Search

Background Methods Results Conclusions Acute exacerbations of chronic rhinosinusitis (AECRS) are thought to arise from common viral infections progressing to secondary bacterial infections. However, the pathophysiology of AECRS remains poorly understood due to a lack of prospective longitudinal studies.We conducted a one‐year prospective longitudinal study involving chronic rhinosinusitis (CRS) adults. At baseline, we assessed subjective symptom scores using a validated upper respiratory infection questionnaire (WURSS), sinonasal outcome testing scores (SNOT‐22), and endoscopic scores (modified Lund‐Kennedy score). Every 2 weeks, we contacted subjects to collect WURSS and SNOT‐22 scores. If WURSS scores were ≥1 and SNOT‐22 scores were ≥ 8.9 compared with baseline, subjects underwent an AECRS assessment. We identified rhinovirus (RV) incidence through viral nasal brushings at each visit and bacterial infection through bacterial swabs if mucus scores were ≥1.Thiry‐five of 80 CRS subjects reported at least one AECRS episode during the year, predominantly occurring in the fall and winter seasons. RV infections were detected in 8 of 35 cases, bacterial infections in 17 of 35, and co‐occurring infections in 7 of 35. All subjects with AECRS visits exhibited significantly higher endoscopic scores compared with baseline. Subjects with co‐occurring RV and bacterial infections demonstrated higher disease severity compared with those with either RV or bacterial infection, or no infection.In a one‐year prospective longitudinal study involving CRS adults, we identified significant risk factors for AECRS including seasonality and the presence of RV and bacterial infections. These data suggest a standard definition of AECRS and the need to target RV and bacterial infections if we are to help reduce disease severity. [ABSTRACT FROM AUTHOR]

As the world population ages, there will be an increasing need for effective therapies for aging‐associated neurodegenerative disorders, which remain untreatable. Dementia due to Alzheimer's disease (AD) is one of the leading neurological diseases in the aging population. Current therapeutic approaches to treat this disorder are solely symptomatic, making the need for new molecular entities acting on the causes of the disease extremely urgent. One of the potential solutions is to use compounds that are already in the market. The structures have known pharmacokinetics, pharmacodynamics, toxicity profiles, and patient data available in several countries. Several drugs have been used successfully to treat diseases different from their original purposes, such as autoimmunity and peripheral inflammation. Herein, we divulge the repurposing of drugs in the area of neurodegenerative diseases, focusing on the therapeutic potential of antineoplastics to treat dementia due to AD and dementia. We briefly touch upon the shared pathological mechanism between AD and cancer and drug repurposing strategies, with a focus on artificial intelligence. Next, we bring out the current status of research on the development of drugs, provide supporting evidence from retrospective, clinical, and preclinical studies on antineoplastic use, and bring in new areas, such as repurposing drugs for the prion‐like spreading of pathologies in treating AD. [ABSTRACT FROM AUTHOR]

Introduction: This work describes a secondary analysis of a qualitative data set originally used to understand parent participants' preferences for the design and implementation of a screening programme for paediatric Type 1 diabetes (T1D). From this, their spontaneous preferences for peer support emerged, described here in the context of existing peer support programmes for the newly diagnosed alongside suggestions for their incorporation into screening programmes for T1D and a range of other conditions. Methods: Data were collected from semi‐structured interviews conducted with parents of children aged 3–13 years to explore their expectations, perceptions and preferences of a T1D paediatric screening programme. A secondary analysis of interviews from participants who spontaneously raised preferences for peer support was used to populate a novel framework informed by NHS England's key principles for the same, namely, Shared experiences and reciprocated support, Accessibility and inclusivity and Person‐centred and integrated peer support. Results: Parents in 29 of 33 interviews spontaneously described the potential value of peer support if receiving a result indicating a positive (presymptomatic T1D result) from a screening programme. Specifically, the value of 'Shared experiences and reciprocated support' in terms of emotional support and reassurance, and access to more directly interpretable and relevant information related to the condition; 'Accessibility and inclusivity' relating to access to a community of similar individuals, whether in person or online; 'Person‐centred and integrated peer‐support' and the need for support reflecting the changing need of the child and the integration of peer support with clinical care. Conclusions: The needs of peer support described by parents involved in T1D paediatric screening appear to be shared with those of families with children diagnosed with a range of life‐altering conditions. Although the needs of peer support for paediatric screening may differ across conditions, our findings are a valuable starting point for its design both in T1D and other examples of similar population screening programmes. Patient or Public Contribution: Patients and the public have been involved throughout the design of the ELSA study and have worked with us to inform the study process. They contributed to the design and content of patient‐facing materials, the content of our topic guides and the analysis and interpretation of our findings. [ABSTRACT FROM AUTHOR]

Co‐filled composites of micro magnesium dihydrate (MDH) and hydrophobically treated nano aluminum nitride (nH‐AlN) fillers in high temperature vulcanizing silicone gum are studied for thermal and dielectric characteristics for use as an insulating material in high voltage applications. The study begins with description of the compounding protocol adopted, followed by spectroscopic and optical characterization. Fourier transform infrared spectroscopy (FTIR) and energy dispersive X‐ray spectroscopy (EDX) analysis are used to verify the presence of nH‐AlN and MDH in the composites. Thermal analysis through thermogravimetric analysis revealed a stark enhancement in the onset of polymer degradation temperature, with an improvement of 208 °C achieved at 30 phr by weight loading level of MDH. Volume resistivity of 9.71 E14 Ω‐cm is obtained at 30 phr weight loading of MDH and 5 phr of nH‐AlN. AC, +DC, and −DC dielectric strength improved by 1.09, 2.06, and 1.08 times for co‐filled composites at 30 phr MDH and 5 phr nH‐AlN loading levels over unitary filled composite. Effect of dielectric polarization on dielectric constant and dissipation factor is studied at various frequencies. Limitations while conducting dry arc resistance test at standard voltage of 12.50 kV is discussed, with modification in dry arc resistance test voltage to 16.95 kV. The results are presented and discussed here. [ABSTRACT FROM AUTHOR]

The global environmental and energy challenges necessitate the development of multifunctional materials that can address both pollutant removal and solar fuel production. In this groundbreaking study, the utilization of the Mo2AlB2 transition‐metal aluminum boron (MAB) phase is introduced as a cocatalyst in the SrTiO3/Mo2AlB2 nanocomposite, marking the first instance of its application in photocatalytic approaches to combat environmental and energy crises. A nanocomposite of SrTiO3/Mo2AlB2 is prepared by ultrasound‐assisted self‐assembly of SrTiO3 nanocubes (STO) with layered Mo2AlB2. The optimized catalyst denoted as STO@5‐MAB is subjected to comprehensive characterization to evaluate its physiochemical properties. Remarkably, the STO@5‐MAB composite demonstrates exceptional performance in both photocatalytic carbendazim (CBZ) degradation, achieving an impressive degradation of 87.5% and CO2 reduction to ethanol with a rate of 9.96 mmol g−1 h−1 under visible‐light illumination. This outstanding performance can be attributed to the composite's 1) hydrophobicity, 2) enhanced light absorption, and 3) the formation of a Schottky junction at the interface, facilitating efficient charge separation. In conclusion, the SrTiO3/Mo2AlB2 nanocomposite demonstrates immense potential in addressing pressing environmental and energy challenges through photocatalytic CBZ degradation and CO2 reduction to ethanol. In this study, the pivotal role of Mo2AlB2 in developing efficient photocatalysts is underscored for environmental and energy applications. [ABSTRACT FROM AUTHOR]

A study published in the journal Diabetes, Obesity & Metabolism examined the impact of hybrid closed-loop (HCL) insulin delivery on cardiac rhythm in older adults with type 1 diabetes (T1D). The study found that HCL devices improved glucose control and reduced the risk of low blood sugar, but did not have a significant impact on cardiac rhythm. The study suggests that HCL systems can be beneficial for managing T1D in older adults without negatively affecting cardiac rhythm. However, more research is needed to understand the relationship between glucose control and cardiac rhythm in individuals with T1D. [Extracted from the article]

