Melatonin and the Human Hair Follicle.

BACKGROUND: Melatonin, a pleiotropic hormone, affects the physiological processes including that of the hair follicle. We seek to identify the scientific evidence to support the potential benefits of melatonin in human hair growth. OBJECTIVE: To summarize the evidence on the association between melatonin and hair health, denoted by hair growth. METHODS: A literature review using 3 databases (PubMed, Google Scholar, and Cochrane) identified studies investigating the relationship between melatonin and hair loss (2022). The following search terms were used: (hair OR hair loss OR alopecia OR hair growth OR effluvium OR scalp) and (melatonin). Two independent reviewers screened studies for inclusion criteria, and data collection included demographics, melatonin intervention, study type, and effects on hair. RESULTS: A total of 11 human studies were identified with evidence of melatonin use in subjects with diagnosed alopecia (2,267 patients; 1,140M). Eight of the studies reviewed observed positive outcomes after topical melatonin use in subjects with androgenetic alopecia (AGA). Most studies report improved scalp hair growth (n=8), density (n=4), and hair shaft thickness (n=2) among melatonin users compared with controls. Effective topical melatonin dosage appears to be 0.0033% or 0.1% solution applied once-daily for 90 to 180 days vs 1.5 mg twice-daily oral melatonin supplementation for 180 days. CONCLUSION: There is evidence to support melatonin use to facilitate scalp hair growth, particularly in men with AGA. Further studies should include more patients and investigate the mechanism of action. J Drugs Dermatol. 2023;22(3): doi:10.36849/JDD.6921.

Efficient and unique cobarcoding of second-generation sequencing reads from long DNA molecules enabling cost-effective and accurate sequencing, haplotyping, and de novo assembly.

Here, we describe single-tube long fragment read (stLFR), a technology that enables sequencing of data from long DNA molecules using economical second-generation sequencing technology. It is based on adding the same barcode sequence to subfragments of the original long DNA molecule (DNA cobarcoding). To achieve this efficiently, stLFR uses the surface of microbeads to create millions of miniaturized barcoding reactions in a single tube. Using a combinatorial process, up to 3.6 billion unique barcode sequences were generated on beads, enabling practically nonredundant cobarcoding with 50 million barcodes per sample. Using stLFR, we demonstrate efficient unique cobarcoding of more than 8 million 20- to 300-kb genomic DNA fragments. Analysis of the human genome NA12878 with stLFR demonstrated high-quality variant calling and phase block lengths up to N50 34 Mb. We also demonstrate detection of complex structural variants and complete diploid de novo assembly of NA12878. These analyses were all performed using single stLFR libraries, and their construction did not significantly add to the time or cost of whole-genome sequencing (WGS) library preparation. stLFR represents an easily automatable solution that enables high-quality sequencing, phasing, SV detection, scaffolding, cost-effective diploid de novo genome assembly, and other long DNA sequencing applications.

Referral and Evaluation for Kidney Transplantation Following Implementation of the 2014 National Kidney Allocation System.

