GGPS1-associated muscular dystrophy with and without hearing loss

Ultra-rare biallelic pathogenic variants in geranylgeranyl diphosphate synthase 1 (GGPS1) have recently been associated with muscular dystrophy/hearing loss/ovarian insufficiency syndrome. Here, we describe 11 affected individuals from four unpublished families with ultra-rare missense variants in GGPS1 and provide follow-up details from a previously reported family. Our cohort replicated most of the previously described clinical features of GGPS1 deficiency; however, hearing loss was present in only 46% of the individuals. This report consolidates the disease-causing role of biallelic variants in GGPS1 and demonstrates that hearing loss and ovarian insufficiency might be a variable feature of the GGPS1-associated muscular dystrophy

Consultas neurológicas e diagnósticos em um grande hospital universitário dedicado a COVID-19

Background: More than one-third of COVID-19 patients present neurological symptomsranging from anosmia to stroke and encephalopathy. Furthermore, pre-existingneurological conditions may require special treatment and may be associated with worseoutcomes. Notwithstanding, the role of neurologists in COVID-19 is probablyunderrecognized. Objective: The aim of this study was to report the reasons forrequesting neurological consultations by internists and intensivists in a COVID-19-dedicated hospital. Methods: This retrospective study was carried out at Hospital dasClínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil, a 900-bedCOVID-19 dedicated center (including 300 intensive care unit beds). COVID-19 diagnosiswas confirmed by SARS-CoV-2-RT-PCR in nasal swabs. All inpatient neurologyconsultations between March 23rd and May 23rd, 2020 were analyzed. Neurologistsperformed the neurological exam, assessed all available data to diagnose theneurological condition, and requested additional tests deemed necessary. Difficultdiagnoses were established in consensus meetings. After diagnosis, neurologists wereinvolved in the treatment. Results: Neurological consultations were requested for 89 outof 1,208 (7.4%) inpatient COVID admissions during that period. Main neurologicaldiagnoses included: encephalopathy (44.4%), stroke (16.7%), previous neurologicaldiseases (9.0%), seizures (9.0%), neuromuscular disorders (5.6%), other acute brainlesions (3.4%), and other mild nonspecific symptoms (11.2%). Conclusions: Mostneurological consultations in a COVID-19-dedicated hospital were requested for severeconditions that could have an impact on the outcome. First-line doctors should be able torecognize neurological symptoms; neurologists are important members of the medicalteam in COVID-19 hospital care.Introdução: Mais de um terço dos pacientes com COVID-19 apresentam sintomasneurológicos que variam de anosmia a AVC e encefalopatia. Além disso, doençasneurológicas prévias podem exigir tratamento especial e estar associadas a pioresdesfechos. Não obstante, o papel dos neurologistas na COVID-19 é provavelmentepouco reconhecido. Objetivo: O objetivo deste estudo foi relatar os motivos para solicitarconsultas neurológicas por clínicos e intensivistas em um hospital dedicado à COVID-19. Métodos: Estudo retrospectivo realizado no Hospital das Clínicas da Faculdade deMedicina da Universidade de São Paulo, Brasil, um centro dedicado à COVID-19 com900 leitos (incluindo 300 leitos para unidades de terapia intensiva). O diagnóstico deCOVID-19 foi confirmado por SARS-CoV-2-RT-PCR em swabs nasais. Todas asinterconsultas de neurologia hospitalar entre 23 de março e 23 de maio de 2020 foramanalisadas. Os neurologistas realizaram o exame neurológico, avaliaram todos os dadosdisponíveis para diagnosticar a patologia neurológica e solicitaram exames adicionaisconforme necessidade. Diagnósticos difíceis foram estabelecidos em reuniões deconsenso. Após o diagnóstico, os neurologistas participaram da condução dos casos.Resultados: Foram solicitadas consultas neurológicas para 89 de 1.208 (7,4%) empacientes internados por COVID-19 durante o período. Os principais diagnósticosneurológicos incluíram: encefalopatia (44,4%), acidente vascular cerebral (16,7%),doenças neurológicas prévias (9,0%), crises epilépticas (9,0%), transtornosneuromusculares (5,6%), outras lesões encefálicas agudas (3,4%) e outros sintomasleves inespecíficos (11,2%). Conclusões: A maioria das consultas neurológicas em umhospital dedicado à COVID-19 foi solicitada para condições graves que poderiam afetaro desfecho clínico. Os médicos na linha de frente devem ser capazes de reconhecersintomas neurológicos. Os neurologistas são membros importantes da equipe médica noatendimento hospitalar à COVID-19

Cell-Free Antigens from Paracoccidioides brasiliensis Drive IL-4 Production and Increase the Severity of Paracoccidioidomycosis

The thermally dimorphic fungus Paracoccidioides brasiliensis (Pb) is the causative agent of paracoccidioidomycosis (PCM), one of the most frequent systemic mycosis that affects the rural population in Latin America. PCM is characterized by a chronic inflammatory granulomatous reaction, which is consequence of a Th1-mediated adaptive immune response. In the present study we investigated the mechanisms involved in the immunoregulation triggered after a prior contact with cell-free antigens (CFA) during a murine model of PCM. The results showed that the inoculation of CFA prior to the infection resulted in disorganized granulomatous lesions and increased fungal replication in the lungs, liver and spleen, that paralleled with the higher levels of IL-4 when compared with the control group. The role of IL-4 in facilitating the fungal growth was demonstrated in IL-4-deficient- and neutralizing anti-IL-4 mAb-treated mice. The injection of CFA did not affect the fungal growth in these mice, which, in fact, exhibited a significant diminished amount of fungus in the tissues and smaller granulomas. Considering that in vivo anti-IL-4-application started one week after the CFA-inoculum, it implicates that IL-4-CFA-induced is responsible by the mediation of the observed unresponsiveness. Further, the characterization of CFA indicated that a proteic fraction is required for triggering the immunosuppressive mechanisms, while glycosylation or glycosphingolipids moieties are not. Taken together, our data suggest that the prior contact with soluble Pb antigens leads to severe PCM in an IL-4 dependent manner

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Educomunicação, Transformação Social e Desenvolvimento Sustentável

Esta publicação apresenta os principais trabalhos dos GTs do II Congresso Internacional de Comunicação e Educação nos temas Transformação social, com os artigos que abordam principalmente Educomunicação e/ou Mídia-Educação, no contexto de políticas de diversidade, inclusão e equidade; e, em Desenvolvimento Sustentável os artigos que abordam os avanços da relação comunicação/educação no contexto da educação ambiental e desenvolvimento sustentável