关键词： Mitochondrial dysfunction   Energy   Metabolism   Metabolic reconfiguration   ATP  

摘要： It is well-established that mitochondria are the powerhouses of the cell, producing adenosine triphosphate (ATP), the universal energy currency. However, the most significant strengths of the electron transport chain (ETC), its intricacy and efficiency, are also its greatest downfalls. A reliance on metal complexes (Fe\\S clusters, hemes), lipid moities such as cardiolipin, and cofactors including alpha-lipoic acid and quinones render oxidative phosphorylation vulnerable to environmental toxins, intracellular reactive oxygen species (ROS) and fluctuations in diet. To that effect, it is of interest to note that temporal disruptions in ETC activity in most organisms are rarely fatal, and often a redundant number of failsafes are in place to permit continued ATP production when needed. Here, we highlight the metabolic reconfigurations discovered in organisms ranging from parasitic Entamoeba to bacteria such as pseudomonads and then complex eukaryotic systems that allow these species to adapt to and occasionally thrive in harsh environments. The overarching aim of this review is to demonstrate the plasticity of metabolic networks and recognize that in times of duress, life finds a way. (c) 2021 Elsevier Inc. All rights reserved.

关键词： medial epicondyle   pediatric fractures   prone position   treatment   elbow fracture   trauma  

摘要： Background: Operative treatment of medial epicondyle fractures can be performed in either a supine or prone position. In the supine position, fracture visualization is sometimes difficult due to the posterior position of the medial epicondyle. However, the prone position requires extensive patient repositioning but may improve visualization. The purpose of this study was to compare the results and complications between the supine and prone position when treating medial epicondyle fractures. Methods: In a retrospective chart review, patients below 18 who underwent open reduction and internal fixation of an acute medial epicondyle fracture from January 2011 to August 2019 were identified. Patients with <2 months follow-up and concomitant fractures were excluded. Surgical variables, outcomes, and complications were recorded and compared between the supine and prone positions. Results: Sixteen surgeons treated the 204 patients evaluated in this study. The mean age was 11.7 years. In all, 122 (60%) patients were treated in the supine position, and 82 (40%) in the prone position. The mean time in the room was 113 minutes in the supine group, and 141 minutes in the prone group (P<0.001). Tourniquet time was similar between groups (P=0.4). Displacement of the fracture on the first postoperative x-rays was 2.06 mm for the supine position and 1.1 mm for the prone position (P<0.001). We also found good interobserver and intraobserver reliability for the measurements. Five patients (2.5%) required reoperation due to stiffness, 2 patients due to nonunion, 1 patient due to tardy ulnar nerve palsy, and 53 (26%) had surgical hardware removal. The surgical position was not associated with complications or reoperation. Conclusions: While the prone position requires additional time in the operating room, presumably for positioning, the length of the surgical procedure itself does not differ between the 2 positions. Although the trend of the surgeons at our center is towards the prone

关键词： ear   frequency of shooting   GSR sampling   gunshot residues   SEM-EDX   shotgun  

摘要： Detection of GSR particles potentially indicates that a person fired a gun or somehow involved to a shooting event. GSR on the shooter's hand, face, and clothing may disappear within hours and with sweat secretion, washing or cleaning to remove evidences. Due to its anatomical properties, ears are relatively protected;therefore, we aimed to identify GSR particles on ears, to compare its anatomical parts of ears, and compare ears with common GSR sampling sites, based on firing frequency. A 12-gauge semi-automatic shotgun was used. In the 4-week study, one shot in the first week, two consecutive shots in second week, three shots in third week, and five shots in fourth week were fired by six participants. Samples were taken from MAE, CA, and AAECA of both ears and common GSR sampling sites. The characteristic 3-component structure (Pb/Sb/Ba) of the samples was analyzed by SEM/EDX. Right CA was the most suitable area for sampling, which might be attributed to posture of body during targeting. Right ear was the most suitable area to take samples from CA or MAE in 3-shot group. Besides, left AAECA in 1- and 2-shot groups and the left MAE in 5-shot group were the most suitable areas for GSR sampling. In conclusion, ear seems to be a valuable alternative for detection of GSR particles, due to its complex anatomical structure potentially preventing loss of GSR with daily cleaning. Findings suggested that crime scene investigation teams and criminal laboratory staff should consider ear as a valuable alternative for GSR detection.

