Classical homocystinuria, is it safe to exercise?

Background Cystationine β-synthase (CBS) deficiency is a genetic disorder characterized by severe hyperhomocysteinemia and thrombotic complications. In healthy individuals, physical exercise may result in a transient increase in plasma total homocysteine (tHcy) raising the possibility that exercise might be detrimental in CBS deficiency. Our main objective was to determine plasma tHcy kinetics in response to physical exercise in homocystinuria patients. Methods Six adult patients (2 males, 4 females) with homocystinuria and 6 age- and gender-matched controls completed a 30-min aerobic exercise of moderate-intensity with fixed power output (50 W for women and 100 W for men). Blood samples were drawn before, immediately, 180 min and 24 h after exercise. tHcy levels were determined by standard procedures; substrate oxidation and energy expenditure were measured using indirect calorimetry. Results Acute exercise was well tolerated and safe in patients and controls. During the exercise bout, heart rate and energy expenditure increased equally in both groups. tHcy levels were higher in patients compared to controls at all time points (p < 0.05). There was no significant effect of exercise on tHcy levels at any time point (p = 0.36). Although two patients with partial pyridoxine responsiveness presented higher homocysteine responses, their highest value remained below 55 μmol/l. Conclusions Overall metabolic responses to acute exercise were similar between homocystinuria patients and controls; specifically, exercise did not significantly change tHcy concentrations. Moderate physical exercise was well tolerated without any adverse event in our cohort of patients. Further studies are needed to identify the effects of different intensities and modes of exercise in larger cohorts of CBS patients with different levels of pyridoxine responsiveness

The Connective Tissue Disorder Associated with Recessive Variants in the SLC39A13 Zinc Transporter Gene (Spondylo-Dysplastic Ehlers-Danlos Syndrome Type 3): Insights from Four Novel Patients and Follow-Up on Two Original Cases.

Recessive loss-of-function variants in SLC39A13, a putative zinc transporter gene, were first associated with a connective tissue disorder that is now called "Ehlers-Danlos syndrome, spondylodysplastic form type 3" (SCD-EDS, OMIM 612350) in 2008. Nine individuals have been described. We describe here four additional affected individuals from three consanguineous families and the follow up of two of the original cases. In our series, cardinal findings included thin and finely wrinkled skin of the hands and feet, characteristic facial features with downslanting palpebral fissures, mild hypertelorism, prominent eyes with a paucity of periorbital fat, blueish sclerae, microdontia, or oligodontia, and-in contrast to most types of Ehlers-Danlos syndrome-significant short stature of childhood onset. Mild radiographic changes were observed, among which platyspondyly is a useful diagnostic feature. Two of our patients developed severe keratoconus, and two suffered from cerebrovascular accidents in their twenties, suggesting that there may be a vascular component to this condition. All patients tested had a significantly reduced ratio of the two collagen-derived crosslink derivates, pyridinoline-to-deoxypyridinoline, in urine, suggesting that this simple test is diagnostically useful. Additionally, analysis of the facial features of affected individuals by DeepGestalt technology confirmed their specificity and may be sufficient to suggest the diagnosis directly. Given that the clinical presentation in childhood consists mainly of short stature and characteristic facial features, the differential diagnosis is not necessarily that of a connective tissue disorder and therefore, we propose that SLC39A13 is included in gene panels designed to address dysmorphism and short stature. This approach may result in more efficient diagnosis

Injection of iodine to the stratosphere

© 2015. American Geophysical Union. All Rights Reserved. We report a new estimation of the injection of iodine into the stratosphere based on novel daytime (solar zenith angle < 45°) aircraft observations in the tropical tropopause layer and a global atmospheric model with the most recent knowledge about iodine photochemistry. The results indicate that significant levels of total reactive iodine (0.25-0.7 parts per trillion by volume), between 2 and 5 times larger than the accepted upper limits, can be injected into the stratosphere via tropical convective outflow. At these iodine levels, modeled iodine catalytic cycles account for up to 30% of the contemporary ozone loss in the tropical lower stratosphere and can exert a stratospheric ozone depletion potential equivalent to, or even larger than, that of very short-lived bromocarbons. Therefore, we suggest that iodine sources and chemistry need to be considered in assessments of the historical and future evolution of the stratospheric ozone layer.Peer Reviewe

Cardiospondylocarpofacial syndrome as a distinct hereditary connective tissue disorder: novel missense variant in MAP3K7 in two unrelated patients

CDKL5 deficiency disorder is a rare X-linked condition that results in early onset of impairedmotor and cognitive skills such as motor rigidity, stereotypical hand movements and deficient language acquisition aswell as recurrent seizures. It is caused by mutations in the cyclin-dependent kinase-like 5 (CDKL5) gene, which encodes a serine/threonine kinase involved in important neuronal processes such as cell signaling and neuron morphogenesis.FCT: UID/Multi/04326/2019 (CCMAR)info:eu-repo/semantics/publishedVersio

Mutations in the heat-shock protein A9 (HSPA9) gene cause the EVEN-PLUS syndrome of congenital malformations and skeletal dysplasia.

