Identification of mutations on the EMD and EYA4 genes associated with Emery-Dreifuss muscular dystrophy and deafness: a case report.

Introduction: Hearing loss is the most common sensory disability, and it is estimated that 50% of cases are caused by genetic factors. One of the genes associated with deafness is the eyes absent homolog 4 (EYA4) gene, a transcription factor related to the development and function of the inner ear. Emery-Dreifuss muscular dystrophy is a rare inherited disease characterized by atrophy and weakness of the humeroperoneal muscles, multi-joint contractures, and cardiac manifestations. It is inherited in an autosomal-dominant, X-linked, or less frequently autosomal recessive manner; one of the genes associated with EDMD is the emerin (EMD) gene. Case description: A total of two Ecuadorian siblings aged 57 (Subject A) and 55 (Subject B) were diagnosed with deafness and an unspecified type of muscular dystrophy based on family history and clinical findings. Next-generation sequencing (NGS) using the TruSight Cardio and Inherited Disease kits at the Centro de Investigación Genética y Genómica CIGG, Universidad UTE, was performed. The genetic analyses showed two mutations: a stop mutation in exon 11/20 (NM_004100.4:c.940G>T) of the EYA4 gene and a missense mutation in exon 6 (NM_000117.2:c.548C>G) of the EMD gene. Discussion and conclusion: The in silico predictions described the EYA4 variant as likely pathogenic and the EMD variant as a variant of uncertain significance (VUS). Moreover, an ancestry analysis was performed using 46 Ancestry Informative Insertion/Deletion Markers (AIM-InDels), and the ancestral composition of subject A was 46% African, 26.1% European, and 27.9% American Indian ancestry, whereas the ancestral composition of subject B was 41.3% African, 38.2% European, and 20.5% American Indian ancestry. The present case report describes two Ecuadorian siblings with a mainly African ancestral component, muscular dystrophy, and deafness phenotypes. Moreover, using next-generation sequencing (NGS), a mutation in the EMD and a novel mutation in EYA4 genes possibly associated with the subjects' phenotype were identified and discussed.

Vaccines for the common cold.

BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8 ºC). Whilst the common cold is generally not harmful, it is a cause of economic burden due to school and work absenteeism. In the United States, economic loss due to the common cold is estimated at more than USD 40 billion per year, including an estimate of 70 million workdays missed by employees, 189 million school days missed by children, and 126 million workdays missed by parents caring for children with a cold. Additionally, data from Europe show that the total cost per episode may be up to EUR 1102. There is also a large expenditure due to inappropriate antimicrobial prescription. Vaccine development for the common cold has been difficult due to antigenic variability of the common cold viruses; even bacteria can act as infective agents. Uncertainty remains regarding the efficacy and safety of interventions for preventing the common cold in healthy people, thus we performed an update of this Cochrane Review, which was first published in 2011 and updated in 2013 and 2017. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (April 2022), MEDLINE (1948 to April 2022), Embase (1974 to April 2022), CINAHL (1981 to April 2022), and LILACS (1982 to April 2022). We also searched three trials registers for ongoing studies, and four websites for additional trials (April 2022). We did not impose any language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccine compared with placebo to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to assess the initial search results. Four review authors independently performed title and abstract screening to identify potentially relevant studies. We retrieved the full-text articles for those studies deemed potentially relevant, and the review authors independently screened the full-text reports for inclusion in the review, recording reasons for exclusion of the excluded studies. Any disagreements were resolved by discussion or by consulting a third review author when needed. Two review authors independently collected data on a data extraction form, resolving any disagreements by consensus or by involving a third review author. We double-checked data transferred into Review Manager 5 software. Three review authors independently assessed risk of bias using RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We carried out statistical analysis using Review Manager 5. We did not conduct a meta-analysis, and we did not assess publication bias. We used GRADEpro GDT software to assess the certainty of the evidence and to create a summary of findings table.  MAIN RESULTS: We did not identify any new RCTs for inclusion in this update. This review includes one RCT conducted in 1965 with an overall high risk of bias. The RCT included 2307 healthy young men in a military facility, all of whom were included in the analyses, and compared the effect of three adenovirus vaccines (live, inactivated type 4, and inactivated type 4 and 7) against a placebo (injection of physiological saline or gelatin capsule). There were 13 (1.14%) events in 1139 participants in the vaccine group, and 14 (1.19%) events in 1168 participants in the placebo group. Overall, we do not know if there is a difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; very low-certainty evidence). Furthermore, no difference in adverse events when comparing live vaccine preparation with placebo was reported. We downgraded the certainty of the evidence to very low due to unclear risk of bias, indirectness because the population of this study was only young men, and imprecision because confidence intervals were wide and the number of events was low. The included study did not assess vaccine-related or all-cause mortality.  AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with very low-certainty evidence, which showed that there may be no difference between the adenovirus vaccine and placebo in reducing the incidence of the common cold. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Future trials on interventions for preventing the common cold should assess a variety of virus vaccines for this condition, and should measure such outcomes as common cold incidence, vaccine safety, and mortality (all-cause and related to the vaccine).

The crystalline state as a dynamic system: IR microspectroscopy under electrochemical control for a [NiFe] hydrogenase.