RATIONALE & OBJECTIVE: The national kidney allocation system (KAS) implemented in December 2014 in the United States redefined the start of waiting time from the time of waitlisting to the time of kidney failure. Waitlisting has declined post-KAS, but it is unknown if this is due to transplant center practices or changes in dialysis facility referral and evaluation. The purpose of this study was to assess the impact of the 2014 KAS policy change on referral and evaluation for transplantation among a population of incident and prevalent patients with kidney failure. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 37,676 incident (2012-2016) patients in Georgia, North Carolina, and South Carolina identified within the US Renal Data System at 9 transplant centers and followed through December 2017. A prevalent population of 6,079 patients from the same centers receiving maintenance dialysis in 2012 but not referred for transplantation in 2012. EXPOSURE: KAS era (pre-KAS vs post-KAS). OUTCOME: Referral for transplantation, start of transplant evaluation, and waitlisting. ANALYTICAL APPROACH: Multivariable time-dependent Cox models for the incident and prevalent population. RESULTS: Among incident patients, KAS was associated with increased referrals (adjusted HR, 1.16 [95% CI, 1.12-1.20]) and evaluation starts among those referred (adjusted HR, 1.16 [95% CI, 1.10-1.21]), decreased overall waitlisting (adjusted HR, 0.70 [95% CI, 0.65-0.76]), and lower rates of active waitlisting among those evaluated compared to the pre-KAS era (adjusted HR, 0.81 [95% CI, 0.74-0.90]). Among the prevalent population, KAS was associated with increases in overall waitlisting (adjusted HR, 1.74 [95% CI, 1.15-2.63]) and active waitlisting among those evaluated (adjusted HR, 2.01 [95% CI, 1.16-3.49]), but had no significant impact on referral or evaluation starts among those referred. LIMITATIONS: Limited to 3 states, residual confounding. CONCLUSIONS: In the southeastern United States, the impact of KAS on steps to transplantation was different among incident and prevalent patients with kidney failure. Dialysis facilities referred more incident patients and transplant centers evaluated more incident patients after implementation of KAS, but fewer evaluated patients were placed onto the waitlist. Changes in dialysis facility and transplant center behaviors after KAS implementation may have influenced the observed changes in access to transplantation.

Early steps to kidney transplantation among persons with HIV and end-stage renal disease in ESRD network 6.

INTRODUCTION: End-stage renal disease is a significant cause of morbidity and mortality in persons with HIV (PWH). Limited data exist on access to kidney transplantation for this population. METHODS: A dataset inclusive of incident dialysis patients between 2012 and 2016 with follow-up through December 2017 that identifies PWH and the general dialysis population of Network 6 (Georgia, North Carolina, South Carolina) was created through merging the United States Renal Data System with the southeastern early transplant access registry. Early steps to kidney transplantation and patient and dialysis facility-level characteristics that serve as barriers to transplantation were described. RESULTS: Twenty-three thousand four hundred fourteen patients were identified; 469 were PWH. Compared to non-HIV individuals, PWH were younger (49 vs. 58 years, p < 0.001), predominantly Black (87% vs. 56% p < 0.001) and male (72% vs. 56% p < 0.001). PWH were less likely to be referred to kidney transplant within 1 year of starting dialysis (36% vs. 41% p < 0.001) and waitlisted within 1 year of evaluation-start (14% vs. 30%, p = 0.05). PWH (vs. non-PWH) waited longer for referral, evaluation-start, and waitlisting and in multivariable analysis; HIV positivity was associated with a lower probability of referral (hazard ratios [HR]: 0.70; 95% confidence intervals [CIs]: 0.62-0.80), evaluation (HR 0.66; 95% CI: 0.55-0.80), and waitlisting (HR 0.29; 95% CI: 0.20-0.41). CONCLUSIONS: Targeted interventions are needed to improve access to kidney transplants, particularly in waitlisting, for PWH.

Opportunity to increase deceased donation for United States veterans.

Recent changes to organ procurement organization (OPO) performance metrics have highlighted the need to identify opportunities to increase organ donation in the United States. Using data from the Organ Procurement and Transplantation Network (OPTN), Scientific Registry of Transplant Recipients (SRTR), and Veteran Health Administration Informatics and Computing Infrastructure Clinical Data Warehouse (VINCI CDW), we sought to describe historical donation performance at Veteran Administration Medical Centers (VAMCs). We found that over the period 2010-2019, there were only 33 donors recovered from the 115 VAMCs with donor potential nationwide. VA donors had similar age-matched organ transplant yields to non-VA donors. Review of VAMC records showed a total of 8474 decedents with causes of death compatible with donation, of whom 5281 had no infectious or neoplastic comorbidities preclusive to donation. Relative to a single state comparison of adult non-VA inpatient deaths, VAMC deaths were 20 times less likely to be characterized as an eligible death by SRTR. The rate of conversion of inpatient donation-consistent deaths without preclusive comorbidities to actual donors at VAMCs was 5.9% that of adult inpatients at non-VA hospitals. Overall, these findings suggest significant opportunities for growth in donation at VAMCs.

