Complex Synaptic and Intrinsic Interactions Disrupt Input/Output Functions in the Hippocampus of Scn1b Knock-Out Mice.

Pathogenic variants in SCN1B have been linked to severe developmental epileptic encephalopathies including Dravet syndrome. Scn1b knock-out (KO) mice model SCN1B loss-of-function (LOF) disorders, demonstrating seizures, developmental delays, and early death. SCN1B encodes the protein ß1, an ion channel auxiliary subunit that also has roles in cell adhesion, neurite outgrowth, and gene expression. The goal of this project is to better understand of how loss of Scn1b alters information processing in the brain, resulting in seizures and associated cognitive dysfunction. Using slice electrophysiology in the CA1 region of the hippocampus from male and female Scn1b KO mice and wild-type (WT) littermates, we found that processing of physiologically relevant patterned Schaffer collateral (SC) stimulation produces larger, prolonged depolarizations and increased spiking in KO neurons compared with WTs. KO neurons exhibit enhanced intrinsic excitability, firing more action potentials with current injection. Interestingly, SC stimulation produces smaller, more facilitating excitatory and IPSCs in KO pyramidal neurons, but larger postsynaptic potentials (PSPs) with the same stimulation. We also found reduced intrinsic firing of parvalbumin (PV)-expressing interneurons and disrupted recruitment of both parvalbumin-expressing and somatostatin (SST)-expressing interneurons in response to patterned synaptic stimulation. Neuronal information processing relies on the interplay between synaptic properties, intrinsic properties that amplify or suppress incoming synaptic signals, and firing properties that produce cellular output. We found changes at each of these levels in Scn1b KO pyramidal neurons, resulting in fundamentally altered cellular information processing in the hippocampus that likely contributes to the complex phenotypes of SCN1B-linked epileptic encephalopathies.SIGNIFICANCE STATEMENT Genetic developmental epileptic encephalopathies have limited treatment options, in part because of our lack of understanding of how genetic changes result in dysfunction at the cellular and circuit levels. SCN1B is a gene linked to Dravet syndrome and other developmental epileptic encephalopathies, and Scn1b knock-out (KO) mice phenocopy the human disease, allowing us to study underlying neurophysiological changes. Here, we found changes at all levels of neuronal information processing in brains lacking Scn1b, including intrinsic excitability, synaptic properties, and synaptic integration, resulting in greatly enhanced input/output functions of the hippocampus. Our study shows that loss of Scn1b results in a complex array of cellular and network changes that fundamentally alters information processing in the hippocampus.

Complex synaptic and intrinsic interactions disrupt input/output functions in the hippocampus of Scn1b knockout mice.

Mutations in the SCN1B gene have been linked to severe developmental epileptic encephalopathies including Dravet syndrome. Scn1b k nock o ut (KO) mice model SCN1B loss of function disorders, demonstrating seizures, developmental delays, and early death. SCN1B encodes the protein ß1, an ion channel auxiliary subunit that also has roles in cell adhesion, neurite outgrowth, and gene expression. The goal of this project is to better understand of how loss of ß1 alters information processing in the brain, resulting in seizures and associated cognitive dysfunction. Using slice electrophysiology in the CA1 region of the hippocampus from male and female Scn1b KO mice and w ild-type (WT) littermates, we found that processing of physiologically relevant patterned S chaffer c ollateral (SC) stimulation produces larger, prolonged depolarizations and increased spiking in KO neurons compared to WTs. KO neurons exhibit enhanced intrinsic excitability, firing more action potentials with current injection. Interestingly, SC stimulation produces smaller, more facilitating excitatory and inhibitory postsynaptic currents in KO pyramidal neurons, but larger postsynaptic potentials with the same stimulation. We also found reduced intrinsic firing of parvalbumin-expressing interneurons and disrupted recruitment of both parvalbumin- and somatostatin-expressing interneurons in response to patterned synaptic stimulation. Neuronal information processing relies on the interplay between synaptic properties, intrinsic properties that amplify or suppress incoming synaptic signals, and firing properties that produce cellular output. We found changes at each of these levels in Scn1b KO pyramidal neurons, resulting in fundamentally altered information processing in the hippocampus that likely contributes to the complex phenotypes of SCN1B -linked epileptic encephalopathies. Significance statement: Genetic developmental epileptic encephalopathies have limited treatment options, in part due to our lack of understanding of how genetic changes result in dysfunction at the cellular and circuit levels. SCN1B is a gene linked to Dravet syndrome and other epileptic encephalopathies, and Scn1b knockout mice phenocopy the human disease, allowing us to study underlying neurophysiological changes. Here we found changes at all levels of neuronal information processing in brains lacking ß1, including intrinsic excitability, synaptic properties, and synaptic integration, resulting in greatly enhanced input/output functions of the hippocampus. Our study shows that loss of ß1 results in a complex array of cellular and network changes that fundamentally alters information processing in the hippocampus.

