Effect Of Metformin On Global Phosphorylation Profiles Of Primary Skeletal Muscle Cells Derived From Overweight/obese Insulin Resistant Human Participants

Metformin is a drug from the biguanide class and it has been in use for the treatment of type 2 diabetes for a long time, and it can improve insulin sensitivity in skeletal muscle. However, the mechanism for metformin’s action is unclear. Phosphatases and kinases, and their subunits are the proteins required for dephosphorylation and phosphorylation of proteins in cells during various signaling pathways. Phosphorylation studies of proteins from primary cell culture derived from skeletal muscle tissue from obese/overweight insulin resistant participants will help to understand the regulation of phosphorylation in phosphatases and kinases by metformin. In the current research, we used primary cell culture cells of human skeletal muscle tissue to identify and quantify the phosphorylation effects of metformin in obese/overweight participants. After treating cells with different conditions which include different concentration of metformin, we identify 2930 phospho sites in 1085 proteins. Among 2930 phospho sites, 325 phospho sites showed significant change among 6 sets of samples (total 24 samples). Of particular interest, metformin treatment significantly changed phosphorylation levels of 23 sites including 6 phosphorylation sites in 4 phosphatase subunits and 17 phosphorylation sites in 9 kinases/kinase subunits. These results provide new information on how metformin works in skeletal muscle cells

ARUBA: An Architecture-Agnostic Balanced Loss for Aerial Object Detection

Deep neural networks tend to reciprocate the bias of their training dataset. In object detection, the bias exists in the form of various imbalances such as class, background-foreground, and object size. In this paper, we denote size of an object as the number of pixels it covers in an image and size imbalance as the over-representation of certain sizes of objects in a dataset. We aim to address the problem of size imbalance in drone-based aerial image datasets. Existing methods for solving size imbalance are based on architectural changes that utilize multiple scales of images or feature maps for detecting objects of different sizes. We, on the other hand, propose a novel ARchitectUre-agnostic BAlanced Loss (ARUBA) that can be applied as a plugin on top of any object detection model. It follows a neighborhood-driven approach inspired by the ordinality of object size. We evaluate the effectiveness of our approach through comprehensive experiments on aerial datasets such as HRSC2016, DOTAv1.0, DOTAv1.5 and VisDrone and obtain consistent improvement in performance.Comment: Accepted to WACV 202

Comparison of Adaptive Optics Scanning Light Ophthalmoscopic Fluorescein Angiography and Offset Pinhole Imaging

Recent advances to the adaptive optics scanning light ophthalmoscope (AOSLO) have enabled finer in vivo assessment of the human retinal microvasculature. AOSLO confocal reflectance imaging has been coupled with oral fluorescein angiography (FA), enabling simultaneous acquisition of structural and perfusion images. AOSLO offset pinhole (OP) imaging combined with motion contrast post-processing techniques, are able to create a similar set of structural and perfusion images without the use of exogenous contrast agent. In this study, we evaluate the similarities and differences of the structural and perfusion images obtained by either method, in healthy control subjects and in patients with retinal vasculopathy including hypertensive retinopathy, diabetic retinopathy, and retinal vein occlusion. Our results show that AOSLO OP motion contrast provides perfusion maps comparable to those obtained with AOSLO FA, while AOSLO OP reflectance images provide additional information such as vessel wall fine structure not as readily visible in AOSLO confocal reflectance images. AOSLO OP offers a non-invasive alternative to AOSLO FA without the need for any exogenous contrast agent

Longitudinal imaging of microvascular remodelling in proliferative diabetic retinopathy using adaptive optics scanning light ophthalmoscopy

