Discovery of a Small-Molecule Modulator of the Autophagy-Lysosome Pathway That Targets Lamin A/C and LAMP1, Induces Autophagic Flux, and Affects Lysosome Positioning in Neurons.

Autophagy is a major catabolic degradation and recycling process that maintains homeostasis in cells and is especially important in postmitotic neurons. We implemented a high-content phenotypic assay to discover small molecules that promote autophagic flux and completed target identification and validation studies to identify protein targets that modulate the autophagy pathway and promote neuronal health and survival. Efficient syntheses of the prioritized compounds were developed to readily access analogues of the initial hits, enabling initial structure-activity relationship studies to improve potency and preparation of a biotin-tagged pulldown probe that retains activity. This probe facilitated target identification and validation studies through pulldown and competition experiments using both an unbiased proteomics approach and western blotting to reveal Lamin A/C and LAMP1 as the protein targets of compound RH1115. Evaluation of RH1115 in neurons revealed that this compound induces changes to LAMP1 vesicle properties and alters lysosome positioning. Dysfunction of the autophagy-lysosome pathway has been implicated in a variety of neurodegenerative diseases, including Alzheimer's disease, highlighting the value of new strategies for therapeutic modulation and the importance of small-molecule probes to facilitate the study of autophagy regulation in cultured neurons and in vivo.

[Abdominal manipulation and other cultural risk factors associated with complication of acute appendicitis in pediatric patients]. / Manipulación abdominal y otros factores de riesgo culturales asociados a complicación de apendicitis aguda en pacientes pediátricos.

In children, acute appendicitis (AA) is usually mistaken for empacho, which, according to popular belief, is caused by the ingestion of undercooked or cold food causing gastrointestinal symptoms. The empirical treatment is abdominal manipulation, consisting of massages with different maneuvers on the abdominal wall, accompanied by home remedies. The effect of these therapies in the presence of AA is unknown. OBJECTIVE: To determine the association between abdominal manipulation and complicated AA in pediatric patients. PATIENTS AND METHOD: Case-control study in a pediatric population under 18 years of age, with acute abdomen symptoms, who underwent surgery for AA, in a tertiary health institution in Honduras. Cases were defined as patients with complicated AA and controls as those with simple AA. A binary logistic regression model was used to determine the risk factors associated with complications of AA. RESULTS: Sixty-two pediatric patients were analyzed (31 cases and 31 controls) with a median age of 11 years. 58.1% were from an urban area. 77.4% of the cases and 9.7% of controls had a history of abdominal manipulation. The most frequent initial symptom was abdominal pain. In the univariate analysis, male sex, prolonged evolution time, use of home remedies, leukocytosis > 20,000/mm3, and abdominal manipulation were risk factors for complicated AA. In the multivariate model, abdominal manipulation was the main risk factor (OR 15.94 [3.4074.59]). CONCLUSION: Cultural beliefs such as empacho and its respective treatments such as abdominal manipulation and use of home remedies are risk factors for the complication of an established AA case, as well as contributing to the delay in diagnosis.

Lung Ultrasound as a Triage Method in Primary Care for Patients with Suspected SARS-CoV-2 Pneumonia.

Background: Currently, there are few studies that have analyzed the benefits of using lung ultrasound in the field of primary care, including in homes and nursing homes, for patients with suspected COVID-19 pneumonia and subsequent follow-ups. The aim of this study was to demonstrate that lung ultrasound is a useful technique for triaging these patients. Methods: An observational and retrospective study of individuals who presented with clinical suspicion of SARS-CoV-2 pneumonia was carried out during the months of March to June 2020 in Health Center number 2 of Ciudad Real and in homes of patients and nursing homes belonging to the Health Service of Castilla-La Mancha (Spain). Results: A total of 209 patients, of whom 86 (41.1%) were male, were included in the study. The most frequent ultrasound findings were bilateral B-lines, with a right predominance, specifically in the posterobasal region. Additionally, there was a statistical significance (p < 0.05) correlation between pathological positivity on lung ultrasound and PCR and chest X-ray positivity. When calculating the sensitivity and specificity of ultrasound and X-ray, ultrasound had a sensitivity of 93%, and X-ray had a sensitivity of 75%. Conclusion: Due to its high sensitivity and negative predictive value, lung ultrasound is very useful as a triage tool for patients with suspected SARS-CoV-2 pneumonia.

