PCR)-positive SARS-CoV-2 samples, with a cycle threshold (Ct) value of less than 25, were processed for SARS-CoV-2 whole genome sequencing between July 10, 2022, and January 12, 2023. All corresponding demographic and clinical data were recorded and analyzed using Microsoft® Excel and Epi Info™. Results Out of the 1,141 samples sequenced, BA.2.75* (63.78%) was the predominant Omicron variant, followed by the XBB* (18.88%), BA.2.38* (4.94%), BA.5* (4.06%), BA.2.10* (3.51%), and BQ.1* (1.65%). A total of 540 cases were contacted telephonically, of whom 494 (91.48%) were symptomatic with mild symptoms. Fever (77.73%) was the most common symptom, followed by cold (47.98%), cough (42.31%), and myalgia and fatigue (18.83%). Of the 540 cases, 414 (76.67%) cases recovered at home, and 126 (23.33%) were institutionally quarantined/hospitalized. Among the home-isolated and hospitalized cases, 416 (99.76%) and 108 (87.80%), respectively, recovered with symptomatic treatment, while one (0.24%) and 15 (12.20%), respectively, succumbed to the disease. Out of the 540 cases, 491 (90.93%) were vaccinated with at least one dose of the COVID-19 vaccine, 41 (7.59%) were unvaccinated, and for eight (1.48%) cases, vaccination data was not available. Conclusions The current study indicates that the XBB* variant is causing mild disease in India. However, as XBB* possesses both immune-escape and infectivity-enhancing mutations, it has the potential to spread to other parts of the world rapidly. Further, anti-SARS-CoV-2 vaccination improves survival rates in COVID-19.

Practice Trends of Neuromodulation Therapies for Pain and Spasticity in India.

BACKGROUND: Neuromodulation has been successfully used globally to address severe refractory chronic pain for over five decades. Compared to the wide acceptance that it enjoys in United States and Europe, it is fairly underutilized in Asia, including India. OBJECTIVES: We conducted the first systematic nationwide survey to provide an overview of neuromodulation in the past 20 years to investigate the practice trends for severe refractory chronic pain and barriers for the uptake of neuromodulation therapies for pain in India. DESIGN: A 20-point detailed questionnaire survey was sent out for online completion in August 2020 to practitioners in India involved in interventions for pain. The survey was completed by 112 practitioners (10% return rate). The response data collected were analyzed, tabulated, and presented as percentages. RESULTS: The average duration of pain practice in India for the majority of respondents was less than a decade. About 70% of practitioners expressed that they manage severe refractory pain without neuromodulation. This survey confirms that neuromodulation is grossly underutilized for pain, comprising only 10% of total neuromodulation implants performed per annum in India. The most common indications were neuropathic pain (45%) and failed back surgery syndrome (42%). The respondents expressed the main barriers to be related to the cost (85%), lack of awareness (68%), and lack of good training (59%). More than 50% of respondents also expressed difficulty of access to neuromodulation therapies for pain and acceptance by patients. CONCLUSION: The younger generation of pain practitioners in India is becoming more aware and convinced about the role of neuromodulation to alleviate severe pain and suffering. An all-round approach combining improved training, awareness at various levels, more flexible options of newer technology and reimbursement approval can positively influence its use. This can be achieved with the collective efforts of physicians, insurers, industry, and focused academic activities of clinical societies.

Removal of Indwelling Urinary Catheter Two Days After Colovesical Fistula Repair: a Single-Arm Prospective Trial.

BACKGROUND: Colovesical fistulas are uncommon but associated with significant morbidity and reduced quality of life. In cases with diverticular etiology, surgical management involves single-stage colonic resection with anastomosis and simple or no bladder repair. No single approach to postoperative bladder management has been widely accepted. Although historically a Foley catheter remained in place for about 2 weeks, elevated risk of the attendant complications has motivated exploring shorter durations. This study examined the feasibility and safety of removing the Foley catheter on postoperative day two. METHODS: Patients with colovesical fistula due to diverticular disease undergoing colectomy with simple or no bladder repair were enrolled in this single-arm prospective trial conducted at a large community health system. The primary outcome was removal of the Foley catheter on postoperative day two after negative cystogram without re-insertion prior to hospital discharge. Secondary outcomes were complications after Foley catheter removal and hospital length of stay. Ninety-five percent confidence intervals were calculated for the outcomes. RESULTS: Twenty-four patients were enrolled. About half (54%) of procedures were open, with 33% requiring simple bladder repair. Ninety-six percent (95% confidence interval, 79-99%) of patients had their Foley catheter removed on postoperative day two after a negative cystogram. There were no complications. Mean (range) hospital length of stay was 4.3 (2-6) days. DISCUSSION: Foley catheter removal after negative cystogram on postoperative day two appears to be feasible and safe in the setting of diverticulitis-related colovesical fistula repair. Further research on a larger number of patients should confirm these findings.