Controlled formation of catalytically-relevant states within crystals of complex metalloenzymes represents a significant challenge to structure-function studies. Here we show how electrochemical control over single crystals of [NiFe] hydrogenase 1 (Hyd1) from Escherichia coli makes it possible to navigate through the full array of active site states previously observed in solution. Electrochemical control is combined with synchrotron infrared microspectroscopy, which enables us to measure high signal-to-noise IR spectra in situ from a small area of crystal. The output reports on active site speciation via the vibrational stretching band positions of the endogenous CO and CN- ligands at the hydrogenase active site. Variation of pH further demonstrates how equilibria between catalytically-relevant protonation states can be deliberately perturbed in the crystals, generating a map of electrochemical potential and pH conditions which lead to enrichment of specific states. Comparison of in crystallo redox titrations with measurements in solution or of electrode-immobilised Hyd1 confirms the integrity of the proton transfer and redox environment around the active site of the enzyme in crystals. Slowed proton-transfer equilibria in the hydrogenase in crystallo reveals transitions which are only usually observable by ultrafast methods in solution. This study therefore demonstrates the possibilities of electrochemical control over single metalloenzyme crystals in stabilising specific states for further study, and extends mechanistic understanding of proton transfer during the [NiFe] hydrogenase catalytic cycle.

Exercise training for adult lung transplant recipients.

BACKGROUND: Pulmonary transplantation is the final treatment option for people with end-stage respiratory diseases. Evidence suggests that exercise training may contribute to speeding up physical recovery in adults undergoing lung transplantation, helping to minimize or resolve impairments due to physical inactivity in both the pre- and post-transplant stages. However, there is a lack of detailed guidelines on how exercise training should be carried out in this specific sub-population. OBJECTIVES: To determine the benefits and safety of exercise training in adult patients who have undergone lung transplantation, measuring the maximal and functional exercise capacity; health-related quality of life; adverse events; patient readmission; pulmonary function; muscular strength; pathological bone fractures; return to normal activities and death. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Specialised Register up to 6 October 2020 using relevant search terms for this review. Studies in the CKTR are identified through CENTRAL, MEDLINE, and EMBASE searches, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) were included comparing exercise training with usual care or no exercise training, or with another exercise training program in terms of dosage, modality, program length, or use of supporting exercise devices. The study population comprised of participants older than 18 years who underwent lung transplantation independent of their underlying respiratory pathology. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed all records identified by the search strategy and selected studies that met the eligibility criteria for inclusion in this review. In the first instance, the disagreements were resolved by consensus, and if this was not possible the decision was taken by a third reviewer. The same reviewers independently extracted outcome data from included studies and assessed risk of bias. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Eight RCTs (438 participants) were included in this review. The median sample size was 60 participants with a range from 16 to 83 participants. The mean age of participants was 54.9 years and 51.9% of the participants were male. The median duration of the exercise training programs for the groups undergoing the intervention was 13 weeks, and the median duration of training in the active control groups was four weeks. Overall the risk of bias was considered to be high, mainly due to the inability to blind the study participants and the selective reporting of the results. Due to small number of studies included in this review, and the heterogeneity of the intervention and outcomes, we did not obtain a summary estimate of the results. Two studies comparing resistance exercise training with no exercise reported increases in muscle strength and bone mineral density (surrogate outcomes for pathological bone fractures) with exercise training (P > 0.05), but no differences in adverse events. Exercise capacity, health-related quality of life (HRQoL), pulmonary function, and death (any cause) were not reported. Three studies compared two different resistant training programs. Two studies comparing squats using a vibration platform (WBVT) compared to squats on the floor reported an improvement in 6-minute walk test (6MWT) (28.4 metres, 95% CI 3 to 53.7; P = 0.029; and 28.3 metres, 95% CI 10.0 to 46.6; P < 0.05) with the WBVT. Supervised upper limb exercise (SULP) program improved 6MWT at 6 months compared to no supervised upper limb exercise (NULP) (SULP group: 561.2 ± 83.6 metres; NULP group: 503.5 ± 115.2 metres; P = 0.01). There were no differences in HRQoL, adverse events, muscular strength, or death (any cause). Pulmonary function and pathological bone fractures were not reported. Two studies comparing multimodal exercise training with no exercise reported improvement in 6MWT at 3 months (P = 0.008) and at 12-months post-transplant (P = 0.002) and muscular strength (quadriceps force (P = 0.001); maximum leg press (P = 0.047)) with multimodal exercise, but no improvement in HRQoL, adverse events, pulmonary function, pathological bone fractures (lumbar T-score), or death (any cause). One study comparing the same multimodal exercise programs given over 7 and 14 weeks reported no differences in 6MWT, HRQoL, adverse events, pulmonary function, muscle strength, or death (any cause). Pathological bone fractures were not reported. According to GRADE criteria, we rated the certainty of the evidence as very low, mainly due to the high risk of bias and serious imprecision. AUTHORS' CONCLUSIONS: In adults undergoing lung transplantation the evidence about the effects of exercise training is very uncertain in terms of maximal and functional exercise capacity, HRQoL and safety, due to very imprecise estimates of effects and high risk of bias.

Growth references for weight, height, and body mass index for Ecuadorian children and adolescents aged 5-19 years. / Referencias de peso, estatura e índice de masa corporal para niñas y niños ecuatorianos de 5 a 19 años de edad.

