Swertisin, a novel SGLT2 inhibitor, with improved glucose homeostasis for effective diabetes therapy.

Failing pancreas and subsequent loss of pancreatic ß cells worsen diabetic conditions which are further alleviated by the mounting up of glucose levels. Inhibition of sodium glucose cotransporter 2 (SGLT2) in the kidney responsible for glucose reabsorption strikingly reduces blood glucose levels. Bioactive swertisin showed a promising glucose-lowering effect. Hence, we aimed to mechanistically dissect the glucose lowering property of swertisin. A systematic in silico, in vitro, and in vivo approach was directed for target analysis of swertisin. Molecular docking was performed with Swertisn-hSGLT2 complex. Glucose uptake assay and protein expression for SGLT2 and regulatory proteins were performed under swertisin effect. Various physiological and metabolic parameters were evaluated in STZ induced BALB/c mice using swertisin treatment. SGLT2 expression was evaluated in the kidney tissue of mice. Swertisn-hSGLT2 molecularly docked complex showed similar binding energy compared to the Canagliflozin-hSGLT2 complex. Swertisin inhibited glucose uptake and decreased expression of SGLT2 in HEK293 cells. Swertisin does not affect GLUT mediated glucose transport. Swertisin treated diabetic mice demonstrated remarkable improvement in overall glucose homeostasis. Reduced expression of SGLT2 was found in kidney tissue along with reduced PKC expression which is one of the key regulators of SGLT2. Our study explored SGLT2 as a selective target of swertisin for its swift glucose-lowering action which not only inhibits SGLT2 but also reduces its expression in diabetic condition. Thus, the potential property of swertisin as a glucose-lowering agent is remarkable which points towards the likelihood of a wider avenue of diabetes therapy.

Impact of triage liaison provider on emergency department throughput: A systematic review and meta-analysis.

INTRODUCTION: Emergency department (ED) overcrowding is linked to poor outcome and decreases patient satisfaction. Strategies to control Emergency department (ED) overcrowding has been subject of research. STUDY OBJECTIVES: The objective of this systematic review and meta-analysis was to investigate the impact of triage liaison providers (TLPs) on the ED throughput. METHODS: We searched PubMed, EMBASE, and Web of Science up to April 2019 for studies done in the United States. Primary outcomes were number of patients left without being seen (LWBS) and patients' emergency department length of stay (ED-LOS). ED-LOS data was pooled using mean difference with random effect model. Risk Ratio (RRs) for LWBS was calculated with random effect model with 95% confidence interval (95% CI). RESULTS: Twelve studies encompassing 329,340patients were included in the meta-analysis. Implementation of the TLP system using attending physicians was associated with a decrease in risk of LWBS 0.62 (95% CI 0.54, 0.71), The change in ED-LOS after implementation of TLP was too heterogeneous to pool the data with the mean ΔED-LOS ranging from -82 to +20 min. Stratification of studies by disposition, admitted versus discharged, did not decrease the heterogeneity. CONCLUSION: Implementation of TLP can decrease the rate of LWBS however this review is inconclusive about the effect of TLP on ED-LOS due to the high heterogeneity observed in the literature.

Epidemiology report: trends in sex-specific cerebrovascular disease mortality in Europe based on WHO mortality data.