Purpose To characterise longitudinal changes in the retinal microvasculature of type 2 diabetes mellitus (T2DM) as exemplified in a patient with proliferative diabetic retinopathy (PDR) using an adaptive optics scanning light ophthalmoscope (AOSLO). Methods A 35-year-old T2DM patient with PDR treated with scatter pan-retinal photocoagulation at the inferior retina 1 day prior to initial AOSLO imaging along with a 24-year-old healthy control were imaged in this study. AOSLO vascular structural and perfusion maps were acquired at four visits over a 20-week period. Capillary diameter and microaneurysm area changes were measured on the AOSLO structural maps. Imaging repeatability was established using longitudinal imaging of microvasculature in the healthy control. Results Capillary occlusion and recanalisation, capillary dilatation, resolution of local retinal haemorrhage, capillary hairpin formation, capillary bend formation, microaneurysm formation, progression and regression were documented over time in a region 2° superior to the fovea in the PDR patient. An identical microvascular network with same capillary diameter was observed in the control subject over time. Conclusions High-resolution serial AOSLO imaging enables in vivo observation of vasculopathic changes seen in diabetes mellitus. The implications of this methodology are significant, providing the opportunity for studying the dynamics of the pathological process, as well as the possibility of identifying highly sensitive and non-invasive biomarkers of end organ damage and response to treatment

\u3cem\u3eIn vivo\u3c/em\u3e Imaging of Human Retinal Microvasculature Using Adaptive Optics Scanning Light Ophthalmoscope Fluorescein Angiography

The adaptive optics scanning light ophthalmoscope (AOSLO) allows visualization of microscopic structures of the human retina in vivo. In this work, we demonstrate its application in combination with oral and intravenous (IV) fluorescein angiography (FA) to the in vivo visualization of the human retinal microvasculature. Ten healthy subjects ages 20 to 38 years were imaged using oral (7 and/or 20 mg/kg) and/or IV (500 mg) fluorescein. In agreement with current literature, there were no adverse effects among the patients receiving oral fluorescein while one patient receiving IV fluorescein experienced some nausea and heaving. We determined that all retinal capillary beds can be imaged using clinically accepted fluorescein dosages and safe light levels according to the ANSI Z136.1-2000 maximum permissible exposure. As expected, the 20 mg/kg oral dose showed higher image intensity for a longer period of time than did the 7 mg/kg oral and the 500 mg IV doses. The increased resolution of AOSLO FA, compared to conventional FA, offers great opportunity for studying physiological and pathological vascular processes

Classification of Human Retinal Microaneurysms Using Adaptive Optics Scanning Light Ophthalmoscope Fluorescein Angiography

Purpose. Microaneurysms (MAs) are considered a hallmark of retinal vascular disease, yet what little is known about them is mostly based upon histology, not clinical observation. Here, we use the recently developed adaptive optics scanning light ophthalmoscope (AOSLO) fluorescein angiography (FA) to image human MAs in vivo and to expand on previously described MA morphologic classification schemes. Methods. Patients with vascular retinopathies (diabetic, hypertensive, and branch and central retinal vein occlusion) were imaged with reflectance AOSLO and AOSLO FA. Ninety-three MAs, from 14 eyes, were imaged and classified according to appearance into six morphologic groups: focal bulge, saccular, fusiform, mixed, pedunculated, and irregular. The MA perimeter, area, and feret maximum and minimum were correlated to morphology and retinal pathology. Select MAs were imaged longitudinally in two eyes. Results. Adaptive optics scanning light ophthalmoscope fluorescein angiography imaging revealed microscopic features of MAs not appreciated on conventional images. Saccular MAs were most prevalent (47%). No association was found between the type of retinal pathology and MA morphology (P = 0.44). Pedunculated and irregular MAs were among the largest MAs with average areas of 4188 and 4116 μm2, respectively. Focal hypofluorescent regions were noted in 30% of MAs and were more likely to be associated with larger MAs (3086 vs. 1448 μm2, P = 0.0001). Conclusions. Retinal MAs can be classified in vivo into six different morphologic types, according to the geometry of their two-dimensional (2D) en face view. Adaptive optics scanning light ophthalmoscope fluorescein angiography imaging of MAs offers the possibility of studying microvascular change on a histologic scale, which may help our understanding of disease progression and treatment response

