TELEMEDICINE IN TIMES OF CORONAVIRUS DISEASE-19 AT A TERTIARY CARE GOVERNMENT HOSPITAL IN UTTAR PRADESH, INDIA

Objective: The present study aimed to describe the common symptoms and diagnosis for each specialty which can be used in future for expansion of teleconsultation services and implementation of the E Sanjeevani model in health care. Methods: This is a cross-sectional observational study which comprises the data collected from various specialties over a 4-month period. The telemedicine consultations were given by the consultants of the concerned specialty in adherence to the telemedicine guidelines issued by the government and mostly generic names of the medicine were advised to the patients. The demographic details, chief complaint of the patient, diagnosis, and treatment were recorded. Results: The total number of calls which was received in 4 months period at the telemedicine center in Government Medical College, Ayodhya, was 4848. Maximum number of calls was attended by the department of obstetrics and gynecology which was 771 (15.9%). Coronavirus disease (COVID-19) had a substantial and transformative influence on routine clinical practice across the entire clinical continuum in a very short period of time. Conclusion: The use of telemedicine emerged as a critical tool to improve the provision of health services. The virtual media and other technologies that can be delivered to patients doorsteps need to strengthened. The trailer which telemedicine showed up in times of COVID-19 can definitely produce a good show in days to come with proper communication between the service provider and receiver

Express: A database of transcriptome profiles encompassing known and novel transcripts across multiple development stages in eye tissues

Advances in sequencing have facilitated nucleotide-resolution genome-wide transcriptomic profiles across multiple mouse eye tissues. However, these RNA sequencing (RNA-seq) based eye developmental transcriptomes are not organized for easy public access, making any further analysis challenging. Here, we present a new database “Express” (http://www.iupui.edu/∼sysbio/express/) that unifies various mouse lens and retina RNA-seq data and provides user-friendly visualization of the transcriptome to facilitate gene discovery in the eye. We obtained RNA-seq data encompassing 7 developmental stages of lens in addition to that on isolated lens epithelial and fibers, as well as on 11 developmental stages of retina/isolated retinal rod photoreceptor cells from publicly available wild-type mouse datasets. These datasets were pre-processed, aligned, quantified and normalized for expression levels of known and novel transcripts using a unified expression quantification framework. Express provides heatmap and browser view allowing easy navigation of the genomic organization of transcripts or gene loci. Further, it allows users to search candidate genes and export both the visualizations and the embedded data to facilitate downstream analysis. We identified total of >81,000 transcripts in the lens and >178,000 transcripts in the retina across all the included developmental stages. This analysis revealed that a significant number of the retina-expressed transcripts are novel. Expression of several transcripts in the lens and retina across multiple developmental stages was independently validated by RT-qPCR for established genes such as Pax6 and Lhx2 as well as for new candidates such as Elavl4, Rbm5, Pabpc1, Tia1 and Tubb2b. Thus, Express serves as an effective portal for analyzing pruned RNA-seq expression datasets presently collected for the lens and retina. It will allow a wild-type context for the detailed analysis of targeted gene-knockout mouse ocular defect models and facilitate the prioritization of candidate genes from Exome-seq data of eye disease patients

Prognostyczne znaczenie ujemnego wyniku echokardiograficznej próby dobutaminowej w warunkach submaksymalnego obciążenia - badanie z 3-letnią obserwacją

Wstęp: Celem badania była ocena wartości predykcyjnej ujemnego wyniku echokardiograficznej próby dobutaminowej w warunkach submaksymalnego obciążenia (NsubDSE) w odniesieniu do występowania poważnych incydentów sercowych. Metody i wyniki: Analizie poddano pacjentów z ujemnym wynikiem echokardiograficznej próby dobutaminowej należących do dwóch grup wyróżnionych w zależności od przewidywanej maksymalnej częstości rytmu serca (PMHR) (< 85% oraz &#8805; 85% PMHR), w których oceniano występowanie poważnych niepożądanych incydentów sercowych w ciągu 3 lat. Spośród 756 pacjentów z ujemnym wynikiem echokardiograficznej próby dobutaminowej u 415 chorych wartość PMHR wyniosła 85% lub więcej. W obu grupach stwierdzono podobny odsetek osób z frakcją wyrzutową powyżej 50% (80,6% vs. 81,9%; p = 0,66). Grupa z NsubDSE charakteryzowała się większą częstością stosowania leków hamujących przewodzenie przez łącze przedsionkowo-komorowe (58,7% vs. 39,9%; p < 0,0001) oraz większą częstością występowania cukrzycy (38,7% vs. 27,6%; p = 0,001). Analiza Kaplana-Meiera nie wykazała różnic przeżycia bez zgonu sercowego (98% vs. 98%; p = 0,88), zawału serca niezakończonego zgonem (94% vs. 94%; p = 0,85) lub wszystkich poważnych incydentów sercowych (81% vs. 78%; p = 0,24). Czynnikami predykcyjnymi incydentów sercowych w analizie wielozmiennej były cukrzyca i zachowana frakcja wyrzutowa (p = 0,005). Wnioski: W niniejszym badaniu osiągnięcie NsubDSE wiązało się z korzystnym rokowaniem. Uzyskiwano je częściej u chorych na cukrzycę, ale w tej grupie częściej występowały też incydenty sercowe pomimo zachowanej frakcji wyrzutowej. U osób z tej grupy dużego ryzyka wskazana jest więc dalsza diagnostyka choroby wieńcowej