INTRODUCTION: The assessment of growth during childhood and adolescence is a critical component of health care at all levels, but it is also part of nutritional status diagnosis and the timely detection of related conditions. Ecuador lacks national growth references, so it has decided to adopt the international standards proposed by the World Health Organization. The objective of this study was to develop national references for weight, height, and body mass index for children and adolescents. METHODS: Ecuadorian schoolchildren and adolescents aged 5-19 years were studied between 1999 and 2012. The LMS method for cross-sectional data, which uses the Box-Cox transformation to normalize data distribution at each age, was applied to estimate the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th centiles for weight, height, and body mass index. RESULTS: A total of 5934 healthy subjects (2788 boys and 3146 girls) participated. Boys were heavier and taller than girls. In all cases, values increased with age. At 18 years old, the differences between sexes averaged 8 kg and 12.5 cm. CONCLUSION: The tables and curves obtained with this study are the first descriptive growth references for Ecuadorian children and adolescents aged 5-19 years. They are relevant for nutritional assessment. Their use at the primary level of care will aid in nutritional status diagnosis, which has traditionally been done based on the World Health Organization's international standards.

Introducción. La evaluación del crecimiento durante la infancia y la adolescencia es un componente fundamental de la atención de salud en todos sus niveles, pues es parte del diagnóstico nutricional y permite la detección oportuna de patologías relacionadas. Ecuador, al no disponer de referencias nacionales de crecimiento, ha adoptado los estándares internacionales de la Organización Mundial de la Salud. El objetivo de este estudio fue construir referencias nacionales de peso, estatura e índice de masa corporal para niños, niñas y adolescentes. Métodos. Se investigaron escolares y adolescentes ecuatorianos entre 5 y 19 años de edad durante 1999 y 2012. Los centilos 3, 10, 25, 50, 75, 90 y 97 de peso, talla e índice de masa corporal fueron estimados por el método LMS para datos transversales, que utiliza la transformación Box- Cox para normalizar la distribución de los datos a cada edad. Resultados. Participaron 5934 sujetos sanos (2788 niños y 3146 niñas). Los niños pesaban más y eran más altos que las niñas. En todos los casos, los valores mostraron un aumento creciente conforme la edad avanzaba. A los 18 años, las diferencias entre sexos promediaron 8 kg y 12,5 cm. Conclusión. Las tablas y curvas producto de este estudio constituyen la primera referencia descriptiva del crecimiento de niños ecuatorianos de 5-19 años. Son un importante instrumento de evaluación nutricional. Su implementación en la atención primaria de salud permitirá complementar el diagnóstico nutricional que, tradicionalmente, se realiza sobre la base de los estándares internacionales de la Organización Mundial de la Salud.

Quality of clinical practice guidelines about red blood cell transfusion.

BACKGROUND: Red blood cell (RBC) transfusions are essential in health care. The quality of recommendations included in clinical practice guidelines (CPG), regarding this intervention, has not been systematically evaluated. This paper systematically assessed CPGs for RBC-transfusion, to appraise their methodological quality, to explore changes in quality over time, and to assess the consistency of the hemoglobin threshold (HT) recommendations. METHODS: We searched for CPGs that included recommendations of RBC-transfusion in generic databases, compiler entities, registries, clearinghouses and guideline developers. Three reviewers extracted data on CPGs characteristics and HT recommendations, independently appraised the quality of the studies using AGREE II and resolved disagreements by consensus. RESULTS: We examined 16 CPGs. Mean scores (mean ± SD) were: scope and purpose (59.4% ± 19.8%), stakeholder involvement (43.2% ± 22.6%), rigor of development (50% ± 25%), clarity of presentation (74.4% ± 12.6%), applicability (19.4% ± 18.8%), and editorial independence (41% ± 30%). Seven CPGs recommended a restrictive strategy for RBC transfusion; four CPGs gave a guarded statement considering an HT of 7 g/dL, as safe to prescribe an RBC transfusion. Eight CPGs did not provide an HT stating that RBC transfusions should not be prescribed by HT alone. CONCLUSIONS: Only 3 out of the 16 evaluated CPGs were "recommended" by the independent evaluators. Four domains "stakeholder involvement," "rigor of development," applicability," and "editorial independence" had serious shortcomings. Recommendations about the use of an HT for RBC-transfusion were heterogeneous among guidelines. Greater efforts are needed to provide high-quality CPGs in the RBC-transfusion practice.

Interventions for treating acute high altitude illness.

