Stigma is associated with health conditions that drive disease burden in low- and middle-income countries (LMICs), including HIV, tuberculosis, mental health problems, epilepsy, and substance use ...disorders. However, the literature discussing the relationship between stigma and health outcomes is largely fragmented within disease-specific siloes, thus limiting the identification of common moderators or mechanisms through which stigma potentiates adverse health outcomes as well as the development of broadly relevant stigma mitigation interventions.
We conducted a scoping review to provide a critical overview of the breadth of research on stigma for each of the five aforementioned conditions in LMICs, including their methodological strengths and limitations.
Across the range of diseases and disorders studied, stigma is associated with poor health outcomes, including help- and treatment-seeking behaviors. Common methodological limitations include a lack of prospective studies, non-representative samples resulting in limited generalizability, and a dearth of data on mediators and moderators of the relationship between stigma and health outcomes.
Implementing effective stigma mitigation interventions at scale necessitates transdisciplinary longitudinal studies that examine how stigma potentiates the risk for adverse outcomes for high-burden health conditions in community-based samples in LMICs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg−1 · d−1. Aging may increase protein requirements, particularly to maintain muscle ...mass.
We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.
In this parallel-group randomized trial, 29 men aged >70 y mean ± SD body mass index (in kg/m2): 28.3 ± 4.2 were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg−1 · d−1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.
Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with −0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (−0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with −11.7 ± 31.0 W, P = 0.180 in RDA).
Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance. This trial was registered at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12616000310460.
Design of a synthetic yeast genome Richardson, Sarah M.; Mitchell, Leslie A.; Stracquadanio, Giovanni ...
Science (American Association for the Advancement of Science),
03/2017, Letnik:
355, Številka:
6329
Journal Article
Recenzirano
Odprti dostop
We describe complete design of a synthetic eukaryotic genome, Sc2.0, a highly modified Saccharomyces cerevisiae genome reduced in size by nearly 8%, with 1.1 megabases of the synthetic genome ...deleted, inserted, or altered. Sc2.0 chromosome design was implemented with BioStudio, an open-source framework developed for eukaryotic genome design, which coordinates design modifications from nucleotide to genome scales and enforces version control to systematically track edits. To achieve complete Sc2.0 genome synthesis, individual synthetic chromosomes built by Sc2.0 Consortium teams around the world will be consolidated into a single strain by “endoreduplication intercross.” Chemically synthesized genomes like Sc2.0 are fully customizable and allow experimentalists to ask otherwise intractable questions about chromosome structure, function, and evolution with a bottom-up design strategy.
Probing RNA structure in vivo Mitchell, David; Assmann, Sarah M; Bevilacqua, Philip C
Current opinion in structural biology,
12/2019, Letnik:
59
Journal Article
Recenzirano
Odprti dostop
Display omitted
•Probing RNA structure in vivo facilitates understanding of its biological context.•All four RNA nucleobases and protein interaction sites can now be probed in vivo.•Ribose-specific ...SHAPE reagents provides complementary in vivo structural data.•Recent use of multiple base-specific reagents improves in vivo structure models.
RNA structure underpins many essential functions in biology. New chemical reagents and techniques for probing RNA structure in living cells have emerged in recent years. High-throughput, genome-wide techniques such as Structure-seq2 and DMS-MaPseq exploit nucleobase modification by dimethylsulfate (DMS) to obtain complete structuromes, and are applicable to multiple domains of life and conditions. New reagents such as 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), glyoxal, and nicotinoyl azide (NAz) greatly expand the capabilities of nucleobase probing in cells. Additionally, ribose-targeting reagents in selective 2’-hydroxyl acylation and primer extension (SHAPE) detect RNA flexibility in vivo. These techniques, coupled with crosslinking nucleobases in psoralen analysis of RNA interactions and structures (PARIS), provide new and diverse ways to elucidate RNA secondary and tertiary structure in vivo and genome-wide.
Here, we report the successful design, construction, and characterization of a 770-kilobase synthetic yeast chromosome II (synII). Our study incorporates characterization at multiple levels-including ...phenomics, transcriptomics, proteomics, chromosome segregation, and replication analysis-to provide a thorough and comprehensive analysis of a synthetic chromosome. Our Trans-Omics analyses reveal a modest but potentially relevant pervasive up-regulation of translational machinery observed in synII, mainly caused by the deletion of 13 transfer RNAs. By both complementation assays and SCRaMbLE (synthetic chromosome rearrangement and modification by
-mediated evolution), we targeted and debugged the origin of a growth defect at 37°C in glycerol medium, which is related to misregulation of the high-osmolarity glycerol response. Despite the subtle differences, the synII strain shows highly consistent biological processes comparable to the native strain.
