The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission

Factors involved in the stability of trinucleotide repeats during transmission were studied in 139 families in which a full mutation, premutation or intermediate allele at either FRAXA or FRAXE was segregating. The transmission of alleles at FRAXA, FRAXE and four microsatellite loci were recorded for all individuals. Instability within the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for FRAXE) was extremely rare; only one example was observed, an increased in size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were unstably transmitted. Instability was more frequent for FRAXA intermediate alleles that had a tract of pure CGG greater than 37 although instability only occurred in two of 13 such transmissions: the changes observed were limited to only one or two repeats. Premutation FRAXA alleles over 100 repeats expanded to a full mutation during female transmission in 100% of cases, in agreement with other published series. There was no clear correlation between haplotype and probability of expansion of FRAXA premutations. Instability at FRAXA or FRAXE was more often observed in conjunction with a second instability at an independent locus suggesting genomic instability as a possible mechanism by which at least some FRAXA and FRAXE mutations arise.      

Lipoma of the temporal region: a rare case series

Lipomas are common benign tumours that can occur in most parts of the body. Lipomas arising from the deep temporal fat pad, found between the two layers of the deep temporal fascia, are rare, however; there has been only one documented case report to our knowledge. We describe a second case arising from the temporal fat pad in a patient treated at our unit, having previously reported the first one, and discuss the relevant anatomy and management.     

Evaluating and Strengthening the Evidence for Nutritional Bone Research: Ready to Break New Ground?

A healthy diet is essential to attain genetically determined peak bone mass and maintain optimal skeletal health across the adult lifespan. Despite the importance of nutrition for bone health, many of the nutritional requirements of the skeleton across the lifespan remain underexplored, poorly understood, or controversial. With increasingly aging populations, combined with rapidly changing diets and lifestyles globally, one anticipates large increases in the prevalence of osteoporosis and incidence of osteoporotic fractures. Robust, transparent, and reproducible nutrition research is a cornerstone for developing reliable public health recommendations to prevent osteoporosis and osteoporotic fractures. However, nutrition research is often criticized or ignored by healthcare professionals due to the overemphasis of weak science, conflicting, confusing or implausible findings, industry interests, common misconceptions, and strong opinions. Conversely, spurious research findings are often overemphasized or misconstrued by the media or prominent figures especially via social media, potentially leading to confusion and a lack of trust by the general public. Recently, reforms of the broader discipline of nutrition science have been suggested and promoted, leading to new tools and recommendations to attempt to address these issues. In this perspective, we provide a brief overview of what has been achieved in the field on nutrition and bone health, focusing on osteoporosis and osteoporotic fractures. We discuss what we view as some of the challenges, including inherent difficulties in assessing diet and its change, disentangling complex interactions between dietary components and between diet and other factors, selection of bone-related outcomes for nutrition studies, obtaining evidence with more unbiased designs, and perhaps most importantly, ensuring the trust of the public and healthcare professionals. This perspective also provides specific recommendations and highlights new developments and future opportunities for scientists studying nutrition and bone health. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Physical fitness and sport activity of children and adolescents: Methodological aspects of a regional survey

Summary Measurement of physical fitness and physical activity in children and adolescents raise a lot of methodological issues, explaining the scarcity of surveys in European countries and in Switzerland. This article exposes the design and the methods used in a survey on physical fitness, physical activity and health conducted in a region of Switzerland, and discuss the choice of the instruments and the quality control procedure selected to measure physical activity and physical fitness. The survey was conducted in a sample of 3540 students 9–19 years-old and included a battery of physical fitness tests, anthropometrics measurements and a self-report questionnaire on physical activity, sports activity and life styles. An ancillary study in a sub sample assessed daily physical activity with a pedometer, dietary intake with a 3-day dietary record, serum lipids and nutritional status. Some results are displayed as example. Quality control techniques are exposed and the choice of the instrument to assess physical fitness, physical activity, sports, and dietary intake are discussed. Local reference tables are now available for fitness tests and the practicability of fitness testing has been demonstrated in physical education. The research process has induced the sensitisation of schools toward health promotion through physical activity.

