The effect of exercise training interventions in adult kidney transplant recipients: a systematic review and meta-analysis of randomised control trials

Background: Kidney transplant recipients (KTRs) are characterised by adverse changes in physical fitness and body composition. Post-transplant management involves being physically active, although evidence for the effect of exercise is limited. Objective: To assess the effects of exercise training interventions in KTRs. Methods: NCBI PubMed (MEDLINE) and CENTRAL (EMBASE, WHO ICTRP) databases were searched up to March 2021 to identify eligible randomized controlled trials (RCTs) that studied exercise training in adult KTRs. Outcomes included exercise capacity, strength, blood pressure, body composition, heart rate, markers of dyslipidaemia and renal function, and health-related quality of life (QoL). Results: Sixteen RCTs, containing 827 KTRs, were included. The median intervention length was 14-weeks with participants exercising between 2–7x/week. Most studies used a mixture of aerobic and resistance exercise. Significant improvements were observed in cardiorespiratory function (VO2peak) (3.21 ml/kg/min, p = 0.003), 6MWT (76.3 meters, p = 0.009), physical function (STS-60, 4.8 repetitions, p = 0.04), and high-density lipoprotein (HDL) (0.13 mg/dL, p = 0.03). A moderate increase in maximum heart rate was seen (p = 0.06). A moderate reduction in creatinine was also observed (0.14 mg/dl, p = 0.05). Isolated studies reported improvements in strength, bone health, lean mass, and QoL. Overall, studies had high risk of bias suggestive of publication bias. Conclusions: Exercise training may confer several benefits in adult KTRs, particularly by increasing cardiorespiratory function and exercise capacity, strength, HDL levels, maximum heart rate, and improving QoL. Additional long-term large sampled RCTs, incorporating complex interventions requiring both exercise and dietary behaviour change, are needed to fully understand the effects of exercise in KTRs

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

A demonstration of an affinity between pyrite and organic matter in a hydrothermal setting

One of the key-principles of the iron-sulphur world theory is to bring organic molecules close enough to interact with each other, using the surface of pyrite as a substrate in a hydrothermal setting. The present paper explores the relationship of pyrite and organic matter in a hydrothermal setting from the geological record; in hydrothermal calcite veins from Carboniferous limestones in central Ireland. Here, the organic matter is accumulated as coatings around, and through, pyrite grains. Most of the pyrite grains are euhedral-subhedral crystals, ranging in size from ca 0.1-0.5 mm in diameter, and they are scattered throughout the matrix of the vein calcite. The organic matter was deposited from a hydrothermal fluid at a temperature of at least 200°C, and gives a Raman signature of disordered carbon. This study points to an example from a hydrothermal setting in the geological record, demonstrating that pyrite can have a high potential for the concentration and accumulation of organic materials

Etiology of Severe Non-malaria Febrile Illness in Northern Tanzania: A Prospective Cohort Study.

The syndrome of fever is a commonly presenting complaint among persons seeking healthcare in low-resource areas, yet the public health community has not approached fever in a comprehensive manner. In many areas, malaria is over-diagnosed, and patients without malaria have poor outcomes. We prospectively studied a cohort of 870 pediatric and adult febrile admissions to two hospitals in northern Tanzania over the period of one year using conventional standard diagnostic tests to establish fever etiology. Malaria was the clinical diagnosis for 528 (60.7%), but was the actual cause of fever in only 14 (1.6%). By contrast, bacterial, mycobacterial, and fungal bloodstream infections accounted for 85 (9.8%), 14 (1.6%), and 25 (2.9%) febrile admissions, respectively. Acute bacterial zoonoses were identified among 118 (26.2%) of febrile admissions; 16 (13.6%) had brucellosis, 40 (33.9%) leptospirosis, 24 (20.3%) had Q fever, 36 (30.5%) had spotted fever group rickettsioses, and 2 (1.8%) had typhus group rickettsioses. In addition, 55 (7.9%) participants had a confirmed acute arbovirus infection, all due to chikungunya. No patient had a bacterial zoonosis or an arbovirus infection included in the admission differential diagnosis. Malaria was uncommon and over-diagnosed, whereas invasive infections were underappreciated. Bacterial zoonoses and arbovirus infections were highly prevalent yet overlooked. An integrated approach to the syndrome of fever in resource-limited areas is needed to improve patient outcomes and to rationally target disease control efforts

