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The article presents a study which investigates the effects of testosterone (T) treatment on men with mild cognitive impairment (MCI) and low serum T levels. The study evaluates the cognition, mood, and quality of life of 351 community-dwelling men and 37 men with MCI and low T. The study determines that verbal memory and depression symptoms can be improved by testosterone treatment.

The ABCB1 gene, coding for the efflux transporter P-glycoprotein (PGP), is a candidate gene for Alzheimer disease (AD). P-glycoprotein is heavily expressed at the blood-brain barrier, where it mediates the efflux of β-amyloid (Aβ) from the brain. In this study, we investigated a possible association between 2 common ABCB1 polymorphisms, G2677T/A (Ala893Ser/Thr) and C3435T, AD, and cerebrospinal fluid (CSF) levels of Aβ. No strong evidence for association was found. [ABSTRACT FROM AUTHOR]

Abstract Background Neuropsychiatric symptoms such as psychosis are prevalent in patients with probable Alzheimer’s disease (AD) and are associated with increased morbidity and mortality. Because these disabling symptoms are generally not well tolerated by caregivers, patients with these symptoms tend to be institutionalized earlier than patients without them. The identification of protective and risk factors for neuropsychiatric symptoms in AD would facilitate the development of more specific treatments for these symptoms and thereby decrease morbidity and mortality in AD. The E4 allele of the apolipoprotein E (APOE) gene is a well-documented risk factor for the development of AD. However, genetic association studies of the APOE 4 allele and BPS in AD have produced conflicting findings. Methods This study investigates the association between APOE and neuropsychiatric symptoms in a large sample of clinically well-characterized subjects with probable AD (n=790) who were systematically evaluated using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) Behavioral Rating Scale for Dementia (BRSD). Results Our study found that hallucinations were significantly more likely to occur in subjects with no APOΕ4 alleles than in subjects with two Ε4 alleles (15% of subjects and 5% of subjects, respectively; p=.0066), whereas there was no association between the occurrence of delusions, aberrant motor behavior, or agitation and the number of Ε4 alleles. However, 94% of the subjects with hallucinations also had delusions (D+H). Conclusion These findings suggest that in AD the Ε4 allele is differentially associated with D+H but not delusions alone. This is consistent with the hypothesis that distinct psychotic subphenotypes may be associated with the APOE allele.

We tested the hypothesis that levels of CSF biomarkers associated with dementia and cognitive impairment are correlated with cognitive performance in non-demented Parkinson's disease (PD) patients. Twenty-two non-demented patients with PD underwent neuropsychological testing and lumbar puncture to collect CSF. We correlated performance scores on the Logical Memory (delayed), Category Fluency, Digit Symbol, and Trails B minus A with CSF concentrations of amyloid (A) β(42), total tau (t-tau), Aβ(42)/t-tau, and Brain Derived Neurotrophic Factor (BDNF). We observed significant associations between performance on the Digit Symbol test and CSF levels of Aβ(42), Aβ(42)/t-tau, and BDNF, and between performance on the Category Fluency (vegetable) and Aβ(42)/t-tau. While several of these associations were attenuated by adjusting for age, our results suggest that it may be possible to use CSF biomarkers to characterize pathophysiologic processes underlying even mild cognitive deficits in non-demented PD patients. [ABSTRACT FROM AUTHOR]

The C-Leg(R) (Otto Bock, Duderstadt, Germany) is a microprocessor-controlled prosthetic knee that may enhance amputee gait. This intrasubject randomized study compared the gait biomechanics of transfemoral amputees wearing the C-Leg with those wearing a common noncomputerized prosthesis, the Mauch SNS (Ossur, Reykjavik, Iceland). After subjects had a 3-month acclimation period with each prosthetic knee, typical gait biomechanical data were collected in a gait laboratory. At a controlled walking speed (CWS), peak swing phase knee-flexion angle decreased for the C-Leg group compared with the Mauch SNS group (55.2 degrees +/- 6.5 degrees vs 64.41 degrees +/- 5.8 degrees, respectively; p = 0.005); the C-Leg group was similar to control subjects' peak swing knee-flexion angle (56.0 degrees +/- 3.4 degrees). Stance knee-flexion moment increased for the C-Leg group compared with the Mauch SNS group (0.142 +/- 0.05 vs 0.067 +/- 0.07 N* m, respectively; p = 0.01), but remained significantly reduced compared with control subjects (0.477 +/- 0.1 N* m). Prosthetic limb step length at CWS was less for the C-Leg group compared with the Mauch SNS group (0.66 +/- 0.04 vs 0.70 +/- 0.06 m, respectively; p = 0.005), which resulted in increased symmetry between limbs for the C-Leg group. Subjects also walked faster with the C-Leg versus the Mauch SNS (1.30 +/- 0.1 vs 1.21 +/- 0.1 m/s, respectively; p = 0.004). The C-Leg prosthetic limb vertical ground reaction force decreased compared with the Mauch SNS (96.3 +/- 4.7 vs 100.3 +/- 7.5% body weight, respectively; p = 0.0092). [ABSTRACT FROM AUTHOR]

