Herpes Simplex virus type 2 myeloradiculitis with a pure motor presentationin a liver transplant recipient

In this case report, we describe the first PCR-confirmed case of HSV2 myeloradiculitis with a purely motor presentation, occurring in a 68-year-old liver transplant recipient. The patient reported ascending weakness with no sensory nor sphincteric symptoms, thereby resembling acute demyelinating inflammatory neuropathy, or Guillain-Barr\ue9 syndrome. HSV2 was detected in cerebrospinal fluid by PCR, and the patient was successfully treated with intravenous Acyclovir

Normal and pathogenic variation of RFC1 repeat expansions: implications for clinical diagnosis

Cerebellar Ataxia, Neuropathy and Vestibular Areflexia Syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing (WGS) data from nearly 10,000 individuals recruited within the Genomics England sequencing project to investigate the normal and pathogenic variation of the RFC1 repeat. We identified three novel repeat motifs, AGGGC (n=6 from 5 families), AAGGC (n=2 from 1 family), AGAGG (n=1), associated with CANVAS in the homozygous or compound heterozygous state with the common pathogenic AAGGG expansion. While AAAAG, AAAGGG and AAGAG expansions appear to be benign, here we show a pathogenic role for large AAAGG repeat configuration expansions (n=5). Long read sequencing was used to fully characterise the entire repeat sequence and revealed a pure AGGGC expansion in six patients, whereas the other patients presented complex motifs with AAGGG or AAAGG interruptions. All pathogenic motifs seem to have arisen from a common haplotype and are predicted to form highly stable G quadruplexes, which have been previously demonstrated to affect gene transcription in other conditions. The assessment of these novel configurations is warranted in CANVAS patients with negative or inconclusive genetic testing. Particular attention should be paid to carriers of compound AAGGG/AAAGG expansions, since the AAAGG motif when very large (>500 repeats) or in the presence of AAGGG interruptions. Accurate sizing and full sequencing of the satellite repeat with long read is recommended in clinically selected cases, in order to achieve an accurate molecular diagnosis and counsel patients and their families

Análisis de la evolución en la adquisición de competencias específicas y transversales en los Grados de Geología e Ingeniería Geológica

Depto. de Mineralogía y PetrologíaFac. de Ciencias GeológicasFALSEsubmitte

Material audiovisual para el mural "El Tiempo en Geología" de la Facultad de Ciencias Geológicas

La Geología abarca toda la historia del planeta, por lo que se hace inviable utilizar conceptos temporales de nuestra vida cotidiana. Por ello, se ha realizado un friso para el hall de la Facultad y para presentarlo, se ha realizado un vídeo explicativo del mismo

Perspectives on hiPSC-Derived Muscle Cells as Drug Discovery Models for Muscular Dystrophies

Muscular dystrophies are a heterogeneous group of inherited diseases characterized by the progressive degeneration and weakness of skeletal muscles, leading to disability and, often, premature death. To date, no effective therapies are available to halt or reverse the pathogenic process, and meaningful treatments are urgently needed. From this perspective, it is particularly important to establish reliable in vitro models of human muscle that allow the recapitulation of disease features as well as the screening of genetic and pharmacological therapies. We herein review and discuss advances in the development of in vitro muscle models obtained from human induced pluripotent stem cells, which appear to be capable of reproducing the lack of myofiber proteins as well as other specific pathological hallmarks, such as inflammation, fibrosis, and reduced muscle regenerative potential. In addition, these platforms have been used to assess genetic correction strategies such as gene silencing, gene transfer and genome editing with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), as well as to evaluate novel small molecules aimed at ameliorating muscle degeneration. Furthermore, we discuss the challenges related to in vitro drug testing and provide a critical view of potential therapeutic developments to foster the future clinical translation of preclinical muscular dystrophy studies

A cross-sectional survey study of the impact of COVID-19 pandemic on the training and quality of life of Italian medical residents in the Lombardy region