We and others have reported mutations in LONP1, a gene coding for a mitochondrial chaperone and protease, as the cause of the human CODAS (cerebral, ocular, dental, auricular and skeletal) syndrome (MIM 600373). Here, we delineate a similar but distinct condition that shares the epiphyseal, vertebral and ocular changes of CODAS but also included severe microtia, nasal hypoplasia, and other malformations, and for which we propose the name of EVEN-PLUS syndrome for epiphyseal, vertebral, ear, nose, plus associated findings. In three individuals from two families, no mutation in LONP1 was found; instead, we found biallelic mutations in HSPA9, the gene that codes for mHSP70/mortalin, another highly conserved mitochondrial chaperone protein essential in mitochondrial protein import, folding, and degradation. The functional relationship between LONP1 and HSPA9 in mitochondrial protein chaperoning and the overlapping phenotypes of CODAS and EVEN-PLUS delineate a family of "mitochondrial chaperonopathies" and point to an unexplored role of mitochondrial chaperones in human embryonic morphogenesis

Severe peripheral joint laxity is a distinctive clinical feature of spondylodysplastic-ehlers-danlos syndrome (Eds)-b4galt7 and spondylodysplastic-eds-b3galt6

Variations in genes encoding for the enzymes responsible for synthesizing the linker region of proteoglycans may result in recessive conditions known as “linkeropathies”. The two phenotypes related to mutations in genes B4GALT7 and B3GALT6 (encoding for galactosyltransferase I and II respectively) are similar, characterized by short stature, hypotonia, joint hypermobility, skeletal features and a suggestive face with prominent forehead, thin soft tissue and prominent eyes. The most outstanding feature of these disorders is the combination of severe connective tissue involvement, often manifesting in newborns and infants, and skeletal dysplasia that becomes apparent during childhood. Here, we intend to more accurately define some of the clinical features of B4GALT7 and B3GALT6-related conditions and underline the extreme hypermobility of distal joints and the soft, doughy skin on the hands and feet as features that may be useful as the first clues for a correct diagnosis

The effects of Transcranial Direct Current Stimulation on psychomotor performance of athletes: a systematic review and meta-analysis

Psychomotor performance is a complex function generated by brain and motor systems integration, measured by accuracy, latency, and movement speed. In sports, to look for ways to improve movements is usual. Also, to utilize Transcranial Direct Current Stimulation (tDCS) as technique of non-invasive stimulation may produce alterations in psychomotor sport skills. We conducted a systematic review including experimental studies with sham or control groups in adults reporting tDCS effects on athletes’ psychomotor performance. Cochrane Manual for Systematic Reviews and the statement on systematic reviews and meta-analysis of PRISMA-P (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols) were followed. PsycINFO, PubMed (central), Scopus, Web of Science, Embase, SPORTDiscus, and Cochrane Library databases were searched. Empirical studies published in English, Spanish, and Portuguese from 2009 onwards and whose primary results presented an effective measure of transcranial direct current stimulation in the psychomotor performance of adult athletes were included. The results list 10 articles, 6 of them entered in the meta-analyses. The articles presented a low risk of bias and low publication bias but great dispersion of stimulation areas. PROSPERO register number: PROSPERO RD4202021055

Conservation Biogeography of the Sahara‐Sahel: additional protected areas are needed to secure unique biodiversity

Aim Identification of priority conservation areas and evaluation of coverage of the current protected areas are urgently needed to halt the biodiversity loss. Identifying regions combining similar environmental traits (climate regions) and species assemblages (biogroups) is needed for conserving the biodiversity patterns and processes. We identify climate regions and biogroups and map species diversity across the Sahara-Sahel, a large geographical area that exhibits wide environmental heterogeneity and multiple species groups with distinct biogeographical affinities, and evaluate the coverage level of current network of protected areas for biodiversity conservation. Location Sahara-Sahel, Africa. Methods We use spatially explicit climate data with the principal component analysis and model-based clustering techniques to identify climate regions. We use distributions of 1147 terrestrial vertebrates (and of 125 Sahara-Sahel endemics) and apply distance clustering methods to identify biogroups for both species groups. We apply reserve selection algorithms targeting 17% of species distribution, climate regions and biogroups to identify priority areas and gap analysis to assess their representation within the current protected areas. Results Seven climate regions were identified, mostly arranged as latitudinal belts. Concentrations of high species richness were found in the Sahel, but the central Sahara gathers most endemic and threatened species. Ten biogroups (five for endemics) were identified. A wide range of biogroups tend to overlap in specific climate regions. Identified priority areas are inadequately represented in protected areas, and six new top conservation areas are needed to achieve conservation targets. Main conclusions Biodiversity distribution in Sahara-Sahel is spatially structured and apparently related to environmental variation. Although the majority of priority conservation areas are located outside the areas of intense human activities, many cross multiple political borders and require internationally coordinated efforts for implementation and management. Optimized biodiversity conservation solutions at regional scale are needed. Our work contradicts the general idea that deserts are uniform areas and provide options for the conservation of endangered species.info:eu-repo/semantics/publishedVersio