Effectiveness of the Use of Three-Dose Intravitreal Ziv-Aflibercept in the Management of Diabetic Macular Edema in a Real-Life Setting.

Purpose: It has been reported that intravitreal Ziv-aflibercept is a safe and effective drug for the treatment of diabetes macular edema (DME). The objective of this study was to evaluate in a real-life setting, the efficacy of intravitreal Ziv-aflibercept in the treatment of DME after the administration of three consecutive monthly doses. Methods: A single arm, prospective cohort study. We included patients with DME who received three doses of intravitreal Ziv-aflibercept. Data such as best corrected visual acuity (BCVA) and tomographic biomarkers before treatment and a month after the third dose were collected. DME was staged using the Panozzo classification. Results: Thirty-eight patients participated for a total of 53 eyes. The mean age was 59 ± 8.1 years. We observed significant changes after the third dose in the parameters studied (BCVA in LogMAR pre-treatment (0.6 ± 0.33) and post-treatment (0.4 ± 0.29) [p<0.001], macular thickness pre-treatment (501 ± 167 µm) and post-treatment (324 ± 114 µm) [p<0.001], macular volume pre-treatment 10.8 (7.5-17.8) mm3 and post-treatment 9.3 (0-13.6) mm3 [p<0.005]). And 73.6% of the patients presented an advanced severe stage during their pre-treatment evaluation and after post-treatment, 64.2% of the patients no longer presented edema. No systemic or ocular adverse events occurred. Conclusion: The use of three consecutive monthly doses of intravitreal Ziv-aflibercept in a real-life setting is effective and safe in the management of diabetic macular edema.

Latin American Registry of Idiopathic Pulmonary Fibrosis (REFIPI): Clinical Characteristics, Evolution and Treatment.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible and frequently fatal disease. Currently there are national and multinational registries in Europe, United States, Australia and China to better understand the magnitude of the problem and the characteristics of the IPF patients. However, there are no national or regional registries in Latin America, so the objective of this study was to carry out a Latin American registry that would allow the identification of IPF patients in our region. METHODOLOGY: A system consisting of 3 levels of control was designed, ensuring that patients met the diagnostic criteria for IPF according to international guidelines ATS/ERS/ALAT/JRS 2011. Demographic, clinical, serological, functional, tomographic, histological and treatment variables were recorded through a digital platform. RESULTS: 761 IPF patients from 14 Latin American countries were included for analysis, 74.7% were male, with a mean age of 71.9+8.3 years. In general there was a long period of symptoms before definitive diagnosis (median 1 year). In functional tests, an average reduction of FVC (70.9%) and DLCO (53.7%) was detected. 72% received at least one antifibrotic drug (pirfenidone or nintedanib) and 11.2% of the patients had an acute exacerbation, of which 38 (45.2%) died from this cause. CONCLUSIONS: Like other registries, we found that there is difficulty in the recognition and excessive delay in the diagnosis of IPF in Latin America. Most of the patients in REFIPI received antifibrotics; these were well tolerated and associated with fewer adverse events than those reported in clinical trials.

