KCNQ1 suppression-replacement gene therapy in transgenic rabbits with type 1 long QT syndrome.

BACKGROUND AND AIMS: Type 1 long QT syndrome (LQT1) is caused by pathogenic variants in the KCNQ1-encoded Kv7.1 potassium channels, which pathologically prolong ventricular action potential duration (APD). Herein, the pathologic phenotype in transgenic LQT1 rabbits is rescued using a novel KCNQ1 suppression-replacement (SupRep) gene therapy. METHODS: KCNQ1-SupRep gene therapy was developed by combining into a single construct a KCNQ1 shRNA (suppression) and an shRNA-immune KCNQ1 cDNA (replacement), packaged into adeno-associated virus serotype 9, and delivered in vivo via an intra-aortic root injection (1E10 vg/kg). To ascertain the efficacy of SupRep, 12-lead electrocardiograms were assessed in adult LQT1 and wild-type (WT) rabbits and patch-clamp experiments were performed on isolated ventricular cardiomyocytes. RESULTS: KCNQ1-SupRep treatment of LQT1 rabbits resulted in significant shortening of the pathologically prolonged QT index (QTi) towards WT levels. Ventricular cardiomyocytes isolated from treated LQT1 rabbits demonstrated pronounced shortening of APD compared to LQT1 controls, leading to levels similar to WT (LQT1-UT vs. LQT1-SupRep, P < .0001, LQT1-SupRep vs. WT, P = ns). Under ß-adrenergic stimulation with isoproterenol, SupRep-treated rabbits demonstrated a WT-like physiological QTi and APD90 behaviour. CONCLUSIONS: This study provides the first animal-model, proof-of-concept gene therapy for correction of LQT1. In LQT1 rabbits, treatment with KCNQ1-SupRep gene therapy normalized the clinical QTi and cellular APD90 to near WT levels both at baseline and after isoproterenol. If similar QT/APD correction can be achieved with intravenous administration of KCNQ1-SupRep gene therapy in LQT1 rabbits, these encouraging data should compel continued development of this gene therapy for patients with LQT1.

Pneumothorax, Pneumomediastinum, and Cervical and Facial Massive Emphysema Secondary to Colonoscopy: A Rare Complication of Colonoscopy.

Background: Colonoscopy is a resource used for the diagnosis, treatment, and monitoring of benign and malignant colorectal pathologies. The incidence of perforation is 0.03%-0.65% in diagnostic colonoscopy; however, the incidence can be up to 10 times higher in therapeutic interventions, such as polypectomies, increasing the risk of complications up to 0.07-2.1%. Materials and methods. Case report of a 71-year-old female who presents a rare complication due to a perforation in the sigmoid which developed pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema as a complication of a diagnostic colonoscopy where a biopsy of a friable lesion was performed. Results: A 71-year-old female that went to the emergency room due to acute generalized abdominal colic spasm pain with a duration of 7 hours, associated with significant abdominal distension, malaise, diaphoresis, progressive dyspnea, and massive subcutaneous emphysema that developed after performing panendoscopy and colonoscopy for diverticulosis follow-up. An abdominal CT scan with double contrast was performed, reporting suggestive data of hollow viscus perforation, pneumoperitoneum, pneumomediastinum, pneumothorax, and massive subcutaneous emphysema in the thorax, neck, and skull base. She underwent an exploratory laparotomy finding a perforation in the sigmoid for which sigmoidectomy was performed, and for the pneumothorax and pneumomediastinum, endopleural tubes were placed in both hemithoraxes. The massive subcutaneous emphysema subsided with observation and oxygen. Conclusion: A rare complication of the use of colonoscopy as a diagnostic and therapeutic method is presented. The purpose of presenting this case is for the doctor who performs these interventions to suspect this complication in a timely manner, not delaying the diagnosis and carrying out an urgent therapeutic approach as in this case with exploratory laparotomy, finding the perforation site and carrying out the corresponding surgical management. We demonstrated that massive subcutaneous emphysema can be managed with observation if there is no other alarm data evident that required another surgical approach.

Clinical practice guideline on the management of vestibular schwannoma.

