Metagenomic outlooks of microbial dynamics influenced by organic manure in tea garden soils of North Bengal, India.

Soil microbial diversity consisted of both culturable and non-culturable microbes. The cultivated microbes can be identified by conventional microbiological processes. However, that is not possible for the non-culturable ones. In those cases, next-generation sequencing (NGS)-based metagenomics become useful. In this study, we targeted two very popular tea gardens of Darjeeling hills-Makaibari (Mak) and Castleton (Cas). The main difference between these two study areas is the type of manure they use. Mak is solely an organic tea garden using all organic manure and fertilizers whereas Cas uses inorganic pesticides and fertilizers. The main aim was to compare the effect of organic manure over chemical fertilizers on the soil microbiomes. We have performed the 16 s metagenomics analysis based on the V3-V4 region. Downstream bioinformatics analysis including reverse ecology was performed. We found that the overall microbial diversity is higher in Mak compared to Cas. Moreover, the use of organic manure has reduced the population of pathogenic bacteria in Mak soil when compared to Cas soil. From the observations made through the metagenomics analysis of Mak and Cas soil samples, we may conclude that the application of organic manure supports the population of good bacteria in the soil which may eventually impact the tea garden workers' health.

Guidelines for the management of diabetes in care homes during the Covid-19 pandemic.

The National Diabetes Stakeholders Covid-19 Response Group was formed in early April 2020 as a rapid action by the Joint British Diabetes Societies for Inpatient Care, Diabetes UK, the Association of British Clinical Diabetologists, and Diabetes Frail to address and support the special needs of residents with diabetes in UK care homes during Covid-19. It was obvious that the care home sector was becoming a second wave of Covid-19 infection and that those with diabetes residing in care homes were at increased risk not only of susceptibility to infection but also to poorer outcomes. Its key purposes included minimising the morbidity and mortality associated with Covid-19 and assisting care staff to identify those residents with diabetes at highest risk of Covid-19 infection. The guidance was particularly created for care home managers, other care home staff, and specialist and non-specialist community nursing teams. The guidance covers the management of hyperglycaemia by discussion of various clinical scenarios that could arise, the management of hypoglycaemia, foot care and end of life care. In addition, it outlines the conditions where hospital admission is required. The guidance should be regarded as interim and will be updated as further medical and scientific evidence becomes available.

Guidelines for the management of diabetes services and patients during the COVID-19 pandemic.

The UK National Diabetes Inpatient COVID Response Group was formed at the end of March 2020 to support the provision of diabetes inpatient care during the COVID pandemic. It was formed in response to two emerging needs. First to ensure that basic diabetes services are secured and maintained at a time when there was a call for re-deployment to support the need for general medical expertise across secondary care services. The second was to provide simple safe diabetes guidelines for use by specialists and non-specialists treating inpatients with or suspected of COVID-19 infection. To date the group, comprising UK-based specialists in diabetes, pharmacy and psychology, have produced two sets of guidelines which will be continually revised as new evidence emerges. It is supported by Diabetes UK, the Association of British Clinical Diabetologists and NHS England.

A Type 1 diabetes technology pathway: consensus statement for the use of technology in Type 1 diabetes.

In both adults and children with diabetes, technologies such as continuous subcutaneous insulin infusion using insulin pumps and continuous glucose monitoring can help improve diabetes control, reduce hypoglycaemia and improve quality of life. Access to these technologies in the UK is very variable. Some technologies are recommended by the National Institute for Health and Care Excellence, while others have not been appraised, and new technologies are emerging all the time. Additionally, different guidelines for adults and children further complicate access to diabetes technology in the transition from paediatric to adult care. Against this background, Diabetes UK and NHS England have brought together a multidisciplinary group of experts, including clinicians and people with diabetes, to develop this consensus guideline, combining the different technologies into a common pathway to aid clinical and policy decision-making. We created a pathway that supports the incremental addition of technology as monotherapy and then dual therapy in the same way that we incrementally add in therapeutic agents to support people with Type 2 diabetes to achieve their personalized glycaemic targets. The pathway emphasizes the importance of structured education, specialist support and appropriate access to psychological therapies, as essential pillars for optimized use of diabetes-related technology, and recommends the re-evaluation of its use when the individual is unable either to use the technology appropriately or to achieve the intended outcomes. This pathway is endorsed by UK-wide clinical and patient associations and we recommend that providers and commissioners use it to ensure the right individual with diabetes has access to the right technology in a timely way to help achieve better outcomes.