Aims: The FLASH‐UK trial showed lower HbA1c with intermittently scanned continuous glucose monitoring (isCGM), as compared with self monitoring of blood glucose (SMBG), in adults with type 1 diabetes and HbA1c ≥58 mmol/mol (≥7.5%). Here, we present results from the pre‐specified subgroup analysis for the 24‐week HbA1c (primary outcome) and selected sensor‐based secondary outcomes. Methods: This was a multi‐centre, parallel‐design, randomised controlled trial. The difference in treatment effect between subgroups (baseline HbA1c [≤75 vs. >75 mmol/mol] [≤9.0 vs >9.0%], treatment modality [pump vs injections], prior participation in structured education, age, educational level, impaired awareness of hypoglycaemia, deprivation index quintile sex, ethnic group and Patient Health Questionnaire‐9 [PHQ‐9] detected depression category) were evaluated. Results: One hundred fifty‐six participants (females 44%, mean [SD] baseline HbA1c 71 [9] mmol/mol 8.6 [0.8%], age 44 [15]) were randomly assigned, in a 1:1 ratio to isCGM (n = 78) or SMBG (n = 78). The mean (SD) baseline HbA1c (%) was 8.7 (0.9) in the isCGM group and 8.5 (0.8) in the SMBG group, lowering to 7.9 (0.8) versus 8.3 (0.9), respectively, at 24 weeks (adjusted mean difference −0.5, 95% confidence interval [CI] −0.7 to −0.3; p < 0.001]. For HbA1c, there was no impact of treatment modality, prior participation in structured education, deprivation index quintile, sex or baseline depression category. The between‐group difference in HbA1c was larger for younger people (a reduction of 2.7 [95% CI 0.3–5.0; p = 0.028] mmol/mol for every additional 15 years of age). Those with HbA1c 76–97 mmol/mol (>9.0%–11.0%) had a marginally non‐significant higher reduction in HbA1c of 8.4 mmol/mol (3.3–13.5) compared to 3.1 (0.3–6.0) in those with HbA1c 58–75 mmol/mol (p = 0.08). For 'Time in range' (% 3.9–10 mmol/L), the difference was larger for those with at least a bachelor's degree. For 'Time below range' (% <3.9 mmol/L), the difference was larger for those using injections, older people and those with less than bachelor's degree. Conclusions: Intermittently scanned continuous glucose monitoring is generally effective across a range of baseline characteristics. [ABSTRACT FROM AUTHOR]

Objective: We previously showed that intermittently scanned continuous glucose monitoring (isCGM) reduces HbA1c at 24 weeks compared with self‐monitoring of blood glucose with finger pricking (SMBG) in adults with type 1 diabetes and high HbA1c levels (58–97 mmol/mol [7.5%–11%]). We aim to assess the economic impact of isCGM compared with SMBG. Methods: Participant‐level baseline and follow‐up health status (EQ‐5D‐5L) and within‐trial healthcare resource‐use data were collected. Quality‐adjusted life‐years (QALYs) were derived at 24 weeks, adjusting for baseline EQ‐5D‐5L. Participant‐level costs were generated. Using the IQVIA CORE Diabetes Model, economic analysis was performed from the National Health Service perspective over a lifetime horizon, discounted at 3.5%. Results: Within‐trial EQ‐5D‐5L showed non‐significant adjusted incremental QALY gain of 0.006 (95% CI: −0.007 to 0.019) for isCGM compared with SMBG and an adjusted cost increase of £548 (95% CI: 381–714) per participant. The lifetime projected incremental cost (95% CI) of isCGM was £1954 (−5108 to 8904) with an incremental QALY (95% CI) gain of 0.436 (0.195–0.652) resulting in an incremental cost‐per‐QALY of £4477. In all subgroups, isCGM had an incremental cost‐per‐QALY better than £20,000 compared with SMBG; for people with baseline HbA1c >75 mmol/mol (9.0%), it was cost‐saving. Sensitivity analysis suggested that isCGM remains cost‐effective if its effectiveness lasts for at least 7 years. Conclusion: While isCGM is associated with increased short‐term costs, compared with SMBG, its benefits in lowering HbA1c will lead to sufficient long‐term health‐gains and cost‐savings to justify costs, so long as the effect lasts into the medium term. [ABSTRACT FROM AUTHOR]

Aims: Children and young people with diabetes (CYPD) from socio‐economically deprived and/or ethnic minority groups tend to have poorer glucose control and greater risk of diabetes‐related complications. In this systematic review of qualitative evidence (qualitative evidence synthesis, QES), we aimed to explore the experiences and views of clinical encounters in diabetes care from the perspectives of CYPD and their family/carers from underserved communities and healthcare professionals in diabetes care. Methods: We searched 6 databases to March 2022 with extensive search terms, and used a thematic synthesis following methods of Thomas and Harden. Results: We identified 7 studies and described 11 descriptive themes based on primary and secondary constructs. From these, three "analytical themes" were developed. (1) "Alienation of CYPD" relates to their social identity and interaction with peers, family and health service practitioners in the context of diabetes self‐ and family/carer management and is impacted by communication in the clinical encounter. (2) "Empowerment of CYPD and family/carers" explores families' understanding of risks and consequences of diabetes and taking responsibility for self‐ and family/carer management in the context of their socio‐cultural background. (3) "Integration of diabetes (into self and family)" focuses on the ability to integrate diabetes self‐management into the daily lives of CYPD and family/carers beyond the clinical consultation. Conclusions: The analytical themes are interdependent and provide a conceptual framework from which to explore and strengthen the therapeutic alliance in clinical encounters and to foster greater concordance with treatment plans. Communicating the biomedical aspects of managing diabetes in the clinical encounter is important, but should be balanced with addressing socio‐emotional factors important to CYPD and family/carers. [ABSTRACT FROM AUTHOR]

Aims: Anti‐insulin antibodies in insulin‐treated diabetes can derange glycaemia, but are under‐recognised. Detection of significant antibodies is complicated by antigenically distinct insulin analogues. We evaluated a pragmatic biochemical approach to identifying actionable antibodies, and assessed its utility in therapeutic decision making. Methods: Forty people with insulin‐treated diabetes and combinations of insulin resistance, nocturnal/matutinal hypoglycaemia, and unexplained ketoacidosis were studied using broad‐specificity insulin immunoassays, polyethylene glycol (PEG) precipitation and gel filtration chromatography (GFC) with or without ex vivo insulin preincubation. Results: Twenty‐seven people had insulin immunoreactivity (IIR) below 3000 pmol/L that fell less than 50% after PEG precipitation. Insulin binding by antibodies in this group was low and judged insignificant. In 8 people IIR was above 3000 pmol/L and fell by more than 50% after PEG precipitation. GFC demonstrated substantial high molecular weight (HMW) IIR in 7 of these 8. In this group antibodies were judged likely significant. In 2 people immunosuppression was introduced, with a good clinical result in one but only a biochemical response in another. In 6 people adjustment of insulin delivery was subsequently informed by knowledge of underlying antibody. In a final group of 5 participants IIR was below 3000 pmol/L but fell by more than 50% after PEG precipitation. In 4 of these GFC demonstrated low levels of HMW IIR and antibody significance was judged indeterminate. Conclusions: Anti‐insulin antibodies should be considered in insulin‐treated diabetes with unexplained glycaemic lability. Combining immunoassays with PEG precipitation can stratify their significance. Antibody depletion may be beneficial, but conservative measures often suffice. [ABSTRACT FROM AUTHOR]