INTRODUCTION: Vestibular schwannoma (VS) is the most common tumour of the cerebellopontine angle. The greater accessibility to radiological tests has increased its diagnosis. Taking into account the characteristics of the tumour, the symptoms and the age of the patient, three therapeutic strategies have been proposed: observation, surgery or radiotherapy. Choosing the most appropriate for each patient is a frequent source of controversy. MATERIAL AND METHODS: This paper includes an exhaustive literature review of issues related to VS that can serve as a clinical guide in the management of patients with these lesions. The presentation has been oriented in the form of questions that the clinician usually asks himself and the answers have been written and/or reviewed by a panel of national and international experts consulted by the Otology Commission of the SEORL-CCC. RESULTS: A list has been compiled containing the 13 most controversial thematic blocks on the management of VS in the form of 50 questions, and answers to all of them have been sought through a systematic literature review (articles published on PubMed and Cochrane Library between 1992 and 2023 related to each thematic area). Thirty-three experts, led by the Otology Committee of SEORL-CCC, have analyzed and discussed all the answers. In Annex 1, 14 additional questions divided into 4 thematic areas can be found. CONCLUSIONS: This clinical practice guideline on the management of VS offers agreed answers to the most common questions that are asked about this tumour. The absence of sufficient prospective studies means that the levels of evidence on the subject are generally medium or low. This fact increases the interest of this type of clinical practice guidelines prepared by experts.

Surgical and non-surgical management of thoracic and cervical paraganglioma.

Thoracic and cervical paragangliomas (PGLs) are rare neuroendocrine tumors arising from chromaffin cells of the neural crest progenitors located outside the adrenal gland. We describe our current protocol as a multidisciplinary team for the management of cervical and thoracic PGLs. Surgery is generally considered the treatment of choice as it offers the best chance for cure. For resection of thoracic PGLs, video-assisted thoracoscopic surgery (VATS) is the main surgical approach, while open thoracotomy is preferred in case of tumors > 6cm, lacking confirmation of a plane of separation with adjacent structures, or with technical difficulties during VATS. In cervical PGLs, the surgical approach should be individualized according to location, mainly based on the Glasscock-Jackson and the Fisch-Mattox classifications. Surgery is the treatment of choice for most cervical and thoracic PGLs, but radiotherapy or observation could be more suitable options in unresectable cervical and thoracic PGLs or when resection has been incomplete.

Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.

To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a general affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.

Analysis of Salivary Mycobiome in a Cohort of Oral Squamous Cell Carcinoma Patients From Sudan Identifies Higher Salivary Carriage of Malassezia as an Independent and Favorable Predictor of Overall Survival.

Background: Microbial dysbiosis and microbiome-induced inflammation have emerged as important factors in oral squamous cell carcinoma (OSCC) tumorigenesis during the last two decades. However, the "rare biosphere" of the oral microbiome, including fungi, has been sparsely investigated. This study aimed to characterize the salivary mycobiome in a prospective Sudanese cohort of OSCC patients and to explore patterns of diversities associated with overall survival (OS). Materials and Methods: Unstimulated saliva samples (n = 72) were collected from patients diagnosed with OSCC (n = 59) and from non-OSCC control volunteers (n = 13). DNA was extracted using a combined enzymatic-mechanical extraction protocol. The salivary mycobiome was assessed using a next-generation sequencing (NGS)-based methodology by amplifying the ITS2 region. The impact of the abundance of different fungal genera on the survival of OSCC patients was analyzed using Kaplan-Meier and Cox regression survival analyses (SPPS). Results: Sixteen genera were identified exclusively in the saliva of OSCC patients. Candida, Malassezia, Saccharomyces, Aspergillus, and Cyberlindnera were the most relatively abundant fungal genera in both groups and showed higher abundance in OSCC patients. Kaplan-Meier survival analysis showed higher salivary carriage of the Candida genus significantly associated with poor OS of OSCC patients (Breslow test: p = 0.043). In contrast, the higher salivary carriage of Malassezia showed a significant association with favorable OS in OSCC patients (Breslow test: p = 0.039). The Cox proportional hazards multiple regression model was applied to adjust the salivary carriage of both Candida and Malassezia according to age (p = 0.029) and identified the genus Malassezia as an independent predictor of OS (hazard ratio = 0.383, 95% CI = 0.16-0.93, p = 0.03). Conclusion: The fungal compositional patterns in saliva from OSCC patients were different from those of individuals without OSCC. The fungal genus Malassezia was identified as a putative prognostic biomarker and therapeutic target for OSCC.

