Noncanonical NF-κB factor p100/p52 regulates homologous recombination and modulates sensitivity to DNA-damaging therapy.

Homologous recombination (HR) serves multiple roles in DNA repair that are essential for maintaining genomic stability, including double-strand DNA break (DSB) repair. The central HR protein, RAD51, is frequently overexpressed in human malignancies, thereby elevating HR proficiency and promoting resistance to DNA-damaging therapies. Here, we find that the non-canonical NF-κB factors p100/52, but not RelB, control the expression of RAD51 in various human cancer subtypes. While p100/p52 depletion inhibits HR function in human tumor cells, it does not significantly influence the proficiency of non-homologous end joining, the other key mechanism of DSB repair. Clonogenic survival assays were performed using a pair DLD-1 cell lines that differ only in their expression of the key HR protein BRCA2. Targeted silencing of p100/p52 sensitizes the HR-competent cells to camptothecin, while sensitization is absent in HR-deficient control cells. These results suggest that p100/p52-dependent signaling specifically controls HR activity in cancer cells. Since non-canonical NF-κB signaling is known to be activated after various forms of genomic crisis, compensatory HR upregulation may represent a natural consequence of DNA damage. We propose that p100/p52-dependent signaling represents a promising oncologic target in combination with DNA-damaging treatments.

The interdependent transport of yeast vacuole Ca2+ and H+ and the role of phosphatidylinositol 3,5-bisphosphate.

Yeast vacuoles are acidified by the v-type H+-ATPase (V-ATPase) that is comprised of the membrane embedded VO complex and the soluble cytoplasmic V1 complex. The assembly of the V1-VO holoenzyme on the vacuole is stabilized in part through interactions between the VO a-subunit ortholog Vph1 and the lipid phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2). PI(3,5)P2 also affects vacuolar Ca2+ release through the channel Yvc1 and uptake through the Ca2+ pump Pmc1. Here, we asked if H+ and Ca2+ transport activities were connected through PI(3,5)P2. We found that overproduction of PI(3,5)P2 by the hyperactive fab1T2250A mutant augmented vacuole acidification, whereas the kinase-inactive fab1EEE mutant attenuated the formation of a H+ gradient. Separately, we tested the effects of excess Ca2+ on vacuole acidification. Adding micromolar Ca2+ blocked vacuole acidification, whereas chelating Ca2+ accelerated acidification. The effect of adding Ca2+ on acidification was eliminated when the Ca2+/H+ antiporter Vcx1 was absent, indicating that the vacuolar H+ gradient can collapse during Ca2+ stress through Vcx1 activity. This, however, was independent of PI(3,5)P2, suggesting that PI(3,5)P2 plays a role in submicromolar Ca2+ flux but not under Ca2+ shock. To see if the link between Ca2+ and H+ transport was bidirectional, we examined Ca2+ transport when vacuole acidification was inhibited. We found that Ca2+ transport was inhibited by halting V-ATPase activity with Bafilomycin or neutralizing vacuolar pH with chloroquine. Together, these data show that Ca2+ transport and V-ATPase efficacy are connected but not necessarily through PI(3,5)P2.

Disparities in physical activity between sexual minority and heterosexual women: A systematic review and meta-analysis.

Research examining potential differences in physical activity (PA) between sexual minority women (SMW) and heterosexual women have yielded inconsistent results. OBJECTIVE: Therefore, the purpose of this systematic review and meta-analysis is to examine potential differences in PA between SMW and heterosexual women and to identify potential moderators that may partially explain observed differences in PA. METHODS: All studies were peer reviewed, published in English, and included a continuous measure of PA for SMW and heterosexual women. A standardized mean difference effect size (ES) was used to compare groups, with random effects models used to estimate a mean ES and 95% CI using a 3-level meta-analysis model to adjust for the correlation between effects nested within studies. RESULTS: The cumulative results of 24 effects gathered from 7 studies indicated there was no difference in PA between SMW (n = 1619) and heterosexual women (n = 103,295) (ES = -0.038, 95%CI -0.179 to 0.102, p = 0.576). Despite no mean differences, moderate-high heterogeneity was observed, indicating that the results were not consistent across effects (I2 = 64.8%, Q23 = 36.7, p = 0.035). The difference in PA was associated with age (ß = -0.018, 95%CI -0.034 to -0.003, p = 0.022) and BMI (ß = -0.145, 95%CI -0.228 to -0.061, p = 0.002), with a quadratic relationship observed for both variables. CONCLUSIONS: Although the results of the current analysis did not indicate significant differences in PA behaviors between SMW and heterosexual women, age and BMI modify the association and are curvilinear in nature; such that smaller differences in PA were observed between SMW and heterosexual women when samples were middle-aged and overweight.

