Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021.

People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes.

Control of mesenchymal stem cell phenotype and differentiation depending on cell adhesion mechanism.

Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor (FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. Elucidation of the glycan structure on the cell membrane may help characterise hMSC function.

Isolation and characterization of broad spectrum bacteriophages lytic to Vibrio harveyi from shrimp farms of Kerala, India.

UNLABELLED: Of 33 phages isolated from various shrimp farms in Kerala, India, six were segregated to have broad spectrum lytic efficiency towards 87 isolates of Vibrio harveyi with cross-infecting potential to a few other important aquaculture pathogens. They were further tested on beneficial aquaculture micro-organisms such as probiotics and nitrifying bacterial consortia and proved to be noninfective. Morphological characterization by transmission electron microscopy (TEM) and molecular characterization by RAPD and SDS-PAGE proved them distinct and positioned under Caudovirales belonging to Myoviridae and Siphoviridae. SIGNIFICANCE AND IMPACT OF THE STUDY: In sustainable aquaculture, application of antibiotics is prohibited to manage vibriosis, including the one caused by Vibrio harveyi. In lieu of antibiotics, an eco-friendly alternative method, phage therapy, is recommended here. To facilitate the same, a set of six broad spectrum V. harveyi phages, as cocktail, has been constituted and characterized based on morphological traits and by employing molecular tools. These phages were also found to infect other aquaculture pathogens belonging to Vibrio and Aeromonas. Subsequent to in vivo trials, they can find application in shrimp hatcheries as prophylactics and therapeutics.

Novel antibacterial silver-silica surface coatings prepared by chemical vapour deposition for infection control.

AIMS: Environmental contamination plays an important role in the transmission of infections, especially healthcare-associated infections. Disinfection transiently reduces contamination, but surfaces can rapidly become re-contaminated. Antimicrobial surfaces may partially overcome that limitation. The antimicrobial activity of novel surface coatings containing silver and silica prepared using a flame-assisted chemical vapour deposition method on both glass and ceramic tiles was investigated. METHODS AND RESULTS: Antimicrobial activity against a variety of bacteria including recent clinical isolates was investigated based on the BS ISO 22196:2007 Plastics--Measurement of antibacterial activity on plastics surfaces, British Standards Institute, London, method. Activity on natural contamination in an in use test in a toilet facility was also determined. Activity on standard test strains gave a log10 reduction of five after 1-4 h. The hospital isolates were more resistant, but MRSA was reduced by a log10 reduction factor of >5 after 24 h. Activity was maintained after simulated ageing and washing cycles. Contamination in situ was reduced by >99.9% after 4 months. Activity was inhibited by protein, but, although this could be overcome by increasing the amount of silver in the films, this reduced the hardness of the coating. CONCLUSIONS: The coatings had a good activity against standard test strains. Clinical isolates were killed more slowly but were still sensitive. The optimum composition for use therefore needs to be a balance between activity and durability. SIGNIFICANCE AND IMPACT OF THE STUDY: The coatings may have applications in health care by maintaining a background antimicrobial activity between standard cleaning and disinfection regimes. They may also have applications in other areas where reduction in microbial contamination is important, for example, in the food industry.

Domestic violence as a risk factor for infant and child mortality: a community-based case-control study from southern India.

BACKGROUND: Violence against women may have an impact on infant and child mortality. We aimed to determine whether domestic violence is a risk factor for infant and child death. METHODS: Eighty infant and child deaths (under 5 years of age) were identified from a central register of a comprehensive community health programme in rural southern India; controls were matched for age, gender and street of residence. RESULTS: Domestic violence during the lifetime (OR 2.63, 95% CI 1.39-4.99), which was severe (OR 4.00, 95% CI 2.02-7.94) and during pregnancy (OR 5.69, 95% CI 2.03-15. 93) and father's smoking status (OR 3.81, 95% CI 1.92-7.55) were significantly related to infant and child death while immunization being completed for age (OR 0.04, 95% CI 0.01-0.19) and having at least one boy child in the family (OR 0.29, 95% CI 0.14-0.59) were protective. These variables remained statistically significantly associated with outcome after adjusting for other determinants using conditional logistic regression. CONCLUSION: There is evidence for an association between domestic violence in mothers, and infant and child death.

Simulating atmospheric drought: Silica gel packets dehumidify mesocosm microclimates.