Management of a Child with Reactive Attachment Disorder in the Dental Clinical Setting: A Case Report / Manejo de un niño con trastorno de apego reactivo en el entorno clínico dental: Reporte de un caso

ABSTRACT Reactive attachment disorder (RAD) is an early childhood mental health disease characterized by impaired social interactions and communication abilities, and neurological deficits in the child's developing brain. This disorder can significantly affect the pediatric patient's behavior in the dental setting. An uncooperative 9-year- old Mexican girl, who was residing in a temporary home, was referred by a general dental practitioner to the Postgraduate Pediatric Dental Clinic with her caretaker, requesting dental examination and treatment. The patient presented with a previous diagnosis of RAD with intellectual/social disability. With the psychiatrist's guidance, an exhaustive oral prophylaxis was carried out in the initial appointments, followed by diverse restorative treatments under the continuous application of behavioral management techniques. These restorative procedures included resin restorations and pit-fissure sealants, under local anesthesia and rubber-dam isolation, on the first four permanent molars. The entire treatment was completed in six weeks. The patient and her caretaker were provided with detailed educational and motivational strategies for improving the patient´s oral hygiene, and they also received nutritional advice. For control reviews and the reinforcement of preventive habits, future appointments were carefully scheduled. An interdisciplinary pediatric collaboration between the dentist, nurse, and psychiatrist was fundamental for improving the patient's oral health and general welfare.

RESUMEN: El trastorno de apego reactivo (RAD, por sus siglas en inglés) es una enfermedad de salud mental en la primera infancia caracterizada por interacciones sociales y capacidades de comunicación deterioradas y por déficits neurológicos en el cerebro en desarrollo del niño. Este trastorno puede afectar significativamente el comportamiento del paciente pediátrico en el entorno dental. Una niña mexicana de 9 años de edad, poco cooperadora, que residía en un hogar temporal, fue remitida a la Clínica de Odontología Pediátrica con su cuidadora, solicitando un examen y tratamiento dental. La paciente presentó un diagnóstico previo de RAD con discapacidad intelectual/ social. Con la orientación del Psiquiatra, se llevó a cabo una profilaxis oral exhaustiva en las citas iniciales, seguidas de diversos tratamientos de restauración bajo la aplicación continua de técnicas de manejo del comportamiento. Estos procedimientos de restauración incluyeron restauraciones de resina y selladores de fosas y fisuras, bajo anestesia local y aislamiento con dique de goma, en los primeros cuatro molares permanentes. Todo el tratamiento se completó en seis semanas. La paciente y su cuidadora recibieron estrategias educativas y motivacionales detalladas para mejorar la higiene oral y también recibieron asesoría nutricional. Para las revisiones de control y refuerzo de los hábitos preventivos, las citas posteriores se programaron cuidadosamente. Una colaboración pediátrica interdisciplinaria entre el dentista, la enfermera y el psiquiatra fue fundamental para mejorar la salud oral y el bienestar general del paciente.

Plasma Aß42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study.

BACKGROUND: To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer's disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aß) levels with the presence of pathological accumulation of Aß in the brain measured by amyloid-PET. Both plasma Aß42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. METHODS: We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aß40 and Aß42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aß-PET positive or negative, and the ability of TP42/40 to detect Aß-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aß biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. RESULTS: Eighteen (30.5%) subjects were Aß-PET positive. TP42/40 ratio alone identified Aß-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779-0.982). Discriminating performance of TP42/40 to detect Aß-PET-positive subjects yielded sensitivity and specificity values at Youden's cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aß-PET scans by 64%. Combination of both FDG-PET scores and plasma Aß biomarkers was found to be the most accurate Aß-PET predictor, with an AUC of 0.965 (95% CI = 0.913-0.100). CONCLUSIONS: Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aß positivity in preclinical and prodromal stages of Alzheimer's disease.

Prevalence of multiple sclerosis in Cuenca, Ecuador.