摘要： The majority of patients and medical students experience some form of psychological trauma or adversity across their life course. All forms of trauma can be associated with adverse health consequences and can negatively affect learning and professional development. Trauma-informed care (TIC) offers a framework to address and mitigate these consequences and promote safety and health. The Substance Abuse and Mental Health Services Administration describes 6 domains of TIC: safety;trust and transparency;peer support;collaboration and mutuality;empowerment, voice, and choice;and cultural, historic, and gender issues. At present, TIC is not taught routinely in undergraduate medical education (UME)-a crucial educational gap given that UME grounds the development of key perspectives and practices that students use throughout their careers. Further, given the prevalence of preexisting trauma among learners and the likelihood of new traumatic exposures during training, medical schools' processes, practices, and learning environments may risk exacerbating or even causing trauma. To address this educational need and support students and their future patients, the authors propose a trauma-informed medical education (TIME) framework. TIME informs medical schools' curricular content and educational context. In UME, curricular content should address trauma epidemiology, physiology, and effects;trauma-informed clinical skills including sensitive communication and physical exam techniques;and trauma-informed self-care techniques including education on organizational resources, how to elicit supports, and personal self-care practices. A trauma-informed educational context encompasses curricular development, including student-faculty coproduction of educational content;curricular delivery, including faculty development on TIC principles;and learning environment, including trauma-informed educational practices, medical student advising, institutional policies, and recruitment. TIME off

关键词： Entactogen   empathogen   MDMA   psychotherapy   PTSD  

摘要： The last two decades have seen a revival of interest in the entactogen 3,4-methylenedioxy-N-methylamphetamine (MDMA) as an adjunct to psychotherapy, particularly for the treatment of post-traumatic stress disorder. While clinical results are highly promising, and MDMA is expected to be approved as a treatment in the near future, it is currently the only compound in its class of action that is being actively investigated as a medicine. This lack of alternatives to MDMA may prove detrimental to patients who do not respond well to the particular mechanism of action of MDMA or whose treatment calls for a modification of MDMA's effects. For instance, patients with existing cardiovascular conditions or with a prolonged history of stimulant drug use may not fit into the current model of MDMA-assisted psychotherapy, and could benefit from alternative drugs. This review examines the existing literature on a host of entactogenic drugs, which may prove to be useful alternatives in the future, paying particularly close attention to any neurotoxic risks, neuropharmacological mechanism of action and entactogenic commonalities with MDMA. The substances examined derive from the 1,3-benzodioxole, cathinone, benzofuran, aminoindane, indole and amphetamine classes. Several compounds from these classes are identified as potential alternatives to MDMA.

关键词： MIS-C   PIMS   SARS-CoV-2 infection   Children   COVID-19  

摘要： Objectives: Multi-system inflammatory syndrome in children (MIS-C) is a post-viral inflammatory vasculopathy of children and adolescents following Covid-19 infection. Since the incidence of SARS-CoVinfections has been increasing in Germany since October 2020, we observe an increasing number of children presenting with MIS-C. Design: We present detailed clinical characteristics of a cohort of nine children with MIS-C admitted to a tertiary PICU at the University Hospital of Cologne between March 2020 and February 2021. Results: The clinical sings and symptoms are largely in line with recent reports. All but one patient had positive SARS-CoV-2 antibodies. Latency form infection to MIS-C was 4-6 weeks. Two children presented with unusual findings: A girl had encephalomyelitis and a boy developed MIS-C side to side with acute leukemia. Conclusion: MIS-C has been increasing in Germany paralell to SARS-CoV-2 infections. Rarely, unuasual findings may be associated with MIS-C. (c) 2021 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://***/licenses/by-ncnd/4.0/).