Creating an ignorance-base: Exploring known unknowns in the scientific literature.

BACKGROUND: Scientific discovery progresses by exploring new and uncharted territory. More specifically, it advances by a process of transforming unknown unknowns first into known unknowns, and then into knowns. Over the last few decades, researchers have developed many knowledge bases to capture and connect the knowns, which has enabled topic exploration and contextualization of experimental results. But recognizing the unknowns is also critical for finding the most pertinent questions and their answers. Prior work on known unknowns has sought to understand them, annotate them, and automate their identification. However, no knowledge-bases yet exist to capture these unknowns, and little work has focused on how scientists might use them to trace a given topic or experimental result in search of open questions and new avenues for exploration. We show here that a knowledge base of unknowns can be connected to ontologically grounded biomedical knowledge to accelerate research in the field of prenatal nutrition. RESULTS: We present the first ignorance-base, a knowledge-base created by combining classifiers to recognize ignorance statements (statements of missing or incomplete knowledge that imply a goal for knowledge) and biomedical concepts over the prenatal nutrition literature. This knowledge-base places biomedical concepts mentioned in the literature in context with the ignorance statements authors have made about them. Using our system, researchers interested in the topic of vitamin D and prenatal health were able to uncover three new avenues for exploration (immune system, respiratory system, and brain development) by searching for concepts enriched in ignorance statements. These were buried among the many standard enriched concepts. Additionally, we used the ignorance-base to enrich concepts connected to a gene list associated with vitamin D and spontaneous preterm birth and found an emerging topic of study (brain development) in an implied field (neuroscience). The researchers could look to the field of neuroscience for potential answers to the ignorance statements. CONCLUSION: Our goal is to help students, researchers, funders, and publishers better understand the state of our collective scientific ignorance (known unknowns) in order to help accelerate research through the continued illumination of and focus on the known unknowns and their respective goals for scientific knowledge.

Phosphatidylinositol 3,5-bisphosphate regulates Ca2+ transport during yeast vacuolar fusion through the Ca2+ ATPase Pmc1.

The transport of Ca2+ across membranes precedes the fusion and fission of various lipid bilayers. Yeast vacuoles under hyperosmotic stress become fragmented through fission events that requires the release of Ca2+ stores through the TRP channel Yvc1. This requires the phosphorylation of phosphatidylinositol-3-phosphate (PI3P) by the PI3P-5-kinase Fab1 to produce transient PI(3,5)P2 pools. Ca2+ is also released during vacuole fusion upon trans-SNARE complex assembly, however, its role remains unclear. The effect of PI(3,5)P2 on Ca2+ flux during fusion was independent of Yvc1. Here, we show that while low levels of PI(3,5)P2 were required for Ca2+ uptake into the vacuole, increased concentrations abolished Ca2+ efflux. This was as shown by the addition of exogenous dioctanoyl PI(3,5)P2 or increased endogenous production of by the hyperactive fab1T2250A mutant. In contrast, the lack of PI(3,5)P2 on vacuoles from the kinase dead fab1EEE mutant showed delayed and decreased Ca2+ uptake. The effects of PI(3,5)P2 were linked to the Ca2+ pump Pmc1, as its deletion rendered vacuoles resistant to the effects of excess PI(3,5)P2 . Experiments with Verapamil inhibited Ca2+ uptake when added at the start of the assay, while adding it after Ca2+ had been taken up resulted in the rapid expulsion of Ca2+ . Vacuoles lacking both Pmc1 and the H+ /Ca2+ exchanger Vcx1 lacked the ability to take up Ca2+ and instead expelled it upon the addition of ATP. Together these data suggest that a balance of efflux and uptake compete during the fusion pathway and that the levels of PI(3,5)P2 can modulate which path predominates.

A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury.

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.

Agreement Between A 2-Dimensional Digital Image-Based 3-Compartment Body Composition Model and Dual Energy X-Ray Absorptiometry for The Estimation of Relative Adiposity.