Language matters: a UK perspective.

AIM: To review the existing evidence regarding the use of language in clinical encounters. BACKGROUND: Awareness of the importance of language in clinical encounters is mostly lacking or located within broader discussions on communication. METHODS: A scoping study was conducted to review existing research that could increase our understanding of the role language plays as well as identify gaps in knowledge and inform the development of a position statement on language in diabetes care. RESULTS: Evidence shows that, although carefully chosen language can have a positive effect, there is a potential negative impact of language on people's experiences of diabetes care. The use of stigmatizing and discriminatory words during communication between healthcare practitioners and people with diabetes can lead to disengagement with health services as well as sub-optimal diabetes self-management. Clinical encounters can be compromised where language barriers exist or where there is limited understanding of cultural differences that may have an impact on diabetes self-management. What little empirical evidence there is shows that training can improve language and communication skills. CONCLUSION: This review raises a number of questions that are being addressed by the NHS England Language Matters Group, which has developed a set of recommendations to support the use of appropriate language in clinical encounters.

Type 2 diabetes mellitus in older people: a brief statement of key principles of modern day management including the assessment of frailty. A national collaborative stakeholder initiative.

Rates of population ageing are unprecedented and this, combined with the progressive urbanization of lifestyles, has led to a dramatic shift in the epidemiology of diabetes towards old age, particularly to those aged 60-79 years. Both ageing and diabetes are recognized as important risk factors for the development of functional decline and disability. In addition, diabetes is associated with a high economic, social and health burden. Traditional macrovascular and microvascular complications of diabetes appear to account for less than half of the diabetes-related disability observed in older people. Despite this, older adults are under-represented in clinical trials. Guidelines from organizations such as the National Institute for Health and Care Excellence (NICE), the European Association for the Study of Diabetes, and the American Diabetes Association acknowledge the need for individualized care, but the glycaemic targets that are suggested to constitute good control [HbA1c 53-59 mmol/mol (7-7.5%)] are too tight for frail older individuals. We present a framework for the assessment of older adults and guidelines for the management of this population according to their frailty status, with the intention of reducing complications and improving quality of life for these people.

Language matters. Addressing the use of language in the care of people with diabetes: position statement of the English Advisory Group.

The language used by healthcare professionals can have a profound impact on how people living with diabetes, and those who care for them, experience their condition and feel about living with it day-to-day. At its best, good use of language, both verbal and written, can lower anxiety, build confidence, educate and help to improve self-care. Conversely, poor communication can be stigmatizing, hurtful and undermining of self-care and can have a detrimental effect on clinical outcomes. The language used in the care of those with diabetes has the power to reinforce negative stereotypes, but it also has the power to promote positive ones. The use of language is controversial and has many perspectives. The development of this position statement aimed to take account of these as well as the current evidence base. A working group, representing people with diabetes and key organizations with an interest in the care of people with diabetes, was established to review the use of language. The work of this group has culminated in this position statement for England. It follows the contribution of Australia and the USA to this important international debate. The group has set out practical examples of language that will encourage positive interactions with those living with diabetes and subsequently promote positive outcomes. These examples are based on a review of the evidence and are supported by a simple set of principles.

Risk factors for vertical transmission of hepatitis E virus infection.

Hepatitis E virus (HEV) infection can be vertically transmitted, but the factors that transmit the disease to foetuses are still unclear. We studied a total of 144 pregnant women with HEV infection. Cord blood and newborn samples were taken for analysis. Nutritional factors were evaluated on the basis of anthropometric parameters and biochemical factors, and HEV viral load was quantified by real-time PCR. Sequencing of HEV-positive samples was performed. Approximately 14.63% (6/41) of pregnant patients with acute liver failure (ALF) died before delivery. Vertical transmission was observed in 46.09% (59/128) of HEV-IgM-positive mothers. Approximately 23.80% (10/42) of newborns in the acute viral hepatitis group and 29.41% (5/17) in the ALF group were positive for HEV-RNA. No significant difference was observed in the occurrence of vertical transmission in HEV groups. Viral load was found to be a significant predictor for vertical transmission of HEV infection adjusted with haemoglobin and folate in derivation cohort group. Incorporating these variables, a new score predicting vertical transmission of HEV was derived. Using these significant predictors, the probability for vertical transmission of HEV was well stratified in the validation group (P>.05). In conclusion, viral load was associated with vertical transmission of HEV infection. A valid prediction score model was generated that was verified in a validation cohort group.

