The emergence of the COVID-19 pandemic has severely affected medical treatment protocols throughout the world. While the pandemic does not affect hand surgeons at first glance, they have a role to ...play. The purpose of this study was to describe the different measures that have been put in place in response to the COVID-19 pandemic by hand surgeons throughout the world. The survey comprised 47 surgeons working in 34 countries who responded to an online questionnaire. We found that the protocols varied in terms of visitors, health professionals in the operating room, patient waiting areas, wards and emergency rooms. Based on these preliminary findings, an international consensus on hand surgery practices for the current viral pandemic, and future ones, needs to be built rapidly.
L’émergence de la pandémie à Covid-19 a bouleversé les pratiques médicales dans le monde. À première vue, cette pandémie ne concerne pas les chirurgiens de la main. Pourtant, ils ont un rôle à jouer. Le but de cette étude était de décrire les différentes pratiques mises en œuvre contre la pandémie à Covid-19 à partir du retour d’expérience de 47 chirurgiens de la main exerçant sur tous les continents. Le matériel comprenait 47 chirurgiens de la main exerçant dans 34 pays qui ont répondu à un questionnaire en ligne portant sur les protocoles Covid-19 mis en place. Les résultats ont montré que les pratiques étaient hétérogènes, tant pour les patients, les visiteurs et le personnel soignant au bloc opératoire, en salle de réunion, aux services d’hébergement des patients, au service d’accueil des urgences et en consultations externes. Il nous semble essentiel de définir un consensus international en chirurgie de la main pour lutter contre les pandémies virales actuelles et futures.
Patients suffering from the metabolic disease hereditary tyrosinemia type I (HT1), caused by fumarylacetoacetate hydrolase deficiency, have a high risk of developing liver cancer. We report that a ...sub-apoptogenic dose of fumarylacetoacetate (FAA), the mutagenic metabolite accumulating in HT1, induces spindle disturbances and segregational defects in both rodent and human cells. Mitotic abnormalities, such as distorted spindles, lagging chromosomes, anaphase/telophase chromatin bridges, aberrant karyokinesis/cytokinesis and multinucleation were observed. Some mitotic asters displayed a large pericentriolar material cloud and/or altered distribution of the spindle pole-associated protein NuMA. FAA-treated cells developed micronuclei which were predominantly CREST-positive, suggesting chromosomal instability. The Golgi complex was rapidly disrupted by FAA, without evident microtubules/tubulin alterations, and a sustained activation of the extracellular signal-regulated protein kinase (ERK) was also observed. Primary skin fibroblasts derived from HT1 patients, not exogenously treated with FAA, showed similar mitotic-derived alterations and ERK activation. Biochemical data suggest that FAA causes ERK activation through a thiol-regulated and tyrosine kinase-dependent, but growth factor receptor- and protein kinase C-independent pathway. Pre-treatment with the MEK inhibitor PD98059 and the Ras farnesylation inhibitor B581 decreased the formation of CREST-positive micronuclei by approximately 75%, confirming the partial contribution of the Ras/ERK effector pathway to the induction of chromosomal instability by FAA. Replenishment of intracellular glutathione (GSH) with GSH monoethylester abolished ERK activation and reduced the chromosomal instability induced by FAA by 80%. Together these results confirm and extend the previously reported genetic instability occurring in cells from HT1 patients and allow us to speculate that this tumorigenic-related phenomenon may rely on the biochemical/cellular effects of FAA as a thiol-reacting and organelle/mitotic spindle-disturbing agent.