BACKGROUND: Acute high altitude illness is defined as a group of cerebral and pulmonary syndromes that can occur during travel to high altitudes. It is more common above 2500 metres, but can be seen at lower elevations, especially in susceptible people. Acute high altitude illness includes a wide spectrum of syndromes defined under the terms 'acute mountain sickness' (AMS), 'high altitude cerebral oedema' and 'high altitude pulmonary oedema'. There are several interventions available to treat this condition, both pharmacological and non-pharmacological; however, there is a great uncertainty regarding their benefits and harms. OBJECTIVES: To assess the clinical effectiveness, and safety of interventions (non-pharmacological and pharmacological), as monotherapy or in any combination, for treating acute high altitude illness. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, ISI Web of Science, CINAHL, Wanfang database and the World Health Organization International Clinical Trials Registry Platform for ongoing studies on 10 August 2017. We did not apply any language restriction. SELECTION CRITERIA: We included randomized controlled trials evaluating the effects of pharmacological and non-pharmacological interventions for individuals suffering from acute high altitude illness: acute mountain sickness, high altitude pulmonary oedema or high altitude cerebral oedema. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the eligibility of study reports, the risk of bias for each and performed the data extraction. We resolved disagreements through discussion with a third author. We assessed the quality of evidence with GRADE. MAIN RESULTS: We included 13 studies enrolling a total of 468 participants. We identified two ongoing studies. All studies included adults, and two studies included both teenagers and adults. The 13 studies took place in high altitude areas, mostly in the European Alps. Twelve studies included participants with acute mountain sickness, and one study included participants with high altitude pulmonary oedema. Follow-up was usually less than one day. We downgraded the quality of the evidence in most cases due to risk of bias and imprecision. We report results for the main comparisons as follows.Non-pharmacological interventions (3 studies, 124 participants)All-cause mortality and complete relief of AMS symptoms were not reported in the three included trials. One study in 64 participants found that a simulated descent of 193 millibars versus 20 millibars may reduce the average of symptoms to 2.5 vs 3.1 units after 12 hours of treatment (clinical score ranged from 0 to 11 ‒ worse; reduction of 0.6 points on average with the intervention; low quality of evidence). In addition, no complications were found with use of hyperbaric chambers versus supplementary oxygen (one study; 29 participants; low-quality evidence).Pharmacological interventions (11 trials, 375 participants)All-cause mortality was not reported in the 11 included trials. One trial found a greater proportion of participants with complete relief of AMS symptoms after 12 and 16 hours when dexamethasone was administered in comparison with placebo (47.1% versus 0%, respectively; one study; 35 participants; low quality of evidence). Likewise, when acetazolamide was compared with placebo, the effects on symptom severity was uncertain (standardized mean difference (SMD) -1.15, 95% CI -2.56 to 0.27; 2 studies, 25 participants; low-quality evidence). One trial of dexamethasone in comparison with placebo in 35 participants found a reduction in symptom severity (difference on change in the AMS score: 3.7 units reported by authors; moderate quality of evidence). The effects from two additional trials comparing gabapentin with placebo and magnesium with placebo on symptom severity at the end of treatment were uncertain. For gabapentin versus placebo: mean visual analogue scale (VAS) score of 2.92 versus 4.75, respectively; 24 participants; low quality of evidence. For magnesium versus placebo: mean scores of 9 and 10.3 units, respectively; 25 participants; low quality of evidence). The trials did not find adverse events from either treatment (low quality of evidence). One trial comparing magnesium sulphate versus placebo found that flushing was a frequent event in the magnesium sulphate arm (percentage of flushing: 75% versus 7.7%, respectively; one study; 25 participants; low quality of evidence). AUTHORS' CONCLUSIONS: There is limited available evidence to determine the effects of non-pharmacological and pharmacological interventions in treating acute high altitude illness. Low-quality evidence suggests that dexamethasone and acetazolamide might reduce AMS score compared to placebo. However, the clinical benefits and harms related to these potential interventions remain unclear. Overall, the evidence is of limited practical significance in the clinical field. High-quality research in this field is needed, since most trials were poorly conducted and reported.

Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase.

Understanding the chemistry of redox proteins demands methods that provide precise control over redox centers within the protein. The technique of protein film electrochemistry, in which a protein is immobilized on an electrode surface such that the electrode replaces physiological electron donors or acceptors, has provided functional insight into the redox reactions of a range of different proteins. Full chemical understanding requires electrochemical control to be combined with other techniques that can add additional structural and mechanistic insight. Here we demonstrate a technique, protein film infrared electrochemistry, which combines protein film electrochemistry with infrared spectroscopic sampling of redox proteins. The technique uses a multiple-reflection attenuated total reflectance geometry to probe a redox protein immobilized on a high surface area carbon black electrode. Incorporation of this electrode into a flow cell allows solution pH or solute concentrations to be changed during measurements. This is particularly powerful in addressing redox enzymes, where rapid catalytic turnover can be sustained and controlled at the electrode allowing spectroscopic observation of long-lived intermediate species in the catalytic mechanism. We demonstrate the technique with experiments on E. coli hydrogenase 1 under turnover (H2 oxidation) and non-turnover conditions.

Evolución de las cajas de polyetheretherketone (PEEK). Estudio clínico y radiológico / Évolution des cages en polyétheréthercétone (PEEK). Étude clinique et radiologique / Evolution of polyetheretherketone (PEEK) boxes. Clinical and radiological study

Introducción: las cajas cervicales son implantes desarrollados como una alternativa a la utilización del injerto óseo estructural para la fusión cervical anterior. El objetivo de este estudio fue analizar la clínica y los resultados radiológicos en una serie de pacientes sometidos a disectomía y descompresión cervical anterior, a los que se les implantó una caja PEEK. Método: estudio retrospectivo, descriptivo, longitudinal de una serie de 78 pacientes incluidos en el estudio desde el año 2007 al 2013. El control radiológico incluyó radiografía anteroposterior y lateral. El seguimiento clínico y radiológico de los pacientes se llevó a cabo desde los 3 meses hasta los 12 meses. Resultados: 65 pacientes tuvieron una evolución clínica favorable (83,3 por ciento) y la evolución radiológica confirmó que 66 pacientes (84,6 por ciento) tenían una buena colocación del injerto, sin lesiones en espacios adyacentes con una fusión correcta. Conclusiones: hasta la fecha hay pocos estudios descriptivos sobre el implante de las cajas PEEK, los resultados mostrados en este trabajo están acordes a los publicados con anterioridad en este mismo campo, lo que da validez al trabajo presentado. Este estudio confirma los buenos resultados clínicos y radiológicos de pacientes a los que se les implantó una caja PEEK; se muestra su eficacia en la discectomía cervical anterior y artrodesis(AU)