100-fold improvement in carrier drift mobilities in alkanephosphonate-passivated monocrystalline TiO2 nanowire arrays.

Single crystal rutile titania nanowires grown by solvothermal synthesis are actively being researched for use as electron transporting scaffolds in perovskite solar cells, in low detection limit ultraviolet photodetectors, in photoelectrochemical water-splitting, and in chemiresistive and electrochemical sensing. The electron drift mobility (µ n ) in solution-grown TiO2 nanowires is very low due to a high density of deep traps, and reduces performance in optoelectronic devices. In this study, the effects of molecular passivation of the nanowire surface by octadecylphosphonic acid (ODPA), on carrier transport in TiO2 nanowire ensembles, were investigated using transient space charge limited current measurements. Infrared spectroscopy indicated the formation of a highly ordered phosphonate monolayer with a high likelihood of bidentate binding of ODPA to the rutile surface. We report the hole drift mobility (µ p ) for the first time in unpassivated solvothermal rutile nanowires to be 8.2 × 10-5 cm2 V-1 s-1 and the use of ODPA passivation resulted in µ p improving by nearly two orders of magnitude to 7.1 × 10-3 cm2 V-1 s-1. Likewise, ODPA passivation produced between a 2 and 3 order of magnitude improvement in µ n from ∼10-5-10-6 cm2 V-1 s-1 to ∼10-3 cm2 V-1 s-1. The bias dependence of the post-transit photocurrent decays in ODPA-passivated nanowires indicated that minority carriers were lost to trapping and/or monomolecular recombination for small values of bias (<5 V). Bimolecular recombination was indicated to be the dominant recombination mechanism at higher bias values.

Role of complement component C4 in treatment response and disease progression in chronic hepatitis C patients.

The basis of hepatitis C virus (HCV) evasion of immune system and its response to treatment is still elusive. There have been studies where the level of C4 has been found to be associated with HCV persistence and disease progression. This study aims to find out relationship between levels of C4 in serum, and its functional SNPs with response to treatment. The study included 84 patients with CHC who received treatment and 75 healthy controls. C4 expression, both at mRNA and protein level, was estimated by Real time and ELISA respectively. Its functional SNP's genotyped by AS-PCR. The mean ± SD baseline C4 levels between the disease and healthy cases was significantly different (1075.74 ± 65.25 vs 1593 ± 24.55 ng/mL, P < 0.001). The mean ± SD baseline C4 levels of CC, GC and GG genotype of rs2857009 in the healthy group were 1540.97 ± 7.87, 1599.53 ± 11.75 and 1604.86 ± 10.79 ng/mL, respectively (P < 0.001), whereas the levels in the CHC group were 1022.81 ± 32.95, 1058.19 ± 55.02 and 1150.26 ± 14.64 ng/mL, respectively (P < 0.001). CC genotype resulted in decreased C4 mRNA levels compared to GG genotype in healthy group (3.81-fold) and CHC group (1.4-fold). The CC genotype of rs2857009 is associated with reduced expression of C4, both at mRNA and protein level. The C4 serum level at baseline and total protein were found to be independent predictors for treatment response. New predictive score using the above factors, a value of ≥ 0.542 was found to predict positive response to treatment. Increased age, rs2857009 SNP and HCV genotype were associated with disease progression.

rs2230201 polymorphism may dictate complement C3 levels and response to treatment in chronic hepatitis C patients.

The basis of response of chronic hepatitis C (CHC) patients to treatment is still unclear, and there may be many other factors which influence treatment outcome other than the existing ones. The serum concentration of C3 closely reflects the total complement activity, and individuals affected by C3 deficiency suffer from recurrent pyogenic infections. This study aims to find out relationship between levels of C3 in serum and its functional SNPs with response to treatment. The study included 132 CHC patients of which 48 received Pegylated IFN+Ribavirin and 81 controls. C3 levels and its three known functional SNP's genotyped by ELISA and SSP PCR, respectively. C3 Level of the healthy group was significantly higher (88.5 ± 19 mg/dL) when compared to CHC group (56 ± 18 mg/dL; P < 0.001). Thirty-three of 36 responders were rs2230201 CC genotype carriers, whereas 9 of 12 nonresponders were non-CC genotype. The 'C' allele of rs2230201 was found to be associated with increased serum C3 levels when compared to other genotypes in healthy group, whereas CT genotype was associated with lowered serum C3 in CHC group. A serum C3 value of <53 mg/dL was predictive of SVR with sensitivity 63.89% and specificity 66.67%. The study supports the observation that rs2230201 'C' allele is associated with increase of serum C3 levels when compared to 'T' allele which may confer advantage in attaining SVR when present in homozygous condition. The study suggests that patients with serum C3 value <53 mg/dL and non-CC genotypes may not respond to treatment.

