TRIO gene segregation in a family with cerebellar ataxia

Aim of the study: To report a family with a novel TRIO gene mutation associated withphenotype of cerebellar ataxia. Materials and methods: Seven family members of Caribbean descent were recruited through our ataxia research protocol; of the family members, the mother and all 3 children were found to be affected with severe young-onset and rapidly progressive truncal and appendicular ataxia leading to early disability. Array comparative genomic hybridization, mitochondrial DNA analysis, and whole-exome sequencing were performed on 3 of the family members (mother and 2 daughters). Results: While the maternal grandmother, great uncle and great aunt were unaffected, the mother and 3 children displayed cognitive dysfunction, severe ataxia, spasticity, and speech disturbances. Age of onset ranged between 3 and 17 years, with average current disease duration of 21 years. Whole-exome sequencing showed a variant p.A1214V in exon 22 of the TRIO gene in 3 of the family members. Array comparative genomic hybridization and mitochondrial DNA analysis were normal. The same variant was later discovered in all but one family member. Conclusions and clinical implications: The TRIO p.A1214V variant is associated with cerebellar ataxia in the studied family; it was present in all affected and unaffected family members. Phenotype is severe and broad. Anticipation seems to be present (based on 2 affected generations). It is warranted to screen additional familial early-onset and rapidly progressive ataxia cases for this genotype. TRIO gene mutations may well represent a novel spinocerebellar ataxia subtype

First families with spinocerebellar ataxia type 7 in Poland

Introduction. We present the first two Polish families diagnosed with spinocerebellar ataxia type 7 (SCA7) and draw attention to cardiac involvement as a new potential manifestation of this disease. Material and methods. Two well-documented kindreds are presented. Results. The proband from Family 1 presented aged 54 years with vision worsening followed by progressive imbalance. Brain MRI demonstrated cerebellar atrophy. Genetic testing confirmed CAG repeat expansion (42/10) in ATXN7 gene. The proband from Family 2 developed imbalance at age 20, followed by progressive deterioration of vision. Brain MRI revealed cerebellar atrophy. Additionally, she developed chronic congestive heart failure and, at age 38, had cardiomyopathy with an ejection fraction of 20% and significant mitral and tricuspid regurgitation. Genetic analysis found abnormal CAG expansion in the ATXN7 (46/10). Conclusions and clinical implications. Vision loss due to pigmentary retinal degeneration is the distinguishing feature of SCA7 and often the initial manifestation. Although SCA7 is one of the most common SCAs in Sweden, it has never been reported in neighbouring Poland. Until now, cardiac abnormalities have only been described in infantile-onset SCA7 with large CAG repeats. The observed cardiac involvement in Family 2 may be coincidental, albeit a new possible manifestation of SCA7 cannot be excluded

Spinocerebellar ataxia type 6 family with phenotypic overlap with Multiple System Atrophy

Aim of the study. Multiple system atrophy (MSA) and spinocerebellar ataxia (SCA) share similar symptomatology. We describe a rare occurrence of familial MSA that proved to be SCA6 upon genetic analysis.Materials and methods. Eighty MSA patients were enrolled in our study; blood samples were collected and genetic screening of the familial case for known SCA loci was performed.Results. A 68-year-old woman presented with recurrent and severe episodes of light-headedness, imbalance, frequent falls, neck and lower back stiffness, subjective arm and leg weakness, and numbness and tingling in both feet. One year later, her condition had declined; she experienced more falls, worsening instability, again more generalised but still subjective weakness, impaired fine motor movements, slurred speech, difficulty swallowing, episodes of choking, bladder incontinence, and constipation. Clinical suspicion included parkinsonism, MSA, and SCA. The patient was enrolled in our MSA study and was found to have 22 and 12 CAG repeats in CACNA1A. The other 79 clinical MSA patients were negative for SCA6 screening.Conclusions and clinical implications. While MSA and SCA may have similar presentations during early disease stages, the presence of both conditions on the list of differential diagnoses can be a diagnostic dilemma. Further analysis will aid in developing a biomarker to distinguish between the two conditions and guide proper management

Mapping 123 million neonatal, infant and child deaths between 2000 and 2017

Since 2000, many countries have achieved considerable success in improving child survival, but localized progress remains unclear. To inform efforts towards United Nations Sustainable Development Goal 3.2—to end preventable child deaths by 2030—we need consistently estimated data at the subnational level regarding child mortality rates and trends. Here we quantified, for the period 2000–2017, the subnational variation in mortality rates and number of deaths of neonates, infants and children under 5 years of age within 99 low- and middle-income countries using a geostatistical survival model. We estimated that 32% of children under 5 in these countries lived in districts that had attained rates of 25 or fewer child deaths per 1,000 live births by 2017, and that 58% of child deaths between 2000 and 2017 in these countries could have been averted in the absence of geographical inequality. This study enables the identification of high-mortality clusters, patterns of progress and geographical inequalities to inform appropriate investments and implementations that will help to improve the health of all populations

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Measurement of the W±Z boson pair-production cross section in pp collisions at √s=13TeV with the ATLAS detector

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Charged-particle distributions at low transverse momentum in √s=13 13 TeV pp interactions measured with the ATLAS detector at the LHC

Measurements of distributions of charged particles produced in proton–proton collisions with a centre-of-mass energy of 13 TeV are presented. The data were recorded by the ATLAS detector at the LHC and correspond to an integrated luminosity of 151 μb −1 μb−1 . The particles are required to have a transverse momentum greater than 100 MeV and an absolute pseudorapidity less than 2.5. The charged-particle multiplicity, its dependence on transverse momentum and pseudorapidity and the dependence of the mean transverse momentum on multiplicity are measured in events containing at least two charged particles satisfying the above kinematic criteria. The results are corrected for detector effects and compared to the predictions from several Monte Carlo event generators

Measurement of the inelastic proton-proton cross section at √s=13 TeV with the ATLAS detector at the LHC

This Letter presents a measurement of the inelastic proton-proton cross section using 60  μb −1 of pp collisions at a center-of-mass energy √s of 13 TeV with the ATLAS detector at the LHC. Inelastic interactions are selected using rings of plastic scintillators in the forward region (2.0710 −6 , where M X is the larger invariant mass of the two hadronic systems separated by the largest rapidity gap in the event. In this ξ range the scintillators are highly efficient. For diffractive events this corresponds to cases where at least one proton dissociates to a system with M X >13  GeV . The measured cross section is compared with a range of theoretical predictions. When extrapolated to the full phase space, a cross section of 78.1±2.9  mb is measured, consistent with the inelastic cross section increasing with center-of-mass energy