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Ionic liquids (ILs) are promising alternative compounds that enable the development of technologies based on their unique properties as solvents or catalysts. These technologies require integrated product and process designs to select ILs with optimal process performances at an industrial scale to promote cost-effective and sustainable technologies. The digital era and multiscale research methodologies have changed the paradigm from experiment-oriented to hybrid experimental-computational developments guided by process engineering. This Review summarizes the relevant contributions (>300 research papers) of process simulations to advance IL-based technology developments by guiding experimental research efforts and enhancing industrial transferability. Robust simulation methodologies, mostly based on predictive COSMO-SAC/RS and UNIFAC models in Aspen Plus software, were applied to analyze key IL applications: physical and chemical CO2 capture, CO2 conversion, gas separation, liquid-liquid extraction, extractive distillation, refrigeration cycles, and biorefinery. The contributions concern the IL selection criteria, operational unit design, equipment sizing, technoeconomic and environmental analyses, and process optimization to promote the competitiveness of the proposed IL-based technologies. Process simulation revealed that multiscale research strategies enable advancement in the technological development of IL applications by focusing research efforts to overcome the limitations and exploit the excellent properties of ILs.
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In utero exposure to maternal antibodies targeting the fetal acetylcholine receptor isoform (fAChR) can impair fetal movement, leading to arthrogryposis multiplex congenita (AMC). Fetal AChR antibodies have also been implicated in apparently rare, milder myopathic presentations termed fetal acetylcholine receptor inactivation syndrome (FARIS). The full spectrum associated with fAChR antibodies is still poorly understood. Moreover, since some mothers have no myasthenic symptoms, the condition is likely underreported, resulting in failure to implement effective preventive strategies. Here we report clinical and immunological data from a multicentre cohort (n = 46 cases) associated with maternal fAChR antibodies, including 29 novel and 17 previously reported with novel follow-up data. Remarkably, in 50% of mothers there was no previously established myasthenia gravis (MG) diagnosis. All mothers (n = 30) had AChR antibodies and, when tested, binding to fAChR was often much greater than that to the adult AChR isoform. Offspring death occurred in 11/46 (23.9%) cases, mainly antenatally due to termination of pregnancy prompted by severe AMC (7/46, 15.2%), or during early infancy, mainly from respiratory failure (4/46, 8.7%). Weakness, contractures, bulbar and respiratory involvement were prominent early in life, but improved gradually over time. Facial (25/34; 73.5%) and variable peripheral weakness (14/32; 43.8%), velopharyngeal insufficiency (18/24; 75%) and feeding difficulties (16/36; 44.4%) were the most common sequelae in long-term survivors. Other unexpected features included hearing loss (12/32; 37.5%), diaphragmatic paresis (5/35; 14.3%), CNS involvement (7/40; 17.5%) and pyloric stenosis (3/37; 8.1%). Oral salbutamol used empirically in 16/37 (43.2%) offspring resulted in symptom improvement in 13/16 (81.3%). Combining our series with all previously published cases, we identified 21/85 mothers treated with variable combinations of immunotherapies (corticosteroids/intravenous immunoglobulin/plasmapheresis) during pregnancy either for maternal MG symptom control (12/21 cases) or for fetal protection (9/21 cases). Compared to untreated pregnancies (64/85), maternal treatment resulted in a significant reduction in offspring deaths (P < 0.05) and other complications, with treatment approaches involving intravenous immunoglobulin/ plasmapheresis administered early in pregnancy most effective. We conclude that presentations due to in utero exposure to maternal (fetal) AChR antibodies are more common than currently recognized and may mimic a wide range of neuromuscular disorders. Considering the wide clinical spectrum and likely diversity of underlying mechanisms, we propose 'fetal acetylcholine receptor antibody-related disorders' (FARAD) as the most accurate term for these presentations. FARAD is vitally important to recognize, to institute appropriate management strategies for affected offspring and to improve outcomes in future pregnancies. Oral salbutamol is a symptomatic treatment option in survivors.