INTRODUCTION: The reorganization of the healthcare system prompted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has posed unique challenges for Residency Training Programs worldwide. To mitigate its potential negative effects, it is crucial to assess how the pandemic influenced the activity and quality of life of residents. The purpose of this study was to assess the impact of the pandemic on residents' competencies, satisfaction, working load, training patterns and occupational exposure in the clinical, surgical, research and didactic fields and to quantify its effects on quality of life and risk perception. METHODS: An online cross-sectional survey was distributed between 1 June 2020 and 31 July 2020 to 1645 residents enrolled in all Residency Programs of four Universities in northern Italy. The survey included questions about clinical, surgical, and research competencies, educational activity, and quality of life pre- and post-pandemic, and on policies and workplace interventions to reduce exposure to SARS-CoV-2. The main outcome measure was the variation in self-perceived clinical, surgical and research competencies and in specialistic training. Data were analysed using the statistical package R Core Team 4.0.0, estimating mean and standard deviation or median and interquartile range for continuous variables. Variables were compared using chi-square test, Fisher exact tests or McNemar test, as appropriate. A multivariate binary logistic regression analysis was performed to test the effect of different factors on the impact of coronavirus disease-2019 (COVID-19) on self-perceived clinical and research competencies and on didactic training. RESULTS: A total of 498 residents completed the survey (response rate 30.3%). The mean age of respondents was 28.9 years, 62.9% were women, and 52.4% were enrolled in the first two years of Training Programs. On the first pandemic wave, over 60% of residents reported a negative impact of the pandemic on their specialistic training. In contrast, 40% of residents involved in clinical duties perceived an improvement in their clinical competences, especially those involved in COVID-19 care, and 34.5% perceived an improvement in their research competences, particularly junior residents, while only 3.5% reported an improvement in surgical skills. Most surgical residents (88.5%) reported a decrease in surgical activities, mainly due to reduced hospital bed capacity and reduction of elective surgery. Almost 90% of all residents experienced a reduction in their didactic activities, but 80% stated their Residency Program adopted virtual training methods. A statistically significant reduction in all examined quality of life items post-pandemic vs. pre-pandemic was found. Even though most survey participants reported the availability of personal protective equipment for residents, 44% considered themselves to be at higher risk of exposure compared to senior staff. CONCLUSION: COVID-19 pandemic caused a significant disruption in surgical training, but it had a positive impact on clinical competencies among residents involved in COVID-19 and urgent care. The pandemic had a detrimental effect on all quality of life aspects, and most residents considered themselves at higher risk of SARS-CoV-2 infection compared to other healthcare professionals. KEY MESSAGES: Coronavirus disease-2019 (COVID-19) pandemic caused a significant disruption in surgical training, but it had a positive impact on clinical competencies among residents involved in COVID-19 and urgent care. Most residents experienced a reduction of didactic activities. Although the majority of training programs implemented virtual training methods to counteract the restrictions imposed by the pandemic, only half of the residents were satisfied of them. A vast proportion of residents had a high occupational exposure to SARS-CoV-2 and considered themselves at higher risk of COVID-19 infection compared to senior staff. The survey highlighted a statistically significant reduction in five key quality of life measures (i.e. sleep, mood, familiar relationships and social relationships quality and employment satisfaction) during the first wave, with mood and social relationships being the most affected. Notably, employment satisfaction was significantly higher in medical compared to surgical residents

Clinical and genetic features of a cohort of patients with MFN2-related neuropathy

Charcot\u2013Marie\u2013Tooth disease type 2A (CMT2A) is a rare inherited axonal neuropathy caused by mutations in MFN2 gene, which encodes Mitofusin 2, a transmembrane protein of the outer mitochondrial membrane. We performed a cross-sectional analysis on thirteen patients carrying mutations in MFN2, from ten families, describing their clinical and genetic characteristics. Evaluated patients presented a variable age of onset and a wide phenotypic spectrum, with most patients presenting a severe phenotype. A novel heterozygous missense variant was detected, p.K357E. It is located at a highly conserved position and predicted as pathogenic by in silico tools. At a clinical level, the p.K357E carrier shows a severe sensorimotor axonal neuropathy. In conclusion, our work expands the genetic spectrum of CMT2A, disclosing a novel mutation and its related clinical effect, and provides a detailed description of the clinical features of a cohort of patients with MFN2 mutations. Obtaining a precise genetic diagnosis in affected families is crucial both for family planning and prenatal diagnosis, and in a therapeutic perspective, as we are entering the era of personalized therapy for genetic diseases

Multi-omics profiling of CSF from spinal muscular atrophy type 3 patients after nusinersen treatment: a 2-year follow-up multicenter retrospective study

Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in the SMN1 gene resulting in reduced levels of the SMN protein. Nusinersen, the first antisense oligonucleotide (ASO) approved for SMA treatment, binds to the SMN2 gene, paralogue to SMN1, and mediates the translation of a functional SMN protein. Here, we used longitudinal high-resolution mass spectrometry (MS) to assess both global proteome and metabolome in cerebrospinal fluid (CSF) from ten SMA type 3 patients, with the aim of identifying novel readouts of pharmacodynamic/response to treatment and predictive markers of treatment response. Patients had a median age of 33.5 [29.5; 38.25] years, and 80% of them were ambulant at time of the enrolment, with a median HFMSE score of 37.5 [25.75; 50.75]. Untargeted CSF proteome and metabolome were measured using high-resolution MS (nLC-HRMS) on CSF samples obtained before treatment (T0) and after 2 years of follow-up (T22). A total of 26 proteins were found to be differentially expressed between T0 and T22 upon VSN normalization and LIMMA differential analysis, accounting for paired replica. Notably, key markers of the insulin-growth factor signaling pathway were upregulated after treatment together with selective modulation of key transcription regulators. Using CombiROC multimarker signature analysis, we suggest that detecting a reduction of SEMA6A and an increase of COL1A2 and GRIA4 might reflect therapeutic efficacy of nusinersen. Longitudinal metabolome profiling, analyzed with paired t-Test, showed a significant shift for some aminoacid utilization induced by treatment, whereas other metabolites were largely unchanged. Together, these data suggest perturbation upon nusinersen treatment still sustained after 22 months of follow-up and confirm the utility of CSF multi-omic profiling as pharmacodynamic biomarker for SMA type 3. Nonetheless, validation studies are needed to confirm this evidence in a larger sample size and to further dissect combined markers of response to treatment