Health worker motivation in the context of HIV care and treatment challenges in Mbeya Region, Tanzania: A qualitative study

Health worker motivation can potentially affect the provision of health services. The HIV pandemic has placed additional strain on health service provision through the extra burden of increased testing and counselling, treating opportunistic infections and providing antiretroviral treatment. The aim of this paper is to explore the challenges generated by HIV care and treatment and their impact on health worker motivation in Mbeya Region, Tanzania. Thirty in-depth interviews were conducted with health workers across the range of health care professions in health facilities in two high HIV-prevalence districts of Mbeya Region, Tanzania. A qualitative framework analysis was adopted for data analysis. The negative impact of HIV-related challenges on health worker motivation was confirmed by this study. Training seminars and workshops related to HIV contributed to the shortage of health workers in the facilities. Lower status workers were frequently excluded from training and were more severely affected by the consequent increase in workload as seminars were usually attended by higher status professionals who controlled access. Constant and consistent complaints by clients have undermined health workers' expectations of trust and recognition. Health workers were forced to take responsibility for dealing with problems arising from organisational inefficiencies within the health system. HIV-related challenges undermine motivation among health workers in Mbeya, Tanzania with the burden falling most heavily on lower status workers. Strained relations between health workers and the community they serve, further undermine motivation of health workers

Defining Multiple Characteristic Raman Bands of α-Amino Acids as Biomarkers for Planetary Missions Using a Statistical Method

Biomarker molecules, such as amino acids, are key to discovering whether life exists elsewhere in the Solar System. Raman spectroscopy, a technique capable of detecting biomarkers, will be on board future planetary missions including the ExoMars rover. Generally, the position of the strongest band in the spectra of amino acids is reported as the identifying band. However, for an unknown sample, it is desirable to define multiple characteristic bands for molecules to avoid any ambiguous identification. To date, there has been no definition of multiple characteristic bands for amino acids of interest to astrobiology. This study examinedL-alanine, L-aspartic acid, L-cysteine, L-glutamine and glycine and defined several Raman bands per molecule for reference as characteristic identifiers. Per amino acid, 240 spectra were recorded and compared using established statistical tests including ANOVA. The number of characteristic bands defined were 10, 12, 12, 14 and 19 for L-alanine (strongest intensity band: 832 cm-1), L-aspartic acid (938 cm-1), L-cysteine (679 cm-1),L-glutamine (1090 cm−1) and glycine (875 cm-1), respectively. The intensity of bands differed by up to six times when several points on the crystal sample were rotated through 360 °; to reduce this effect when defining characteristic bands for other molecules, we find that spectra should be recorded at a statistically significant number of points per sample to remove the effect of sample rotation. It is crucial that sets of characteristic Raman bands are defined for biomarkers that are targets for future planetary missions to ensure a positive identification can be made

Warm Body Temperature Facilitates Energy Efficient Cortical Action Potentials

The energy efficiency of neural signal transmission is important not only as a limiting factor in brain architecture, but it also influences the interpretation of functional brain imaging signals. Action potential generation in mammalian, versus invertebrate, axons is remarkably energy efficient. Here we demonstrate that this increase in energy efficiency is due largely to a warmer body temperature. Increases in temperature result in an exponential increase in energy efficiency for single action potentials by increasing the rate of Na+ channel inactivation, resulting in a marked reduction in overlap of the inward Na+, and outward K+, currents and a shortening of action potential duration. This increase in single spike efficiency is, however, counterbalanced by a temperature-dependent decrease in the amplitude and duration of the spike afterhyperpolarization, resulting in a nonlinear increase in the spike firing rate, particularly at temperatures above approximately 35°C. Interestingly, the total energy cost, as measured by the multiplication of total Na+ entry per spike and average firing rate in response to a constant input, reaches a global minimum between 37–42°C. Our results indicate that increases in temperature result in an unexpected increase in energy efficiency, especially near normal body temperature, thus allowing the brain to utilize an energy efficient neural code

The proteasome inhibitor MG-132 sensitizes PC-3 prostate cancer cells to ionizing radiation by a DNA-PK-independent mechanism