Comparación del ángulo de la guía condílea sagital obtenida del registro radiográfico y clínico en pacientes dentados / Comparison of sagittal condylar guidance obtained from radiographic and and clinical records in dentate patients

Objetivo: Comparar el ángulo de la guía condílea sagital obtenida del registro radiográfico y clínico en pacientes dentados. Materiales y métodos: La muestra estuvo conformada por un grupo único de estudio de 32 pacientes, en el que se evaluó la radiografía lateral estricta y los registros posicionales: en relación céntrica, registro protrusivo a 5 mm en lateralidad derecha y registro protrusivo a 5 mm en lateralidad izquierda. Con el registro posicional del arco facial se articuló el modelo superior, con el registro posicional en relación céntrica se articuló el modelo inferior, con los registros laterales protrusivos de los lados derecho e izquierdo se obtuvo la medida del ángulo de la guía condílea sagital para la programación del articulador semiajustable. El plan estadístico en la presente investigación utilizó el programa SPSS versión 24, la normalidad fue evaluada usando el test de Shapiro-Wilk, también se realizaron las pruebas de T de Student y correlación de Pearson. Resultados: Se determinó estadísticamente que el género y la edad influyen en la medida del ángulo de la guía condílea sagital. El método radiográfico presentó un ángulo de guía condílea de 35,69 ±5,18 y con el método clínico fue 35,69 ± 5,16 (p > 0,05). La prueba de correlación de Pearson sí mostró una correlación importante entre ambos métodos r = 0,948, p < 0,001. Conclusiones: Existe alta correlación en las medidas obtenidas del ángulo de la guía condílea sagital con los registros radiográficos y clínicos; esta concordancia permitiría reemplazar un método por el otro. (AU)

Objective: To compare the angle of the sagittal condylar guidance obtained from the radiographic and clinical records of dentate patients. Materials and Methods: The sample consisted of 32 patients in whom strict lateral radiography and positional records were performed: in centric relation, protrusive recording 5 mm in right laterality and protrusive recording 5 mm in left laterality. With the positional registration of the facebow, the upper model was articulated, while the lower model was articulated with the positional registration in centric relation, and with the protrusive lateral registrations on the right and left side the condylar guidance was obtained for programming the semi-adjustable articulator. Statistics were performed with the SPSS program version 24 in Spanish. Normality was evaluated using the Shapiro-Wilk test, for data with normal distribution, and the Student's T test and Pearson's correlation were performed in descriptive statistics. Results: The statistical analyses showed that gender and age influence the angle measurement of the sagittal condylar guide. The radiographic method presented a condylar guide angle of 35.69 ± 5.18, being 35.69 ± 5.16 with the clinical method (p> 0.05). Pearson's correlation test showed an important correlation between the two methods (r = 0.948, p <0.001). Conclusions: There is a high correlation in the measurements obtained from the angle of the sagittal condylar guide and the radiographic and clinical records, indicating that both methods are effective. (AU)

Can elastic band resistance training programs mitigate holiday weight gain and improve hand-grip strength in older women? / ¿Pueden los programas de entrenamiento de resistencia con banda elástica mitigar el aumento de peso durante las vacaciones y mejorar la fuerza de agarre de las manos en mujeres mayores?

SUMMARY: This study evaluated the effect of resistance exercise training (RET) on body composition and muscle strength in 16 older women during summer holidays (70.5 ± 8.4 years old; Range 60-87). Exercise sessions were carried out for twelve weeks, two sessions per week, with 60 minutes of exercise per session. We measured body mass index (BMI), fat mass percentage (FM%, by bioimpedance) and grip strength with a dynamometer before and after the intervention. The participants showed a significant increase in BMI (p<0.05), FM% (p<0.001), and a significant gain in grip strength (p<0.05). The RET program could be an important strategy for improving strength for older women, but we would suggest combining it with other interventions, such as aerobic exercises with gradually increasing intensity and nutrition interventions, in order to maintain a steady weight during holiday periods.

RESUMEN: Este estudio evaluó el efecto del entrenamien- to con ejercicios de resistencia (EER) sobre la composición corpo- ral y la fuerza muscular en 16 mujeres adultas mayores durante las vacaciones de verano (70,5 ± 8,4 años; Rango 60-87). Las sesio- nes de ejercicio se llevaron a cabo durante doce semanas, dos ve- ces por semana, con 60 minutos de ejercicio por sesión. Se evaluó el índice de masa corporal (IMC), el porcentaje de masa grasa (% MG, por bioimpedancia) y la fuerza de presión con un dinamómetro manual antes y después de la intervención. Las participantes mos- traron un aumento significativo en el IMC (p< 0,05), % de MG (p<0,001) y un incremento significativo en la fuerza prensil (p <0,05). El programa de EER podría ser una estrategia importante para mejorar la fuerza de mujeres adultas mayores durante el periodo estival. El EER se sugiere combinarlo con otras variables, como ejercicios aeróbicos con intensidad gradualmente creciente y una intervención nutricional, para mantener un peso constante durante los períodos de vacaciones.