Introduction: Cervical cases are implants developed as an alternative to the use of structural bone graft for anterior cervical fusion. The objective of this study was to analyze the clinical and radiological results in a series of patients submitted to anterior cervical dissectomy and decompression, to whom a PEEK box was implanted. Method: A retrospective, descriptive, longitudinal study was conducted in a series of 78 patients included in the study from 2007 to 2013. Radiological control included anteroposterior and lateral radiographies. Clinical and radiological follow-up of these patients was carried out from 3 months to 12 months. Results: 65 patients had a favorable clinical course (83.3 percent) and the radiological evolution confirmed that 66 patients (84.6 percent) had a good placement of the graft without lesions in adjacent spaces with a correct fusion. Conclusions: To date there are few descriptive studies on the implantation of PEEK boxes. This paper results are in line with those published previously in this same field, which legitimate the presented work. This study confirms the good clinical and radiological results in patients who were implanted with a PEEK box; its effectiveness in anterior cervical discectomy and arthrodesis is shown(AU)

Introduction: Les cages cervicales sont des implants développés comme alternative de la greffe osseuse structurelle pour la fusion cervicale antérieure. Le but de cette étude est d'analyser la technique et les résultats radiologiques dans une série de patients traités par discectomie et décompression cervicale antérieure, et implantation d'une cage PEEK. Méthodes: Étude rétrospective, descriptive et longitudinale d'une série de 78 patients inclus dans une étude depuis l'année 2007 jusqu'à l'année 2013. L'étude radiologique a compris des clichés en position antéro-postérieure et latérale. Le suivi clinique et radiologique des patients a pris de 3 à 12 mois. Résultats: L'évolution clinique a été satisfaisante chez 65 patients (83,3 pourcent), tandis que l'étude radiologique a confirmé que le greffon était bien placé, il n'y avait pas de lésions dans les espaces adjacentes, et la fusion était correcte chez 66 patients (84,6 pourcent). Conclusions: Jusqu'à maintenant, il y a peu d'études descriptives abordant l'implantation des cages PEEK. Le présent travail est validé, car ses résultats sont en concordance avec les travaux publiés auparavant dans ce domaine. Cette étude confirme les bons résultats obtenus chez les patients ayant subi l'implantation d'une cage PEEK ; son efficacité est démontrée dans la discectomie cervicale antérieure et l'arthrodèse(AU)

Infiltraciones epidurales de esteroides en el tratamiento del dolor radicular en el contexto laboral / Infiltrations épidurales de stéroïdes pour le traitement de la douleur radiculaire dans un contexte de travail / Epidural Infiltration of Steroids in the Treatment of Root Pain in the Occupation Context

Introducción : el dolor ciático es un tipo de dolor en la extremidad inferior que normalmente sigue una distribución metamérica específica. A menudo es causado por una compresión o irritación del nervio ciático, comúnmente debido a hernia discal lumbar. Es uno de los motivos más habituales de consulta en unidades de cirugía de columna vertebral. Objetivo: determinar si las infiltraciones epidurales de esteroides pueden mejorar los síntomas en pacientes con una hernia discal, y así evitar la cirugía, lo que les permite una pronta vuelta al trabajo. Método: se reclutaron 71 pacientes con hernia discal, con historia de dolor ciático de al menos 3 meses de duración. Los pacientes recibieron un máximo de 3 infiltraciones epidurales de esteroides administradas con 2 semanas de separación, seguidas por un programa de rehabilitación. Resultados: de los 71 pacientes, 71,8 por ciento presentaron hernia discal en L5-S1, 87 por ciento eran hombres, edad media de 40,2 años y un 57,7 por ciento tenían trabajos asociados con altas demandas funcionales. El promedio de semanas de baja laboral fue 16,63. Al año, el 63,4 por ciento de los pacientes fueron dados de baja y un 36,6 por ciento requirió cirugía debido a la persistencia del dolor a pesar del tratamiento con inyecciones epidurales de esteroides. El índice de discapacidad de Oswestry y la puntuación EVA reflejaron una mejoría estadísticamente significativa (p < 0,001) después de las infiltraciones en la mayoría de los casos. Conclusiones: en nuestro contexto, la administración de infiltraciones esteroides epidurales en pacientes con dolor radicular secundario con hernia discal es un procedimiento mínimamente invasivo y efectivo que alivia el dolor, reduce la discapacidad y permite un rápido retorno a la actividad laboral(AU)

Introduction: Sciatic pain is a type of pain in the lower extremity that usually follows a specific metameric distribution. The compression or irritation of the sciatic nerve is often the cause, commonly due to lumbar disc herniation. It is one of the most common reasons for consultation in spinal surgery units. Objective: Determine if epidural steroid infiltrations can improve symptoms in patients with a herniated disc, thus avoiding surgery, which allows them to return to work soon. Method: We recruited 71 patients with a herniated disc, with a history of sciatic pain of at least 3 months. Patients received a maximum of three epidural infiltrations of steroids given 2 weeks apart, followed by a rehabilitation program. Results: Out of the 71 patients, 71.8 percent had L5-S1 disc hernia, 87 percent were men, mean age was 40.2 years and 57.7 percent had jobs associated with high functional demands. The average number of weeks off from work was 16.63. At one year, 63.4 percent of patients were discharged and 36.6 percent required surgery because of persistent pain despite treatment with epidural steroid injections. The Oswestry disability index and Visual Analog Scale (VAS) reflected a statistically significant improvement (p <0.001) after infiltrations in most cases. Conclusions: In our context, the administration of epidural steroid infiltrations in patients with secondary radicular pain with a herniated disc is a minimally invasive and effective procedure that alleviates pain, reduces disability and allows a quick return to work activity(AU)