关键词： Lung squamous cell carcinoma   Alternative splicing   Splicing factor   LASSO   Signature  

摘要： Increasing evidence demonstrated that alternative splicing (AS) plays a vital role in tumorigenesis and clinical outcome of patient. However, systematical analysis of AS in lung squamous cell carcinoma (LUSC) is lacking and greatly necessary. Thus, this study was to systematically estimate the function of AS events served as prognostic indicators in LUSC. Among 31,345 mRNA AS events in 9633 genes, we detected 1996 AS in 1409 genes which have significant connection with overall survival (OS) of LUSC patients. Then, prognostic model based on seven types of AS events was established and we further constructed a combined prognostic model. The Kaplan-Meier curve results suggested that seven types of AS signatures and the combined prognostic model could exhibit robust performance in predicting prognosis. Patients in the high-risk group had significantly shorter OS than those in the low-risk group. The ROC showed all prognostic models had high accuracy and powerful predictive performance with different AUC ranging from 0.837 to 0.978. Moreover, the combined prognostic model had highest performance in risk stratification and predictive accuracy than single prognostic models and had higher accuracy than other mRNA model. Finally, a significant correlation network between survival-related AS genes and prognostic splicing factors (SFs) was established. In conclusion, our study provided several potential prognostic AS models and constructed splicing network between AS and SFs in LUSC, which could be used as potential indicators and treatment targets for LUSC patients.

关键词： stimulants   amphetamine   methylphenidate   attention   adult ADHD  

摘要： Purpose/Background This study aimed to evaluate the frequency of needing to switch the initial treatment of a stimulant to the alternative family in newly referred, medication-naive adults with attention-deficit/hyperactivity disorder (ADHD) initiating treatment with stimulants. Methods/Procedures Subjects were 49 unmedicated adults (18-45 years old) with Diagnostic and Statistical Manual of Disorders (Fifth Edition) ADHD who initiated treatment with a stimulant. Before the clinical assessment with an expert clinician, participants completed the Adult Self-Report, Behavior Rating Inventory of Executive Function-Adult Version, Emotional Dysregulation Subscale of the Barkley Current Behavior Scale-Self-report, and Mind Wandering Questionnaire. The rate of switching was examined using information from the electronic medical record for up to three clinical follow-up visits. Comparisons were made between those who did and did not need to switch on baseline demographic and clinical characteristics. Findings/Results Sixty-seven percent of ADHD patients were initially prescribed a methylphenidate product, and 33%, an amphetamine product. Forty-one percent of ADHD patients needed to switch from their initially prescribed stimulant family within 90 days of initiating treatment because of poor tolerability. Whereas the rate of switching was significantly higher in those initially prescribed methylphenidate, the rate of patients who required changes in formulation (long- to short-acting and vice versa) or additional antianxiety or antidepressant treatment ("strugglers") was higher in those taking amphetamine. Switchers were more impaired on the Adult Self-Report Intrusive scale, whereas nonswitchers were more impaired on the Behavior Rating Inventory of Executive Function Inhibit and Task Monitor scales. However, these findings were small and of unclear clinical significance. Implications/Conclusions Forty-one percent of medication-naive adults with ADHD initiating stimulant tr

关键词： Musculoskeletal injury   Informal caregiver   Patient handling   Lumbar spine  

摘要： Manual patient handling tasks put formal and informal caregivers at risk of musculoskeletal injury. Intervention research to reduce risks to informal caregivers is limited. This study examined effects of slide sheet use when individual informal caregivers performed patient boosting and turning tasks. Three methods of slide sheet use and a baseline method (no slide sheet) were compared, to reposition a 70 kg individual. Muscle activity, ground reaction force, posture, and rating of perceived exertion were significantly affected by task method. Erector Spinae activity was reduced in boosting and turning away tasks with the slide sheet. Shoulder elevation, torso angle, and normalized vertical ground reaction force were also reduced with the slide sheet during boosting. The turn towards task was generally not improved with the slide sheet. Overall, using a slide sheet provided biomechanical benefits to individual caregivers performing two common patient handling tasks: boosting and turning patient away from caregiver.