Women's attitude towards prenatal screening for red blood cell antibodies, other than RhD

Background

Pregnancy-related low back pain is considered an important health problem and potentially leads to long-lasting pain and disability. Investigators draw particular attention to biomedical factors but there is growing evidence that psychosocial and social factors might be important. It prompted us to start a large cohort study (n = 7526) during pregnancy until one year after delivery and a nested randomized controlled intervention study in the Netherlands.

Methods

A randomized controlled trial (n = 126) nested within a cohort study, of brief self-management techniques versus usual care for treatment of women with persisting non-specific pregnancy-related low back pain three weeks after delivery. Women in the intervention group were referred to a participating physiotherapist. Women in the usual care group were free to choose physiotherapy, guidance by a general practitioner or no treatment. Follow up took place at 3 months, 6 months and one year after delivery. Outcomes included change in limitations in activities (RDQ), pain (VAS), severity of main complaints (MC), global feeling of recovery (GPE), impact on participation and autonomy (IPA), pain-related fear (TSK), SF-36, EuroQol and a cost diary. For the outcome measures, series of mixed models were considered. For the outcome variable global perceived effect (GPE) a logistic regression analysis is performed.

Results

Intention-to-treat outcomes showed a statistical significant better estimated regression coefficient RDQ -1.6 {-2.9;-0.5} associated with treatment, as well as better IPA subscale autonomy in self-care -1.0 {-1.9;-0.03} and TSK -2.4 {-3.8;-1.1} but were not clinical relevant over time. Average total costs in the intervention group were much lower than in usual care, primarily due to differences in utilization of sick leave but not statistically significant.

Conclusion

Brief self-management techniques applied in the first 3 months after delivery may be a more viable first-line approach but further research is needed to draw inference on costs and to determine whether no care is a better option in the long term.

Trial Registration

[ISRCTN08477490]     

Oral sodium phenylbutyrate therapy in homozygous beta thalassemia: a clinical trial

Butyrate analogues have been shown to increase fetal hemoglobin (HbF) production in vitro and in vivo. Sodium phenylbutyrate (SPB), an oral agent used to treat individuals with urea-cycle disorders, has been shown to increase HbF in nonanemic individuals and in individuals with sickle cell disease. We have treated eleven patients with homozygous beta thalassemia (three transfusion dependent) and one sickle-beta- thalassemia patient with 20 g/d (forty 500-mg tablets) of SPB for 41 to 460 days. All patients showed an increase in the percent of F reticulocytes associated with treatment, but only four patients responded by increasing their Hb levels by greater than 1 g/dL (mean increase, 2.1 g/dL; range, 1.2 to 2.8 g/dL). None of the transfusion- dependent thalassemia subjects responded. Increase in Hb was associated with an increase in red blood cell number (mean increase, 0.62 x 10(12)/L), and mean corpuscular volume (mean increase, 6 fL). Changes in percent HbF, absolute HbF levels, or alpha- to non-alpha-globin ratios as measured by levels of mRNA and globin protein in peripheral blood did not correlate with response to treatment. Response to treatment was not associated with the type of beta-globin mutation, but baseline erythropoietin levels of greater than 120 mU/mL was seen in all responders and only two of eight nonresponders to SPB. Compliance with treatment was greater than 90% as measured by pill counts. Side effects of the drug included weight gain and/or edema caused by increase salt load in 2/12, transient epigastric discomfort in 7/12, and abnormal body odor in 3/12 subjects. Two splenectomized patients who were not on prophylactic antibiotics developed sepsis while on treatment. We conclude that SPB increases Hb in some patients with thalassemia, but the precise mechanism of action is unknown.     

粉防己碱、颅通定对兔窦房结动作电位及豚鼠心室肌单细胞钙电流的协同作用

采用标准微电极技术和膜片钳记录技术，分别研究了粉防己碱（Ｔｅｔ）和颅通定（ｒｏｔｕｎｄｉｎｅ）对家兔窦房结动作电位及豚鼠心室肌单细胞钙电流的影响。结果表明：Ｔｅｔ１～２００μｍｏｌ·Ｌ－１，ｒｏｔｕｎｄｉｎｅ３～３００μｍｏｌ·Ｌ－１能浓度依赖性地降低兔窦房结动作电位的ＡＰＡ，Ｖｍａｘ和ＳＰ４，延长ＳＣＬ。Ｔｅｔ０．３μｍｏｌ·Ｌ－１与ｒｏｔｕｎｄｉｎｅ１μｍｏｌ·Ｌ－１合用亦有作用。在膜片钳实验中Ｔｅｔ０．１μｍｏｌ·Ｌ－１和ｒｏｔｕｎｄｉｎｅ１μｍｏｌ·Ｌ－１合用能有效抑制豚鼠心室肌单细胞钙电流，抑制率为１９．２％。提示，两种植物源性抗钙剂有良好的协同效果。     

Muscle fiber dysfunction contributes to weakness in inclusion body myositis

Atrophy and fatty infiltration are important causes of muscle weakness in inclusion body myositis (IBM). Muscle weakness can also be caused by reduced specific force; i.e. the amount of force generated per unit of residual muscle tissue. This study investigates in vivo specific force of the quadriceps and ex vivo specific force of single muscle fibers in patients with IBM. We included 8 participants with IBM and 12 healthy controls, who all underwent quantitative muscle testing, quantitative MRI of the quadriceps and paired muscle biopsies of the quadriceps and tibialis anterior. Single muscle fibers were isolated to measure muscle fiber specific force and contractile properties. Both in vivo quadriceps specific force and ex vivo muscle fiber specific force were reduced. Muscle fiber dysfunction was accompanied by reduced active stiffness, which reflects a decrease in the number of attached actin-myosin cross-bridges during activation. Myosin concentration was reduced in IBM fibers. Because reduced specific force contributes to muscle weakness in patients with IBM, therapeutic strategies that augment muscle fiber strength may provide benefit to patients with IBM.     