Psicodermatología: una introducción a sus conceptos, nosología y modelos de abordaje / Psychodermatology: An introduction to its concepts, nosology and approach models

Es imposible separar la enfermedad física de la enfermedad mental, puesto que la fisiopatología de cualquier enfermedad contiene a la esfera psicológica dentro de sus múltiples elementos. En ese sentido, muchas especialidades médicas pueden reclamar su relación con la Psiquiatría, puesto que son innumerables las enfermedades que tienen nexo con signos y síntomas psiquiátricos (por ejemplo, la enfermedad inflamatoria intestinal en Gastroenterología; el asma bronquial en Neumología, entre otras). No obstante, con la Dermatología la relación es mucho más evidente. La Psicodermatología es una especialidad que surge de la conjunción de dos ramas aparentemente divergentes de la Medicina: la Psiquiatría y la Dermatología. En Psicodermatología, algunos pacientes presentan enfermedades principalmente dermatológicas con comorbilidades psicosociales secundarias, mientras que otros tienen trastornos psiquiátricos primarios con sintomatología cutánea significativa. Así también, debido a que varias enfermedades dermatológicas no solo se acompañan frecuentemente de dolor e incomodidad, sino que son inmediatamente visibles para los demás, las personas afectadas por estas condiciones pueden sufrir consecuencias sociales y emocionales. Con base en lo anterior, este artículo de revisión presenta los conceptos, nosología y modelos de abordaje de esta ciencia médica, haciendo hincapié que, debido a la interacción permanente entre la mente y la piel, se hace necesario que el paciente sea tratado como una unidad constituida por varios niveles, incluyendo aspectos cutáneos, emocionales y mentales.

It is impossible to separate the physical illness from the mental illness, since the pathophysiology of any disease contains the psychological sphere within its multiple elements. In this sense, many medical specialties can claim their relationship with Psychiatry, since there are innumerable diseases that have a link with psychiatric signs and symptoms (for example, inflammatory bowel disease in Gastroenterology; bronchial asthma in Pneumology, among others). However, with Dermatology the relationship is much more evident. Psychodermatology is a specialty that arises from the conjunction of two apparently divergent branches of Medicine: Psychiatry and Dermatology. In Psychodermatology, some patients present mainly dermatological diseases with secondary psychosocial comorbidities, while others have primary psychiatric disorders with significant cutaneous symptoms. Also, because various dermatologic diseases are not only frequently accompanied by pain and discomfort, but are immediately visible to others, people affected from these conditions can suffer social and emotional consequences. Based on the above, this review article presents the concepts, nosology, and approach models of this medical science, emphasizing that due to the permanent interaction between the mind and the skin, it is necessary for the patient to be treated as an unit made up of several levels, including cutaneous, emotional and mental aspects.

Tobacco smoking is an independent factor associated with retinal damage in systemic lupus erythematosus: a cross-sectional and retrospective study.

To analyze the influence of tobacco smoking on systemic lupus erythematosus (SLE) clinical features and damage. Cross-sectional and retrospective, case-control study comparing SLE patients with and without tobacco exposure. Cumulative clinical data and comorbidities were collected, and severity (Katz index) and damage (SLICC/ACR damage index) (SDI) indices were calculated. Pack-years (PY) was used to estimate lifetime tobacco exposure. A logistic regression was carried out to explore the impact of tobacco use on retinal damage. 216 patients were included. The mean age was 49 years (± 12.7), 93% were females, and median disease duration was 17 years [interquartile range (IQR):9-25]. Fifty-three percent of patients were smokers at some point. The median PY was 13 (IQR: 6-20.5). Only 54.8% of active smokers recalled having been informed of the negative effects of smoking, versus 83.3% of never smokers (< 0.001). In a bivariant analysis, an association between tobacco use at any time and discoid lupus [OR: 3.5(95%CI 1.5-8.9); p = 0.002] photosensitivity [OR: 2.06(95%CI 1.16-3.7); p = 0.01] and peripheral arteriopathy (p = 0.007) was found. Considering SDI item by item, a significant association with retinal damage, adjusted for age [OR: 1.03(95%CI 1-1.07); p = 0.04], was found. Using PYs, an association was found with discoid lupus (p = 0.01), photosensitivity (p = 0.03) and peripheral arteriopathy (p = 0.01), global SDI > 0 (p = 0.002) and retinal damage (p = 0.02). In a multivariate analysis exploring factors associated with retinal damage, any previous smoking history and SDI remained associated with retinal damage. Tobacco smoking is associated with cutaneous manifestations and damage and is an independent predictor of retinal damage in SLE patients.

