Healthy lifestyles and wellbeing reduce neuroinflammation and prevent neurodegenerative and psychiatric disorders.

Since the mid-20th century, Western societies have considered productivity and economic outcomes are more important than focusing on people's health and wellbeing. This focus has created lifestyles with high stress levels, associated with overconsumption of unhealthy foods and little exercise, which negatively affect people's lives, and subsequently lead to the development of pathologies, including neurodegenerative and psychiatric disorders. Prioritizing a healthy lifestyle to maintain wellbeing may slow the onset or reduce the severity of pathologies.

Patterned Stimulation of the Chrimson Opsin in Glutamatergic Motor Thalamus Neurons Improves Forelimb Akinesia in Parkinsonian Rats.

Parkinson's disease (PD) is a motor disorder charactertised by altered neural activity throughout the basal ganglia-thalamocortical circuit. Electrical deep brain stimulation (DBS) is efficacious in alleviating motor symptoms, but has several notable side-effects, most likely reflecting the non-specific nature of electrical stimulation and/or the brain regions targeted. We determined whether specific optogenetic activation of glutamatergic motor thalamus (Mthal) neurons alleviated forelimb akinesia in a chronic rat model of PD.

Stigma and mental health challenges among adolescents living with HIV in selected adolescent-specific antiretroviral therapy clinics in Zomba District, Malawi.

Background: Of the 1.8 million adolescents between the ages of 10 and 19 living with HIV globally in 2020; approximately 1.5 million of these live in sub-Saharan Africa.

Reducing neuroinflammation via therapeutic compounds and lifestyle to prevent or delay progression of Parkinson's disease.

Parkinson's disease (PD) is the second most common age-associated neurodegenerative disorder and is characterised by progressive loss of dopamine neurons in the substantia nigra. Peripheral immune cell infiltration and activation of microglia and astrocytes are observed in PD, a process called neuroinflammation. Neuroinflammation is a fundamental response to protect the brain but, when chronic, it triggers neuronal damage.

Process evaluation of an implementation strategy to support uptake of a tuberculosis treatment adherence intervention to improve TB care and outcomes in Malawi.

Objective: To assess implementation and to identify barriers and facilitators to implementation, sustainability and scalability of an implementation strategy to provide lay health workers (LHWs) with the knowledge, skills and tools needed to implement an intervention to support patient tuberculosis (TB) treatment adherence.

Design: Mixed-methods design including a cluster randomised controlled trial and process evaluation informed by the RE-AIM framework.

Setting: Forty-five health centres (HCs) in four districts in the south east zone of Malawi, who had an opportunity to receive cascade training.

Impact of a tuberculosis treatment adherence intervention versus usual care on treatment completion rates: results of a pragmatic cluster randomized controlled trial.

Background: With the global shortage of skilled health workers estimated at 7.2 million, outpatient tuberculosis (TB) care is commonly task-shifted to lay health workers (LHWs) in many low- and middle-income countries where the shortages are greatest. While shown to improve access to care and some health outcomes including TB treatment outcomes, lack of training and supervision limit the effectiveness of LHW programs.

Unrestrained ESCRT-III drives micronuclear catastrophe and chromosome fragmentation.

The ESCRT-III membrane fission machinery maintains the integrity of the nuclear envelope. Although primary nuclei resealing takes minutes, micronuclear envelope ruptures seem to be irreversible. Instead, micronuclear ruptures result in catastrophic membrane collapse and are associated with chromosome fragmentation and chromothripsis, complex chromosome rearrangements thought to be a major driving force in cancer development.

Impact of peer-trainer leadership style on uptake of a peer led educational outreach intervention to improve tuberculosis care and outcomes in Malawi: a qualitative study.

Background: Little is known about how to build leadership capacity to support implementation of evidence-based practices within health systems. We observed substantial variability across sites in uptake and sustainability of a peer-led educational outreach intervention for lay health workers (LHWs) providing tuberculosis care in Malawi. Feedback from peer-trainers (PTs) suggested that leadership may have contributed to the variation.

Tuberculosis treatment outcomes among prisoners and general population in Zomba, Malawi.