Systematic Review of Literature Examining Bacterial Urinary Tract Infections in Diabetes.

This systematic review addresses the central research question, "what is known from the published, peer-reviewed literature about the impact of diabetes on the risk of bacterial urinary tract infections (UTI)?" We examine the results from laboratory studies where researchers have successfully adapted mouse models of diabetes to study the pathophysiology of ascending UTI. These studies have identified molecular and cellular effectors shaping immune defenses against infection of the diabetic urinary tract. In addition, we present evidence from clinical studies that in addition to diabetes, female gender, increased age, and diabetes-associated hyperglycemia, glycosuria, and immune impairment are important risk factors which further increase the risk of UTI in diabetic individuals. Clinical studies also show that the uropathogenic genera causing UTI are largely similar between diabetic and nondiabetic individuals, although diabetes significantly increases risk of UTI by drug-resistant uropathogenic bacteria.

Vaxi-DL: A web-based deep learning server to identify potential vaccine candidates.

The development of a new vaccine is a challenging exercise involving several steps including computational studies, experimental work, and animal studies followed by clinical studies. To accelerate the process, in silico screening is frequently used for antigen identification. Here, we present Vaxi-DL, web-based deep learning (DL) software that evaluates the potential of protein sequences to serve as vaccine target antigens. Four different DL pathogen models were trained to predict target antigens in bacteria, protozoa, fungi, and viruses that cause infectious diseases in humans. Datasets containing antigenic and non-antigenic sequences were derived from known vaccine candidates and the Protegen database. Biological and physicochemical properties were computed for the datasets using publicly available bioinformatics tools. For each of the four pathogen models, the datasets were divided into training, validation, and testing subsets and then scaled and normalised. The models were constructed using Fully Connected Layers (FCLs), hyper-tuned, and trained using the training subset. Accuracy, sensitivity, specificity, precision, recall, and AUC (Area under the Curve) were used as metrics to assess the performance of these models. The models were benchmarked using independent datasets of known target antigens against other prediction tools such as VaxiJen and Vaxign-ML. We also tested Vaxi-DL on 219 known potential vaccine candidates (PVC) from 37 different pathogens. Our tool predicted 175 PVCs correctly out of 219 sequences. We also tested Vaxi-DL on different datasets obtained from multiple resources. Our tool has demonstrated an average sensitivity of 93% and will thus be a useful tool for prioritising PVCs for preclinical studies.

Glycosuria Alters Uropathogenic Escherichia coli Global Gene Expression and Virulence.

Uropathogenic Escherichia coli (UPEC) is the principal etiology of more than half of urinary tract infections (UTI) in humans with diabetes mellitus. Epidemiological data and studies in mouse model of ascending UTI have elucidated various host factors responsible for increasing the susceptibility of diabetic hosts to UPEC-UTI. In contrast, diabetic urinary microenvironment-mediated alterations in UPEC physiology and its contributions to shaping UPEC-UTI pathogenesis in diabetes have not been examined. To address our central hypothesis that glycosuria directly induces urinary virulence of UPEC, we compared virulence characteristics and gene expression in human UPEC strains UTI89 (cystitis) and CFT073 (pyelonephritis), exposed for 2 h in vitro to urine from either male or female donors that was either plain or supplemented with glucose to mimic glycosuria. Compared to control UPEC exposed to nutrient-rich culture medium, lysogeny broth, glycosuria-exposed UPEC exhibited significant increase in biofilm formation and reduction in the hemagglutination of Guinea pig erythrocytes (a measure of type 1 piliation). In addition, the analysis of UTI89 transcriptome by RNA sequencing revealed that 2-h-long, in vitro exposure to glycosuria also significantly alters expression of virulence and metabolic genes central to urinary virulence of UPEC. Addition of galactose as an alternative carbon source affected biofilm formation and gene expression profile of UPEC to an extent similar to that observed with glucose exposure. In summary, our results provide novel insights into how glycosuria-mediated rapid changes in UPEC fitness may facilitate UTI pathogenesis in the diabetic urinary microenvironment. IMPORTANCE Uropathogenic Escherichia coli (UPEC) is an important causative agent of urinary tract infections in diabetic humans. We examined the effects of in vitro exposure to glycosuria (presence of glucose in urine) on the virulence and gene expression by UPEC. Our results show that glycosuria rapidly (in 2 h) alters UPEC gene expression, induces biofilm formation, and suppresses type 1 piliation. These results offer novel insights into the pathogenesis of UPEC in the urinary tract.