Purpose of Review
Vulnerable children with medical complexity are silent victims of the COVID-19 pandemic, impacted by lack of resources and sick caregivers. In this article, we examine ways in which ...the pandemic has increased the significant difficulties already experienced by these patients and their families. Increased awareness will lead to improvement in the disparities experienced by this population and improve the ability of healthcare providers to care for them.
Recent Findings
The number of children living with medical complexity is rapidly increasing. They face unique circumstances which can lead to compromise in care. This population is especially at risk for complications related to COVID, so may have a more prolonged admission with more morbidities. Children of ethnic minorities are also more impacted by severe illness and death. Finally, access to palliative care has been limited, which is a huge part in caring for these children who have life-long medical care needs.
Summary
Children with medical complexity have unique circumstances and the entirety of the effect of the coronavirus pandemic on this group is unknown. While the medical world has found ways to adapt, these changes can increase disparities for this population. Given the increase in number of children with medical complexity living in the USA, it is important to continue to consider the unique challenges they face in the current pandemic and improve the care delivery for both the child and his or her family.
Recent consensus defines four SCLC subtypes on the basis of transcription factor expression: ASCL1, NEUROD1, POU2F3, and YAP1. The rare YAP1 subtype is associated with “neuroendocrine (NE)-low” cells ...among SCLC cell lines and patient samples. We evaluated YAP1 in 39 patients with phenotypically diverse circulating tumor cell–derived explant (CDX) models and revisited YAP1 in terms of prevalence, cell phenotype, and intertumor and intratumor heterogeneity.
YAP1 transcript and protein expression were assessed by RNA sequencing and immunohistochemistry or multiplexed immunofluorescence of NE and non-NE CDX subpopulations. Physically separated NE and non-NE CDX ex vivo culture lysates were Western blotted for YAP1, NE marker SYP, and AXL.
RNA sequencing normalized for the four subtype transcription factors identified YAP1 expression in 14 of 39 CDX. A total of 10 CDX expressed YAP1 protein, and eight had strong YAP1 expression confined to rare non-NE cell clusters. This was confirmed in ex vivo CDX cultures in which adherent non-NE cells lacking SYP expression expressed YAP1. However, in two CDX, weaker cellular YAP1 expression was observed, widely dispersed in SYP-positive NE cells.
YAP1 was predominantly expressed in non-NE cell clusters in SCLC CDX, but two of 39 CDX expressed YAP1 in NE cells. CDX22P, with relatively high YAP1 expression, is an ASCL1 NE subtype with a low NE score and an outlier within this subtype in our CDX biobank. These descriptive data reveal subtly different YAP1 expression profiles, paving the way for functional studies to compare YAP1 signaling in non-NE and low NE cell contexts for potentially personalized therapeutic approaches.
The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk ...factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs).
The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2024 AHA Statistical Update is the product of a full year's worth of effort in 2023 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. The AHA strives to further understand and help heal health problems inflicted by structural racism, a public health crisis that can significantly damage physical and mental health and perpetuate disparities in access to health care, education, income, housing, and several other factors vital to healthy lives. This year's edition includes additional global data, as well as data on the monitoring and benefits of cardiovascular health in the population, with an enhanced focus on health equity across several key domains.
Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics.
The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
We designed and synthesized a 976,067-base pair linear chromosome, synXII, based on native chromosome XII in
SynXII was assembled using a two-step method, specified by successive megachunk ...integration and meiotic recombination-mediated assembly, producing a functional chromosome in
Minor growth defect "bugs" detected in synXII, caused by deletion of tRNA genes, were rescued by introducing an ectopic copy of a single tRNA gene. The ribosomal gene cluster (rDNA) on synXII was left intact during the assembly process and subsequently replaced by a modified rDNA unit used to regenerate rDNA at three distinct chromosomal locations. The signature sequences within rDNA, which can be used to determine species identity, were swapped to generate a
synXII strain that would be identified as
by standard DNA barcoding procedures.
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