Correlation of severity & clinical outcomes of COVID-19 with virus variants: A prospective, multicentre hospital network study.

BACKGROUND OBJECTIVES: The clinical course of COVID-19 and its prognosis are influenced by both viral and host factors. The objectives of this study were to develop a nationwide platform to investigate the molecular epidemiology of SARS-CoV-2 (Severe acute respiratory syndrome Corona virus 2) and correlate the severity and clinical outcomes of COVID-19 with virus variants. METHODS: A nationwide, longitudinal, prospective cohort study was conducted from September 2021 to December 2022 at 14 hospitals across the country that were linked to a viral sequencing laboratory under the Indian SARS-CoV-2 Genomics Consortium. All participants (18 yr and above) who attended the hospital with a suspicion of SARS-CoV-2 infection and tested positive by the reverse transcription-PCR method were included. The participant population consisted of both hospitalized as well as outpatients. Their clinical course and outcomes were studied prospectively. Nasopharyngeal samples collected were subjected to whole genome sequencing to detect SARS-CoV-2 variants. RESULTS: Of the 4972 participants enrolled, 3397 provided samples for viral sequencing and 2723 samples were successfully sequenced. From this, the evolution of virus variants of concern including Omicron subvariants which emerged over time was observed and the same reported here. The mean age of the study participants was 41 yr and overall 49.3 per cent were female. The common symptoms were fever and cough and 32.5 per cent had comorbidities. Infection with the Delta variant evidently increased the risk of severe COVID-19 (adjusted odds ratio: 2.53, 95% confidence interval: 1.52, 4.2), while Omicron was milder independent of vaccination status. The independent risk factors for mortality were age >65 yr, presence of comorbidities and no vaccination. INTERPRETATION CONCLUSIONS: The authors believe that this is a first-of-its-kind study in the country that provides real-time data of virus evolution from a pan-India network of hospitals closely linked to the genome sequencing laboratories. The severity of COVID-19 could be correlated with virus variants with Omicron being the milder variant.

Determination of chlorantraniliprole for managing Helicoverpa armigera and Spodoptera litura in cotton ecosystem.

Cotton bollworm incidence and damages are high in India. In addition, it causes considerable yield loss. A new insecticide formulation Chlorantraniliprole 600 g/L SC was used along with recommended insecticides for managing Spodoptera litura and Helicoverpa armigera in two consecutive experimental trials during the period October 2021 to September 2022. Two foliar applications of Chlorantraniliprole (40 and 30 g a. i/ha) at ten days interval period reduced significantly the larval populations of H. armigera, S. litura without any phytotoxic symptoms in cotton. Chlorantraniliprole application in open field condition was found to be harmless to natural enemy (coccinellids and spiders). Even though, a temporary lessening of natural enemy populations was noticed after spray, progressively the population was increased within a week time. Cotton yield was high in chlorantraniliprole @ 40 g a. i/ha treated plot (22.66, 22.12 q/ha) when compared to untreated control. Similar effect was also noticed in the dose at 30 g a. i/ha (22.35, 21.81 q/ha) and it was statistically on par in both experiments. Residue analysis results confirming that, cotton lint, cotton seed and soil samples collected from treated (30 and 60 g a. i/ha) and untreated samples during harvest were free from chlorantraniliprole residues (below detectable levels of 0.008 µg/g).

Clinicopathological comparison of VHL expression as a prognostic tumor marker in renal cell carcinoma: A single center experience.

