Targeting modulation of noradrenalin release in the brain for amelioration of REMS loss-associated effects

Rapid eye movement sleep (REMS) loss affects most of the physiological processes, and it has been proposed that REMS maintains normal physiological processes. Changes in cultural, social, personal traits and life-style severely affect the amount and pattern of sleep, including REMS, which then manifests symptoms in animals, including humans. The effects may vary from simple fatigue and irritability to severe patho-physiological and behavioral deficits such as cognitive and behavioral dysfunctions. It has been a challenge to identify a molecule(s) that may have a potential for treating REMS loss-associated symptoms, which are very diverse. For decades, the critical role of locus coeruleus neurons in regulating REMS has been known, which has further been supported by the fact that the noradrenalin (NA) level is elevated in the brain after REMS loss. In this review, we have collected evidence from the published literature, including those from this laboratory, and argue that factors that affect REMS and vice versa modulate the level of a common molecule, the NA. Further, NA is known to affect the physiological processes affected by REMS loss. Therefore, we propose that modulation of the level of NA in the brain may be targeted for treating REMS loss-related symptoms. Further, we also argue that among the various ways to affect the release of NAlevel, targeting α2 adrenoceptor autoreceptor on the pre-synaptic terminal may be the better option for ameliorating REMS loss-associated symptoms

Involutions and the Chern-Simons filtration in instanton Floer homology

Building on the work of Nozaki, Sato and Taniguchi, we develop an instanton-theoretic invariant aimed at studying strong corks and equivariant bounding. Our construction utilizes the Chern-Simons filtration and is qualitatively different from previous Floer-theoretic methods used to address these questions. As an application, we give an example of a cork whose boundary involution does not extend over any 4-manifold $X$ with $H_1(X, \mathbb{Z}_2) = 0$ and $b_2(X) \leq 1$. In particular, this yields a strong cork which survives stabilization by either of $\smash{\mathbb{CP}^2}$ or $\smash{\overline{\mathbb{CP}}}^2$. We also prove that every nontrivial linear combination of $1/n$-surgeries on the strongly invertible knot $\smash{\overline{9}_{46}}$ constitutes a strong cork. Although Yang-Mills theory has been used to study corks via the Donaldson invariant, this is the first instance where the critical values of the Chern-Simons functional have been utilized to produce such examples. Finally, we discuss the geography question for nonorientable surfaces in the case of extremal normal Euler number.Comment: 57 pages, 11 figure

Efflux Pumps In Antimicrobial Resistance: Mechanism, Regulation And Therapeutic Implications

Efflux pumps play a crucial role in antimicrobial resistance, enabling bacteria to extrude a wide range of antibiotics and other antimicrobial compounds, thereby reducing their intracellular concentration and rendering them ineffective. Understanding the mechanisms underlying efflux pump-mediated resistance is essential for the development of effective strategies to combat this growing threat. This review paper provides an overview of the various efflux pump systems, their regulation mechanisms, and their impact on antimicrobial resistance. Additionally, we discuss the potential therapeutic interventions that target efflux pumps to restore the efficacy of antimicrobial agents

Bank credit risk and macro-prudential policies: role of counter-cyclical capital buffer

This paper investigates the impact of macro-prudential policy (proxied by the counter-cyclical capital buffer (CCyB)) on bank credit risk during uncertain times, as banking sector stability is crucial in promoting financial intermediation. Using a unique daily data set consisting of 4939 credit default swaps (CDS) of 70 banks from 25 countries over the period 2010–2019, we find that CCyB tightening decreases bank-level CDS spreads, while CCyB loosening increases CDS spreads. This heterogeneous effect of CCyB arises due to its asymmetric effect on the capital ratio (i.e., the equity-to-total assets ratio) of banks. Tightening CCyB significantly increases capital, whereas loosening CCyB does not impact capital. Thus, the risks that emanate from the banking sector during periods of heightened uncertainty and financial distress can be significantly dampened when CCyB regulation is enabled. Consequently, macro-prudential policies for banks to hold higher levels of capital during good times are justified to contain financial market risks during downturns

A study of the prevalence of various lower urinary tract symptoms in children with analysis of comorbidities and uroflowmetry

Background: The International Children’s Continence Society (ICCS) in its standardization article in 2006 and subsequent revision in 2014 have provided guidelines for the diagnosis and management of lower urinary tract symptoms (LUTS) in children. However, the terminologies are still not in common parlance and colloquial terms are being heavily used in India. Objective: The objective of the study was to evaluate the clinical spectrum of LUTS and their comorbidities in children. Materials and Methods: This was an observational cross-sectional study conducted in a tertiary care hospital in Northern India. Children, included in the study, aged 5–12 years who presented with LUTS as defined in the ICCS 2014 updated guidelines. A simultaneous analysis of uroflowmetry graphs was also done in these children and the observations presented in this paper. Results: Enuresis was the most common LUTS with which children presented to the OPD (78% cases) followed by increased frequency of micturition (42%). Among comorbidities, constipation was present in one-third patients of LUTS. Uroflowmetry done in LUTS often yields a normal “bell-shaped” graph in majority of the patients (71%). The study shows that many enuretics have underlying other LUTS and comorbidities that we should be aware of and uroflowmetry, if not coupled with urodynamic studies, is not a game changer. Conclusion: There are not many studies post the standardization of the ICCS conducted in India and this study aims at increasing the awareness of the same among physicians and researchers alike