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Artrogripose , Miastenia Gravis , Doenças Neuromusculares , Gravidez , Feminino , Adulto , Humanos , Imunoglobulinas Intravenosas , Receptores Colinérgicos , Miastenia Gravis/terapia , Miastenia Gravis/complicações , Autoanticorpos , Artrogripose/complicaçõesRESUMO
AIM: To facilitate multisite studies and international clinical research, this study aimed to identify consensus-based, standardized common data elements (CDEs) for arthrogryposis multiplex congenita (AMC). METHOD: A mixed-methods study comprising of several focus group discussions and three rounds of modified Delphi surveys to achieve consensus using two tiered-rating scales were conducted. RESULTS: Overall, 45 clinical experts and adults with lived experience (including 12 members of an AMC consortium) participated in this study from 11 countries in North America, Europe, and Australia. The CDEs include 321 data elements and 19 standardized measures across various domains from fetal development to adulthood. Data elements pertaining to AMC phenotypic traits were mapped according to the Human Phenotype Ontology. A universal governance structure, local operating protocols, and sustainability plans were identified as the main facilitators, whereas limited capacity for data sharing and the need for a federated informatics infrastructure were the main barriers. INTERPRETATION: Collection of systematic data on AMC using CDEs will allow investigations on etiological pathways, describe epidemiological profile, and establish genotype-phenotype correlations in a standardized manner. The proposed CDEs will facilitate international multidisciplinary collaborations by improving large-scale studies and opportunities for data sharing, knowledge translation, and dissemination.
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BACKGROUND: Up to 7% of patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) remain genetically undiagnosed after routine genetic testing. These patients are thought to carry deep intronic variants, structural variants or splicing alterations not detected through multiplex ligation-dependent probe amplification or exome sequencing. METHODS: RNA was extracted from seven muscle biopsy samples of patients with genetically undiagnosed DMD/BMD after routine genetic diagnosis. RT-PCR of the DMD gene was performed to detect the presence of alternative transcripts. Droplet digital PCR and whole-genome sequencing were also performed in some patients. RESULTS: We identified an alteration in the mRNA level in all the patients. We detected three pseudoexons in DMD caused by deep intronic variants, two of them not previously reported. We also identified a chromosomal rearrangement between Xp21.2 and 8p22. Furthermore, we detected three exon skipping events with unclear pathogenicity. CONCLUSION: These findings indicate that mRNA analysis of the DMD gene is a valuable tool to reach a precise genetic diagnosis in patients with a clinical and anatomopathological suspicion of dystrophinopathy that remain genetically undiagnosed after routine genetic testing.
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Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Distrofina/genética , RNA Mensageiro/genética , Mutação , Reação em Cadeia da Polimerase MultiplexRESUMO
BACKGROUND: Limb-girdle muscular dystrophies (LGMD) are a heterogeneous group of genetically determined muscle disorders. TRAPPC11-related LGMD is an autosomal-recessive condition characterised by muscle weakness and intellectual disability. METHODS: A clinical and histopathological characterisation of 25 Roma individuals with LGMD R18 caused by the homozygous TRAPPC11 c.1287+5G>A variant is reported. Functional effects of the variant on mitochondrial function were investigated. RESULTS: The c.1287+5G>A variant leads to a phenotype characterised by early onset muscle weakness, movement disorder, intellectual disability and elevated serum creatine kinase, which is similar to other series. As novel clinical findings, we found that microcephaly is almost universal and that infections in the first years of life seem to act as triggers for a psychomotor regression and onset of seizures in several individuals with TRAPPC11 variants, who showed pseudometabolic crises triggered by infections. Our functional studies expanded the role of TRAPPC11 deficiency in mitochondrial function, as a decreased mitochondrial ATP production capacity and alterations in the mitochondrial network architecture were detected. CONCLUSION: We provide a comprehensive phenotypic characterisation of the pathogenic variant TRAPPC11 c.1287+5G>A, which is founder in the Roma population. Our observations indicate that some typical features of golgipathies, such as microcephaly and clinical decompensation associated with infections, are prevalent in individuals with LGMD R18.