Sickle Cell Trait and Risk of Ischemic Stroke in Young Adults.

BACKGROUND AND PURPOSE: Approximately 8% of Blacks have sickle cell trait (SCT), and there are conflicting reports from recent cohort studies on the association of SCT with ischemic stroke (IS). Most prior studies focused on older populations, with few data available in young adults. METHODS: A population-based case-control study of early-onset IS was conducted in the Baltimore-Washington region between 1992 and 2007. From this study, 342 Black IS cases, ages 15 to 49, and 333 controls without IS were used to examine the association between SCT and IS. Each participant's SCT status was established by genotyping and imputation. For analysis, χ2 tests and logistic regression models were performed with adjustment for potential confounding variables. RESULTS: Participants with SCT (n=55) did not differ from those without SCT (n=620) in prevalence of hypertension, previous myocardial infarction, diabetes mellitus, and current smoking status. Stroke cases had increased prevalence in these risk factors compared with controls. We did not find an association between SCT and early-onset IS in our overall population (odds ratio=0.9 [95% CI, 0.5-1.7]) or stratified by sex in males (odds ratio=1.26 [95% CI, 0.56-2.80]) and females (odds ratio=0.67 [95% CI, 0.28-1.69]). CONCLUSIONS: Our data did not find evidence of increased risk of early-onset stroke with SCT.

High-beta/low-gamma frequency activity reflects top-down predictive coding during a spatial working memory test.

Numerous mental health disorders are characterized by cognitive impairments that result in poor vocational and social outcomes. Among the cognitive domains commonly affected, working memory deficits have been noted in patients with attention-deficit/hyperactivity disorder (Martinussen et al. in J Am Acad Child Adolesc Psychiatry 44:377-384, 2005), post-traumatic stress disorder (Honzel et al. in Cogn Affect Behav Neurosci 14:792-804, 2014), and consistently with schizophrenia patients (Callicott et al. in Cereb Cortex 10:1078-1092, 2000; Lewis et al. in Front Hum Neurosci 10:85, 2005; Amann et al. in Brain Res Bull 83:147-161, 2010; Limongi et al. in Schizophr Res 197:386-391, 2018). Oscillations in neural activity from electroencephalogram (EEG) recordings are decomposed by frequency, and band-specific decreases in gamma power (> 30 Hz) have been correlated with working memory ability. This study examined within-subject changes in power of frequency-specific bands during sample versus choice trials during a spatial working memory paradigm (T-maze). EEG was recorded using a relatively novel wireless EEG telemetry system fully implanted within the mouse, enabling uninhibited movement during behavioral tasks. No significant differences were found between sample and correct choice phases in the alpha, theta or gamma frequency ranges. Evoked power was significantly higher during the choice phase than the sample phase in the high-beta/low-gamma frequency range. This frequency range has been implicated in the propagation of cortical predictions to lower levels of stimuli encoding in a top-down hierarchical manner. Results suggest there is an increase in brain activity during correct trials when the mouse enters the opposite arm during the choice phase compared to the sample phase, likely due to prediction error resulting from a discrepancy between present and prior experience. Future studies should identify specific cortical networks involved and investigate neural activity at the neuronal level.

Emergency department use among kidney transplant recipients in the United States.

