Sleep Disorders and Medical Conditions in Women

Abstract Sleep disorders affect women differently than they affect men and may have different manifestations and prevalences. With regard to obstructive sleep apnea (OSA), variations in symptoms may cause misdiagnoses and delay of appropriate treatment. The prevalence of OSA appears to increase markedly after the time of menopause. Although OSA as defined by the numbers of apneas/hypopneas may be less severe in women, its consequences are similar and perhaps worse. Therapeutic issues related to gender should be factored into the management of OSA. The prevalence of insomnia is significantly greater in women than in men throughout most of the life span. The ratio of insomnia in women to men is approximately 1.4:1.0, but the difference is minimal before puberty and increases steadily with age. Although much of the higher prevalence of insomnia in women may be attributable to the hormonal or psychological changes associated with major life transitions, some of the gender differences may result from the higher prevalence of depression and pain in women. Insomnia's negative impact on quality of life is important to address in women, given the high relative prevalence of insomnia as well as the comorbid disorders in this population. Gender differences in etiology and symptom manifestation in narcolepsy remain understudied in humans. There is little available scientific information to evaluate the clinical significance and specific consequences of the diagnosis of narcolepsy in women. Restless legs syndrome (RLS) is characterized by an urge to move the legs or other limbs during periods of rest or inactivity and may affect as much as 10% of the population. This condition is more likely to afflict women than men, and its risk is increased by pregnancy. Although RLS is associated with impaired quality of life, highly effective treatment is available.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63103/1/jwh.2007.0561.pd

Proinsulin expression shapes the TCR repertoire but fails to control the development of low-avidity insulin-reactive CD8+ T cells

NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8+ T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/TRBJ2-3 gene rearrangements, contributes to the development of diabetes. In this study, we used fixed TRAV8-1/TRAJ9 TCRα-chain transgenic mice to assess the impact of PI isoform expression on the insulin-reactive CD8+ T-cell repertoire. The key findings were: 1) PI2 deficiency increases the frequency of insulin B15-23–reactive TRBV19+CD8+ T cells and causes diabetes; 2) insulin B15-23–reactive TRBV19+CD8+ T cells are more abundant in the pancreatic lymph nodes of mice lacking PI1 and/or PI2; 3) overexpression of PI2 decreases TRBV19 usage in the global CD8+ T-cell compartment; 4) a biased repertoire of insulin-reactive CD8+ T cells emerges in the periphery regardless of antigen exposure; and 5) low-avidity insulin-reactive CD8+ T cells are less affected by antigen exposure in the thymus than in the periphery. These findings inform our understanding of the diabetogenic process and reveal new avenues for therapeutic exploitation in type 1 diabetes

The Multisite Violence Prevention Project: Impact of a Universal School-Based Violence Prevention Program on Social-Cognitive Outcomes

This study evaluated the impact of a universal school-based violence prevention program on social-cognitive factors associated with aggression and nonviolent behavior in early adolescence. The effects of the universal intervention were evaluated within the context of a design in which two cohorts of students at 37 schools from four sites (N=5,581) were randomized to four conditions: (a) a universal intervention that involved implementing a student curriculum and teacher training with sixth grade students and teachers; (b) a selective intervention in which a family intervention was implemented with a subset of sixth grade students exhibiting high levels of aggression and social influence; (c) a combined intervention condition; and (d) a no-intervention control condition. Short-term and long-term (i.e., 2-year post-intervention) universal intervention effects on social-cognitive factors targeted by the intervention varied as a function of students' pre-intervention level of risk. High-risk students benefited from the intervention in terms of decreases in beliefs and attitudes supporting aggression, and increases in self-efficacy, beliefs and attitudes supporting nonviolent behavior. Effects on low-risk students were in the opposite direction. The differential pattern of intervention effects for low- and high-risk students may account for the absence of main effects in many previous evaluations of universal interventions for middle school youth. These findings have important research and policy implications for efforts to develop effective violence prevention programs

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Spousal involvement and CPAP adherence: A dyadic perspective

Poor adherence to continuous positive airway pressure (CPAP) treatment is associated with substantial health care costs, morbidity and mortality, and has been a leading obstacle in the effective management of obstructive sleep apnea (OSA). Successful interventions to improve CPAP adherence may ultimately include a variety of components. For patients living with spouses (refers to all domestic partners), the spouse will likely be an integral component to any successful intervention. Developing understanding of the role of spouses in adherence to CPAP has been identified to be a critical research need. This review expands the investigation of CPAP adherence to a broader context, from an exclusive focus on individual patients to a dyadic perspective encompassing both patients and their spouses. A conceptual framework based on social support and social control theories is proposed to understand spousal involvement in CPAP adherence. Methodologies for future investigations are discussed, along with implications for developing interventions that engage both patients and their spouses to improve CPAP use

