Heroin- and Fentanyl-Induced Respiratory Depression in a Rat Plethysmography Model: Potency, Tolerance, and Sex Differences.

The opioid overdose death toll in the United States is an ongoing public health crisis. We characterized the magnitude and duration of respiratory depression, the leading cause of death in opioid overdose cases, induced by heroin or fentanyl and the development of tolerance in male and female rats. We used whole-body plethysmography to first establish dose-response curves by recording breathing for 60 minutes post-intravenous opioid injection. We then tested the development of respiratory tolerance to acute heroin or fentanyl over several weeks and to chronic fentanyl with acute fentanyl or heroin challenge. Heroin and fentanyl each provoked dose-dependent respiratory depression. Heroin caused prolonged (45-60 minute) respiratory depression in female and male rats, characterized by decreased frequency, tidal volume, and minute ventilation and increased inspiratory time and apneic pause. Fentanyl produced similar changes with a shorter duration (10-15 minutes). High-dose heroin or fentanyl produced robust respiratory depression that was slightly more severe in females and, when given intermittently (acute doses 2 to 3 weeks apart), did not lead to tolerance. In contrast, chronic fentanyl delivered with an osmotic minipump resulted in tolerance to acute fentanyl and heroin, characterized by a shorter duration of respiratory depression. This effect persisted during withdrawal in males only. Our model and experimental design will allow for investigation of the neurobiology of opioid-induced respiratory depression and for testing potential therapeutics to reverse respiratory depression or stimulate breathing. SIGNIFICANCE STATEMENT: Fentanyl was more potent and had shorter duration in producing respiratory depression than heroin in both sexes, whereas female rats were more sensitive than males to heroin-induced respiratory depression. Tolerance/cross-tolerance develops in chronic fentanyl administration but is minimized with long interadministration intervals.

Remote, asynchronous training and feedback enables development of neurodynamic skills in physiotherapy students.

BACKGROUND: During the COVID-19 pandemic, face-to-face teaching and learning of physiotherapy practical skills was limited. Asynchronous, remote training has been effective in development of clinical skills in some health professions. This study aimed to determine the effect of remote, asynchronous training and feedback on development of neurodynamic skills in physiotherapy students. METHODS: Longitudinal repeated measurements study, across four training sessions. Participants engaged in a remote training program for development of upper limb neurodynamic techniques. In this sequential training, participants viewed the online tutorial, practiced independently, and uploaded a video of their performance for formative assessment and feedback from a trained instructor via a checklist and rubric. RESULTS: Intra-subject analyses of 60 third-year physiotherapy students showed that the target standard of performance, with no further significant change in scores, was attained following session 2 for the checklist and session 3 for the rubric. This shows that two sessions are required to learn the procedures, and three sessions yield further improvements in performance quality. CONCLUSION: The remote, asynchronous training and feedback model proved to be an effective strategy for students' development of neurodynamic testing skills and forms a viable alternative to in-person training. This study contributes to the future of acquiring physiotherapy clinical competencies when distance or hybrid practice is required.

Epidemiologic Study of Gene Distribution in Romanian and Brazilian Patients with Non-Cicatricial Alopecia.

Background: Androgenetic alopecia (AGA) and alopecia areata (AA) are the most common types of non-cicatricial alopecia. Both diseases have limited effective therapeutic options and affect patient quality of life. Pharmacogenetic tests can help predict the most appropriate treatment option by evaluating the single nucleotide polymorphisms (SNPs) corresponding to genes related to alopecia. The objective of the study was to evaluate and compare selected SNPs and genes in AA and AGA patients from Romania and Brazil. Materials and Methods: We performed a retrospective study regarding the associations between AA and AGA and 45 tag SNPs of 15 genes in 287 Romanian and 882 Brazilian patients. The DNA samples were collected from oral mucosa using a swab. The SNPs were determined by the qPCR technique. Each genetic test displays the subject's genotype of the selected gene and the prediction of a successful treatment (e.g., genotype AA of the GR-alpha gene is related to a predisposition to normal sensibility to topical glucocorticoid, and, therefore, glucocorticoids should be effective). Results: The GR-alpha, GPR44-2, SULT1A1, and CRABP2 genes were statistically significantly different in Brazil compared to Romania. The SULT1A1 activity that predicts the response to minoxidil treatment showed in our analysis that minoxidil is recommended in half of the cases of AGA and AA. Patients with AGA and a high expression of SRD5A1 or PTGFR-2 may benefit from Dutasteride or Latanoprost treatment, respectively. Most of the studied genes showed no differences between the two populations. Conclusions: The DNA analysis of the patients with alopecia may contribute to a successful treatment.

Acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination: A report of three cases and review of the literature.

Small fiber neuropathy usually presents with gradual and progressive chronic length-dependent pain. Acute small fiber neuropathy is rarely reported. Three patients with acute onset neuropathic pain after Oxford-AstraZeneca ChAdOx1-S vaccination are described. Two patients were identified at the Oxford University NHS Foundation Trust, Oxford, UK and one patient in Red de Salud UC Christus, Santiago, Chile. All patients underwent a clinical assessment that included a detailed neurological examination, laboratory investigations, nerve conduction studies, thermal threshold testing, and skin biopsy for intra-epidermal nerve fiber density. Patients seen in Oxford underwent MRI of the brain and spinal cord. Cerebrospinal analysis was not performed. Neuropathic symptoms (burning pain, dysaesthesias) developed in the hands and feet within 2 weeks of vaccination. On clinical examination, there was pinprick and thermal hyposensitivity in the area of neuropathic pain. Laboratory investigation, nerve conduction tests, sympathetic skin responses, and MRI showed no relevant abnormalities. Thermal thresholds were abnormal and intra-epidermal nerve fiber density in the lower leg was reduced. In two cases symptoms persist after several months. Three cases of definite acute small fiber neuropathy after Oxford-AstraZeneca ChAdOx1-S vaccination are described. At follow up, neuropathic pain was present in two of the patients.

Epidemiological and Clinical Characteristics of Hospitalized Pediatric Patients with SARS-CoV-2 Infection in Mexico City, Mexico.

Background: Evidence from across the world suggests that the pediatric population shows different clinical manifestations and has a lower risk of severe presentation of SARS-CoV-2 infection compared to adults. However, Mexico has one of the highest mortality rates in the pediatric population due to SARS-CoV-2 infection. Therefore, our objective was to explore the epidemiological and clinical characteristics associated with a positive confirmatory test in the Mexican pediatric population admitted to a tertiary care hospital in Mexico City. Methods: Clinical, imaging and laboratory data were retrospectively collected from 121 children hospitalized during the period from March 4th, 2020, to August 8th, 2021. The patients were identified as suspicious cases according to the guidelines of the General Directorate of Epidemiology of Mexico. Real-time polymerase chain reaction (RT-PCR) tests were used to confirm SARS-CoV-2 infection. Categorical variables were compared using the Chi-square test, and propensity score matching was performed to determine univariate and multivariate odds ratios of the population regarding a positive vs. negative SARS-CoV-2 result. Results: Of the 121 children, 36 had laboratory-confirmed SARS-CoV-2 infection. The main risk for SARS-CoV-2-associated pediatric hospitalization was contact with a family member with SARS-CoV-2. It was also found that fever and fatigue were statistically significantly associated with a positive SARS-CoV-2 test in multivariate models. Clinical and laboratory data in this Mexican hospitalized pediatric cohort differ from other reports worldwide; the mortality rate (1.6%) of the population studied was higher than that seen in reports from other countries. Conclusion: Our study found that fever and fatigue at hospital presentation as well as an antecedent exposure to a family member with SARS-CoV-2 infection were important risk factors for SARS-CoV-2 positivity in children at hospital admission.

Safety of Allogeneic Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Complex Perianal Fistulas Not Associated With Crohn's Disease: A Phase I Clinical Trial.