1. As global temperatures rise, droughts are becoming more frequent and severe. To predict how drought might affect plant communities, ecologists have traditionally designed experiments with controlled watering regimes and rainout shelters. Both treatments have proven effective for simulating soil drought. However, neither are designed to directly modify atmospheric drought. 2. Here, we detail the efficacy of a silica gel atmospheric drought treatment in outdoor mesocosms with and without a cooccurring soil drought treatment. At California State University, Los Angeles, we monitored relative humidity (RH), temperature, and vapor pressure deficit (VPD) every 10 minutes for five months in a bare-ground experiment featuring mesocosms treated with soil drought (reduced watering) and/or atmospheric drought (silica packets suspended 12 cm above soil). 3. We found that silica packets dehumidified these microclimates most effectively (-5% RH) when combined with reduced soil water, regardless of the ambient humidity levels of the surrounding air. Further, packets increased microclimate VPD most effectively (+0.4 kPa) when combined with reduced soil water and ambient air temperatures above 20°C. Finally, packets simulated atmospheric drought most consistently when replaced within three days of deployment. 4. Our results demonstrate the use of silica packets as effective dehumidification agents in outdoor drought experiments. We emphasize that incorporating atmospheric drought in existing soil drought experiments can improve our understandings of the ecological impacts of drought.

What can the Interventional Endoscopist Offer in the Management of Upper Gastrointestinal Malignancies?

The therapeutic possibilities of endoscopy have rapidly increased in the last decades and now allow organ-sparing treatment of early upper gastrointestinal malignancy as well as an increasing number of options for symptom palliation. This review contains an overview of the interventional endoscopic procedures in upper gastrointestinal malignancies. It describes endoscopic treatment of early oesophageal and gastric cancers, and the palliative options in managing dysphagia and gastric outlet obstruction. It also provides an overview of the therapeutic possibilities of biliary endoscopy, such as retrograde stenting and radiofrequency biliary ablation. Endoscopic ultrasound-guided therapeutic options are discussed, including biliary drainage, gastrojejunostomy and coeliac axis block. To aid in clinical decision making, the procedures are described in the context of their indication, efficacy, risks and limitations.

Histopathological spectrum of adult renal tumours: A single center experience and review of literature.

Background: Renal tumors constitute approximately 3% of all malignancies in adults. They form a heterogenous group with variable morphological, immunohistochemical, and molecular features. Aim: The objective of this study was to analyze the spectrum of adult renal tumors at a tertiary care center and study the demographic and histomorphological features. Materials and Methods: In this study, 55/87 nephrectomy specimens resected for adult renal tumors during a 1-year period were analyzed retrospectively. Results: There were 4 benign (7.2%) and 51 (92.7%) malignant tumors. There was a male preponderance with a male: female ratio of 3.42:1. The tumors were seen to occur equally in both kidneys. The most common tumor was clear cell renal cell carcinoma (RCC), the conventional type accounting for 65.5% of our study group. There were one each of multilocular cystic renal neoplasm of low malignant potential, papillary RCC, chromophobe RCC, Mit family RCC, oncocytoma and angiomyolipoma and two clear cell papillary RCC during this 1-year period. Uncommon tumors included neuroendocrine carcinoma (1), epithelioid angiomyolipoma (1), mixed epithelial stromal tumor (1), Ewings sarcoma (2), and glomangioma (1). Five cases of urothelial carcinoma of renal pelvis/ureter also were present. Conclusion: This article gives an overview of the spectrum of adult renal tumors at a tertiary care center with an in-depth literature review providing recent advances in each category of tumors.

Cerebrospinal fluid neurofilament light predicts the rate of executive function decline in younger-onset dementia.

INTRODUCTION: Determining disease severity and predicting prognosis in younger onset-dementia (YOD) remains challenging. Whether CSF biomarkers neurofilament light (NfL), tau and amyloidß 42 (Aß42) can help provide such information has been underexplored. METHODS: Patients with YOD and CSF analysis were identified. We compared baseline NfL, tau and Aß42 concentrations with contemporaneous Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG) scores to assess their association with severity of cognitive impairment. Cognitive decline, as measured by longitudinal NUCOG assessment, was correlated against baseline biomarker levels to assess their utility in predicting the rate of cognitive decline. RESULTS: 78 patients with YOD (mean age = 56 years, SD = 8) and CSF analysis were identified. Dementia types included Alzheimer's disease, behavioural variant frontotemporal dementia, dementia not-otherwise-specified and other. Tau was associated with contemporaneous memory dysfunction (r = -0.556, 95% CI:[-0.702,-0.393], p < .001). 21 patients had longitudinal cognitive assessment up to 82 months from CSF sampling. NfL was associated with the rate of executive function decline (r = 0.755, 95% CI:[0.259,0.937], p < .001). Aß42 was associated with the rate of memory decline (r = -0.582, 95% CI:[-0.855,-0.274], p = .007) and rate of total NUCOG decline (r = -0.515, 95% CI: [-0.809, -0.227], p = .017). CONCLUSION: CSF tau is related to contemporaneous memory impairment in YOD. NfL and Aß42 levels are associated with the rate of executive function and memory decline, respectively, and may have a role in prognostication in YOD.