Prevalence of menopausal symptoms among women in Vadodara, Central Gujarat: The urban-rural divide.

Aim: The aim of this article is to estimate prevalence of menopausal symptoms among women in the menopausal age group and study the urban-rural differences. Methods and Design: Analytical cross-sectional study conducted in rural and urban field practice areas of a tertiary care center affiliated to Medical College, where 290 women (145 each from urban and rural areas) were interviewed to measure prevalence of menopausal symptoms. Forty-one symptoms were divided into 'Psycho-somatic' (17 symptoms), 'genito-urinary (9 symptoms)' and musculo-skeletal (5 symptoms) domains. The prevalence of each of these symptoms is reported as proportion and the differences in the median scores in the two groups were tested using Mann-Whitney U test. Results: From among 145 women each, in urban and rural settings, most common psychosomatic symptoms were physical exhaustion-fatigue (73.1%), difficulty climbing stairs (59.3%), sleep problems (45.2%), body ache (43.4%), and hot flushes (41.4%). Among the urban participants, most common was physical exhaustion (42.1%), difficulty climbing stairs (62.1%), anger (46.9%), sleep problems (45.5%), and irritability (42.1%), while among the rural participants they were physical exhaustion (66.2%), difficulty climbing stairs (56.6%), insomnia (54.5%), and body ache (46.2%). Most common genito-urinary symptoms overall and in rural areas were urinary urgency (35.9% and 38.6%), increased frequency of urine (31.7% and 37.2%) and incontinence (30% and 35.2% respectively). Among the urban women, common symptoms were urinary urgency (33.1%) followed by itching of private parts (30.3%) and increased frequency of urination (26.2%). Among musculo-skeletal symptoms, joint pain (74.1%, 74.5%, 73.8%) was the most common symptom followed by joint and muscular discomfort (71.7%, 73.8%, 69.7%) among the overall, urban and rural participants. There was a significant difference in the median psychosomatic score as per the symptoms experienced by the urban and rural participants (U = 36, Z statistic = 2.31, and P = 0.02). However, there was no significant difference in the scores for genito-urinary and musculo-skeletal symptoms; thereby, median scores under both these domains were almost similar in both urban and rural groups. Conclusion: There was significant difference in the median psychosomatic score as per the symptoms experienced by the urban and rural participants however; there was no significant difference in genito-urinary and musculo-skeletal symptom scores.

Photodecarboxylative Amination of Redox-Active Esters with Diazirines.

Diazirines have been recently demonstrated to serve as electrophilic amination reagents that afford diaziridines, versatile heterocycles that are readily transformed into amines, hydrazines, and nitrogen-containing heterocycles. Here, we report the photodecarboxylative amination of redox-active esters with diazirines using inexpensive photoactivators under mild conditions with an enhanced scope for primary substrates. The stability of diazirines to blue light is demonstrated, paving the way for further research into other photochemical amination methods with these unique heterocycles.

Identification of vaccine targets in pathogens and design of a vaccine using computational approaches.