The purpose of this study was to compare relative adiposity (%Fat) derived from a 2-dimensional image-based 3-component (3C) model (%Fat3C-IMAGE) and dual-energy X-ray absorptiometry (DXA) (%FatDXA) against a 5-component (5C) laboratory criterion (%Fat5C). 57 participants were included (63.2% male, 84.2% White/Caucasian, 22.5±4.7 yrs., 23.9±2.8 kg/m2). For each participant, body mass and standing height were measured to the nearest 0.1 kg and 0.1 cm, respectively. A digital image of each participant was taken using a 9.7 inch, 16g iPad Air 2 and analyzed using a commercially available application (version 1.1.2, made Health and Fitness, USA) for the estimation of body volume (BV) and inclusion in %Fat3C-IMAGE . %Fat3C-IMAGE and %Fat5C included measures of total body water derived from bioimpedance spectroscopy. The criterion %Fat5C included BV estimates derived from underwater weighing and bone mineral content measures via DXA. %FatDXA estimates were calculated from a whole-body DXA scan. A standardized mean effect size (ES) assessed the magnitude of differences between models with values of 0.2, 0.5, and 0.8 for small, moderate, and large differences, respectively. Data are presented as mean ± standard deviation. A strong correlation (r = 0.94, p <.001) and small mean difference (ES = 0.24, p <.001) was observed between %Fat3C-IMAGE (19.20±5.80) and %Fat5C (17.69±6.20) whereas a strong correlation (r = 0.87, p <.001) and moderate-large mean difference (ES = 0.70, p <.001) was observed between %FatDXA (22.01±6.81) and %Fat5C. Furthermore, %Fat3C-IMAGE (SEE = 2.20 %Fat, TE= 2.6) exhibited smaller SEE and TE than %FatDXA (SEE = 3.14 %Fat, TE = 5.5). The 3C image-based model performed slightly better in our sample of young adults than the DXA 3C model. Thus, the 2D image analysis program provides an accurate and non-invasive estimate of %Fat within a 3C model in young adults. Compared to DXA, the 3C image-based model allows for a more cost-effective and portable method of body composition assessment, potentially increasing accessibility to multi-component methods.

Copper blocks V-ATPase activity and SNARE complex formation to inhibit yeast vacuole fusion.

The accumulation of copper in organisms can lead to altered functions of various pathways and become cytotoxic through the generation of reactive oxygen species. In yeast, cytotoxic metals such as Hg+ , Cd2+ and Cu2+ are transported into the lumen of the vacuole through various pumps. Copper ions are initially transported into the cell by the copper transporter Ctr1 at the plasma membrane and sequestered by chaperones and other factors to prevent cellular damage by free cations. Excess copper ions can subsequently be transported into the vacuole lumen by an unknown mechanism. Transport across membranes requires the reduction of Cu2+ to Cu+ . Labile copper ions can interact with membranes to alter fluidity, lateral phase separation and fusion. Here we found that CuCl2 potently inhibited vacuole fusion by blocking SNARE pairing. This was accompanied by the inhibition of V-ATPase H+ pumping. Deletion of the vacuolar reductase Fre6 had no effect on the inhibition of fusion by copper. This suggests that Cu2+ is responsible for the inhibition of vacuole fusion and V-ATPase function. This notion is supported by the differential effects of chelators. The Cu2+ -specific chelator triethylenetetramine rescued fusion, whereas the Cu+ -specific chelator bathocuproine disulfonate had no effect on the inhibited fusion.

Transcutaneous carbon dioxide pattern and trend over time in preterm infants.

BACKGROUND: Chronic lung disease remains a burden for extremely preterm infants. The changes in ventilation over time and optimal ventilatory management remains unknown. Newer, non-invasive technologies provide insight into these patterns. METHODS: This single-center prospective cohort study enrolled infants ≤32 0/7 weeks. We obtained epochs of transcutaneous carbon dioxide (TcCO2) measurements twice each week to describe the pattern of hypercarbia throughout their hospitalization. RESULTS: Patterns of hypercarbia varied based on birth gestational age and post-menstrual age (PMA) (p = 0.03), regardless of respiratory support. Infants receiving the most respiratory support had values 16-21 mmHg higher than those on room air (p < 0.001). Infants born at the youngest gestational ages had the greatest total change but the rate of change was slower (p = 0.049) compared to infants born at later gestational ages. All infants had TcCO2 values stabilize by 31-33 weeks PMA, when values were not significantly different compared to discharge. No rebound was observed when infants weaned off invasive support. CONCLUSIONS: Hypercarbia improves as infants approached 31-33 weeks PMA. Hypercarbia was the highest in the most immature infants and improved with age and growth despite weaning respiratory support. IMPACT: This study describes the evolution of hypercarbia as very preterm infants grow and develop. The pattern of ventilation is significantly different depending on the gestational age at birth and post-menstrual age. Average transcutaneous carbon dioxide (TCO2) decreased over time as infants became more mature despite weaning respiratory support. This improvement was most significant in infants born at the lowest gestational ages.

