Exercise to combat neurocognitive decline in older adults

Background: Older adults with type 2 diabetes (T2D) experience cognitive decline and neural atrophy, and therefore are at high risk for developing dementia. Consequently, older adults at-risk for developing T2D (i.e., overweight or pre-diabetic individuals) are at higher risk for cognitive decline, and intervening at this point may prevent or delay the onset of such decline. One promising lifestyle intervention that may improve neurocognitive function is exercise. For example, 6 months of aerobic training improves cognitive function in overweight or pre-diabetic older adults, but research has not examined whether resistance training (RT) can produce comparable results in this population. Hypothesis: To address whether similar findings would occur in older adults at-risk for T2D, a 6-month progressive RT intervention is needed. We predict that 6 months of thrice-weekly RT will improve cognitive and brain function in older adults at-risk for T2D. Methods: We are conducting a pilot RCT resistance exercise intervention. Participants (n=20) are: 1) community-dwelling men and women aged 60-80 years, 2) sedentary, and 3) have BMI\u3e25 or blood glucose levels of 6.1-7.0 mmol/L. Participants are randomized into one of two groups: 1) RT or 2) balance and tone (BAT; control). Preliminary Results: Our preliminary results suggest that RT improves memory and executive function (assessed via neuropsychological tests) and brain health (increased total brain volume) in older adults at-risk for T2D, compared to BAT. Discussion: Thus far, our findings offer a feasible, cost-efficient lifestyle intervention strategy to improve cognitive and brain health in a population of older adults at-risk for early decline

“A content and thematic analysis of #instagramvsreality images and captions on Instagram” (PowerPoint)

A couple of years ago, the “Instagram vs. reality” trend sprung from Instagram’s body positivity movement. The trend encourages Instagram users to post side-by-side images of themselves — one side being the highly curated “Instagram” depiction and the other being a more ‘real’ depiction. One study has explored the trend academically, and it found that engaging with “Instagram vs reality” and “reality” images decreased body dissatisfaction amongst its participants relative to viewing idealized “Instagram” images. In an effort to understand who is participating in the trend, what they are contributing to the trend, and why they are engaging with it, this study examined 150 images and their captions from #instagramvsreality on Instagram. Results demonstrated that the subjects participating in the trend are less diverse in appearance than those in the body positivity movement. Yet, many subjects spoke about how Instagram is ‘fake’ and that people ought to not compare themselves to the images they see online. While subjects often did engage with body positive messaging, the authors concluded that the Instagram vs reality trend may be more about promoting media literacy, and hence, that could explain why the trend contains less diversity in appearance than the body positivity movement, which aims to challenge the narrowly-defined standards that govern beauty and appearance. (This is the lay output for the research project. The research paper will be available elsewhere or on this site at a later period.

How genomics reclassifies diseases : the case of Alport syndrome

Altres ajuts: The author's research is funded by the Instituto de Salud Carlos III/Fondo Europeo de Desarrollo Regional (FEDER) funds, RETIC REDINREN RD16/0009 FIS FEDER FUNDS.In this issue, Matthews et al. provide a comprehensive review of published cohorts with heterozygous pathogenic variants in COL4A3 or COL4A4, documenting the wide spectrum of the disease. Due to the extreme phenotypes that patients with heterozygous pathogenic variants in COL4A3 or COL4A4 may show, the disease has been referred to in a variety of ways, including 'autosomal dominant Alport syndrome', 'thin basement membrane disease', 'thin basement membrane nephropathy', 'familial benign hematuria' and 'carriers of autosomal dominant Alport syndrome'. This confusion over terminology has prevented nephrologists from being sufficiently aware of the relevance of the entity. Nowadays, however, next-generation sequencing facilitates the diagnosis and it is becoming a relatively frequent finding in haematuric-proteinuric nephropathies of unknown origin, even in non-familial cases. There is a need to raise awareness among nephrologists about the disease in order to improve diagnosis and provide better management for these patients

The effects of resistance training on cognition and brain health in older adults at risk for diabetes: A pilot feasibility study

Type 2 diabetes is associated with neurocognitive deficits and increased risk for dementia, with high prevalence of diabetes occurring in old age. There are many known risk factors for diabetes, including physical inactivity, obesity, and prediabetes. Studies show that individuals who are at risk for diabetes (i.e., have one or more risk factors) already experience some brain deficits seen in diabetes. One way to combat these deficits is aerobic exercise; however, the effects of resistance exercise in this population are relatively unknown. The objectives of this thesis were to report on the current evidence of brain deficits in prediabetes, and to assess the feasibility and preliminary efficacy of resistance training to improve cognition and brain health (structure and function) in older adults at risk for diabetes. A systematic review of cross-sectional and longitudinal studies assessing brain dysfunction in prediabetes was conducted, as well as a 26-week pilot feasibility randomized controlled trial of resistance exercise among older adults at risk for diabetes (i.e., those living with prediabetes and/or obesity). The systematic review found that adults with prediabetes may experience deficits in structural connectivity, but whether deficits in brain volume and cerebrovascular health are present is somewhat inconclusive and may be due to inconsistencies across study methodologies. Results from the pilot feasibility trial found that resistance exercise, compared to balance and stretching exercise, may improve selective cognitive functions, mainly task-switching, selective attention, and response inhibition. Resistance exercise also led to less age-related decline in total brain volume, less hippocampal atrophy, and increased functional activation patterns that mimic that of younger adults and healthy older adults. When assessing feasibility, study adherence, retention, and self-reported enjoyment were high, but recruitment was shown to be challenging. As such, important recruitment recommendations for improving future trials are included in this thesis. In conclusion, resistance exercise may lead to some improvements in cognition and brain health in older adults at risk for diabetes, however a full-scale, powered RCT is needed to further explore these possible effects