Introduction: La douleur sciatique est une sorte de douleur localisée aux membres inférieurs suivant généralement une distribution métamérique spécifique. Elle est en général causée par une compression ou irritation du nerf sciatique, surtout due à une hernie discale lombaire. Elle est l'une des causes les plus fréquentes de consultation aux services de chirurgie de colonne vertébrale. Objectif: Définir si les infiltrations épidurales de stéroïdes peuvent soulager les symptômes chez les patients atteints d'hernie discale et éviter ainsi la chirurgie, leur permettant un prompt retour au travail. Méthodes: Soixante-onze patients atteints d'hernie discale et avec une histoire de douleur sciatique d'au moins 3 mois de durée ont été inclus dans cette étude. Les patients ont subi un maximum de 3 infiltrations épidurales de stéroïdes, administrées avec 2 semaines d'intervalle, et suivies d'un programme de rééducation. Résultats: Sur 71 patients, la plupart souffrait d'une hernie discale en L5-S1 (71,8 pourtent), était du sexe masculin (87 pourtent), âgée de 40,2 ans en moyenne, et avec des occupations d'une grande charge fonctionnelle (57,7 pourtent). L'arrêt de travail pour maladie a eu une durée de 16,63 semaines en moyenne. Au bout d'un an, la majorité des patients (63,4 pourtent) ont été licenciés, et une minorité (36,6 pourtent) a eu besoin d'une chirurgie, malgré les injections épidurales de stéroïdes (douleur persistante). Dans la plupart des cas, l'évaluation de l'incapacité fonctionnelle (questionnaire d'Oswestry) et l'échelle d'auto-évaluation de la douleur (score EVA) ont montré une amélioration statistiquement significative (p < 0.001) après les infiltrations épidurales de stéroïdes. Conclusion: Dans notre contexte, l'administration d'infiltrations épidurales de stéroïdes chez des patients ayant une douleur radiculaire secondaire et une hernie discale est un procédé peu invasif mais effectif, soulageant la douleur, réduisant l'incapacité, et permettant un retour rapide aux activités de travail(AU)

Vaccines for the common cold.

BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat, and fever (usually < 37.8º C). The widespread morbidity caused by the common cold worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. This is an update of a Cochrane review first published in 2011 and previously updated in 2013. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (September 2016), MEDLINE (1948 to September 2016), Embase (1974 to September 2016), CINAHL (1981 to September 2016), and LILACS (1982 to September 2016). We also searched three trials registers for ongoing studies and four websites for additional trials (February 2017). We included no language or date restrictions. SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccines compared with placebo to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted trial data. We resolved disagreements by discussion or by consulting a third review author. MAIN RESULTS: We found no additional RCTs for inclusion in this update. This review includes one RCT dating from the 1960s with an overall high risk of bias. The RCT included 2307 healthy participants, all of whom were included in analyses. This trial compared the effect of an adenovirus vaccine against placebo. No statistically significant difference in common cold incidence was found: there were 13 (1.14%) events in 1139 participants in the vaccines group and 14 (1.19%) events in 1168 participants in the placebo group (risk ratio 0.95, 95% confidence interval 0.45 to 2.02; P = 0.90). No adverse events related to the live vaccine were reported. The quality of the evidence was low due to limitations in methodological quality and a wide 95% confidence interval. AUTHORS' CONCLUSIONS: This Cochrane Review was based on one study with low-quality evidence. We found no conclusive results to support the use of vaccines for preventing the common cold in healthy people compared with placebo. We identified a need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety, and mortality related to the vaccine.

Proton Transfer in the Catalytic Cycle of [NiFe] Hydrogenases: Insight from Vibrational Spectroscopy.

Catalysis of H2 production and oxidation reactions is critical in renewable energy systems based around H2 as a clean fuel, but the present reliance on platinum-based catalysts is not sustainable. In nature, H2 is oxidized at minimal overpotential and high turnover frequencies at [NiFe] catalytic sites in hydrogenase enzymes. Although an outline mechanism has been established for the [NiFe] hydrogenases involving heterolytic cleavage of H2 followed by a first and then second transfer of a proton and electron away from the active site, details remain vague concerning how the proton transfers are facilitated by the protein environment close to the active site. Furthermore, although [NiFe] hydrogenases from different organisms or cellular environments share a common active site, they exhibit a broad range of catalytic characteristics indicating the importance of subtle changes in the surrounding protein in controlling their behavior. Here we review recent time-resolved infrared (IR) spectroscopic studies and IR spectroelectrochemical studies carried out in situ during electrocatalytic turnover. Additionally, we re-evaluate the significant body of IR spectroscopic data on hydrogenase active site states determined through more conventional solution studies, in order to highlight mechanistic steps that seem to apply generally across the [NiFe] hydrogenases, as well as steps which so far seem limited to specific groups of these enzymes. This analysis is intended to help focus attention on the key open questions where further work is needed to assess important aspects of proton and electron transfer in the mechanism of [NiFe] hydrogenases.

Synchrotron-Based Infrared Microanalysis of Biological Redox Processes under Electrochemical Control.

We describe a method for addressing redox enzymes adsorbed on a carbon electrode using synchrotron infrared microspectroscopy combined with protein film electrochemistry. Redox enzymes have high turnover frequencies, typically 10-1000 s(-1), and therefore, fast experimental triggers are needed in order to study subturnover kinetics and identify the involvement of transient species important to their catalytic mechanism. In an electrochemical experiment, this equates to the use of microelectrodes to lower the electrochemical cell constant and enable changes in potential to be applied very rapidly. We use a biological cofactor, flavin mononucleotide, to demonstrate the power of synchrotron infrared microspectroscopy relative to conventional infrared methods and show that vibrational spectra with good signal-to-noise ratios can be collected for adsorbed species with low surface coverages on microelectrodes with a geometric area of 25 × 25 µm(2). We then demonstrate the applicability of synchrotron infrared microspectroscopy to adsorbed proteins by reporting potential-induced changes in the flavin mononucleotide active site of a flavoenzyme. The method we describe will allow time-resolved spectroscopic studies of chemical and structural changes at redox sites within a variety of proteins under precise electrochemical control.