AIMS: There have been substantial declines in cerebrovascular disease mortality across much of Europe, mirroring trends in deaths from cardiovascular disease as a whole. No study has investigated trends in cerebrovascular disease, and its subtypes within all European countries. This study aimed to examine sex-specific trends in cerebrovascular disease, and three of its sub-types: ischaemic stroke, haemorrhagic stroke, and subarachnoid haemorrhage (SAH), in Europe between 1980 and 2016. METHODS AND RESULTS: Sex-specific mortality data for each country of the World Health Organization (WHO) Europe region were extracted from the WHO global mortality database and analysed using Joinpoint software to examine trends. The number and location of significant joinpoints for each country by sex and subtype was determined using a log-linear model. The annual percentage change within each segment was calculated along with the average annual percentage change over the duration of all available data. The last 35 years have seen large overall declines in cerebrovascular disease mortality rates in the majority of European countries. While these declines have continued steadily in more than half of countries, this analysis has revealed evidence of recent plateauing and even increases in stroke mortality in a number of countries, in both sexes, and in all four geographical sub-regions of Europe. Analysis by stroke sub-type revealed that recent plateauing was most common for haemorraghic stroke and increases were most common for ischaemic stroke. CONCLUSION: These findings highlight the need for continued research into the inequalities in both current stroke mortality outcomes and trends across Europe, as well as the causes behind any recent plateauing of total cerebrovascular disease or its subtypes.

Impact of Provider-In-Triage in a Safety-Net Hospital.

BACKGROUND: Increasing emergency department (ED) utilization has contributed to ED overcrowding, with longer ED length of stay (EDLOS) and more patients leaving without being seen (LWBS), and is associated with higher morbidity and mortality rates. Previous studies of provider in triage (PIT) have shown decreased LWBS, but variable improvements in EDLOS. OBJECTIVES: We evaluated the impact of PIT implementation in an urban safety-net hospital on commonly reported ED throughput metrics. METHODS: This before-and-after study was performed at an academic urban safety hospital. We implemented a PIT team that screened ambulatory ED patients for early discharge or expedited workup. The PIT intervention was implemented 3 days a week from January through April 2019. As controls, we compared throughput metrics from when PIT was unavailable (Group 2) and from 1 year prior (Group 3). RESULTS: There were significantly (p < 0.001) lower rates of LWBS in Group 1 (4.8%, 95% confidence interval [CI] 4.1-5.8%) compared with 2 (7.3%, 95% CI 5.5-9.7%) and 3 (7.8%, 95% CI 6.9-9.0%). Door-to-doctor times were significantly (p < 0.001) lower for Group 1 (148 min, interquartile range [IQR] 88, 226 min) compared with 2 (187 min, IQR 95.5, 266 min) and 3 (215 min, IQR 131, 290 min). EDLOS was significantly (p < 0.001) shorter for Group 1 (337 min, IQR 215, 468 min) compared with 2 (385 min, IQR 271, 516 min) and 3 (413 min, IQR 299, 538 min). CONCLUSIONS: We found significantly lower LWBS rates, shorter EDLOS, and shorter door-to-doctor times after PIT implementation. Compared with previous studies in a variety of settings, we found that PIT significantly improved LWBS and all throughput metrics in a safety net setting.

Fast Diffusion and Segregation along Threading Dislocations in Semiconductor Heterostructures.

Heterogeneous integration of semiconductors combines the functionality of different materials, enabling technologies such as III-V lasers and solar cells on silicon and GaN LEDs on sapphire. However, threading dislocations generated during the epitaxy of these dissimilar materials remain a key obstacle to the success of this approach due to reduced device efficiencies and reliability. Strategies to alleviate this and understand charge carrier recombination at threading dislocations now need an accurate description of the structure of threading dislocations in semiconductor heterostructures. We show that the composition around threading dislocations in technologically important InGaAs/GaAs/Ge/Si heterostructures are indeed different from that of the matrix. Site-specific atom probe tomography enabled by electron channeling contrast imaging reveals this at individual dislocations. We present evidence for the simultaneous fast diffusion of germanium and indium up and down a dislocation, respectively, leading to unique compositional profiles. We also detect the formation of clusters of metastable composition at the interface between Ge and GaAs, driven by intermixing in these two nearly immiscible materials. Together, our results have important implications for the properties of dislocations and interfaces in semiconductors and provide new tools for their study.

Ionic Liquid-Modified Disposable Electrochemical Sensor Strip for Analysis of Fentanyl.

