Central serous chorioretinopathy (CSC) is a common cause of central vision loss, primarily affecting men 20–60 years of age. To date, no consensus has been reached regarding the classification of ...CSC, and a wide variety of interventions have been proposed, reflecting the controversy associated with treating this disease. The recent publication of appropriately powered randomised controlled trials such as the PLACE trial, as well as large retrospective, non-randomised treatment studies regarding the treatment of CSC suggest the feasibility of a more evidence-based approach when considering treatment options. The aim of this review is to provide a comprehensive overview of the current rationale and evidence with respect to the variety of interventions available for treating CSC, including pharmacology, laser treatment, and photodynamic therapy. In addition, we describe the complexity of CSC, the challenges associated with treating CSC, and currently ongoing studies. Many treatment strategies such as photodynamic therapy using verteporfin, oral mineralocorticoid antagonists, and micropulse laser treatment have been reported as being effective. Currently, however, the available evidence suggests that half-dose (or half-fluence) photodynamic therapy should be the treatment of choice in chronic CSC, whereas observation may be the preferred approach in acute CSC. Nevertheless, exceptions can be considered based upon patient-specific characteristics.
•The treatment of central serous chorioretinopathy (CSC) is controversial.•In chronic CSC, the most effective treatment appears to be half-dose (or half-fluence) photodynamic therapy (PDT).•In acute CSC, observation or early half-dose (or half-fluence) PDT can be considered.•Future studies will shed light on the efficacy of new treatment strategies.
Human papillomavirus (HPV)-driven oropharyngeal cancer incidence in the United States has steadily increased in the past decades and has now become the most frequently diagnosed HPV-associated cancer ...type, surpassing cervical cancer. Variations in the HPV genome correlate with tumorigenic risk, and the distribution of genetic variants is extensively studied in cervical cancer, but very little is known about new mutations or the distribution of HPV types and variants in oropharyngeal cancer. Here we present an archival tissue cohort study that compares genomic characteristics of HPV associated with cervical versus oropharyngeal tumors using DNA sequence analysis. We found HPV16 to be more prevalent in oropharyngeal samples than in cervical samples (91.2% versus 52.9%), while HPV18 (1.5% versus 18.2%) and HPV45 (0.7% versus 9.9%) were much less prevalent. Differences between cervix and oropharynx in HPV16 variants distribution were more subtle, but the combined European + Asian (EUR+AS) variant group was more prevalent (90.2% versus 71.4%), while the American Asian 1 + American Asian 2 (AA1+AA2) variant group was much less prevalent (4.4% versus 22.5%) in oropharyngeal cancers. HPV prevalence in oropharyngeal cancers showed an increasing trend from 60% in 2003 to 80% in 2016. We also identified over nine times more nonsynonymous mutations in the HPV E6 gene amplified from oropharyngeal samples, but for E7 the difference in mutation rates between the two anatomical locations was not significant. Overall, we showed that HPV genome in oropharyngeal cancer presents important differences when compared to cervical cancer and this may explain the distinct pathomechanisms and susceptibility to treatment of HPV-associated oropharyngeal cancer.
Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space ...travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.
An international group of spaceflight researchers detail how spaceflight affects human biology from the molecular to physiological level and identify key challenges for making space exploration compatible with human health.
Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence ...indicates that adding metformin to exercise antagonizes the exercise‐induced improvement in insulin sensitivity and cardiorespiratory fitness. The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years). In a double‐blinded fashion, participants were randomized to placebo (n = 26) or metformin (n = 27) treatment during 12 weeks of AET. Independent of treatment, AET decreased fat mass, HbA1c, fasting plasma insulin, 24‐hr ambulant mean glucose, and glycemic variability. However, metformin attenuated the increase in whole‐body insulin sensitivity and VO2max after AET. In the metformin group, there was no overall change in whole‐body insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exercise‐mediated increase in skeletal muscle mitochondrial respiration. The change in whole‐body insulin sensitivity was correlated to the change in mitochondrial respiration. Mitochondrial protein synthesis rates assessed during AET were not different between treatments. The influence of metformin on AET‐induced improvements in physiological function was highly variable and associated with the effect of metformin on the mitochondria. These data suggest that prior to prescribing metformin to slow aging, additional studies are needed to understand the mechanisms that elicit positive and negative responses to metformin with and without exercise.
Twins, Telomeres, and Aging-in Space Luxton, Jared J; Bailey, Susan M
Plastic and reconstructive surgery (1963),
2021-Jan-01, 2021-01-00, Letnik:
147, Številka:
1S-2
Journal Article
Recenzirano
The landmark National Aeronautics and Space Administration Twins Study represented an integrated effort to launch human space life science research into the modern age of molecular- and "omics"-based ...studies. As part of the first One-Year Mission aboard the International Space Station, identical twin astronauts Scott and Mark Kelly were the subjects of this "out of this world" research opportunity. Telomeres, the natural ends of chromosomes that shorten with cell division and a host of lifestyle factors and stresses, are key molecular determinants of aging and aging trajectories.
We proposed that telomere length dynamics (changes over time) represent a particularly relevant and integrative biomarker for astronauts, as they reflect the combined experiences and environmental exposures encountered during spaceflight. Telomere length (quantitative polymerase chain reaction and telomere fluorescence in situ hybridization) and telomerase activity (quantitative polymerase chain reaction -telomere repeat amplification protocol) were longitudinally assessed in the space- and earth-bound twins. Chromosome aberrations (directional genomic hybridization), signatures of radiation exposure, were also evaluated.