Single-exon coding sequences (CDSs), also known as 'single-exon genes' (SEGs), are defined as nuclear, protein-coding genes that lack introns in their CDSs. They have been studied not only to ...determine their origin and evolution but also because their expression has been linked to several types of human cancers and neurological/developmental disorders, and many exhibit tissue-specific transcription. We developed SinEx DB that houses DNA and protein sequence information of SEGs from 10 mammalian genomes including human. SinEx DB includes their functional predictions (KOG (euKaryotic Orthologous Groups)) and the relative distribution of these functions within species. Here, we report SinEx 2.0, a major update of SinEx DB that includes information of the occurrence, distribution and functional prediction of SEGs from 60 completely sequenced eukaryotic genomes, representing animals, fungi, protists and plants. The information is stored in a relational database built with MySQL Server 5.7, and the complete dataset of SEG sequences and their GO (Gene Ontology) functional assignations are available for downloading. SinEx DB 2.0 was built with a novel pipeline that helps disambiguate single-exon isoforms from SEGs. SinEx DB 2.0 is the largest available database for SEGs and provides a rich source of information for advancing our understanding of the evolution, function of SEGs and their associations with disorders including cancers and neurological and developmental diseases. Database URL: http://v2.sinex.cl/.
The aim of this study was to determine the effectiveness of early versus delayed motion on the functional outcomes in patients with distal radius fracture (DRF) treated with a volar locking plate. A ...systematic review and meta-analysis of randomized clinical trials was performed. An electronic search was performed in the Medline, Central, Embase, PEDro, Lilacs, Cinahl, SPORTDiscus, and Web of Science databases. The eligibility criteria included randomized clinical trials that compared the effect of early versus delayed motion on wrist and/or upper limb function, pain, grip strength, and wrist range of motion in subjects older than 18 years with DRF treated with a volar locking plate. Five clinical trials were included that met the eligibility criteria for the quantitative synthesis. At 6 weeks, the PRWE questionnaire showed a mean difference (MD) of −10.6 points (p < 0.001), the MD was −11.1 points for the DASH questionnaire (p < 0.001), −0.56 cm for pain on VAS (p = 0.01), 5.0 kg for grip strength (p = 0.01), 12.5 degrees for wrist flexion (p = 0.07), and 12.8 degrees for wrist extension (p = 0.05). All differences favored the early motion treatment. At 3 months of follow-up, only the DASH, pain on VAS, and grip strength showed significant differences in favor of early motion. At 1 year of follow-up, none of the variables studied were different between groups. In the short term, there was moderate to high evidence of clinically and statistically significant differences in the functional outcomes in favor of early versus delayed motion in patients with DRF treated with a volar locking plate. But these differences were not observed at 1 year of follow-up.
PROSPERO registration no.: CRD42020158706.
Le but de cette étude était de déterminer l’efficacité de la mobilisation précoce versus mobilisation retardée dans les résultats fonctionnels des fractures de l’extrémité distale du radius (FEDR) traitées par plaque antérieure verrouillée. Une revue systématique et une métaanalyse d’essais cliniques contrôlés randomisés ont été réalisées. Une recherche informatique a été menée dans les bases de données Medline, Central, Embase, PEDro, Lilacs, Cinahl, SPORTDiscus, et Web of Science. Les critères d’éligibilité des études incluaient les essais cliniques randomisés qui comparaient mobilisation précoce versus isolation22Remplacer “isolation” par “mobilisation”. retardée en termes de fonction du poignet et du membre supérieur, douleur, force et mobilités du poignet chez des sujets de plus de 18 ans présentant une FEDR traitée par plaque antérieure verrouillée. Cinq essais cliniques respectant les critères d’éligibilité ont été inclus. A 6 semaines, la différence moyenne était de -10,65 points pour la fonction du poignet (p < 0,001) et -11,11 points pour la fonction du membre supérieur (p < 0,001), de -0,56 cm pour l’intensité de la douleur (p = 0,01), de 5,04 kg pour la force (p = 0,01), de 12,49° pour la flexion du poignet (p = 0,07) et de 12,82° pour l’extension du poignet (p = 0,05). Toutes les différences étaient en faveur de la mobilisation précoce. A 3 mois de suivi, seule33Ajouter un “s” à “seule” : “seules”. la fonction du membre supérieur, la douleur et la force montraient une différence significative en faveur de la mobilisation précoce. A un an de suivi, aucune des variables étudiées ne montrait de différence significative entre les groupes. A court terme, il existe des différences cliniques statistiquement significatives dans les résultats fonctionnels, en faveur de la mobilisation précoce dans les FEDR traitées par plaque antérieure verrouillées.