Rehabilitation versus surgical reconstruction for non-acute anterior cruciate ligament injury (ACL SNNAP): a pragmatic randomised controlled trial

BackgroundAnterior cruciate ligament (ACL) rupture is a common debilitating injury that can cause instability of the knee. We aimed to investigate the best management strategy between reconstructive surgery and non-surgical treatment for patients with a non-acute ACL injury and persistent symptoms of instability.MethodsWe did a pragmatic, multicentre, superiority, randomised controlled trial in 29 secondary care National Health Service orthopaedic units in the UK. Patients with symptomatic knee problems (instability) consistent with an ACL injury were eligible. We excluded patients with meniscal pathology with characteristics that indicate immediate surgery. Patients were randomly assigned (1:1) by computer to either surgery (reconstruction) or rehabilitation (physiotherapy but with subsequent reconstruction permitted if instability persisted after treatment), stratified by site and baseline Knee Injury and Osteoarthritis Outcome Score—4 domain version (KOOS4). This management design represented normal practice. The primary outcome was KOOS4 at 18 months after randomisation. The principal analyses were intention-to-treat based, with KOOS4 results analysed using linear regression. This trial is registered with ISRCTN, ISRCTN10110685, and ClinicalTrials.gov, NCT02980367.FindingsBetween Feb 1, 2017, and April 12, 2020, we recruited 316 patients. 156 (49%) participants were randomly assigned to the surgical reconstruction group and 160 (51%) to the rehabilitation group. Mean KOOS4 at 18 months was 73·0 (SD 18·3) in the surgical group and 64·6 (21·6) in the rehabilitation group. The adjusted mean difference was 7·9 (95% CI 2·5–13·2; p=0·0053) in favour of surgical management. 65 (41%) of 160 patients allocated to rehabilitation underwent subsequent surgery according to protocol within 18 months. 43 (28%) of 156 patients allocated to surgery did not receive their allocated treatment. We found no differences between groups in the proportion of intervention-related complications.InterpretationSurgical reconstruction as a management strategy for patients with non-acute ACL injury with persistent symptoms of instability was clinically superior and more cost-effective in comparison with rehabilitation management

CDKN2A loss is associated with shortened overall survival in lower-grade (World Health Organization Grades II-III) astrocytomas.

Lower-grade (World Health Organization Grades II and III) gliomas vary widely in clinical behavior and are classified as astrocytic, oligodendroglial, or mixed. Anaplasia depends greatly on mitotic activity, with CDKN2A loss considered as the most common mechanism for cell cycle dysregulation. We investigated whether loss of the CDKN2A gene is associated with overall survival across pathologically and genetically defined glioma subtypes. After adjustment for IDH mutation, sex, and age, CDKN2A deletion was strongly associated with poorer overall survival in astrocytomas but not in oligodendrogliomas or oligoastrocytomas. Molecular classification of astrocytomas by IDH mutation, TP53 mutation, and /or ATRX loss of expression revealed that CDKN2A loss in IDH/TP53 mutated tumors was strongly associated with worse overall survival. CDKN2A loss in IDH mutated tumors with ATRX loss was only weakly associated with worse overall survival. These findings suggest that CDKN2A testing may provide further clinical aid in lower-grade glioma substratification beyond IDH mutation and 1p19q codeletion status, particularly in IDH/TP53 mutated astrocytomas

Proinsulin Expression Shapes the TCR Repertoire but Fails to Control the Development of Low-Avidity Insulin-Reactive CD8 +

NOD mice, a model strain for human type 1 diabetes, express proinsulin (PI) in the thymus. However, insulin-reactive T cells escape negative selection, and subsequent activation of the CD8+ T-cell clonotype G9C8, which recognizes insulin B15-23 via an αβ T-cell receptor (TCR) incorporating TRAV8-1/TRAJ9 and TRBV19/TRBJ2-3 gene rearrangements, contributes to the development of diabetes. In this study, we used fixed TRAV8-1/TRAJ9 TCRα-chain transgenic mice to assess the impact of PI isoform expression on the insulin-reactive CD8+ T-cell repertoire. The key findings were: 1) PI2 deficiency increases the frequency of insulin B15-23–reactive TRBV19+CD8+ T cells and causes diabetes; 2) insulin B15-23–reactive TRBV19+CD8+ T cells are more abundant in the pancreatic lymph nodes of mice lacking PI1 and/or PI2; 3) overexpression of PI2 decreases TRBV19 usage in the global CD8+ T-cell compartment; 4) a biased repertoire of insulin-reactive CD8+ T cells emerges in the periphery regardless of antigen exposure; and 5) low-avidity insulin-reactive CD8+ T cells are less affected by antigen exposure in the thymus than in the periphery. These findings inform our understanding of the diabetogenic process and reveal new avenues for therapeutic exploitation in type 1 diabetes