Toxic tau: structural origins of tau aggregation in Alzheimer's disease

Alzheimer’s disease is characterized by the extracellular accumulation of the amyloidβin the form of amyloid plaques and the intracellular deposition of the microtubule-associated protein tau in the form of neurofibrillary tangles.Most of the Alzheimer’s drugs targeting amyloidβhave been failed in clinical trials.Particularly,tau pathology connects greatly in the pathogenesis of Alzheimer’s disease.Tau protein enhances the stabilization of microtubules that leads to the appropriate function of the neuron.Changes in the quantity or the conformation of tau protein could affect its function as a microtubules stabilizer and some of the processes wherein it is involved.The molecular mechanisms leading to the accumulation of tau are principally signified by numerous posttranslational modifications that change its conformation and structural state.Therefore,aberrant phosphorylation,as well as truncation of tau protein,has come into focus as significant mechanisms that make tau protein in a pathological entity.Furthermore,the shape-shifting nature of tau advocates to comprehend the progression of Alzheimer’s disease precisely.In this review,we emphasize the recent studies about the toxic and shape-shifting nature of tau in the pathogenesis of Alzheimer’s disease.     

Exploring the impact of COVID-19 pandemic lockdown on informal settlements in Tshwane Gauteng Province,South Africa

ABSTRACT

Informal settlements remain a public health problem as they lack basic infrastructure. Furthermore, it is challenging to enforce public health regulations and protocols to prevent the spread of infection during a pandemic. This paper was set out to explore the impact of lockdown during COVID-19 among people living in informal settlements. An exploratory qualitative design was utilised. Purposive sampling was used to select research participants. In-depth one-to-one interviews were held involving 30 research participants through a WhatsApp online telephone platform. A thematic approach underpinned by the four stages of data analysis in interpretive phenomenological analysis was utilised to analyse the data. The study found that during the the research participants were affected by lack of space to practice social distancing, over-burdened infrastructure, lack of savings, loss of income and shortage of food, hunger and diseases, anxiety and depression and poor access to education. There is a need to prioritise the needs of informal settlers and endeavour to establish permanent homes. Health promotion and communication initiatives and pandemic awareness programmes are needed to mitigate the impact of lockdown during a pandemic in informal settlements.     

Automated classification of depression from structural brain measures across two independent community‐based cohorts

Major depressive disorder (MDD) has been the subject of many neuroimaging case–control classification studies. Although some studies report accuracies ≥80%, most have investigated relatively small samples of clinically‐ascertained, currently symptomatic cases, and did not attempt replication in larger samples. We here first aimed to replicate previously reported classification accuracies in a small, well‐phenotyped community‐based group of current MDD cases with clinical interview‐based diagnoses (from STratifying Resilience and Depression Longitudinally cohort, ‘STRADL’). We performed a set of exploratory predictive classification analyses with measures related to brain morphometry and white matter integrity. We applied three classifier types—SVM, penalised logistic regression or decision tree—either with or without optimisation, and with or without feature selection. We then determined whether similar accuracies could be replicated in a larger independent population‐based sample with self‐reported current depression (UK Biobank cohort). Additional analyses extended to lifetime MDD diagnoses—remitted MDD in STRADL, and lifetime‐experienced MDD in UK Biobank. The highest cross‐validation accuracy (75%) was achieved in the initial current MDD sample with a decision tree classifier and cortical surface area features. The most frequently selected decision tree split variables included surface areas of bilateral caudal anterior cingulate, left lingual gyrus, left superior frontal, right precentral and paracentral regions. High accuracy was not achieved in the larger samples with self‐reported current depression (53.73%), with remitted MDD (57.48%), or with lifetime‐experienced MDD (52.68–60.29%). Our results indicate that high predictive classification accuracies may not immediately translate to larger samples with broader criteria for depression, and may not be robust across different classification approaches.     

Lithium-induced changes in the body mass index

A total of 117 manic-depressives who had been on lithium for a mean duration of 4.7 years were examined before lithium therapy and subsequently at intervals. Information relating to pre-lithium height and weight and current weight were determined and used to calculate the body mass index (BMI) for each individual. Other relevant variables such as age, sex, cumulative lithium dose, duration of therapy, thyroid profile and serum lithium levels were recorded. The results indicated that, although there was a nonsignificant increase in BMI for the whole population, lithium and sex were not significant predictors of any increase in BMI. In nearly 27% of patients BMI actually slightly decreased during lithium therapy. The overall conclusions from this study are that, in the population studied, lithium may not have exerted any pharmacological effects to increase BMI.     

Follow up of patients with colorectal polyps: are the BSG guidelines being adhered to?

OBJECTIVE: The publication of the BSG guidelines in 2002 provided a framework for the follow up of patients with colorectal polyps. The aim of the present study was to determine whether they had, or were being correctly adhered to in a moderately sized District General Hospital. METHOD: A total of 598 patients were on the waiting list for colonoscopy at Airedale General Hospital (AGH) in February 2005. Of these, 203 were being followed up as a result of the previous finding of a polyp. RESULTS: Only 14.8% of patients had been or were being followed up according to the BSG guidelines. The majority of the 85.2% of patients who did not comply with follow up did so as a result of over investigation. Seventy-eight per cent of the low-risk group and 55% of the intermediate-risk group had been colonoscoped, or were waiting to have colonoscopy, too soon or too frequently according to the BSG guidelines. Twenty-four patients with hyperplastic polyps were being followed up incorrectly, as were 17 patients discovered to have a polyp pathology on flexible sigmoidoscopy. It was established that 131 extra colonoscopies had been, or were planned to be performed unnecessarily. CONCLUSION: These data have major implications with regard to patient safety, service provision and cost to the NHS.