Patients with end-stage renal disease use the emergency department (ED) at a 6-fold higher rate than do other US adults. No national studies have described ED use rates among kidney transplant (KTx) recipients, and the factors associated with higher ED use. We examined a cohort of 132 725 adult KTx recipients in the United States Renal Data System (2005-2013). Data on ED visits, hospitalization, and outpatient nephrology visits were obtained from Medicare claims databases. Nearly half (46.1%) of KTx recipients had at least one ED visit (1.61 ED visits/patient-year [PY]), and 39.7% of ED visits resulted in hospitalization in the first year posttransplantation. ED visit rate was high in the first 30 days (5.26 visits/PY) but declined substantially thereafter (1.81 visits/PY in months 1-3; 1.13 visits/PY in months 3-12 posttransplantation). ED visit rates were higher in the first 30 days versus rates for dialysis patients but less than half the rate thereafter. Female sex, public insurance, medical comorbidities, longer pretransplantation dialysis vintage, and delayed graft function were associated with higher ED use in the first year post-KTx. Policies and strategies addressing potentially preventable ED visits should be promoted to help improve patient care and increase efficient use of ED resources.

Detection and phasing of single base de novo mutations in biopsies from human in vitro fertilized embryos by advanced whole-genome sequencing.

Currently, the methods available for preimplantation genetic diagnosis (PGD) of in vitro fertilized (IVF) embryos do not detect de novo single-nucleotide and short indel mutations, which have been shown to cause a large fraction of genetic diseases. Detection of all these types of mutations requires whole-genome sequencing (WGS). In this study, advanced massively parallel WGS was performed on three 5- to 10-cell biopsies from two blastocyst-stage embryos. Both parents and paternal grandparents were also analyzed to allow for accurate measurements of false-positive and false-negative error rates. Overall, >95% of each genome was called. In the embryos, experimentally derived haplotypes and barcoded read data were used to detect and phase up to 82% of de novo single base mutations with a false-positive rate of about one error per Gb, resulting in fewer than 10 such errors per embryo. This represents a ∼ 100-fold lower error rate than previously published from 10 cells, and it is the first demonstration that advanced WGS can be used to accurately identify these de novo mutations in spite of the thousands of false-positive errors introduced by the extensive DNA amplification required for deep sequencing. Using haplotype information, we also demonstrate how small de novo deletions could be detected. These results suggest that phased WGS using barcoded DNA could be used in the future as part of the PGD process to maximize comprehensiveness in detecting disease-causing mutations and to reduce the incidence of genetic diseases.

Clinical and genetic analysis of a rare syndrome associated with neoteny.

PurposeWe describe a novel syndrome in seven female patients with extreme developmental delay and neoteny.MethodsAll patients in this study were female, aged 4 to 23 years, were well below the fifth percentile in height and weight, had failed to develop sexually, and lacked the use of language. Karyotype and array chromosome genomic hybridization analysis failed to identify large-scale structural variations. To further understand the underlying cause of disease in these patients, whole-genome sequencing was performed.ResultsIn five patients, coding de novo mutations (DNMs) were found in five different genes. These genes fell into similar functional categories of transcription regulation and chromatin modification. Comparison to a control population suggested that individuals with neotenic complex syndrome (NCS)-a name that we propose herein-could have an excess of rare inherited variants in genes associated with developmental delay and autism, although the difference was not significant.ConclusionWe describe an extreme form of developmental delay, with the defining characteristic of neoteny. In most patients we identified coding DNMs in a set of genes intolerant of haploinsufficiency; however, it is not clear whether these contributed to NCS. Rare inherited variants may also be associated with NCS, but more samples need to be analyzed to achieve statistical significance.

Advanced Whole-Genome Sequencing and Analysis of Fetal Genomes from Amniotic Fluid.