Description of basic competencies in clinical ultrasound imaging for emergency departments. / Competencias básicas de la ecografía clínica en los servicios de urgencias y emergencias.

TEXT: Recent years have seen great advances in the use of clinical ultrasound imaging in both hospital emergency departments and out-of-hospital settings. However, all new techniques require up-to-date definitions of competencies relevant to the clinical realities of different specialties and the geographic settings in which specialists work. To that end, a group of experts in clinical ultrasound reviewed the evidence available in the literature and strictly applied the Delphi method to define the competencies relevant to emergency physicians. The group worked with the starting premise that clinical ultrasound imaging should be a common competency across the specialty.

TEXTO: En los últimos años, la ecografía clínica (EC) ha sufrido un avance muy importante en su implantación dentro de los servicios de urgencias, tanto hospitalarios como extrahospitalarios, pero como toda técnica requiere un ámbito competencial definido, actualizado y enmarcado, tanto en la realidad clínica de la especialidad que desempeñamos como en la geográfica del país donde ejercemos. Por ello, un grupo de expertos en la materia ha desarrollado el presente documento en el que basándose por un lado en la evidencia disponible en la bibliografía científica y por otro en una metodología Delphi, planteó el objetivo de establecer un claro marco competencial base para todos los urgenciólogos, asumiendo como premisa inicial que la EC debería ser una competencia transversal común.

Competencias básicas de la ecografía clínica en los servicios de urgencias y emergencias / Description of basic competencies in clinical ultrasound imaging for emergency departments

En los últimos años, la ecografía clínica (EC) ha sufrido un avance muy importante en su implantación dentro de los servicios de urgencias, tanto hospitalarios como extrahospitalarios, pero como toda técnica requiere un ámbito competencial definido, actualizado y enmarcado, tanto en la realidad clínica de la especialidad que desempeñamos como en la geográfica del país donde ejercemos. Por ello, un grupo de expertos en la materia ha desarrollado el presente documento en el que basándose por un lado en la evidencia disponible en la bibliografía científica y por otro en una metodología Delphi, planteó el objetivo de establecer un claro marco competencial base para todos los urgenciólogos, asumiendo como premisa inicial que la EC debería ser una competencia transversal común. (AU)

Recent years have seen great advances in the use of clinical ultrasound imaging in both hospital emergency departments and out-of-hospital settings. However, all new techniques require up-to-date definitions of competencies relevant to the clinical realities of different specialties and the geographic settings in which specialists work. To that end, a group of experts in clinical ultrasound reviewed the evidence available in the literature and strictly applied the Delphi method to define the competencies relevant to emergency physicians. The group worked with the starting premise that clinical ultrasound imaging should be a common competency across the special (AU)

Complicated acute appendicitis in pediatric patients with "empacho" and abdominal manipulation history: Case series. / Apendicitis aguda complicada en pacientes pediátricos con antecedentes de "empacho" y manipulación abdominal: Serie de casos.

