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Heritable thoracic aortic disease can result from null variants in MYLK, which encodes myosin light-chain kinase (MLCK). Data on which MYLK missense variants are pathogenic and information to guide aortic disease management are limited. Clinical data from 60 cases with MYLK pathogenic variants were analyzed (five null and two missense variants), and the effect of missense variants on kinase activity was assessed. Twenty-three individuals (39%) experienced an aortic event (defined as aneurysm repair or dissection); the majority of these events (87%) were aortic dissections. Aortic diameters were minimally enlarged at the time of dissection in many cases. Time-to-aortic-event curves showed that missense pathogenic variant (PV) carriers have earlier-onset aortic events than null PV carriers. An MYLK missense variant segregated with aortic disease over five generations but decreases MYLK kinase acitivity marginally. Functional Assays fail to identify all pathogenic variants in MYLK. These data further define the aortic phenotype associated with MYLK pathogenic variants. Given minimal aortic enlargement before dissection, an alternative approach to guide the timing of aortic repair is proposed based on the probability of a dissection at a given age.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder caused by mutations in ENG , ACVRL1 and SMAD4 , which function in regulating the transforming growth factor beta and bone morphogenetic protein signaling pathways. Symptoms of HHT can be present in individuals who test negative for mutations in these three genes indicating other genes may be involved. In this study, we tested for mutations in two genes, RASA1 and GDF2 , which were recently reported to be involved in vascular disorders. To determine whether RASA1 and GDF2 have phenotypic overlap with HHT and should be included in diagnostic testing, we developed a next-generation sequencing assay to detect mutations in 93 unrelated individuals who previously tested negative for mutations in ENG , ACVRL1 and SMAD4 , but were clinically suspected to have HHT. Pathogenic mutations in RASA1 were identified in two samples (2.15%) and a variant of unknown significance in GDF2 was detected in one sample. All three individuals experienced epistaxis with dermal lesions described in medical records as telangiectases. These results indicate that the inclusion of RASA1 and GDF2 screening in individuals suspected to have HHT will increase the detection rate and aid clinicians in making an accurate diagnosis. Hereditary hemorrhagic telangiectasia: New gene mutation candidates Researchers in the USA have identified two genes with mutations which could be involved in a hereditary vascular disorder. Hereditary hemorrhagic telangiectasia (HHT) is a condition in which malformed blood vessels cause frequent nosebleeds, skin lesions and, in serious cases, hemorrhaging in the brain and lungs. The condition can be difficult to diagnose, and some patients exhibit HHT symptoms but test negative for mutations in three genes currently known to be associated with the disorder. Aaron Elliott at Ambry Genetics, California, and co-workers developed a next generation sequencing assay to test for mutations in two further genes already linked with other vascular disorders. They analyzed DNA samples from 93 unrelated individuals suspected to have HHT. Three of the patients had mutations in the two genes. The researchers recommend inclusion of these gene candidates in future HHT screening tests.

Background Advances in sequencing technology have led to expanded use of multi‐gene panel tests (MGPTs) for clinical diagnostics. Well‐designed MGPTs must balance increased detection of clinically significant findings while mitigating the increase in variants of uncertain significance (VUS). To maximize clinical utililty, design of such panels should include comprehensive gene vetting using a standardized clinical validity (CV) scoring system. Methods To assess the impact of CV‐based gene vetting on MGPT results, data from MGPTs for cardiovascular indications were retrospectively analyzed. Using our CV scoring system, genes were categorized as having definitive, strong, moderate, or limited evidence. The rates of reported pathogenic or likely pathogenic variants and VUS were then determined for each CV category. Results Of 106 total genes, 42% had definitive, 17% had strong, 29% had moderate, and 12% had limited CV. The detection rate of variants classified as pathogenic or likely pathogenic was higher for genes with greater CV, while the VUS rate showed an inverse relationship with CV score. No pathogenic or likely pathogenic findings were observed in genes with a limited CV. Conclusion These results demonstrate the importance of a standardized, evidence‐based vetting process to establish CV for genes on MGPTs. Using our proposed system may help to increase the detection rate while mitigating higher VUS rates. To maximize clinical utility of multi‐gene panel tests, clinical validity of genes for cardiovascular indications was assessed. We observed an increase in pathogenic and likely pathogenic findings as clinical validity score strengthened. Inclusion of genes with limited clinical validity scores fail to increase detection rate, while increasing the potential burden of variants of uncertain significance.

The invasion of jumping worms, a small group of pheretimoid earthworm species from Asia, has increasingly become an ecological, environmental and conservation issue in forest ecosystems and urban-suburban landscapes around the world. Their presence is often noticed due to their high abundance, distinctive “jumping” behavior, and prominent granular casts on the soil surface. Although they are known to affect soil carbon dynamics and nutrient availability, no single paper has summarized their profound impacts on soil biodiversity, plant community, and animals of all trophic groups that rely on soil and the leaf litter layer for habitat, food, and shelter. In this study, we summarize the biology, invasion, and ecological impacts of invasive jumping worms across North America. We highlight potential impacts of this second wave of earthworm invasion, contrast them with the preceding European earthworm invasion in temperate forests in North America, and identify annual life cycle, reproductive and cocoon survival strategies, casting behavior and co-invasion dynamics as the key factors that contribute to their successful invasion and distinct ecological impacts. We then suggest potential management and control strategies for practitioners and policy makers, underscore the importance of coordinated community science projects in tracking the spread, and identify knowledge gaps that need to be addressed to understand and control the invasion.

The study aimed to determine the prevalence of documented side effects and drug–drug interactions in older adults using antidepressants and their implications for adherence. Data were from the MarketScan Medicare Database, which comprises insurance claims from retirees with employer-sponsored Medicare supplemental insurance. Subjects were aged 65 years or older, new antidepressant users, and had a depression diagnosis between July 1, 2001, and December 31, 2006. Twelve commonly reported antidepressant side effects were identified in the month after drug initiation through International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses. Potential drug-drug interactions involving an anti-depressant and another drug were identified during the 1 year after antidepressant initiation using MicroMedex DRUG-REAX software. Multinomial logistic regression was used to determine the association of side effects and potential interactions with refills rates, switching, and discontinuation. The presence of a side effect was associated with a 4.7 percentage point increase in the probability of switching (from 16.5% to 21.7%) and a 3.7 percentage point increase in the discontinuation rate (from 22% to 25.7%). Among the 39,512 treatment-naive antidepressants users, 25.4% had potential contraindicated or major interactions, 36.1% had moderate interactions, and 38.5% had minor or no interactions. The presence of potential contraindicated or potential major interactions increased the probability of switching by 19.5 percentage points and had a minimal effect on discontinuation. Although antidepressant medications have been demonstrated to be effective in treatment of geriatric depression, this study highlights the complexity of antidepressant prescribing in this population and the need for clinicians to be aware of potential drug-drug interactions and side effects. (Am J Geriatr Psychiatry 2011; 19:2117–221)

The access to, and cost of, mental health insurance coverage are problems encountered in both urban and rural areas because often there is a lack of local and within network providers creating barriers which influence suicide rates (CDC, 2018). Integration of information from other sources such as the medical record, health care professionals, or family members, to identify social history, risk factors, and chronic conditions, along with the responses to the C-SSRS short version, can guide proper care. According to The Columbia Lighthouse Project (2016), use of the CSSRS short version in combination with clinical judgment can aid in making clinical decisions about care. According to the medical center's triage guidelines, patients identified at low risk were provided connections to a crisis text line, local crisis response number, national suicide hotline, and their established mental health provider.