BACKGROUND: Amniocentesis is a common procedure, the primary purpose of which is to collect cells from the fetus to allow testing for abnormal chromosomes, altered chromosomal copy number, or a small number of genes that have small single- to multibase defects. Here we demonstrate the feasibility of generating an accurate whole-genome sequence of a fetus from either the cellular or cell-free DNA (cfDNA) of an amniotic sample. METHODS: cfDNA and DNA isolated from the cell pellet of 31 amniocenteses were sequenced to approximately 50× genome coverage by use of the Complete Genomics nanoarray platform. In a subset of the samples, long fragment read libraries were generated from DNA isolated from cells and sequenced to approximately 100× genome coverage. RESULTS: Concordance of variant calls between the 2 DNA sources and with parental libraries was >96%. Two fetal genomes were found to harbor potentially detrimental variants in chromodomain helicase DNA binding protein 8 (CHD8) and LDL receptor-related protein 1 (LRP1), variations of which have been associated with autism spectrum disorder and keratosis pilaris atrophicans, respectively. We also discovered drug sensitivities and carrier information of fetuses for a variety of diseases. CONCLUSIONS: We were able to elucidate the complete genome sequence of 31 fetuses from amniotic fluid and demonstrate that the cfDNA or DNA from the cell pellet can be analyzed with little difference in quality. We believe that current technologies could analyze this material in a highly accurate and complete manner and that analyses like these should be considered for addition to current amniocentesis procedures.

Pyramidal cell-selective GluN1 knockout causes impairments in salience attribution and related EEG activity.

Schizophrenia is a disabling psychiatric disease characterized by symptoms including hallucinations, delusions, social withdrawal, loss of pleasure, and inappropriate affect. Although schizophrenia is marked by dysfunction in dopaminergic and glutamatergic signaling, it is not presently clear how these dysfunctions give rise to symptoms. The aberrant salience hypothesis of schizophrenia argues that abnormal attribution of motivational salience to stimuli is one of the main contributors to both positive and negative symptoms of schizophrenia. The proposed mechanisms for this hypothesis are overactive striatal dopaminergic and hypoactive glutamatergic signaling. The current study assessed salience attribution in mice (n = 72) using an oddball paradigm in which an infrequent stimulus either co-occurred with shock (conditioned group) or was presented alone (non-conditioned group). Behavioral response (freezing) and electroencephalogram (whole brain and amygdala) were used to assess salience attribution. Mice with pyramidal cell-selective knockout of ionotropic glutamate receptors (GluN1) were used to reproduce a prominent physiological change involved in schizophrenia. Non-conditioned knockout mice froze significantly more in response to the unpaired stimulus than non-conditioned wild-type mice, suggesting that this irrelevant cue acquired motivational salience for the knockouts. In accordance with this finding, low-frequency event-related spectral perturbation was significantly increased in non-conditioned knockout mice relative to both conditioned knockout and non-conditioned wild-type mice. These results suggest that pyramidal cell-selective GluN1 knockout leads to inappropriate attribution of salience for irrelevant stimuli as characterized by abnormalities in both behavior and brain circuitry functions.

Child stunting is associated with weaker human capital among native Amazonians.

OBJECTIVES: We assessed associations between child stunting, recovery, and faltering with schooling and human capital skills in a native Amazonian society of horticulturalists-foragers (Tsimane'). METHODS: We used cross-sectional data (2008) from 1262 children aged 6 to 16 years in 53 villages to assess contemporaneous associations between three height categories: stunted (height-for-age Z score, HAZ<-2), moderately stunted (-2 ≤ HAZ≤-1), and nonstunted (HAZ>-1), and three categories of human capital: completed grades of schooling, test-based academic skills (math, reading, writing), and local plant knowledge. We used annual longitudinal data (2002-2010) from all children (n = 853) in 13 villages to estimate the association between changes in height categories between the first and last years of measure and schooling and academic skills. RESULTS: Stunting was associated with 0.4 fewer completed grades of schooling (∼24% less) and with 13-15% lower probability of showing any writing or math skills. Moderate stunting was associated with ∼20% lower scores in local plant knowledge and 9% lower probability of showing writing skills, but was not associated with schooling or math and writing skills. Compared with nonstunted children, children who became stunted had 18-21% and 15-21% lower probabilities of showing math and writing skills, and stunted children had 0.4 fewer completed grades of schooling. Stunted children who recovered showed human capital outcomes that were indistinguishable from nonstunted children. CONCLUSIONS: The results confirm adverse associations between child stunting and human capital skills. Predictors of growth recovery and faltering can affect human capital outcomes, even in a remote, economically self-sufficient society.

