Adherence to resistance training and hypocaloric diet among persons near retirement age - A secondary data analysis of three randomized controlled trials.

OBJECTIVES: Adherence to lifestyle interventions is crucial for the treatment of obesity. However, there is little research about adherence to lifestyle interventions in persons around retirement age. The objectives of this study are (1) to identify factors associated with the adherence to resistance training and a hypocaloric diet and (2) to describe the association between adherence and changes in body composition outcome parameters. DESIGN: This secondary data analysis included three randomized controlled trials. SETTING & PARTICIPANTS: The inclusion criteria of the participants were an age of 55-75 years, a BMI ≥ 25 kg/m2 and receiving both a hypocaloric diet and resistance training. All participants were residing in the community. MEASUREMENTS: Adherence to hypocaloric diet was measured through the mean dietary intake on the basis of a 3-day dietary record. If the participant consumed at least 600 kcal less than the individual caloric requirements, they were considered adherent. Adherence to resistance training was achieved if ≥67% of the recommended training sessions were attended over the course of the study periods. RESULTS: 232 participants were included, 47.0% female, mean age 64.0 (±5.5) years. 80.2% adhered to resistance training and 51.3% adhered to a hypocaloric diet. Older age (Beta 0.41; 95% CI 0.05, 0.78; p = 0.028) and male sex (Beta 7.7; 95% CI 3.6, 11; p < 0.001) were associated with higher resistance training adherence. A higher BMI at baseline (Beta 6.4; 95% CI 3.6, 9.2; p < 0.001) and male sex (Beta 65; 95% CI 41, 88; p < 0.001) were associated with higher adherence to hypocaloric diet. CONCLUSION: We identified several associated factors (sex, age and BMI at baseline) that should be considered to promote adherence in future lifestyle intervention studies in persons around retirement age. We recommend including behavior change techniques in lifestyle interventions and consider sex-specific interventions to improve the adherence of women.

A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element.

The Charcot-Marie Tooth disease type 1A (CMT1A) duplication and hereditary neuropathy with liability to pressure palsies (HNPP) deletion are reciprocal products of an unequal crossing-over event between misaligned flanking CMT1A-REP repeats. The molecular aetiology of this apparently homologous recombination event was examined by sequencing the crossover region. Through the detection of novel junction fragments from the recombinant CMT1A-REPs in both CMT1A and HNPP patients, a 1.7-kb recombination hotspot within the approximately 30-kb CMT1A-REPs was identified. This hotspot is 98% identical between CMT1A-REPs indicating that sequence identity is not likely the sole factor involved in promoting crossover events. Sequence analysis revealed a mariner transposon-like element (MITE) near the hotspot which we hypothesize could mediate strand exchange events via cleavage by a transposase at or near the 3' end of the element.

The taxonomic composition of the donor intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in therapy refractory ulcerative colitis.

BACKGROUND: Faecal microbiota transplantation is an experimental approach for the treatment of patients with ulcerative colitis. Although there is growing evidence that faecal microbiota transplantation is effective in this disease, factors affecting its response are unknown. AIMS: To establish a faecal microbiota transplantation treatment protocol in ulcerative colitis patients, and to investigate which patient or donor factors are responsible for the treatment success. METHODS: This is an open controlled trial of repeated faecal microbiota transplantation after antibiotic pre-treatment (FMT-group, n = 17) vs antibiotic pre-treatment only (AB-group, n = 10) in 27 therapy refractory ulcerative colitis patients over 90 days. Faecal samples of donors and patients were analysed by 16SrRNA gene-based microbiota analysis. RESULTS: In the FMT-group, 10/17 (59%) of patients showed a response and 4/17 (24%) a remission to faecal microbiota transplantation. Response to faecal microbiota transplantation was mainly influenced by the taxonomic composition of the donor's microbiota. Stool of donors with a high bacterial richness (observed species remission 946 ± 93 vs no response 797 ± 181 at 15367 rps) and a high relative abundance of Akkermansia muciniphila (3.3 ± 3.1% vs 0.1 ± 0.2%), unclassified Ruminococcaceae (13.8 ± 5.0% vs 7.5 ± 3.7%), and Ruminococcus spp. (4.9 ± 3.5% vs 1.0 ± 0.7%) were more likely to induce remission. In contrast antibiotic treatment alone (AB-group) was poorly tolerated, probably because of a sustained decrease of intestinal microbial richness. CONCLUSIONS: The taxonomic composition of the donor's intestinal microbiota is a major factor influencing the efficacy of faecal microbiota transplantation in ulcerative colitis patients. The design of specific microbial preparation might lead to new treatments for ulcerative colitis.

Renin angiotensinogen system gene polymorphisms and essential hypertension among people of West African descent: a systematic review.

