RESUMO
The impact on the provision of care within the NHS due to COVID-19 can not be understated. It has created various challenges for Oral and Maxillofacial Surgeons due to the high-risk nature of working within this specialty. The aims of this study were to identify the ongoing clinical activities at the height of pandemic, the guidance issued to staff regarding the use of personal protective equipment and the changes to maxillofacial practice. A prospective analysis was commenced within six Oral and Maxillofacial Surgery units in the East Midlands, UK with data being collected by means of a 10-item questionnaire relating to changes in patient care during this time. The responses were analysed to identify compliance with the national guidance produced by the British Association of Oral and Maxillofacial Surgeons. An 87% response rate was obtained (26 respondents from 30 invitations). 73.1% of participants confirmed all surgical members of staff were offered fit tests for FFP3 masks. All units reported a continuation of Head and Neck cancer and emergency operations with a complete reduction in TMJ and orthognathic surgery. FFP3 masks were the most popular masks used for theatre activity whilst FFP2 and surgical masks were more widely used for examining patients and performing procedures in the emergency department. Changes in maxillofacial practice included the use of local flaps compared to free flaps, use of intermaxillary fixation (IMF) where appropriate for craniofacial trauma and routine COVID-19 testing for all inpatients.
Assuntos
COVID-19/epidemiologia , Controle de Infecções/organização & administração , Procedimentos Cirúrgicos Bucais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Cirurgia Bucal/organização & administração , COVID-19/prevenção & controle , COVID-19/transmissão , Humanos , Equipamento de Proteção Individual , Inquéritos e Questionários , Reino UnidoRESUMO
Intraventricular hemorrhage (IVH) in preterm infants leads to cerebral inflammation, reduced myelination of the white matter, and neurological deficits. No therapeutic strategy exists against the IVH-induced white matter injury. AMPA-kainate receptor induced excitotoxicity contributes to oligodendrocyte precursor cell (OPC) damage and hypomyelination in both neonatal and adult models of brain injury. Here, we hypothesized that IVH damages white matter via AMPA receptor activation, and that AMPA-kainate receptor inhibition suppresses inflammation and restores OPC maturation, myelination, and neurologic recovery in preterm newborns with IVH. We tested these hypotheses in a rabbit model of glycerol-induced IVH and evaluated the expression of AMPA receptors in autopsy samples from human preterm infants. GluR1-GluR4 expressions were comparable between preterm humans and rabbits with and without IVH. However, GluR1 and GluR2 levels were significantly lower in the embryonic white matter and germinal matrix relative to the neocortex in both infants with and without IVH. Pharmacological blockade of AMPA-kainate receptors with systemic NBQX, or selective AMPA receptor inhibition by intramuscular perampanel restored myelination and neurologic recovery in rabbits with IVH. NBQX administration also reduced the population of apoptotic OPCs, levels of several cytokines (TNFα, IL-ß, IL-6, LIF), and the density of Iba1(+) microglia in pups with IVH. Additionally, NBQX treatment inhibited STAT-3 phosphorylation, but not astrogliosis or transcription factors regulating gliosis. Our data suggest that AMPA-kainate receptor inhibition alleviates OPC loss and IVH-induced inflammation and restores myelination and neurologic recovery in preterm rabbits with IVH. Therapeutic use of FDA-approved perampanel treatment might enhance neurologic outcome in premature infants with IVH. SIGNIFICANCE STATEMENT: Intraventricular hemorrhage (IVH) is a major complication of prematurity and a large number of survivors with IVH develop cerebral palsy and cognitive deficits. The development of IVH leads to inflammation of the periventricular white matter, apoptosis and arrested maturation of oligodendrocyte precursor cells, and hypomyelination. Here, we show that AMPA-kainate receptor inhibition by NBQX suppresses inflammation, attenuates apoptosis of oligodendrocyte precursor cells, and promotes myelination as well as clinical recovery in preterm rabbits with IVH. Importantly, AMPA-specific inhibition by the FDA-approved perampanel, which unlike NBQX has a low side-effect profile, also enhances myelination and neurological recovery in rabbits with IVH. Hence, the present study highlights the role of AMPA-kainate receptor in IVH-induced white matter injury and identifies a novel strategy of neuroprotection, which might improve the neurological outcome for premature infants with IVH.