BACKGROUND: Cuenca, a city in the Andean Region of southern Ecuador, has 591,996 inhabitants. A decade-old study showed the prevalence of multiple sclerosis in Cuenca was 0.75 cases per 100,000 inhabitants but no new epidemiological studies in this city have been performed since then. The aim of this study, conducted in 2016, was to update the prevalence records of multiple sclerosis in Cuenca. METHODS: We performed a descriptive cross-sectional study in which we investigated prevalence rates in November of 2016. We estimated the prevalence of multiple sclerosis by cross-matching registries from the two neurological referral hospitals in Cuenca. RESULTS: A total of 23 records were obtained from the two sources. The estimated prevalence was 3.88 per 100,000 inhabitants (95% confidence interval: 3.83-3.94). The disease was predominant among women (60%). The mean age of this cohort was 37 years (standard deviation ±12.4). Of the cases, 78% were relapsing-remitting multiple sclerosis. The mean Expanded Disability Status Scale score was 2.5. CONCLUSIONS: This study is an update to the first study conducted 10 years ago and shows the prevalence of multiple sclerosis in Cuenca has increased. However, the prevalence of multiple sclerosis is still low and very similar to that reported in neighbouring countries.

Local Ketamine Improves Postoperative Analgesia After Third Molar Surgery.

PURPOSE: Evidence exists to support the peripheral analgesic effect of local administration of ketamine (LAK) after third molar surgery. The aim of the present systematic review and meta-analysis was to determine the efficacy of LAK in the control of pain, swelling, and trismus after third molar surgery. MATERIALS AND METHODS: The study design was a systematic review with a meta-analysis of the effect of LAK after third molar surgery. A search in electronic databases was performed from September 2017 to February 2019. Only prospective clinical trials and randomized controlled trials that had evaluated LAK after third molar surgery were included. The meta-analysis was based on the random effects model. The outcome measures evaluated were postoperative acute pain, swelling, and trismus. The estimated overall effect size was a standardized mean difference (SMD). RESULTS: A total of 110 study subjects (men and women aged 18 to 50 years) were evaluated for the analgesic effect. The SMD showed a significant analgesic effect (postoperative pain control) favoring LAK (SMD, -1.7403; 95% confidence interval [CI], -2.45 to -1.04). Evaluation of the anti-inflammatory effect of LAK included 105 study subjects and resulted in significantly less swelling in the first postoperative day (SMD, -0.6169; 95% CI, -1.1654 to -0.0683). However, LAK did not reduce the incidence of trismus after third molar surgery (SMD, -0.7241; 95% CI, -2.2765 to 0.8284). CONCLUSIONS: The use of LAK can reduce the incidence and severity of postoperative pain after third molar surgery and had an anti-inflammatory effect, although only in the first postoperative day. However, LAK had no effect on trismus reduction after third molar surgery.

Autism and Paediatric Dentistry: A Scoping Review.

PURPOSE: The objectives of this scoping review were: first, to pose a research question; second, to identify relevant studies to answer the research question; third, to select and retrieve the studies; fourth, to chart the critical data; and finally, to collate, summarise, and report the results from selected articles on the dental management of children affected with autism. MATERIALS AND METHODS: Relevant articles (randomised controlled trials, reviews, observational studies, and clinical case reports) published over an 11-year period were identified and retrieved from five internet databases: PubMed, Embase/Ovid, Cochrane Library, Google Scholar, and EBSCO. RESULTS: By title and abstract screening and after removing duplicates, 25 articles were finally included in the present scoping review. According to the extracted data, the following four clinical issues were found to be most important: patient behavioural control, prevalence/incidence of dental caries, adverse effects and interactions with medications, and orthodontic management. Additionally, several useful clinical recommendations are provided. CONCLUSIONS: Paediatric dentists should bear in mind that early diagnosis and treatment, effective communication skills, and a long-term follow-up of children with autism continue to be the best approaches for achieving enhanced patient psychological well-being and consequently a better quality of life.