INTRODUCTION: According to Latin American popular culture, empacho is a gastrointestinal disease caused by ex cessive intake of cold or under-cooked food. Abdominal manipulation or sobada is one of the popular treatments used for empacho and consists of an abdominal massage, where the skin is rubbed and stretched, applying pressure on the abdomen. OBJECTIVES: To characterize clinical evolution and complications secondary to diagnostic delay in pediatric patients with acute appendicitis, with history of empacho and abdominal manipulation. PATIENTS AND METHOD: Descriptive, observational, How to cite this article: Andes pediatr. 2021;92(1):86-92. DOI: 10.32641/andespediatr.v92i1.3352 prospective study of pediatric patients with complicated acute appendicitis and history of abdominal manipulation, identified in the pediatric surgery room between November 2019 and June 2020 at the Mario Catarino Rivas Hospital. Descriptive statistics were used for analysis. RESULTS: 10 patients were studied, aged ranging from 6 to 16 years (median age 14 years). Half of them were from rural areas. The main symptoms that appeared before abdominal manipulation were vomiting, nausea, and loss of appetite, followed by sudden diarrhea or constipation, and increased pain intensity. Complications were gastrointestinal perforation (5/10), appendicular mass (3/10), intra-abdominal abscess (3/10), and gangrenous appendicitis (1/10). The median time between initial symptom and hospitalization was 60 hours [IQR, 33.0 - 72.0]. CONCLUSION: This study describes the influence of the empacho and its respective treatment on clinical deterioration due to the delay in diagnosis and treatment of acute appendicitis, resulting in different complications.

Detección de prediabetes y sospecha de diabetes mediante tamizaje con ADA RISK SCORE© y glucometrías / Detection of prediabetes and suspected diabetes through screening with ADA RISK SCORE© and glucometry

La diabetes es una enfermedad crónica no transmisible de alta prevalencia y con alta tasa de compli- caciones. Su diagnóstico precoz y tratamiento oportuno resulta una estrategia necesaria para reducir el gasto en salud pública. Objetivo: Determinar la frecuencia de prediabetes y sospecha de diabetes mediante tamizaje con el ADA Risk SCORE© y glucometrías en pacientes del Centro Integral de Salud (CIS) Ramón Bográn. Pacientes y método: Estudio cuantitativo, de alcance descriptivo, transversal y prospectivo en individuos de ambos sexos mayores de 20 años que asistieron al CIS Ramón Bográn en Quimistán Santa Bárbara. Población/muestra por convenencia de 80 pacientes. El instrumento utilizado fue la escala de Riesgo ADA Risk Score©. Resultados: El 86.25% (69) de los 80 participan- tes eran mujeres, 52.5% (42) eran mayores de 40 años. La media del ADA Risk SCORE© en nuestra población fue 4 ±1.8 puntos. Del total de pacientes 56.25% (45) resultaron con Risk SCORE © menor de 4 (con riesgo normal), mientras que el 41.25% (33) y el 2.5% (2) de los sujetos obtuvieron SCORE entre 5 a 7 y mayor o igual a 8 respectivamente, lo que los pone en riesgo elevado de diabetes. Del total de glucometrías en ayuno realizadas, 56.25% (45) tuvieron valores normoglucémicos entre 60-99 mg/dL, mientras que 22.50% (18) estaban en rango de prediabetes; 21.25 % (17) estaban en rango de sospecha de diabetes. Conclusión: La mayoría de pacientes mostraron alteraciones glucémicas sugestivas de DM, mostrando altos porcentajes de sospecha de prediabetes y diabetes subdiagnosti- cada...(AU)

Respuesta: Comentario acerca de la precisión, seguridad y eficiencia de la ecografía realizada por urgenciólogos en el diagnóstico de la trombosis venosa profunda en servicios de urgencias hospitalarios / Reply: Comment on "Ultrasound imaging obtained by emergency department physicians to diagnose deep vein thrombosis: accuracy, safety, and efficiency"

No disponible

Ultrasound imaging obtained by emergency department physicians to diagnose deep vein thrombosis: accuracy, safety, and efficiency. / Precisión, seguridad y eficiencia de la ecografía realizada por urgenciólogos en el diagnóstico de la trombosis venosa profunda en servicios de urgencias hospitalarios.