The increasing prevalence of fentanyl and its analogues as contaminating materials in illicit drug products presents a major hazard to first responder and law enforcement communities. Electrochemical techniques have the potential to provide critical information to these personnel via rapid, facile field detection of these materials. Here we demonstrate the use of cyclic square wave voltammetry (CSWV) with screen-printed carbon electrodes (SPCE), modified with the room temperature ionic liquid (RTIL) 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide [C4C1pyrr][NTf2], toward such rapid "on-the-spot" fentanyl detection. This CSWV-based disposable sensor strip system provides an information-rich electrochemical fingerprint of fentanyl, composed of an initial oxidation event at +0.556 V (vs Ag/AgCl) and a reversible reduction and oxidation reaction at -0.235 and -0.227 V, respectively. The combined current and potential characteristics of these anodic and cathodic fentanyl peaks, generated using two CSWV cycles, thus lead to a distinct electrochemical signature. This CSWV profile facilitates rapid (1 min) identification of the target opioid at micromolar concentrations in the presence of other cutting agents commonly found in illicit drug formulations. The new protocol thus holds considerable promise for rapid decentralized fentanyl detection at the "point of need".

Neutral Organic Super Electron Donors Made Catalytic.

Neutral organic super electron donors (SEDs) display impressive reducing power but, until now, it has not been possible to use them catalytically in radical chain reactions. This is because, following electron transfer, these donors form persistent radical cations that trap substrate-derived radicals. This paper unlocks a conceptually new approach to super electron donors that overcomes this issue, leading to the first catalytic neutral organic super electron donor.

Asymmetric syntheses of nakinadine D, nakinadine E, and nakinadine F: confirmation of their relative (RS,SR)-configurations and proposal of their absolute (2S,3R)-configurations.

The syn- and anti-diastereoisomeric forms of the reported structures of the marine alkaloids nakinadines D-F have been synthesized, for the first time in all cases, via an approach involving asymmetric Mannich-type (imino-aldol) reactions of methyl phenylacetate with N-tert-butylsulfinyl imines as the key steps to control the stereochemistry. Comparison of the (1)H and (13)C NMR spectroscopic data reported for the natural materials with those acquired for these synthetic samples confirms the initially assigned relative (RS,SR)-configurations of these three alkaloids. In the absence of specific rotation (or other diagnostic) data for the natural materials, it is not possible to unambiguously assign their absolute configurations, although given the absolute (2S)-configurations assigned to nakinadines B and C, and the absolute (2S,3R)-configuration previously established for nakinadine A, the data herein uphold our proposal that nakinadines D-F share the absolute (2S,3R)-configuration.

Metagenomic-based study of the phylogenetic and functional gene diversity in Galápagos land and marine iguanas.

In this study, a metagenome-based analysis of the fecal samples from the macrophytic algae-consuming marine iguana (MI; Amblyrhynchus cristatus) and terrestrial biomass-consuming land iguanas (LI; Conolophus spp.) was conducted. Phylogenetic affiliations of the fecal microbiome were more similar between both iguanas than to other mammalian herbivorous hosts. However, functional gene diversities in both MI and LI iguana hosts differed in relation to the diet, where the MI fecal microbiota had a functional diversity that clustered apart from the other terrestrial-biomass consuming reptilian and mammalian hosts. A further examination of the carbohydrate-degrading genes revealed that several of the prevalent glycosyl hydrolases (GH), glycosyl transferases (GT), carbohydrate binding modules (CBM), and carbohydrate esterases (CE) gene classes were conserved among all examined herbivorous hosts, reiterating the important roles these genes play in the breakdown and metabolism of herbivorous diets. Genes encoding some classes of carbohydrate-degrading families, including GH2, GH13, GT2, GT4, CBM50, CBM48, CE4, and CE11, as well as genes associated with sulfur metabolism and dehalogenation, were highly enriched or unique to the MI. In contrast, gene sequences that relate to archaeal methanogenesis were detected only in LI fecal microbiome, and genes coding for GH13, GH66, GT2, GT4, CBM50, CBM13, CE4, and CE8 carbohydrate active enzymes were highly abundant in the LI. Bacterial populations were enriched on various carbohydrates substrates (e.g., glucose, arabinose, xylose). The majority of the enriched bacterial populations belong to genera Clostridium spp. and Enterococcus spp. that likely accounted for the high prevalence of GH13 and GH2, as well as the GT families (e.g., GT2, GT4, GT28, GT35, and GT51) that were ubiquitously present in the fecal microbiota of all herbivorous hosts.

