Splinting or surgery for carpal tunnel syndrome? Design of a randomized controlled trial [ISRCTN18853827]

Background  

Carpal tunnel syndrome is a common disorder, which can be treated with surgery or conservative options. However, there is insufficient evidence and no consensus among physicians with regard to the preferred treatment for carpal tunnel syndrome. Therefore, a randomized controlled trial is conducted to compare the short- and long-term efficacy of surgery and splinting in patients with carpal tunnel syndrome. An attempt is also made to avoid the (methodological) limitations encountered in earlier trials on the efficacy of various treatment options for carpal tunnel syndrome.     

Food environment and diabetes mellitus in South Asia: A geospatial analysis of health outcome data

BackgroundThe global epidemic of type 2 diabetes mellitus (T2DM) renders its prevention a major public health priority. A key risk factor of diabetes is obesity and poor diets. Food environments have been found to influence people’s diets and obesity, positing they may play a role in the prevalence of diabetes. Yet, there is scant evidence on the role they may play in the context of low- and middle-income countries (LMICs). We examined the associations of food environments on T2DM among adults and its heterogeneity by income and sex.Methods and findingsWe linked individual health outcome data of 12,167 individuals from a network of health surveillance sites (the South Asia Biobank) to the density and proximity of food outlets geolocated around their homes from environment mapping survey data collected between 2018 and 2020 in Bangladesh and Sri Lanka. Density was defined as share of food outlets within 300 m from study participant’s home, and proximity was defined as having at least 1 outlet within 100 m from home. The outcome variables include fasting blood glucose level, high blood glucose, and self-reported diagnosed diabetes. Control variables included demographics, socioeconomic status (SES), health status, healthcare utilization, and physical activities. Data were analyzed in ArcMap 10.3 and STATA 15.1. A higher share of fast-food restaurants (FFR) was associated with a 9.21 mg/dl blood glucose increase (95% CI: 0.17, 18.24; p < 0.05). Having at least 1 FFR in the proximity was associated with 2.14 mg/dl blood glucose increase (CI: 0.55, 3.72; p < 0.01). A 1% increase in the share of FFR near an individual’s home was associated with 8% increase in the probability of being clinically diagnosed as a diabetic (average marginal effects (AMEs): 0.08; CI: 0.02, 0.14; p < 0.05). Having at least 1 FFR near home was associated with 16% (odds ratio [OR]: 1.16; CI: 1.01, 1.33; p < 0.05) and 19% (OR: 1.19; CI: 1.03, 1.38; p < 0.05) increases in the odds of higher blood glucose levels and diagnosed diabetes, respectively. The positive association between FFR density and blood glucose level was stronger among women than men, but the association between FFR proximity and blood glucose level was stronger among men as well as among those with higher incomes. One of the study’s key limitations is that we measured exposure to food environments around residency geolocation; however, participants may source their meals elsewhere.ConclusionsOur results suggest that the exposure to fast-food outlets may have a detrimental impact on the risk of T2DM, especially among females and higher-income earners. Policies should target changes in the food environments to promote better diets and prevent T2DM.

Dian Kusuma and colleagues investigate the associations between exposure to the density and proximity of healthy and unhealthy food outlets and diabetes in Bangladesh and Sri Lanka.     

Microsatellite evolution in congeneric mammals: domestic and bighorn sheep

We compared genotypes at eight (AC)n microsatellite loci in domestic sheep (Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The domestic sheep had greater genetic variation, higher allele-size variances, and larger allele sizes than the wild sheep. Accumulating evidence from higher taxonomic comparisons shows that these parameters are biased if microsatellite loci are selected in one taxon and used in another. Our results demonstrate similar biases between congeneric species. We compared standard measures of genetic variation, differentiation, and distance within and between species (H, D, FST) to newer measures based on allele-size variance (SW, SB, RST). The size-based distances better detected species-level divergence, but standard measures better distinguished allopatric populations. Empirical calibration of these measures at the subspecies level is needed to establish their useful ranges.      