OBJECTIVES: To assess the accuracy, safety, and efficiency of ultrasound images obtained by emergency physician to diagnose deep vein thrombosis (DVT). patients with acute heart failure (AHF) attended in a hospital emergency department (ED). MATERIAL AND METHODS: Prospective multicenter cohort study. We assigned patients suspected of having DVT to an intervention or control group. Emergency physicians took ultrasound images that were later evaluated by a radiologist in the intervention group. In the control group, images were evaluated only by the radiologist. We analyzed patient, physician, and episode variables. Test results, times until imaging, and 30-day adverse events were also analyzed. Sensitivity, specificity, positive and negative likelihood ratios, and agreement between physicians and radiologists (κ statistic) were calculated. RESULTS: A total of 304 patients (209 in the intervention group and 95 controls) were included. The groups were comparable. The overall prevalence of DVT was 35.5% (95% CI, 30.3-41.0). The sensitivity of ultrasound images obtained by emergency physicians was superior in relation to experience: 71.4 (95% CI, 50.0-86.0) for those in a training course, 75.0 (95% CI, 80.0-95.4) for those with at least 2 months' practical experience, and 94.7 (95% CI, 82.7-98.5) for routine users. Specificity statistics for the 3 levels of physician experience were 83.3 (95% CI 55.2- 95.2), 100 (95% CI 83.0-100), and 96.6 (95% CI 88.4-99.0), respectively. The positive and negative likelihood ratios for ultrasound imaging by physicians were 27.94 and 0.054, respectively. The κ statistic was 0.80. Mean (SD) time until a physician took ultrasound images was 1.81 (1.46) hours versus 4.39 (1.81) hours until a radiologist obtained images (P = .007). Three deaths occurred within 30 days. They were not attributable to recurrence or bleeding. CONCLUSION: Ultrasound images taken by emergency physicians to diagnose DVT are accurate and safe and may be efficient. However, routine experience with ultrasound is necessary.

OBJETIVO: Evaluar la precisión, la seguridad y la eficiencia de la ecografía realizada por urgenciólogos para el diagnóstico de la trombosis venosa profunda (TVP). METODO: Estudio prospectivo multicéntrico de cohortes que incluyó pacientes con sospecha de TVP asignados a un grupo intervención (evaluados ecográficamente por el urgenciólogo y posteriormente por el radiólogo) y a un grupo control (evaluados únicamente por el radiólogo). Se analizaron las variables relacionadas con el paciente, el urgenciólogo, el episodio, el resultado de la prueba y los tiempos de estancia y acontecimientos a 30 días. Se calcularon la sensibilidad, la especificidad, las razones de verosimilitud positiva y negativa, y el índice kappa. RESULTADOS: Se incluyeron 304 pacientes (95 control, 209 intervención). Ambos grupos fueron comparables. La prevalencia de TVP en la cohorte global fue de 35,5% (IC 95% 30,3-41,0). La sensibilidad de la ecografía realizada por urgenciólogos fue superior según la experiencia-curso vs meses vs uso habitual: 71,4 (IC 95% 50,0-86,0) vs 75,0 (IC 95% 80,0-95,4) vs 94,7 (IC 95% 82,7-98,5), así como la especificidad 83,3 (IC 95% 55,2-95,2) vs 100 (IC 95% 83,0- 100) vs 96,6 (IC 95% 88,4-99,0). Las razones de verosimilitud positiva y negativa para la ecografía realizada por urgenciólogos fueron del 27,94 y del 0,054, respectivamente. El índice de kappa fue de 0,80. El tiempo hasta la realización de la ecografía por el urgenciólogo fue de 1,81 (DE 1,46) frente a 4,39 (DE 1,81) horas del radiólogo (p = 0,007). Durante el seguimiento a 30 días, se registraron 3 muertes, ninguna de ellas por recurrencia o hemorragia. CONCLUSIONES: La ecografía realizada por urgenciólogos para el diagnóstico de TVP es precisa, segura y podría resultar eficiente. Sin embargo, se requiere de experiencia basada en el uso habitual de esta técnica.