Evolution of spontaneous portosystemic shunts over time and following aetiological intervention in patients with cirrhosis.

Background & Aims: Spontaneous portosystemic shunts (SPSS) develop frequently in cirrhosis. Changes over time and the effect of aetiological interventions on SPSS are unknown, so we aimed to explore the effect of these variables on SPSS evolution. Methods: Patients with cirrhosis from the Baveno VI-SPSS cohort were selected provided a follow-up abdominal CT or MRI scan was available. Clinical and laboratory data were collected at baseline and follow-up. Imaging tests were reviewed to evaluate changes in the presence and size of SPSS (large (L)-SPSS was ≥8 mm) over time. Regarding alcohol- or HCV-related cirrhosis, two populations were defined: cured patients (abstinent from alcohol or successful HCV therapy), and non-cured patients. Results: A total of 617 patients were included. At baseline SPSS distribution was 22% L-SPSS, 30% small (S)-SPSS, and 48% without (W)-SPSS. During follow-up (median follow-up of 63 months), SPSS distribution worsened: L-SPSS 26%, S-SPSS 32%, and W-SPSS 42% (p <0.001). Patients with worse liver function during follow-up showed a simultaneous aggravation in SPSS distribution. Non-cured patients (n = 191) experienced a significant worsening in liver function, more episodes of liver decompensation and lower transplant-free survival compared to cured patients (n = 191). However, no differences were observed regarding SPSS distribution at inclusion and at follow-up, with both groups showing a trend to worsening. Total shunt diameter increased more in non-cured (52%) than in cured patients (28%). However, total shunt area (TSA) significantly increased only in non-cured patients (74 to 122 mm2, p <0.001). Conclusions: The presence of SPSS in cirrhosis increases over time and parallels liver function deterioration. Aetiological intervention in these patients reduces liver-related complications, but SPSS persist although progression is decreased. Impact and implications: There is no information regarding the evolution of spontaneous portosystemic shunts (SPSS) during the course of cirrhosis, and especially after disease regression with aetiological interventions, such as HCV treatment with direct-acting antivirals or alcohol abstinence. These results are relevant for clinicians dealing with patients with cirrhosis and portal hypertension because they have important implications for the management of cirrhosis with SPSS after disease regression. From a practical point of view, physicians should be aware that in advanced cirrhosis with portal hypertension, after aetiological intervention, SPSS mostly persist despite liver function improvement, and complications related to SPSS may still develop.

Artificial intelligence enabled COVID-19 detection: techniques, challenges and use cases.

Deep Learning and Machine Learning are becoming more and more popular as their algorithms get progressively better, and their use is expected to have the large effect on improving the health care system. Also, the pandemic was a chance to show how adding AI to healthcare infrastructure could help, since infrastructures around the world are overworked and falling apart. These new technologies can be used to fight COVID-19 because they are flexible and can be changed. Based on these facts, we looked at how the ML and DL-based models can be used to deal with the COVID-19 pandemic problem and what the pros and cons of each are. This paper gives a full look at the different ways to find COVID-19. We looked at the COVID-19 issues in a systematic way and then rated the methods and techniques for finding it based on their availability, ease of use, accuracy, and cost. We have also shown in pictures how well each of the detection techniques works. We did a comparison of different detection models based on the above factors. This helps researchers understand the different methods and the pros and cons of using them as the basis for their research. In the last part, we talk about the open challenges and research questions that come with putting these techniques together with other detection methods.

