Notes

ITSN1: a novel choice gene involved with autosomal dominant neurodevelopmental condition spectrum.
The specialty must once again engage policymakers by drawing on evidence gleaned and lessons learned from past cuts of optional Medicaid services to avert counterproductive coverage restrictions intended to mitigate the financial impact of the COVID-19 pandemic.Advances in genome editing technologies have enabled manipulation of genomes at the single base level. #link# These technologies are based on programmable nucleases (PNs) that include meganucleases, zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated 9 (Cas9) nucleases and have given researchers the ability to delete, insert or replace genomic DNA in cells, tissues and whole organisms. The great flexibility in re-designing the genomic target specificity of PNs has vastly expanded the scope of gene editing applications in life science, and shows great promise for development of the next generation gene therapies. PN technologies share the principle of inducing a DNA double-strand break (DSB) at a user-specified site in the genome, followed by cellular repair of the induced DSB. PN-elicited DSBs are mainly repaired by the non-homologous end joining (NHEJ) and the microhomology-mediated end joininy occurring indels and their detection. Next, we review the methods that have been developed for detection of PN-induced indels. link2 We briefly outline the experimental steps and describe the pros and cons of the various methods to help users decide a suitable method for their editing application. We highlight recent advances that enable accurate and sensitive quantification of indel events in cells regardless of their genome complexity, turning a complex pool of different indel events into informative indel profiles. Finally, we review what has been learned about PN-elicited indel formation through the use of the new methods and how this insight is helping to further advance the genome editing field.The aim of structural biology has been always the study of biological macromolecules structures and their mechanistic behaviour at molecular level. To achieve its goal, multiple biophysical methods and approaches have become part of the structural biology toolbox. Considered as one of the pillars of structural biology, X-ray crystallography has been the most successful method for solving three-dimensional protein structures at atomic level to date. It is however limited by the success in obtaining well-ordered protein crystals that diffract at high resolution. This is especially true for challenging targets such as membrane proteins (MPs). Understanding structure-function relationships of MPs at the biochemical level is vital for medicine and drug discovery as they play critical roles in many cellular processes. Though difficult, structure determination of MPs by X-ray crystallography has significantly improved in the last two decades, mainly due to many relevant technological and methodological developments. Today, numerous MP crystal structures have been solved, revealing many of their mechanisms of action. Yet the field of structural biology has also been through significant technological breakthroughs in recent years, particularly in the fields of single particle electron microscopy (cryo-EM) and X-ray free electron lasers (XFELs). Here we summarise the most important advancements in the field of MP crystallography and the significance of these developments in the present era of modern structural biology.
The "unexpected career" of caregiving has previously been conceptualized in stages community care through institutional placement/residence, ending with death of the care recipient. Transition programs such as Money Follows the Person (MFP) created a new stage of the caregiving career, caring for someone post-long-term institutionalization, about which little is known. Using Pearlin's Caregiver Stress Process Model, this study explores effects on caregivers from the return of their loved ones to the community after a long-term institutional stay.

Cross-sectional surveys of 656 caregivers of persons transitioned through Connecticut's MFP program 2014-18, completed 6 months post-transition.

Regardless of the age/disability of the care recipient, and despite experiencing high caregiving intensity, caregivers experienced less burden, anxiety, and depression, and higher benefits of caregiving than demonstrated in literature for the general caregiving population. find more felt less stressed than before and duringement. Positive results for Black and Hispanic caregivers may reflect cultural expectations in caring for family that buffer the adverse effects of caregiving.
Prevalence of hypertension (both primary and secondary) in children and adolescents in the US ranges from 3% to 4%. Primary hypertension in children and adolescents occurs primarily in children older than 13 years and has no known cause but is associated with several risk factors, including family history and higher body mass index. Secondary hypertension occurs primarily in younger children and is most commonly caused by genetic disorders, renal disease, endocrine disorders, or cardiovascular abnormalities.

To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of screening, test accuracy, the effectiveness and harms of treatment, and the association between hypertension and markers of cardiovascular disease in childhood and adulthood.