Aims: Identifying children at risk of type 1 diabetes allows education for symptom recognition and monitoring to reduce the risk of diabetic ketoacidosis at presentation. We aimed to explore stakeholder views towards paediatric general population screening for type 1 diabetes in the United Kingdom (UK). Methods: Qualitative interviews were undertaken with 25 stakeholders, including diabetes specialists, policymakers and community stakeholders who could be involved in a future type 1 diabetes screening programme in the UK. A thematic framework analysis was performed using the National Screening Committee's evaluative criteria as the overarching framework. Results: Diabetic ketoacidosis prevention was felt to be a priority and proposed benefits of screening included education, monitoring and helping the family to better prepare for a future with type 1 diabetes. However, diabetes specialists were cautious about general population screening because of lack of evidence for public acceptability. Concerns were raised about the harms of living with risk, provoking health anxiety and threatening the child's right to an 'open future'. Support systems that met the clinical and psychological needs of the family living with risk were considered essential. Stakeholders were supportive of research into general population screening and acknowledged this would be a priority if an immunoprevention agent were licensed in the UK. Conclusions: Although stakeholders suggested the harms of UK paediatric general population screening currently outweigh the benefits, this view would potentially be altered if prevention therapies were licensed. In this case, an evidence‐based screening strategy would need to be formulated and public acceptability explored. [ABSTRACT FROM AUTHOR]

Aims: Use of the CamAPS FX hybrid closed loop (CL) system is associated with improved time in range and glycated haemoglobin A1c across the age span, but little is known about its effects on patient‐reported outcomes (PROs). Methods: This open‐label, randomized, multi‐site study compared CamAPS FX to sensor‐augmented pump (SAP) in a sample of older adults (≥60 years) with type 1 diabetes (T1D). Thirty‐five older adults completed PROs surveys at the start of the study and after each period of 16 weeks using either CL or SAP. At the end of the study, 19 participated in interviews about their experiences with CL. Results: Results examining the 16 weeks of CL use showed that the overall Diabetes Distress Scale score and two subscales (powerlessness and physician distress) improved significantly along with trust on the Glucose Monitoring Satisfaction Survey. User experience interview responses were consistent in noting benefits of 'improved glycaemic control' and 'worrying less about diabetes'. Conclusion: In this sample of older adults with T1D who have previously shown glycaemic benefit, there are indicators of improved PROs and subjective user experience benefits. [ABSTRACT FROM AUTHOR]

Keywords: autoantibodies; screening; teplizumab; type 1 diabetes EN autoantibodies screening teplizumab type 1 diabetes 2051 2057 7 07/04/23 20230801 NES 230801 INSULIN TREATMENT AND TYPE 1 DIABETES: TIME FOR SOMETHING DIFFERENT In 1921, the discovery of insulin by Banting and Best presented a new era for people with type 1 diabetes (T1D), transitioning from calorific restriction and early death to enabling longer lives with insulin dependency. 2 Abbreviations: DKA, diabetic ketoacidosis; T1D, type 1 diabetes. Table adapted from Besser et al. (2022).[46] 4 Abbreviations: DKA, diabetic ketoacidosis; T1D, type 1 diabetes. One hundred years later, the United States Food and Drug Administration (FDA) licensed the first immunoprevention agent, teplizumab, to delay the onset of T1D.[1] This marks a new era for T1D, focusing on identification of those at risk and treatment to modify the early disease course. [Extracted from the article]

Aims: To investigate characteristics of people hospitalized with coronavirus‐disease‐2019 (COVID‐19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. Materials and methods: Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID‐19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age‐adjusted odds ratios were calculated using logistic regression. Results: In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID‐19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p <.001). A higher proportion of patients with HHS than with DKA were of non‐White ethnicity (71.4% vs 39.0% p =.038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non‐users [21.4% vs. 52.2%; age‐adjusted odds ratio 0.13 (95% CI 0.03‐0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p =.001) and in statin users versus non‐users (36.4% vs. 100%; p =.035) but these were not statistically significant after age adjustment. Conclusions: Hospitalization with COVID‐19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes‐associated DKA. [ABSTRACT FROM AUTHOR]

Objective: To assess the association of ethnicity and birthplace on emotional and psychosexual well‐being in women with polycystic ovary syndrome (PCOS). Design: Cross‐sectional study. Setting: Community recruitment via social media campaigns. Population: Women with PCOS completing an online questionnaire in September–October 2020 (UK) and May–June 2021 (India). Methods: The survey has five components, with a baseline information and sociodemographic section followed by four validated questionnaires: Hospital Anxiety and Depression Scale (HADS); Body Image Concern Inventory (BICI); Beliefs About Obese Persons Scale (BAOP); and Female Sexual Function Index (FSFI). Main outcome measures: We used adjusted linear and logistic regression models, adjusting for age, education, marital status and parity, to evaluate the impact of ethnicity and birthplace on questionnaire scores and outcomes (anxiety and/or depression, HADS ≥ 11; body dysmorphic disorder (BDD), BICI ≥ 72). Results: A total of 1008 women with PCOS were included. Women of non‐white ethnicity (613/1008) reported higher rates of depression (OR 1.96, 95% CI 1.41–2.73) and lower BDD (OR 0.57, 95% CI 0.41–0.79) than white women (395/1008). Women born in India (453/1008) had higher anxiety (OR 1.57, 95% CI 1.00–2.46) and depression (OR 2.20, 95% CI 1.52–3.18) but lower BDD rates (OR 0.42, 95% CI 0.29–0.61) than women born in the UK (437/1008). All sexual domains, excluding desire, scored lower for non‐white women and women born in India. Conclusions: Non‐white women and women born in India reported higher emotional and sexual dysfunction, whereas white women and women born in the UK reported higher body image concerns and weight stigma. Ethnicity and birthplace need to be considered for tailored, multidisciplinary care. [ABSTRACT FROM AUTHOR]

Aims: Facilitated self‐management support programmes have become central to the treatment of chronic diseases including diabetes. For many children and young people with diabetes (CYPD), the impact on glycated haemoglobin (HbA1c) and a range of self‐management behaviours promised by these programmes remain unrealised. This warrants an appraisal of current thinking and the existing evidence to guide the development of programmes better targeted at this age group. Methods: Create a narrative review of systematic reviews produced in the last 3 years that have explored the impact on CYPD of the four key elements of self‐management support programmes: education, instruction and advice including peer support; psychological counselling via a range of therapies; self‐monitoring, including diaries and telemetric devices; and telecare, the technology‐enabled follow‐up and support by healthcare providers. Results: Games and gamification appear to offer a promising means of engaging and educating CYPD. Psychological interventions when delivered by trained practitioners, appear to improve HbA1c and quality of life although effect sizes were small. Technology‐enabled interactive diaries can increase the frequency of self‐monitoring and reduce levels of HbA1c. Telecare provided synchronously via telephone produced significant improvements in HbA1c. Conclusions: The cost‐effective flexibility of increasing the reliance on technology is an attractive proposition; however, there are resource implications for digital connectivity in underserved populations. The need remains to improve the understanding of which elements of each component are most effective in a particular context, and how to optimise the influence and input of families, caregivers and peers. [ABSTRACT FROM AUTHOR]

Keywords: randomized trial; type 1 diabetes; insulin pump therapy; continuous glucose monitoring (CGM) EN randomized trial type 1 diabetes insulin pump therapy continuous glucose monitoring (CGM) 889 893 5 02/03/23 20230301 NES 230301 INTRODUCTION Healthy sleep supports general health and well-being.[[1]] Sleep disturbance in type 1 diabetes (T1DM) can be caused by factors including fear of hypoglycaemia and suboptimal glucose control.[3] For example, hypoglycaemia or hyperglycaemia can disturb sleep, through mechanisms including sympathetic activation and neuropathic pain, respectively.[4] Several observational studies have suggested that hybrid closed-loop (HCL) system initiation is associated with improved sleep,[[5]] but these data could be limited by confounding and other biases. Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study. The proportion of participants with self-reported poor sleep quality (PSQI score >5) was nonsignificantly higher during the SAP period compared to the HCL period (40.5 [24.8-57.9]% vs. 29.7 [15.9-47.0]%; I P i = 0.15). Effects of closed-loop insulin delivery on glycemia during sleep and sleep quality in older adults with type 1 diabetes: results from the ORACL trial. [Extracted from the article]