AIM: To assess the VHL gene expression as a prognostic marker in Renal Cell Carcinoma (RCC) and compare it with clinicopathologic features. MATERIALS AND METHODS: This retrospective observational study was conducted in the department of Urology and Renal Transplantation in Sri Ramachandra Institute of Higher Education and Research, Chennai from August 2016 to August 2018. Thirty patients who have undergone a radical/partial nephrectomy with biopsy proven histological diagnosis of RCC during the study period were included in the study. Data was analyzed using Statistical package for Social Sciences version 17. RESULTS: A complete loss and retained VHL expression were noted in 60% and 40% of the RCC specimens. Association between smoking and VHL expression was found to be statistically significant. There was no statistical significance found between age group, sex, chief complaints, BMI. ECOG score, hypertension, family history, location of tumor, calcification, venous system or lymphnode involvement. However, rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant. CONCLUSION: Complete loss of VHL expression was noted in majority of the specimens that leads to the development of RCC. Smoking has been found to be statistically significant in tumors that retain VHL expression which may contributes to more aggressive form of tumor. Association between rT staging, nature of lesion and cut surface, HPE type, pT staging, HPE grade, necrosis and lympho-vascular invasion were also found to be statistically significant.

Cardiovascular disease management in people with diabetes outside North America and Western Europe in 2006 and 2015.

AIM: Optimal treatment of cardiovascular disease is essential to decrease mortality among people with diabetes, but information is limited on how actual treatment relates to guidelines. We analysed changes in therapeutic approaches to anti-hypertensive and lipid-lowering medications in people with Type 2 diabetes from 2006 and 2015. METHODS: Summary data from clinical services in seven countries outside North America and Western Europe were collected for 39 684 people. Each site summarized individual-level data from outpatient medical records for 2006 and 2015. Data included: demographic information, blood pressure (BP), total cholesterol levels and percentage of people taking statins, anti-hypertensive medication (angiotensin-converting enzyme inhibitors, calcium channel blockers, angiotensin II receptor blockers, thiazide diuretics) and antiplatelet drugs. RESULTS: From 2006 to 2015, mean cholesterol levels decreased in six of eight sites (range: -0.5 to -0.2), whereas the proportion with BP levels > 140/90 mmHg increased in seven of eight sites. Decreases in cholesterol paralleled increases in statin use (range: 3.1 to 47.0 percentage points). Overall, utilization of anti-hypertensive medication did not change. However, there was an increase in the use of angiotensin II receptor blockers and a decrease in angiotensin-converting enzyme inhibitors. The percentage of individuals receiving calcium channel blockers and aspirin remained unchanged. CONCLUSIONS: Our findings indicate that control of cholesterol levels improved and coincided with increased use of statins. The percentage of people with BP > 140/90 mmHg was higher in 2015 than in 2006. Hypertension treatment shifted from using angiotensin-converting enzyme inhibitors to angiotensin II receptor blockers. Despite the potentially greater tolerability of angiotensin II receptor blockers, there was no associated improvement in BP levels.

Gingival, oral hygiene and periodontal status of the teeth restored with stainless steel crown: A prospective study.

AIM: To compare the gingival health and periodontal status in primary molars restored with stainless steel crowns with unrestored contralateral teeth. MATERIALS AND METHODS: A split mouth design study was conducted on 60 children aged 5- 10 years who required stainless steel crown restoration on deciduous molars. The molar teeth restored with stainless steel crown were selected for study and healthy unrestored contralateral teeth were selected as controls. Bitewing radiograph of study and control tooth was taken at initial, three months and at six months. The gingival status, oral hygiene status was evaluated at three months and six month intervals using gingival index and oral hygiene index respectively. RESULT: On evaluating the oral hygiene status at three months study group showed the mean value of 0.7±0.700 whereas in control group it was 1±0.368. At six months it was 1.183±0.390 in study group and 1.5±0.504 in control group. Chi square test shows that the crown marginal adaptation produced statistically significant difference at six months. Crown marginal extension did not produce any difference on gingival index and oral hygiene index. CONCLUSION: When compared to control teeth, the teeth restored with stainless steel crown showed lesser plaque and debris accumulation at three months and six months. Radiographic bone level the control teeth showed higher level of bone resorption compared to the teeth restored with stainless steel crown.

Acute Internal Medicine Trainee Survey 2016.

