Abstract: Objective: To investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping. Background: Zambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC). Methods: We evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task- shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics. Results: From 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurologi- cal diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills. Conclusions: Epilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substan- tially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.

Abstract: Objective: To investigate opportunities for task shifting to decongest an outpatient neurology clinic in Zambia by describing current patient flow through the clinic and potential nodes for intervention using process mapping. Background: Zambia has a population of approximately 18 million people with 4 full-time adult neurologists, as of 2018, who all practice at the University Teaching Hospital (UTH), the main tertiary care center in the country. As a result of this provider-to-patient ratio, the outpatient neurology clinic is overcrowded and overbooked. Task-shifting programs have shown to improve efficiency, access and quality of care through the use of less specialized healthcare workers in low- and middle-income countries (LMIC). Methods: We evaluated patient flow in the UTH neurology outpatient clinic through the development and analysis of a process map. The characteristics of the clinic population between 2014 and 2018 were retrospectively reviewed from the clinic register. Between July and August 2018, we prospectively collected appointment lag times and time each patient spent waiting at various points in the clinic process. We conducted interviews with clinic staff and neurologists to generate a detailed process map of current pathways to care within the clinic. We then devised task- shifting strategies to help reduce patient wait times based on the overview of clinic process mapping and patient demographics. Results: From 2014 to 2018, there were 4701 outpatients seen in the neurology clinic. The most common neurologi- cal diagnoses were epilepsy (39.2%), headache (21.5%) and cerebrovascular disease (16.7%). During prospective data collection, patients waited an average of 57.8 (SD 73.4) days to be seen by a neurologist. The average wait time from arrival in the clinic to departure was 4.0 (SD 2.5) h. The process map and interviews with clinic staff revealed long waiting times due to a paucity of providers. Nurses and clerks represent an influential stakeholder group, but are not actively involved in any activity to reduce wait times. A large proportion of follow-up patients were stable and seen solely to obtain medication refills. Conclusions: Epilepsy, headache, and stroke make up the largest percentage of outpatient neurological illness in Zambia. Targeting stable patients in these diagnostic categories for a task-shifting intervention may lead to substan- tially decreased patient wait times. Potential interventions include shifting clinical follow-ups and medication refills to less specialized healthcare workers.

Abstract: The cell envelope is essential for the survival and adaptation of bacteria. Bacterial membrane proteins include the major porins that mediate the influx of nutrients and several classes of antimicrobial drugs. Consequently, membrane remodelling is closely linked to antimicrobial resistance (AMR). Knowledge of bacterial membrane protein biogenesis and turnover underpins our understanding of bacterial membrane remodelling and the consequences that this process has in the evolution of AMR phenotypes. At the population level, the evolution of phenotypes is a reversible process, and we can use these insights to deploy evolutionary principles to resensitize bacteria to existing antimicrobial drugs. In our opinion, fundamental knowledge is opening a new way of thinking towards sustainable solutions to the mounting crisis in AMR. Here we discuss what is known about outer-membrane remodelling in bacteria and how the process could be targeted as a means to restore sensitivity to antimicrobial drugs. Bacteriophages are highlighted as a powerful means to exert this control over membrane remodelling but they require careful selection so as to reverse, and not exacerbate AMR phenotypes.