Aims: We conducted a proof-of-concept randomized controlled trial of the mu-opioid receptor antagonist, naltrexone, augmented with the alpha-1 adrenergic receptor antagonist, prazosin, for alcohol use disorder in veterans. We sought a signal that the naltrexone plus prazosin combination regimen would be superior to naltrexone alone., Methods: Thirty-one actively drinking veterans with alcohol use disorder were randomized 1:1:1:1 to naltrexone plus prazosin (NAL-PRAZ [n = 8]), naltrexone plus placebo (NAL-PLAC [n = 7]), prazosin plus placebo (PRAZ-PLAC [n = 7]), or placebo plus placebo (PLAC-PLAC [n = 9]) for 6 weeks. Prazosin was titrated over 2 weeks to a target dose of 4 mg QAM, 4 mg QPM, and 8 mg QHS. Naltrexone was administered at 50 mg QD. Primary outcomes were the Penn Alcohol Craving Scale (PACS), % drinking days (PDD), and % heavy drinking days (PHDD)., Results: In the NAL-PRAZ condition, % reductions from baseline for all three primary outcome measures exceeded 50% and were at least twice as large as % reductions in the NAL-PLAC condition (PACS: 57% vs. 26%; PDD: 51% vs. 22%; PHDD: 69% vs. 15%) and in the other two comparator conditions. Standardized effect sizes between NAL-PRAZ and NAL-PLAC for each primary outcome measure were >0.8. All but one participant assigned to the two prazosin containing conditions achieved the target prazosin dose of 16 mg/day and maintained that dose for the duration of the trial., Conclusion: These results suggest that prazosin augmentation of naltrexone enhances naltrexone benefit for alcohol use disorder. These results strengthen rationale for an adequately powered definitive randomized controlled trial., (Published by Oxford University Press on behalf of Medical Council on Alcohol 2024.)

Women veterans are exposed to high rates of trauma, including military sexual trauma (MST), and face unique barriers to posttraumatic stress disorder (PTSD) treatment. Telehealth interventions that are tailored to women veterans' unique lived experiences may improve treatment engagement and outcomes. It is important to ascertain how beneficial new telehealth interventions are in the context of different patient characteristics and trauma types, particularly for lower-intensity telehealth interventions (e.g., web-based programs or apps). This secondary analysis of a randomized clinical trial conducted in a sample of 102 women veterans examines predictors of treatment response to a self-management, telehealth intervention for PTSD: Delivery of Self Training and Education for Stressful Situations-Women Veterans (DESTRESS-WV). In the trial, women veterans with PTSD received either an online cognitive behavioral intervention with phone coaching, or phone monitoring alone. We examined associations between baseline patient characteristics (demographics, trauma types, and clinical symptoms) and treatment outcome at post-treatment, 3 months, and 6 months, focusing on the association between treatment outcome and MST. Our primary outcomes were changes in PTSD (PTSD Symptom Checklist, Version 5, PCL-5) and depression (8-item Patient Health Questionnaire, PHQ-8) in the full sample, adjusting for treatment condition. Women veterans who identified MST as the primary trauma for which they were seeking PTSD treatment experienced a nearly nine-point lesser improvement on the PCL-5 than those seeking PTSD treatment for other trauma types (e.g., childhood abuse, combat trauma; p  = .0073). Similar patterns were found for depression symptoms. To our knowledge, this is the first study to examine the association between trauma type and treatment outcomes within the context of a self-management, telehealth treatment for PTSD. While the study was not powered to examine differential treatment response for patient subgroups, our exploratory findings suggest that gaps remain in providing effective PTSD care for women veterans who experienced MST. Trial registration : The trial and analysis plan were preregistered in ClinicalTrials.gov (Identifier: NCT02917447)., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background and Objectives: Moderate-to-severe traumatic brain injuries (TBI) have been reported to increase the risk of Alzheimer disease (AD). Whether mild TBI (mTBI) in veterans confers a similar increased risk of AD is less known. This study investigated early AD changes using CSF biomarkers in veterans with blast mTBI., Methods: This was a cross-sectional case-control study of veterans with mTBI and non-mTBI veterans and civilians from 2 study sources. Blast-mTBI veterans had at least 1 war zone blast or combined blast/impact mTBI meeting Veterans Affairs (VA) and Department of Defense (DoD) criteria for mTBI. Non-mTBI participants had no lifetime history of TBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of the CSF. CSF biomarkers were measured using MesoScale Discovery assays for Aβ40 and Aβ42 and INNOTEST ELISAs for phosphorylated tau181 (p-tau181) and total tau (t-tau)., Results: Our sample comprised 51 participants with mTBI and 85 non-mTBI participants with mean (SD) ages 34.0 (10.1) and 33.5 years (8.9), respectively. All participants but 1 (99%) were male. Differences in CSF AD biomarkers between mTBI and non-mTBI groups were age dependent and most pronounced at older ages (omnibus test p ≤ 0.08). At age 50 years, the mTBI group had lower mean [95% CI] CSF Aβ42 and Aβ40 than the non-mTBI group by 154 [-12 to 319] and 1864 [610-3,118] pg/mL, respectively. By contrast, CSF p-tau181 and t-tau mean levels remained relatively constant with age in participants with mTBI, while tending to be higher at older ages for the non-mTBI group. The mTBI group also demonstrated poorer cognitive performance at older ages (omnibus p < 0.08): at age 50 years, the mean TMT-B time was higher by 34 seconds [10-58] and the mean CVLT-II short-delay recall was lower by 4.2 points [1.9-6.6]. Poorer verbal memory and verbal fluency performance were associated with lower CSF Aβ42 ( p ≤ 0.05) in older participants., Discussion: CSF Aβ levels decreased in middle-aged veterans with blast-related mTBI. These data suggest that chronic neuropathologic processes associated with blast mTBI share properties in common with pathogenic processes known to portend AD onset, thus raising concern that veterans with blast-related mTBI may develop a dementing disorder later in life.