Waitlist Hospital Admissions Predict Resource Utilization and Survival After Renal Transplantation.

OBJECTIVE: To determine whether fitness for transplant can be determined by candidates' hospitalizations although waitlisted. BACKGROUND: Renal transplantation must increasingly serve a population of multiply comorbid patients in an environment defined by organ scarcity and premiums on value-based care. Determining those at excess risk for transplant is critical to these imperatives. METHODS: United States Renal Data Systems patient and claims data for all adult renal transplant recipients between 2000 and 2010 with continuous primary Medicare coverage for 1 year before and after transplantation were examined. Outcomes included readmissions within the first-year post-transplant and 3-year graft and patient survival. Chi-square statistics, Kaplan-Meier methods (log-rank test), and goodness of fit calculations (c-statistics) were performed for models of transplant outcome. RESULTS: Among 37,623 patients, the percentages of patients admitted for 0, 1 to 7, 8 to 14, or 15 or more days in the pretransplant year were 51%, 25%, 11%, and 13%. Overall readmission-free survival at 1 year was 31%. Heavily preadmitted patients were more likely to have a greater length of stay during their transplant admission, and had a greater service needs at discharge. Pretransplant admission strongly predicted more frequent post-transplant admission. Among all factors studied, preadmission was the strongest predictor of post-transplant death, and had a dose-dependent effect on both death and graft loss. CONCLUSIONS: In summary, hospitalization in the year before transplant is an objective, readily ascertainable, and powerful predictor of excess resource utilization and inferior outcome. Incorporation of a rolling assessment of patient hospitalization has potential policy implications for maximizing value in renal transplantation.

Catch-up growth and growth deficits: Nine-year annual panel child growth for native Amazonians in Bolivia.

BACKGROUND: Childhood growth stunting is negatively associated with cognitive and health outcomes, and is claimed to be irreversible after age 2. AIM: To estimate growth rates for children aged 2-7 who were stunted (sex-age standardised z-score [HAZ] <-2), marginally-stunted (-2 ≤ HAZ ≤-1) or not-stunted (HAZ >-1) at baseline and tracked annually until age 11; frequency of movement among height categories; and variation in height predicted by early childhood height. SUBJECTS AND METHODS: This study used a 9-year annual panel (2002-2010) from a native Amazonian society of horticulturalists-foragers (Tsimane'; n = 174 girls; 179 boys at baseline). Descriptive statistics and random-effect regressions were used. RESULTS: This study found some evidence of catch-up growth in HAZ, but persistent height deficits. Children stunted at baseline improved 1 HAZ unit by age 11 and had higher annual growth rates than non-stunted children. Marginally-stunted boys had a 0.1 HAZ units higher annual growth rate than non-stunted boys. Despite some catch up, ∼ 80% of marginally-stunted children at baseline remained marginally-stunted by age 11. The height deficit increased from age 2 to 11. Modest year-to-year movement was found between height categories. CONCLUSIONS: The prevalence of growth faltering among the Tsimane' has declined, but hurdles still substantially lock children into height categories.

Flexibility in surface-exposed loops in a virus capsid mediates escape from antibody neutralization.