BACKGROUND: Anal fistula treatment aims to eradicate the fistula, preserve the sphincter, prevent recurrence, and allow an early return to daily activities for the patient. Because of the difficulty of achieving these goals, stem cell-based therapy has emerged for the treatment of complex perianal fistula with promising results. OBJECTIVE: The objective of this study was to evaluate the safety of allogeneic mesenchymal stem cells in the treatment of complex anal fistula in patients without Crohn's disease. DESIGN: This was a prospective nonrandomized phase I clinical trial. SETTINGS: This study was conducted at a second-level hospital. PATIENTS: Twenty consecutive patients diagnosed with a complex fistula were included. INTERVENTIONS: All patients received 40 × 106 allogeneic mesenchymal stem cells. In patients with 2 tracts, 20 × 106 stem cells were applied on each tract. MAIN OUTCOME MEASURES: The patients were discharged 24 hours after the procedure and were evaluated at 1, 2, 4, 8, 16, and 24 weeks after the application. The long-term follow-up was performed 1 year after the procedure. RESULTS: The procedure was performed in a total of 20 patients from October 1, 2016, to October 31, 2017; 1 patient was eliminated from the final data analysis. No adverse effects were reported within the first 24 hours, and all the patients were discharged asymptomatic. Three patients (15%) presented with perianal abscess. In 1 patient, the abscess appeared at the fourth week, and, in the other 2 patients, the abscess was diagnosed at week 8. Complete closure was achieved in 13 (69%) patients. LIMITATIONS: This was a nonrandomized controlled trial. CONCLUSION: The use of allogeneic mesenchymal stem cells as a treatment is a safe option for the management of complex perianal fistula not associated with Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B443. SEGURIDAD DE LAS CLULAS MADRE MESENQUIMALES ALOGNICAS DERIVADAS DEL TEJIDO ADIPOSO PARA EL TRATAMIENTO DE FSTULAS PERIANALES COMPLEJAS NO ASOCIADAS CON LA ENFERMEDAD DE CROHN ENSAYO CLNICO DE FASE I: ANTECEDENTES:El tratamiento de la fístula anal tiene como objetivo erradicar la fístula, preservar el esfínter, prevenir la recurrencia y permitir un retorno temprano a las actividades diarias del paciente. Debido a la dificultad de alcanzar estos objetivos, ha surgido una terapia basada en células madre para el tratamiento de la fístula perianal compleja con resultados prometedores.OBJETIVO:El objetivo de este estudio fue evaluar la seguridad de las células madre mesenquimales alogénicas en el tratamiento de la fístula anal compleja en pacientes sin enfermedad de Crohn.DISEÑO:Este fue un ensayo clínico prospectivo no aleatorizado de fase I.AMBIENTE:Este estudio se realizó en un hospital de segundo nivel.PACIENTES:Veinte pacientes consecutivos diagnosticados de fístula compleja.INTERVENCIONES:Todos los pacientes recibieron 40 x 106 células madre mesenquimales alogénicas, en pacientes con dos tractos, se aplicaron 20 x 106 células madre en cada tracto.PRINCIPALES MEDIDAS DE RESULTADO:Los pacientes fueron dados de alta 24 horas después del procedimiento y fueron evaluados 1, 2, 4, 8, 16, 24 semanas después de la aplicación. El seguimiento a largo plazo se realizó un año después del procedimiento.RESULTADOS:El procedimiento se realizó en un total de 20 pacientes desde el 1 de octubre de 2016 al 31 de octubre de 2017; un paciente fue eliminado del análisis de datos final. No se informaron efectos adversos en las primeras 24 horas, todos los pacientes fueron dados de alta asintomáticos. Tres pacientes (15%) presentaron absceso perianal. En un paciente, el absceso apareció a la cuarta semana y en los otros dos pacientes el absceso se diagnosticó en la octava semana. El cierre completo se logró en 13 (69%) de los pacientes.LIMITACIONES:Este fue un ensayo controlado no aleatorio.CONCLUSIÓN:El uso de células madre mesenquimales alogénicas como tratamiento es una opción segura para el manejo de la fístula perianal compleja no asociada con la enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B443.

Multiple severe vertebral fractures during the 3-month period following a missed dose of denosumab in a postmenopausal woman with osteoporosis previously treated with alendronate
.