Implante de válvula de Ahmed vía pars plana para el manejo del glaucoma uveítico refractario / Placement of Ahmed Valve through the pars plana for the management of refractory uveitic glaucoma

La uveítis es la tercera causa de ceguera evitable, siendo una de sus complicaciones el glaucoma uveítico. Presentamos el caso de una paciente de 25 años tratada con extracción extra capsular de cristalino y trabeculectomía AO, con posterior ciclocrioterapia bilateral, llegando a controlar la enfermedad inflamatoria de fondo y presión intraocular (PIO) en el ojo derecho por siete años con posterior pérdida de la visión (pthisis bulbi). El ojo izquierdo se mantuvo estable por 15 años, presentando luego una PIO de 50 mmHg, por lo que se implanta una válvula de Ahmed por vía pars plana con previa vitrectomía, debido a las alteraciones anatómicas del segmento anterior. Se controló la PIO y se obtuvo una visión de 20/70 con correctores, sin uso de antihipertensivo ocular. El manejo adecuado de la enfermedad de fondo y el uso de dispositivos de drenaje valvulados son la mejor opción para el glaucoma uveítico. Una gran alternativa de abordaje es el implante vía pars plana, previa vitrectomía.

Uveitis is the third preventable cause of blindness, and uveitic glaucoma is one of its complications. We present the case of a 25-year old female patient who underwent an extracapsular lens excision and AO trabeculectomy, and afterwards bilateral cyclocryotherapy was performed. The underlying inflammatory condition was controlled, and the intraocular pressure (IOP) in the right eye was also controlled for seven years, although she later lost sight (pthisis bulbi). The left eye remained in a stable condition for 15 years, but afterwards it developed 50 mm Hg IOP, so an Ahmed Valve through the pars plana was placed, after having performed a vitrectomy because of the anatomic alterations in the anterior segment. The IOP got controlled and 20/70 vision using glasses was attained, without the use of an ocular antihypertensive compound. Adequate management of the underlying disease and the use of valve drainage systems constitute the best choice for the management of uveitic glaucoma. A good approach option is placing the device through the pars plana, after having performed a vitrectomy.

Significant dose reduction is feasible in FDG PET/CT protocols without compromising diagnostic quality.

PURPOSE: To reduce the radiation dose to patients by optimizing oncological FDG PET/CT protocols. METHODS: The baseline PET/CT protocol in our institution for oncological PET/CT examinations consisted of the administration of 5.18 MBq/kg of FDG and a CT acquisition with a reference current-time product of 120 mAs. In 2016, FDG activity was reduced to 4.44 and 3.70 MBq/kg and reference CT current-time-product was reduced to 100 and 80 mAs. 322 patients scanned with different protocols were retrospectively evaluated. For each patient, effective dose was calculated. The overall image quality was subjectively rated by the referring physician on a 4-point scale (IQ score: 1 excellent, 2 good, 3 poor but interpretable, 4 poor not interpretable). Image quality was quantitatively evaluated measuring noise in the liver. RESULTS: CT Results: Effective dose was progressively reduced from 9.5 ±â€¯2.8 to 8.0 ±â€¯2.3 and 6.2 ±â€¯1.5 mSv (p < 0.001). A mean dose reduction of 34.9% was achieved. There was a significant degradation of IQ score (p < 0.05) and noise (p < 0.001). Nevertheless, the number of poor quality studies (IQ score >2) did not increase. PET Results: Effective dose was gradually reduced from 6.5 ±â€¯1.4 to 5.7 ±â€¯1.3 and 5.0 ±â€¯1.0 mSv (p < 0.001). Average dose reduction was 23.4%. IQ score (p < 0.05) and noise (p < 0.001) significantly degraded for lower activity protocols. However, all images with reduced activity were scored as interpretable (IQ score ≤ 3). CONCLUSIONS: A significant radiation dose reduction of 28.7% was reached. Despite a slight reduction in image quality, the new regime was successfully implemented with readers reporting unchanged clinical confidence.

