Antidepressant and antipsychotic drug prescribing and diabetes outcomes: A systematic review of observational studies

AIMS: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. METHODS: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. RESULTS: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. CONCLUSIONS: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Liquor licences issued to Australian schools

BACKGROUND: Children's positive socialisation to alcohol is associated with early initiation of drinking and alcohol-related harm in adult life. Internationally, there have been reports of adults' alcohol consumption at school events in the presence of children. The aim of this research was to identify the conditions under which Australian schools are required to apply for a liquor licence and the associated prevalence of liquor licences for these events where children were likely to be present. METHODS: A document review was conducted to examine temporary liquor licensing legislation. Quantitative analysis was used to examine relevant licensing data. Coding criteria was developed to determine school type, student year levels and the likely presence of children. RESULTS: Four jurisdictions provided data on 1817 relevant licences. The average annual licences/100 schools was highest amongst Independent schools followed by Catholic and public (government) schools. The rates were highest in Queensland and Victoria where children were present at 61% and 32% of events respectively. CONCLUSIONS: While there are legislative differences across jurisdictions, the prevalence of adults' alcohol use at school events in the presence of children may reflect the various education department policies and principals' and school communities' beliefs and attitudes. Licences are not required for all events where liquor is consumed so the prevalence of adults' use of alcohol at school events is likely to be higher than our analyses imply. Such practices may undermine teaching about alcohol use in the school curriculum and health promotion efforts to develop alcohol-free events when children are present

Antidepressant and antipsychotic drug prescribing and diabetes outcomes: A systematic review of observational studies

Aims: Psychotropic medication may be associated with adverse effects, including among people with diabetes. We conducted a systematic review of observational studies investigating the association between antidepressant or antipsychotic drug prescribing and type 2 diabetes outcomes. Methods: We systematically searched PubMed, EMBASE, and PsycINFO to 15th August 2022 to identify eligible studies. We used the Newcastle-Ottawa scale to assess study quality and performed a narrative synthesis. Results: We included 18 studies, 14 reporting on antidepressants and four on antipsychotics. There were 11 cohort studies, one self-controlled before and after study, two case-control studies, and four cross-sectional studies, of variable quality with highly heterogeneous study populations, exposure definitions, and outcomes analysed. Antidepressant prescribing may be associated with increased risk of macrovascular disease, whilst evidence on antidepressant and antipsychotic prescribing and glycaemic control was mixed. Few studies reported microvascular outcomes and risk factors other than glycaemic control. Conclusions: Studies of antidepressant and antipsychotic drug prescribing in relation to diabetes outcomes are scarce, with shortcomings and mixed findings. Until further evidence is available, people with diabetes prescribed antidepressants and antipsychotics should receive monitoring and appropriate treatment of risk factors and screening for complications as recommended in general diabetes guidelines

Identification of the first ATRIP-deficient patient and novel mutations in ATR define a clinical spectrum for ATR-ATRIP Seckel Syndrome

A homozygous mutational change in the Ataxia-Telangiectasia and RAD3 related (ATR) gene was previously reported in two related families displaying Seckel Syndrome (SS). Here, we provide the first identification of a Seckel Syndrome patient with mutations in ATRIP, the gene encoding ATR-Interacting Protein (ATRIP), the partner protein of ATR required for ATR stability and recruitment to the site of DNA damage. The patient has compound heterozygous mutations in ATRIP resulting in reduced ATRIP and ATR expression. A nonsense mutational change in one ATRIP allele results in a C-terminal truncated protein, which impairs ATR-ATRIP interaction; the other allele is abnormally spliced. We additionally describe two further unrelated patients native to the UK with the same novel, heterozygous mutations in ATR, which cause dramatically reduced ATR expression. All patient-derived cells showed defective DNA damage responses that can be attributed to impaired ATR-ATRIP function. Seckel Syndrome is characterised by microcephaly and growth delay, features also displayed by several related disorders including Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type II and Meier-Gorlin Syndrome (MGS). The identification of an ATRIP-deficient patient provides a novel genetic defect for Seckel Syndrome. Coupled with the identification of further ATR-deficient patients, our findings allow a spectrum of clinical features that can be ascribed to the ATR-ATRIP deficient sub-class of Seckel Syndrome. ATR-ATRIP patients are characterised by extremely severe microcephaly and growth delay, microtia (small ears), micrognathia (small and receding chin), and dental crowding. While aberrant bone development was mild in the original ATR-SS patient, some of the patients described here display skeletal abnormalities including, in one patient, small patellae, a feature characteristically observed in Meier-Gorlin Syndrome. Collectively, our analysis exposes an overlapping clinical manifestation between the disorders but allows an expanded spectrum of clinical features for ATR-ATRIP Seckel Syndrome to be define