Denosumab is a monoclonal antibody that decreases bone resorption and increases bone mass and strength in trabecular and cortical bone leading to a reduction in fracture in women and men. Its effects are reversed after discontinuation. Recently, there has been concern about the discontinuation of denosumab and the increased risk of multiple vertebral fractures that would be associated with rapid bone loss due to high bone turnover and consequent increase in markers of bone remodeling, far above the baseline values. Some case reports have demonstrated the occurrence of more than two fractures within a period of 8 - 16 months after the drug's discontinuation. A 56-year-old female presented with multiple vertebral fractures in a short period of time after denosumab withdrawal. She took alendronate for 12 years since the occurrence of a rib fracture (from the age of 30 to 42 years). After a long period with no medication (12 years), she was placed on denosumab. On the day she was due to take the fourth injection, she had sudden back pain, and magnetic resonance imaging (MRI) showed a grade II fracture at T9. She had simply forgot to take the scheduled dose of denosumab. Three months later, she presented with several episodes of severe back pain and loss of height and was diagnosed with multiple new severe vertebral fractures. This case illustrates an uncommon and severe bone disease following the inadvertent discontinuation of denosumab treatment.
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Effectiveness of a 16-month multi-component and environmental school-based intervention for recovery of poor income overweight/obese children and adolescents: study protocol of the health multipliers program.

BACKGROUND: Excess of weight is a serious public health concern in almost all countries, afflicting people of different ages and socioeconomic backgrounds. Studies have indicated the need for developing treatment strategies that intervene directly in the obesogenic environment. This study aims to evaluate the effectiveness of a multi-component and environmental school-based intervention, lasting 16 months, on the recovery of the nutritional status of low-income children and adolescents with overweight/ obesity. METHODS/STUDY DESIGN: The study was conducted by the Center for Recovery and Nutritional Education (CREN) in São Paulo, Brazil. Two schools located in poor neighborhoods were selected for the intervention, between March 2016 and June 2017. The participants were all students aged 8 to 12 years from the two participating schools. At the beginning of the intervention, anthropometric measurements were carried out to assess the nutritional status of the students. For convenience, students from one of the schools were considered as the control group, while those from the other school formed the experimental group. The intervention in the experimental group (n = 438) consists of the following weekly activities at school: psychological counseling in groups, theoretical/practical nutrition workshops, and supervised physical education classes. In addition, theoretical and practical educational activities are held regularly for parents, teachers, and cooks. Students with excess of weight (≥1 body mass index [BMI] -for-age Z score, n = 138) received clinical and nutritional care periodically at the outpatient care at CREN. Students enrolled in the control group (n = 353) participated in psychological counseling groups and theoretical/practical nutrition workshops for 6 months held in the school environment to provide motivation to entire classrooms. In the following 10 months, students with excess of weight from the control group (n = 125) were invited to attend the routine outpatient care at CREN. DISCUSSION: This study is the first to assess the effectiveness of a multi-component and environmental school-based intervention for the recovery of low-income, overweight/obese children and adolescents. If positive, the results demonstrate the feasibility for the recovery of excess of weight in populations of similar conditions and age. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials - ReBEC Primary Id Number RBR-9t2jr8 . Registration Date: Nov. 30, 2016. Retrospectively registered. Protocol version: 3.

ASP-G: an ASP-based method for finding attractors in genetic regulatory networks.

MOTIVATION: Boolean network models are suitable to simulate GRNs in the absence of detailed kinetic information. However, reducing the biological reality implies making assumptions on how genes interact (interaction rules) and how their state is updated during the simulation (update scheme). The exact choice of the assumptions largely determines the outcome of the simulations. In most cases, however, the biologically correct assumptions are unknown. An ideal simulation thus implies testing different rules and schemes to determine those that best capture an observed biological phenomenon. This is not trivial because most current methods to simulate Boolean network models of GRNs and to compute their attractors impose specific assumptions that cannot be easily altered, as they are built into the system. RESULTS: To allow for a more flexible simulation framework, we developed ASP-G. We show the correctness of ASP-G in simulating Boolean network models and obtaining attractors under different assumptions by successfully recapitulating the detection of attractors of previously published studies. We also provide an example of how performing simulation of network models under different settings help determine the assumptions under which a certain conclusion holds. The main added value of ASP-G is in its modularity and declarativity, making it more flexible and less error-prone than traditional approaches. The declarative nature of ASP-G comes at the expense of being slower than the more dedicated systems but still achieves a good efficiency with respect to computational time. AVAILABILITY AND IMPLEMENTATION: The source code of ASP-G is available at http://bioinformatics.intec.ugent.be/kmarchal/Supplementary_Information_Musthofa_2014/asp-g.zip.