Phase I interim results of a phase I/II study of the IgG-Fc fusion COVID-19 subunit vaccine, AKS-452

To address the coronavirus disease 2019 (COVID-19) pandemic caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a recombinant subunit vaccine, AKS-452, is being developed comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain (SP/RBD) antigen and human IgG1 Fc emulsified in the water-in-oil adjuvant, Montanide™ ISA 720. A single-center, open-label, phase I dose-finding and safety study was conducted with 60 healthy adults (18–65 years) receiving one or two doses 28 days apart of 22.5 µg, 45 µg, or 90 µg of AKS-452 (i.e., six cohorts, N = 10 subjects per cohort). Primary endpoints were safety and reactogenicity and secondary endpoints were immunogenicity assessments. No AEs ≥ 3, no SAEs attributable to AKS-452, and no SARS-CoV-2 viral infections occurred during the study. Seroconversion rates of anti-SARS-CoV-2 SP/RBD IgG titers in the 22.5, 45, and 90 µg cohorts at day 28 were 70%, 90%, and 100%, respectively, which all increased to 100% at day 56 (except 89% for the single-dose 22.5 µg cohort). All IgG titers were Th1-isotype skewed and efficiently bound mutant SP/RBD from several SARS-CoV-2 variants with strong neutralization potencies of live virus infection of cells (including alpha and delta variants). The favorable safety and immunogenicity profiles of this phase I study (ClinicalTrials.gov: NCT04681092) support phase II initiation of this room-temperature stable vaccine that can be rapidly and inexpensively manufactured to serve vaccination at a global scale without the need of a complex distribution or cold chain

Assessing the knowledge, attitudes and practice of type 2 diabetes among patients of Saurashtra region, Gujarat

As India will ranks first in diabetes now and will continue to do so in 2025, we must prevent the disease by various measures. Before setting the programmes, we should have ample data on the population's knowledge, attitude and practice (KAP) of diabetes. There are some epidemiological studies from southern India, Mumbai and north India, but there is no KAP study from Gujarat. The study was conducted between the period of June 2007 to November 2007 at three centers of Saurashtra region. Out of 300 patients who were given questionnaire, 238 patients were included for the analysis, rest were excluded due to various reasons. 52% were male. Mean age of patients was 55.82±10.2 years (95% CI 54.5-57.1) with mean weight of 64.52±10.96 Kg (95% CI 62.8-66.2). Mean duration of diabetes was 8.2±6.8 years (95% CI 7.2-9.1). 46% of patients knew the pathophysiology of diabetes. Nearly 50% knew the complications of diabetes. Dietary modifications were relied more than exercises among the interviewed subjects. Most of the lacunae in knowledge prevailed in drug therapy of diabetes. Insulin was not favored by most of patients. An encouraging finding in our study was that most believed in self-care and ready to change. Consultation time given by their treating doctors was less than 5 minutes in nearly 50%. Foot care and education to prevent complications were least suggested by doctors

Peripheral ossifying fibroma

Here we report an unusual case of peripheral ossifying fibroma in a 57-year-old woman, who reported to the KLES Institute of Dental Sciences, Belgaum. Clinically, the lesion appeared as a nodular swelling on the gingiva. Though the possibility exists that the lesion is reactive, it appears to be true neoplastic growth and a purely soft tissue process arising from the gingiva. Thus, we proposed the term peripheral ossifying fibroma for this distinct lesion

Coblator assisted resection of sinonasal Hemangiopericytoma-A case report

Hemangiopericytomas are vascular tumors arising from the capillary pericytes of Zimmermann present around the capillaries and post capillary venules. Known for a high rate of recurrence, a wide surgical excision is the treatment of choice of these tumors. These tumors are very vascular making surgical excision difficult. The coblation system has made it easier in resection of these vascular tumors. We present a case report of a extensive sinonasal hemangiopericytoma in a old man which was successfully resected with coblation technology