A Meta-Analysis of Brain-Derived Neurotrophic Factor Effects on Brain Volume in Schizophrenia: Genotype and Serum Levels.

AIM: The Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene has established pleiotropic effects on schizophrenia incidence and morphologic alterations in the illness. The effects of brain-derived neurotrophic factor (BDNF) on brain volume measurements are however mixed seeming to be less established for most brain regions. The current meta-analytic review examined (1) the association of the Val66Met SNP and brain volume alterations in schizophrenia by comparing Met allele carriers to Val/Val homozygotes and (2) the association of serum BDNF with brain volume measurements. METHOD: Studies included in the meta-analyses were identified through an electronic search of PubMed and PsycInfo (via EBSCO) for English language publications from January 2000 through December 2017. Included studies had conducted a genotyping procedure of Val66Met or obtained assays of serum BDNF and obtained brain volume data in patients with psychotic disorders. Nonhuman studies were excluded. RESULTS: Study 1 which included 52 comparisons of Met carriers and Val/Val homozygotes found evidence of lower right and left hippocampal volumes among Met allele carriers with schizophrenia. Frontal measurements, while also lower among Met carriers, did not achieve statistical significance. Study 2 which included 7 examinations of the correlation between serum BDNF and brain volume found significant associations between serum BDNF levels and right and left hippocampal volume with lower BDNF corresponding to lower volumes. DISCUSSION: The meta-analyses provided evidence of associations between brain volume alterations in schizophrenia and variations on the Val66Met SNP and serum BDNF. Given the limited number of studies, it remains unclear if BDNF effects are global or regionally specific.

Six-minute walk test is reliable and valid in spinal muscular atrophy.

INTRODUCTION: The Six-Minute Walk Test (6MWT) was adopted as a clinical outcome measure for ambulatory spinal muscular atrophy (SMA). However, a systematic review of measurement properties reported significant variation among chronic pediatric conditions. Our purpose was to assess the reliability/validity of the 6MWT in SMA. METHODS: Thirty participants performed assessments, including the 6MWT, strength, and function. Reproducibility was evaluated by intraclass correlation coefficients. Criterion/convergent validity were determined using Pearson correlation coefficients. RESULTS: Test-retest reliability was excellent. The 6MWT was associated positively with peak oxygen uptake, Hammersmith Functional Motor Scale Expanded (HFMSE), lower extremity manual muscle testing, knee flexion hand-held dynamometry, and inversely with 10-m walk/run. The 6MWT discriminates between disease severity, unlike the HFMSE. CONCLUSIONS: This study documents measurement properties of reproducibility, positive criterion validity, and convergent validity with established clinical assessments and reaffirms the value of the 6MWT as a pivotal outcome measure in SMA clinical trials. Muscle Nerve 54: 836-842, 2016.

Performance of the timed "up & go" test in spinal muscular atrophy.

INTRODUCTION: The timed "up & go" (TUG) test is a quick measure of balance and mobility. TUG scores correlate with clinical, functional, and strength assessment and decline linearly over time. Reliability and validity have not been tested in spinal muscular atrophy (SMA). METHODS: Fifteen ambulatory SMA participants performed TUG testing and strength, functional, and clinical assessments. Intraclass correlation coefficients quantified test-retest reliability. Convergent validity was determined using Pearson correlation coefficients. RESULTS: Test-retest reliability was excellent for all participants. TUG was associated significantly with total leg and knee flexor strength, as well as the Hammersmith Functional Motor Scale Expanded, the 10-meter walk/run, and 6-minute walk tests. TUG findings were not associated with knee extensor strength, pulmonary function, or fatigue. CONCLUSIONS: In SMA, the TUG test is easily administered, reliable, and correlates with established outcome measures. TUG testing is a potentially useful outcome measure for clinical trials and a measure of disability in ambulatory patients with SMA.

Effects of hydration during strontium exchange into nanoporous hydrogen niobium titanium silicate.