Predictive value of serum actin-free Gc-globulin for complications and outcome in acute liver failure.

This prospective study was designed to evaluate whether early changes in actin-free Gc-globulin levels were associated with complications and outcomes and to identify factors associated with persistent low actin-free Gc-globulin levels in acute liver failure (ALF). Thirty-two consecutive ALF patients admitted from October 2011 to December 2012 were followed up until death or complete recovery. All had serum actin-free Gc-globulin estimation at admission and at day three or expiry. Logistic regression analysis was performed to identify independent predictors of mortality. A receiver operating characteristic curve analysis was also performed. Nonsurvivors had significantly lower median actin-free Gc-globulin levels than survivors (87.32 vs 180 mg/L; P < 0.001). A receiver operating characteristic curve analysis revealed an area under curve (AUC) of 0.771 and showed that serum actin-free Gc-globulin level of ≤124 mg/L would predict mortality with 92% sensitivity and 71.4% specificity. Patients with lower serum actin-free Gc-globulin levels and decreasing trend in serum actin-free Gc-globulin levels were found to have more mortality and developed more complications. Logistic regression analysis showed that serum actin-free Gc-globulin, total leucocyte count and serum creatinine at admission were independent predictors of mortality. Incorporating these variables, a score predicting mortality risk at admission was derived. The scoring system was compared to MELD score and King's College Criteria as individual predictor of mortality. Serum actin-free Gc-globulin level at presentation is predictive of outcome and can be used for risk stratification. Its persistent low-level predicts mortality and is correlated with various complications.

Role of nitric oxide synthase genes in hepatitis E virus infection.

Hepatitis E virus (HEV) is the most common cause of endemic and epidemic acute hepatitis. A correlation between iNOS, eNOS polymorphisms, levels and severity of disease has been reported, and here, we examined the role of iNOS and eNOS gene polymorphisms and their levels in HEV-related acute viral hepatitis and acute liver failure. Hepatitis E virus-related cases of acute hepatitis (294 patients) and liver failure (82 patients) and age- and sex-matched healthy controls (331 subjects) were included in the study. PCR-RFLP was performed to identify the polymorphisms in the iNOS and eNOS genes. iNOS and eNOS levels were studied using ELISA assays and HEV viral load, genotype and combined effects of iNOS genotype, levels and parameters for disease severity were examined. The frequency of iNOS (CT + TT) and eNOS (GT + TT) genotypes was higher in subjects with liver failure compared with controls. iNOS and eNOS levels in patients with acute liver failure (55.51 ± 6.33 IU/mL, 60.2 ± 3.69) cases were significantly increased as compared to patients with acute viral hepatitis (17.8 ± 6.08 IU/mL, 23.7 ± 6.57) and controls (P < 0.05). A significant positive correlation was observed between the iNOS and eNOS levels in our study population when compared with the severity of disease parameters. Hence, the iNOS C150T polymorphism and the eNOS G894T polymorphism and high levels of iNOS and eNOS are associated with an increased risk of HEV-related acute hepatitis and liver failure. This study supports the possible role of nitric oxide synthase genes (iNOS and eNOS) in determining the severity of HEV infection.

Identification of inhibitors for neurodegenerative diseases targeting dual leucine zipper kinase through virtual screening and molecular dynamics simulations.

Neurodegenerative diseases lead to a gradual decline in cognitive and motor functions due to the progressive loss of neurons in the central nervous system. The role of dual leucine zipper kinase (DLK) in regulating stress responses and neuronal death pathways highlights its significance as a target against neurodegenerative diseases. The non-availability of FDA-approved drugs emphasizes a need to identify novel DLK-inhibitors. We screened NPAtlas (Natural products) and MedChemExpress (FDA-approved) libraries to identify potent ATP-competitive DLK inhibitors. ADMET analyses identified four compounds (two natural products and two FDA-approved) with favourable features. Subsequently, we performed molecular dynamics simulations to examine the binding-stability and ligand-induced conformational dynamics. Molecular mechanics Poisson Boltzmann surface area (MM-PBSA) calculations demonstrated CID139591660, dithranol, and danthron having greater affinity, while CID156581477 showed lower affinity than control sunitinib. PCA and network analysis results indicated structural and network alteration post-ligand binding. Furthermore, we identified an analogue of CID156581477 using the deep learning-based web server DeLA Drug which demonstrated a higher affinity than its parent compound and the control and identified several crucial interacting residues. Overall, our study provides significant theoretical guidance for designing potent novel DLK inhibitors and compounds that could emerge as promising drug candidates against DLK following laboratory validation.