Blockchain-Based Deep Learning to Process IoT Data Acquisition in Cognitive Data.

Remote health monitoring can help prevent disease at the earlier stages. The Internet of Things (IoT) concepts have recently advanced, enabling omnipresent monitoring. Easily accessible biomarkers for neurodegenerative disorders, namely, Alzheimer's disease (AD) are needed urgently to assist the diagnoses at its early stages. Due to the severe situations, these systems demand high-quality qualities including availability and accuracy. Deep learning algorithms are promising in such health applications when a large amount of data is available. These solutions are ideal for a distributed blockchain-based IoT system. A good Internet connection is critical to the speed of these system responses. Due to their limited processing capabilities, smart gateway devices cannot implement deep learning algorithms. In this paper, we investigate the use of blockchain-based deep neural networks for higher speed and delivery of healthcare data in a healthcare management system. The study exhibits a real-time health monitoring for classification and assesses the response time and accuracy. The deep learning model classifies the brain diseases as benign or malignant. The study takes into account three different classes to predict the brain disease as benign or malignant that includes AD, mild cognitive impairment, and normal cognitive level. The study involves a series of processing where most of the data are utilized for training these classifiers and ensemble model with a metaclassifier classifying the resultant class. The simulation is conducted to test the efficacy of the model over that of the OASIS-3 dataset, which is a longitudinal neuroimaging, cognitive, clinical, and biomarker dataset for normal aging and AD, and it is further trained and tested on the UDS dataset from ADNI. The results show that the proposed method accurately (98%) responds to the query with high speed retrieval of classified results with an increased training accuracy of 0.539 and testing accuracy of 0.559.

Temporal mechanisms of myogenic specification in human induced pluripotent stem cells.

Understanding the mechanisms of myogenesis in human induced pluripotent stem cells (hiPSCs) is a prerequisite to achieving patient-specific therapy for diseases of skeletal muscle. hiPSCs of different origin show distinctive kinetics and ability to differentiate into myocytes. To address the unique cellular and temporal context of hiPSC differentiation, we perform a longitudinal comparison of the transcriptomic profiles of three hiPSC lines that display differential myogenic specification, one robust and two blunted. We detail temporal differences in mechanisms that lead to robust myogenic specification. We show gene expression signatures of putative cell subpopulations and extracellular matrix components that may support myogenesis. Furthermore, we show that targeted knockdown of ZIC3 at the outset of differentiation leads to improved myogenic specification in blunted hiPSC lines. Our study suggests that ß-catenin transcriptional cofactors mediate cross-talk between multiple cellular processes and exogenous cues to facilitate specification of hiPSCs to mesoderm lineage, leading to robust myogenesis.

Satisfaction of in-patients concerning patient care in a tertiary care hospital in Punjab.

Patient satisfaction is defined as a patient's personal evaluation of health care services and providers and thus a vital component of health care outcome and remains an area of interest and need in health care. Hence to assess in-patient satisfaction a study was conducted in a private tertiary care hospital on a stratified random sample of 100 in-patients drawn from four different general wards using a structured questionnaire. Overall the patients were found to be generally satisfied with care and services provided with a score of 87.12%.

First isolation of Ascotricha chartarum from bronchoalveolar lavage of two patients with pulmonary infections.

Ascotricha chartarum is a rare human pathogen. We describe the isolation and characterization of A. chartarum from bronchoalveolar lavage samples of two patients with underlying pulmonary infections. The identity of both isolates was established by typical phenotypic characteristics and by sequencing of the internal transcribed spacer region and D1/D2 domains of recombinant DNA and ß-tubulin gene fragment. The demonstration of branched, septate hyphae in direct microscopic examination of both the specimens and isolation of the fungus in pure cultures suggest its aetiologic role in the disease process. Because of phenotypic similarities of A. chartarum with Chaetomium spp. and other Chaetomium-like fungi, the application of molecular methods is needed for its accurate identification. Although in the absence of histopathologic evidence the aetiologic role of A. chartarum could not be established unequivocally, nonetheless, in view of the rarity of its isolation from clinical specimens and demonstration of hyphal elements in bronchoalveolar lavage sample, this report assumes considerable significance. It serves to create awareness about environmental fungi that previously have missed attention but may play a role in respiratory infections.