Accurate diagnosis of liver diseases through the application of deep convolutional neural network on biopsy images

Accurate detection of non-alcoholic fatty liver disease (NAFLD) through biopsies is challenging. Manual detection of the disease is not only prone to human error but is also time-consuming. Using artificial intelligence and deep learning, we have successfully demonstrated the issues of the manual detection of liver diseases with a high degree of precision. This article uses various neural network-based techniques to assess non-alcoholic fatty liver disease. In this investigation, more than five thousand biopsy images were employed alongside the latest versions of the algorithms. To detect prominent characteristics in the liver from a collection of Biopsy pictures, we employed the YOLOv3, Faster R-CNN, YOLOv4, YOLOv5, YOLOv6, YOLOv7, YOLOv8, and SSD models. A highlighting point of this paper is comparing the state-of-the-art Instance Segmentation models, including Mask R-CNN, U-Net, YOLOv5 Instance Segmentation, YOLOv7 Instance Segmentation, and YOLOv8 Instance Segmentation. The extent of severity of NAFLD and non-alcoholic steatohepatitis was examined for liver cell ballooning, steatosis, lobular, and periportal inflammation, and fibrosis. Metrics used to evaluate the algorithms' effectiveness include accuracy, precision, specificity, and recall. Improved metrics are achieved by optimizing the hyperparameters of the associated models. Additionally, the liver is scored in order to analyse the information gleaned from biopsy images. Statistical analyses are performed to establish the statistical relevance in evaluating the score for different zones

Evidence-based focused approach for fulfillment of aims: Experiences of an asthma clinic

Background: A new health system for the 21st century should be based on the best scientific knowledge, according to the Institute of Medicine, US. Objective: We have evaluated the effectiveness of asthma clinic providing comprehensive care based on the best available scientific evidence. Materials and Methods: This intervention study was conducted in a tertiary care hospital having a devoted asthma clinic for the  comprehensive management. All children diagnosed as having asthma were included, and data of cases managed from July 2014 to June 2016 were analyzed. Intervention - comprehensive management of asthma including assessment, monitoring, health education, avoidance of triggers, management of comorbid conditions, appropriate medications, written asthma action plan, and counseling for follow-up. Outcome measures were treatment direction, asthma control, emergency visits, and hospitalizations. Results: 260 children were treated over a 2-year period. The effects of focused approach with progressive expertise lead to statistically significant benefits over the two successive years from July 2014 to June 2015 and July 2015 to June2016. These were in: (i) Treatment direction: Cases requiring stepping up of treatment decreased from 36.49% to 17.24% (relative risk [RR]: 0.473 [95% confidence interval {CI}: 0.249-0.895]); p=0.01229, (ii) asthma control: Cases with not well-controlled asthma decreased from 16.44% to 7.02% (RR 0.427: [95% CI: 0.199-0.914]); p=0.045, (iii) emergency department visits decreased from 35.62% to 21.05% (RR 0.591: [95% CI: 0.39-0.897]), p=0.00766, (iv) hospitalizations decreased from 16.44% to 5.26% (RR 0.32: [95% CI: 0.135-0.757]), p=0.00462. Conclusion: Establishing an asthma clinic and progressive expertise leads to significant beneficial results

Temporal trends and factors associated with increased mortality among atrial fibrillation weekend hospitalizations: an insight from National Inpatient Sample 2005–2014

Abstract Objective Atrial fibrillation (AF) weekend hospitalizations were reported to have poor outcomes compared to weekday hospitalizations. The relatively poor outcomes on the weekends are usually referred to as ‘weekend effect’. We aim to understand trends and outcomes among weekend AF hospitalizations. The primary purpose of this study is to evaluate the trends for weekend AF hospitalizations using Nationwide Inpatient Sample 2005–2014. Hospitalizations with AF as the primary diagnosis, in-hospital mortality, length of stay, co-morbidities and cardioversion procedures have been identified using the international classification of diseases 9 codes. Results Since 2005, the weekend AF hospitalizations increased by 27% (72,216 in 2005 to 92,220 in 2014), mortality decreased by 29% (1.32% in 2005 to 0.94% in 2014), increase in urban teaching hospitalizations by 72% (33.32% in 2005 to 57.64% in 2014), twofold increase in depression and a threefold increase in the prevalence of renal failure were noted over the period of 10 years. After adjusting for significant covariates, weekend hospitalizations were observed to have higher odds of in-hospital mortality OR 1.17 (95% CI 1.108–1.235, P < 0.0001). Weekend AF hospitalizations appear to be associated with higher in-hospital mortality. Opportunities to improve care in weekend AF hospitalizations need to be explored.https://deepblue.lib.umich.edu/bitstream/2027.42/152157/1/13104_2019_Article_4440.pd