Background: Selection of a foot is an important aspect of prosthetic prescription and vital to maximizing mobility and functional goals after lower limb amputation. Development of a standardized approach to soliciting user experiential preferences is needed to improve evaluation and comparison of prosthetic feet., Objective: To develop rating scales to assess prosthetic foot preference and to evaluate use of these scales in people with transtibial amputation after trialing different prosthetic feet., Design: Participant-blinded, repeated measures crossover trial., Setting: Veterans Affairs and Department of Defense Medical Centers, laboratory setting., Participants: Seventy-two male prosthesis users with unilateral transtibial amputation started, and 68 participants completed this study., Interventions: Participants trialed three mobility-level appropriate commercial prosthetic feet briefly in the laboratory., Main Outcome Measures: "Activity-specific" rating scales were developed to assess participants' ability with a given prosthetic foot to perform typical mobility activities (eg, walking at different speeds, on inclines, and stairs) and "global" scales to rate overall perceived energy required to walk, satisfaction, and willingness to regularly use the prosthetic foot. Foot preference was determined by comparing the rating scale scores, after laboratory testing., Results: The greatest within-participant differences in scores among feet were observed in the "incline" activity, where 57% ± 6% of participants reported 2+ point differences. There was a significant association (p < .05) between all "activity-specific" rating scores (except standing) and each "global" rating score., Conclusions: The standardized rating scales developed in this study could be used to assess prosthetic foot preference in both the research and clinical settings to guide prosthetic foot prescription for people with lower limb amputation capable of a range of mobility levels., (© 2023 American Academy of Physical Medicine and Rehabilitation.)

Background: Total ankle arthroplasty (TAA) continues to be investigated as a primary treatment for end-stage ankle arthritis. The objective of this study is to report mid- to long-term results of the Salto Talaris TAA using prospectively collected patient-reported outcomes and implant survival rates with 4- to 13-year follow-up., Methods: This was a retrospective study of prospectively collected data from 2 multicenter cohort studies from 3 centers. Three hundred fourteen subjects who received a Salto Talaris TAA from 2005 to 2015 were included in the study. Follow-up ranged 4-13 years following index procedure. Outcomes included 36-Item Short Form Health Survey (SF-36) mental and physical component summary scores, pain scores, and adverse events including additional surgeries, revision, or removal of components., Results: Significant improvements were seen in pain and physical function scores at 2-year follow-up and were generally maintained through most recent follow-up. The survival rate of the prosthesis was >95% (n = 30/32 at >10 years, n = 272/282 at 4.5-10 years). Thirteen patients (4.1%) underwent revision or removal of their prosthesis. Time to revision ranged from 2 months to 6.5 years following the index procedure. Twenty-two patients (7.0%) had additional surgery that did not involve revision or removal of components., Conclusion: Treatment of end-stage ankle arthritis with this implant provided patients with improved pain and functional outcome scores at mid- to long-term follow-up. The significant improvements reported at 2-4 years appeared to endure through the extended follow-up period., Level of Evidence: Level III, retrospective cohort study., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: J. Chris Coetzee, MD, reports royalties or licenses from Arthrex, DePuy Synthes, Smith & Nephew, and Responsive Arthroscopy; consulting fees from Medtronic, and Smith & Nephew; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Smith & Nephew and Arthrex; and stock or stock options from Paragon and Responsive Arthroscopy. ICMJE forms for all authors are available online.

Objective: Prior studies have found conflicting results when evaluating the association between rheumatoid arthritis (RA) disease activity and bone mineral density (BMD). Whether or not cumulative RA disease activity is associated with BMD remains unanswered., Methods: Data were from the University of California San Francisco RA Cohort from years 2006-2018. Those with BMD measures and at least two study visits prior to BMD measure were included in the study. The association between low cumulative disease activity, as measured by DAS28ESR, with the primary outcome of femoral neck BMD was assessed using multivariable linear regression. Sensitivity analyses were performed substituting CDAI for the disease activity measure as well as total hip and lumbar spine BMD as outcomes., Results: 161 participants with RA were studied. The cohort was 62.4 ± 10.2 years old and 88% female. Hispanic/Latino (N = 73, 45%) and Asian (N = 59, 37%) were the most common racial/ethnic groups in our cohort. Mean RA duration was 10.5 ± 7.3 years and 83% were ACPA positive. Low disease activity was independently associated with higher femoral neck BMD compared to the moderate/high disease activity group (β= 0.071 [95%CI: 0.021 to 0.122], p = 0.020). The relationship between low cumulative disease activity was similar when CDAI and other BMD sites were substituted in the multivariable models., Conclusion: Low cumulative disease activity as measured by DAS28ESR was associated with higher femoral neck BMD, independent of traditional osteoporosis risk factors (e.g., age, sex, BMI) in a unique RA cohort. Results were similar when evaluating cumulative low CDAI and other BMD sites., (Published by Elsevier Inc.)