A Nb-substituted titanium silicate with the sitinakite (NbTS) topology was exchanged with Sr(2+) to determine the mechanisms and pathways of ion diffusion through this mixed polyhedral nanoporous framework. The refined structural models yield unit cell parameters and atomic positions of Sr(2+) and suggest that there was a two-step process during cation diffusion. The starting material of the exchange experiment was the H(+)-exchanged material, H(1.4)Nb(0.6)Ti(1.4)SiO(7)·1.9H(2)O, with space group P4(2)/mcm. In the beginning of the exchange process, Sr filled the 8-membered-ring channel near the 4(2) axis in the center. Once the Sr(2+) fractional occupancy reached approximate 0.11, Sr positions and extra-framework H(2)O molecules shifted away from the central 8-membered-ring toward the framework, and an increase in Sr hydration and framework bonding was observed. The new H(2)O positions resulted in a lowering of symmetry to the P ̅42m space group, and it is thought that the Sr migration served to enhance Sr(2+) ion diffusion capacity into the channels of NbTS since the exchange rate briefly accelerated after the 0.11 fractional occupancy level was passed. Exchange of Sr(2+) into the nanoporous material reached maximum fractional site occupancy of approximately 0.20 using a 10.0 mM SrCl(2) solution.

Contraceptive Use Among Women With End-Stage Kidney Disease on Dialysis in the United States.

RATIONALE & OBJECTIVE: Although end-stage kidney disease (ESKD) adversely affects fertility, pregnancies can occur among women receiving dialysis. ESKD increases the risk for adverse pregnancy outcomes and little is known about contraceptive use in women undergoing dialysis. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using the US Renal Data System covering January 1, 2005, through December 31, 2014, we evaluated for each calendar year women who for the entire year were aged 15 to 44 years, receiving dialysis, and with Medicare as the primary payer. PREDICTORS: Age, race/ethnicity, and calendar year of prevalent ESKD. OUTCOME: Contraceptive use. ANALYTIC APPROACH: We determined rates of contraceptive use and used multivariable logistic regression to identify factors associated with contraceptive use. RESULTS: The study cohort included 35,732 women and represented 115,713 person-years. The rate of contraceptive use was 5.30% of person-years (95% CI, 5.17%-5.42%). Overall, contraceptive use increased from 2005 to 2014 (4.21%; 95% CI, 3.84%-4.59% vs 6.54%, 95% CI, 6.10%-6.99%). Compared with women aged 25 to 29 years, contraceptive use was higher in women aged 15 to 24 years (OR, 1.30; 95% CI, 1.18-1.43) and lower in women aged 30 to 34 years (OR, 0.74; 95% CI, 0.68-0.81), 35 to 39 years (OR, 0.46; 95% CI, 0.42-0.50), and 40 to 44 years (OR, 0.30; 95% CI, 0.27-0.34). Compared with White women, contraceptive use was higher in Black (OR, 1.12; 95% CI, 1.02-1.24) and Native American women (OR, 1.60; 95% CI, 1.25-2.05). Women with ESKD due to glomerulonephritis had a higher likelihood of contraceptive use than women with ESKD due to diabetes (OR, 1.22; 95% CI, 1.06-1.42). Women receiving peritoneal dialysis had a lower likelihood of contraceptive use than women receiving hemodialysis (OR, 0.85; 95% CI, 0.78-0.93). Compared with women without predialysis nephrology care, contraceptive use was higher in women who received predialysis nephrology care for 12 or fewer months (OR, 1.22; 95% CI, 1.09-1.37) and more than 12 months (OR, 1.33; 95% CI, 1.20-1.47). LIMITATIONS: Retrospective design and use of administrative data. CONCLUSIONS: Among women with ESKD undergoing dialysis, contraceptive use remains low at 5.30%. Younger age, Native American and Black race/ethnicity, ESKD due to glomerulonephritis, hemodialysis, and predialysis nephrology care are associated with a higher likelihood of contraceptive use. The study highlights the importance of prepregnancy counseling for contraceptive use in women receiving dialysis.

Perceived Fatigue in Spinal Muscular Atrophy: A Pilot Study.