This recommendation statement applies to children and adolescents aged 3 to 18 years not known to have hypertension or who are asymptomatic.

The USPSTF concludes that the evidence to support screening for high blood pressure in children and adolescents is insufficient and that the balance of benefits and harms cannot be determined.

The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents. (I statement).
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for high blood pressure in children and adolescents. (I statement).
Childhood hypertension can result in adverse outcomes during adulthood; identifying and treating primary and secondary childhood hypertension may reduce such risks.

To update the evidence on screening and treatment of hypertension in childhood and adolescence for the US Preventive Services Task Force.

PubMed, Cochrane Library, International Pharmaceutical Abstracts, EMBASE, and trial registries through September 3, 2019; bibliographies from retrieved articles, experts, and surveillance of the literature through October 6, 2020.

Fair- or good-quality English-language studies evaluating diagnostic accuracy of blood pressure screening; cohort studies assessing the association of hypertension in childhood and adolescence with blood pressure or other intermediate outcomes in adulthood; randomized clinical trials (RCTs) or meta-analyses of pharmacological and lifestyle interventions.

Two reviewers independently assessed titles/abstracts and full-text articles, extracted data, and assessed study quality; twever, the evidence is inconclusive whether the diagnostic accuracy of blood pressure measurements is adequate for screening asymptomatic children and adolescents in primary care.
Medicare recently concluded a national voluntary payment demonstration, Bundled Payments for Care Improvement (BPCI) model 3, in which skilled nursing facilities (SNFs) assumed accountability for patients' Medicare spending for 90 days from initial SNF admission. There is little evidence on outcomes associated with this novel payment model.

To evaluate the association of BPCI model 3 with spending, health care utilization, and patient outcomes for Medicare beneficiaries undergoing lower extremity joint replacement (LEJR).

Observational difference-in-difference analysis using Medicare claims from 2013-2017 to evaluate the association of BPCI model 3 with outcomes for 80 648 patients undergoing LEJR. The preintervention period was from January 2013 through September 2013, which was 9 months prior to enrollment of the first BPCI cohort. The postintervention period extended from 3 months post-BPCI enrollment for each SNF through December 2017. BPCI SNFs were matched with control SNFs using propensity score ayments in other clinical contexts.
Electronic cigarettes (e-cigarettes) for smoking cessation remain controversial.

To evaluate e-cigarettes with individual counseling for smoking cessation.

A randomized clinical trial enrolled adults motivated to quit smoking from November 2016 to September 2019 at 17 Canadian sites (801 individuals screened; 274 ineligible and 151 declined). link3 Manufacturing delays resulted in early termination (376/486 participants, 77% of target). Outcomes through 24 weeks (March 2020) are reported.

Randomization to nicotine e-cigarettes (n = 128), nonnicotine e-cigarettes (n = 127), or no e-cigarettes (n = 121) for 12 weeks. All groups received individual counseling.

The primary end point was point prevalence abstinence (7-day recall, biochemically validated using expired carbon monoxide) at 12 weeks, changed from 52 weeks following early termination. Participants missing data were assumed to be smoking. The 7 secondary end points, examined at multiple follow-ups, were point prevalence abstinence at other follow-upmost common being cough (64%) and dry mouth (53%).

Among adults motivated to quit smoking, nicotine e-cigarettes plus counseling vs counseling alone significantly increased point prevalence abstinence at 12 weeks. However, the difference was no longer significant at 24 weeks, and trial interpretation is limited by early termination and inconsistent findings for nicotine and nonnicotine e-cigarettes, suggesting further research is needed.

ClinicalTrials.gov Identifier NCT02417467.
ClinicalTrials.gov Identifier NCT02417467.
The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear.

To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults.

Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017.

Participants were randomized to 3 years of intervention in 1 of the following 8 groups 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270).

The 6 primary outcomes wereIR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups.

Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes.

ClinicalTrials.gov Identifier NCT01745263.
ClinicalTrials.gov Identifier NCT01745263.
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