Fall prevention is an important way to prevent fractures in person with osteoporosis. We developed and implemented a fall screening program in the context of routine osteoporosis care. This program was found to be feasible and showed that a significant proportion of persons with osteoporosis are at risk of falling., Purpose: Falls are the most common cause of fracture in persons with osteoporosis. However, osteoporosis care rarely includes assessment and prevention of falling. We thus sought to assess the feasibility of a fall screening and management program integrated into routine osteoporosis care., Methods: The program was developed and offered to patients with osteoporosis or osteopenia seen at an outpatient clinic between May 2015 and May 2016. Feasibility was measured by physical therapist time required to conduct screening and ease of integrating the screening program into the usual clinic workflow. Self-report responses and mobility testing were conducted to describe the fall and fracture risk profile of osteoporosis patients screened. Effects on fall-related care processes were assessed via chart abstraction of patient participation in fall prevention exercise., Results: Of the 154 clinic patients who presented for a clinic visit, 68% met screening criteria and completed in two thirds of persons. Screening was completed in a third of the time typically allotted for traditional PT evaluations and did not interfere with clinic workflow. Forty percent of those screened reported falling in the last year, and over half had two or more falls in the past year. Over half reported a balance or lower extremity impairment, and over 40% were below norms on one or more performance tests. Most patients who selected a group exercise fall prevention program completed all sessions while only a quarter completed either supervised or independent home-based programs., Conclusions: Implementation of a fall risk screening program in an outpatient osteoporosis clinic appears feasible. A substantial proportion of people with osteoporosis screened positive for being at risk of falling, justifying integration of fall prevention into routine osteoporosis care.

Past studies describe numerous endophenotypes associated with schizophrenia (SZ), but many endophenotypes may overlap in information they provide, and few studies have investigated the utility of a multivariate index to improve discrimination between SZ and healthy community comparison subjects (CCS). We investigated 16 endophenotypes from the first phase of the Consortium on the Genetics of Schizophrenia, a large, multi-site family study, to determine whether a subset could distinguish SZ probands and CCS just as well as using all 16. Participants included 345 SZ probands and 517 CCS with a valid measure for at least one endophenotype. We used both logistic regression and random forest models to choose a subset of endophenotypes, adjusting for age, gender, smoking status, site, parent education, and the reading subtest of the Wide Range Achievement Test. As a sensitivity analysis, we re-fit models using multiple imputations to determine the effect of missing values. We identified four important endophenotypes: antisaccade, Continuous Performance Test-Identical Pairs 3-digit version, California Verbal Learning Test, and emotion identification. The logistic regression model that used just these four endophenotypes produced essentially the same results as the model that used all 16 (84% vs. 85% accuracy). While a subset of endophenotypes cannot replace clinical diagnosis nor encompass the complexity of the disease, it can aid in the design of future endophenotypic and genetic studies by reducing study cost and subject burden, simplifying sample enrichment, and improving the statistical power of locating those genetic regions associated with schizophrenia that may be the easiest to identify initially., (Published by Elsevier B.V.)

Background: Ankle arthritis, like hip and knee arthritis, has a substantial impact on patient function. Understanding the functional limitations of ankle arthritis may help to stratify treatment strategies., Methods: We measured the preoperative demographic characteristics, physical function, and self-assessed function of patients with end-stage ankle arthritis and identified correlations among these metrics. Participants wore a StepWatch 3 Activity Monitor for two weeks and completed the Musculoskeletal Function Assessment and Short Form-36 surveys. Gait kinematics and kinetics were also measured as participants walked at a self-selected pace., Results: Musculoskeletal Function Assessment and Short Form-36 scores revealed reduced perceived function for patients with end-stage ankle arthritis compared with healthy controls. These patients also took fewer total steps per day, took fewer high-intensity steps, and chose to walk at a slower walking speed. Gait analysis revealed reduced ankle motion, peak ankle plantar flexor moment, peak ankle power absorbed, and peak ankle power generated for the affected limb compared with the unaffected limb. High-intensity step count was also correlated with both survey scores, walking speed, step length, peak ankle plantar flexor moment, and peak ankle power generated. Walking speed, step length, and ankle motion were correlated with peak ankle plantar flexor moment and power generated., Conclusions: Generally, patients with end-stage ankle arthritis have reduced physical and perceived function compared with healthy individuals. Additionally, high-intensity step count was a better indicator of physical and perceived function compared with total steps per day for this population.