OBJECTIVES: To ascertain the views of current Acute Internal Medicine (AIM) trainees on the strengths and weakness of the specialty, their training programmes, practical procedures and the provision of training days. METHODS: Online electronic survey circulated to all Higher Specialty Trainees (HST) in AIM. Participation was voluntary and all answers confidential. A total of 108 trainees responded. RESULTS: There were respondents from across the United Kingdom. The majority of respondents are happy or quite happy with their training (61%), with 11% unhappy or very unhappy. The variety of workload (68%), specialty exposure (69%) and practical procedures (67%) were strengths while lack of respect from other specialties (55%) and rota gaps (59%) remain significant problems. 53% of respondents feel they are expected to cover more rota gaps than their GIM colleagues, and 54% trainees feel they do not get a session a week allocated to them for specialist skill training/admin. Only 33% of trainees expect to get dedicated leadership and/or management training during their programme, and a large proportion of trainees (78%) feel that some form of ultrasound training should be a core part of the curriculum. Despite the difficulties, 85% of respondents would recommend AIM as a specialty. CONCLUSIONS: This survey highlights some of the positives and negatives of training in AIM, and highlights areas where potential improvements to programmes could be made. Comparison of the data with 2015 shows small improvements in a number of areas, but still some significant concerns remain. The findings were fed back to the Training Committee in March.

Engineering 3D Nanoplasmonic Assemblies for High Performance Spectroscopic Sensing.

We demonstrate the fabrication of plasmonic sensors that comprise gold nanopillar arrays exhibiting high surface areas, and narrow gaps, through self-assembly of amphiphilic diblock copolymer micelles on silicon substrates. Silicon nanopillars with high integrity over arbitrary large areas are obtained using copolymer micelles as lithographic templates. The gaps between metal features are controlled by varying the thickness of the evaporated gold. The resulting gold metal nanopillar arrays exhibit an engineered surface topography, together with uniform and controlled separations down to sub-10 nm suitable for highly sensitive detection of molecular analytes by Surface Enhanced Raman Spectroscopy (SERS). The significance of the approach is demonstrated through the control exercised at each step, including template preparation and pattern-transfer steps. The approach is a promising means to address trade-offs between resolutions, throughput, and performance in the fabrication of nanoplasmonic assemblies for sensing applications.

Hunter's syndrome: a case report.

Hunter's syndrome or mucopolysaccharidosis (MPS) type II is an X-linked recessive mucopolysaccharide disorder caused by a defect in the metabolism of glycosaminoglycans (GAGs) characterized by involvement of nervous, cardiovascular, respiratory, and mucoskeletal systems along with numerous oral manifestations. This is a case report of a 13-year-old boy referred to the Department of Pediatric Dentistry with a chief complaint of irregularly placed teeth from a general physician. Here we highlight the pivotal role of pediatric dentists in diagnosis and treatment planning for patients diagnosed with such systemic conditions and the provision of advanced dental care in the management of the same.

Weil's disease presenting as atypical pneumonia.

Leptospirosis is a disease caused by spp. Leptospira, also known as Weil's disease if it manifests with jaundice. It can be associated with respiratory, renal, hepatic and haematological complications and most importantly carries a high mortality when untreated. We describe a case of a 53 year old man presenting with myalgia and fever in whom the diagnosis of leptospirosis was not initially considered. Following a deterioration in his condition a careful history revealed an apparent brief exposure to animal urine and subsequent grossly positive Leptospira serology. Treatment of his condition led to complete resolution after a brief stay on the intensive care unit. This case highlights the atypical nature of a presentation of Leptospirosis, its respiratory complications, and importance of serological testing in its diagnosis.

Gentamicin use in neonates: should we have a change of practice?