Identification of biomedical journals in Spain and Latin America.

OBJECTIVES: Journals in languages other than English that publish original clinical research are often not well covered in the main biomedical databases and therefore often not included in systematic reviews. This study aimed to identify Spanish language biomedical journals from Spain and Latin America and to describe their main features. METHODS: Journals were identified in electronic databases, publishers' catalogues and local registries. Eligibility was determined by assessing data from these sources or the journals' websites, when available. FINDINGS: A total of 2457 journals were initially identified; 1498 met inclusion criteria. Spain (27.3%), Mexico (16.0%), Argentina (15.1%) and Chile (11.9%) had the highest number of journals. Most (85.8%) are currently active; 87.8% have an ISSN. The median and mean length of publication were 22 and 29 years, respectively. A total of 66.0% were indexed in at least one database; 3.0% had an impact factor in 2012. A total of 845 journals had websites (56.4%), of which 700 (82.8%) were searchable and 681 (80.6%) free of charge. CONCLUSIONS: Most of the identified journals have no impact factor or are not indexed in any of the major databases. The list of identified biomedical journals can be a useful resource when conducting hand searching activities and identifying clinical trials that otherwise would not be retrieved.

Discovery of Dark pH-Dependent H(+) Migration in a [NiFe]-Hydrogenase and Its Mechanistic Relevance: Mobilizing the Hydrido Ligand of the Ni-C Intermediate.

Despite extensive studies on [NiFe]-hydrogenases, the mechanism by which these enzymes produce and activate H2 so efficiently remains unclear. A well-known EPR-active state produced under H2 and known as Ni-C is assigned as a Ni(III)-Fe(II) species with a hydrido ligand in the bridging position between the two metals. It has long been known that low-temperature photolysis of Ni-C yields distinctive EPR-active states, collectively termed Ni-L, that are attributed to migration of the bridging-H species as a proton; however, Ni-L has mainly been regarded as an artifact with no mechanistic relevance. It is now demonstrated, based on EPR and infrared spectroscopic studies, that the Ni-C to Ni-L interconversion in Hydrogenase-1 (Hyd-1) from Escherichia coli is a pH-dependent process that proceeds readily in the dark-proton migration from Ni-C being favored as the pH is increased. The persistence of Ni-L in Hyd-1 must relate to unassigned differences in proton affinities of metal and adjacent amino acid sites, although the unusually high reduction potentials of the adjacent Fe-S centers in this O2-tolerant hydrogenase might also be a contributory factor, impeding elementary electron transfer off the [NiFe] site after proton departure. The results provide compelling evidence that Ni-L is a true, albeit elusive, catalytic intermediate of [NiFe]-hydrogenases.

Infrared Spectroscopy During Electrocatalytic Turnover Reveals the Ni-L Active Site State During H2 Oxidation by a NiFe Hydrogenase.

A novel in situ IR spectroscopic approach is demonstrated for the characterization of hydrogenase during catalytic turnover. E. coli hydrogenase 1 (Hyd-1) is adsorbed on a high surface-area carbon electrode and subjected to the same electrochemical control and efficient supply of substrate as in protein film electrochemistry during spectral acquisition. The spectra reveal that the active site state known as Ni-L, observed in other NiFe hydrogenases only under illumination or at cryogenic temperatures, can be generated reversibly in the dark at ambient temperature under both turnover and non-turnover conditions. The observation that Ni-L is present at all potentials during turnover under H2 suggests that the final steps in the catalytic cycle of H2 oxidation by Hyd-1 involve sequential proton and electron transfer via Ni-L. A broadly applicable IR spectroscopic technique is presented for addressing electrode-adsorbed redox enzymes under fast catalytic turnover.

Avaliação da taxa de sobrevida dos implantes dentários em estudos longitudinais com mais de 10 anos de acompanhamento: uma revisão sistemática de literatura / Assessing the survival rates of dental implants in longitudinal studies with more than ten years of follow-up: a systematic review

Objetivo: avaliar, por meio de uma revisão sistemática de literatura, a taxa de sobrevida de implantes osseointegráveis, em estudos longitudinais que realizaram um acompanhamento superior a 10 anos. Métodos: foi realizada uma ampla busca eletrônica — nas bases MEDLINE/PubMed, LILACS e Colaboração Cochrane — por publicações relevantes em revistas indexadas, publicadas a partir do ano de 1981, avaliando o desempenho clínico dos implantes. Usando critérios de inclusão e exclusão, dois revisores analisaram títulos, resumos e artigos completos, dando prioridade aos estudos controlados randomizados (RCTs). Resultados: no total, 16 artigos foram incluídos nessa revisão. Foram selecionados 6 estudos prospectivos, 7 estudos retrospectivos e 3 ensaios clínicos randomizados, que avaliaram 6.515 implantes, ao todo. A média do tempo de acompanhamento foi de 13,4 anos. Após as análises estatísticas, foi encontrada uma média cumulativa de sobrevivência de 95,5 ± 4,2% (n = 6.515). Conclusão: os resultados dessa revisão sistemática demonstraram que os implantes apresentam altas taxas de sobrevivência em longo prazo, desde que haja um correto planejamento e que os pacientes estejam incluídos em um criterioso programa de manutenção pós-tratamento.