Colchicine-Induced Rhabdomyolysis: Clinical, Biochemical, and Neurophysiological Features and Review of the Literature.

We report the case of a 46-years-old man with long-term asymptomatic hyperuricemia who started taking colchicine (0.5 mg/day) and allopurinol (100 mg/d) for normalization of biochemical values. After the third week of starting treatment, acute weakness was present; and by the fifth week, profound weakness in lower extremities and tenderness and cramps on thighs and calves with inability to climb stairs were also observed. Biochemical evaluation showed elevated muscle enzymes (creatinine kinase [CK] raised to five-folds its normal value) and electromyographic features were consistent with myopathy (at rest, fibrillations, positive sharp waves, high-frequency myotonic discharges; motor unit action potentials [MUAPs] of small amplitude, small duration, increased polyphasic Index and occasional satellite potentials; at maximal effort, interferential recruitment pattern with reduced amplitudes were observed). Normal motor and sensitive nerve conduction studies and normal late F-responses and H-reflex discarded neuropathy. Rapid improvement in muscle strength and prompt resolution of abnormal elevated muscle enzymes was observed after withdrawal of both medications. Colchicine is associated with some cases of myotoxicity but very small cases of colchicine-induced rhabdomyolysis are reported on the literature. Colchicine-induced rhabdomyolysis is related to the concomitant use of drugs (statins, steroids, erythromycin, and cyclosporine), renal, and/or hepatic impairment. To the best of our knowledge, this is an uncommon presentation of a case of colchicine-induced rhabdomyolysis reported in a patient without renal or hepatic dysfunction. Therefore, patients receiving colchicine even in the absence of renal insufficiency should be monitored for the development of myopathy and more rarely to rhabdomyolysis.

Narrow band imaging endoscopy improves visualization of vessels of the perforated tympanic membrane.

PURPOSE: Because successful healing of a tympanic membrane perforation (TMP) depends upon the maintenance of blood supply to the injured area, we assessed the usefulness of narrow band imaging (NBI) video endoscopy to evaluate its vascularization. To our knowledge, the use of NBI to assess tympanic membrane (TM) vascular patterns has never been attempted. METHODS: Prospective observational study. NBI and cold white light (CWL) flexible videoendoscopy was used to explore perforated TMs of 100 patients. Main outcome measures were visualization of vessels among abnormal TM findings: monomeric areas (MA) (n = 6), myringosclerosis plaques (MP) (n = 65) and perforation edges (n = 100). They were graded by a vascular otoendoscopic score (VOS) comparing both types of lights (Wilcoxon test). Location and vascularization patterns were analyzed (Fisher's test). RESULTS: NBI was better to observe vascularization of 32% of perforation edges and 75.4% of MP (p < 0.001). NBI displayed higher (better) VOS when evaluating TMP edges (1.05 vs. 0.73) and MP (1.56 vs. 0.81, p < 0.001). The majority of TMP edges showed a ring pattern (66%), followed by irregular (19%), avascular (12%) and radial patterns (3%). The avascular pattern was more frequent in posterior perforations (p = 0.003). The radial pattern was most frequently found in MP, especially at posterior quadrants (p = 0.048). MA presented an irregular pattern in 83.3% of TMs. CONCLUSIONS: NBI videoendoscopy is a promising non-invasive technique, superior to CWL for visualizing vessels among TMP edges and MP, based on further study, could become a supplementary diagnostic tool in the workup of TMP and the decision-making surgical field.

Morphometric and molecular differences among Calvertius tuberosus (Coleoptera: Curculionidae) populations associated with Andean and coastal populations of Araucaria araucana in the La Araucanía Region, Chile

Abstract Calvertius tuberosus (Curculionidae) lives exclusively on Araucaria araucana trees (commonly known as pehuen) in southern Chile. In this study, morphometric and molecular genetic analyses of Andean and coastal populations of C. tuberosus were performed to evaluate evolutionary divergence associated with the discontinuity of the Araucaria forest between the coastal and Andean regions. Specimens of C. tuberosus were collected in Nahuelbuta National Park, Villa Las Araucarias, and Malalcahuello National Reserve and were classified and stored at the Animal Biotechnology Researching Laboratory (LINBA), University of La Frontera, Temuco, Chile. Thirteen morphometric parameters and the expression patterns of ISSR (inter-simple sequence repeat) markers were analyzed. Morphometric data revealed high phenotypic similarity between coastal populations. The genetic analysis revealed a high similarity between coastal populations (genetic identity, 93%), which were differentiated from the Andean population (genetic identity, 84%). This study contributes new genotypic and phenotypic data for the C. tuberosus populations in forest ecosystems of A. araucana, and clarifies the associations between these characteristics and the geographic distributions of populations.