Utility of an integrated health system specialty pharmacy in provision of extended-release buprenorphine for patients with opioid use disorder.

PURPOSE: Extended-release (ER) monthly injectable buprenorphine offers an alternative to daily sublingual (SL) dosing for treatment of opioid use disorder (OUD) that may be attractive to several patient populations, including those with barriers to adherence and the frequent follow-up that are necessary for traditional SL buprenorphine. Despite the potential benefits of ER-buprenorphine, there are significant barriers to healthcare provider adoption that may prevent utilization in the populations that would benefit. SUMMARY: Our health system began providing clinic-administered ER-buprenorphine as treatment for OUD in May 2018 at a single clinic. Expansion was limited due to difficulties with delayed and inaccurate medication delivery and heavy administrative burden. To facilitate uptake of ER-buprenorphine for patients who could benefit, our integrated health-system specialty pharmacy (HSSP) assumed responsibility for medication distribution and administrative management beginning in October 2019. The HSSP provided accurate medication delivery, alleviated administrative burdens of benefits investigation and Risk Evaluation and Mitigation Strategy compliance, and decreased medication wastage by implementing a medication return process. Subsequently, ER-buprenorphine services were expanded to 4 additional sites, allowing 244 more patients to receive treatment. CONCLUSION: HSSP support can provide significant benefit to patients and the health system through coordinating ER-buprenorphine dispensing and delivery.

Fournier's gangrene reconstruction: A 10-year retrospective analysis of practice at Guys and St Thomas's NHS Foundation Trust.

Fournier's gangrene is a rare and potentially fatal condition that affects the external genitalia and perineum as a necrotizing soft-tissue infection. It is equally prevalent in men and women and although there are many ways to manage the condition, it must be done so effectively because there is a chance that life-threatening complications could develop. This retrospective study set out to fill any knowledge gaps, compare reconstructive options to those described in the literature, and promote reflection on current management. Between January 2010 and January 2020, all perineal debridement operation notes were examined. The primary conclusions were that a large majority of defects could be repaired using split skin grafts to reduce surgical time and donor site morbidity. To avoid secondary contracture and the need for revision surgery, full-thickness skin grafts should be used whenever possible to treat penile defects.

Vitamins and Minerals for Blood Pressure Reduction in the General, Normotensive Population: A Systematic Review and Meta-Analysis of Six Supplements.

Hypertension is the leading preventable risk factor for cardiovascular disease and all-cause mortality worldwide. However, studies have shown increased risk of mortality from heart disease and stroke even within the normal blood pressure (BP) range, starting at BPs above 110-115/70-75 mm Hg. Nutraceuticals, such as vitamins and minerals, have been studied extensively for their efficacy in lowering BP and may be of benefit to the general, normotensive population in achieving optimal BP. Our study investigated the effects of six nutraceuticals (Vitamins: C, D, E; Minerals: Calcium, Magnesium, Potassium) on both systolic blood pressure (SBP) and diastolic blood pressure (DBP) in this population. We performed a systematic review and pairwise meta-analysis for all six supplements versus placebo. Calcium and magnesium achieved significant reductions in both SBP and DBP of -1.37/-1.63 mm Hg and -2.79/-1.56 mm Hg, respectively. Vitamin E and potassium only yielded significant reductions in SBP with values of -1.76 mm Hg and -2.10 mm Hg, respectively. Vitamins C and D were not found to significantly lower either SBP or DBP. Future studies should determine optimal dosage and treatment length for these supplements in the general, normotensive population.

Double-layer biodegradable temporising matrix reconstruction for abdominal skin and soft-tissue reconstruction.