UNLABELLED: New human norovirus strains emerge every 2 to 3 years, partly due to mutations in the viral capsid that allow escape from antibody neutralization and herd immunity. To understand how noroviruses evolve antibody resistance, we investigated the structural basis for the escape of murine norovirus (MNV) from antibody neutralization. To identify specific residues in the MNV-1 protruding (P) domain of the capsid that play a role in escape from the neutralizing monoclonal antibody (MAb) A6.2, 22 recombinant MNVs were generated with amino acid substitutions in the A'B' and E'F' loops. Six mutations in the E'F' loop (V378F, A382K, A382P, A382R, D385G, and L386F) mediated escape from MAb A6.2 neutralization. To elucidate underlying structural mechanisms for these results, the atomic structure of the A6.2 Fab was determined and fitted into the previously generated pseudoatomic model of the A6.2 Fab/MNV-1 virion complex. Previously, two distinct conformations, A and B, of the atomic structures of the MNV-1 P domain were identified due to flexibility in the two P domain loops. A superior stereochemical fit of the A6.2 Fab to the A conformation of the MNV P domain was observed. Structural analysis of our observed escape mutants indicates changes toward the less-preferred B conformation of the P domain. The shift in the structural equilibrium of the P domain toward the conformation with poor structural complementarity to the antibody strongly supports a unique mechanism for antibody escape that occurs via antigen flexibility instead of direct antibody-antigen binding. IMPORTANCE: Human noroviruses cause the majority of all nonbacterial gastroenteritis worldwide. New epidemic strains arise in part by mutations in the viral capsid leading to escape from antibody neutralization. Herein, we identify a series of point mutations in a norovirus capsid that mediate escape from antibody neutralization and determine the structure of a neutralizing antibody. Fitting of the antibody structure into the virion/antibody complex identifies two conformations of the antibody binding domain of the viral capsid: one with a superior fit and the other with an inferior fit to the antibody. These data suggest a unique mode of antibody neutralization. In contrast to other viruses that largely escape antibody neutralization through direct disruption of the antibody-virus interface, we identify mutations that acted indirectly by limiting the conformation of the antibody binding loop in the viral capsid and drive the antibody binding domain into the conformation unable to be bound by the antibody.

Gait Speed and Mortality, Hospitalization, and Functional Status Change Among Hemodialysis Patients: A US Renal Data System Special Study.

BACKGROUND: Slow walk (gait) speed predicts functional decline, institutionalization, and mortality risks in the geriatric population. A gait speed evidence base for dialysis patient outcomes is needed. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 752 prevalent hemodialysis (HD) patients aged 20 to 92 years evaluated in 2009 to 2012 in 7 Atlanta and 7 San Francisco clinics in a US Renal Data System special study. PREDICTOR: Usual walk speed in meters per second, categorized as ≥0.6 m/s (baseline n=575), <0.6 m/s (baseline n=94), and unable to perform walk test (baseline n=83). OUTCOMES: Survival; hospitalization; activities of daily living (ADL) difficulty; 36-Item Short Form Health Survey (SF-36) Physical Function score. MEASUREMENTS: Cox proportional hazards models investigated gait speed and mortality over a median follow-up of 703 days. Multivariable logistic or linear regression models estimated associations of baseline gait speed with hospitalization, need for ADL assistance, and SF-36 Physical Function score after 12 months. RESULTS: Participants who walked ≥0.6 m/s had 53 (9%) deaths, those who walked <0.6 m/s had 19 (20%) deaths, and those unable to walk had 37 (44%) deaths. Adjusted mortality hazard ratios were 2.17 (95% CI, 1.19-3.98) for participants who walked <0.6 m/s and 6.93 (95% CI, 4.01-11.96) for those unable to walk, compared with participants walking ≥0.6 m/s. After 12 months, compared with baseline walk speed ≥ 1.0 m/s (n=169 participants), baseline walk speed of 0.6 to <0.8 m/s (n=116) was associated with increased odds of hospitalization (OR, 2.04; 95% CI, 1.19-3.49) and ADL difficulty (OR, 3.88; 95% CI, 1.46-10.33) and a -8.20 (95% CI, -13.57 to -2.82) estimated change in SF-36 Physical Function score. LIMITATIONS: Cohort not highly representative of overall US in-center HD population. CONCLUSIONS: Because walking challenges the heart, lungs, and circulatory, nervous, and musculoskeletal systems, gait speed provides an informative marker of health status. The association of gait speed with HD patients' risk for functional decline warrants continued study.