Functional role of highly conserved residues of the N-terminal tail and first transmembrane segment of a P4-ATPase.

The P4 family of P-type ATPases (P4-ATPases) plays an important role in maintaining phospholipid asymmetry in eukaryotic cell membranes. Leishmania miltefosine transporter (LMT) is a plasma membrane (PM) P4-ATPase that catalyses translocation into the parasite of the leishmanicidal drug miltefosine as well as phosphatidylcholine and phosphatidylethanolamine analogues. In the present study, we analysed the role, in LMT, of a series of highly conserved amino acids previously undescribed in the N-terminal region of P4-ATPases. Seven residues were identified and, according to an LMT structural model, five were located in the cytosolic N-terminal tail (Asn58, Ile60, Lys64, Tyr65 and Phe70) and the other two (Pro72 and Phe79) in the first transmembrane segment (TM1). Alanine-scanning mutagenesis analysis showed that N58A, Y65A and F79A mutations caused a considerable reduction in the LMT translocase activity. These mutations did not affect protein expression levels. We generated additional mutations in these three residues to assess the influence of the conservation degree on LMT translocase activity. Some of these mutations reduced expression levels without affecting the interaction between LMT and its CDC50 subunit, LRos3. Conserved and non-conserved mutations in the invariant residue Asn58 drastically reduced the translocase activity. Consequently, Asn58 may be necessary to achieve optimal catalytic LMT activity as previously described for the potentially equivalent Asn39 of the sarco/endoplasmic reticulum Ca2+-ATPase isoform 1a (SERCA1a). Additionally, conservation of a hydrophobic residue at position 79 is crucial for LMT stability.

Endovascular aortic sealing with Nellix reduces intraoperative radiation dose when compared to endovascular aortic repair.

OBJECTIVE: To analyze radiation exposure during endovascular aortic sealing (EVAS) in comparison with standard endovascular aortic repair (EVAR) in clinical practice. METHODS: From December 2013 to October 2016 (35 months), 60 patients were analyzed for intraoperative radiation exposure during EVAR: 30 consecutive patients (mean age, 73.10 years; 28 male) received EVAS (Nellix Endologix); within the same time frame, 30 patients were treated with standard EVAR (mean age, 71.87 years; 30 male). An indirect dose analysis was performed for both groups of patients, including effective dose and cumulative air kerma. Furthermore, fluoroscopy time (FT), dose area product, and time of procedure were included in the study. RESULTS: The effective dose was significantly reduced in the EVAS group (3.72 mSv) compared with the group treated with standard EVAR (6.8 mSv; P ≤ .001). The cumulative air kerma was also lowered in EVAS (67.65 mGy vs 139 mGy in EVAR; P ≤ .001). FT for the entire group was 13 minutes and was shorter (P < .001) for EVAS (9 minutes) in comparison with EVAR (19 minutes). The dose area product for the entire cohort was 16.95 Gy.cm2 and was lower during EVAS (12.4 Gy.cm2) than during EVAR (22.6 Gy.cm2; P < .001). The median operating time for the entire group was 123.5 minutes and was significantly shorter (P < .01) for EVAS (119 minutes vs EVAR at 132 minutes). The FT shows a significant correlation with the patient's weight (P = .022), body mass index (P = .004), and time of procedure (P = .005). CONCLUSIONS: EVAS is associated with a relevant decrease in indirect measured radiation dose and time of procedure compared with standard EVAR. A relevant reduction in dose during EVAS is highly likely to result in lower exposure to radiation for physicians and staff. Such a result would be highly advantageous and calls for further analysis.

Levator Palpebrae Superioris Muscle Direct Neurotization.

Direct muscle neurotization has been proved to be a feasible technique for facial reanimation microsurgical procedures. Direct muscle neurotization is performed by implanting the interposition nerve graft directly into the substance of the muscle. The authors present the case of a 36-year-old male patient with upper eyelid dysfunction secondary to facial trauma. The levator palpebrae superioris muscle was macroscopically unaffected; however, neurophysiological test proved a selective denervation of the CN III motor branch to the levator palpebrae superioris muscle. Direct muscle neurotization was performed by means of 2 separate nerve procedures. The authors have made follow-up for 3 months after surgery. The authors have noted development of upper eyelid movement meaning adequate function of the neurotized muscle. The authors believe that this procedure could be integrated into the surgical options to treat selective nerve injuries should the right patient is encountered.