The effect of mTBI and PTSD symptoms on computerized cognitive performance: Results from a sample of treatment-seeking active duty US service members.

TBI and PTSD occur in a significant number of service members and can each result in considerable distress and cognitive challenges. Past research has established the individual impact of mild TBI (mTBI) and PTSD on cognitive performance; however, findings regarding the combined effects of mTBI and PTSD on cognitive performance are inconsistent. The present study examined the potentially synergistic effects of mTBI and PTSD symptoms on cognitive performance in a sample of 180 treatment-seeking active duty service members. As part of a larger clinical study, participants completed several self-report measures and an objective cognitive assessment via computer-based testing. Compared to norms, service members with mTBI-only, PTSD-symptoms-only, and comorbid TBI and PTSD performed significantly worse on cognitive tests, and there was a significant effect of group on cognitive performance, even when controlling for performance validity. Notably, individuals experiencing both mTBI and PTSD performed worse than those with either condition alone; service members with mTBI-only and those with PTSD symptoms-only did not differ. Findings further illustrate the complexity of the relationship between these two conditions, indicating comorbid mTBI and PTSD may represent a unique challenge to cognitive performance. Additional research is needed to clarify their combined impact on post-injury functioning.

Intraventricular Hemorrhage and Patent Ductus Arteriosus Ligation Association with Infant Mortality.

BACKGROUND: Practice patterns for the management of patent ductus arteriosus (PDA) in premature infants are changing with advances in medical management. We sought to determine the increased mortality for premature infants who had a PDA ligation with a co-existing diagnosis of intraventricular hemorrhage (IVH). METHODS: Premature neonates (<1 y old with known gestational week ≤36 wk) with a diagnosis of IVH were identified within the Kids' Inpatient Database (KID) for the years 2006, 2009, and 2012. Diagnoses and procedures were analyzed by ICD-9 codes and stratified by a diagnosis of PDA and procedure of ligation. Case weighting was used to make national estimations. Multivariable logistic regression was performed to adjust for confounders. RESULTS: We identified 7567 hospitalizations for premature neonates undergoing PDA ligation. The population was predominately male (51.6%), non-Hispanic white (41.1%), were from the lowest income quartile (33.1%), had a gestational week of 25-26 wk (34.0%), and a birthweight between 500 and 749 g (37.3%). There was an increased mortality (10.7% versus 6.3%, P < 0.01) and an increased length of stay (88.2 d versus 74.4 d, P < 0.01) in those with any diagnosis of IVH compared with those without. Adjusted multivariable logistic regression demonstrated that high-grade IVH (III or IV) was associated with a significantly increased risk of mortality in those undergoing PDA ligation (aOR 2.59, P < 0.01). Specifically, grade III and IV were associated with an increased odds of in-hospital mortality (aOR 1.99 and 3.16, respectively, P < 0.01). CONCLUSIONS: Attitudes regarding the need for surgical intervention for PDA have shifted in recent years. This study highlights that premature neonates with grade III or IV IVH are at significantly increased risk of mortality if undergoing PDA ligation during the same hospitalization. LEVEL OF EVIDENCE: III.

Anti-OspA DNA-Encoded Monoclonal Antibody Prevents Transmission of Spirochetes in Tick Challenge Providing Sterilizing Immunity in Mice.

We recently developed anti-OspA human immunoglobulin G1 monoclonal antibodies (HuMAbs) that are effective in preventing Borrelia transmission from ticks in a murine model. Here, we investigated a novel approach of DNA-mediated gene transfer of HuMAbs that provide protection against Lyme disease. Plasmid DNA-encoded anti-OspA HuMAbs inoculated in mice achieved a serum antibody concentration of >6 µg/mL. Among mice injected with DNA-encoded monoclonal antibodies, 75%-77% were protected against an acute challenge by Borrelia-infected ticks. Our results represent the first demonstration of employing DNA transfer as a delivery system for antibodies that block transmission of Borrelia in animal models.

Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673. At the same time, primary MPN cell samples from individual patients displayed a high degree of variability in sensitivity to these drugs. Ruxolitinib inhibited 2 major DSB repair mechanisms, BRCA-mediated homologous recombination and DNA-dependent protein kinase-mediated nonhomologous end-joining, and, when combined with olaparib, caused abundant accumulation of toxic DSBs resulting in enhanced elimination of MPN primary cells, including the disease-initiating cells from the majority of patients. Moreover, the combination of BMN673, ruxolitinib, and hydroxyurea was highly effective in vivo against JAK2(V617F)+ murine MPN-like disease and also against JAK2(V617F)+, CALR(del52)+, and MPL(W515L)+ primary MPN xenografts. In conclusion, we postulate that ruxolitinib-induced deficiencies in DSB repair pathways sensitized MPN cells to synthetic lethality triggered by PARP inhibitors.

The Relationship Between Social Identity, Stereotype Threat, and Academic Success Among Prenursing Students.

The relationships between social identity, stereotype threat, and academic success were explored among prenursing students. Stereotype threat has been linked to academic success in students from underrepresented populations within the social sciences and educational literature but has not been explored in nursing. A descriptive correlational design was used with Picho and Brown's Social Identities and Attitudes Scale emailed to 159 prenursing students. Stereotype threat was significantly related to race/ethnicity with no significant relationship between stereotype threat and academic success. Further exploration of stereotype threat in nursing is warranted; there may be implications for retention and support of diverse students.

Targeting BRCA1- and BRCA2-deficient cells with RAD52 small molecule inhibitors.

RAD52 is a member of the homologous recombination (HR) pathway that is important for maintenance of genome integrity. While single RAD52 mutations show no significant phenotype in mammals, their combination with mutations in genes that cause hereditary breast cancer and ovarian cancer like BRCA1, BRCA2, PALB2 and RAD51C are lethal. Consequently, RAD52 may represent an important target for cancer therapy. In vitro, RAD52 has ssDNA annealing and DNA strand exchange activities. Here, to identify small molecule inhibitors of RAD52 we screened a 372,903-compound library using a fluorescence-quenching assay for ssDNA annealing activity of RAD52. The obtained 70 putative inhibitors were further characterized using biochemical and cell-based assays. As a result, we identified compounds that specifically inhibit the biochemical activities of RAD52, suppress growth of BRCA1- and BRCA2-deficient cells and inhibit RAD52-dependent single-strand annealing (SSA) in human cells. We will use these compounds for development of novel cancer therapy and as a probe to study mechanisms of DNA repair.

Body-weight-supported treadmill rehabilitation after stroke.

BACKGROUND: Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. METHODS: We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. RESULTS: At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). CONCLUSIONS: Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Aerobic fitness levels and validation of a non exercise VO2max prediction equation for HIV-infected patients on HAART.

BACKGROUND: Non-exercise (N-EX) questionnaires have been developed to determine maximal oxygen consumption (VO2max) in healthy populations. There are limited reliable and validated N-EX questionnaires for the HIV+ population that provide estimates of habitual physical activity and not VO2max. OBJECTIVES: To determine how well regression equations developed previously on healthy populations, including N-EX prediction equations for VO2max and age-predicted maximal heart rates (APMHR), worked on an HIV+ population; and to develop a specific N-EX prediction equation for VO2max and APMHR for HIV+ individuals. METHODS: Sixty-six HIV+ participants on stable HAART completed 4 N-EX questionnaires and performed a maximal graded exercise test. RESULTS: Sixty males and 6 females were included; mean (SD) age was 49.2 (8.2) years; CD4 count was 516.0 ± 253.0 cells·mm-3; and 92% had undetectable HIV PCR. Mean VO2max was 29.2 ± 7.6 (range, 14.4-49.4) mL·kg-1·min-1 Despite positive correlations with VO2max, previously published N-EX VO2max equations produced results significantly different than actual VO2 scores (P < .0001). An HIV+ specific N-EX equation was developed and produced similar mean VO2max values, R = 0.71, when compared to achieved VO2max (P = .53). CONCLUSION: HIV+ individuals tend to be sedentary and unfit, putting them at increased risk for the development of chronic diseases associated with a sedentary lifestyle. Based on the level of error associated with utilizing APMHR and N-EX VO2max equations with HIV+ individuals, neither should be used in this population for exercise prescription.