BACKGROUND: Fatigue is a common complaint in spinal muscular atrophy (SMA). Fatigability is well described in ambulatory SMA but the relationship to perceived fatigue has not been evaluated. Understanding this relationship has proven challenging for most disorders. OBJECTIVE: To assess the relationship of perceived fatigue to fatigability, function, and quality of life in SMA. METHODS: Thirty-two participants with SMA (21.9% type 2, 78.1% type 3) were recruited. Perceived fatigue and fatigability, function, and quality of life were assessed using standardized questionnaires and assessments. Associations were analyzed using Pearson correlation coefficients (p = 0.05). Also, the effects of age, type, and ambulatory status were determined on perceived fatigue. RESULTS: All SMA participants reported fatigue. Perceived fatigue was not associated with function, quality of life, or fatigability in ambulatory SMA patients. Neither age, type, nor ambulatory status influenced perceived fatigue. CONCLUSIONS: Perceived fatigue can be quantified in SMA. Interestingly, perceived fatigue did not correlate with fatigability or function, suggesting that cognitive, homeostatic, or psychologic factors may be more relevant as co-morbid factors. Clinical trials targeting perceived fatigue in SMA should focus on these patient-reported assessments. A multilevel approach is required to separate the various mechanisms involved in perceived fatigue.

Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

BACKGROUND: The benefits of exercise on long-term health and well-being are well established. The possible benefits of exercise in Spinal Muscular Atrophy (SMA) have not been explored in a controlled clinical trial format. OBJECTIVE: To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients. METHODS: Fourteen participants, ages 10-48 years, were randomized to control and exercise cohorts after a 1 month lead-in period. The exercise group received 6 months of intervention. Thereafter, both groups received the intervention for the remaining 12 months. Participants were monitored for a total of 19 months. Exercise included individualized home-based cycling and strengthening. The primary outcome measure was distance walked during the six-minute walk test (6MWT). Secondary outcomes included strength, function, exercise capacity, quality of life and fatigue. RESULTS: Twelve participants completed the first 7 months of the study, and 9 completed all 19 months. At baseline, the groups were similar on all clinical variables. There were no group changes at any time point in the 6MWT, fatigue, or function. Percent-predicted VO2 max improved 4.9% in all participants in 6 months (p = 0.036) (n = 10). CONCLUSION: Daily exercise is safe in ambulatory SMA and should be encouraged. We did not uncover any deleterious effects on strength, function, or fatigue. Our study documented a reduction in oxidative capacity and a blunted conditioning response to exercise possibly representing an important insight into underlying pathophysiological mechanisms. These findings also may be linked causally to mitochondrial depletion in SMA and warrant further study.

A Randomized, Controlled Clinical Trial of Exercise in Patients with Spinal Muscular Atrophy: Methods and Baseline Characteristics.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a recessively-inherited neuromuscular disease characterized by weakness and muscle atrophy. Although anecdotal benefits from exercise have been noted, and despite promising pre-clinical and pilot reports, the effect of exercise has not been addressed in a controlled trial in SMA. OBJECTIVE: To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients. METHODS/DESIGN: An evaluator-blinded, randomized, controlled trial of aerobic and strengthening exercise in 14 ambulatory SMA patients aged 8-50 years. Patients will be randomized to either the exercise or control arm after the 1 month lead in period. During the first 6-months, the exercise group will receive the intervention while the other group serves as a control. After those 6 months, both groups will receive the intervention. The last 6-months of the study are designed to mimic real-world conditions where all participants are encouraged to continue on their own. Participants will be monitored throughout this 19 month study and will have in-person visits every three months. The primary outcome measure is the change in the total distance walked over 6-months on the six minute walk test (6MWT). Secondary outcome measures include maximal oxygen uptake (VO2 max), functional and strength assessments, pulmonary function, fatigue, and quality of life. DISCUSSION: The result of this prospective, single blinded, randomized and controlled clinical trial of exercise on an established functional outcome measure will have impact on clinical practice by providing important guidance to clinical management of SMA patients.