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non‐invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [15O]H2O and [18F]FDG. Despite the success of these techniques, it became apparent that more specific probes were needed to understand the neurochemical bases of psychiatric disorders. The first neurochemical PET imaging probes targeted sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. Based on the centrality of monoamine dysfunction in psychiatric disorders and the measured success of monoamine‐enhancing drugs in treating them, the next 30 years witnessed the development of an armamentarium of PET radiopharmaceuticals and imaging methodologies for studying monoamines. Continued development of monoamine‐enhancing drugs over this time however was less successful, realizing only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely paralleled drug development priorities resulting in the development of new PET imaging agents for non‐monoamine targets. Part one of this review will briefly survey novel PET imaging targets with relevance to the field of psychiatry, which include the metabotropic glutamate receptor type 5 (mGluR5), purinergic P2X7 receptor, type 1 cannabinoid receptor (CB1), phosphodiesterase 10A (PDE10A), and describe radiotracers developed for these and other targets that have matured to human subject investigations. Current limitations of the targets and techniques will also be discussed. [ABSTRACT FROM AUTHOR]

Early applications of positron emission tomography (PET) in psychiatry sought to identify derangements of cerebral blood flow and metabolism. The need for more specific neurochemical imaging probes was soon evident, and these probes initially targeted the sites of action of neuroleptic (dopamine D2 receptors) and psychoactive (serotonin receptors) drugs. For nearly 30 years, the centrality of monoamine dysfunction in psychiatric disorders drove the development of an armamentarium of monoaminergic PET radiopharmaceuticals and imaging methodologies. However, continued investments in monoamine‐enhancing drug development realized only modest gains in efficacy and tolerability. As patent protection for many widely prescribed and profitable psychiatric drugs lapsed, drug development pipelines shifted away from monoamines in search of novel targets with the promises of improved efficacy, or abandoned altogether. Over this period, PET radiopharmaceutical development activities closely parallelled drug development priorities, resulting in the development of new PET imaging agents for non‐monoamine targets. In part two of this review, we survey clinical research studies using the novel targets and radiotracers described in part one across major psychiatric application areas such as substance use disorders, anxiety disorders, eating disorders, personality disorders, mood disorders, and schizophrenia. Important limitations of the studies described are discussed, as well as key methodologic issues, challenges to the field, and the status of clinical trials seeking to exploit these targets for novel therapeutics. [ABSTRACT FROM AUTHOR]

Nano alumina and micro aluminum tri hydrate filled high‐temperature vulcanizing silicone rubber composites were prepared with dispersing aids of surfactant Triton™‐X‐100 (TX‐100) and silane coupling agent 3‐methacryloxypropyltrimethoxysilane (KH‐570), through an in situ modification technique. Fourier transform infrared spectroscopy (FTIR) and X‐ray diffraction (XRD) analysis were carried out to understand the effects of dispersing aids on the structural and crystallographic properties of composites. Scanning electron microscopy images of TX‐100 dispersed composites revealed the presence of several localized regions of agglomeration, whereas KH‐570 dispersed composites showed moderate dispersion. Measurements of volume resistivity demonstrated an increment of four decades for KH‐570 dispersed nanocomposite over TX‐100. Better compatibility between fillers and base matrix through KH‐570 was evident from the low loss factor values. Inclined plane tracking and erosion results were discussed in detail with leakage current analysis. The binary composite prepared with KH‐570 was observed to resist the detrimental dry band arcing and subsequent erosion by 2 h and 20 min over TX‐100 dispersed composite. Dry arc resistance and the formation of thermal pathways connecting micro and nanofillers were discussed in detail. FTIR analysis of ash generated after inclined plane tracking and erosion test confirmed the surfacing of added fillers. KH‐570 dispersed composites showed superior properties as compared to composites prepared with TX‐100. [ABSTRACT FROM AUTHOR]

Emerging experimental evidence suggests tau pathology spreads between neuroanatomically connected brain regions in a prion‐like manner in Alzheimer's disease (AD). Tau seeding, the ability of prion‐like tau to recruit and misfold naïve tau to generate new seeds, is detected early in human AD brains before the development of major tau pathology. Many antitumour drugs have been reported to confer protection against neurodegeneration, supporting the repurposing of approved and experimental or investigational oncology drugs for AD therapy. In this study, we evaluated whether antitumour drugs that abrogate the generation of seed‐competent aggregates of tau Repeat 3 (R3) domain peptides can prevent tau seeding and toxicity in Tau‐RD P301S FRET Biosensor cells and Caenorhabditis elegans. We demonstrate that drugs that interact with the N‐terminal VQIVYK or the C‐terminal region housing the Cys322 prevent R3 dimerisation, abolishing the generation of prion‐like R3 seeds. Preformed R3 seeds (fibrils) capped with, or R3 seeds formed in the presence of VQIVYK‐ or Cys322‐targeting drugs have a reduced potency to cause aggregation of naïve tau in biosensor cells and protect worms from aggregate toxicity. These findings indicate that VQIVYK‐ or Cys322‐targeting drugs may act as prophylactic agents against tau seeding. [ABSTRACT FROM AUTHOR]

Coronaviridae is a family of single‐stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS‐CoV‐2 is responsible for the ongoing global pandemic, and SARS‐CoV and MERS‐CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229‐E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of delivery on the pO2/FiO2 ratio (P/F ratio) in patients with COVID‐19‐related acute respiratory distress syndrome (ARDS) and to compare characteristics between delivered and undelivered pregnant patients with COVID‐19. Design: Retrospective cohort. Setting: Four hospitals in Houston, Texas. Population: Pregnant patients admitted to the hospital for COVID‐19. Methods: Among patients with ARDS who were delivered during their hospitalisation for COVID‐19, linear mixed models were used to investigate time trends before and after delivery of the P/F ratio. Patient characteristics were compared between patients delivered during their hospitalisation for COVID‐19 and those discharged undelivered. Main outcome measures: The P/F ratio, age, gestational age, length of stay and severity of illness, Results: Between 4 May 2020 and 26 July 2020, a total of 61 pregnant patients were admitted for COVID‐19. Baseline characteristics were similar between the study groups. Delivery occurred in 21 (34%) of patients during their hospitalisation for COVID‐19. Delivered patients had more severe disease and were admitted at a later gestational age than patients not delivered. Ten of these 21 patients (48%) were delivered preterm; of these, six were delivered due to complications of COVID‐19 and four were delivered for obstetric indications. In patients with ARDS who were delivered (n = 17), the P/F ratio had a negative slope that improved after delivery. Conclusions: COVID‐19‐related ARDS in pregnancy requires multidisciplinary care and individualised decision‐making, but delivery slows the deterioration of the P/F ratio in these patients. Delivery improves the P/F ratio in COVID‐19‐related ARDS, though individualised delivery management is needed. Delivery improves the P/F ratio in COVID‐19‐related ARDS, though individualised delivery management is needed. [ABSTRACT FROM AUTHOR]

The aim was to evaluate the effectiveness of autologous platelet‐rich fibrin (PRF) as an adjunct to scaling and root planing (SRP) in moderate periodontal pockets. The split‐mouth study involved 32 sites from 16 patients. Baseline parameters were recorded followed by complete full‐mouth SRP. The test and control sites were randomly selected and autologous PRF was placed in the test site and other site served as control. The blinded examiner recorded clinical parameters at baseline, 60 days, and 90 days. No statistical significance was found at baseline in probing depth (PD) and clinical attachment level (CAL). Statistically, significant improvement was observed within test and control groups at 90 days compared to baseline values. A statistically significant difference in test sites was found in terms of reduction in PD and clinical attachment gain (CAG) compared to the control sites at the end of the study period (p value <0.05). This split‐mouth pilot study emphasized a statistically significant improvement in pocket depth reduction and CAL gain when PRF was used as an adjunct to SRP in moderate periodontal pockets. [ABSTRACT FROM AUTHOR]