Subcutaneous phaeohyphomycosis caused by Amesia atrobrunnea in Kuwait.

The recently described genus Amesia encompasses four species but only Amesia atrobrunnea (=Chaetomium atrobrunneum) is known to be pathogenic to humans. Here, we describe a case of subcutaneous phaeohyphomycosis in Kuwait in an apparently immunocompetent patient diagnosed by direct microscopy of the infected tissue and culture. The identity of A. atrobrunnea was established by typical morphological characteristics and by sequencing of internally transcribed spacer (ITS) region and D1/D2 domains of rDNA. To the best of our knowledge, this is the first report documenting etiologic role of this species in causing a locally invasive subcutaneous infection.

Treatment with inhaled steroids in patients with symptoms suggestive of asthma but with normal lung function.

A total of 144 patients with lower airway symptoms suggestive of asthma, but who did not fulfil the functional criteria of asthma, were included in a randomised, double-blind, placebo-controlled 8-week "proof-of-concept" study with mometasone furoate (MF), 400 microg once daily. The primary efficacy variable was the mean change from baseline in six morning and evening weekly symptom scores: cough, sputum production, wheeze, shortness of breath, chest tightness and exercise-induced cough/wheeze. Total symptom scores were calculated after treatment for 4 and 8 weeks. Compared with placebo, MF improved total morning symptom score at 8 weeks. Changes in total evening symptom scores did not differ between treatments. MF improved all individual symptom scores more than placebo, although the differences in changes between treatments were not always statistically significant. Morning and evening peak expiratory flow rates increased with MF compared with placebo. MF reduced eosinophils and the levels of eosinophilic cationic protein in induced sputum. The results show that symptoms suggestive of asthma exist in patients without significant beta(2)-agonist reversibility or diurnal variability in peak flow. Once-daily MF may benefit some of these patients and a short course with inhaled corticosteroids may be tried. Responders should be better identified in further studies.

Azole-resistant Candida blankii as a newly recognized cause of bloodstream infection.

Candida blankii is a newly recognized human pathogen. Here we describe a case of bloodstream infection in a preterm neonate. The yeast was repeatedly isolated from blood, and its identity was confirmed by PCR sequencing of rDNA. Additionally, C. blankii DNA was detected directly in a blood sample. The isolates initially developed pink colonies on CHROMagar Candida which later turned into dark metallic blue similar to Candida tropicalis. Inaccurate identification by the VITEK 2 yeast identification system as Stephanoascus ciferrii and intrinsic resistance to fluconazole (MIC 12-16 µg/mL) underscore the need for its accurate identification for appropriate therapeutic management.

Does autonomic dysfunction in cirrhosis liver influence variceal bleed?

BACKGROUND: Autonomic dysfunction has been documented in cirrhosis liver. Its influence on variceal bleed is not known. AIM: To determine the autonomic function amongst variceal bleeders in cirrhosis of the liver. MATERIALS AND METHODS: Fifty cirrhotics (variceal bleeders: 34) belonging to either sex, Childs B, age more than 15 years and non diabetic constituted the study group. Parasympathetic function tests included valsalva ratio (E:I ratio) and deep breathing test. (Max.-Min. heart rate); sympathetic function included postural fall of B.P and a rise in diastolic B.P. with sustained hand grip. A cirrhotic was considered to have 'True' autonomic dysfunction when both parasympathetic and one of the two sympathetic tests were abnormal. RESULTS: The mean age for men was 39.64 + 10.6 yrs and for women 39.54 + 15.8 yrs. The male female ratio was 3.5:1. Only 10 of the 50 patients (all bleeders) had 'true' autonomic dysfunction i.e. 20%. Parasympathetic dysfunction alone was positive in 19 (38%) and sympathetic in 10 patients (20%). The E:I ratio (p < 0.001) and an increase in diastolic B.P. during sustained hand grip (p < 0.04) were significantly positive amongst variceal bleeders. CONCLUSION: 'True' autonomic dysfunction can predispose a cirrhotic to variceal bleed.