Bat Reservoirs for Rabies Virus and Epidemiology of Rabies in Colombia: a review / Murciélagos reservorios del virus de la Rabia y epidemiologia de la Rabia en Colombia: una revisión / Reservatórios de morcegos do vírus da raiva e epidemiologia da raiva na Colômbia: uma revisão

Abstract Rabies is a fatal zoonotic disease caused by a neurotropic RNA virus part of the family Rhabdoviridae. The disease is characterized by encephalitic inflammation and is responsible for a number of annual fatal deaths of people and animals in the world. Chiropters such as insectivorous, frugivorous and hematophagous bats are the major transmitters, reservoirs, and vectors of the rabies virus. In Colombia, a total of thirty-five cases of human rabies occurred between 2000 2014. Of the thirty-five cases twenty-two were transmitted by bats. The genetic variant V3 (hematophagous bats) were responsible for 24 human deaths, while the genetic variant V4, carried by insectivorous bats, caused three human deaths. The disease is mainly linked to infected cats that may have hunted infected bats and then transmitted the virus to humans. Diagnosis is usually made by detection of the virus from infected animals and techniques such as RT-PCR, which might be used to promote active surveillance in bat populations. Rabies is a preventable disease and vaccination of pets confers protective immunity, however, vaccination coverage of pets in Colombia is still limited. This review article collects epidemiological data of rabies virus genetic variants associated with chiropters species that have been reported to transmit the virus in the world and emphasizes on rabies cases reported in Colombia during the last decades.

Resumen La rabia es una enfermedad zoonóticas mortal causada por un virus ARN neurotrópico de la familia Rhabdoviridae. La enfermedad se caracteriza por encefalitis y es responsable de múltiples muertes anuales de personas y animales. Quirópteros insectívoros, frugívoros y hematófagos son los principales transmisores, reservorios y vectores del virus. En Colombia, un total de 35 casos de rabia humana fueron reportados entre 2000- 2014, veintidós de ellos fueron transmitidos por murciélagos. La variante genética V3 (murciélagos hematófagos) fue responsable de 24 muertes humanas, mientras que la variante genética V4 (murciélagos insectívoros) causó tres muertes humanas. La enfermedad es transmitida al humano principalmente por gatos infectados que pudieron haber cazado murciélagos infectados. El diagnóstico se realiza mediante la detección del virus en animales rabiosos y técnicas como RT-PCR podrían utilizarse para promover la vigilancia activa de las poblaciones de murciélagos. La rabia es una enfermedad prevenible y la vacunación en animales domésticos confiere inmunidad protectora, sin embargo, la cobertura de vacunación en animales domésticos en Colombia es aún limitada. Esta revisión recoge datos epidemiológicos de las variantes genéticas del virus en especies de quirópteros reportadas como transmisores del virus en el mundo y enfatiza en los casos de rabia reportados en Colombia durante las últimas décadas.

Resumo A raiva é uma enfermidade zoonótica fatal causada pelo vírus neurotrópico do ARN da família Rhabdoviridae. A enfermidade é conhecida por encefalite e é responsável das numerosas mortes anuais de animais e pessoas. Quirópteros e insetívoros, frugívoros e sanguessugas são os principais transmissores, reservatórios e vetores do vírus. Na Colômbia o Instituto Nacional de Saúde relatou um total de 35 casos de raiva humana entre 2000- 2014. Vinte dois deles foram transmitidos pelos morcegos. A variante genética V3 (morcegos hematófagos) foi responsável de 24 mortes humanas. Enquanto a variante genética V4 (morcegos insetívoros) provoco três mortes humanas. A enfermidade está ligada principalmente á os gatos infectados que poderiam ter caçado morcegos infectados e, em seguida, transmitida a os seres humanos. Diagnóstico e normalmente feito a través da detecção do vírus em animais raivosos e técnicas tais como RT- PCR poderiam se utilizar para promover a vigilância ativa das populações de morcegos. A raiva é uma enfermidade evitável em animais domésticos cuja vacinação confere imunidade protetora, no entanto, a cobertura de vacinação em animais de estimação na Colômbia ainda é limitada, precisando de mais cobertura. Este artigo de revisão recolha dados epidemiológicos e variantes genéticas do vírus, e a diversidade de espécies de morcego reportado como transmissores do vírus no mundo. O manuscrito também resume os principais casos de raiva reportados na Colômbia nas últimas décadas e enfatiza a necessidade de reforçar a vigilância ativa para o diagnóstico de raiva em morcegos em todo o país.