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Deficiência Intelectual , Microcefalia , Distrofia Muscular do Cíngulo dos Membros , Distrofias Musculares , Roma (Grupo Étnico) , Humanos , Roma (Grupo Étnico)/genética , Fenótipo , Distrofia Muscular do Cíngulo dos Membros/genética , Debilidade Muscular , Proteínas de Transporte VesicularRESUMO
Pathogenic variants in LMNA have been associated with a wide spectrum of muscular conditions: the laminopathies. LMNA-related congenital muscular dystrophy is a laminopathy characterised by the early onset of symptoms and often leads to a fatal outcome at young ages. Children face a heightened risk of malignant arrhythmias. No established paediatric protocols for managing this condition are available. We review published cases and provide insights into disease progression in two twin sisters with LMNA-related muscular dystrophy. Our objective is to propose a cardiac surveillance and management plan tailored specifically for paediatric patients. We present a family of five members, including two twin sisters with LMNA-related muscular dystrophy. A comprehensive neuromuscular and cardiac work-up was performed in all family members. Genetic analysis using massive sequencing technology was performed in both twins. Clinical assessment showed that only the twins showed diagnoses of LMNA-related muscular dystrophy. Follow-up showed an early onset of symptoms and life-threatening arrhythmias, with differing disease progressions despite both twins passing away. Genetic analysis identified a de novo rare missense deleterious variant in the LMNA gene. Other additional rare variants were identified in genes associated with myasthenic syndrome. Early-onset neuromuscular symptoms could be related to a prognosis of worse life-threatening arrhythmias in LMNA related muscular dystrophy. Being a carrier of other rare variants may be a modifying factor in the progression of the phenotype, although further studies are needed. There is a pressing need for specific cardiac recommendations tailored to the paediatric population to mitigate the risk of malignant arrhythmias.
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Lamina Tipo A , Distrofias Musculares , Gêmeos Monozigóticos , Humanos , Lamina Tipo A/genética , Gêmeos Monozigóticos/genética , Feminino , Distrofias Musculares/genética , Distrofias Musculares/terapia , Masculino , Criança , Linhagem , Pré-Escolar , Arritmias Cardíacas/genética , Arritmias Cardíacas/etiologiaRESUMO
DTNA encodes α-dystrobrevin, a component of the macromolecular dystrophin-glycoprotein complex (DGC) that binds to dystrophin/utrophin and α-syntrophin. Mice lacking α-dystrobrevin have a muscular dystrophy phenotype, but variants in DTNA have not previously been associated with human skeletal muscle disease. We present 12 individuals from four unrelated families with two different monoallelic DTNA variants affecting the coiled-coil domain of α-dystrobrevin. The five affected individuals from family A harbor a c.1585G > A; p.Glu529Lys variant, while the recurrent c.1567_1587del; p.Gln523_Glu529del DTNA variant was identified in the other three families (family B: four affected individuals, family C: one affected individual, and family D: two affected individuals). Myalgia and exercise intolerance, with variable ages of onset, were reported in 10 of 12 affected individuals. Proximal lower limb weakness with onset in the first decade of life was noted in three individuals. Persistent elevations of serum creatine kinase (CK) levels were detected in 11 of 12 affected individuals, 1 of whom had an episode of rhabdomyolysis at 20 years of age. Autism spectrum disorder or learning disabilities were reported in four individuals with the c.1567_1587 deletion. Muscle biopsies in eight affected individuals showed mixed myopathic and dystrophic findings, characterized by fiber size variability, internalized nuclei, and slightly increased extracellular connective tissue and inflammation. Immunofluorescence analysis of biopsies from five affected individuals showed reduced α-dystrobrevin immunoreactivity and variably reduced immunoreactivity of other DGC proteins: dystrophin, α, ß, δ and γ-sarcoglycans, and α and ß-dystroglycans. The DTNA deletion disrupted an interaction between α-dystrobrevin and syntrophin. Specific variants in the coiled-coil domain of DTNA cause skeletal muscle disease with variable penetrance. Affected individuals show a spectrum of clinical manifestations, with severity ranging from hyperCKemia, myalgias, and exercise intolerance to childhood-onset proximal muscle weakness. Our findings expand the molecular etiologies of both muscular dystrophy and paucisymptomatic hyperCKemia, to now include monoallelic DTNA variants as a novel cause of skeletal muscle disease in humans.