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Zusammenfassung Das Messen der physischen Kondition und der physischen Aktivität von Kindern und Adoleszenten wirft eine Vielzahl methodologischer Fragen auf, weshalb wohl in europäischen Ländern und in der Schweiz bisher nur wenige solche Untersuchungen durchgeführt wurden. Es sollen in dieser Studie, welche in einer Region der Schweiz zum Thema physische Kondition, körperliche Betätigung und Gesundheit durchgeführt wurde, die zur Anwendung gekommenen Untersuchungsmethoden dargestellt und das eigentliche Vorgehen beschrieben werden. Ebenfalls werden die instrumentenwahl sowie die für diese Studie ausgearbeiteten Verfahren zur Qualitätssicherung der Messungen der physischen Kondition und der physischen Aktivität diskutiert. Die Untersuchung wurde mit einer Auswahl von 3540 neun-bis neunzehnjährigen Schülern durchgeführt und beinhaltet die Messung der physischen Kondition mit Hilfe einer Testserie, anthropometrische Messungen und einen Fragebogen zur physischen Aktivität, sportlichen Betätigung und zum Lebensstil. Eine Zusatzstudie wurde in einem Teilkollektiv durchgeführt. Dabei wurden die tägliche physische Aktivität mit Hilfe eines Pedometers gemessen, während drei Tagen ein Tagebuch über die Nahrungsaufnahme geführt und die Lipidwerte im Blut sowie der Ernährungszustand analysiert. Einige Ergebnisse werden als Beispiel aufgeführt. Die zur Qualitätsgarantie der erfassten Daten eingesetzten Massnahmen, sowie die Wahl der für die Messungen der physischen Kondition, der körperlichen Aktivität, der sportlichen Betätigung und der Ernährung verwandten Instrumente werden diskutiert. Das Erstellen von lokalen Referenztabellen zur physischen Kondition von Jugendlichen erlaubte es, die Konditionstests in den Sportunterricht einzuführen und schulnahe Kreise dafür zu sensibilisieren, dass die körperliche Betätigung für eine Strategie der Gesundheitsförderung eine wichtige Rolle spielt.

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Résumé La mesure de la condition physique et de l'activité physique des enfants et des adolescents pose des problèmes méthodologiques particuliers, qui expliquent sans doute le petit nombre d'études de ce type dans les pays européens et en Suisse. Cet article présente la procédure et les méthodes utilisées dans une enquête sur la condition physique, l'activité physique et la santé, réalisée dans un canton de Suisse et discute le choix des instruments et des procédures mises en uvre pour assurer la qualité des mesures de la condition physique et d'activité physique. L'enquête a été conduite dans un échantillon de 3'540 élèves de 9 à 19 ans et comprenait des mesures de la condition physique grâce à une batterie de tests, des mesures anthropométriques et un questionnaire sur l'activité physique, la pratique sportive et les habitudes de vie. Dans un souséchantillon, on a utilisé un pédomètre mesurant l'activité physique quotidienne, un journal alimentaire de trois jours et un dosage sanguin des lipides et du status nutritionnel. Quelques résultats sont donnés à titre d'exemple. Les mesures mises en place pour assurer la qualité des données recueillies sont discutées, ainsi que le choix des instruments de mesure de la condition physique, de l'activité physique, de la pratique sportive et de l'alimentation. La réalisation de tables de référence locales pour les tests de condition physique a permis d'introduire l'utilisation des tests de condition physique dans l'enseignement de l'éducation physique, et de sensibiliser le milieu scolaire à l'importance de l'activité physique dans une stratégie de promotion de la santé.

     

Effects of photodynamic therapy using verteporfin on experimental choroidal neovascularization and normal retina and choroid up to 7 weeks after treatment.