Trying to solve the ‘worst situation’ together: participatory autism research

The importance of participatory autism research is discussed in relation to a project involving six autistic researchers and five non-autistic university researchers collaborating to investigate anxiety in autistic adolescents. The paper describes the process of establishing a research partnership and the values and philosophy behind this inclusive method of research. Lessons were learnt about neurodivergent thinking and the benefits it brings to the development of research questions and analysis of data

Structure and Recognition of a Novel HIV-1 gp120-gp41 Interface Antibody that Caused MPER Exposure through Viral Escape

A comprehensive understanding of the regions on HIV-1 envelope trimers targeted by broadly neutralizing antibodies may contribute to rational design of an HIV-1 vaccine. We previously identified a participant in the CAPRISA cohort, CAP248, who developed trimer-specific antibodies capable of neutralizing 60% of heterologous viruses at three years post-infection. Here, we report the isolation by B cell culture of monoclonal antibody CAP248-2B, which targets a novel membrane proximal epitope including elements of gp120 and gp41. Despite low maximum inhibition plateaus, often below 50% inhibitory concentrations, the breadth of CAP248-2B significantly correlated with donor plasma. Site-directed mutagenesis, X-ray crystallography, and negative-stain electron microscopy 3D reconstructions revealed how CAP248-2B recognizes a cleavage-dependent epitope that includes the gp120 C terminus. While this epitope is distinct, it overlapped in parts of gp41 with the epitopes of broadly neutralizing antibodies PGT151, VRC34, 35O22, 3BC315, and 10E8. CAP248-2B has a conformationally variable paratope with an unusually long 19 amino acid light chain third complementarity determining region. Two phenylalanines at the loop apex were predicted by docking and mutagenesis data to interact with the viral membrane. Neutralization by CAP248-2B is not dependent on any single glycan proximal to its epitope, and low neutralization plateaus could not be completely explained by N- or O-linked glycosylation pathway inhibitors, furin co-transfection, or pre-incubation with soluble CD4. Viral escape from CAP248-2B involved a cluster of rare mutations in the gp120-gp41 cleavage sites. Simultaneous introduction of these mutations into heterologous viruses abrogated neutralization by CAP248-2B, but enhanced neutralization sensitivity to 35O22, 4E10, and 10E8 by 10-100-fold. Altogether, this study expands the region of the HIV-1 gp120-gp41 quaternary interface that is a target for broadly neutralizing antibodies and identifies a set of mutations in the gp120 C terminus that exposes the membrane-proximal external region of gp41, with potential utility in HIV vaccine design

Exploiting unexpected situations in the mathematics classroom

The professional development of mathematics teachers needs to support teachers in orchestrating the mathematics classroom in ways that enable them to respond flexibly and productively to the unexpected. When a situation arises in the classroom which is not connected in an obvious way to the mathematical learning intentions of the lesson, it can be challenging for the teacher to improvise so as to craft this situation into an opportunity for doing and learning mathematics. In this study, as teacher-researcher I maintained a record of unexpected situations as they arose in my own secondary mathematics classroom. Details are given of four unexpected situations which I found ways to exploit mathematically, and these are analysed to highlight factors which may enhance a mathematics teacher’s preparedness for dealing with the unexpected. The results of this study indicate that deviating from the intended lesson to exploit an unexpected situation in which students have shown some interest can lead them into enjoyable and worthwhile mathematical engagement

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

With good intentions: complexity in unsolicited informal support for Aboriginal and Torres Strait Islander peoples. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Understanding people's social lived experiences of chronic illness is fundamental to improving health service delivery and health outcomes, particularly in relation to self-management activity. In explorations of social lived experiences this paper uncovers the ways in which Aboriginal and Torres Strait Islander people with chronic illness experience informal unsolicited support from peers and family members.</p> <p>Methods</p> <p>Nineteen Aboriginal and Torres Islander participants were interviewed in the Serious and Continuing Illness Policy and Practice Study (SCIPPS). Participants were people with Type 2 diabetes (N = 17), chronic obstructive pulmonary disease (N = 3) and/or chronic heart failure (N = 11) and family carers (N = 3). Participants were asked to describe their experience of having or caring for someone with chronic illness. Content and thematic analysis of in-depth semi-structured interviews was undertaken, assisted by QSR Nvivo8 software.</p> <p>Results</p> <p>Participants reported receiving several forms of unsolicited support, including encouragement, practical suggestions for managing, nagging, growling, and surveillance. Additionally, participants had engaged in 'yarning', creating a 'yarn' space, the function of which was distinguished as another important form of unsolicited support. The implications of recognising these various support forms are discussed in relation to responses to unsolicited support as well as the needs of family carers in providing effective informal support.</p> <p>Conclusions</p> <p>Certain locations of responsibility are anxiety producing. Family carers must be supported in appropriate education so that they can provide both solicited and unsolicited support in effective ways. Such educational support would have the added benefit of helping to reduce carer anxieties about caring roles and responsibilities. Mainstream health services would benefit from fostering environments that encourage informal interactions that facilitate learning and support in a relaxed atmosphere.</p