One-year human experience with a novel endoluminal, endoscopic gastric bypass sleeve for morbid obesity.

INTRODUCTION: Here, we report the first series of patients with 1-year implantation of a novel, endoluminal, endoscopically delivered and retrieved gastro-duodeno-jejunal bypass sleeve (GJBS) (ValenTx, Inc. Carpinteria, CA, USA). In this report, we present the safety, feasibility of the device, weight loss, and changes in comorbidities. METHODS AND PROCEDURES: A prospective, single-center, 12-month trial was designed. The patients are morbidly obese individuals who meet the NIH criteria for bariatric surgery. The GJBS is a 120-cm sleeve secured at the esophago-gastric junction with endoscopic and laparoscopic techniques that is designed to create an endoluminal gastro-duodeno-jejunal bypass. The device was implanted and, at the completion of the trial, retrieved with an endoscopic technique. The primary endpoints were safety and incidence of adverse events. The secondary outcomes included the percentage of excess weight loss (EWL) and changes in comorbidities, specifically glucose control, use of antihyperglycemics, and changes in hemoglobin A1C levels. RESULTS: From July 2009 until October 2009, 13 patients were prospectively enrolled for the 1-year trial. The study included five men and eight women with a mean preoperative BMI of 42 kg/m(2). One patient was excluded, at the time of endoscopic evaluation, due to inflammation at the GE junction. Two additional patients required early explantation of the device, within the first 4 weeks, due to patient intolerance. Upon explant of the device, both patients' symptoms improved. In the remaining ten patients, the device was implanted, left in situ for 12 months, and then retrieved endoscopically. Safe delivery of the cuff at the gastro-esophageal junction was seen in all ten patients whom had device implants, without complication. No esophageal leak was seen immediately post-procedure or during follow-up. The sleeve device was well tolerated within the bowel lumen during the 12-month study, specifically, no bowel erosions, ulceration, or pancreatitis was observed. All ten patients reached the 1-year mark. Of the ten, six had fully attached and functional devices throughout the follow-up, verified by endoscopy. The mean percentage EWL, at 1 year, in this group was 54 %. In the remaining four patients, partial cuff detachment was observed at follow-up endoscopy. The percentage EWL was lower in this group. Of the six patients that reached a year with a fully attached device, five were followed at an average of 14-months post-explant (26 months from the time of device implant). These five maintained an average percentage EWL of 30 % at the 14-month post-explant follow-up. Co-morbidites measured included diabetes mellitus, hypertension, hyperlipidemia, and use of antihyperglycemics. Each of the measured comorbidities showed improvement during the 12-month trial. DISCUSSION: The endoluminal, GJBS can be safely placed and retrieved. The short-term data show it is well tolerated with a good safety profile. It achieves excellent weight loss results with over 70 % of all comorbidities resolved or significantly improved.

Antibacterial activity of new oxazolidin-2-one analogues in methicillin-resistant Staphylococcus aureus strains.

Staphylococcus aureus is one of the most common causes of nosocomial infections. The purpose of this study was the synthesis and in vitro evaluation of antimicrobial activity of 10 new 3-oxazolidin-2-one analogues on 12 methicillin resistant S. aureus (MRSA) clinical isolates. S. aureus confirmation was achieved via catalase and coagulase test. Molecular characterization of MRSA was performed by amplification of the mecA gene. Antimicrobial susceptibility was evaluated via the Kirby-Bauer disc diffusion susceptibility test protocol, using commonly applied antibiotics and the oxazolidinone analogues. Only (R)-5-((S)-1-dibenzylaminoethyl)-1,3-oxazolidin-2-one (7a) exhibited antibacterial activity at 6.6 µg. These results, allow us to infer that molecules such as 7a can be potentially used to treat infections caused by MRSA strains.