Aims: Type 1 diabetes is characterised by the destruction of pancreatic β‐cells. Significant levels of β‐cells remain at diagnosis. Preserving these cells improves glucose control and protects from long‐term complications. We undertook a systematic review and meta‐analyses of all randomised controlled trials (RCTs) of interventions to preserve β‐cell function in people newly diagnosed with type 1 diabetes. This paper reports the results of interventions for improving glucose control to assess whether they preserve β‐cell function. Methods: Searches for RCTs in MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov and WHO International Clinical Trials Registry. Eligible studies included newly diagnosed patients with type 1 diabetes, any intervention to improve glucose control and at least 1 month of follow‐up. Data were extracted using a pre‐defined data‐extraction sheet with 10% of extractions checked by a second reviewer. Results: Twenty‐eight studies with 1662 participants were grouped by intervention into six subgroups (alternative insulins, subcutaneous and intravenous insulin delivery, intensive therapy, glucose sensing, adjuncts). Only three studies demonstrated an improvement in glucose control as well as β‐cell function. These interventions included intensive insulin therapy and use of an alternative insulin. Conclusions: This is the largest comprehensive review of RCTs in this area. It demonstrates a lack of robust evidence that interventions to improve glucose control preserve β‐cell function in new onset type 1 diabetes, although analysis was hampered by low‐quality evidence and inconsistent reporting of studies. Development of guidelines to support the design of trials in this field is a priority. [ABSTRACT FROM AUTHOR]

Introduction: To assess if in adults with COVID‐19, whether those with diabetes and complications (DM+C) present with a more severe clinical profile and if that relates to increased mortality, compared to those with diabetes with no complications (DM‐NC) and those without diabetes. Methods: Service‐level data was used from 996 adults with laboratory confirmed COVID‐19 who presented to the Queen Elizabeth Hospital Birmingham, UK, from March to June 2020. All individuals were categorized into DM+C, DM‐NC, and non‐diabetes groups. Physiological and laboratory measurements in the first 5 days after admission were collated and compared among groups. Cox proportional hazards regression models were used to evaluate associations between diabetes status and the risk of mortality. Results: Among the 996 individuals, 104 (10.4%) were DM+C, 295 (29.6%) DM‐NC and 597 (59.9%) non‐diabetes. There were 309 (31.0%) in‐hospital deaths documented, 40 (4.0% of total cohort) were DM+C, 99 (9.9%) DM‐NC and 170 (17.0%) non‐diabetes. Individuals with DM+C were more likely to present with high anion gap/metabolic acidosis, features of renal impairment, and low albumin/lymphocyte count than those with DM‐NC or those without diabetes. There was no significant difference in mortality rates among the groups: compared to individuals without diabetes, the adjusted HRs were 1.39 (95% CI 0.95–2.03, p = 0.093) and 1.18 (95% CI 0.90–1.54, p = 0.226) in DM+C and DM‐C, respectively. Conclusions: Those with COVID‐19 and DM+C presented with a more severe clinical and biochemical profile, but this did not associate with increased mortality in this study. [ABSTRACT FROM AUTHOR]

Aim: To identify the baseline demographic and clinical characteristics associated with diabetes‐related distress (DRD) and factors associated with improvement in DRD after initiating use of the FreeStyle Libre (FSL) in people living with type 1 diabetes (T1D). Methods: The study was performed using baseline and follow‐up data from the Association of British Clinical Diabetologists nationwide audit of people with diabetes who initiated use of the FSL in the United Kingdom. DRD was assessed using the two‐item diabetes‐related distress scale (DDS; defined as the average of the two‐item score ≥3). People living with T1D were categorized into two groups: those with high DRD, defined as an average DDS score ≥3 and those with lower DRD, defined as a DDS score <3. We used a gradient‐boosting machine‐learning (GBM) model to identify the relative influence (RI) of baseline variables on average DDS score. Results: The study population consisted of 9159 patients, 96.6% of whom had T1D. The median (interquartile range [IQR]) age was 45.1 (32‐56) years, 50.1% were women, the median (IQR) baseline body mass index was 26.1 (23.2‐29.6) kg/m2 and the median (IQR) duration of diabetes was 20 (11‐32) years. The two components of the DDS were significantly correlated (r2 = 0.73; P < 0.0001). Higher DRD was prevalent in 53% (4879/9159) of people living with T1D at baseline. In the GBM model, the top baseline variables associated with average DDS score were baseline glycated haemoglobin (HbA1c; RI = 51.1), baseline Gold score (RI = 23.3), gender (RI = 7.05) and fear of hypoglycaemia (RI = 4.96). Follow‐up data were available for 3312 participants. The top factors associated with improvement in DDS score following use of the FSL were change in Gold score (RI = 28.2) and change in baseline HbA1c (RI = 19.3). Conclusions: In this large UK cohort of people living with T1D, diabetes distress was prevalent and associated with higher HbA1c, impaired awareness of hypoglycaemia and female gender. Improvement in glycaemic control and hypoglycaemia unawareness with the use of the FSL was associated with improvement in DRD in people living with T1D. [ABSTRACT FROM AUTHOR]

Transpeople in India forge identities at the confluence of contradictory social forces. Interviews conducted in the state of Kerala suggest that the experience of transphobic stigma results in self‐employed transpeople being abjectified. Social abjectification, in turn, triggers their identity work within liminal social spaces located between the everyday lifeworld and postcolonial legal institutions. Through this work, the participants in this study navigated the contradictions between two identity‐constituting external structures: culture and law. Culture is a source of identity threat, but it also supplies a socially legitimated identity template—the hijra—used in the vital self‐formative work of mirroring and witnessing. Similarly, trans‐supportive social policies and laws provide institutional scaffolding for identities. Yet, despite the agential nature of the participants' identity work, the inherent limitations of the law and the vulnerability of embodiment render them susceptible to the ongoing threat posed by the transphobia emanating from ambient cultural norms. [ABSTRACT FROM AUTHOR]

Background/Objective: Newborn infant skin is functional but immature, and diapering products can play a significant role in infant diapered skin health. Previous work demonstrated a regimen consisting of a diaper with an emollient and apertures on the inner liner (topsheet) with an acidic, pH‐buffered wipe (Regimen A) lowered newborn skin pH and reduced the enzymatic activity on skin post‐stool cleaning versus a regimen without these features (Regimen B). This study extends these findings to determine the impact of Regimen A on diaper area erythema severity over a 2‐week use period. Methods: This IRB‐approved, blinded, randomized, crossover study enrolled newborn infants >7 days and ≤8 weeks. Participants exclusively used two unique diaper and wipe combinations, Regimen A and Regimen B (non‐emollient, non‐aperture containing topsheet and wipe with limited buffering capacity), each for 14 days and preceded by a 3‐day washout regimen. Results: Diapered skin pH was reduced during Regimen A use to values similar to that of a non‐diapered control site (chest), while use of Regimen B was associated with a more alkaline skin pH. Regimen A resulted in significantly fewer severe erythema episodes. At the site of highest erythema, the perianal space, the average erythema score was significantly lower and more newborns were free of erythema while using Regimen A vs. Regimen B (P <.05). Conclusions: These findings demonstrate that diapering products can have a significant impact on newborn skin. They reinforce the need to support the physiological normalization of skin pH and protection from skin irritation and damage. [ABSTRACT FROM AUTHOR]