Biallelic variants in WARS2 encoding mitochondrial tryptophanyl‐tRNA synthase in six individuals with mitochondrial encephalopathy

Mitochondrial protein synthesis involves an intricate interplay between mitochondrial DNA encoded RNAs and nuclear DNA encoded proteins, such as ribosomal proteins and aminoacyl‐tRNA synthases. Eukaryotic cells contain 17 mitochondria‐specific aminoacyl‐tRNA synthases. WARS2 encodes mitochondrial tryptophanyl‐tRNA synthase (mtTrpRS), a homodimeric class Ic enzyme (mitochondrial tryptophan‐tRNA ligase; EC 6.1.1.2). Here, we report six individuals from five families presenting with either severe neonatal onset lactic acidosis, encephalomyopathy and early death or a later onset, more attenuated course of disease with predominating intellectual disability. Respiratory chain enzymes were usually normal in muscle and fibroblasts, while a severe combined respiratory chain deficiency was found in the liver of a severely affected individual. Exome sequencing revealed rare biallelic variants in WARS2 in all affected individuals. An increase of uncharged mitochondrial tRNA^Trp and a decrease of mtTrpRS protein content were found in fibroblasts of affected individuals. We hereby define the clinical, neuroradiological, and metabolic phenotype of WARS2 defects. This confidently implicates that mutations in WARS2 cause mitochondrial disease with a broad spectrum of clinical presentation.     

ORIGINAL ARTICLE: Association between 25‐hydroxyvitamin D,somatic muscle weakness and falls risk in end‐stage renal failure

Objective Suboptimal levels of 25‐hydroxyvitamin D (25OHD) are common in haemodialysis patients (Chronic Kidney disease‐5D: CKD‐5D) and may be associated with reduced muscle strength and increased falls risk. We tested the hypothesis that 25OHD levels may be independently associated with falls risk in CKD‐5D. Background Supplementation with calcium and cholecalciferol reduces hip and other nonvertebral fractures in elderly individuals, and this effect may in part be attributable to reduction in falls frequency. The relationship between 25OHD and falls risk has not been investigated in CKD‐5D. Design and Patients This is a cross‐sectional study of 25 CKD‐5D patients with predialysis 25OHD, 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and intact parathyroid hormone (iPTH) measurement. Falls risk was assessed by quadriceps muscle strength, FallsScreen^© test (FST), Berg Balance Scale (BBS), timed ‘up and go’ (TUG) test, Modified Barthel Index (MBI) and Falls Efficacy Scale (FES). Results Mean age was 69·8 ± 12·1 years, and median time on dialysis was 3·1 years. Median 25OHD level was 55·3 nmol/l (range 20·8–125·8 nmol/l). Muscle strength was significantly positively correlated with 25OHD (P = 0·024) but not with 1,25(OH)₂D (P = 0·477) or PTH (P = 0·461). Statistically significant correlation between 25OHD levels and FST (P = 0·028) plus MBI (P = 0·0046) was noted. No significant correlation was detected between falls risk and 1,25(OH)₂D or PTH. Conclusions Suboptimal levels of 25OHD in CKD‐5D are associated with reduced quadriceps muscle strength and increased falls risk. 25OHD may be more important than the active renal metabolite 1,25(OH)₂D for muscle strength with implications for vitamin D choice and goals of supplementation. Further investigation is required to examine effectiveness of calciferol supplementation on the incidence of falls in CKD‐5D.     

Cryopreservation of single human spermatozoa

A procedure is described that allows cryopreservation and efficient post-thaw recovery of either a single or a small group of human spermatozoa. This is achieved by injecting them into cell-free human, mouse or hamster zonae pellucidae before the addition of cryoprotectant. The method involves a combination of physical micromanipulation procedures and glycerol-mediated cryoprotection. Zonae were tracked by positioning them in straws between two small air bubbles prior to freezing. Spermatozoa from poor specimens were cryopreserved and their fertilizing ability after thawing was compared with that of fresh spermatozoa from fertile men. Human eggs used for fertilization testing were either 1 day old or in-vitro matured. Only 2% of the frozen zonae were lost and >75% of spermatozoa cryopreserved in this manner were recovered and prepared for intracytoplasmic sperm injection. The feasibility of cryopreserving a single spermatozoon was assessed. Fifteen motile spermatozoa were frozen in 15 zonae, of which 14 were recovered after thawing. Ten were injected into spare eggs, of which eight became fertilized. Spermatozoa recovered mechanically from human zonae fertilized the same proportion of oocytes as fresh fertile control spermatozoa. The recovery and fertilization rates with spermatozoa frozen in animal zonae were 87 and 78% respectively. The fertilization rate was marginally higher (P < 0.05) than that for spermatozoa frozen in human zonae, perhaps because the latter may have acrosome reacted more frequently. The zona pellucida appears to be an ideally suited sterile vehicle for storage of single spermatozoa.