Dermatofibrosarcoma protuberans (DFSP) is a rare, locally invasive dermal sarcoma. The management is generally surgical, with wide local excision (WLE) forming the mainstay of treatment. Large abdominal wall defects are most aesthetically reconstructed using pedicled or free flaps; however, these require tumour-free surgical margins, and are off-set by donor site morbidity. We describe an alternative, aesthetic and low-morbidity technique for reconstruction of a subfascial defect following WLE of DFSP in a young woman in her early 20s, using two layers of a novel synthetic dermal matrix (NovoSorbBTM). To our knowledge, a double-layer reconstruction using an artificial dermal matrix has never been described for trunk reconstruction. We found that double-layer biodegradable temporising matrix can restore the inherent thickness and pliability of skin in a partial-thickness abdominal wall defect and offers improved durability and cosmesis compared with skin grafting or indeed single layer skin substitutes alone.

A National Survey on Perineal Reconstruction Following Standard and Extralevator Abdominoperineal Excision: Current Practices and Trends in the UK.

Background Challenging perineal defects resulting from extralevator (ELAPE) and standard abdominoperineal excision (APE) have given rise to an emerging multidisciplinary approach between colorectal and plastic surgeons. At present, there is a relative paucity of evidence on best practice. This study sought to assess current national practice concerning perineal reconstruction following APE/ELAPE in the United Kingdom (UK) and to determine the factors involved in reconstruction choice. Methodology An anonymised survey was circulated to consultant plastic surgeons at all 48 UK centres performing perineal reconstruction following APE/ELAPE. Responses were collected between October 2021 and April 2022. Results Complete responses were received from 24 units nationally. All units had a dedicated APE/ELAPE service. Overall, 70% adopted a standardised reconstructive approach, the most common being the inferior gluteal artery perforator flap (n = 11). Significant variation was identified in the reconstructive technique. Similar differences were observed in the perceived importance of surgical factors guiding the reconstructive decision-making process, the top priorities being the size of the defect and previous radiotherapy. Conclusions The variability of responses suggests a lack of national consensus on optimal reconstruction following APE/ELAPE, despite the majority of centres employing a standardised approach to reconstruction. Our study highlights important surgical decision-making factors and provides valuable insight to aid in developing national collaborative evidence-based guidelines on best practice.

Management of a rare, giant multicompartmental lipoma of the hand: a case report and review of the literature.

Lipomas are the commonest benign tumour, made up exclusively of adipose tissue, and can arise anywhere in the body. However, giant lipomas of the hand, defined as >5 cm in diameter, are rare. They have the potential to invade into surrounding areas and cause a multitude of symptoms due to the compression and proximity of underlying structures. We describe a case of a 64-year-old woman who presents with a swelling of the left thenar eminence, associated with numbness and tingling in all fingers. Magnetic resonance imaging and nerve conduction studies confirmed the diagnosis of a lipoma causing median nerve compression. The patient underwent elective surgical excision with good postoperative recovery. The excised lesion, measuring 12 × 7 × 2.4 cm, is one of the largest giant lipomas of the hand reported in literature, and the first to demonstrate invasion from the mid palmar space into both the dorsal sub-aponeurotic space and carpal tunnel.

The role of biodegradable temporizing matrix in the management of a patient with major burns and anorexia nervosa.

Severe malnutrition secondary to anorexia nervosa results in deeper burns and significantly impacts wound healing, which represents a major challenge to burn management. The use of acellular dermal matrices, such as biodegradable temporizing matrix (BTM), is a valuable tool to overcome the surgical limitations. We describe a case of a 36-year-old female with a background of anorexia nervosa (body mass index of 12.3) presenting with a 30% total burns surface area (TBSA) burn. All of her burns were excised down to fascia due to the absence of subcutaneous fat. Her thin skin and depleted nutritional status significantly impacted reconstructive options. BTM was utilized to create a neodermis and provide adequate time to optimize the nutritional status before autologous skin resurfacing 3 weeks later, which yielded robust coverage with minimal donor site morbidity. Despite initial surgical and nutritional challenges, excellent outcomes were achieved in terms of wound healing, scar contractures and mobility.