This systematic review investigates the high level of hypertension found among urban dwellers in West Africa and in the West African Diaspora in the Americas in relation to variants within the genes encoding the renin angiotensinogen system. For comparison, the results from the Caucasian populations are reviewed as well. Through a PubMed search, 1252 articles were identified and 28 eligible articles assessed in detail of which 13 included a Caucasian population. The results suggest that among the people of West African descent and among the people of Caucasian descent, hypertension is partly related to a number of single nucleotide polymorphisms (SNPs) and haplotypes in the renin gene, the angiotensinogen gene, the angiotensinogen I-converting enzyme gene and the angiotensinogen II type 1 receptor gene. Concordance between these two populations was found for some SNPs. However, for others, it was found that the SNPs associating with hypertension and the disease allele frequencies differed between these populations. Understanding the importance of these variants in a modern life setting may assist our understanding of the increased risk of developing hypertension among West Africans. Because of inconsistency in the results, low statistical power and methodological differences between studies, these results can only be taken as indicative of an association.

Charcot-Marie-Tooth disease and related inherited neuropathies.

Charcot-Marie-Tooth disease (CMT) was initially described more than 100 years ago by Charcot, Marie, and Tooth. It was only recently, however, that molecular genetic studies of CMT have uncovered the underlying causes of most forms of the diseases. Most cases of CMT1 are associated with a 1.5-Mb tandem duplication in 17p11.2-p12 that encompasses the PMP22 gene. Although many genes may exist in this large duplicated region, PMP22 appears to be the major dosage-sensitive gene. CMT1A is the first autosomal dominant disease associated with a gene dosage effect due to an inherited DNA rearrangement. There is no mutant gene, but instead the disease phenotype results from having 3 copies of a normal gene. Furthermore, these findings suggest that therapeutic intervention in CMT1A duplication patients may be possible by normalizing the amount of PMP22 mRNA levels. Alternatively, CMT1A can be caused by mutations in the PMP22 gene. Other forms of CMT are associated with mutations in the MPZ (CMT1B) and Cx32 (CMTX) genes. Thus, mutations in different genes can cause similar CMT phenotypes. The related but more severe neuropathy, Dejerine-Sottas syndrome (DSS), can also be caused by mutations in the PMP22 and MPZ genes. All 3 genes thus far identified by CMT researchers appear to play an important role in the myelin formation or maintenance of peripheral nerves. CMT1A, CMT1B, CMTX, hereditary neuropathy with liability to pressure palsies (HNPP), and DSS have been called myelin disorders or "myelino-pathies." Other demyelinating forms, CMT1C and CMT-AR, may be caused by mutations of not yet identified myelin genes expressed in Schwann cells. The clinically distinct disease HNPP is caused by a 1.5-Mb deletion in 17p11.2-p12, which spans the same region duplicated in most CMT1A patients. Underexpression of the PMP22 gene causes HNPP just as overexpression of PMP22 causes CMT1A. Thus, 2 different phenotypes can be caused by dosage variations of the same gene. It is apparent that the CMT1A duplication and HNPP deletion are the reciprocal products of a recombination event during meiosis mediated through the CMT1A-REPs. CMT1A and HNPP could be thought of as a "genomic disease" more than single gene disorders. Other genetic disorders may also prove to arise from recombination events mediated by specific chromosomal structural features of the human genome (102). Further studies on the recombination mechanism of CMT and HNPP might reveal the causes of site specific homologous recombination in the human genome. The discovery of the PMP22 gene in the 1.5-Mb CMT1A duplication/HNPP deletion critical region also suggests that the clinical phenotype of chromosome aneuploid syndromes may result from the effect of a small subset of dosage-sensitive genes mapping within the region of aneuploidy. The understanding of the molecular basis of CMT1 and related disorders has allowed accurate DNA diagnosis and genetic counseling of inherited peripheral neuropathies and will make it possible to develop rational strategies for therapy. As several loci for CMT2 have been identified, the genes responsible for CMT2 will most likely be disclosed using positional cloning and candidate gene approaches in the near future.

Antiulcer agents. 4-substituted 2-guanidinothiazoles: reversible, competitive, and selective inhibitors of gastric H+,K(+)-ATPase.

A series of 4-substituted 2-guanidinothiazoles has been found to inhibit the gastric proton-pump enzyme H+,K(+)-ATPase. In general, these compounds were reversible inhibitors of canine gastric H+,K(+)-ATPase, competitive at the K+ site, and selective relative to canine renal Na+,K(+)-ATPase. Structure-activity relationship (SAR) studies on this series revealed no general replacement for the guanidinothiazole. On the other hand, use of pyrrolyl, phenyl, and indolyl groups as the C-4 substituent yielded active compounds. Extensive studies of substitution patterns on these 4-aryl groups led to more active compounds, but no consistent SAR became apparent. Monosubstitution of the guanidine and substitution of the thiazole at C-5 both often led to increased activity, but combining these changes generated compounds less active than the parents. Despite 100-fold improvement in in vitro inhibitory potency, only a 3-fold increase in gastric antisecretory activity in rats was observed for these agents.