Precisión, seguridad y eficiencia de la ecografía realizada por urgenciólogos en el diagnóstico de la trombosis venosa profunda en servicios de urgencias hospitalarios / Ultrasound imaging obtained by emergency department physicians to diagnose deep vein thrombosis: accuracy, safety, and efficiency

Objetivos: Evaluar la precisión, la seguridad y la eficiencia de la ecografía realizada por urgenciólogos para el diagnóstico de la trombosis venosa profunda (TVP). Métodos: Estudio prospectivo multicéntrico de cohortes que incluyó pacientes con sospecha de TVP asignados a un grupo intervención (evaluados ecográficamente por el urgenciólogo y posteriormente por el radiólogo) y a un grupo control (evaluados únicamente por el radiólogo). Se analizaron las variables relacionadas con el paciente, el urgenciólogo, el episodio, el resultado de la prueba y los tiempos de estancia y acontecimientos a 30 días. Se calcularon la sensibilidad, la especificidad, las razones de verosimilitud positiva y negativa, y el índice kappa. Resultados: Se incluyeron 304 pacientes (95 control, 209 intervención). Ambos grupos fueron comparables. La prevalencia de TVP en la cohorte global fue de 35,5% (IC 95% 30,3-41,0). La sensibilidad de la ecografía realizada por urgenciólogos fue superior según la experiencia-curso vs meses vs uso habitual: 71,4 (IC 95% 50,0-86,0) vs 75,0 (IC 95% 80,0-95,4) vs 94,7 (IC 95% 82,7-98,5), así como la especificidad 83,3 (IC 95% 55,2-95,2) vs 100 (IC 95% 83,0100) vs 96,6 (IC 95% 88,4-99,0). Las razones de verosimilitud positiva y negativa para la ecografía realizada por urgenciólogos fueron del 27,94 y del 0,054, respectivamente. El índice de kappa fue de 0,80. El tiempo hasta la realización de la ecografía por el urgenciólogo fue de 1,81 (DE 1,46) frente a 4,39 (DE 1,81) horas del radiólogo (p = 0,007). Durante el seguimiento a 30 días, se registraron 3 muertes, ninguna de ellas por recurrencia o hemorragia. Conclusión: La ecografía realizada por urgenciólogos para el diagnóstico de TVP es precisa, segura y podría resultar eficiente. Sin embargo, se requiere de experiencia basada en el uso habitual de esta técnica

Objective: To assess the accuracy, safety, and efficiency of ultrasound images obtained by emergency physician to diagnose deep vein thrombosis (DVT). Methods: Prospective multicenter cohort study. We assigned patients suspected of having DVT to an intervention or control group. Emergency physicians took ultrasound images that were later evaluated by a radiologist in the intervention group. In the control group, images were evaluated only by the radiologist. We analyzed patient, physician, and episode variables. Test results, times until imaging, and 30-day adverse events were also analyzed. Sensitivity, specificity, positive and negative likelihood ratios, and agreement between physicians and radiologists ( Kappa statistic) were calculated. Results: A total of 304 patients (209 in the intervention group and 95 controls) were included. The groups were comparable. The overall prevalence of DVT was 35.5% (95% CI, 30.3-41.0). The sensitivity of ultrasound images obtained by emergency physicians was superior in relation to experience: 71.4 (95% CI, 50.0-86.0) for those in a training course, 75.0 (95% CI, 80.0-95.4) for those with at least 2 months' practical experience, and 94.7 (95% CI, 82.7-98.5) for routine users. Specificity statistics for the 3 levels of physician experience were 83.3 (95% CI 55.2- 95.2), 100 (95% CI 83.0-100), and 96.6 (95% CI 88.4-99.0), respectively. The positive and negative likelihood ratios for ultrasound imaging by physicians were 27.94 and 0.054, respectively. The Kappa statistic was 0.80. Mean (SD) time until a physician took ultrasound images was 1.81 (1.46) hours versus 4.39 (1.81) hours until a radiologist obtained images (P = .007). Three deaths occurred within 30 days. They were not attributable to recurrence or bleeding. Conclusions: Ultrasound images taken by emergency physicians to diagnose DVT are accurate and safe and may be efficient. However, routine experience with ultrasound is necessary

Evaluación de la ingesta dietética en estudiantes de cuarto año de medicina / Dietary intake evaluation in students of fourth year of medicine