Validation of the Oxford WebQ online 24-hour dietary questionnaire using biomarkers

Oxford WebQ is an online dietary questionnaire covering 24 hours, appropriate for repeated administration in large-scale prospective studies including UK Biobank and the Million Women Study. We compared performance of the Oxford WebQ and a traditional interviewer-administered multi-pass 24-hour recall against biomarkers for protein, potassium and total sugar intake, and total energy expenditure estimated by accelerometry. 160 participants were recruited between 2014 and 2016 in London, UK, and measured at 3 non-consecutive time-points. The measurement error model simultaneously compared all 3 methods. Attenuation factors for protein, potassium, sugars and total energy intake estimated by the mean of 2 Oxford WebQs were 0.37, 0.42, 0.45, and 0.31 respectively, with performance improving incrementally for the mean of more measures. Correlation between the mean of 2 Oxford WebQs and estimated true intakes, reflecting attenuation when intake is categorised or ranked, was 0.47, 0.39, 0.40, and 0.38 respectively, also improving with repeated administration. These were similar to the more administratively burdensome interviewer-based recall. Using objective biomarkers as the standard, Oxford WebQ performs well across key nutrients in comparison with more administratively burdensome interviewer-based 24-hour recalls. Attenuation improves when the average is taken over repeated administration, reducing measurement error bias in assessment of diet-disease associations

Modelling the impact of intermittent preventive treatment for malaria on selection pressure for drug resistance

BACKGROUND: Intermittent preventive treatment (IPT) is a promising intervention for malaria control, although there are concerns about its impact on drug resistance. METHODS: The key model inputs are age-specific values for a) baseline anti-malarial dosing rate, b) parasite prevalence, and c) proportion of those treated with anti-malarials (outside IPT) who are infected. These are used to estimate the immediate effect of IPT on the genetic coefficient of selection (s). The scenarios modelled were year round IPT to infants in rural southern Tanzania, and three doses at monthly intervals of seasonal IPT in Senegal. RESULTS: In the simulated Tanzanian setting, the model suggests a high selection pressure for drug resistance, but that IPTi would only increase this by a small amount (4.4%). The percent change in s is larger if parasites are more concentrated in infants, or if baseline drug dosing is less common or less specific. If children aged up to five years are included in the Tanzanian scenario then the predicted increase in s rises to 31%. The Senegalese seasonal IPT scenario, in children up to five years, results in a predicted increase in s of 16%. CONCLUSION: There is a risk that the useful life of drugs will be shortened if IPT is implemented over a wide childhood age range. On the other hand, IPT delivered only to infants is unlikely to appreciably shorten the useful life of the drug used

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Impact of combining intermittent preventive treatment with home management of malaria in children less than 10 years in a rural area of Senegal: a cluster randomized trial