Targeted and untargeted serum NMR metabolomics to reveal initial kidney disease in diabetes mellitus.

Serum 1H NMR metabolomics has been used as a diagnostic tool for screening type 2 diabetes (T2D) with chronic kidney disease (CKD) as comorbidity. This work aimed to evaluate 1H NMR data to detect the initial kidney damage and CKD in T2D subjects, through multivariate statistical analysis. Clinical data and biochemical parameters were obtained for classifying five experimental groups using KDIGO guidelines: Control (healthy subjects), T2D, T2D-CKD-mild, T2D-CKD-moderate, and T2D-CKD-severe. Serum 1H NMR spectra were recorded to follow two strategies: one based on metabolite-to-creatinine (Met/Cr) ratios as targeted metabolomics, and the second one based on untargeted metabolomics from the 1H NMR profile. A prospective biomarkers panel of the early stage of T2D-CKD based in metabolite-to-creatinine ratio (ornithine/Cr, serine/Cr, mannose/Cr, acetate/Cr, acetoacetate/Cr, formate/Cr, and glutamate/Cr) was proposed. Later, a statistical model based on non-targeted metabolomics was used to predict initial CKD, and its metabolic pathway analysis allowed identifying the most affected pathways: phenylalanine, tyrosine, and tryptophan biosynthesis; valine, leucine, and isoleucine degradation; glyoxylate and dicarboxylate metabolism; glycine, serine, and threonine metabolism; and histidine metabolism. Nonetheless, further studies with a larger cohort are advised to precise ranges in metabolite-to-creatinine ratios and evaluate the prediction pertinency to detect initial CKD in T2D patients in both statistical models proposed.

Severe dysphagia due to an esophageal duplication cyst in sixth decade, unusual presentation of a rare pathology.

BACKGROUND: Esophageal duplication cysts are rare congenital tumors usually diagnosed and treated during childhood. Most of them are located in the mediastinum and appear as a mass besides the esophagus. Unfortunately, symptoms are non-specific and depend on the size and location of the mass; therefore, they can easily be missed. If symptoms appear, surgical resection is necessary to prevent troublesome complications. CASE PRESENTATION: We present the case of a 60-year-old woman who presented with severe progressive dysphagia and epigastric pain. After further evaluation, a paraesophageal cystic mass was found, and surgery was required. Non-communicating esophageal duplication cyst was the final diagnosis. CONCLUSION: Esophageal duplication cysts are a rare pathology in adults; their symptoms will vary depending on their size and location. Preoperative diagnosis is difficult as symptoms are non-specific and can be missed. If severe dysphagia, pain, or any other complication appears, surgery should not be delayed.

Interactive virtual scenarios as a technological resource to improve musculoskeletal clinical reasoning skills of undergraduate physiotherapy students.

BACKGROUND: Clinical reasoning is a fundamental competency in the learning process of health professionals. Since learning with traditional methods presents difficulties, teaching with interactive virtual scenarios is a good alternative. OBJECTIVE: To describe the impact of a blended training with interactive virtual scenarios for the development of clinical reasoning skills in undergraduate physiotherapy students. METHODS: A sample of 92 students solved eight storylines. Assessment error percentage, clinical pattern recognition, satisfaction, and the perception of difficulty were obtained. A proportions test was used to compare baseline and final assessments. To analyze the relationship between the variables, multilevel univariate logistic regression models were built. RESULTS: A significant difference was observed in the error percentage between baseline and final assessment (p < .001). Comparing the last storyline to the first one, there were 2.63 times more possibilities to correctly recognize the pattern. The error percentage was associated with the opportunity to recognize the pattern precisely (p < .001). Thus, for each increasing unit in the error percentage, the possibility to correctly recognize the pattern decreased by 11% (OR = 0.89). CONCLUSIONS: The use of this innovative blended training with virtual scenarios allowed students to systematically improve their recognition abilities of clinical patterns and decrease mistakes in the decision-making process.

Effects of Elbow Crutch Locomotion on Gluteus Medius Activation During Stair Ascending.