Assuntos
Encéfalo/metabolismo , Hemorragia/complicações , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/metabolismo , Receptores de AMPA/metabolismo , Recuperação de Função Fisiológica/fisiologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/ultraestrutura , Sinalização do Cálcio/efeitos dos fármacos , Ventrículos Cerebrais/fisiopatologia , Ventrículos Cerebrais/ultraestrutura , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Glicerol/toxicidade , Hemorragia/induzido quimicamente , Hemorragia/patologia , Humanos , Leucoencefalopatias/tratamento farmacológico , Leucoencefalopatias/etiologia , Masculino , Doenças do Sistema Nervoso/tratamento farmacológico , Nitrilas , Gravidez , Piridonas/farmacologia , Piridonas/uso terapêutico , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Coelhos , Receptores de AMPA/genética , Recuperação de Função Fisiológica/efeitos dos fármacosRESUMO
The intrinsic anisotropy of NbSe2 provides a favorable prerequisite of second harmonic generation (SHG) and rich possibilities for tailoring its nonlinear optical (NLO) properties. Here we report the highly efficient SHG of mechanically exfoliated NbSe2 flakes. The nonlinear optical response changes with excitation wavelengths, layer thicknesses, and polarizations of the excitation laser. The anisotropic SHG response further exhibits the intrinsic non-centrosymmetric crystal structure and could effectively assign the crystalline orientation of NbSe2 flakes. Interestingly, although NbSe2 flakes with tens of nanometers thickness experience attenuations in SHG performance, more efficient SHG anisotropy ratios were obtained, which are around 4 times higher than that of the 5-layer counterpart. The determined second-order nonlinearities of NbSe2 flakes (monolayer: â¼1.0 × 103 pm/V; 3-layer: â¼73 pm/V) are comparable to those of the commonly reported two-dimensional materials (e.g., MoS2, WSe2, graphene) with the same number of layers and much higher than those of commercial nonlinear optical crystals.
RESUMO
The decision about the choice of load-sharing (LS) or load-bearing (LB) osteosynthesis is determined by an interplay of fracture-related and patient-related factors. In some situations a similar fracture in two different patients may be treated successfully by either of these methods. Our aim was to identify preoperative patient-related factors that may assist in deciding which form of osteosynthesis is employed. All adult patients who underwent open reduction and internal fixation of mandibular fractures (excluding condyle) between 1 October 2018 and 1 June 2021 were retrospectively identified. The odds of developing postoperative complications and requiring a return to theatre (RTT) were calculated for each method of fixation together with the following patient factors: smoking, excess alcohol, substance misuse, and severe mental health issues. Of 337 fractures treated using LS principles, 27 (8%) developed complications, of which 20 (6%) required a RTT for repeat osteosynthesis. Of 74 fractures treated using LB principles, seven (10%) developed complications and two (3%) required a RTT for repeat osteosynthesis. The only patient factor that had statistically significant increased odds of a complication requiring RTT was LS osteosynthesis in patients who admitted drinking excess alcohol (ORâ¯=â¯7.83, pâ¯=â¯0.00, 95% CIâ¯=â¯3.13 to 19.60). Complications when treating mandibular fractures are rarely reported in the literature, and lack standardisation in their clinical significance. Figures generally represent overall numbers of patients, whereas the number of individual fractures treated is more accurate. In our study complications occurred in 8% of treated fractures and 10% of patients. The RTT rate was 7% of patients, which compares favourably with a recently stated standard of 10% of patients, as suggested by the Getting it Right First Time (GIRFT) report.