Nucleotide sequence of the Acinetobacter calcoaceticus trpGDC gene cluster

A plasmid library of Acinetobacter calcoaceticus HindIII fragments was constructed, and clones that complemented an Escherichia coli pabA mutant were selected. Plasmids containing a 3.9-kb fragment of A. calcoaceticus DNA that also complemented E. coli trpD and trpC-(trpF+) mutants were obtained. We infer that complementation of E. coli pabA mutants was the result of the expression of the amphibolic anthranilate- synthase/p-aminobenzoate-synthase glutamine-amidotransferase gene and that the plasmid insert carried the entire trpGDC gene cluster. In E. coli minicells, the plasmid insert directed the synthesis of polypeptides of 44,000, 33,000, and 20,000 daltons, molecular masses that are consistent with the reported molecular masses of phosphoribosylanthranilate transferase, indoleglycerol-phosphate synthase, and anthranilate-synthase component II, respectively. A 3,105- bp nucleotide sequence was determined. Comparison of the A. calcoaceticus trpGDC sequences with other known trp gene sequences has allowed insight into (1) the evolution of the amphibolic trpG gene, (2) varied strategies for coordinate expression of trp genes, and (3) mechanisms of gene fusions in the trp operon.      

Distributions of two recently inserted long interspersed elements of the L1 repetitive family at the Alb and beta h3 loci in wild mice populations

The presence of the L1 sequences, L1Md4 next to the pseudogene beta h3 and I12 found in the twelfth intron of the albumin gene, in certain strains of laboratory mice but not of others has led to the suggestion that these sequences were recent insertions into the Mus mus domesticus genome. To be sure that they are really recent insertions and not relics of an ancestral chromosome, we investigated the presence or absence of these sequences in populations of wild mice belonging to the semispecies M. m. domesticus and M. m. musculus as well as in other species of the genus Mus and in related murids. The sequence I12 in the albumin gene was found in 34% of the chromosomes of the wild mice belonging to M. m. domesticus and to a lesser extent (6%) in M. m. musculus. Of 114 M. m. domesticus chromosomes, L1Md4 was found in only nine, seven of which came from the same locality. Its presence was associated with the haplotype Hbbp, which is relatively rare in European populations of M. musculus. Since there was no evidence for the presence of these two L1 sequences in more distantly related species, we conclude that they are recent insertions in the M. musculus genome.      

Evidence for a multiple function of the alcohol dehydrogenase allozyme ADH71k of Drosophila melanogaster

Alcohol dehydrogenase of Drosophila melanogaster catalyzes the oxidation of many primary and secondary alcohols. We show that sarcosine, choline and dihydroorotate are substrates of ADH in vitro. The first two substrates are regular substrates of the choline shunt, and the latter of the de novo pyrimidine synthesis. Differences in oxidative ability towards sarcosine and dihydroorotate between two ADH allozymes, ADH71k and ADHF, are observed. The catalytic activity of ADH71k towards sarcosine and dihydroorotate might be responsible for its allelic fixation in Notch8 mutant stocks, in which Notch females have a decreased level of the regular enzymes for these substrates. Their oxidation by ADH71k might act as a bypass, which restores at least part of the decreased activity of enzymes encoded by the Notch locus.     

Protein and m-RNA expression of farnesyl-transferases,RhoA and RhoB in rat liver hepatocytes: action of perillyl alcohol and vitamin A <Emphasis Type="BoldItalic">in vivo</Emphasis>.

