What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

10.1371/journal.pone.0049969PLoS ONE711

Should social enterprises complement or supplement public health provision?

Purpose This paper explores how stable employment, company culture, and tailored health, digital, and core skills training provided by a social enterprise (SE) in the Philippines affect survivors of exploitation. Research shows survivors experience adverse social conditions and physical and mental health outcomes caused by their exploitative experience. Stable, decent employment has been identified as critical to their recovery and reintegration. This paper discusses the SE’s impact on the employees’ physical, mental, and social health and behaviour. Based on our findings, we discuss the contribution of SE in improving health outcomes and providing health services, and conclude that SEs should not replace but complement public health government programmes. Design/methodology/approach This paper uses mixed methods, presenting data from a longitudinal survey (household income, mental health, and social wellbeing, among others), and a follow-up qualitative study, which uses in-depth interviews and participatory videos to explore survey findings. Findings The quantitative analysis demonstrates positive, but gradual, changes in sexual and reproductive health behaviour; personal empowerment; and trauma, anxiety, and depressive symptoms. The qualitative findings show how improvements in executive functioning, self-regulation, and self-esteem occur incrementally over time. As their self-efficacy improves, employees need to avoid being overly dependent on the SE, to support their autonomy, therefore access to complementary public health services is fundamental. Originality/value This paper focuses, to our knowledge, on a unique SE, which hires survivors of exploitation, without losing their competitiveness in the market

Climbing for survival? A new altitudinal limit from black-cheeked gnateater (Conopophaga melanops) in Atlantic Forest:

The Brazilian Atlantic Forest, despite being one of the most threatened biomes in the world, remains one of the great hotspots of global biodiversity and bird endemism. Elevation plays a significant role in influencing the high number of endemic bird species in this region. The Black-cheeked Gnateater (Conopophaga melanops), endemic to the Atlantic Forest, is typically found in lowland forests along the east coast of Brazil, ranging from sea level to 800 meters above sea level. Due to its high sensitivity to ecological disturbances, it serves as an excellent bioindicator of environmental quality. During a field sampling expedition in Parque Nacional da Serra dos Órgãos, we captured two individuals of C. melanops at altitudes of 1287 and 1409 meters. To explain this new altitude record, we propose two hypotheses. First, the lack of previous sampling in the highest regions of the Atlantic Forest, likely due to limited access and scarce historical studies, may have resulted in the underreporting of this species at higher elevations. Second, there is the possibility that bird populations are migrating to more pristine areas at higher elevations due to habitat loss in the lowland regions. The second hypothesis raises important implications for the conservation of the Black-cheeked Gnateater. Since this species relies on intact habitats for its survival, we must consider whether deforestation in its historic range could be driving these new altitude records.A pesar de ser uno de los biomas más amenazados del mundo, la Mata Atlántica brasileña sigue siendo uno de los grandes puntos calientes de la biodiversidad global y del endemismo de aves. La altitud juega un papel significativo en la influencia del alto número de especies de aves endémicas en esta región. El Chupadientes Enmascarado (Conopophaga melanops), endémico de la Mata Atlántica, se encuentra típicamente en bosques de tierras bajas a lo largo de la costa este de Brasil, desde el nivel del mar hasta 800 metros sobre el nivel del mar. Debido a su alta sensibilidad a las perturbaciones ecológicas, sirve como un excelente bioindicador de la calidad ambiental. Durante una expedición de muestreo en el Parque Nacional da Serra dos Órgãos, capturamos dos individuos de C. melanops a altitudes de 1287 y 1409 metros. Para explicar este nuevo registro de altitud, proponemos dos hipótesis: En primer lugar, la falta de muestreo previo en las regiones más altas de la Mata Atlántica, probablemente debido al acceso limitado y a escasos estudios históricos, podría haber resultado en la subnotificación de esta especie en altitudes más elevadas. En segundo lugar, existe la posibilidad de que las poblaciones de aves estén migrando a áreas más prístinas a altitudes más elevadas debido a la pérdida de hábitat en las regiones de tierras bajas. La segunda hipótesis plantea importantes implicaciones para la conservación del Chupadientes Enmascarado. Dado que esta especie depende de hábitats intactos para su supervivencia, debemos considerar si la deforestación en su área histórica podría estar impulsando estos nuevos registros de altitud.The Brazilian Atlantic Forest, despite being one of the most threatened biomes in the world, remains one of the great hotspots of global biodiversity and bird endemism. Elevation plays a significant role in influencing the high number of endemic bird species in this region. The Black-cheeked Gnateater (Conopophaga melanops), endemic to the Atlantic Forest, is typically found in lowland forests along the east coast of Brazil, ranging from sea level to 800 meters above sea level. Due to its high sensitivity to ecological disturbances, it serves as an excellent bioindicator of environmental quality. During a field sampling expedition in Parque Nacional da Serra dos Órgãos, we captured two individuals of C. melanops at altitudes of 1287 and 1409 meters. To explain this new altitude record, we propose two hypotheses. First, the lack of previous sampling in the highest regions of the Atlantic Forest, likely due to limited access and scarce historical studies, may have resulted in the underreporting of this species at higher elevations. Second, there is the possibility that bird populations are migrating to more pristine areas at higher elevations due to habitat loss in the lowland regions. The second hypothesis raises important implications for the conservation of the Black-cheeked Gnateater. Since this species relies on intact habitats for its survival, we must consider whether deforestation in its historic range could be driving these new altitude records