Study Objective: To evaluate a surveillance protocol in managing the risk of hepatitis B virus (HBV) reactivation among lymphoma patients with resolved HBV infection receiving rituximab. Design: Prospective, single‐arm study. Setting: National Cancer Centre, Singapore. Patients: Lymphoma patients with resolved HBV infection and scheduled to receive rituximab‐based treatment. Intervention: Close monitoring of HBV DNA levels, ie. every 4–6 weeks during rituximab treatment, every 6–8 weeks in the first year post‐treatment, and every 3–4 months in the second year post‐treatment. Measurements: The efficacy of the surveillance protocol was examined by evaluating the rates of reactivation‐related events. Feasibility was evaluated based on patient adherence. An economic analysis using a cost‐minimization approach was conducted to compare the costs between the surveillance protocol and universal prophylaxis with entecavir 0.5 mg daily up to 1 year after cessation of rituximab. Main Results: A total of 66 patients provided analyzable data with a follow‐up period of 966.6 months. No hepatitis flare or reactivation‐related events were detected. The median adherence rate to the surveillance protocol was 90.5%. Cost savings of US$946.40 per patient over the entire surveillance period were achieved if the surveillance protocol was adopted and was most affected by changes in prophylaxis duration and the cost of antiviral prophylaxis. Conclusions: The surveillance protocol is an effective, feasible and cost‐saving strategy to manage HBV reactivation among lymphoma patients with resolved HBV infection receiving rituximab. [ABSTRACT FROM AUTHOR]

Background: Infant diaper dermatitis (DD) is a prevalent condition due to multiple, interactive factors including increased skin hydration, irritant exposure, and increased skin pH. We examined diaper dermatitis vs within diaper and non‐diaper controls over time and characterized the association of skin color and texture relative to skin barrier integrity, hydration, and pH. Materials and Methods: The prospective study included 46 infants with DD at well‐child visits. Skin integrity was evaluated over 15 days, including visual skin condition, rate of stratum corneum transepidermal water accumulation, hydration, pH, and skin color and texture from high‐resolution digital skin surface images. Effects by site and time were evaluated with general linear models. Results: Six distinct texture patterns were observed. All three sites differed significantly for texture class frequency. Normal dermatoglyphics were more frequent for non‐diaper vs both within diaper and rash sites. Dermatoglyphics with marked furrows or lines (class 3) were common within diaper vs rash but not for non‐diaper vs within diaper. Streaks were highest for DD and lowest for non‐diaper. Flat regions were more frequent DD. Barrier integrity, that is, moisture accumulation rate, was lower for normal dermatoglyphics than streaks or flat texture. DD severity decreased over 15 days. Barrier properties of within diaper and non‐diaper areas were not well‐differentiated. Conclusion: The incidence of streak texture in the within diaper high magnification images was high despite being visually normal. This finding suggests that it is an "early indicator" of skin damage and may be clinically useful for early detection and treatment. [ABSTRACT FROM AUTHOR]

Sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors are widely prescribed in people with type 2 diabetes. We aimed to investigate whether SGLT2 inhibitor prescription is associated with COVID‐19, when compared with an active comparator. We performed a propensity‐score‐matched cohort study with active comparators and a negative control outcome in a large UK‐based primary care dataset. Participants prescribed SGLT2 inhibitors (n = 9948) and a comparator group prescribed dipeptidyl peptidase‐4 (DPP‐4) inhibitors (n = 14 917) were followed up from January 30 to July 27, 2020. The primary outcome was confirmed or clinically suspected COVID‐19. The incidence rate of COVID‐19 was 19.7/1000 person‐years among users of SGLT2 inhibitors and 24.7/1000 person‐years among propensity‐score‐matched users of DPP‐4 inhibitors. The adjusted hazard ratio was 0.92 (95% confidence interval 0.66 to 1.29), and there was no evidence of residual confounding in the negative control analysis. We did not observe an increased risk of COVID‐19 in primary care amongst those prescribed SGLT2 inhibitors compared to DPP‐4 inhibitors, suggesting that clinicians may safely use these agents in the everyday care of people with type 2 diabetes during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

The article discusses that high doses of glucocorticoids exacerbate hyperglycaemia in people with diabetes. It mentions that glucocorticoids are the commonest cause of people with diabetes developing potentially life-threating hyperglycaemic hyperosmolar state (HHS) in hospital. It also mentions that COVID-19 infection is associated with significant insulin resistance.

Aim: We aimed to explore the association between South Asian ethnicity and complications of type 1 diabetes, and whether this is affected by migration. Methods: In this retrospective cohort study, data on diabetes control and complications were obtained for South Asians in India (South AsiansIndia, n = 2592) and the UK (South AsiansUK, n = 221) and white Europeans in the UK (n = 1431). Multivariable logistic regression was used to identify associations between ethnicity and diabetic kidney disease, retinopathy and neuropathy adjusting for age, sex, BMI, disease duration, HbA1c, blood pressure (BP) and cholesterol. Results: South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease [odds ratio (OR) 5.0, 95% confidence intervals (CI) 3.6–7.1] and retinopathy (OR 1.8, 95% CI 1.2–2.5), but lower odds of neuropathy (OR 0.5, 95% CI 0.4–0.6) than white Europeans. South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease (OR 3.0, 95% 1.8–5.3) than South AsiansUK, but there was no significant difference in the odds of other complications. Conclusions: In this hypothesis‐generating study, we report that South Asian ethnicity is associated with greater risk of diabetic kidney disease and retinopathy, and lower risk of neuropathy than white European ethnicity. Part of the excess diabetic kidney disease risk is reduced in South AsiansUK. These associations cannot be accounted for by differences in vascular risk factors. Our findings in South Asians with type 1 diabetes mirror previous findings in type 2 diabetes and now need to be validated in a study of the effect of ethnicity on type 1 diabetes complications where healthcare is provided in the same setting. What's new?: The impact of South Asian ethnicity and migration on the natural history of type 1 diabetes is not well understood.South Asians in India have a greater risk of retinopathy and diabetic kidney disease and lower risk of neuropathy than white Europeans in the UK. The excess risk of diabetic kidney disease is mitigated for South Asians in the UK.These associations persist despite adjusting for classical risk factors for microvascular complications such as glycaemic control, blood pressure, disease duration or markers of insulin resistance.The results call for us to be particularly vigilant for the complications of type 1 diabetes in South Asians. [ABSTRACT FROM AUTHOR]

The article discusses the guidance on the management of inpatient hyperglycaemia in the midst of the coronavirus disease 2019 (COVID-19) pandemic, published by the British National Diabetes Inpatient COVID-19 Response Group. Topics explored include the impact of the pandemic on the delivery of acute inpatient care to individuals with diabetes, the recommendations on the adjustment of long-acting insulin dosages, and brief details about the updates to the existing clinical guidance.

Background/Objectives: Diaper dermatitis is one of the most frequent skin conditions affecting infants and is associated with elevated skin pH, exposure to urine and feces, and increased fecal protease and lipase activity, resulting in stratum corneum barrier damage and increased risk of infection. The study aim was to determine the impact of two diaper and wipe regimens on newborn infant skin pH and residual enzyme activity after stool cleaning. Methods: Two diaper and wipe regimens were compared in a randomized, single‐blinded crossover study. Regimen A paired an emollient‐containing diaper with an acidic, pH‐buffered wipe. Regimen B was a non‐emollient diaper and wipe with limited buffering capacity. A 3‐day washout period preceded each 3‐day regimen use period. Skin pH at the perianal/buttocks interface (PBI), genital region, and undiapered chest control were measured at baseline and day 3. Skin swabs were collected for residual enzyme activity after a stool cleaning event. Results: Diapered skin pH at the PBI was similar to undiapered skin after 3 days of use for Regimen A, while PBI pH for Regimen B was elevated versus control. PBI pH was lower for Regimen A versus Regimen B. After a stool cleaning, PBI skin pH for Regimen A was lower immediately and had lower residual enzyme activity versus Regimen B (P <.05), and the pH‐lowering effect was sustained up to 60 minutes. Conclusions: These results suggest that the use of an emollient‐containing diaper with a pH‐buffered wipe creates conditions favorable to optimum diapered skin health. [ABSTRACT FROM AUTHOR]

