Insulin resistance, age and depression's impact on cognition in middle-aged adults from the PREVENT cohort.

BACKGROUND: Alzheimer's disease (AD), type 2 diabetes mellitus (characterised by insulin resistance) and depression are significant challenges facing public health. Research has demonstrated common comorbidities among these three conditions, typically focusing on two of them at a time. OBJECTIVE: The goal of this study, however, was to assess the inter-relationships between the three conditions, focusing on mid-life (defined as age 40-59) risk before the emergence of dementia caused by AD. METHODS: In the current study, we used cross-sectional data from 665 participants from the cohort study, PREVENT. FINDINGS: Using structural equation modelling, we showed that (1) insulin resistance predicts executive dysfunction in older but not younger adults in mid-life, that (2) insulin resistance predicts self-reported depression in both older and younger middle-aged adults and that (3) depression predicts deficits in visuospatial memory in older but not younger adults in mid-life. CONCLUSIONS: Together, we demonstrate the inter-relations between three common non-communicable diseases in middle-aged adults. CLINICAL IMPLICATIONS: We emphasise the need for combined interventions and the use of resources to help adults in mid-life to modify risk factors for cognitive impairment, such as depression and diabetes.

How Does HIV Persist Under Antiretroviral Therapy: A Review of the Evidence.

HIV-1 is a retrovirus capable of establishing viral reservoirs that remain stable for extended periods under suppressive antiretroviral therapy (ART). Immune dysfunction and latency are well known to contribute to this longevity, but the respective roles of viral replication and latently infected (LI) cell proliferation under suppressive antiretroviral therapy (ART) have long been controversial. This historical review critically appraises the body of evidence regarding possible viral replication and proliferation of infected cells under ART. An ever-growing body of genetic and phylogenetic studies has demonstrated that HIV-infected cells are able to proliferate and contribute to the longevity of the reservoir in ART-treated patients. The role of ongoing replication remains controversial: it has been well established that HIV does not undergo evolution during ART or develop drug resistance, but some genetic, phylogenetic, and in vivo imaging studies have suggested that there may be ongoing replication despite this. The respective roles of viral replication and cellular proliferation in maintaining the LI reservoir remains an area of controversy. Elucidating these processes may allow us design interventions to reduce the size of the LI reservoir, increasing the length of treatment interruptions during which the virus will remain adequately suppressed, bringing us closer to a functional cure. Novel experimental techniques such as immuno-PET and digital droplet PCR (ddPCR) are increasingly being employed, and these, along with rapid particle sorting techniques currently in develop-ment, will be necessary to fully answer this question.

The rules for online clinical engagement in the COVID era.

Coronavirus disease-2019 (COVID-19) has generated a need to rapidly increase online consulting in secondary care, an area in which it has previously been underutilised. We sought to review the guidance on conducting remote consultations and found that while there is a large amount of information about the implementation of remote consultations at an organisation level, there is a paucity of high-quality papers considering the guidelines for online consultations alongside practical advice for their implementation at the individual level. We reviewed guidelines from reputable medical sources and generated practical advice to assist practitioners to perform safe and effective video consultation. Additionally, we noted reports in the literature of a lack of transparency and resulting confusion regarding the choice of telemedicine platforms. We, therefore, sought to summarise key characteristics of a number of major telemedicine platforms. We recognised a lack of clarity regarding the legal status of performing remote consultations, and reviewed advice from medico-legal sources. Finally, we address the sources of these individual uncertainties, and give recommendations on how these might be addressed systematically, so the practitioners are well trained and competent in the use of online consultations, which will inevitably play an increasingly large role in both primary and secondary care settings in the future.