Aims: In comparison with non-occlusive lesions, percutaneous coronary intervention (PCI) of chronic total occlusions (CTO) represents a greater challenge for the interventionalist, due to lower procedural success rates, relatively higher incidence of procedural complications and the increased rate of restenosis. The European Registry of Chronic Total Occlusion (ERCTO) was created with the goal of evaluating the real impact of CTO PCI in the European context, trying to analyse the rates of procedural success, technical information from the CTO procedures and patient outcome., Methods and Results: Data collection was carried out in 16 centres across Europe, starting from the beginning of January 2008. In two years of activity, a total of 1,914 patients with 1,983 CTO lesions were consecutively enrolled in the registry. Overall procedural success was achieved in 1,607 lesions (82.9%); anterograde procedures obtained higher procedural success of retrograde ones (83.2% versus 64.5%, p<0.001). Coronary perforation occurred more frequently in patients who underwent retrograde approach (4.7% versus 2.1%, p=0.04). Although no differences were observed in terms of 30-day major adverse cardiac events between anterograde and retrograde treated patients, a trend toward higher periprocedural non-Q-wave myocardial infarction was found in patients in which the retrograde approach was attempted (2.1% versus 1% p=0.08). Moreover, retrograde approach was related with longer procedural and fluoroscopy times (156.9±62.5 min vs. 98.2±52.8 min and 73.3±59.9 min vs. 38.2±43.9 min respectively, p<0.001) and higher contrast load administration (402±161 cc vs. 302±184 cc, p<0.001)., Conclusions: The first report of the ERCTO registry by the EuroCTO club shows a high procedural success rate obtained by expert European operators in a "real-world" consecutive series of patients, comparable with those reported by Japanese registries. The rate of observed procedural adverse events was low and similar to the non-CTO PCI series. In this registry, retrograde procedures were associated with extended fluoroscopy exposure and procedural time, increased contrast load administration as well as a higher incidence of coronary perforations. Such outcomes should become the standard of care that all centres undertaking CTO PCI should aspire to.

Psychosocial stress is thought to negatively impact fecundity, but human studies are confounded by variation in nutrition and lifestyle. Baboons offer a useful model to test the effect of prolonged mild stress on reproductive indicators in a controlled setting. Following relocation from social groups to solitary housing, a previously documented stressful event for nonhuman primates, daily urine samples, tumescence, and menstrual bleeding were monitored in twenty baboons (Papio sp.) for 120-150 days. Specimens were assayed for estrone conjugates (E1C), pregnanediol-3-glucuronide (PDG), follicle-stimulating hormone (FSH), and cortisol. Linear mixed effects models examined (1) the effects of stress on frequency of anovulation, hormone levels, tumescence and cycle length, and (2) the relationship of cortisol with reproductive indicators. Despite cortisol levels indicative of stress, anovulation was negligible (1% in 102 cycles). PDG, FSH, cycle length, and tumescence declined during the first four cycles, but began recovery by the fifth. Cortisol was negatively associated with FSH but not associated with PDG, E1C or tumescence. Ovulation, E1C, and luteal phase length were not affected. Tumescence tracked changes in FSH and PDG, and thus may be a useful indicator of stress on the reproductive axis. Elevated cortisol was associated with reduced FSH, supporting a model of cortisol action at the hypothalamus rather than the gonad. After four to five menstrual cycles the reproductive indicators began recovery, suggesting adjustment to new housing conditions. In conclusion, individual housing is stressful for captive baboons, as reflected by cortisol and reproductive indicators, although ovulation, a relatively direct proxy for fecundity, is unaffected., (Copyright © 2011 Wiley-Liss, Inc.)

C-reactive protein (CRP) is used as a biomarker of morbidity and mortality risk in studies of population health, and is essential to interpretation of several micronutrient biomarkers. There is thus a need for a robust high-sensitivity CRP (hsCRP) measurement method for large-scale, non-clinical studies. We developed an efficient, inexpensive assay suitable for quantifying CRP across the physiological range using any blood specimen type. The ELISA uses readily available monoclonal antibodies to measure CRP in serum, plasma, or dried blood spots (DBS) made from venous or capillary blood. Assay performance was evaluated by standard methods, including comparison with a previously described assay. Effects of specimen type were tested by measuring CRP in 52 matched serum, plasma, and venous and capillary dried blood spot specimens. Long- and short-term CRP stability were evaluated. Assessments of assay limits of detection, linearity, recovery, imprecision, and concordance with an established method (Pearson correlation=0.988, n=20) demonstrated the validity of the new assay. CRP measurements in serum, plasma, and DBS had Pearson correlations from 0.974 to 0.995, n=52, but CRP in serum was on average 1.6 times (SD 0.37) higher than in DBS. CRP was stable in frozen serum for up to 34 months, but DBS CRP declined quickly with exposure to ambient temperatures, and across long-term storage at -20°C. This hsCRP assay is a robust and inexpensive tool designed for use in large-scale population health research. Our results indicate that DBS CRP is less stable than previously reported., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Low-back pain is an important cause of secondary disability in transfemoral amputees. The primary aim of our study is to assess the differences in lumbar spine kinematics during gait between transfemoral amputees with and without low-back pain., Design: Lumbar spine kinematics in three planes were measured when the subjects walked in a motion analysis laboratory. Nine transfemoral amputees with low-back pain, eight transfemoral amputees without low-back pain, and six healthy, nonamputee subjects participated., Results: The Amputee Pain and Amputee No Pain groups were essentially the same in terms of all demographic and potentially confounding variable measures. Transfemoral amputees with low-back pain showed greater transverse plane rotational excursion in their lumbar spine during walking when compared with transfemoral amputees without low-back pain (P = 0.029; effect size = 1.03). There were no significant differences in sagittal or coronal plane lumbar spine excursions during walking between these two groups., Conclusions: Although our study design does not allow for proving causation, increased transverse plane rotation has been associated with intervertebral disc degeneration, suggesting that increased transverse plane rotation secondary to walking with a prosthetic limb may be a causative factor in the etiology of low-back pain in transfemoral amputees. Identifying differences in lumbar motion can lead to potential preventative and therapeutic intervention strategies.