La malnutrición, ya sea por déficit o exceso de nutrientes, constituye un problema creciente a nivel mundial, siendo los jóvenes universitarios uno de los grupos más vulnera- bles. Objetivo: Evaluar la ingesta dietética de los estudiantes de Farmacología II y/o Fisiopatología II de medicina de la Universi- dad Nacional Autónoma de Honduras en el Valle de Sula (UNAH-VS) en mayo del 2017. Pacientes y métodos: Se realizó un estudio cuantitativo, descriptivo, transversal, en el mes de mayo del 2017, en estudiantes del cuarto año de medicina. Mediante muestreo probabilístico aleatorio estratificado se obtuvo una muestra de 65 estudiantes. La información fue recolectada mediante dos encuestas de recordatorio de 24 horas reali- zadas en dos días diferentes. Dicha informa- ción fue procesada mediante el software NutrINCAP y Microsoft Excel. Resultados: Se encontró que los participantes tenían una ingesta energética media de 3892.88 kcal/día y de 2245.16 kcal/día y una ingesta de proteí- nas de 136.06 y 82.79 gramos al día para hombres y mujeres, respectivamente. La ingesta media de colesterol en hombres fue de 490.04 mg/día, mientras que en las muje- res fue de 268.31 mg/día. En promedio, el consumo de calcio que se encontró para ambos sexos fue 640.56 mg/día y 946.59 mg/día, mientras que de hierro fue 27.32 mg y 38.63 mg/día, para mujeres y hombres, respectivamente. Conclusiones: Los hom- bres evaluados presentaron una dieta hiper- calórica, con exceso de colesterol y déficit de calcio y hierro. Por su parte, las mujeres man- tienen una dieta hipocalórica, hiperproteica y con déficit de calcio y hierro...(AU)

Frecuencia de hipoacusia y características audiométricas en pacientes con diabetes de un hospital de la ciudad de Chiclayo, Perú, 2015 / Frequency of hearing loss and audiometric characteristics of patients with diabetes in a hospital in Chiclayo city-Peru, 2015

Introducción: La diabetes es un trastorno metabólico que afecta a más de 347 millones de personas en el mundo y aproximadamente 1,1 millones en el Perú; si bien se han estudiado sus complicaciones, poco se sabe sobre su efecto en la audición. Se han planteado algunas hipótesis para intentar explicarla, sin embargo, la relación entre diabetes mellitus y la hipoacusia es motivo aún de discusión en la actualidad. Objetivos: Determinar la frecuencia de hipoacusia y las características audiométricas en pacientes con diabetes de un hospital nivel II de la Ciudad de Chiclayo durante el año 2015. Materiales y métodos: Estudio transversal descriptivo en el que se realizaron audiometrías a 185 pacientes con diabetes atendidos en el servicio de Endocrinología. Se incluyó a pacientes entre 18 y 70 años, con diagnóstico confirmado de diabetes mellitus tipo 1 y 2, que vivan en la ciudad de Chiclayo. El muestreo fue probabilístico aleatorio simple. Se excluyó a pacientes con sordera súbita, otitis media aguda o crónica, antecedente o presencia de perforación timpánica detectados durante la exploración ótica y que utilizaran material auxiliar auditivo, consumían fármacos ototóxicos, con antecedente de hipoacusia y de exposición laboral a ruido. Los datos se registraron en una ficha de audiometría convencional en la que se agregaron las variables de interés (edad, sexo, tiempo de enfermedad y otras variables clínicas). Se describieron medidas de tendencia central y de dispersión. Resultados: El 49% de los pacientes diabéticos presentaron hipoacusia, destacando la hipoacusia leve (35%), bilateral (41%) de tipo neurosensorial (45%) y con una tendencia a tonos agudos (42%). La mayoría de los pacientes con hipoacusia tuvo un tiempo de enfermedad mayor o igual a 10 años. Conclusiones: La frecuencia de hipoacusia en pacientes con diabetes es elevada en nuestro medio. Por lo general es una hipoacusia leve, de tipo neurosensorial y bilateral, independiente del tiempo de evolución. Estos datos obligan a tener un mayor énfasis en la revisión sistemática de alteraciones a nivel auditivo en los pacientes con diabetes.