Aim: To develop a structured education programme for individuals with Type 1 diabetes who are engaging in regular exercise. Method: A multidisciplinary team of experts in supporting exercise and physical activity for people with Type 1 diabetes, alongside researchers with experience of developing self‐management education, developed an exercise programme using the Medical Research Council framework. The programme was informed by a review of the evidence relating to Type 1 diabetes and exercise, the behaviour change literature (including the behaviour change taxonomy), and qualitative interviews with stakeholders. The programme and supporting resources were refined using an iterative process of testing, delivery and collecting feedback from participants and the wider development team. Results: The outcome of the intervention development was the design of a feasible and acceptable intervention for people with Type 1 diabetes to support safe exercise. The pilot allowed refinement of the intervention prior to testing in a two‐site feasibility randomized controlled trial. Key findings from the pilot informed minor restructuring of the timetable (timings and order) and adaptation of supporting educational materials (participant handbook and teaching materials). Conclusion: The 'EXercise in people with Type One Diabetes' (EXTOD) education programme has been developed using robust methodology for the generation of educational interventions. It now needs testing in a randomized controlled trial. What's new?: Currently there is no dedicated structured education programme that supports the management of Type 1 diabetes for exercise.A self‐management education programme to support safe and effective exercise for people with Type 1 diabetes has been developed using the Medical Research Council framework.In the exercise programme we developed, participants were able to adjust their regimens and plan their exercise in a more structured way.The programme was delivered by trained healthcare professionals, meaning it can be embedded into the specialist care setting.If demonstrated to be effective, this programme could potentially expand currently available support for adults with Type 1 diabetes who wish to exercise. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?Hypoglycaemia is a commonly cited barrier to exercise in type 1 diabetes mellitus (T1D). Knowledge of approaches to prevent or manage exercise‐induced hypoglycaemia can support patients to exercise and help clinicians to give advice. This review presents evidence‐based strategies to prevent exercise‐induced hypoglycaemia in T1D.What advances does it highlight?This review highlights approaches that can be used before, during and after exercise to mitigate the risk of hypoglycaemia. The approaches include the timing of exercise, the type of exercise, adjustments to insulin and carbohydrate, use of novel technology and education. Exercise is a key component for the management of type 1 diabetes mellitus (T1D) and is associated with reduced risk of cardiovascular disease, decreased daily insulin requirements and improved quality of life. Owing to these benefits, people with T1D are recommended to undertake regular physical activity, 150 min per week for adults and 60 min per day for children and adolescents. Despite the recommendations, many people do not meet these targets. One of the commonly cited barriers to exercise is fear of hypoglycaemia along with limited knowledge of effective preventative strategies. Hypoglycaemia can be difficult to predict, and symptoms are often masked during exercise or stress of competition. For athletes with T1D, hypoglycaemia can also limit sporting success. Hypoglycaemia before an event increases the risks of hypoglycaemia during competition and can reduce performance. To avoid hypoglycaemia, people with T1D may avoid exercise altogether or consume excessive amounts of carbohydrates, which mitigates many of the health benefits of exercise. Increased understanding of approaches to prevent or manage hypoglycaemia is therefore important to help increase levels of physical activity in people with T1D and to support athletes with T1D to compete at the highest level. This review outlines the prevalence of exercise‐related hypoglycaemia, its underlying physiology and the strategies that can be used to prevent and manage exercise‐induced hypoglycaemia in T1D. Our hope is that this knowledge will be used by people with T1D and their clinicians to find individual approaches to manage exercise‐related hypoglycaemia. [ABSTRACT FROM AUTHOR]

New Findings: What is the topic of this review?This review discusses the evidence of the benefits of exercise training for β‐cell health through improvements in function, proliferation and survival which may have implications in the treatment of diabetes.What advances does it highlight?This review highlights how exercise may modulate β‐cell health in the context of diabetes and highlights the need for further exploration of whether β‐cell preserving effects of exercise translates to T1D. Physical exercise is a core therapy for type 1 and type 2 diabetes. Whilst the benefits of exercise for different physiological systems are recognised, the effect of exercise specifically on the pancreatic β‐cell is not well described. Here we review the effects of physical exercise on β‐cell health. We show that exercise improves β‐cell mass and function. The improved function manifests primarily through the increased insulin content of the β‐cell and its increased ability to secrete insulin in response to a glucose stimulus. We review the evidence relating to glucose sensing, insulin signalling, β‐cell proliferation and β‐cell apoptosis in humans and animal models with acute exercise and following exercise training programmes. Some of the mechanisms through which these benefits manifest are discussed. [ABSTRACT FROM AUTHOR]

Background and Purpose: Nociceptin/orphanin FQ (N/OFQ) peptide and its cognate receptor (NOP) are widely expressed in mesolimbic brain regions where they play an important role in modulating reward and motivation. Early evidence suggested that NOP receptor activation attenuates the rewarding effects of drugs of abuse, including alcohol. However, emerging data indicate that NOP receptor blockade also effectively attenuates alcohol drinking and relapse. To advance our understanding of the role of the N/OFQ-NOP receptor system in alcohol abuse, we examined the effect of NOP receptor blockade on voluntary alcohol drinking at the neurocircuitry level.Experimental Approach: Using male and female genetically selected alcohol-preferring Marchigian Sardinian (msP) rats, we initially evaluated the effects of the selective NOP receptor antagonist LY2817412 (3, 10, and 30 mg·kg-1 , p.o.) on alcohol consumption in a two-bottle free-choice paradigm. We then microinjected LY2817412 (3 and 6 μg·μl-1 per rat) in the central nucleus of the amygdala (CeA), ventral tegmental area (VTA), and nucleus accumbens (NAc).Key Results: Peripheral LY2817412 administration dose-dependently and selectively reduced voluntary alcohol intake in male and female msP rats. Central injections of LY2817412 markedly attenuated voluntary alcohol intake in both sexes following administration in the CeA and VTA but not in the NAc.Conclusion and Implications: The present results revealed that the CeA and VTA are neuroanatomical substrates that mediate the effects of NOP receptor antagonism on alcohol consumption. Overall, our findings support the potential of NOP receptor antagonism as a treatment strategy to attenuate alcohol use and addiction. [ABSTRACT FROM AUTHOR]

Aims: To assess whether glycaemic control is associated with a lifelong increased risk of fracture in people with newly diagnosed Type 1 diabetes. Methods: People with newly diagnosed Type 1 diabetes between 1 January 1995 and 10 May 2016 were identified in The Health Improvement Network database. Longitudinal HbA1c measurements from diagnosis to fracture or study end or loss to follow‐up were collected. A Cox proportional hazards model with HbA1c included as a time‐dependent variable was fitted to these data. Results: Some 5368 people with newly diagnosed Type 1 diabetes were included. The estimated adjusted hazard ratio (aHR) for HbA1c was statistically significant [aHR 1.007; 95% confidence interval (CI) 1.002–1.011 (mmol/mol) and aHR 1.07; 95% CI 1.03–1.12 (%)]. An incremental higher risk of fracture was observed with increasing levels of HbA1c. Conclusions: In people with newly diagnosed Type 1 diabetes, higher HbA1c is associated with an increased risk for fractures. What's new?: Type 1 diabetes is associated with an increased incidence of fractures. The effect of glycemia is unknown, because change of glycaemic control over time has never been considered.HbA1c was associated with an increased fracture risk in people with newly diagnosed Type 1 diabetes (7% increments for each per cent increase in HbA1c).This information may be considered in fracture risk assessment, and even in prompting early anti‐osteoporotic intervention in the context of Type 1 diabetes, especially when another established risk factor is present. [ABSTRACT FROM AUTHOR]