Motor learning in children with hemiplegic cerebral palsy: feedback effects on skill acquisition.

AIM: Motor learning is enhanced with practice and feedback. This cohort control study investigated the effect of different relative feedback frequencies during skill acquisition in children with cerebral palsy (CP) and children with typical development. METHOD: Nineteen children with spastic hemiplegic CP (nine males, 10 females; mean age 11 y 7 mo; range 8-16 y) and 20 children with typical development (12 males, eight females; mean age 10 y 8 mo; range 8-14 y) were assigned to 100% or reduced (62%) feedback subgroups as they practised 200 trials of a discrete arm movement with specific spatiotemporal parameters. Children with CP used their less involved hand. Learning was inferred by delayed (24 h) retention and reacquisition tests. RESULTS: All children improved in accuracy and consistency. Children with typical development demonstrated significantly greater accuracy than children with CP during acquisition (p=0.001), retention (p=0.031), and reacquisition (p=0.001), and greater consistency during retention (p=0.038). The typically developing group who received 100% feedback performed with significantly less error than the 62% feedback group during acquisition (p=0.001), and with greater retention (p=0.017). No statistically significant difference was found between feedback subgroups of children with CP, although the 100% feedback group consistently demonstrated less error. INTERPRETATION: Children with CP use feedback in a manner similar to children with typical development when learning new skills with their less involved hand, but demonstrate less accuracy and consistency.

Impact of Statewide Statute Limiting Days' Supply to Opioid-Naive Patients.

INTRODUCTION: To address the ongoing opioid crisis, states use policy enactment to restrict prescribing by licensed healthcare providers and mandate the use of Prescription Drug Monitoring Programs. There have been mixed results regarding the effectiveness of such state policies. The purpose of this study is to evaluate the impact of Colorado Senate Bill 18-022, which limits opioid prescriptions to ≤7-day supply among patients without an opioid prescription in the previous year (i.e., are opioid naive). METHODS: This is a retrospective interrupted time-series analysis of opioid prescribing to evaluate the weekly percentage of opioid prescriptions consistent with statutory limits for ≤7-day supply among opioid-naive patients before and after enactment using Prescription Drug Monitoring Programs data from May 21, 2017 to May 25, 2019. Statistical analysis was performed in 2021-2022. RESULTS: The weekly percentage of opioid prescriptions ≤7-day supply increased by an average of 0.12% per week (p<0.0001) from 79.7% to 87.4% in the week before enactment. The week after enactment, the average increased by 0.2% (p=0.67). The year after enactment, the average weekly percentage change was 0.07% per week, a 0.05% decrease (p=0.01). CONCLUSIONS: Statutory limits on days' supply among opioid-naive patients had little impact on opioid prescribing in Colorado. Legislating limits on opioid prescribing should be evaluated using Prescription Drug Monitoring Program data and considered for deimplementation when not impactful.

Body composition estimates using a 2D image analysis system across different environmental conditions: An agreement study.

PURPOSE: This study examined the agreement between %Fat measurements using a smartphone-based application (IMAGE) across different environmental conditions. METHODS: A single reference image was obtained using an 8 MP smartphone camera under Ambient Light in front of a white background. Additional photos were obtained using a 0.7 MP, 5 MP, and 12 MP smartphone cameras; low-, moderate-, and bright-lighting conditions; and various color backgrounds including black, green, orange, and gray. RESULTS: %Fat measured using the 0.7 MP camera (27.8 ± 6.2 %Fat) was higher than the reference (26.8 ± 6.1 %Fat) (p < 0.001). The black (32.0 ± 12.0 %Fat), green (27.5 ± 6.3 %Fat), and gray (27.8 ± 6.3 %Fat) backgrounds yielded higher %Fat than the white (p = 0.03, 0.01, and 0.001). All camera, lighting, and background conditions were strongly correlated with the reference (all intraclass correlation coefficient [ICC] >0.98, all standard error of the estimate [SEE] <1.5 %Fat, all p < 0.001), except the black background which yielded poorer agreement with the white background (ICC = 0.69, SEE = 4.5%, p < 0.001). CONCLUSION: %Fat from IMAGE were strongly correlated across various environmental conditions.