An RYR1 mutation associated with malignant hyperthermia is also associated with bleeding abnormalities.

Malignant hyperthermia is a potentially fatal hypermetabolic disorder triggered by halogenated anesthetics and the myorelaxant succinylcholine in genetically predisposed individuals. About 50% of susceptible individuals carry dominant, gain-of-function mutations in RYR1 [which encodes ryanodine receptor type 1 (RyR1)], though they have normal muscle function and no overt clinical symptoms. RyR1 is predominantly found in skeletal muscle but also at lower amounts in immune and smooth muscle cells, suggesting that RYR1 mutations may have a wider range of effects than previously suspected. Mild bleeding abnormalities have been described in patients with malignant hyperthermia carrying gain-of-function RYR1 mutations. We sought to determine the frequency and molecular basis for this symptom. We found that some patients with specific RYR1 mutations had abnormally high bleeding scores, whereas their healthy relatives did not. Knock-in mice with the malignant hyperthermia susceptibility RYR1 mutation Y522S (MHS RYR1Y522S) had longer bleeding times than their wild-type littermates. Primary vascular smooth muscle cells from RYR1Y522S knock-in mice exhibited a higher frequency of subplasmalemmal Ca(2+) sparks, leading to a more negative resting membrane potential. The bleeding defect of RYR1Y522S mice and of one patient was reversed by treatment with the RYR1 antagonist dantrolene, and Ca(2+) sparks in primary vascular smooth muscle cells from the MHS RYR1Y522S mice were blocked by ryanodine or dantrolene. Thus, RYR1 mutations may lead to prolonged bleeding by altering vascular smooth muscle cell function. The reversibility of the bleeding phenotype emphasizes the potential therapeutic value of dantrolene in the treatment of such bleeding disorders.

Effect of summer holidays on anthropometric measures and body composition of older adults, inadequacy of body mass index to detect changes during a critical period: a pilot study / Efecto de las vacaciones de verano en la composición corporal de adultos mayores, insuficiencia del índice de masa corporal para detectar cambios durante un período crítico: un estudio piloto

Obesity is a major health problem worldwide. Obesity prevalence in Chilean older adults (OA) is increasing, associated with several negative health outcomes. Therefore, determining critical periods of adiposity increase is relevant in OA. The aim of the study was to assess body composition changes in OA during summer holidays. This observational study involved two test visits, without a control group. Twelve OA (9 females) with an average age of 71.92±6.97 years participated in an initial evaluation (E1) and final evaluation (E2) at the beginning and at the end of the summer in 2015. Weight, height, and body mass index (BMI) were assessed; fat-free mass (FFM), fat mass (FM), and muscular mass (MM) data were collected through foot-to-foot bioimpedance analysis. No significant variations were reported in weight and BMI between E1 and E2. This prevalence was maintained between E1 and E2. The FM significantly increased between E1 (27.63±10.91) and E2 (28.64±11.39) (p= 0.007), while the FFM significantly decreased between E1 (45.38±5.89) and E2 (44.33±5.36) (P= 0.006), also the MM between E1 (43.08±5.62) and E2 (42.07±5.10). Both, weight and BMI are insufficient measures for detecting changes during this critical summer holiday period. However, the body composition measures identified significant changes in the OA during the study.

La obesidad es el principal problema de salud en todo el mundo. La prevalencia de obesidad en adultos mayores (AM) chilenos es cada vez mayor, lo que se ha asociado con varios efectos negativos para la salud. Por lo tanto, la determinación de períodos críticos de aumento de la adiposidad es relevante en AM. El objetivo fue evaluar los cambios de la composición corporal en adultos mayores AM durante las vacaciones de verano. Doce AM participaron en una evaluación inicial (E1) y final (E2) del verano 2015. Se evaluó: peso, talla, índice de masa corporal (IMC), masa libre de grasa (MLG), masa grasa (MG) y masa muscular (MM). No hubo diferencias significativas en peso e IMC. La MG aumentó entre E1 (27,63±10,91) y E2 (28,64±11,39) (p= 0,007), la MLG disminuyó significativamente entre E1 (45,38±5,89) y E2 (44,33±5,36), como también la MM entre E1 (43,08±5,62) y E2 (42,07±5,10). Tanto el peso como el IMC son medidas insuficientes para detectar cambios durante este período crítico de vacaciones de verano. Sin embargo, las medidas de la composición corporal identificaron cambios significativos en AM durante el estudio.