The twins had relatively similar telomere lengths before spaceflight, and the earth-bound twins' telomeres remained relatively stable over the course of the study. Surprisingly, the space twins' telomeres were longer during spaceflight, and upon return to Earth shortened rapidly, resulting in many more short telomeres after spaceflight than before. Chromosomal signatures of space radiation exposure were also elevated during spaceflight, and increased inversion frequencies persisted after spaceflight, suggestive of ongoing genome instability.
Although the definitive mechanisms underlying such dramatic spaceflight-associated shifts in telomere length remain unclear, improved maintenance of telomere length has important implications for aging science and improving healthspan for those on Earth, as well.
Telomeres are regions of repetitive nucleotide sequences capping the ends of eukaryotic chromosomes that protect against deterioration, and whose lengths can be correlated with age and adverse health ...risk factors. Yet, given their length and repetitive nature, telomeric regions are not easily reconstructed from short-read sequencing, thus making telomere sequencing, mapping, and variant resolution challenging problems. Recently, long-read sequencing, with read lengths measuring in hundreds of kilobase pairs, has made it possible to routinely read into telomeric regions and inspect their sequence structure. Here, we describe a framework for extracting telomeric reads from whole-genome single-molecule sequencing experiments, including de novo identification of telomere repeat motifs and repeat types, and also describe their sequence variation. We find that long, complex telomeric stretches and repeats can be accurately captured with long-read sequencing, observe extensive sequence heterogeneity of human telomeres, discover and localize noncanonical telomere sequence motifs (both previously reported, as well as novel), and validate them in short-read sequence data. These data reveal extensive intra- and inter-population diversity of repeats in telomeric haplotypes, reveal higher paternal inheritance of telomeric variants, and represent the first motif composition maps of multi-kilobase-pair human telomeric haplotypes across three distinct ancestries (Ashkenazi, Chinese, and Utah), which can aid in future studies of genetic variation, aging, and genome biology.
Telomeres, repetitive terminal features of chromosomes essential for maintaining genome integrity, shorten with cell division, lifestyle factors and stresses, and environmental exposures, and so they ...provide a robust biomarker of health, aging, and age-related diseases. We assessed telomere length dynamics (changes over time) in three unrelated astronauts before, during, and after 1-year or 6-month missions aboard the International Space Station (ISS). Similar to our results for National Aeronautics and Space Administration’s (NASA’s) One-Year Mission twin astronaut (Garrett-Bakelman et al., 2019), significantly longer telomeres were observed during spaceflight for two 6-month mission astronauts. Furthermore, telomere length shortened rapidly after return to Earth for all three crewmembers and, overall, telomere length tended to be shorter after spaceflight than before spaceflight. Consistent with chronic exposure to the space radiation environment, signatures of persistent DNA damage responses were also detected, including mitochondrial and oxidative stress, inflammation, and telomeric and chromosomal aberrations, which together provide potential mechanistic insight into spaceflight-specific telomere elongation.
Display omitted
•Telomere elongation during spaceflight was observed for two 6-month mission astronauts•Telomere elongation was not dependent on mission duration, sample, or measurement type•Chronic space radiation exposure was associated with persistent DNA damage responses•Telomeres shortened rapidly after return to Earth, and long-term individual differences were observed
Consistent with findings first observed for NASA’s One-Year Mission twin astronaut, Luxton et al. report spaceflight-specific telomere elongation in ISS crewmembers on shorter duration missions. Signatures of persistent DNA damage responses in the space radiation environment are also observed, providing potential mechanistic insight into telomere maintenance pathways during spaceflight.
Information on mental health and substance use challenges among gay, bisexual, and other MSM (GBMSM) is needed to focus resources on these issues and optimize services for HIV prevention and care. We ...determined factors associated with depressive symptoms and problematic alcohol and other substance use among GBMSM in Kenya.
Self-identified GBMSM in three HIV research studies in Kenya provided information on depressive symptoms Patient Health Questionnaire 9 (PHQ-9), alcohol use Alcohol Use Disorder Identification Test (AUDIT), and other substance use Drug Abuse Screening Test 6 (DAST-6). Associations were evaluated using mixed effects Poisson regression.
Of 1476 participants, 452 (31%) reported moderate-to-severe depressive symptoms (PHQ-9 ≥ 10), 637 (44%) hazardous alcohol use (AUDIT ≥ 8), and 749 (51%) problematic substance use (DAST-6 ≥ 1). Known HIV-positive status was not associated with these outcomes. Transactional sex was associated with hazardous alcohol use adjusted prevalence ratio (aPR) 1.34, 95% confidence interval (CI) 1.12-1.60. Childhood abuse and recent trauma were associated with moderate-to-severe depressive symptoms (aPR 1.43, 95% CI 1.10-1.86 and aPR 2.43, 95% CI 1.91-3.09, respectively), hazardous alcohol use (aPR 1.36, 95% CI 1.10-1.68 and aPR 1.60, 95% CI 1.33-1.93, respectively), and problematic substance use (aPR 1.32, 95% CI 1.09-1.60 and aPR 1.35, 95% CI 1.14-1.59, respectively).
GBMSM in rights-constrained settings need culturally appropriate services for treatment and prevention of mental health and substance use disorders, in addition to human rights advocacy to prevent abuse. Mental health and substance use screening and treatment or referral should be an integral part of programs, including HIV prevention and treatment programs, providing services to GBMSM.
Background
The rapid provision of blood products is life‐saving for patients with massive hemorrhage. Ideally, RhD‐negative blood products would be supplied to a woman of childbearing potential whose ...Rh type is unknown due to the risk of D‐alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD‐positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory.
Methods
After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test.
Results
The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics.
Discussion
These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation.
PDF