Background: TB remains a major global health problem. It is particularly prevalent in prisons in sub-Saharan Africa due to overcrowding, malnutrition, high HIV prevalence and insufficient medical services. Prisoners have experienced worse TB treatment outcomes than the general population.

Inhibition of MALT1 Decreases Neuroinflammation and Pathogenicity of Virulent Rabies Virus in Mice.

Rabies virus is a neurovirulent RNA virus, which causes about 59,000 human deaths each year. Treatment for rabies does not exist due to incomplete understanding of the pathogenesis. MALT1 mediates activation of several immune cell types and is involved in the proliferation and survival of cancer cells.

Synchronous tropical and polar temperature evolution in the Eocene.

Palaeoclimate reconstructions of periods with warm climates and high atmospheric CO concentrations are crucial for developing better projections of future climate change. Deep-ocean and high-latitude palaeotemperature proxies demonstrate that the Eocene epoch (56 to 34 million years ago) encompasses the warmest interval of the past 66 million years, followed by cooling towards the eventual establishment of ice caps on Antarctica. Eocene polar warmth is well established, so the main obstacle in quantifying the evolution of key climate parameters, such as global average temperature change and its polar amplification, is the lack of continuous high-quality tropical temperature reconstructions.

MALT1 Controls Attenuated Rabies Virus by Inducing Early Inflammation and T Cell Activation in the Brain.

MALT1 is involved in the activation of immune responses, as well as in the proliferation and survival of certain cancer cells. MALT1 acts as a scaffold protein for NF-κB signaling and a cysteine protease that cleaves substrates, further promoting the expression of immunoregulatory genes. Deregulated MALT1 activity has been associated with autoimmunity and cancer, implicating MALT1 as a new therapeutic target.

Impact of caspase-1/11, -3, -7, or IL-1/IL-18 deficiency on rabies virus-induced macrophage cell death and onset of disease.

Rabies virus is a highly neurovirulent RNA virus, which causes about 59000 deaths in humans each year. Previously, we described macrophage cytotoxicity upon infection with rabies virus. Here we examined the type of cell death and the role of specific caspases in cell death and disease development upon infection with two laboratory strains of rabies virus: Challenge Virus Standard strain-11 (CVS-11) is highly neurotropic and lethal for mice, while the attenuated Evelyn-Rotnycki-Abelseth (ERA) strain has a broader cell tropism, is non-lethal and has been used as an oral vaccine for animals.

Alcohol use and abuse among patients with multidrug-resistant tuberculosis in Botswana.

Background: Data on alcohol abuse as a risk factor for the development of multidrug-resistant tuberculosis (MDR-TB) are scarce.

Objective: To describe the patterns of alcohol use in MDR-TB patients and to determine whether alcohol use is associated with the development of MDR-TB in Botswana.

Methods: We compared the level of alcohol use among MDR-TB patients against three control groups: 1) non-MDR-TB patients, 2) human immunodeficiency virus (HIV) infected patients without a history of TB, and 3) the general population.

Lessons learned during tuberculosis screening in public medical clinics in Francistown, Botswana.

In Botswana, where one quarter of the adult population is infected with the human immunodeficiency virus and the annual tuberculosis (TB) incidence is among the highest globally, intensified TB case finding is needed in health care facilities to detect and treat TB cases early and prevent transmission. During August-December 2009, TB screening was implemented among adults at patient intake in five clinics in Francistown. Among 11 779 TB screenings at intake, 926 were positive.

Patients' adherence to anti-retroviral therapy in Botswana.

Purpose: To identify factors influencing patients' anti-retroviral therapy (ART) adherence at four clinics in Botswana.

Design: Quantitative descriptive. Structured interviews were conducted with a random sample of 400 patients out of the population of all patients attending the four randomly selected ART clinics in Botswana during April and May 2007.

Addition of treatment for trichomoniasis to syndromic management of urethritis in Malawi: a randomized clinical trial.

Background: Male urethritis is generally treated syndromically, but failure of empirical treatment is common.

Goal: The study goal was to evaluate the addition of metronidazole to the syndromic management of urethritis in Malawi in a randomized clinical trial.

Study Design: Men with urethritis were randomized to receive either 2 g of metronidazole by mouth or placebo, in addition to standard care for urethritis (i.