Antigen identification is an important step in the vaccine development process. Computational approaches including deep learning systems can play an important role in the identification of vaccine targets using genomic and proteomic information. Here, we present a new computational system to discover and analyse novel vaccine targets leading to the design of a multi-epitope subunit vaccine candidate. The system incorporates reverse vaccinology and immuno-informatics tools to screen genomic and proteomic datasets of several pathogens such as Trypanosoma cruzi, Plasmodium falciparum, and Vibrio cholerae to identify potential vaccine candidates (PVC). Further, as a case study, we performed a detailed analysis of the genomic and proteomic dataset of T. cruzi (CL Brenner and Y strain) to shortlist eight proteins as possible vaccine antigen candidates using properties such as secretory/surface-exposed nature, low transmembrane helix (< 2), essentiality, virulence, antigenic, and non-homology with host/gut flora proteins. Subsequently, highly antigenic and immunogenic MHC class I, MHC class II and B cell epitopes were extracted from top-ranking vaccine targets. The designed vaccine construct containing 24 epitopes, 3 adjuvants, and 4 linkers was analysed for its physicochemical properties using different tools, including docking analysis. Immunological simulation studies suggested significant levels of T-helper, T-cytotoxic cells, and IgG1 will be elicited upon administration of such a putative multi-epitope vaccine construct. The vaccine construct is predicted to be soluble, stable, non-allergenic, non-toxic, and to offer cross-protection against related Trypanosoma species and strains. Further, studies are required to validate safety and immunogenicity of the vaccine.

Lung shunt fraction calculation using 99mTc-MAA SPECT/CT imaging for 90Y microsphere selective internal radiation therapy of liver tumors.

BACKGROUND: 99mTc-macroaggregated albumin (99mTc-MAA) scintigraphy is utilized in treatment planning for Yttrium-90 (90Y) Selective Internal Radiation Therapy (SIRT) of liver tumors to evaluate hepatopulmonary shunting by calculating the lung shunt fraction (LSF). The purpose of this study was to evaluate if LSF calculation using SPECT/CT instead of planar gamma camera imaging is more accurate and if this can potentially lead to more effective treatment planning of hepatic lesions while avoiding excessive pulmonary irradiation. RESULTS: LSF calculation was obtained using two different methodologies in 85 cases from consecutive patients intended to receive 90Y SIRT. The first method was based on planar gamma camera imaging in the anterior and posterior views with geometric mean calculation of the LSF from regions of interest of the liver and lungs. The second method was based on segmentation of the liver and lungs from SPECT/CT images of the thorax and abdomen. The differences in planar imaging versus SPECT/CT derived LSF values along with the estimated absorbed lung mean dose (LMD) were evaluated. The LSF values were higher in planar imaging versus SPECT/CT in 81/85 cases, with a mean value of 8.5% vs. 4.6% respectively; the difference was statistically significant using a paired t-test (alpha = 0.05). In those patients who received SIRT, the estimated absorbed LMD calculated with planar imaging was significantly higher than with SPECT/CT (t-test, P < 0.005). Repeated phantom experiments using an anthropomorphic torso phantom with variable 99mTc activity concentrations for the liver and lungs were performed with the standard patient protocol, demonstrated improved accuracy of the LSF calculation based on SPECT/CT than planar imaging (mean overestimated value of 6% vs. 26%). CONCLUSIONS: This study demonstrates that LSF calculation using planar imaging can be significantly overestimated while calculation using SPECT/CT imaging and appropriate segmentation tools can be more accurate. Minimizing the errors in obtaining the LSF can lead to more effective 90Y SIRT treatment planning for hepatic tumors while ensuring the lung dose will not exceed the standard acceptable safety thresholds.

Exposure to Moderate Glycosuria Induces Virulence of Group B Streptococcus.

To explore whether glycosuria induces virulence of uropathogens, in turn facilitating urinary tract infection (UTI), we exposed group B Streptococcus (GBS) strain 10/84 to human urine plain or with 300 mg/dL glucose (mimicking moderate glycosuria). Exposure to moderate glycosuria significantly augmented bacterial growth, kidney bacterial burden in a mouse model of ascending UTI, and virulence characteristics and expression of corresponding genes. Exposure to glycosuria increased GBS adherence to human bladder epithelial cell line and expression of corresponding PI2a fimbrial gene, antimicrobial peptide LL-37 resistance and bacterial surface charge modulating dltA, and GBS hemolytic ability and expression of genes encoding pore-forming toxins.

Decarboxylative Amination: Diazirines as Single and Double Electrophilic Nitrogen Transfer Reagents.