Objective: To assess, by means of a systematic literature review, the survival rates of osseointegrated implants, in longitudinal studies with a follow-up exceeding 10 years.Methods: MEDLINE/PubMed, LILACS and Cochrane Collaboration were used to retrieve relevant publications published in indexed journals from the year 1981 on, and which assessed the clinical performance of implants. Based on previously established inclusion and exclusion criteria, two reviewers assessed titles, abstracts and full papers giving priority to randomized controlled trials (RCTs). Results: A total of 16 articles were included in this review. Six prospective studies, sevenretrospective studies and three randomized controlled trials, assessing 6,515 implants, were selected.The mean follow-up time was 13.4 years. Statistical analysis revealed a mean cumulative survival rate of 95.5 ± 4.2 (n = 6,515). Conclusion: The results of this systematic review revealed thatimplants have high success rates in the long-term, provided there is proper planning and patients are included in a thorough maintenance post-treatment program.

Comparison of carbon materials as electrodes for enzyme electrocatalysis: hydrogenase as a case study.

We present a study of electrocatalysis by an enzyme adsorbed on a range of carbon materials, with different size, surface area, morphology and graphitic structure, which are either commercially available or prepared via simple, established protocols. We choose as our model enzyme the hydrogenase I from E. coli (Hyd-1), which is an active catalyst for H2 oxidation, is relatively robust and has been demonstrated in H2 fuel cells and H2-driven chemical synthesis. The carbon materials were characterised according to their surface area, surface morphology and graphitic character, and we use the electrocatalytic H2 oxidation current for Hyd-1 adsorbed on these materials to evaluate their effectiveness as enzyme electrodes. Here, we show that a variety of carbon materials are suitable for adsorbing hydrogenases in an electroactive configuration. This unified study provides insight into selection and design of carbon materials for study of redox enzymes and different applications of enzyme electrocatalysis.

Vaccines for the common cold.

BACKGROUND: The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat and fever (usually < 37.8˚C). The widespread morbidity it causes worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. OBJECTIVES: To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS: We searched CENTRAL (2012, Issue 12), MEDLINE (1948 to January week 1, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013) and LILACS (1982 to January 2013). SELECTION CRITERIA: Randomised controlled trials (RCTs) of any virus vaccines to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS: Two review authors independently evaluated methodological quality and extracted trial data. Disagreements were resolved by discussion or by consulting a third review author. MAIN RESULTS: This review included one RCT with 2307 healthy participants; all of them were analysed. This trial compared the effect of an adenovirus vaccine against a placebo. No statistically significant difference in common cold incidence was found: there were 13 events in 1139 participants in the vaccines group and 14 events in 1168 participants in the placebo group; risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 2.02, P = 0.90). No adverse events related to the live vaccine were reported. AUTHORS' CONCLUSIONS: This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine.

Pharmacological interventions for treating heart failure in patients with chagas cardiomyopathy.

BACKGROUND: Chagas disease-related cardiomyopathy is a major cause of morbidity and mortality in Latin America. Despite the substantial burden to the healthcare system, there is uncertainty regarding the efficacy and safety of pharmacological interventions for treating heart failure in patients with Chagas disease. OBJECTIVES: To assess the benefits and harms of current pharmacological interventions for treating heart failure in patients with Chagas cardiomyopathy. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) Issue 1, 2011, MEDLINE (Ovid), EMBASE (Ovid), LILACS and ISI Web of Science to April 2011. We checked the reference lists of included papers. No language restrictions were applied. SELECTION CRITERIA: We included randomized clinical trials assessing the effects of pharmacological interventions for treating heart failure in adult patients (≥18 years) with symptomatic heart failure (New York Heart Association class II to IV), irrespective of the left ventricular ejection fraction stage, reduced or preserved, with Chagas cardiomyopathy. No limits were applied with respect to the follow-up duration. Primary outcomes were all-cause mortality, cardiovascular mortality at 30 days, time to heart decompensation and disease-free period (at 30, 60 and 90 days), and adverse events. DATA COLLECTION AND ANALYSIS: Two authors independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) and the respective 95% confidence intervals (CIs) for dichotomous outcomes. We measured statistical heterogeneity using the I(2) statistic. We used a fixed-effect model to synthesize the findings. We contacted authors for additional data. MAIN RESULTS: We included two randomized clinical trials involving 69 participants. Both trials compared carvedilol against placebo, and had a high risk of bias. Carvedilol compared with placebo did not significantly affect all-cause mortality (2/34 (5.88%) versus 3/35 (5.87%); pooled RR 0.69, 95% CI 0.12 to 3.88, I(2) = 0%). None of the trials reported on cardiovascular mortality, time to heart decompensation or disease-free period. Evidence on the adverse effects of carvedilol is inconclusive. AUTHORS' CONCLUSIONS: This Cochrane review has found a lack of evidence on the effects of carvedilol for treating heart failure in patients with Chagas disease. The two included trials were underpowered and had a high risk of bias. There are no conclusive data to support the use of carvedilol for treating Chagas cardiomyopathy. Unless randomized clinical trials provide evidence of a treatment effect, and the trade off between potential benefits and harms is established, policy-makers, clinicians, and academics should be cautious when recommending and administering carvedilol for treating heart failure in patients with Chagas disease. The efficacy and safety of other pharmacological interventions for treating heart failure in patients with Chagas disease is unknown.