BACKGROUND: By modulating the expression levels of specific signal transduction molecules, the 26S proteasome plays a central role in determining cell cycle progression or arrest and cell survival or death in response to stress stimuli, including ionizing radiation. Inhibition of proteasome function by specific drugs results in cell cycle arrest, apoptosis and radiosensitization of many cancer cell lines. This study investigates whether there is also a concomitant increase in cellular radiosensitivity if proteasome inhibition occurs only transiently before radiation. Further, since proteasome inhibition has been shown to activate caspase-3, which is involved in apoptosis, and caspase-3 can cleave DNA-PKcs, which is involved in DNA-double strand repair, the hypothesis was tested that caspase-3 activation was essential for both apoptosis and radiosensitization following proteasome inhibition. METHODS: Prostate carcinoma PC-3 cells were treated with the reversible proteasome inhibitor MG-132. Cell cycle distribution, apoptosis, caspase-3 activity, DNA-PKcs protein levels and DNA-PK activity were monitored. Radiosensitivity was assessed using a clonogenic assay. RESULTS: Inhibition of proteasome function caused cell cycle arrest and apoptosis but this did not involve early activation of caspase-3. Short-time inhibition of proteasome function also caused radiosensitization but this did not involve a decrease in DNA-PKcs protein levels or DNA-PK activity. CONCLUSION: We conclude that caspase-dependent cleavage of DNA-PKcs during apoptosis does not contribute to the radiosensitizing effects of MG-132

Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius

quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and SogR1 (a LuxR homolog) interacts with OHHL to modulate transcription of specific target genes. and SOPE. and SOPE indicates the potential for neofunctionalization to occur during the process of genome degeneration

Dystropathology increases energy expenditure and protein turnover in the mdx mouse model of Duchenne muscular dystrophy

The skeletal muscles in Duchenne muscular dystrophy and the mdx mouse model lack functional dystrophin and undergo repeated bouts of necrosis, regeneration, and growth. These processes have a high metabolic cost. However, the consequences for whole body energy and protein metabolism, and on the dietary requirements for these macronutrients at different stages of the disease, are not well-understood. This study used juvenile (4- to 5- wk-old) and adult (12- to 14-wk-old) male dystrophic C57BL/10ScSn-mdx/J and age-matched C57BL/10ScSn/J control male mice to measure total and resting energy expenditure, food intake, spontaneous activity, body composition, whole body protein turnover, and muscle protein synthesis rates. In juvenile mdx mice that have extensive muscle damage, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were higher than in age-matched controls. Adaptations in food intake and decreased activity were insufficient to meet the increased energy and protein needs of juvenile mdx mice and resulted in stunted growth. In (non-growing) adult mdx mice with less severe dystropathology, energy expenditure, muscle protein synthesis, and whole body protein turnover rates were also higher than in age-matched controls. Food intake was sufficient to meet their protein and energy needs, but insufficient to result in fat deposition. These data show that dystropathology impacts the protein and energy needs of mdx mice and that tailored dietary interventions are necessary to redress this imbalance. If not met, the resultant imbalance blunts growth, and may limit the benefits of therapies designed to protect and repair dystrophic muscles

Developmental malformation of the corpus callosum: a review of typical callosal development and examples of developmental disorders with callosal involvement

This review provides an overview of the involvement of the corpus callosum (CC) in a variety of developmental disorders that are currently defined exclusively by genetics, developmental insult, and/or behavior. I begin with a general review of CC development, connectivity, and function, followed by discussion of the research methods typically utilized to study the callosum. The bulk of the review concentrates on specific developmental disorders, beginning with agenesis of the corpus callosum (AgCC)—the only condition diagnosed exclusively by callosal anatomy. This is followed by a review of several genetic disorders that commonly result in social impairments and/or psychopathology similar to AgCC (neurofibromatosis-1, Turner syndrome, 22q11.2 deletion syndrome, Williams yndrome, and fragile X) and two forms of prenatal injury (premature birth, fetal alcohol syndrome) known to impact callosal development. Finally, I examine callosal involvement in several common developmental disorders defined exclusively by behavioral patterns (developmental language delay, dyslexia, attention-deficit hyperactive disorder, autism spectrum disorders, and Tourette syndrome)

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. // Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. // Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. // Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

Velocity-space sensitivity of the time-of-flight neutron spectrometer at JET

The velocity-space sensitivities of fast-ion diagnostics are often described by so-called weight functions. Recently, we formulated weight functions showing the velocity-space sensitivity of the often dominant beam-target part of neutron energy spectra. These weight functions for neutron emission spectrometry (NES) are independent of the particular NES diagnostic. Here we apply these NES weight functions to the time-of-flight spectrometer TOFOR at JET. By taking the instrumental response function of TOFOR into account, we calculate time-of-flight NES weight functions that enable us to directly determine the velocity-space sensitivity of a given part of a measured time-of-flight spectrum from TOFOR