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

Sleep Quality and Sexual Satisfaction in Distressed Breast Cancer Survivors: Secondary Analysis of Prospective Longitudinal Data from the ARCS Trial

Purpose: Sleep quality and sexual functioning are interrelated, with problems in these domains frequent among breast cancer survivors. As there is limited evidence on how these constructs influence one another over time, this secondary analysis examines the prospective association between breast cancer survivors’ sleep quality and sexual satisfaction. Methods: 313 distressed breast cancer survivors (age M=52, 84% non-Hispanic White) were randomized to either a mobile app distress intervention (IntelliCare) or a psychoeducational control app. Participants reported sleep quality (Pittsburgh Sleep Quality Index; PSQI) and sexual satisfaction (PROMIS Satisfaction with Sex Life Scale; SWSLS) at baseline, 8 weeks, 6 months, and 12 months. Parallel process latent growth modeling was used to examine associations between constructs over time, controlling for age and partner status. Moderation by study condition was tested. Results: The final parallel process model fit the data (χ²(29)=24.47, p=.71; CFI=1.00; SRMR=.025) with no moderation effects by study condition. Both sleep quality (slope B=0.54, p<.001) and sexual satisfaction (slope B=0.58, p=.004) improved over time, with worse initial scores in the domain predicting greater improvement (PSQI intercept-slope covariance: B=-1.02, p=.01; SWSLS: B=-4.62, p=.01). Sleep quality and sexual satisfaction were positively associated at baseline (PSQI-SWSLS intercept covariance B=6.74, p<.001), but initial levels of one domain did not predict changes in the other, nor were the trajectories of the two domains related (ps>.05). Conclusions: Poor sleep quality and sexual satisfaction were common and concurrently related in distressed breast cancer survivors, yet changes in these domains were not related. Survivors reporting concerns in one domain should be evaluated for concerns in the other; however, improving sleep or sexual satisfaction alone is unlikely to produce lasting benefits in the other domain

Sleep Quality and Sexual Satisfaction in Distressed Breast Cancer Survivors: Secondary Analysis of Prospective Longitudinal Data from the ARCS Trial

Purpose: Sleep quality and sexual functioning are interrelated, with problems in these domains frequent among breast cancer survivors. As there is limited evidence on how these constructs influence one another over time, this secondary analysis examines the prospective association between breast cancer survivors’ sleep quality and sexual satisfaction. Methods: 313 distressed breast cancer survivors (age M=52, 84% non-Hispanic White) were randomized to either a mobile app distress intervention (IntelliCare) or a psychoeducational control app. Participants reported sleep quality (Pittsburgh Sleep Quality Index; PSQI) and sexual satisfaction (PROMIS Satisfaction with Sex Life Scale; SWSLS) at baseline, 8 weeks, 6 months, and 12 months. Parallel process latent growth modeling was used to examine associations between constructs over time, controlling for age and partner status. Moderation by study condition was tested. Results: The final parallel process model fit the data (χ²(29)=24.47, p=.71; CFI=1.00; SRMR=.025) with no moderation effects by study condition. Both sleep quality (slope B=0.54, p<.001) and sexual satisfaction (slope B=0.58, p=.004) improved over time, with worse initial scores in the domain predicting greater improvement (PSQI intercept-slope covariance: B=-1.02, p=.01; SWSLS: B=-4.62, p=.01). Sleep quality and sexual satisfaction were positively associated at baseline (PSQI-SWSLS intercept covariance B=6.74, p<.001), but initial levels of one domain did not predict changes in the other, nor were the trajectories of the two domains related (ps>.05). Conclusions: Poor sleep quality and sexual satisfaction were common and concurrently related in distressed breast cancer survivors, yet changes in these domains were not related. Survivors reporting concerns in one domain should be evaluated for concerns in the other; however, improving sleep or sexual satisfaction alone is unlikely to produce lasting benefits in the other domain

Hippocampal Insulin Resistance Impairs Spatial Learning and Synaptic Plasticity

Insulin receptors (IRs) are expressed in discrete neuronal populations in the central nervous system, including the hippocampus. To elucidate the functional role of hippocampal IRs independent of metabolic function, we generated a model of hippocampal-specific insulin resistance using a lentiviral vector expressing an IR antisense sequence (LV-IRAS). LV-IRAS effectively downregulates IR expression in the rat hippocampus without affecting body weight, adiposity, or peripheral glucose homeostasis. Nevertheless, hippocampal neuroplasticity was impaired in LV-IRAS–treated rats. High-frequency stimulation, which evoked robust long-term potentiation (LTP) in brain slices from LV control rats, failed to evoke LTP in LV-IRAS–treated rats. GluN2B subunit levels, as well as the basal level of phosphorylation of GluA1, were reduced in the hippocampus of LV-IRAS rats. Moreover, these deficits in synaptic transmission were associated with impairments in spatial learning. We suggest that alterations in the expression and phosphorylation of glutamate receptor subunits underlie the alterations in LTP and that these changes are responsible for the impairment in hippocampal-dependent learning. Importantly, these learning deficits are strikingly similar to the impairments in complex task performance observed in patients with diabetes, which strengthens the hypothesis that hippocampal insulin resistance is a key mediator of cognitive deficits independent of glycemic control.</jats:p

“Another Tool in Your Toolkit”: Pediatric Occupational and Physical Therapists’ Perspectives of Initiating Telehealth during the COVID-19 Pandemic

Pediatric occupational and physical therapy service delivery via telehealth increased during the COVID-19 pandemic. Real-world experience can guide service improvement. This study explored experiences, barriers, and facilitators of initial telehealth implementation from the therapist’s perspective. Qualitative descriptive approach. Semi-structured interviews were conducted with occupational therapists (n = 4) and physical therapists (n = 4) between May-June 2020. Interviews were recorded, and transcribed verbatim. Data were coded inductively to generate themes, then re-coded deductively to classify barriers and facilitators to telehealth acceptance and use using the Unified Technology Acceptance Theory. Participants had 16.5 [(2-35); median (range)] years of experience (3 months with telehealth) and predominantly worked with preschool children. Three themes about telehealth were identified: a practical option; requires skill development and refinement; beneficial in perpetuity. Most frequently cited barriers were the lack of opportunity for ‘hands-on’ assessment/intervention and the learning curve required. Most frequently cited facilitators included seeing a child in their own environment, attendance may be easier for some families, and families’ perception that telehealth was useful. Despite rapid implementation, therapists largely described telehealth as a positive experience. Telehealth facilitated continued service provision and was perceived as relevant post-pandemic. Additional training and ensuring equitable access to services are priorities as telehealth delivery evolves.</p