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Transtorno do Espectro Autista , Distrofias Musculares , Neuropeptídeos , Camundongos , Humanos , Animais , Criança , Distrofina/genética , Distrofina/metabolismo , Transtorno do Espectro Autista/metabolismo , Distrofias Musculares/metabolismo , Distroglicanas/metabolismo , Processamento Alternativo , Músculo Esquelético/patologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Proteínas Associadas à Distrofina/genética , Proteínas Associadas à Distrofina/metabolismoRESUMO
PURPOSE: An estimated 34 % of reported operating room fires involve the airway. Despite the inherent risks in otolaryngologic surgery, education regarding prevention and management of airway fires is limited in graduate medical training. One contributing factor is a lack of reporting of such rare events in our literature. METHODS: The U.S. Food and Drug Administration's Manufacturer and User Facility Device Experience database was queried for reports of adverse events related to fires occurring during surgical procedures of the airway from January 1, 2010, to March 31, 2020. RESULTS: 3687 reports were identified and 49 unique reports of airway fire were included. Sustained fires were described in 16 (32.7 %) reports and 33 (67.3 %) described transient flares. 2 fires extended beyond the airway and 9 (18.4 %) were noted to have occurred at the start of the case. Fires were reported most commonly during tonsillectomy (n = 22 [44.9 %]), vocal fold excision (n = 5 [10.2 %]), and adenoidectomy (n = 4 [8.2 %]). 46 reports attributed flare initiation to a specific element of the fire triangle. 16 patient and 2 operator injuries were reported. Saline washing was utilized in 7 (14.3 %) cases overall. Patients were extubated immediately in 2 (12.5 %) of the 16 reports of sustained fires. 0 mortalities were reported. CONCLUSION: Airway fires were reported in a variety of upper airway procedures performed regularly by otolaryngologists. The triggering factor that led to fire was identified as a spark or char in about half of the reported cases, and only 2 reports described immediate removal of the endotracheal tube.
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Incêndios , Laringe , Humanos , Incêndios/prevenção & controle , Salas Cirúrgicas , Procedimentos Cirúrgicos Otorrinolaringológicos/efeitos adversos , Intubação IntratraquealRESUMO
The characterization of suspended dust near the Martian surface is extremely relevant to understand the climate of Mars. In this frame, a Dust Sensor instrument, an infrared device designed to obtain the effective parameters of Martian dust using the scattering properties of the dust particles, was developed. The purpose of this article is to present a novel methodology to calculate, from experimental data, an instrumental function of the Dust Sensor that allows solving the direct problem and providing the signal that this instrument would provide given a distribution of particles. The experimental method is based on recording the signal measured when a Lambertian reflector is gradually introduced into the interaction volume at different distances from the detector and source and applying tomography techniques (inverse Radon transform) to obtain the image of a section of the interaction volume. This method provides a complete mapping of the interaction volume experimentally, which determines the Wf function. The method was applied to solve a specific case study. Among the advantages of this method, it should be noted that it avoids assumptions and idealizations of the dimensions of the volume of interaction and reduces the time required to carry out simulations.
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Poeira , Marte , Poeira/análise , Meio Ambiente Extraterreno , CalibragemRESUMO
Several clinical trials are working on drug development for Duchenne and Becker muscular dystrophy (DMD and BMD) treatment, and, since the expected increase in dystrophin is relatively subtle, high-sensitivity quantification methods are necessary. There is also a need to quantify dystrophin to reach a definitive diagnosis in individuals with mild BMD, and in female carriers. We developed a method for the quantification of dystrophin in DMD and BMD patients using spectral confocal microscopy. It offers the possibility to capture the whole emission spectrum for any antibody, ensuring the selection of the emission peak and allowing the detection of fluorescent emissions of very low intensities. Fluorescence was evaluated first on manually selected regions of interest (ROIs), proving the usefulness of the methodology. Later, ROI selection was automated to make it operator-independent. The proposed methodology correctly classified patients according to their diagnosis, detected even minimal traces of dystrophin, and the results obtained automatically were statistically comparable to the manual ones. Thus, spectral imaging could be implemented to measure dystrophin expression and it could pave the way for detailed analysis of how its expression relates to the clinical course. Studies could be further expanded to better understand the expression of dystrophin-associated protein complexes (DAPCs).