Detailed characterization of estrogen dynamics during the transition to menopause is an important step toward understanding its potential implications for reproductive cancers developing in the transition years. We conducted a 5-year prospective study of endogenous levels of total and unopposed estrogen. Participants (n=108; ages 25-58 years) collected daily urine specimens for 6 months in each of 5 consecutive years. Specimens were assayed for estrone-3-glucuronide (E1G) and pregnanediol-3-glucuronide. Linear mixed-effects models were used to estimate exposure to total and unopposed estrogen by age and reproductive stage. Reproductive stage was estimated using menstrual cycle length variance. E1G mean area under the curve and mean E1G 5th and 95th percentiles represented total estrogen exposure. An algorithm identifying days of above-baseline E1G that coincided with the days of baseline pregnanediol-3-glucuronide was used to identify days of unopposed estrogen. Mean E1G area under the curve increased with age in the pretransition and early transition and decreased in the late transition. Ninety-fifth percentile E1G levels did not decline until after menopause, whereas 5th percentile levels declined from the early transition to the postmenopause. The number of days of unopposed estrogen was significantly higher during the transition compared with the pretransition. Given the length of time women spend in the transition, they are exposed to more total and unopposed estrogen than has been previously appreciated. Coupled with epidemiologic evidence on lifetime exposure to estrogen, these results suggest that variation in the amount of time spent in the transition may be an important risk factor for reproductive cancers.

Background: Retinol-binding protein (RBP) is accepted as a surrogate biochemical marker for retinol to determine vitamin A (VA) status. A recently developed enzyme immunoassay for RBP uses serum or whole blood stored as dried blood spots (DBS). However, the stability of RBP in DBS has not been examined., Methods: RBP stability was studied in a laboratory and in field conditions in northern Kenya. For the laboratory study, 63 DBS collected by finger prick and stored sealed in a plastic bag with desiccant were exposed to 1 of 5 time/storage-temperature treatments: (a) baseline, (b) 30 degrees C/7 days, (c) 30 degrees C/14 days, (d) 30 degrees C/28 days, and (e) 4 degrees C/38 days. Baseline RBP concentrations were compared to those obtained after the storage treatments. For the field study, 50 paired DBS and serum specimens were prepared from venous blood obtained in northern Kenya. DBS were stored in a sealed plastic bag with desiccant at ambient temperature (12 degrees C-28 degrees C) for 13-42 days, and sera were stored at -20 degrees C to -70 degrees C. Recovered RBP concentrations were compared with serum retinol for stability, correlation, sensitivity, and specificity., Results: RBP in DBS stored in the laboratory at 30 degrees C remained stable for 2-4 weeks, but specimens stored at 4 degrees C for 38 days produced values below baseline (P = 0.001). DBS stored under field conditions remained stable for 2-6 weeks, as demonstrated by good correlation with serum retinol, a result that suggests that RBP in DBS will have good sensitivity and specificity for predicting VA deficiency., Conclusion: RBP in DBS can withstand storage at a relatively high ambient temperature and thus facilitate accurate VA assessments in populations in locations where serum collection and storage are unfeasible.

Background: Excessive brain responsiveness to norepinephrine appears to contribute to post-traumatic stress disorder (PTSD), particularly at night. Prazosin, a brain active alpha-1 adrenergic receptor antagonist, significantly reduced trauma nightmares and sleep disturbance in 10 Vietnam War combat veterans in a previous placebo-controlled crossover study. The current parallel group trial in a larger sample of veterans evaluated prazosin effects on trauma nightmares, sleep quality, global clinical status, dream characteristics, and comorbid depression., Methods: Forty veterans (mean age 56 +/- 9) with chronic PTSD and distressing trauma nightmares and sleep disturbance were randomized to evening prazosin (13.3 +/- 3 mg/day) or placebo for 8 weeks., Results: In the evaluable sample (n = 34), primary outcome measures demonstrated that prazosin was significantly superior to placebo for reducing trauma nightmares and improving sleep quality and global clinical status with large effect sizes. Prazosin shifted dream characteristics from those typical of trauma-related nightmares toward those typical of normal dreams. Blood pressure changes from baseline to end study did not differ significantly between prazosin and placebo., Conclusions: Prazosin is an effective and well-tolerated treatment for trauma nightmares, sleep disturbance and global clinical status in veterans with chronic PTSD.