Saturación de oxígeno, respiración periódica y apnea durante el sueño en lactantes de 1 a 4 meses a 3200 metros de altura / Oxygen saturation, periodic breathing, and sleep apnea in infants aged 1-4 months old living at 3200 meters above sea level

Objetivos: describir, en niños de 1-4 meses, a 3200 m de altura, la saturación de oxígeno (SpO2), los índices de apnea y la respiración periódica (RP) durante el sueño. Se realizaron polisomnografías en 18 lactantes sanos. Resultados: las medianas fueron de 87% para la SpO2 y de 7,2% para la RP del tiempo total de sueño. El índice de apnea central tuvo una mediana de 30,5 /hora, que disminuyó a 5,4/hora al descontar las apneas asociadas a RP. El p5 de la SpO2 para niños despiertos fue de 76% y, para niños dormidos, de 66%. Conclusiones: la SpO2 fue inferior a la del nivel del mar y la RP y el índice de apnea central, mayores; al descontar las apneas centrales asociadas a RP. Este último, fue similar a la del nivel del mar. A 3200 m, se requieren puntos diferentes para la SpO2 normal, uno para niños despiertos y otro si están dormidos.

Objectives: To describe, in infants aged 1-4 months old living at 3200 meters above sea level (MASL), oxygen saturation (SpO2), sleep apnea indices, and periodic breathing (PB) during sleep. Polysomnographies were done in 18 healthy infants. Results: The median SpO2 was 87%, and the median PB was 7.2% for the total sleep time. The median central sleep apnea index was 30.5/hour, which decreased to 5.4/hour once sleep apneas associated with PB were excluded. The 5th percentile for SpO2 was 76% among awake infants, and 66% among asleep infants. Conclusions: The SpO2 was lower than that observed at sea level, whereas PB and the central sleep apnea index were higher, once sleep apneas associated with PB were excluded. The latter was similar to that observed at sea level. At 3200 MASL, different cut-off points are required for a normal SpO2, one for infants during the waking state and one for infants during sleep.

Oxygen saturation, periodic breathing, and sleep apnea in infants aged 1-4 months old living at 3200 meters above sea level. / Saturación de oxígeno, respiración periódica y apnea durante el sueño en lactantes de 1 a 4 meses a 3200 metros de altura.

OBJECTIVES: To describe, in infants aged 1-4 months old living at 3200 meters above sea level (MASL), oxygen saturation (SpO2), sleep apnea indices, and periodic breathing (PB) during sleep. Polysomnographies were done in 18 healthy infants. RESULTS: The median SpO2 was 87%, and the median PB was 7.2% for the total sleep time. The median central sleep apnea index was 30.5/hour, which decreased to 5.4/hour once sleep apneas associated with PB were excluded. The 5th percentile for SpO2 was 76% among awake infants, and 66% among asleep infants. CONCLUSIONS: The SpO2 was lower than that observed at sea level, whereas PB and the central sleep apnea index were higher, once sleep apneas associated with PB were excluded. The latter was similar to that observed at sea level. At 3200 MASL, different cut-off points are required for a normal SpO2, one for infants during the waking state and one for infants during sleep.

Objetivos: describir, en niños de 1-4 meses, a 3200 m de altura, la saturación de oxígeno (SpO2 ), los índices de apnea y la respiración periódica (RP) durante el sueño. Se realizaron polisomnografías en 18 lactantes sanos. Resultados: las medianas fueron de 87% para la SpO2 y de 7,2% para la RP del tiempo total de sueño. El índice de apnea central tuvo una mediana de 30,5/hora, que disminuyó a 5,4/hora al descontar las apneas asociadas a RP. El p5 de la SpO2 para niños despiertos fue de 76% y, para niños dormidos, de 66%. Conclusiones: la SpO2 fue inferior a la del nivel del mar y la RP y el índice de apnea central, mayores; al descontar las apneas centrales asociadas a RP. Este último, fue similar a la del nivel del mar. A 3200 m, se requieren puntos diferentes para la SpO2 normal, uno para niños despiertos y otro si están dormidos.