BACKGROUND: Gentamicin, one of the most commonly used antibiotics in neonates, has potential toxicity. This study was performed to determine the incidence of potential toxicity of gentamicin in term and preterm neonates. METHODS: A one-year retrospective study in neonates admitted to Special Baby Care Units at University Hospital of North Durham and Darlington Memorial Hospitals. We reviewed each admission and looked through the case notes in detail to document information about gentamicin administration, dosage and elevated gentamicin levels in the blood. Pre-third dose gentamicin levels >2 mg/L were classified as elevated. RESULTS: Overall, 192 babies (83 term and 109 preterm) had documented gentamicin levels. Of these, 43% (84/192) manifested elevated gentamicin levels. Of the babies with elevated gentamicin levels, 67% (56/84) weighed less than 2.5 kg. When a combination of gestation period and weight was considered, 61% (51/84) of preterm infants weighing <2.5 kg had elevated levels whereas only one term infant <2.5 kg exhibited elevated levels. CONCLUSION: Preterm neonates and specifically low birth weight neonates tolerate gentamicin poorly. Dosage and/or interval of administration of the medication may need modification in this group to minimise toxicity.

Viewpoint: norovirus outbreak on the AMU: a lesson in shared clinical leadership.

Three times a year, the first Wednesday of the month heralds a changeover of junior doctors within our hospital. This year, the first Wednesday in December provided a different kind of challenge. The voice on the phone confirmed the words that no one wanted to hear: "You have three confirmed cases of Norovirus and you have to close to new admissions".

SU-E-I-71: Susceptibility Weighted Imaging (SWI) Software for Post-Processing of SWI Data.

PURPOSE: To develop open source software for post processing of susceptibility weighted (SWI) MR images using magnitude and phase data. METHODS: SWI data was acquired using Philips MRI 3T scanner with the following parameter: 3D T1 FFE axial with TR=40ms, TE=25ms, FOV=22 cm, acquisition matrix of 440×440 and 40 slices. Both magnitude and phase data was stored for SWI post processing. The SWI homodyne filtering is performed by converting the magnitude and phase image to complex real and imaginary images. The SWI software was implemented in C++ using ITK (Image registration and segmentation toolkit) toolkit. To generate SWI maps the user needs to provide the DICOM data directory, the series number of DICOM SWI series, low pass filter size and the weighting factor of phase mask. This outputted SWI series is saved as DICOM and appended to the patient series and can be viewed in any DICOM compatible viewer. The software also outputs SWI filtered phase maps which can be further used for iron quantification in organs like brain, liver etc. RESULTS: An open source implementation of SWI post-processing tool using ITK was provided. The SWI processed phase weighted data can be used for qualitative assessment of iron deposits. The filtered phase map outputted can be used for quantitative iron measurements. CONCLUSIONS: SWI post processing software is implemented here to provide qualitative SWI maps of iron deposits in brain and other organs. The post processed images can also be useful for MR Venography with minimum intensity projection. This tool would be useful to study disease processes involved with accumulation of iron in different organs.

Role of Many-Body Effects in Describing Low-Lying Excited States of π-Conjugated Chromophores: High-Level Equation-of-Motion Coupled-Cluster Studies of Fused Porphyrin Systems.

The unusual photophysical properties of the π-conjugated chromophores make them potential building blocks of various molecular devices. In particular, significant narrowing of the HOMO-LUMO gaps can be observed as an effect of functionalization chromophores with polycyclic aromatic hydrocarbons (PAHs). In this paper we present equation-of-motion coupled cluster (EOMCC) calculations for vertical excitation energies of several functionalized forms of porphyrins. The results for free-base porphyrin (FBP) clearly demonstrate significant differences between functionalization of FBP with one- (anthracene) and two-dimensional (coronene) structures. We also compare the EOMCC results with the experimentally available results for anthracene fused zinc-porphyrin. The impact of various types of correlation effects is illustrated on several benchmark models, where the comparison with the experiment is possible. In particular, we demonstrate that for all excited states considered in this paper, all of them being dominated by single excitations, the inclusion of triply excited configurations is crucial for attaining qualitative agreement with experiment. We also demonstrate the parallel performance of the most computationally intensive part of the completely renormalized EOMCCSD(T) approach (CR-EOMCCSD(T)) across 120 000 cores.