Association of SUMOlation Pathway Genes With Stroke in a Genome-wide Association Study in India

OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker–based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10(−8). The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p(lowest) = 1.74 × 10(−58)) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10(−9)) and 18-carbon fatty acid metabolism (p = 7.36 × 10(−12)). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10(−6). Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke

Transient receptor potential canonical 5 (TRPC5) protects against pain and vascular inflammation in arthritis and joint inflammation

Objective: Transient receptor potential canonical 5 (TRPC5) is functionally expressed on a range of cells including fibroblast-like synoviocytes, which play an important role in arthritis. A role for TRPC5 in inflammation has not been previously shown in vivo. We investigated the contribution of TRPC5 in arthritis. Methods: Male wild-type and TRPC5 knockout (KO) mice were used in a complete Freund’s adjuvant (CFA)-induced unilateral arthritis model, assessed over 14 days. Arthritis was determined by measurement of knee joint diameter, hindlimb weightbearing asymmetry and pain behaviour. Separate studies involved chronic pharmacological antagonism of TRPC5 channels. Synovium from human post-mortem control and inflammatory arthritis samples were investigated for TRPC5 gene expression. Results: At baseline, no differences were observed. CFA-induced arthritis resulted in increased synovitis in TRPC5 KO mice assessed by histology. Additionally, TRPC5 KO mice demonstrated reduced ipsilateral weightbearing and nociceptive thresholds (thermal and mechanical) following CFA-induced arthritis. This was associated with increased mRNA expression of inflammatory mediators in the ipsilateral synovium and increased concentration of cytokines in synovial lavage fluid. Chronic treatment with ML204, a TRPC5 antagonist, augmented weightbearing asymmetry, secondary hyperalgesia and cytokine concentrations in the synovial lavage fluid. Synovia from human inflammatory arthritis demonstrated a reduction in TRPC5 mRNA expression. Conclusions: Genetic deletion or pharmacological blockade of TRPC5 results in an enhancement in joint inflammation and hyperalgesia. Our results suggest that activation of TRPC5 may be associated with an endogenous anti-inflammatory/analgesic pathway in inflammatory joint conditions

Prognostic implications of negative dobutamine stress echocardiography in African Americans compared to Caucasians

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Prognostic significance of submaximal negative dobutamine stress echocardiography: A 3-year follow-up study

Background: To estimate the prognostic value of submaximal negative dobutamine stress echocardiography (NDSE) on major cardiac events. Methods and results: Patients with NDSE were analyzed in 2 cohorts based on predicted maximal heart rate (PMHR) (< 85% or &#8805; 85% PMHR) and were assessed for major adverse cardiac events over 3 years. Of 756 patients with NDSE, 415 achieved &#8805; 85% PMHR. Both groups had comparable ejection fractions (EF) > 50% (80.6% vs. 81.9%, p = 0.66). The NsubDSE group had higher rates of atrioventricular nodal blocker use (58.7% vs. 39.9%, p < 0.0001), and diabetes (38.7% vs. 27.6%, p = 0.001). Kaplan-Meier survival analysis showed no differences in freedom from cardiac death (98% vs. 98%, p = 0.88), nonfatal myocardial infarction (94% vs. 94%, p = 0.85), or combined major cardiac events (81% vs. 78%, p = 0.24). Diabetes and preserved ejection fraction were predictive of cardiac events in a multi-variate analysis (p = 0.005). Conclusions: In our study, NsubDSE carried a favorable prognosis. Diabetics were more likely to have an NsubDSE and suffer from a cardiac event despite a preserved ejection fraction. Hence further evaluation for coronary artery disease in this high risk cohort should be pursued. (Cardiol J 2008; 15: 237-244

The anti-ageing hormone klotho induces Nrf2-mediated antioxidant defences in human aortic smooth muscle cells

Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2‐related factor 2 (Nrf2). The anti‐ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated. AngII contributes to vascular ageing and atherogenesis by enhancing VSMC oxidative stress, senescence and apoptosis. This study demonstrates that soluble klotho (1 nM, 24 hrs) significantly induces expression of Nrf2 and the antioxidant enzymes haeme oxygenase (HO‐1) and peroxiredoxin‐1 (Prx‐1) and enhances glutathione levels in human aortic smooth muscle cells (HASMC). Silencing of Nrf2 attenuated the induction of HO‐1 and Prx‐1 expression by soluble klotho. Furthermore, soluble klotho protected against AngII‐mediated HASMC apoptosis and senescence via activation of Nrf2. Thus, our findings highlight a novel Nrf2‐mediated mechanism underlying the protective actions of soluble klotho in HAMSC. Targeting klotho may thus represent a therapeutic strategy against VSMC dysfunction and cardiovascular ageing