Strongyloides stercoralis age-1: A Potential Regulator of Infective Larval Development in a Parasitic Nematode

Infective third-stage larvae (L3i) of the human parasite Strongyloides stercoralis share many morphological, developmental, and behavioral attributes with Caenorhabditis elegans dauer larvae. The ‘dauer hypothesis’ predicts that the same molecular genetic mechanisms control both dauer larval development in C. elegans and L3i morphogenesis in S. stercoralis. In C. elegans, the phosphatidylinositol-3 (PI3) kinase catalytic subunit AGE-1 functions in the insulin/IGF-1 signaling (IIS) pathway to regulate formation of dauer larvae. Here we identify and characterize Ss-age-1, the S. stercoralis homolog of the gene encoding C. elegans AGE-1. Our analysis of the Ss-age-1 genomic region revealed three exons encoding a predicted protein of 1,209 amino acids, which clustered with C. elegans AGE-1 in phylogenetic analysis. We examined temporal patterns of expression in the S. stercoralis life cycle by reverse transcription quantitative PCR and observed low levels of Ss-age-1 transcripts in all stages. To compare anatomical patterns of expression between the two species, we used Ss-age-1 or Ce-age-1 promoter::enhanced green fluorescent protein reporter constructs expressed in transgenic animals for each species. We observed conservation of expression in amphidial neurons, which play a critical role in developmental regulation of both dauer larvae and L3i. Application of the PI3 kinase inhibitor LY294002 suppressed L3i in vitro activation in a dose-dependent fashion, with 100 µM resulting in a 90% decrease (odds ratio: 0.10, 95% confidence interval: 0.08–0.13) in the odds of resumption of feeding for treated L3i in comparison to the control. Together, these data support the hypothesis that Ss-age-1 regulates the development of S. stercoralis L3i via an IIS pathway in a manner similar to that observed in C. elegans dauer larvae. Understanding the mechanisms by which infective larvae are formed and activated may lead to novel control measures and treatments for strongyloidiasis and other soil-transmitted helminthiases

Global estimates on the number of people blind or visually impaired by Uncorrected Refractive Error: a meta-analysis from 2000 to 2020

Background: Uncorrected refractive error (URE) is a readily treatable cause of visual impairment (VI). This study provides updated estimates of global and regional vision loss due to URE, presenting temporal change for VISION 2020 Methods: Data from population-based eye disease surveys from 1980–2018 were collected. Hierarchical models estimated prevalence (95% uncertainty intervals [UI]) of blindness (presenting visual acuity (VA) < 3/60) and moderate-to-severe vision impairment (MSVI; 3/60 ≤ presenting VA < 6/18) caused by URE, stratified by age, sex, region, and year. Near VI prevalence from uncorrected presbyopia was defined as presenting near VA < N6/N8 at 40 cm when best-corrected distance (VA ≥ 6/12). Results: In 2020, 3.7 million people (95%UI 3.10–4.29) were blind and 157 million (140–176) had MSVI due to URE, a 21.8% increase in blindness and 72.0% increase in MSVI since 2000. Age-standardised prevalence of URE blindness and MSVI decreased by 30.5% (30.7–30.3) and 2.4% (2.6–2.2) respectively during this time. In 2020, South Asia GBD super-region had the highest 50+ years age-standardised URE blindness (0.33% (0.26–0.40%)) and MSVI (10.3% (8.82–12.10%)) rates. The age-standardized ratio of women to men for URE blindness was 1.05:1.00 in 2020 and 1.03:1.00 in 2000. An estimated 419 million (295–562) people 50+ had near VI from uncorrected presbyopia, a +75.3% (74.6–76.0) increase from 2000 Conclusions: The number of cases of VI from URE substantively grew, even as age-standardised prevalence fell, since 2000, with a continued disproportionate burden by region and sex. Global population ageing will increase this burden, highlighting urgent need for novel approaches to refractive service delivery.publishedVersio

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Disorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021. METHODS: We estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined. FINDINGS: Globally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer. INTERPRETATION: As the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019

BACKGROUND: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. METHODS: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. FINDINGS: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. INTERPRETATION: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. FUNDING: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)