Background: Decreased cerebrospinal fluid (CSF) beta-amyloid 42 (A beta 42) concentration, but not A beta 40 concentration, is a biomarker for Alzheimer disease. This A beta 42 concentration decrease in CSF likely reflects precipitation of A beta 42 in amyloid plaques in brain parenchyma. This pathogenic plaque deposition begins years before the clinical expression of dementia in Alzheimer disease. Normal aging and the presence of the apolipoprotein E (APOE*4) allele are the most important known risk factors for Alzheimer disease., Objective: To estimate the interactive effects of normal aging and presence of the APOE*4 allele on CSF A beta 42 concentration in adults with normal cognition across the life span., Design: The CSF was collected in the morning after an overnight fast using Sprotte 24-g atraumatic spinal needles. The CSF A beta 42 and A beta 40 concentrations were measured in the 10th milliliter of CSF collected by sandwich enzyme-linked immunosorbent assay. The APOE genotype was determined by a restriction digest method. Subjects One hundred eighty-four community volunteers with normal cognition aged 21 to 88 years., Results: The CSF A beta 42, but not the A beta 40, concentration decreased significantly with age. There was a sharp decrease in CSF A beta 42 concentration beginning in the sixth decade in subjects with the APOE*4 allele. This age-associated decrease in CSF A beta 42 concentration was significantly and substantially greater in subjects with the APOE*4 allele compared with those without the APOE*4 allele., Conclusion: These CSF A beta 42 findings are consistent with acceleration by the APOE*4 allele of pathogenic A beta 42 brain deposition starting in later middle age in persons with normal cognition.

Background: We evaluate the performance of ovulation detection methods and present new approaches, including evaluation of methods for precision, combining multiple markers into a hierarchical system and using ovulation markers in intermittent sampling designs., Methods: With serum LH peak day as the 'gold standard' of ovulation, we estimated accuracy and precision of ovulation day algorithms using 30 ovulatory menstrual cycles with daily urinary and serum hormones and transvaginal ultrasound. Sensitivity and specificity for estimating the presence of ovulation were tested using visually assessed ovulatory (30) and anovulatory (22) cycles., Results: Sensitivity and specificity ranged from 70 to 100% for estimating presence of ovulation with twice-per-cycle, weekly, twice weekly, every-other-day and daily specimens. A combined hierarchical method estimated ovulation day using daily specimens within +/-2 days of the gold standard in 93% of cases. Accuracy of estimating ovulation day within +/-2 days using intermittent sampling ranged from 40% (weekly sampling) to 97% (every-other-day)., Conclusions: A combined hierarchical algorithm using precise and accurate markers allows maximal use of available data for efficient and objective identification of ovulation using daily specimens. In intermittent sampling designs, the presence and the timing of ovulation can be estimated with good sensitivity, specificity and accuracy.

Background: Plantar pressure measurements often are used as a tool to evaluate pathologic gait. Previous studies, often done at self-selected walking speeds, have used peak plantar pressure to try to predict ulcer formation, compare surgical outcomes, and evaluate orthotic device efficacy. However, the relationship between walking speed and plantar pressures at specific plantar regions has not been clearly defined., Methods: Twenty normal subjects walked on a treadmill at six speeds (0.75 to 2.00 m/s). In-shoe peak plantar pressure was measured at five plantar regions and compared across the range of speeds., Results: Walking speed affected peak plantar pressure differently at the five examined plantar regions. The hallux and heel regions had the highest pressures, which increased linearly with faster speeds. The central and medial forefoot pressures initially increased but plateaued at the faster speeds, while the lateral forefoot had the lowest overall peak pressures, which decreased at the faster walking speeds. Therefore, significant quadratic effects were found at the forefoot. Best-fit regression equations defined distinct pressure-speed relationships at each plantar region (p < 0.0001)., Conclusion: The effect of walking speed on peak plantar pressure varied with plantar region. To achieve more robust peak plantar pressure measurements, walking speed should be controlled. Determining the normal plantar function across a range of speeds can aid in the development of shoes and foot orthoses. The pressure-speed relationships presented in this study can be used as a comparative tool for evaluating the efficacy of clinical interventions for pressure reduction, especially when walking speed changes may confound the outcomes.