Genetic variants of heat shock protein A1L2437 and A1B1267 as possible risk factors for hepatocellular carcinoma in India.

To study the role of heat shock protein A1L (HSPA1L) and A1B (HSPA1B) polymorphisms and subsequent risk of hepatocellular carcinoma (HCC) in India. Subjects enrolled included 185 cases of HCC, 182 cases of chronic hepatitis (CH) and 200 healthy controls. Genomic DNA was typed for HSPA1L2437 and HSPA1B1267 SNP using polymerase chain reaction with restriction fragment length polymorphism. Other risk factors were also analysed. Hepatitis B virus (HBV) infection, older age >35 years and high aflatoxin level in urine increased the risk of HCC. The frequencies of HSPA1L BB genotype and B allele in HCC were more than in CH [odds ratio (OR): 9.83; P = 0.000], but also in HBV-related HCC than Chronic Hepatitis B (CHB) [OR: 3.44; P = 0.004] and HCV-related HCC compared to CHC [OR: 6.32; P = 0.010]. The frequency of HSPA1B genotype in the homozygous state was more in CH [OR: 6.01; P = 0.001] and is a good marker to predict the risk of HCV-related CH (CHC) compared to controls. HCV-related HCC has a higher frequency of the B allele of HSPA1B than healthy controls [OR: 3.95; P = 0.000] and CHC [OR: 2.35; P = 0.000], respectively. The frequencies increased further significantly in CHC compared to healthy controls [OR: 9.26; P = 0.000]. The risk for the development of CH and HCC compared to healthy controls irrespective of the aetiology was significant in terms of the HSPA1B marker than HSPA1L in the Indian population.

Long-term cardiac and vascular disease outcomes following adjuvant tamoxifen therapy: current understanding of impact on physiology and overall survival.

The relative impact of tamoxifen therapy in women with breast cancer on overall survival, especially as it pertains to cardiac and cardiovascular outcomes, remains under debate in the literature. This review focuses specifically on outcomes of studies that examined large clinical trials with longest duration in patient follow-up relative to these parameters in which compliance with therapy could be documented. Over time, evidence supports potential cardioprotective effects and capacity of adjuvant therapy to improve lipid profiles in women treated with tamoxifen. While some benefit to cardiac health is supported, outcomes related to cardiovascular events remain variable across studies and challenging to interpret. In summary, overall survival in women treated with tamoxifen over time has increasingly shown a trend towards positive outcomes in the context of evaluation of post-treatment cardiac and vascular health. Potential mechanisms underlying the cardioprotective effects of tamoxifen are briefly discussed.

Exploring molecular interactions of potential inhibitors against the spleen tyrosine kinase implicated in autoimmune disorders via virtual screening and molecular dynamics simulations.

The spleen tyrosine kinase (Syk) plays a pivotal role in immune cells' signal transduction mechanism. While fostamatinib, an FDA-approved Syk inhibitor, is currently used to treat immune thrombocytopenia, the search for improved Syk-targeted medications to treat autoimmune diseases is still underway. Herein, we screened 38,493 compounds against Syk and selected eight leads based on the docking score and ADMET properties, and performed 3×200 ns long molecular dynamics simulations of the apo and Syk-ligand complexes. We considered R406, the active component of fostamatinib, as a control. The molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations demonstrated the lead1 (ΔGbind = -30.35 kcal/mol) exhibited a similar binding free energy as the control (ΔGbind= -29.82 kcal/mol). The Syk stabilizing effect of lead1 was also indicated in its network features, sampling space, and residual correlation motion analysis. We further generated 100 structural analogues of lead1 using deep learning, and one of the analogues displayed a better binding free energy (ΔGbind= -47.58 kcal/mol) compared to the control or lead1, facilitated by more favourable van der Waals interactions and lesser binding-opposing net polar forces. This analogue may be further exploited to develop effective therapeutics against Syk-associated diseases after validation in vitro and in vivo.