PURPOSE: To study the long-term effects of photodynamic therapy (PDT), using liposomal benzoporphyrin derivative (BPD) or Verteporfin, on experimental choroidal neovascularization (CNV) and on normal retina and choroid (with no CNV) in the cynomolgus monkey eye. METHODS: Photodynamic therapy was performed in 8 cynomolgus monkey eyes with experimental CNV induced by laser injury. The effect of PDT on normal retina and choroid (with no CNV) was studied in 9 monkey eyes. Liposomal BPD was administered intravenously (0.375 mg/kg) either as a bolus, as a slow infusion over 32 minutes, or as a fast infusion over 10 minutes. Photodynamic therapy was performed using light at a wavelength of 689 or 692 nm, with an irradiance of 600 mW/cm2 and fluence of 150 J/cm2. Follow-up studies, including fundus photography and FA, were performed at 24 hours after PDT and then weekly. Indocyanine green and BPD angiography were performed in selected cases. Tissues were examined with light and electron microscopy at the end of follow-up. RESULTS: Twenty-three of the 32 areas of CNV treated with PDT showed absence of angiographic leakage at 24 hours. Twenty-eight areas of CNV were followed for 4 weeks; 22 of 28 showed absence of angiographic leakage at 2 weeks; and 20 of 28 at 4 weeks of follow-up. Forty spots on the normal retina and choroid were treated with PDT and were followed for 4 to 7 weeks. These spots showed pigment-laden cells in the outer retina, variably pigmented retinal pigment epithelium (RPE) in the treated area, intact neurosensory retina, and reperfusion of the choriocapillaris. CONCLUSIONS: Photodynamic therapy leads to absence of angiographic leakage for at least 4 weeks in experimental CNV in the monkey model. In the normal monkey eye the RPE and choriocapillaris show generalized recovery with preservation of the neurosensory retina 7 weeks after PDT.     

Agenesis of the vermis with fusion of the cerebellar hemispheres,septo-optic dysplasia and associated anomalies

Summary Agenesis of the cerebellar vermis with fusion of the dentate nuclei and cerebellar hemispheres (rhombencephalosynapsis) is a rare cerebral malformation. We report the case of a 7-h-old girl whose mother had taken the drug phencyclidine during the first 6 weeks of pregnancy. Absence of the septum pellucidum, hypoplasia of the commissural system, optic nerves, chiasm and tracts, moderate hydrocephalus, and agenesis of the posterior lobe of the pituitary were also found. Extracranial congenital anomalies involved the cardiovascular, respiratory, urinary, and musculoskeletal systems. Death was secondary to severe respiratory distress and bradycardia. The literature concerning this rare form of cerebellar malformation is reviewed.     

Ultraviolet-light induced p53 mutational spectrum in yeast is indistinguishable from p53 mutations in human skin cancer

Ultraviolet (UV) light has been associated with the development of human non-melanoma skin cancers (NMSC). Such cancers often exhibit mutations in the p53 tumour suppressor gene. In order to determine the UV-induced p53 mutation spectrum, a yeast expression vector that harbours a human wild-type p53 cDNA was UV-irradiated in vitro and transfected into a yeast strain that contained the ADE2 gene regulated by a p53-responsive promoter. Forty-five mutant clones contained 51 mutations. Seven mutations were tandem base pair substitutions, four of which being CC-->TT, hallmark mutations of UV mutagenesis. Eighty percent (41/51) of the mutations were single or non-tandem base pair substitutions, the majority of which (27/41) were C-->T transitions. Ninety-five percent of such mutations occurred at dipyrimidine sites. Through a rigorous statistical test, the UV-induced p53 mutation spectrum appears to differ significantly (P < 0.008) from the one induced by the antineoplastic drug chloroethyl-cyclohexyl-nitrosourea, and to be indistinguishable from the one observed in NMSC (P = 0.4). These results demonstrate that the assay allows the determination of carcinogen-specific p53 mutation fingerprints and represents a new tool for molecular epidemiology.      

Periodic arm movements in patients with the restless legs syndrome

A high proportion of patients with restless legs syndrome (RLS) also complain of arm paresthesia but the presence of periodic arm movements (PAM) has never been documented in a sleep laboratory in these patients. We investigated the prevalence of PAM during nocturnal sleep and awakenings in 22 RLS patients. Fifteen patients had a PAM index >5 movements per hour during wakefulness and among them only 3 had a PAM index >5 during sleep. Twenty patients had a periodic leg movement (PLM) index >5 during wakefulness and 17 had a PLM index >5 during sleep. In 42.8% of cases, PAM showed temporal relationship with PLM during wakefulness. These results show that PAM is frequent in RLS and suggest that the basic neurological dysfunction responsible for RLS is probably not located exclusively at the level of the lumbar spinal cord but involves neuronal systems located at upper levels.