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Distrofina , Distrofia Muscular de Duchenne , Humanos , Feminino , Distrofina/genética , Distrofina/metabolismo , Distrofia Muscular de Duchenne/diagnóstico por imagem , Distrofia Muscular de Duchenne/metabolismoRESUMO
A proper interaction between muscle-derived collagen XXV and its motor neuron-derived receptors protein tyrosine phosphatases σ and δ (PTP σ/δ) is indispensable for intramuscular motor innervation. Despite this, thus far, pathogenic recessive variants in the COL25A1 gene had only been detected in a few patients with isolated ocular congenital cranial dysinnervation disorders. Here we describe five patients from three unrelated families with recessive missense and splice site COL25A1 variants presenting with a recognizable phenotype characterized by arthrogryposis multiplex congenita with or without an ocular congenital cranial dysinnervation disorder phenotype. The clinical features of the older patients remained stable over time, without central nervous system involvement. This study extends the phenotypic and genotypic spectrum of COL25A1 related conditions, and further adds to our knowledge of the complex process of intramuscular motor innervation. Our observations indicate a role for collagen XXV in regulating the appropriate innervation not only of extraocular muscles, but also of bulbar, axial, and limb muscles in the human.
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Artrogripose , Artrogripose/diagnóstico , Artrogripose/genética , Face , Humanos , Músculo Esquelético , Mutação , FenótipoRESUMO
Insulin-like growth factor-I (IGF-I) signaling plays a key role in neuroinflammation. Here we show that IGF-1 also regulates phagocytosis of reactive astrocytes through p110α isoform of phosphatidylinositol 3-kinase (PI3K), differentially in both sexes. Systemic bacterial lipopolysaccharide (LPS)-treatment increased the expression of GFAP, a reactive astrocyte marker, in the cortex of mice in both sexes and was blocked by IGF-1 only in males. In primary astrocytes, LPS enhanced the mRNA expression of Toll-like receptors (TLR2,4) and proinflammatory factors: inducible nitric oxide synthase (iNOS), chemokine interferon-γ-inducible protein-10 (IP-10) and cytokines (IL-1ß, IL-6, and IL-10) in male and female. Treatment with IGF-1 counteracted TLR4 but not TLR2, iNOS, and IP10 expression in both sexes and cytokines expression in males. Furthermore, reactive astrocyte phagocytosis was modulated by IGF-1 only in male astrocytes. IGF-1 was also able to increase AKT-phosphorylation only in male astrocytes. PI3K inhibitors, AG66, TGX-221, and CAL-101, with selectivity toward catalytic p110α, p110ß, and p110δ isoforms respectively, reduced AKT-phosphorylation in males. All isoforms interact physically with IGF-1-receptor in both sexes. However, the expression of p110α is higher in males while the expression of IGF-1-receptor is similar in male and female. AG66 suppressed the IGF-1 effect on cytokine expression and counteracted the IGF-1-produced phagocytosis decrease in male reactive astrocytes. Results suggest that sex-differences in the effect of IGF-1 on the AKT-phosphorylation could be due to a lower expression of the p110α in female and that IGF-1-effects on the inflammatory response and phagocytosis of male reactive astrocytes are mediated by p110α/PI3K subunit.