Genetic kidney diseases as an underrecognized cause of chronic kidney disease : the key role of international registry reports

Inherited kidney diseases (IKDs) are among the leading causes of early-onset chronic kidney disease (CKD) and are responsible for at least 10-15% of cases of kidney replacement therapy (KRT) in adults. Paediatric nephrologists are very aware of the high prevalence of IKDs among their patients, but this is not the case for adult nephrologists. Recent publications have demonstrated that monogenic diseases account for a significant percentage of adult cases of CKD. A substantial number of these patients have received a non-specific/incorrect diagnosis or a diagnosis of CKD of unknown aetiology, which precludes correct treatment, follow-up and genetic counselling. There are a number of reasons why genetic kidney diseases are difficult to diagnose in adulthood: (i) adult nephrologists, in general, are not knowledgeable about IKDs; (ii) existence of atypical phenotypes; (iii) genetic testing is not universally available; (iv) family history is not always available or may be negative; (v) lack of knowledge of various genotype-phenotype relationships and (vi) conflicting interpretation of the pathogenicity of many sequence variants. Registries can contribute to visualize the burden of IKDs by regularly grouping all IKDs in their annual reports, as is done for glomerulonephritis or interstitial diseases, rather than reporting only cystic disease and hiding other IKDs under labels such as 'miscellaneous' or 'other'. Any effort to reduce the percentage of patients needing KRT with a diagnosis of 'nephropathy of unknown etiology' or an unspecific/incorrect diagnosis should be encouraged as a step towards precision nephrology. Genetic testing may be of value in this context but should not be used indiscriminately, but rather on the basis of a deep knowledge of IKDs

Favorable impact of long-term exercise on disease symptoms in pediatric patients with inflammatory bowel disease

Evidence is growing that both short- and long-term physical exercise have the potential to positively impact on the physiological system related to inflammatory indices, though, such patterns are unknown for pediatric patients with Inflammatory Bowel Disease (IBD). The aim of the present intervention study was to investigate the influence of a single bout and chronic moderate-intensity exercise on IBD-related inflammatory indices and exercise capacity among pediatric individuals with IBD and healthy controls.; Twenty-one pediatric patients with IBD, split into a "remission-group" (IBD-RE; n = 14) and an "active disease group" (IBD-AD; n = 7), were compared to 23 age matched healthy controls (HC). All participants completed a single bout of exercise at baseline and an 8-week exercise intervention. Before and after the single bout of exercise IBD-related inflammatory indices (erythrocyte sedimentation rate (ESR), albumin, C-reactive protein (CRP), cortisol, hemoglobin, hematocrit, thrombocytes and leukocytes) were assessed.; At baseline, after a single bout of exercise, inflammation (albumin, hemoglobin, erythrocytes, hematocrit and leukocytes) increased in all three groups IBD-AD, IBD-RE and HC. CRP and thrombocytes were only elevated in IBD-AD and IBD-RE, compared to HC. After a longer-term exercise intervention, ESR, CRP and thrombocytes significantly decreased in all groups. The longer-term exercise intervention did not decrease acute immunopathologic responses after a single bout of exercise, compared to baseline.; Whereas a single bout of exercise increases albumin, erythrocytes and leukocytes, longer-term moderate-intensity exercise reduced inflammatory markers in pediatric patients with IBD. Children and teenagers with IBD should be encouraged to engage in regular moderate-intensity exercise activities, as such activities may contribute to inflammation suppression and improved disease management

Growth of Infants Fed Formula with Evolving Nutrition Composition: A Single-Arm Non-Inferiority Study.

The nutritional composition of human milk evolves over the course of lactation, to match the changing needs of infants. This single-arm, non-inferiority study evaluated growth against the WHO standards in the first year of life, in infants consecutively fed four age-based formulas with compositions tailored to infants' nutritional needs during the 1st, 2nd, 3rd-6th, and 7th-12th months of age. Healthy full-term formula-fed infants (n = 32) were enrolled at ≤14 days of age and exclusively fed study formulas from enrollment, to the age of four months. Powdered study formulas were provided in single-serving capsules that were reconstituted using a dedicated automated preparation system, to ensure precise, hygienic preparation. The primary outcome was the weight-for-age z-score (WAZ) at the age of four months (vs. non-inferiority margin of -0.5 SD). Mean (95% CI) z-scores for the WAZ (0.12 (-0.15, 0.39)), as well as for the length-for-age (0.05 (-0.19, 0.30)), weight-for-length (0.16 (-0.16, 0.48)), BMI-for-age (0.11 (-0.20, 0.43)), and head circumferencefor-age (0.41 (0.16, 0.65)) at the age of four months, were non-inferior. Throughout the study, anthropometric z-scores tracked closely against the WHO standards (within ±1 SD). In sum, a fourstage, age-based infant formula system with nutritional compositions tailored to infants' evolving needs, supports healthy growth consistent with WHO standards, for the first year of life