[Characteristics of mistreatment in medical students of a public university in Peru]. / Características del maltrato hacia estudiantes de medicina de una universidad pública del Perú.

OBJECTIVES: To determine the characteristics of mistreatment among medical students at a public university in the province Ica, Peru. MATERIALS AND METHODS: This cross-sectional study was performed in 2012, and used a probability sample of medical students (freshman to sixth year) at the Universidad Nacional San Luis Gonzaga. A 23-item survey with a Likert scale was used to measure the students' perceptions of psychological, physical, academic and sexual mistreatment. Univariate and bivariate statistical analysis were performed. RESULTS: A total of 281 students were surveyed. The perception of psychological mistreatment was 96.8%; academic, 86.8%; physical, 62.6% and sexual, 20.6%. Physical abuse increased during the clinical-surgical study cicle (p = 0.001). Medical doctors and residents were the main aggressors. Male students reported of receiving assignments as a punishment, not receiving credits for their work, physical mistreatment, verbal threats, insults, or being teased because of their etnic background. Female students were more likely to have experienced sexual abuse. Report of sexual abuse frequently ocurred at the university (45.3%, p=0.002) and hospital (45.0%, p=0.046). Women frequently reported not knowing to whom or where to denounce the abuse (54.6%, p=0.042) and not reporting it because it stopped (56.9%, p=0.048). CONCLUSIONS: There is a high prevalence of abuse among students in which their characteristics as sex, level of study and aggressor allow to identify the types of abuse that they receive.

Demencia de rápida progresión en enfermedad esporádica por priones: reporte de inédito caso en Ecuador y actualización / Rapidly progressive dementia in sporadic prion disease: report of unprecedented event in Ecuador and update

Es escasa literatura sobre la enfermedad por priones en poblaciones latinomericanas. La etiología es la alteración genética que origina una proteína aberrante mal plegada, que se acumula en distintas estructuras encefálicas, generando demencia de rápida instauración y posteriormente déficits neurológicos variables. El objetivo es presentar un particular deterioro multisistémico relacionado con la variante esporádica de la enfermedad de Creutzfeldt-Jakob que por este hecho lo convierte en un reto diagnóstico.

Sporadic prion disease is an unusual condition in Latin American populations. The etiology is genetic alteration that causes an aberrant misfolded protein that accumulates in various encephalic structures, generating rapid dementia and subsequently variables neurological deficits. The aim is to present a particular multisystem impairment related to the sporadic variant of Creutzfeldt-Jakob disease that this fact makes it a diagnostic challenge.

Características del maltrato hacia estudiantes de medicina de una universidad pública del Perú / Characteristics of mistreatment in medical students of a public university in Peru

Determinar las características del maltrato hacia estudiantes de Medicina de una universidad pública en la provincia de Ica, Perú. Materiales y métodos. Investigación transversal realizada el 2012 en una muestra probabilística de estudiantes de Medicina de primer a sexto año de la Universidad Nacional San Luis Gonzaga. Se elaboró una encuesta con un total de 23 ítems en una escala likert, para medir la percepción de maltrato de tipo psicológico, físico, académico y sexual; se usaron análisis estadísticos univariados y bivariados. Resultados. Se encuestaron 281 estudiantes. La percepción de maltrato psicológico fue 96,8%, académico 86,8%, físico 62,6% y sexual 20,6%; el maltrato físico se incrementó durante el ciclo de estudio clínico-quirúrgico (p=0,001). Los médicos docentes y médicos residentes fueron los principales agresores. Estudiantes hombres reportaron con mayor frecuencia haber recibido tareas como castigo, no recibir los créditos por su trabajo, maltrato físico, amenazas verbales, insultos o recibir burlas con respecto a su etnia; mientras que el maltrato sexual fue mayor en mujeres. El reporte de maltrato sexual fue más frecuente en la universidad (45,3%, p=0,002) y el hospital (45,0%, p=0,046). Las mujeres reportaron con mayor frecuencia no saber a quién o dónde acudir para denunciar el maltrato (54,6%, p=0,042) y no denunciarlo porque se detuvo el maltrato (56,9%, p=0,048). Conclusiones. Existe una alta prevalencia de maltrato, donde las características de los estudiantes según el sexo, los ciclos de estudio y el agresor permiten identificar los tipos de maltrato que reciben los estudiantes de medicina...