Summary We analysed the action, in rats in vivo, of the protein isoprenylation inhibitor perillyl alcohol (POH) and that of vitamin A, alone or in association, on m-RNA and protein expression of farnesyltransferases (FTases α and β subunits) and their protein substrates RhoA and RhoB, in isolated hepatocytes. Combined administration of POH and vitamin A induced a sharp decrease in FTase α protein after 96 h, suggesting an involvement not only of farnesyltransferases but also of geranylgeranyltransferases, which share the FTase α protein. FTase β protein did not decrease. POH plus vitamin A, in contrast with POH or vitamin A alone, induced a decrease in RhoB protein, probably because of different cleavages. No modification was observed in RhoA protein. Vitamin A alone increased RhoB m-RNA and protein expression. As one of the functions of RhoB is cell polarisation, these data support our previous hypothesis of a polarised transport of vitamin A from hepatocytes to hepatic stellate cells. As the behaviours of m-RNAs and proteins in this study were often different, cytoplasmic metabolic pathways must be considered for the parameters studied. The behaviour of Rho B, which is thought to have an antioncogene function, is discussed in view of its isoprenylated forms in the membranes. These preliminary findings stress the need, when studying the association of two isoprenoids in cancer therapy, to consider normal as well as tumour-bearing animals.     

The mechanism of copper uptake mediated by human CTR1: a mutational analysis

Cellular copper uptake is a prerequisite for the biosynthesis of many copper-dependent enzymes; disruption of copper uptake results in embryonic lethality. In humans, copper is transported into cells by hCTR1, a membrane protein, composed of 190 amino acids with only three trans-membrane segments. To provide insight into the mechanism of this unusual transporter, we characterized the functional properties of various hCTR1 mutants stably expressed in Sf9 cells. Most single amino acid substitutions involving charged and potential copper-coordinating residues have some influence on the V(max) and K(m) values for copper uptake but do not greatly alter hCTR1-mediated copper transport. However, there were two notable exceptions. Replacement of Tyr(156) with Ala greatly reduced the maximal transport rate without effect on the K(m) value for copper. Also, replacement of His(139) in the second trans-membrane segment with Arg caused a dramatic increase in the rate of copper uptake and a large increase in the K(m) value for copper. This effect was not seen with an Ala replacement, pointing to the role of a positive charge in modulating copper exit from the pathway. Truncated mutants demonstrated that the deletion of a large portion of the N-terminal domain only slightly decreased the apparent K(m) value for copper and decreased the rate of transport. Similar effects were observed with the removal of the last 11 C-terminal residues. The results suggested that the N and C termini, although nonessential for transport, may have an important role in facilitating the delivery of copper to and retrieving copper from, respectively, the translocation pathway. A model of how hCTR1 mediates copper entry into cells was proposed that included a rate-limiting site in the pore close to the intracellular exit.     

Stable plasma membrane levels of hCTR1 mediate cellular copper uptake

The human copper transporter 1 (hCtr1), when heterologously overexpressed in insect cells, mediates saturable Cu uptake. In mammalian expression systems, a rapid Cu-dependent internalization of hCtr1 has been reported in cells that overexpress epitope-tagged hCtr1 when exposed to Cu in the external medium. This finding led to the suggestion that such internalization may be a step in the hCtr1 transmembrane Cu transport mechanism. We have demonstrated that preincubation in Cu-containing media of sf9 cells stably expressing hCtr1 has no effect on the initial rate of Cu transport. Furthermore, Western blot analyses of fractionated sf9 cell membranes show no evidence of a regulatory Cu-dependent internalization from the plasma membrane. In similar studies on human embryonic kidney (HEK) 293 cells, we showed that incubation with Cu does not alter the initial rate of Cu uptake mediated by endogenous levels of hCtr1 compared with untreated cells. Confirmation that hCtr1 mediates this transport is provided by specific small interfering RNA-dependent decreases in hCtr1 protein levels and in Cu transport rates. Western blot analysis and confocal microscopy of human embryonic kidney 293 cells showed that the majority of hCtr1 protein is localized at the plasma membrane and no significant internalization is detected upon Cu treatment. We concluded that internalization of hCtr1 is not a required step in the transport pathway; we suggest that oligomeric hCtr1 acts as a conventional transporter providing a permeation pathway for Cu through the membrane and that internalization of endogenous hCtr1 in response to elevated extracellular Cu levels does not play a significant regulatory role in Cu homeostasis.