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ghtsavers International, and University of Heidelberg.

Many causes of vision impairment can be prevented or treated. With an ageing global population, the demands for eye health services are increasing. We estimated the prevalence and relative contribution of avoidable causes of blindness and vision impairment globally from 1990 to 2020. We aimed to compare the results with the World Health Assembly Global Action Plan (WHA GAP) target of a 25% global reduction from 2010 to 2019 in avoidable vision impairment, defined as cataract and undercorrected refractive error.

We did a systematic review and meta-analysis of population-based surveys of eye disease from January, 1980, to October, 2018. We fitted hierarchical models to estimate prevalence (with 95% uncertainty intervals [UIs]) of moderate and severe vision impairment (MSVI; presenting visual acuity from <6/18 to 3/60) and blindness (<3/60 or less than 10° visual field around central fixation) by cause, age, region, and year. Because of data sparsity at younger ages, our analysis focused on adults agedrefractive error (86·1 million cases [74·2-101·0]) and cataract (78·8 million cases [67·2-91·4]).

Results suggest eye care services contributed to the observed reduction of age-standardised rates of avoidable blindness but not of MSVI, and that the target in an ageing global population was not reached.

Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.

Brien Holden Vision Institute, Fondation Théa, The Fred Hollows Foundation, Bill & Melinda Gates Foundation, Lions Clubs International Foundation, Sightsavers International, and University of Heidelberg.

Strengthening the capacity of midwives to deliver high-quality maternal and newborn health services has been highlighted as a priority by global health organisations. XL184 To support low-income and middle-income countries (LMICs) in their decisions about investments in health, we aimed to estimate the potential impact of midwives on reducing maternal and neonatal deaths and stillbirths under several intervention coverage scenarios.

For this modelling study, we used the Lives Saved Tool to estimate the number of deaths that would be averted by 2035, if coverage of health interventions that can be delivered by professional midwives were scaled up in 88 countries that account for the vast majority of the world's maternal and neonatal deaths and stillbirths. We used four scenarios to assess the effects of increasing the coverage of midwife-delivered interventions by a modest amount (10% every 5 years), a substantial amount (25% every 5 years), and the amount needed to reach universal coverage of these intervention by 2035. These deaths averted would be particularly concentrated in the group B countries, which currently account for a large proportion of the world's population and have high mortality rates compared with group C.

Midwives can help to substantially reduce maternal and neonatal mortality and stillbirths in LMICs. However, to realise this potential, midwives need to have skills and competencies in line with recommendations from the International Confederation of Midwives, to be part of a team of sufficient size and skill, and to work in an enabling environment. Our study highlights the potential of midwives but there are many challenges to the achievement of this potential. If increased coverage of midwife-delivered interventions can be achieved, health systems will be better able to provide effective coverage of essential sexual, reproductive, maternal, newborn, and adolescent health interventions.

New Venture Fund.

New Venture Fund.Alzheimer's disease (AD) is the most common cause of dementia and is the leading lethal disease among the elderly. Dexmedetomidine (Dex) has been reported to have multiple neuroprotective effects, but its effect against beta-amyloid (Aβ) has not been completely determined and understood. Dex can activate both α2 adrenoceptor/cAMP/PKA and imidazoline I receptors/ERK1/2 signals. To determine which signal is critical for the effect of Dex on Aβ toxicity, we treated SH-SY5Y and PC12 cells with inhibitors of α2 adrenoceptor and ERK1/2. Dex suppressed the apoptosis of neuronal cells and production of reactive oxygen species induced by Aβ. These suppressive effects were attenuated by both inhibitors. As indicated by western blot, Dex stimulates both pro-apoptosis (activating death-associated protein kinase 1 [DAPK-1] and p53) and anti-apoptotic (up-regulating bcl-2 and bcl-xL) signals in Aβ-treated neuronal cells. This effect is likely associated with ERK1/2 signaling because ERK1/2 inhibitor disrupts the effect of Dex on these signals. To eliminate the pro-apoptotic effect of Dex while retaining its anti-apoptosis action, we screened miRNA-151-3p to target DAPK-1 and p53. Transfection with miRNA-151-3p mimics suppressed DAPK-1 and TP53 expression induced by Dex and increased Nrf-2 and SOD expression. More importantly, increasing miRNA-151-3p enhanced the anti-apoptotic and antioxidative effects of Dex in Aβ-treated neuronal cells. Overall, this study revealed that Dex additionally stimulated pro-apoptosis signaling, although it suppressed Aβ-induced apoptosis of neuronal cells. miRNA-151-3p enhanced the neuroprotective effect of Dex against Aβ by targeting DAPK-1 and TP53.Molecular characterizations of the microsporidian pathogen Enterocytozoon bieneusi at the ribosomal internal transcribed spacer (ITS) locus have identified nearly 500 genotypes in 11 phylogenetic groups with different host ranges. Among those, one unique group of genotypes, Group 11, is commonly found in dogs. Genetic characterizations of those and many divergent E. bieneusi genotypes at other genetic loci are thus far impossible. In this study, we sequenced 151 E. bieneusi isolates from several ITS genotype groups at the 16S rRNA locus and two new semi-conservative genetic markers (casein kinase 1 (ck1) and spore wall protein 1 (swp1)). Comparison of the near full (~1,200 bp) 16S rRNA sequences showed mostly two to three nucleotide substitutions between Group 1 and Group 2 genotypes, while Group 11 isolates differed from those by 26 (2.2%) nucleotides. Sequence analyses of the ck1 and swp1 loci confirmed the genetic uniqueness of Group 11 genotypes, which produced sequences very divergent from other groups. In contrast, genotypes in Groups 1 and 2 produced similar nucleotide sequences at these genetic loci, and there was discordant placement of ITS genotypes among loci in phylogenetic analyses of sequences.

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