To determine the characteristics of mistreatment among medical students at a public university in the province Ica, Peru. Materials and methods. This cross-sectional study was performed in 2012, and used a probability sample of medical students (freshman to sixth year) at the Universidad Nacional San Luis Gonzaga. A 23-item survey with a Likert scale was used to measure the students' perceptions of psychological, physical, academic and sexual mistreatment. Univariate and bivariate statistical analysis were performed. Results. A total of 281 students were surveyed. The perception of psychological mistreatment was 96.8%; academic, 86.8%; physical, 62.6% and sexual, 20.6%. Physical abuse increased during the clinical-surgical study cicle (p = 0.001). Medical doctors and residents were the main aggressors. Male students reported of receiving assignments as a punishment, not receiving credits for their work, physical mistreatment, verbal threats, insults, or being teased because of their etnic background. Female students were more likely to have experienced sexual abuse. Report of sexual abuse frequently ocurred at the university (45.3%, p=0.002) and hospital (45.0%, p=0.046). Women frequently reported not knowing to whom or where to denounce the abuse (54.6%, p=0.042) and not reporting it because it stopped (56.9%, p=0.048). Conclusions. There is a high prevalence of abuse among students in which their characteristics as sex, level of study and aggressor allow to identify the types of abuse that they receive...

Co-conformational Exchange Triggered by Molecular Recognition in a Di(acylamino)pyridine-Based Molecular Shuttle Containing Two Pyridine Rings at the Macrocycle.

We describe the incorporation of endo-pyridine units into the tetralactam ring of di(acylamino)pyridine-based rotaxanes. This macrocycle strongly associates with the linear interlocked component as confirmed by X-ray diffraction studies of rotaxane 2 b. Dynamic NMR studies of 2 b in solution revealed a rotational energy barrier that was higher than that of the related rotaxane 2 a, which lacks of pyridine rings in the macrocycle. The macrocycle distribution of the molecular shuttle 4 b, containing two endo-pyridine rings, shows that the major co-conformer is that with the cyclic component sitting over the di(acylamino)pyridine station. DFT calculations also support the marked preference of the ring for occupying the heterocyclic binding site. The association of N-hexylthymine with the di(acylamino)pyridine binding site of 4 b led to the formation of a rare 'S'-shaped co-conformer in which the tetralactam ring interacts simultaneously with both stations of the thread.

Dethreading of Tetraalkylsuccinamide-Based [2]Rotaxanes for Preparing Benzylic Amide Macrocycles.

The dethreading of a series of succinamide-based [2]rotaxanes bearing benzylic amide macrocycles is reported herein. These transformations proceeded quantitatively either under flash vacuum pyrolysis, conventional heating, or microwave irradiation. Studying the size complementarity of the stoppers at the ends of the thread and the cavity of the macrocycle allowed us to set up the best substituents for implementing the extrusion of the thread from the interlocked precursors. A variety of (1)H NMR kinetic experiments were carried out in order to evaluate the rate constants of the dethreading process, the half-life times of the rotaxanes, and the influence of temperature and solvents on these processes. The use of dibutylamino groups as stoppers yielded the rotaxane precursor in a reasonable yield and allowed the quantitative deslipping of the rotaxane. The overall process, including the rotaxane formation and its further dethreading, has been exploited for preparing benzylic amide macrocycles enhancing, in most cases, the results of the classical (2 + 2) condensation and other reported stepwise syntheses. The kinetics of the dethreading process is fairly sensitive to the electronic effects of the substituents on the isophthalamide unit or to the electronic nature of the pyridine rings through a conformational equilibrium expanding or contracting the cavity of the interlocked precursor.