Crutches can help with the locomotion of people with walking disorders or functional limitations. However, little is known about hip muscle activation during stair ascending using different crutch locomotion patterns in people without disorders and limitations. Thus, we determined the acute effects of elbow crutch locomotion on gluteus medius (GM) activity during stair ascending. This comparative analytic cross-sectional study enrolled ten healthy men (22.0 ± 0.47 years). Participants climbed up the stairs with elbow crutches using one or two crutches, with ipsilateral or contralateral use, and after loading or unloading a limb. EMG signals were recorded from anterior, middle, and posterior portions of the GM and compared between the crutch conditions. The Kruskal-Wallis test and Dunn's multiple comparison test were performed (α = 5%). The activation of the GM increased with the ipsilateral use of crutches, with two crutches and three points, and when all the load depended only on one limb. GM activation decreased with contralateral use and in the unload limb. In conclusion, ascending stairs with elbow crutches alters the GM activation. The more critical factors were choosing the crutches' lateral use, the number of crutches, and if the limb is loaded or unloaded while ascending the stairs. Our findings can be helpful to increase or decrease the GM activation for those who use or will use crutches.

Human experience with an endoluminal, endoscopic, gastrojejunal bypass sleeve.

BACKGROUND: This report describes the authors' experience with a unique endoluminal, endoscopically delivered and retrieved gastroduodenojejunal bypass sleeve, including short-term weight loss and changes in comorbidities. METHODS: A prospective, single-center trial was designed. The patients were morbidly obese individuals who met the National Institutes of Health criteria for bariatric surgery. The device used was a unique gastroduodenojejunal bypass sleeve secured at the esophagogastric junction with endoscopic and laparoscopic techniques and designed to create an endoluminal gastroduodenojejunal bypass. At completion of the trial, the device was explanted with endoscopic retrieval. The primary end points were safety and incidence of adverse events. The secondary outcomes included the percentage of excess weight loss and changes in comorbidities, specifically glucose control, use of antihyperglycemic medications, and changes in hemoglobin A1c levels. RESULTS: From July 2008 to February 2010, 24 patients were enrolled in the trial. The gastroduodenojejunal bypass sleeve was implanted, left in situ, and then retrieved. The 7 men and 17 women in the study had a mean preoperative body mass index of 42 kg/m(2). The device was successfully delivered in 22 of the 24 patients (92%) and retrieved endoscopically from all 22 patients in whom it was implanted (100%). Two patients were excluded from the study preprocedurally. The one patient was excluded preoperatively due to noncompliance with the preoperative liquid diet. For the other excluded patient, the device was not attempted endoscopically due to significant inflammation at the gastroesophageal junction at the time of laparoscopic evaluation. Of the 22 patients who had the device implanted, 17 maintained it (77%) and completed the full 12-week trial. These patients had 39.7% excess weight loss at completion of the study. The primary reason for early explantation of the device was early postoperative dysphagia. The seven patients with preoperative diabetes mellitus all had normal blood glucose levels throughout the trial, and none required antihyperglycemic medications. All four patients with elevated hemoglobin A1c levels preoperatively showed improvement by the end of the trial. CONCLUSIONS: This trial demonstrated that the endoluminal gastroduodenojejunal sleeve can achieve excellent weight loss at 12 weeks. No patient safety issues were encountered. Adverse effects were minimal and resolved at endoscopic device removal. Effective glycemic control was demonstrated through use of the device during the trial. Long-term results are needed.

Correlation between electrocardiographic features and mechanical dyssynchrony in heart failure patients with left bundle branch block.