Underreporting of nursing home utilization on the CMS-2728 in older incident dialysis patients and implications for assessing mortality risk.

BACKGROUND: The usage of nursing home (NH) services is a marker of frailty among older adults. Although the Centers for Medicare & Medicaid Services (CMS) revised the Medical Evidence Report Form CMS-2728 in 2005 to include data collection on NH institutionalization, the validity of this item has not been reported. METHODS: There were 27,913 patients ≥ 75 years of age with incident end-stage renal disease (ESRD) in 2006, which constituted our analysis cohort. We determined the accuracy of the CMS-2728 using a matched cohort that included the CMS Minimum Data Set (MDS) 2.0, often employed as a "gold standard" metric for identifying patients receiving NH care. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the CMS-2728 NH item. Next, we compared characteristics and mortality risk by CMS-2728 and MDS NH status agreement. RESULTS: The sensitivity, specificity, PPV and NPV of the CMS-2728 for NH status were 33%, 97%, 80% and 79%, respectively. Compared to those without the MDS or CMS-2728 NH indicator (No MDS/No 2728), multivariable adjusted hazard ratios (95% confidence interval) for mortality associated with NH status were 1.55 (1.46 - 1.64) for MDS/2728, 1.48 (1.42 - 1.54) for MDS/No 2728, and 1.38 (1.25 - 1.52) for No MDS/2728. NH utilization was more strongly associated with mortality than other CMS-2728 items in the model. CONCLUSIONS: The CMS-2728 underestimated NH utilization among older adults with incident ESRD. The potential for misclassification may have important ramifications for assessing prognosis, developing advanced care plans and providing coordinated care.

Genetic variation for sexual dimorphism in developmental traits in Drosophila melanogaster.

Sexual dimorphism in traits of insects during the developmental stages could potentially be the direct or indirect result of sex-specific selection provided that genetic variation for sexual dimorphism is present. We investigated genetic variation in sexual dimorphism in a set of Drosophila melanogaster inbred lines for 2 traits: egg to adult development time and pupation site preference. We observed considerable genetic variation in sexual dimorphism among lines in both traits. The sexual dimorphic patterns remained relatively consistent across multiple trials, despite both traits being sensitive to environmental conditions. Additionally, we measured 2 sexually dimorphic adult morphological traits in 6 sampled lines and investigated correlations in the sexual dimorphism patterns with the 2 developmental traits. The abundance of genetic variation in sexual dimorphism for D. melanogaster developmental traits demonstrated in this study provides evidence for a high degree of evolvability of sex differences in preadult traits in natural populations.

High Hepatitis C Cure Rates Among Patients With Alcohol Use at a Safety-Net Hepatitis C Clinic.

OBJECTIVES: We set out to examine several aspects of the relationship between alcohol use and hepatitis C virus (HCV) among a cohort of patients treated at an HCV clinic within a safety net hospital. We examined (1) the prevalence of alcohol use among patients treated for HCV, (2) the likelihood of being started on treatment among patients who reported drinking alcohol compared with those who did not, and (3) the associations between alcohol use and HCV cure. METHODS: We performed a retrospective chart abstraction study using data from the Grady Liver Clinic, a specialty HCV clinic colocated in Grady Memorial Hospital's primary care clinic and run by general internists. RESULTS: Nine hundred fifty-four patients were included. The sustained virologic response rate among those with 12-week posttreatment measurement was 99.2%, with only 5 patients experiencing virologic failure. None of the alcohol use indicators significantly impacted sustained virologic response or loss to follow-up. Estimates of alcohol use ranged from 28.9% (by International Classification of Diseases, Tenth Revision, code) to 48.9% (clinician documentation). Treatment initiation rates were the same among those who did and did not report alcohol use. CONCLUSIONS: Alcohol use was not associated with decreased HCV cure rates. Our findings validate the inclusion of patients with alcohol use in HCV treatment programs.