The ubiquity of nitrogen-containing small molecules in medicine necessitates the continued search for improved methods for C-N bond formation. Electrophilic amination often requires a disparate toolkit of reagents whose selection depends on the specific structure and functionality of the substrate to be aminated. Further, many of these reagents are challenging to handle, engage in undesired side reactions, and function only within a narrow scope. Here we report the use of diazirines as practical reagents for the decarboxylative amination of simple and complex redox-active esters. The diaziridines thus produced are readily diversifiable to amines, hydrazines, and nitrogen-containing heterocycles in one step. The reaction has also been applied in fluorous phase synthesis with a perfluorinated diazirine.

Prevalence and determinants of the dangerous selfie among medical and nursing students: a cross-sectional study from eastern India.

BACKGROUND: Globally, there has been an exponential rise in smartphone use and selfie taking among youth. To make selfies exciting, dangerous selfies are often taken that may lead to catastrophic consequences, including death. This study aims to estimate the prevalence of dangerous selfies and to determine the factors associated with dangerous selfies among medical and nursing students in India. METHODS: The study was conducted at the All India Institute of Medical Sciences (AIIMS), Bhubaneswar, India, in April-August 2018. The inclusion criteria were students enrolled in the Bachelor of Medicine and Bachelor of Surgery (MBBS) and nursing courses of AIIMS, Bhubaneswar. Students who did not use smartphones were excluded from the study. The interview schedule and Selfitis Behaviour Scale (SBS) were used to collect information on sociodemographic variables, smartphone use and variables related to selfies and dangerous selfies. Forward stepwise logistic regression was undertaken with the probability of entry and removal as 0.05 and 0.10, respectively. RESULTS: Of 633 eligible participants, 595 were included in the study. The mean (SD) age of the participants was 21.2 (1.6) years. More than half (56.8%) of the participants were female, 384 (64.5%) were medical students and 211 (35.5%) were nursing students. Nearly two-thirds of the participants (70.6%) preferred to take selfie. One hundred thirty three (40.3%) of the participants posted selfies on social media daily. The prevalence of dangerous selfies was 8.74% (95% CI: 6.73-11.28). Eight injury episodes while taking selfies were reported by seven (1.2%) participants. Being male (AOR 4.96, 95% CI 2.53-9.74), posting selfies on social media daily (AOR 3.33, 95% CI 1.71-6.47) and an SBS score > 75 (AOR 4.97, 95% CI 1.43-17.28) were independent predictors of dangerous selfies. CONCLUSION: Nearly one in ten medical and nursing students reported having taken a dangerous selfie, and one in one hundred reported having been injured while attempting to take a selfie. Being male, posting selfies on social media daily and an SBS score > 75 were independent predictors of dangerous selfies. Further research is required to identify the community burden of dangerous selfies and to develop strategies to prevent selfie-related fatalities among youths.

Elucidation of the Reaction Mechanism of C2 + N1 Aziridination from Tetracarbene Iron Catalysts.

A combined computational and experimental study was undertaken to elucidate the mechanism of catalytic C2 + N1 aziridination supported by tetracarbene iron complexes. Three specific aspects of the catalytic cycle were addressed. First, how do organic azides react with different iron catalysts and why are alkyl azides ineffective for some catalysts? Computation of the catalytic pathway using density functional theory (DFT) revealed that an alkyl azide needs to overcome a higher activation barrier than an aryl azide to form an iron imide, and the activation barrier with the first-generation catalyst is higher than the activation barrier with the second-generation variant. Second, does the aziridination from the imide complex proceed through an open-chain radical intermediate that can change stereochemistry or, instead, via an azametallacyclobutane intermediate that retains stereochemistry? DFT calculations show that the formation of aziridine proceeds via the open-chain radical intermediate, which qualitatively explains the formation of both aziridine diastereomers as seen in experiments. Third, how can the formation of the side product, a metallotetrazene, be prevented, which would improve the yield of aziridine at lower alkene loading? DFT and experimental results demonstrate that sterically bulky organic azides prohibit formation of the metallotetrazene and, thus, allow lower alkene loading for effective catalysis. These multiple insights of different aspects of the catalytic cycle are critical for developing improved catalysts for C2 + N1 aziridination.