Association of methylenetetrahydrofolate reductase gene polymorphisms & colorectal cancer in India.

BACKGROUND & OBJECTIVES: Methylenetetrahydrofolate reductase (MTHFR) is a critical enzyme in folate metabolism and involved in DNA synthesis, DNA repair and DNA methylation. The two common functional polymorphisms of MTHFR, 677 C-->T and 1298 A-->C have shown to impact several diseases including cancer. This case-control study was undertaken to analyse the association of the MTHFR gene polymorphisms 677 C-->T and 1298 A-->C and risk of colorectal cancer (CRC). METHODS: One hundred patients with a confirmed histopathologic diagnosis of CRC and 86 age and gender matched controls with no history of cancer were taken for this study. DNA was isolated from peripheral blood samples and the genotypes were determined by PCR-RFLP. The risk association was estimated by compounding odds ratio (OR) with 95 per cent confidence interval (CI). RESULTS: Genotype frequency of MTHFR 677 CC, CT and TT were 76.7, 22.1 and 1.16 per cent in controls, and 74, 25 and 1.0 per cent among patients. The 'T' allele frequency was 12.21 and 13.5 per cent in controls and patients respectively. The genotype frequency of MTHFR 1298 AA, AC, and CC were 25.6, 58.1 and 16.3 per cent for controls and 22, 70 and 8 per cent for patents respectively. The 'C' allele frequency for 1298 A-->C was 43.0 and 45.3 per cent respectively for controls and patients. The OR for 677 CT was 1.18 (95% CI 0.59-2.32, P = 0.642), OR for 1298 AC was 1.68 (95% CI 0.92-3.08, P = 0.092) and OR for 1298 CC was 0.45 (95% CI 0.18-1.12, P = 0.081). The OR for the combined heterozygous state (677 CT and 1298 AC) was 1.18 (95% CI 0.52-2.64, P =0.697). INTERPRETATION & CONCLUSION: The frequency of the MTHFR 677 TT genotype is rare as compared to 1298 CC genotype in the population studied. There was no association between 677 C-->T and 1298 A-->C polymorphisms and risk of CRC either individually or in combination. The homozygous state for 1298 A-->C polymorphism appears to slightly lower risk of CRC. This needs to be confirmed with a larger sample size.

Primary intrarenal teratoma in an adult: A case report and review of literature.

A 35-year-old male presented with left loin pain. On evaluation, he was diagnosed to have a left renal lower polar mass. He underwent partial nephrectomy. The histopathological examination was suggestive of teratoma of the kidney. We present this case, as intrarenal teratomas in adults are extremely rare and only a very few cases are reported in literature.

Thrombosis prophylaxis in patients with ischaemic (cardioembolic) stroke. How long is long enough?

Cardioembolism accounts for approximately 20% of ischaemic strokes, and is associated with high mortality and propensity to recurrences. Approximately, 30% of ischaemic strokes remain cryptogenic despite improved imaging modalities and technological improvements to identify their cause. Of the long list of various cardiac conditions associated with an increased risk of cardioembolic strokes, non-valvular atrial fibrillation is the most common cause. Unsurprisingly, the stroke risk associated with these conditions is highly variable and non-homogenous, with many risk factors additive to the overall risk profile. Treatment with vitamin K-antagonists substantially reduces the long-term complications associated with cardioembolism in some high-risk patients, for example, in atrial fibrillation. Careful selection of antithrombotic drug regime needs to be carried out in patients individually to minimise the risk of bleeding encountered with such therapy. Apart from atrial fibrillation, there is relatively limited evidence for the role of antithrombotic therapy for other cardiac conditions associated with cardioembolism and how long one should treat.