Glycolytic metabolism in meiotic and post-meiotic spermatogenic cells shows differentiation-related changes. The developmental and physiological significance of these metabolic changes is not known. ...The aim of the present study was to test the hypothesis that glucose and lactate metabolism can modulate intracellular calcium Ca2+(i) in spermatogenic cells in an opposing and dynamic manner. Fluorescent probes were used to measure Ca2+(i) and pH(i), and HPLC was used to measure intracellular adenine nucleotides and mitochondrial sensing of ATP turnover. Ca2+(i) in pachytene spermatocytes and round spermatids was modulated by changes in lactate and glucose concentrations in the media. The kinetics and magnitude of the Ca2+(i) changes induced by lactate and glucose were different in meiotic and post-meiotic spermatogenic cells. The presence of glucose in the medium induced a decrease in pH(i) in spermatogenic cells. This glucose-induced pH(i) decrease occurred later than the changes in Ca2+(i), which were also observed when the pH(i) decrease was inhibited, indicating that the glucose-induced Ca2+(i) increase was not a consequence of pH(i) changes. Hexose phosphorylation in glycolysis was part of the mechanism by which glucose metabolism induced a Ca2+(i) increase in spermatogenic cells. The sensitivity of Ca2+(i) to carbohydrate metabolism was higher in round spermatids than in pachytene spermatocytes. Thus, differentiation-related changes in carbohydrate metabolism in spermatogenic cells determine a dynamic and differential modulation of their Ca2+(i) by glucose and lactate, two substrates secreted by the Sertoli cells.
Hereditary tyrosinemia type I (HTI) is the most severe disease of the tyrosine degradation pathway. HTI is caused by a deficiency of fumarylacetoacetate hydrolase (FAH), the enzyme responsible for ...the hydrolysis of fumarylacetoacetate (FAA). As a result, there is an accumulation of metabolites such as maleylacetoacetate, succinylacetone, and FAA. The latter was shown to display mutagenic, cytostatic, and apoptogenic activities and to cause chromosomal instability. Herein, we demonstrate that FAA also causes a cellular insult leading to the endoplasmic reticulum (ER) stress signaling. Treatment of V79 Chinese hamster lung cells with an apoptogenic dose of FAA (100 μm) causes an early induction of the ER resident chaperone GRP78/BiP and a simultaneous phosphorylation of the eIF2α. FAA treatment also causes a subsequent induction of the proapoptotic CHOP (CEBP homologous protein) transcription factor as well as a late activation of caspase-12. Data obtained from fah–/– mice taken off the therapeutic 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3 cyclohexanedione drug are similar. However, in this mouse model, there is also an increase in proteasome activity indicative of ER-associated degradation. This difference observed between the two models may be due to the fact that the murine model measures the effects of all metabolites accumulating in hereditary tyrosinemia type I as opposed to the cellular model that only measures the effects of exogenous FAA.
Hereditary tyrosinemia type I (HT I, McKusick 276,700) is a metabolic disease with a pattern of autosomal recessive inheritance. The disease is caused by a deficiency of the enzyme involved in the ...last step in the degradation of the amino acid tyrosine, fumarylacetoacetate hydrolase (FAH). The result of this block is the accumulation of catabolites some of which have been proposed to be highly toxic due to their alkylating potential. In humans, hereditary tyrosinemia is often associated with the development of hepatocellular carcinoma in young patients. The reasons for the high incidence of hepatocellular carcinoma are unknown but it has been suggested that it may be caused by accumulated metabolites such as fumarylacetoacetate (FAA) and maleylacetoacetate (MAA). The various mutational defects in the FAH gene are reviewed. The use of two mouse models of this disease to study the molecular basis of the pathologies associated with HT I are discussed. Finally, some preliminary data on the mutagenic potential of FAA and MAA in a gene reversal assay are presented.
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![[122] CAFFEINE TREATMENT IN...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0168-8278_1600-0641/small "[122] CAFFEINE TREATMENT INHIBITS LIVER ACTIVATION OF Akt SURVIVAL PATHWAY IN THE fah−/− MURINE MODEL OF HEREDITARY TYROSINEMIA TYPE 1")
