Geospatial transmission hotspots of recent HIV infection — Malawi, October 2019–March 2020

What is already known about this topic? A novel HIV infection surveillance initiative was implemented in Malawi to collect data on recent HIV infections among new diagnoses to characterize the epidemic and guide the public health response. What is added by this report? Higher proportions of recent infections were identified among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Spatial analysis identified three hotspots of health facilities with significantly higher rates of recent infection than expected across five districts. What are the implications for public health practice? Geospatial analysis of recent HIV infection surveillance data can identify potential transmission hotspots. This information could be used to tailor program activities to strengthen HIV testing, prevention, and treatment services and ultimately interrupt transmission

Accumulation of Endogenous LITAF in Aggresomes

LITAF is a 161 amino acid cellular protein which includes a proline rich N-terminus and a conserved C-terminal domain known as the simple-like domain. Mutations in LITAF have been identified in Charcot-Marie tooth disease, a disease characterized by protein aggregates. Cells transfected with cellular LITAF reveal that LITAF is localized to late endosomes/lysosomes. Here we investigated the intracellular localization of endogenous LITAF. We demonstrated that endogenous LITAF accumulates at a discrete cytoplasmic site in BGMK cells that we identify as the aggresome. To determine the domain within LITAF that is responsible for the localization of LITAF to aggresomes, we created a construct that contained the C-terminal simple-like domain of LITAF and found that this construct also localizes to aggresomes. These data suggest the simple-like domain is responsible for targeting endogenous LITAF to the aggresome

The Artelon CMC spacer compared with tendon interposition arthroplasty: A randomized, controlled, multicenter study of 109 patients with osteoarthritis followed for 1 year

Background and purpose The Artelon CMC spacer is designed for surgical treatment of osteoarthritis (OA) in the carpometacarpal joint of the thumb (CMC-I). Good results using this degradable device were previously presented in a pilot study. We now present results from a larger randomized, controlled, multicenter study

Comorbidity, limitations in activities and pain in patients with osteoarthritis of the hip or knee

BACKGROUND: This study aims to contribute to the knowledge of the influence of comorbidity in OA. The objectives of the study were (i) to describe the prevalence of comorbidity and (ii) to describe the relationship between comorbidity (morbidity count, severity and the presence of specific diseases) and limitations in activities and pain in elderly patients with knee or hip OA using a comprehensive inventory of comorbidity. METHODS: A cross-sectional cohort study was conducted, in which 288 elderly patients with hip or knee osteoarthritis were included. Apart from demographic and clinical data, information about comorbidity, limitations in activities (WOMAC, SF-36 and timed walking test) and pain (VAS) was collected by questionnaires and tests. Statistical analyses included descriptive statistics, multivariate regression techniques, t-tests and one-way ANOVA. RESULTS: Almost all patients suffered from at least one comorbid disease, with cardiac diseases, diseases of eye, ear, nose, throat and larynx, other urogenital diseases and endocrine/metabolic diseases being most prevalent. Morbidity count and severity index were associated with more limitations in activities and with more pain. The presence of most of the moderate or severe diseases and obesity was associated with limitations in activities or with pain. CONCLUSION: The results of this study emphasize the importance of comorbidity in the rehabilitation of elderly patients with osteoarthritis of the hip or knee. Clinical practitioners should be aware of the relationship of comorbidity with functional problems in OA patients. (aut. ref.

Differential Scanning Fluorometry Signatures as Indicators of Enzyme Inhibitor Mode of Action: Case Study of Glutathione S-Transferase

Differential scanning fluorometry (DSF), also referred to as fluorescence thermal shift, is emerging as a convenient method to evaluate the stabilizing effect of small molecules on proteins of interest. However, its use in the mechanism of action studies has received far less attention. Herein, the ability of DSF to report on inhibitor mode of action was evaluated using glutathione S-transferase (GST) as a model enzyme that utilizes two distinct substrates and is known to be subject to a range of inhibition modes. Detailed investigation of the propensity of small molecule inhibitors to protect GST from thermal denaturation revealed that compounds with different inhibition modes displayed distinct thermal shift signatures when tested in the presence or absence of the enzyme's native co-substrate glutathione (GSH). Glutathione-competitive inhibitors produced dose-dependent thermal shift trendlines that converged at high compound concentrations. Inhibitors acting via the formation of glutathione conjugates induced a very pronounced stabilizing effect toward the protein only when GSH was present. Lastly, compounds known to act as noncompetitive inhibitors exhibited parallel concentration-dependent trends. Similar effects were observed with human GST isozymes A1-1 and M1-1. The results illustrate the potential of DSF as a tool to differentiate diverse classes of inhibitors based on simple analysis of co-substrate dependency of protein stabilization

Dopaminergic Activation of Estrogen Receptors Induces Fos Expression within Restricted Regions of the Neonatal Female Rat Brain

Steroid receptor activation in the developing brain influences a variety of cellular processes that endure into adulthood, altering both behavior and physiology. Recent data suggests that dopamine can regulate expression of progestin receptors within restricted regions of the developing rat brain by activating estrogen receptors in a ligand-independent manner. It is unclear whether changes in neuronal activity induced by dopaminergic activation of estrogen receptors are also region specific. To investigate this question, we examined where the dopamine D1-like receptor agonist, SKF 38393, altered Fos expression via estrogen receptor activation. We report that dopamine D1-like receptor agonist treatment increased Fos protein expression within many regions of the developing female rat brain. More importantly, prior treatment with an estrogen receptor antagonist partially reduced D1-like receptor agonist-induced Fos expression only within the bed nucleus of the stria terminalis and the central amygdala. These data suggest that dopaminergic activation of estrogen receptors alters neuronal activity within restricted regions of the developing rat brain. This implies that ligand-independent activation of estrogen receptors by dopamine might organize a unique set of behaviors during brain development in contrast to the more wide spread ligand activation of estrogen receptors by estrogen

Oxidative stress causes ERK phosphorylation and cell death in cultured retinal pigment epithelium: Prevention of cell death by AG126 and 15-deoxy-delta 12, 14-PGJ(2)

BACKGROUND: The retina, which is exposed to both sunlight and very high levels of oxygen, is exceptionally rich in polyunsaturated fatty acids, which makes it a favorable environment for the generation of reactive oxygen species. The cytotoxic effects of hydrogen peroxide (H(2)O(2)) induced oxidative stress on retinal pigment epithelium were characterized in this study. METHODS: The MTT cell viability assay, Texas-Red phalloidin staining, immunohistochemistry and Western blot analysis were used to assess the effects of oxidative stress on primary human retinal pigment epithelial cell cultures and the ARPE-19 cell line. RESULTS: The treatment of retinal pigment epithelial cells with H(2)O(2 )caused a dose-dependent decrease of cellular viability, which was preceded by a significant cytoskeletal rearrangement, activation of the Extracellular signal-Regulated Kinase, lipid peroxidation and nuclear condensation. This cell death was prevented partially by the prostaglandin derivative, 15d-PGJ(2 )and by the protein kinase inhibitor, AG126. CONCLUSION: 15d-PGJ(2 )and AG126 may be useful pharmacological tools in the future capable of preventing oxidative stress induced RPE cell death in human ocular diseases

Limits to modern contraceptive use among young women in developing countries: a systematic review of qualitative research

<p>Abstract</p> <p>Background</p> <p>Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses.</p> <p>Methods</p> <p>Literature searches of 23 databases, including Medline, Embase and POPLINE^®, were conducted. Literature from 1970–2006 concerning the 11–24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data.</p> <p>Results</p> <p>Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13–19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health.</p> <p>Conclusion</p> <p>Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.</p