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Fator de Crescimento Insulin-Like I , Fosfatidilinositol 3-Quinases , Animais , Astrócitos/metabolismo , Feminino , Inflamação , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Camundongos , Fagocitose , Fosfatidilinositol 3-Quinase , Fosfatidilinositol 3-Quinases/metabolismo , Isoformas de ProteínasRESUMO
BACKGROUND AND PURPOSE: Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients. METHODS: Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included. Bedside functional scales (Egen Klassification [EK2], Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]) were also collected when available. Spearman's rho correlations (rs) and Bangdiwala's concordance test (B) were used to evaluate the scales' construct validity. Monthly slopes of change were used to calculate their responsiveness of the scales. RESULTS: The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong correlations with each other (rs > 0.70). A floor effect in motor function scales was found in the weakest patients (HFMSE < 5 and RULM < 10), and a ceiling effect was found in stronger patients (HFMSE > 60 and RULM > 35). The ALSFRS-R (B = 0.72) showed a strong ability to discriminate between walkers, sitters and non-sitters, and the HFMSE (B = 0.86) between walkers and sitters. The responsiveness was low overall, although in treated patients a moderate responsiveness was found for the ALSFRS-R and HFMSE in walkers (0.69 and 0.61, respectively) and for EK2 in sitters (0.65) and non-sitters (0.60). CONCLUSIONS: This study shows the validity and limitations of the scales most frequently used to assess adult SMA patients. Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness.
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Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Criança , Adulto , Humanos , Avaliação de Resultados em Cuidados de Saúde , Extremidade SuperiorRESUMO
BACKGROUND AND PURPOSE: The aim was to assess the safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients. METHODS: Patients older than 15 years and followed for at least 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb Module, RULM) in five referral centers were included. The clinical and patients' global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percentage predicted forced vital capacity were collected when available. RESULTS: Seventy-nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points (±0.46) in RULM (p < 0.001) after 6 months. After a mean follow-up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (odds ratio [OR] 1.15, p = 0.006), the 6-min walk test (OR = 1.07, p < 0.001) and the EK2 (OR = 0.81, p = 0.001). Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p = 0.033), ALSFRS-R (p = 0.005) and EK2 (p < 0.001). According to the CGI-C and PGI-C, 64.1% and 61.5% of treated patients improved with treatment. Being a non-sitter was associated with less response to treatment, whilst a longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild. CONCLUSIONS: Nusinersen treatment is associated with some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk-benefit ratio.
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Atrofia Muscular Espinal , Atrofias Musculares Espinais da Infância , Adulto , Humanos , Injeções Espinhais , Atrofia Muscular Espinal/tratamento farmacológico , Oligonucleotídeos/efeitos adversos , Atrofias Musculares Espinais da Infância/tratamento farmacológicoRESUMO
PURPOSE: The present study was developed to evaluate the effectiveness of a simple rapid technique for de-epithelializing cutaneous flaps and grafts in parotidectomy reconstruction. MATERIALS AND METHODS: 109 patients who underwent a parotidectomy with abdominal free dermal fat graft (FDFG) reconstruction between 2018 and 2021 were evaluated based on demographic factors, past medical/surgical history, type of parotidectomy performed, operative factors, and post-operative complications. These data were then stratified based on de-epithelialization technique as well as tumor malignancy status to determine any differences in complication rates or perioperative factors between electrocautery (EC) and cold knife (CK) techniques within both benign and malignant subgroups. RESULTS: 77 of the 109 participants underwent FDFG de-epithelialization using monopolar electrocautery (EC) and the remaining 32 participants underwent de-epithelialization using traditional cold knife (CK) technique. There was no statistical difference among the two groups in overall complication rate. The EC group had a significantly shorter operation time ("EC vs. CK": 144.2 min vs. 174.7 min; p = 0.031). Additionally, histopathologic samples showed that both techniques left the underlying dermis intact and without damage. CONCLUSIONS: This study demonstrated that there is no difference in complication rate or histology of FDFGs de-epithelialized using EC compared to CK. It was also shown that when controlling for confounders by looking solely at the benign subgroup of patients, EC de-epithelialization was a faster technique than CK. These findings suggest that EC is just as effective as CK, and may actually be a more efficient surgical technique to accomplish de-epithelialization of FDFG.