Novel homozygous OSGEP gene pathogenic variants in two unrelated patients with Galloway-Mowat syndrome : case report and review of the literature

Galloway-Mowat syndrome (GAMOS) is a rare autosomal recessive disorder characterized by early-onset nephrotic syndrome and microcephaly with brain anomalies. WDR73 pathogenic variants were described as the first genetic cause of GAMOS and, very recently, four novel causative genes, OSGEP, LAGE3, TP53RK, and TPRKB, have been identified. We present the clinical and genetic characteristics of two unrelated infants with clinical suspicion of GAMOS who were born from consanguineous parents. Both patients showed a similar clinical presentation, with early-onset nephrotic syndrome, microcephaly, brain atrophy, developmental delay, axial hypotonia, and early fatality. We identified two novel likely disease-causing variants in the OSGEP gene. These two cases, in conjunction with the findings of a literature review, indicate that OSGEP pathogenic variants are associated with an earlier onset of nephrotic syndrome and shorter life expectancy than WDR73 pathogenic variants. Our findings expand the spectrum of pathogenic variants in the OSGEP gene and, taken in conjunction with the results of the literature review, suggest that the OSGEP gene should be considered the main known monogenic cause of GAMOS. Early genetic diagnosis of GAMOS is of paramount importance for genetic counseling and family planning

Motilitätsstörungen des Ösophagus

Zusammenfassung: Motilitätsstörungen des Ösophagus umfassen ein heterogenes Spektrum von Erkrankungen. Primäre Fehlbildungen des Ösophagus sind heute zwar einer verbesserten chirurgischen und gastroenterologischen Therapie zugänglich, führen jedoch zu langfristig persistierender ösophagealer Dysmotilität. Die Achalasie resultiert aus einer gestörten Relaxation des gastroösophagealen Sphinkters. Systemische Erkrankungen können mit einer sekundären ösophagealen Motilitätsstörung einhergehen. Zahlreiche neuromuskuläre Erkrankungen mit viszeraler Manifestation zeigen eine ösophageale Beteiligung. Selten kann eine Aganglionose bis in den Ösophagus reichen. Die wachsende Gruppe der Myopathien schließt metabolische und mitochondriale Störungen ein, deren zunehmende Charakterisierung genetischer Defekte vereinzelt bereits therapeutische Ansätze eröffnet. Infektbedingte Ösophagitiden zeigen besonders bei immunkompromittierten Patienten eine schwere Störung der Motilität. Immunologisch vermittelte Entzündungsprozesse im und um den Ösophagus werden allmählich besser verstanden. Schließlich können seltene Tumoren und tumorartige Läsionen eine Dysmotilität des Ösophagus verursache

Comparative analysis of tools to predict rapid progression in autosomal dominant polycystic kidney disease

Background: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and shows a wide phenotype. Only patients with rapid progression (RP) are included in clinical trials or are approved to receive disease-modifying drugs. This study aims at comparing different available predictive tools in ADPKD with the Mayo classification (MC) identification of rapid progressors based on high total kidney volume (TKV) according to age. Methods: A total of 164 ADPKD patients were recruited retrospectively from a single centre. The performance of diverse tools to identify RP defined as being in MC categories 1C-1E was assessed. Results: A total of 118 patients were MC 1C-1E. The algorithm developed by the European Renal Association-European Dialysis and Transplant Association Working Group on Inherited Kidney Disorders/European Renal Best Practice had a low sensitivity in identifying MC 1C-1E. The sensitivity and specificity of TKV to predict RP depend on the cut-off used. A kidney length of >16.5 cm before age 45 years has high specificity but low sensitivity. Assessing the MC by ultrasonography had high levels of agreement with magnetic resonance imaging (MRI) data, especially for 1A, 1D and 1E. The estimated glomerular filtration rate (eGFR) decline was very sensitive but had low specificity. In contrast, the Predicting Renal Outcome in Polycystic Kidney Disease (PROPKD) score was very specific but had poor sensitivity. Having hypertension before 35 years of age is a good clinical predictor of MC 1C-1E. Family history can be of help in suggesting RP, but by itself it lacks sufficient sensitivity and specificity. Conclusions: The MC by ultrasonography could be an option in hospitals with limited access to MRI as it performs well generally, and especially at the extremes of the MC, i.e. classes 1A, 1D and 1E. The eGFR decline is sensitive but not very specific when compared with the MC, whereas the PROPKD score is very specific but has low sensitivity. Integrating the different tools currently available to determine RP should facilitate the identification of rapid progressors among patients with ADPKD