Assuntos
Fraturas Mandibulares , Adulto , Humanos , Fraturas Mandibulares/cirurgia , Fraturas Mandibulares/etiologia , Estudos Retrospectivos , Fixação Interna de Fraturas/efeitos adversos , Fixação Interna de Fraturas/métodos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Redução Aberta/efeitos adversos , Placas Ósseas , Resultado do TratamentoRESUMO
Rheumatic heart disease (RHD) is commonly seen in people from developing and low-income countries. More cases are being recorded in developed countries due to migration and globalization. RHD develops in people with a history of rheumatic fever; it is an autoimmune response to group A streptococcal infection due to similarities at the molecular level. Congestive heart failure, arrhythmia, atrial fibrillation, stroke, and infective endocarditis are a few of the many complications associated with RHD. Here we present a case of a 48-year-old male with a past medical history of rheumatic fever at the age of 12 years, who presented to the emergency room (ER) complaining of bilateral ankle swelling, dyspnea on exertion, and palpitations. The patient was tachycardic with a heart rate of 146 beats per minute and tachypneic with a respiratory rate of 22 breaths per minute. On physical exam, there was a harsh systolic and diastolic murmur at the right upper sternal border. A 12-lead electrocardiogram (EKG) revealed atrial flutter with a variable block. Chest X-ray revealed an enlarged cardiac silhouette with a pro-brain natriuretic peptide (proBNP) of 2,772 pg/mL (normal ≤ 125 pg/mL). The patient was stabilized with metoprolol and furosemide and was admitted to the hospital for further investigation. Transthoracic echocardiogram showed left ventricular ejection fraction (LVEF) of 50-55% with severe concentric hypertrophy of the left ventricle with a severely dilated left atrium. Increased thickness of the aortic valve with severe stenosis and a peak gradient of 139 mm Hg and a mean gradient of 82 mm Hg was noted. The valve area was measured to be 0.8 cm2. Transesophageal echocardiogram showed a tri-leaflet aortic valve with commissural fusion of valve cusps with severe leaflet thickening consistent with rheumatic valve disease. The patient underwent tissue aortic valve replacement with a bioprosthetic valve. The pathology report showed extensive fibrosis and calcification of the aortic valve. The patient came in for a follow-up visit 6 months later and expressed feeling better and more active.
RESUMO
Bacterial transposons are known to move to new genomic sites using either a replicative or a conservative mechanism. The behavior of transposon Tn5 is anomalous. In vitro studies indicate that it uses a conservative mechanism while in vivo results point to a replicative mechanism. To explain this anomaly, a model is presented in which the two mechanisms are not independent--as widely believed--but could represent alternate outcomes of a common transpositional pathway.
Assuntos
Bactérias/genética , Elementos de DNA Transponíveis , Modelos GenéticosRESUMO
The mandible is the most common bone to develop complications following treatment of facial fractures. This is due to a complex interaction of both fracture specific and patient factors. Our aim was to identify those patient factors, with a specific focus on those that may be potentially modifiable to reduce the incidence of complications. A systematic review of the literature was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology to identify patient factors ascribed to an increased risk of complications following the treatment of mandibular fracture. These were divided into non- modifiable and potentially modifiable factors. A meta-analysis was performed to weight those factors for which statistical analysis had been performed. Twenty-two pertinent papers were identified, of which eight described non-modifiable and seven potentially modifiable factors. The most common potentially modifiable factor identified was smoking. Meta-analysis established that tobacco smoking demonstrated an increased risk of complications in three studies (Odds Ratio: 4.04 - 8.09). Division of patient factors into those that are potentially modifiable and those that are not will enable clinicians to focus on those in which change within the immediate postoperative period can be instigated. This includes smoking cessation assistance, education as to the need for a soft diet, and facilitating postoperative clinic attendance. It also enables stratification of risk in terms of consent, and choice of treatment. Further research should use standardised terminology, particularly in stopping the use of generalisable terms such as patient compliance and instead describing its individual components.
Assuntos
Fraturas Mandibulares , Humanos , Incidência , Mandíbula , Fraturas Mandibulares/cirurgia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , FumarRESUMO
Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and is a useful measure in drug design. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. Performing such analyses to cover the entire chemical space of small molecules requires intense computational power. Recent developments using deep learning have enabled us to make sense of massive amounts of complex data sets where the ability of the model to "learn" intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated convolutional neural networks to find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies toward a diverse set of ligands without the need of a docked pose or complex as user input. The models were trained and validated using a stringent methodology for feature extraction. Our model performs better in comparison to some existing methods used widely and is suitable for predictions on high-resolution protein crystal (⩽2.5 Å) and nonpeptide ligand as individual inputs. Our approach to network construction and training on protein-ligand data set prepared in-house has yielded significant insights. We have also tested DEELIG on few COVID-19 main protease-inhibitor complexes relevant to the current public health scenario. DEELIG-based predictions can be incorporated in existing databases including RSCB PDB, PDBMoad, and PDBbind in filling missing binding affinity data for protein-ligand complexes.