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Procedimentos de Cirurgia Plástica , Retalhos Cirúrgicos , Eletrocoagulação , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Período Pós-Operatório , Procedimentos de Cirurgia Plástica/métodos , Estudos RetrospectivosRESUMO
OBJECTIVE: The purpose of this study was to examine the role intraoperative otolaryngology stretching microbreak (OSMB) has on musculoskeletal (MSK) pain and discomfort in otolaryngologists. BACKGROUND: Otolaryngology procedures subject surgeons to significant amounts of pain and strain over their years of training. MSK pain is a serious concern for otolaryngologists' career longevity as well as their general wellbeing. METHODS: Participants from two different hospitals and one private practice were recruited to participate in this study. An initial ergonomic survey was obtained to assess baseline MSK pain, and its subjective impact on operative performance. The participants then completed three control days without OSMB exercises, followed by three intervention days with OSMB exercises which were completed at 20-40 minute intervals. Preoperative and postoperative pain rating surveys were completed before and after each procedure and at the end of the day to determine changes in pain and/or discomfort. RESULTS: Ten otolaryngologists (50 % men, 50 % women; mean age 35.6 years) participated in this study. Half of the participants indicated that they were concerned their pain would limit their ability to operate in the future. 70 % of participants indicated that they have not attempted to treat this pain and 60 % did not try any stretching exercises outside the operating room (OR) to mitigate their symptoms. Participants reported neck, upper back, and lower back to be the primary MSK discomfort. OSMB improved participants' pain scores in neck, shoulders, hands, and lower back pain (p < 0.05). CONCLUSION: MSK pain has shown to be a serious concern for the ability of otolaryngologists to continue performing surgery in the future. OSMB may be an effective strategy that can be implemented by otolaryngologists intraoperatively to improve MSK pain and overall well being.
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Dor Musculoesquelética , Doenças Profissionais , Cirurgiões , Masculino , Feminino , Humanos , Adulto , Dor Musculoesquelética/etiologia , Dor Musculoesquelética/prevenção & controle , Otorrinolaringologistas , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controle , ErgonomiaRESUMO
PURPOSE: Office-based procedures in otolaryngology are increasingly utilized to increase efficiency, reduce cost, and eliminate risks associated with surgery. Gland-preserving surgical management of sialadenitis and sialolithiasis are often performed in the operating room, although many surgeons are moving this practice to clinic. We aim to determine the difference in patient charges and perioperative outcomes for salivary gland procedures performed in the clinic versus the OR. METHODS: Retrospective series of patients presenting with sialolithiasis, acute or chronic sialadenitis, and stricture between 2010 and 2019. Demographics, perioperative variables, setting, and charge data were collected. RESULTS: 528 patients underwent operative intervention (n = 427 office, n = 101 OR). Cohort demographics were comparable. Sialolithiasis was the most common presenting diagnosis in both cohorts. Both cohorts had similar rates of complete (p = 0.09) and partial (p = 0.97) response to treatment. A higher percentage of patients in the OR group reported no improvement (21.4 vs 12.2%, p = 0.034). Overall complications were similar (p = 0.582). Mean charges were statistically greater in the OR ($5560.35 OR vs $1298.33 office, p < 0.001). Operative time was significantly reduced in the office group (21.8 min vs 60.85 min, p < 0.001). CONCLUSIONS: Appropriately selected patients can be successfully treated in outpatient clinic without compromising patient safety or quality while significantly reducing the financial burden to patients and the healthcare system.