BACKGROUND: Few electrocardiographic parameters beyond the QRS duration were studied with regard to the correlation with mechanical dyssynchrony. This study aims to analyze the correlation between electrocardiographic parameters and mechanical dyssynchrony in patients with symptomatic heart failure (HF) and left bundle branch block (LBBB). METHODS: Patients with HF, ejection fraction ≤ 35%, and QRS interval ≥ 120 ms with a LBBB were prospectively studied. We analyzed the correlation between electrocardiographic parameters (QRS duration, R voltage in limb leads, S voltage in precordial leads, Sokolow and Cornell indexes, QRS axis deviation, and QRS notches in lateral and inferior leads) and mechanical dyssynchrony measured by tissue Doppler imaging (TDI). RESULTS: A group of 50 patients were studied, 60% male, 78% with nonischemic cardiomyopathy, NYHA Class III-IV (86%), and ejection fraction of 0.22 ± 0.6. Intra- and interventricular dyssynchrony occurred in 68% and 74% of patients, respectively. The S amplitude in precordial leads and the Sokolow and Cornel indexes show a weak correlation with the degree of dyssynchrony. In the patients with QRS notching in the lateral and inferior leads, we observed significantly greater prevalence of intraventricular dyssynchrony, with sensitivity and specificity of 85% and 56%, respectively, for notches in lateral leads. The QRS duration presents moderate correlation with the degree of both intraventricular (r = 0.48) and interventricular dyssynchrony (r = 0.46). CONCLUSION: The following electrocardiographic parameters were related to the degree of mechanical dyssynchrony: QRS duration and notches in QRS. In addition, the patients tend to have highest S amplitude in precordial leads.

Review of current intracranial aneurysm flow diversion technology and clinical use.

Endovascular treatment of intracranial aneurysms (IAs) has evolved considerably over the past decades. The technological advances have been driven by the experience that coils fail to completely exclude all IAs from the blood circulation, the need to treat the diseased parent vessel segment leading to the aneurysm formation, and expansion of endovascular therapy to treat more complex IAs. Stents were initially developed to support the placement of coils inside wide neck aneurysms. However, early work on stent-like tubular braided structure led to a more sophisticated construct that then later was coined as a flow diverter (FD) and found its way into clinical application. Although FDs were initially used to treat wide-neck large and giant internal carotid artery aneurysms only amenable to surgical trap with or without a bypass or endovascular vessel sacrifice, its use in other types of IAs and cerebrovascular pathology promptly followed. Lately, we have witnessed an explosion in the application of FDs and subsequently their modifications leading to their ubiquitous use in endovascular therapy. In this review we aim to compile the available FD technology, evaluate the devices' peculiarities from the authors' perspective, and analyze the current literature to support initial and expanded indications, recognizing that this may be outdated soon.

Pioneer plant species and fungal root endophytes in metal-polluted tailings deposited near human populations and agricultural areas in Northern Mexico.

As a consequence of industrial mining activity, high volumes of tailings are scattered around Mexico. Frequently, tailings contain heavy metals (HM) which entail threats against all organisms. The aim of this research was to identify plants and root fungal endophytes in polymetallic polluted tailings with the potential to be used in strategies of bioremediation. Four deposits of mine wastes, situated in a semi-arid region near urban and semi-urban populations, and agricultural areas, were studied. The physical and chemical characteristics of substrates, accumulation of HM in plant tissues, root colonization between arbuscular mycorrizal (AMF) and dark septate endophyte (DSE) fungi, and the identification of DSE fungi isolated from the roots of two plant species were studied. Substrates from all four sites exhibited extreme conditions: high levels in sand; low water retention; poor levels in available phosphorus and nitrogen content; and potentially toxic levels of lead (Pb), cadmium (Cd), and zinc (Zn). The native plants Lupinus campestris, Tagetes lunulata, and Cerdia congestiflora, as well as the exotic Cortaderia selloana and Asphodelus fistulosus, demonstrated a relevant potential role in the phytostabilization and/or phytoextraction of Pb, Cd, and Zn, according to the accumulation of metal in roots and translocation to shoots. Roots of eleven analyzed plant species were differentially co-colonized between AMF and DSE fungi; the presence of arbuscules and microsclerotia suggested an active physiological interaction. Fourteen DSE fungi were isolated from the inner area of roots of T. lunulata and Pennisetum villosum; molecular identification revealed the predominance of Alternaria and other Pleosporales. The use of native DSE fungi could reinforce the establishment of plants for biological reclamation of mine waste in semi-arid climate. Efforts are needed in order to accelerate a vegetation practice of mine wastes under study, which can reduce, in turn, their potential ecotoxicological impact on organisms, human populations, and agricultural areas.