Aim: To conduct a systematic review and meta‐analysis to evaluate the effect of carbohydrate restriction on glycaemic control in Type 2 diabetes. Methods: We searched Medline, EMBASE and CINAHL for the period between 1976 and April 2018. We included randomized controlled trials comparing carbohydrate restriction with a control diet which aimed to maintain or increase carbohydrate intake, and that reported HbA1c as an outcome and reported the amount of carbohydrate consumed during or at the end of the study, with outcomes reported at ≥3 months. Results: We identified 1402 randomized controlled trials, 25 of which met the inclusion criteria, incorporating 2132 participants for the main outcome. Definitions of low carbohydrate varied among the studies. The pooled effect estimate from meta‐analysis was a weighted mean difference of –0.09% [95% CI –0.27, 0.08 (P = 0.30); I2 72% (P <0.001)], suggesting no effect on HbA1c of restricting the quantity of carbohydrate. A subgroup analysis of diets containing 50–130 g carbohydrate resulted in a pooled effect estimate of –0.49% [95% CI –0.75, –0.23 (P <0.001); I2 0% (P = 0.56)], suggesting a clinically and statistically significant effect on HbA1c in favour of low‐carbohydrate diets in studies of ≤6 months' duration. Conclusions: There was no overall pooled effect on HbA1c in favour of restricting carbohydrate; however, restriction of carbohydrate to 50–130 g per day had beneficial effects on HbA1c in trials up to 6 months. Future randomized controlled trials should be of >12 months' duration, assess pre‐study carbohydrate intake, use recognized definitions of low‐carbohydrate diets and examine reasons for non‐adherence to prescribed diets in greater detail. What's new?: A large number of trials and systematic reviews have obtained conflicting results regarding the effect of restricting carbohydrate on glycaemic control.The present study includes analysis of trials reporting adherence to carbohydrate‐restricted diets, showing this has no material impact on the outcome and bringing the evidence up to date by including more recent trials.Clinicians should inform people with Type 2 diabetes that there are a number of effective dietary approaches for improving glycaemic control, which may include restricting carbohydrate to 50–130 g per day. [ABSTRACT FROM AUTHOR]

Phosphodiesterase‐10a (PDE10a) is located exclusively in medium spiny neurons (MSN). Rodent studies show an increase in striatal MSN spine density following exposure to cocaine. These increases in MSN spine density are suggested to underlie neurobiological changes which contribute to cocaine self‐administration. No postmortem or imaging studies have confirmed this finding in humans. Here, we hypothesized an increase in the MSN marker PDE10a in subjects with cocaine use disorder ("cocaine users") compared to controls. PDE10a availability was measured with [11C]IMA107 and positron emission tomography in 15 cocaine users and 15 controls matched for age, gender, and nicotine status. Cocaine users with no comorbid psychiatric, medical, or drug abuse disorders were scanned following two weeks of outpatient‐monitored abstinence. [11C]IMA107 binding potential relative to nondisplaceable uptake (BPND) in the regions of interest was derived with the simplified reference tissue method. No significant effect of diagnosis on BPND was demonstrated using linear mixed modeling with [11C]IMA107 BPND as the dependent variable and regions of interest as a repeated measure. There were no significant relationships between BPND and clinical rating scales. To the extent that PDE10a is a valid proxy for MSN spine density, these results do not support its increase in recently abstinent cocaine users. [C‐11]IMA‐107 BPND is not different between cocaine users (black bars) and healthy controls (white bars). Regions shown are: GP‐Globus pallidus; VST‐ventral striatum; CAD‐caudate; PUT‐putamen; MID‐midbrain; and THA‐thalamus [ABSTRACT FROM AUTHOR]

Chemotherapeutic drugs are known to cause retinal toxicity along with ischaemia.1-5 Platinum analogues (cisplatin/carboplatin), used for treating various malignancies, are the most common drugs associated with ischaemic retinopathy.1-4 Paclitaxel, an anti-microtubule agent, is mostly used in combination with platinum analogues. Optical coherence tomography (OCT) of both eyes demonstrated oedematous optic discs, macular oedema, subretinal fluid and hyper-reflective inner retinal layers indicating retinal ischaemia (Figure 1C,D). C, Optical coherence tomography (OCT) of the right eye showing oedematous optic disc, macular oedema with neurosensory detachment and hyper-reflective inner retinal layers indicating retinal ischaemia. [Extracted from the article]

The article discusses the guidance on the management of diabetic ketoacidosis (DKA) in the midst of the coronavirus disease 2019 (COVID-19) pandemic, published by the British National Diabetes Inpatient COVID-19 Response Group. Topics explored include the subcutaneous insulin regimen that clinicians need to ensure availability in case of DKA, the required monitoring of oxygen saturations and fluid balance in concerned patients, and the recommended use of rapid acting insulin analogues.

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. What's new?: Diabetes specialist services help avoid unnecessary admission and readmission of people with diabetes to secondary care facilities and inpatient teams facilitate their care whilst admitted.Clinicians and trainees without diabetes expertise are providing diabetes care during the COVID‐19 pandemic.This Position Statement outlines the need to maintain key elements of specialist diabetes services with a focus on delivering safe inpatient diabetes care.The Position Statement also outlines simple pathways for the management of inpatients with diabetes by admitting teams in secondary care.This Position Statement will be useful to trusts/health boards in redesigning clinical services during the COVID‐19 pandemic and helping ensure that the safe care of people with diabetes. [ABSTRACT FROM AUTHOR]

Abstract: Studies in nonhuman primates and humans have demonstrated that amphetamine‐induced dopamine release in the cortex can be measured with [11C]FLB 457 and PET imaging. This technique has been successfully used in recent clinical studies to show decreased dopamine transmission in the prefrontal cortex in schizophrenia and alcohol dependence. Here, we present data from a cohort of twelve healthy controls in whom an oral amphetamine challenge (0.5 mg kg−1) did not lead to a significant reduction in [11C]FLB 457 BPND (i.e., binding potential relative to non‐displaceable uptake). Two factors that likely contributed to the inability to displace [11C]FLB 457 BPND in this cohort relative to successful cohorts are: (a) the acquisition of the baseline and post‐amphetamine scans on different days as opposed to the same day and (b) the initiation of the post‐amphetamine [11C]FLB 457 scan at ∼5 hours as opposed to ∼3 hours following oral amphetamine. Furthermore, we show [11C]FLB 457 reproducibility data from a legacy dataset to support greater variability in cortical BPND when the test and retest scans are acquired on different days as compared to the same day. These results highlight the methodological challenges that continue to plague the field with respect to imaging dopamine release in the cortex. [ABSTRACT FROM AUTHOR]

Abstract: Cyanobacteria are used as anode catalysts in photo‐bioelectrochemical cells to generate electricity in a sustainable, economic, and environmental friendly manner using only water and sunlight. Though cyanobacteria (CB) possess unique advantage for solar energy conversion by virtue of its robust photosynthesis, they cannot efficiently perform extracellular electron transfer (EET). The reasons being, unlike dissimilatory metal reducing bacteria (that are usually exploited in microbial fuel cells to generate electricity), (1) CB do not possess any special features on their outer membrane to carry out EET and, (2) the electrons generated in photosynthetic electron transport chain are channeled into competing respiratory pathways rather than to the anode. CB, genetically engineered to express outer membrane cytochrome S (OmcS), was found to generate ∼nine‐fold higher photocurrent compared to that of wild‐type cyanobacterium in our previous work. In this study, each of the three respiratory terminal oxidases in Synechococcus elongatus PCC7942 namely bd‐type quinol oxidase, aa3‐type cytochrome oxidase, and cbb3‐type cytochrome oxidase was knocked‐out one at a time (cyd‐, cox‐, and cco‐ respectively) and its contribution for extracellular ferricyanide reduction and photocurrent generation was investigated. The knock‐out mutant lacking functional bd‐type quinol oxidase (cyd‐) exhibited greater EET by reducing more ferricyanide compared to other single knock‐out mutants as well as the wild type. Further, cyd‐omcs (the cyd‐ mutant expressing OmcS) was found to generate more photocurrent than the corresponding single knock out controls and the wild‐type. This study clearly demonstrates that the bd‐quinol oxidase diverted more electrons from the photosynthetic electron transport chain towards respiratory oxygen reduction and knocking it out had certainly enhanced the cyanobacterial EET. [ABSTRACT FROM AUTHOR]