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Cálculos das Glândulas Salivares , Sialadenite , Endoscopia/métodos , Humanos , Salas Cirúrgicas , Estudos Retrospectivos , Cálculos das Glândulas Salivares/cirurgia , Sialadenite/diagnóstico , Sialadenite/cirurgia , Resultado do TratamentoRESUMO
Collagen VI-related disorders are the second most common congenital muscular dystrophies for which no treatments are presently available. They are mostly caused by dominant-negative pathogenic variants in the genes encoding α chains of collagen VI, a heteromeric network forming collagen; for example, the c.877G>A; p.Gly293Arg COL6A1 variant, which alters the proper association of the tetramers to form microfibrils. We tested the potential of CRISPR/Cas9-based genome editing to silence or correct (using a donor template) a mutant allele in the dermal fibroblasts of four individuals bearing the c.877G>A pathogenic variant. Evaluation of gene-edited cells by next-generation sequencing revealed that correction of the mutant allele by homologous-directed repair occurred at a frequency lower than 1%. However, the presence of frameshift variants and others that provoked the silencing of the mutant allele were found in >40% of reads, with no effects on the wild-type allele. This was confirmed by droplet digital PCR with allele-specific probes, which revealed a reduction in the expression of the mutant allele. Finally, immunofluorescence analyses revealed a recovery in the collagen VI extracellular matrix. In summary, we demonstrate that CRISPR/Cas9 gene-edition can specifically reverse the pathogenic effects of a dominant negative variant in COL6A1.
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Sistemas CRISPR-Cas , Colágeno Tipo VI , Alelos , Sistemas CRISPR-Cas/genética , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Humanos , MutaçãoRESUMO
Thymidine kinase (TK2) deficiency causes mitochondrial DNA depletion syndrome. We aimed to report the clinical, biochemical, genetic, histopathological, and ultrastructural features of a cohort of paediatric patients with TK2 deficiency. Mitochondrial DNA was isolated from muscle biopsies to assess depletions and deletions. The TK2 genes were sequenced using Sanger sequencing from genomic DNA. All muscle biopsies presented ragged red fibres (RRFs), and the prevalence was greater in younger ages, along with an increase in succinate dehydrogenase (SDH) activity and cytochrome c oxidase (COX)-negative fibres. An endomysial inflammatory infiltrate was observed in younger patients and was accompanied by an overexpression of major histocompatibility complex type I (MHC I). The immunofluorescence study for complex I and IV showed a greater number of fibres than those that were visualized by COX staining. In the ultrastructural analysis, we found three major types of mitochondrial alterations, consisting of concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles. The pathological features in the muscle showed substantial differences in the youngest patients when compared with those that had a later onset of the disease. Additional ultrastructural features are described in the muscle biopsy, such as sarcomeric de-structuration in the youngest patients with a more severe phenotype.
Assuntos
Miopatias Mitocondriais , Timidina Quinase/metabolismo , DNA Mitocondrial/análise , DNA Mitocondrial/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Miopatias Mitocondriais/genética , Miopatias Mitocondriais/patologia , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Succinato Desidrogenase , Timidina Quinase/genéticaRESUMO
BACKGROUND: Prior to thyroid surgery, a subset of patients chronically uses steroids to manage medical conditions such as Grave's disease, auto-immune conditions, or organ transplantation. Existing literature describes adverse effects of prolonged steroid use on surgical outcomes, however there remains a paucity of data investigating the specific effects of steroid use on postoperative outcomes after thyroidectomy. This study aims to identify complication risks steroid users are predisposed to after thyroidectomy. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program Database (ACS-NSQIP) was queried to identify and isolate all patients who had undergone thyroidectomy procedures by Current Procedure Terminology codes from 2005 through 2018. Univariate analysis was performed to compare steroid uses and non-steroid users. Coarsened exact matching was utilized to homogenize the two cohorts based on demographics and preoperative comorbidities. RESULTS: A total of 153,595 thyroidectomies were initially included. After Coarsened exact matching, 116,861 patients were categorized as non-steroid users, and 2,965 as steroid users. The steroid cohort demonstrated significantly higher rates of any complication (P < 0.001) as well as overall surgical, cardiopulmonary, and renal complications. Individual complications such as superficial surgical site infections (P = 0.013), pulmonary embolism (P = 0.016), deep vein thrombosis (P = 0.011), progressive renal insufficiency (P = 0.006), and unplanned readmission (P = 0.026) were also increased. CONCLUSIONS: Patients with chronic steroid use undergoing thyroidectomy are at an increased risk for surgical, cardiopulmonary, and renal complications. Further research on preoperative steroid management is necessary for optimizing outcomes in this population.