Introduction: Diabetes is a metabolic disorder that affects more than 347 million people worldwide, and approximately 1.1 million in Peru. Its complications have been studied, but there is little about its effect on hearing. Although there are some hypotheses to try to explain this, the relationship between diabetes mellitus and hearing loss is still controversial. Objectives: To determine the frequency of hearing loss and the audiometric characteristics of diabetic patients in a Level II Hospital of Chiclayo City during 2015. Materials and methods: A descriptive cross-sectional study in which audiometry was performed on 185 patients with diabetes treated in the Endocrinology Department. The patients included where between 18 and 70 years, diagnosed with diabetes mellitus type 1 and 2, and lived in Chiclayo city. Simple random probability sampling was used. Those patients with sudden deafness, acute or chronic otitis media, a history or presence of tympanic perforation detected during ear examination, using hearing aid materials, on cytotoxic drugs, family history of hearing loss, and occupational exposure to noise, were excluded. Data were recorded in a conventional audiometry table in which other variables of interest (age, gender, and duration of the disease) were added. Measures of central tendency and dispersion were described. Results: Almost half (49%) of diabetic patients had hearing loss, mainly slight (35%), bilateral (41%), sensorineural (45%), and with a tendency towards higher-pitched tones (42%). Most patients with hearing loss had more than 10 years of disease. Conclusions: The frequency of hearing loss in patients with diabetes is high in our environment. It is usually a minor, sensorineural and bilateral type, independent of duration of disease. These data show that greater emphasis should be placed on the systematic review of changes in hearing levels in patients with diabetes.

BLOC-1 Brings Together the Actin and Microtubule Cytoskeletons to Generate Recycling Endosomes.

Recycling endosomes consist of a tubular network that emerges from vacuolar sorting endosomes and diverts cargoes toward the cell surface, the Golgi, or lysosome-related organelles. How recycling tubules are formed remains unknown. We show that recycling endosome biogenesis requires the protein complex BLOC-1. Mutations in BLOC-1 subunits underlie an inherited disorder characterized by albinism, the Hermansky-Pudlak Syndrome, and are associated with schizophrenia risk. We show here that BLOC-1 coordinates the kinesin KIF13A-dependent pulling of endosomal tubules along microtubules to the Annexin A2/actin-dependent stabilization and detachment of recycling tubules. These components cooperate to extend, stabilize and form tubular endosomal carriers that function in cargo recycling and in the biogenesis of pigment granules in melanocytic cells. By shaping recycling endosomal tubules, our data reveal that dysfunction of the BLOC-1-KIF13A-Annexin A2 molecular network underlies the pathophysiology of neurological and pigmentary disorders.

Pituitary abscess in an adolescent girl: a case report and review of the literature.

We report the case of a 15-year-old girl who presented with a history of recurrent bitemporal headaches for the last 2 months. In the prior few days, she complained of neck pain, emesis, phonophobia and photophobia, but no fever. Additional symptoms included polydipsia, polyuria and weight gain in the last year. Magnetic resonance imaging (MRI) of the brain demonstrated a cystic sellar and suprasellar mass with peripheral enhancement. Cerebrospinal fluid studies showed pleocytosis. Serum hormone levels were consistent with panhypopituitarism. Transnasal sphenoidotomy was performed, and 2 mL of purulent material was drained, confirming the diagnosis of pituitary abscess. The patient completed 6 weeks of parenteral antibiotics. She improved but continued to require home hormonal replacement therapy. A repeated MRI 3 months later showed abscess resolution. In addition to tumors, pituitary abscess should be considered in children who present with headache and panhypopituitarism, particularly in those who present with signs of meningeal inflammation. Prolonged parenteral antibiotics and surgical drainage are effective.