Background: Immobilization to limit muscle activity is a common therapeutic and posttreatment event. There are potential time and resource savings if a prefabricated boot can replace a custom applied cast. The purpose of this study was to determine if muscle activity reduction is similar using a fiberglass cast versus a prefabricated (Aircast FoamWalker) boot., Methods: Surface EMG data were recorded from the gastrocnemius, soleus, and peroneals of 12 normal adults while walking barefoot, in a fiberglass cast with a cast shoe (cast), and while wearing an Aircast FoamWalker (boot). Subjects walked at their self-selected speed for 10 trials in each condition, and the order of barefoot, cast, and boot was randomly assigned. The data were rectified, integrated across stance phase and normalized to a percent of each subject's barefoot mean integrated EMG (iEMG) value. For each muscle, a linear mixed-effects statistical model (subject by trial by condition) was utilized to determine if iEMG activity levels were reduced by immobilization compared to barefoot walking., Results: Activity for all muscles was significantly lower in the boot compared with barefoot (p <.05). The cast iEMG levels were significantly different from barefoot for the soleus and peroneals (p <.05). Gastrocnemius activity was significantly decreased in the boot when compared with the cast (p <.0001). The greater reduction in iEMG levels for the boot indicates that it is superior to a fiberglass cast in reducing gastrocnemius muscle activity during the stance phase of gait., Conclusions: The data show that a prefabricated boot is as effective as a custom applied cast in reducing soleus and peroneal muscle iEMG during stance phase. The boot was more effective in reducing gastrocnemius activity when compared to the cast., Clinical Relevance: This study suggests that a prefabricated boot may be used in place of a custom cast when the goal of treatment is to limit muscle activity of the leg.

Background: Specific gravity (SG) may perform as well as creatinine (CR) correction for adjusting urinary hormone concentrations, as well as offer some advantages. We compared the two methods and applied them to US and Bangladeshi specimens to evaluate their use in different populations., Methods: Pearson correlations between serum concentrations and SG, CR, and uncorrected urinary concentrations were compared using paired daily urine and serum specimens from one menstrual cycle from 30 US women. Corrected urinary estrone conjugate and pregnanediol glucuronide concentrations were compared with serum estradiol and progesterone. Urine specimens across one menstrual cycle from 13 Bangladeshi women were used to evaluate the applicability of both methods to a nonindustrialized population. Linear mixed-effects models were used to compare CR and SG values in the Bangladeshi vs US specimens., Results: There was no significant difference between SG-corrected vs serum and CR-corrected vs serum correlations for either assay. Usable CR results were obtained for all US specimens, but 37% of the Bangladeshi specimens were below the CR assay limit of detection. The Bangladeshi sample had significantly lower CR and higher inter- and intrasubject CR variability than the US sample., Conclusions: SG is a potentially useful alternative to CR correction for normalizing urinary steroid hormone concentrations, particularly in settings where CR values are highly variable or unusually low.

Background: Despite having lower average body mass indexes (BMIs) than do whites, Asians are at high risk of type 2 diabetes, possibly because of their greater central adiposity. The criteria for identifying individuals at risk of obesity-related conditions are usually not population specific., Objective: Our goal was to determine whether the National Heart, Lung, and Blood Institute (NHLBI) overweight and obesity guidelines are useful for identifying diabetes risk in Japanese Americans., Design: This was a prospective, cohort study of 466 nondiabetic Japanese Americans [age: 52.2 +/- 0.6 y; BMI (in kg/m(2)): 24.1 +/- 0.2; +/- SEM]. Diabetes status at a 5-y follow-up visit was assessed with an oral-glucose-tolerance test., Results: Among 240 subjects aged < or = 55 y, incident diabetes was strongly associated with overweight (BMI > or = 25) at baseline [relative risk (RR): 22.4; 95% CI: 2.7, 183; adjusted for age, sex, smoking, and family history] and weight gain of > 10 kg since the age of 20 y (adjusted RR: 4.5; 95% CI: 1.4, 14.5). NHLBI definitions of central obesity (waist circumference > or = 88 cm for women and > or = 102 cm for men) were unsuitable for this population because only 15 of 240 subjects met these criteria. A waist circumference greater than or equal to the third tertile was associated with diabetes (adjusted RR: 5.4; 95% CI: 1.7, 17.0). Among 226 subjects aged >55 y, incident diabetes was not associated with BMI, weight gain, or waist circumference., Conclusions: NHLBI definitions are useful for identifying overweight Japanese Americans aged < 55 y who are at high risk of diabetes. Although central adiposity is an important risk factor, the guidelines for waist circumference are insensitive predictors of diabetes risk in this population.

This is a review of research carried out in Japanese Americans that points towards possible approaches to prevention of type 2 diabetes mellitus. The natural history of type 2 diabetes usually includes both insulin resistance and beta-cell dysfunction. Insulin secretion may compensate for insulin resistance. Alternatively, enhanced insulin sensitivity may mask an insulin secretory defect. Epidemiological data support the view that in the vast majority of cases of type 2 diabetes, insulin resistance is essential to the pathogenesis of hyperglycemia. Increased diabetes prevalence as ethnic groups migrate to more urban or westernized regions has been attributed to increased occurrence of insulin resistance. Research among Japanese Americans in Seattle, Washington, showed a higher prevalence of type 2 diabetes than in Japan, which suggested that factors associated with 'westernization' might be playing a role in bringing out underlying susceptibility to diabetes. Our research has shown that these impressions were correct and that the abnormalities that characterize the metabolic syndrome play a significant role. Due to increased intra-abdominal fat deposition, Japanese Americans were likely to be 'metabolically obese' despite relatively normal BMI. A diet higher in animal fat and lower levels of physical activity were risk factors leading to increased intra-abdominal fat deposition, insulin resistance, and diabetes. Information from epidemiological studies such as these may be used to determine whether diabetes may be prevented through changes in lifestyle or application of specific therapies targeted towards identified metabolic abnormalities.