Discovery of the hemifumarate and (alpha-L-alanyloxy)methyl ether as prodrugs of an antirheumatic oxindole: prodrugs for the enolic OH group.

Ether, ester, and carbonate derivatives of the antirheumatic oxindole 1 were prepared and screened as potential prodrugs of 1. This effort led to the discovery of the (alpha-L-alanyloxy)-methyl ether and hemifumarate derivatives of 1 which deliver the drug efficiently into the circulation of test animals, are stable in the solid state, and possess good stability in solution at low pH as required to ensure gastric stability. Success in achieving acceptable bioavailabilities of 1 across species (rats, dogs, and monkeys) followed the inclusion of ionizable functionality within the promoiety to compensate for masking the polar enolic OH group of the free drug. However, the introduction of ionizable functionality was often associated with decreased stability, as demonstrated by the hemisuccinate, hemiadipate, hemisuberate, and alpha-amino ester derivatives of 1 which could not be isolated. A clear exception was the hemifumarate derivative of 1 which was not only isolable but actually more stable at neutral pH than the nonionizable ester analogues. The solution and solid state stability of the hemifumarate, together with its activity as a prodrug of 1, suggests that hemifumarate be considered as an alternative to hemisuccinate as a prodrug derivative for alcohols, particularly in situations where solution state stability is an issue.

Use of activity measures in behavioral toxicology.

Locomotor activity measurements have been used extensively to evaluate chemically-induced changes in CNS function. This paper focuses on several factors including apparatus, age, biological rhythm, and social setting, which influence both locomotor activity levels per se and chemically induced changes in these activity levels. These data illustrate that failure to recognize, specify, and consider these factors is likely to result in equivocal studies subject to possible misinterpretation.

Developmental and behavioral changes in the rat during chronic exposure to lead.

Young male and female Sprague-Dawley rats were given drinking water containing 5 or 50 ppm Pb for 40 days prior to mating. Pregnant females were continued on these regimens throughout gestation and lactation. After weaning the offspring were similarly exposed through adulthood. Reflex development, body weights, and locomotor activity were measured in the offspring. Significant delays were noted in the development of the righting reflex at 5 and 50 ppm and in eye opening at 50 ppm. No difference was observed in development of the startle reflex at either dose. Mean body weights of treatment groups during this developmental period were not significantly different from controls. Locomotor activity was measured in adult males utilizing a residential maze. Both levels of lead produced a significant reduction in locomotor activity. When groups were treated with d-amphetamine (4.0 mg/kg subcutaneous), lead treatment caused a dose-related diminution in the amphetamine-induced hyperactivity. These results indicate that rats exposed to low levels of lead from conception until adulthood show a delay in nervous system development. As adults, these animals exhibit hypoactivity and decreased responsiveness to amphetamine.

The U.S. federal framework for research on endocrine disruptors and an analysis of research programs supported during fiscal year 1996.

The potential health and ecological effects of endocrine disrupting chemicals has become a high visibility environmental issue. The 1990s have witnessed a growing concern, both on the part of the scientific community and the public, that environmental chemicals may be causing widespread effects in humans and in a variety of fish and wildlife species. This growing concern led the Committee on the Environment and Natural Resources (CENR) of the National Science and Technology Council to identify the endocrine disruptor issue as a major research initiative in early 1995 and subsequently establish an ad hoc Working Group on Endocrine Disruptors. The objectives of the working group are to 1) develop a planning framework for federal research related to human and ecological health effects of endocrine disrupting chemicals; 2) conduct an inventory of ongoing federal research programs; and 3) identify research gaps and develop a coordinated interagency plan to address priority research needs. This communication summarizes the activities of the federal government in defining a common framework for planning an endocrine disruptor research program and in assessing the status of the current effort. After developing the research framework and compiling an inventory of active research projects supported by the federal government in fiscal year 1996, the CENR working group evaluated the current federal effort by comparing the ongoing activities with the research needs identified in the framework. The analysis showed that the federal government supports considerable research on human health effects, ecological effects, and exposure assessment, with a predominance of activity occurring under human health effects. The analysis also indicates that studies on reproductive development and carcinogenesis are more prevalent than studies on neurotoxicity and immunotoxicity, that mammals (mostly laboratory animals) are the main species under study, and that chlorinated dibenzodioxins and polychlorinated biphenyls are the most commonly studied chemical classes. Comparison of the inventory with the research needs should allow identification of underrepresented research areas in need of attention.