<p>Abstract</p> <p>Background</p> <p>Current malaria control strategies recommend (i) early case detection using rapid diagnostic tests (RDT) and treatment with artemisinin combination therapy (ACT), (ii) pre-referral rectal artesunate, (iii) intermittent preventive treatment and (iv) impregnated bed nets. However, these individual malaria control interventions provide only partial protection in most epidemiological situations. Therefore, there is a need to investigate the potential benefits of integrating several malaria interventions to reduce malaria prevalence and morbidity.</p> <p>Methods</p> <p>A randomized controlled trial was carried out to assess the impact of combining seasonal intermittent preventive treatment in children (IPTc) with home-based management of malaria (HMM) by community health workers (CHWs) in Senegal. Eight CHWs in eight villages covered by the Bonconto health post, (South Eastern part of Senegal) were trained to diagnose malaria using RDT, provide prompt treatment with artemether-lumefantrine for uncomplicated malaria cases and pre-referral rectal artesunate for complicated malaria occurring in children under 10 years. Four CHWs were randomized to also administer monthly IPTc as single dose of sulphadoxine-pyrimethamine (SP) plus three doses of amodiaquine (AQ) in the malaria transmission season, October and November 2010. Primary end point was incidence of single episode of malaria attacks over 8 weeks of follow up. Secondary end points included prevalence of malaria parasitaemia, and prevalence of anaemia at the end of the transmission season. Primary analysis was by intention to treat. The study protocol was approved by the Senegalese National Ethical Committee (approval 0027/MSP/DS/CNRS, 18/03/2010).</p> <p>Results</p> <p>A total of 1,000 children were enrolled. The incidence of malaria episodes was 7.1/100 child months at risk [95% CI (3.7-13.7)] in communities with IPTc + HMM compared to 35.6/100 child months at risk [95% CI (26.7-47.4)] in communities with only HMM (aOR = 0.20; 95% CI 0.09-0.41; <it>p </it>= 0.04). At the end of the transmission season, malaria parasitaemia prevalence was lower in communities with IPTc + HMM (2.05% versus 4.6% <it>p </it>= 0.03). Adjusted for age groups, sex, <it>Plasmodium falciparum </it>carriage and prevalence of malnutrition, IPTc + HMM showed a significant protective effect against anaemia (aOR = 0.59; 95% CI 0.42-0.82; <it>p </it>= 0.02).</p> <p>Conclusion</p> <p>Combining IPTc and HMM can provide significant additional benefit in preventing clinical episodes of malaria as well as anaemia among children in Senegal.</p

Heritable Differences in Schooling Behavior among Threespine Stickleback Populations Revealed by a Novel Assay

Identifying the proximate and ultimate mechanisms of social behavior remains a major goal of behavioral biology. In particular, the complex social interactions mediating schooling behavior have long fascinated biologists, leading to theoretical and empirical investigations that have focused on schooling as a group-level phenomenon. However, methods to examine the behavior of individual fish within a school are needed in order to investigate the mechanisms that underlie both the performance and the evolution of schooling behavior. We have developed a technique to quantify the schooling behavior of an individual in standardized but easily manipulated social circumstances. Using our model school assay, we show that threespine sticklebacks (Gasterosteus aculeatus) from alternative habitats differ in behavior when tested in identical social circumstances. Not only do marine sticklebacks show increased association with the model school relative to freshwater benthic sticklebacks, they also display a greater degree of parallel swimming with the models. Taken together, these data indicate that marine sticklebacks exhibit a stronger tendency to school than benthic sticklebacks. We demonstrate that these population-level differences in schooling tendency are heritable and are shared by individuals within a population even when they have experienced mixed-population housing conditions. Finally, we begin to explore the stimuli that elicit schooling behavior in these populations. Our data suggest that the difference in schooling tendency between marine and benthic sticklebacks is accompanied by differential preferences for social vs. non-social and moving vs. stationary shelter options. Our study thus provides novel insights into the evolution of schooling behavior, as well as a new experimental approach to investigate the genetic and neural mechanisms that underlie this complex social behavior

Genome-wide analyses for personality traits identify six genomic loci and show correlations with psychiatric disorders

Personality is influenced by genetic and environmental factors1 and associated with mental health. However, the underlying genetic determinants are largely unknown. We identified six genetic loci, including five novel loci2,3, significantly associated with personality traits in a meta-analysis of genome-wide association studies (N = 123,132–260,861). Of these genomewide significant loci, extraversion was associated with variants in WSCD2 and near PCDH15, and neuroticism with variants on chromosome 8p23.1 and in L3MBTL2. We performed a principal component analysis to extract major dimensions underlying genetic variations among five personality traits and six psychiatric disorders (N = 5,422–18,759). The first genetic dimension separated personality traits and psychiatric disorders, except that neuroticism and openness to experience were clustered with the disorders. High genetic correlations were found between extraversion and attention-deficit– hyperactivity disorder (ADHD) and between openness and schizophrenia and bipolar disorder. The second genetic dimension was closely aligned with extraversion–introversion and grouped neuroticism with internalizing psychopathology (e.g., depression or anxiety)