Introducción: el artículo reporta un caso clínico de intento suicida de un paciente con síndrome intermedio a causa de intoxicación por organofosforados. Para ello se analizó la historia clínica, los exámenes complementarios y el estudio electromiográfico, y se realizó revisión no sistemática de la literatura. Presentación del caso: se describe un caso diagnosticado en la unidad de cuidado intensivo, el cual presentó trastornos neuromotores, requerimiento de soporte ventilatorio con destete difícil y extubación fallida, así como el tratamiento médico y fisioterapéutico instaurado. Dentro del manejo de la intoxicación por organofosforados se incluye la descontaminación del tóxico, administración de atropina y pralidoxima, diagnóstico oportuno del síndrome intermedio y la prescripción de ejercicio terapéutico. El paciente recibió manejo interdisciplinario, logrando liberación de su condición crítica, pero con persistencia de debilidad muscular proximal; sin embargo, con el ejercicio alcanzó recuperación funcional de sus actividades básicas cotidianas. Conclusión: el panorama mundial de las intoxicaciones por sustancias químicas muestra que son causa de morbilidad y discapacidad importante. Los organofosforados son los plaguicidas más frecuentemente involucrados. Los síntomas y signos clínicos de este tipo de intoxicaciones se clasifican en manifestaciones colinérgicas, el síndrome intermedio y la neuropatía retardada.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and its incidence is rising. The introduction of new systemic therapies, including immune-based therapies and biomarker driven therapies, has improved survival in patients at advanced stages. However, overall survival is still poor, and recent advances in understanding of the molecular alterations of HCC have not translated yet into novel biomarkers. Over the past decade, major advancements in 'omic' technologies have enabled monitoring of a variety of molecular and organismal processes. A comprehensive analysis of single gene mutations in HCC might lead to detect biomarkers that improve our prognosis and treatment. We developed a bioinformatics pipeline capable of analyzing genomic data to identify key regulatory molecular changes in HCC development and their influence in patient’s prognosis. By looking at genetically determined subgroups of HCC in the TCGA Liver Cancer dataset, we managed to obtain 15 genes frequently affected by oncogenic mutations and analyzed their influence in patient’s survival, identifying CSMD1 as a prognostic biomarker candidate. Nevertheless, the validation in the ICGC HCC database showed that it did not have any statistically significant influence in overall survival. This work reveals that the most frequent single gene mutations are not enough for significant survival changes in HCC and that we should focus our efforts in integrative analysis of clinical information and multi-omics to maximize our clinical benefits in this devastating disease. Resumen: El carcinoma hepatocelular (CHC) es el tipo más común de cáncer de hígado y su incidencia está aumentando. La introducción de nuevas terapias sistémicas, incluidas las inmunoterapias y las terapias impulsadas por biomarcadores, ha mejorado la supervivencia de los pacientes en etapas avanzadas. Sin embargo, la supervivencia general sigue siendo escasa y los avances recientes en la comprensión de las alteraciones moleculares del CHC aún no se han traducido en nuevos biomarcadores. Durante la última década, los principales avances en las tecnologías "ómicas" han permitido el seguimiento de una variedad de procesos moleculares y orgánicos. Un análisis completo de las mutaciones de un solo gen en el CHC podría conducir a detectar biomarcadores que mejoren nuestro pronóstico y tratamiento. Desarrollamos un protocolo de bioinformática capaz de analizar datos genómicos para identificar cambios moleculares reguladores clave en el desarrollo del CHC y su influencia en el pronóstico del paciente. Al observar subgrupos genéticamente determinados de CHC en la base de datos TCGA-Liver Cancer, logramos obtener 15 genes frecuentemente afectados por mutaciones oncogénicas y analizamos su influencia en la supervivencia del paciente, identificando CSMD1 como un candidato a biomarcador pronóstico. Sin embargo, la validación en la base de datos ICGC-CHC mostró que no tuvo ninguna influencia estadísticamente significativa en la supervivencia global. Este trabajo revela que las mutaciones de un solo gen más frecuentes no son suficientes para cambios significativos en la supervivencia del CHC y que debemos centrar nuestros esfuerzos en el análisis integrador de la información clínica y la multi-ómica para maximizar nuestros beneficios clínicos en esta devastadora enfermedad.

Background: Esophageal cancer occurs as a local disease in 22% of cases, and a minority of this disease is limited to the mucosa or submucosa (early lesions). Endoscopic mucosal resection, endoscopic submucosal dissection, photodynamic therapy, laser therapy, and argon plasma coagulation have emerged as alternatives to surgical resection for early lesions. Objective: The aim of this systematic review is to identify studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated with cancer in the endoscopic versus surgical therapies. Results: The survival rates after 3 and 5 years were different and exhibited superiority with the surgical therapies over time. Endoscopy is superior in the control of mortality related to cancer with a high rate of disease recurrence. With regard to the comorbidity and the mortality associated with the procedure, endoscopy is superior. Conclusion: There is no evidence from clinical trials. In this systematic review, surgical therapies showed superiority for survival, and endoscopic therapies showed superiority in the control of mortality related to cancer with a high rate of disease recurrence; also, for the comorbidity and the mortality associated with the procedure, endoscopy is superior. Prospective, controlled trials with large sample sizes are necessary to confirm the results of the current analysis.

La trama del texto se construye tensionando experiencias y reflexiones de prácticas desarrolladas en instituciones públicas de salud, en las que el espacio de supervisión se propone como dispositivo privilegiado de entrenamiento de habilidades clínicas. Supervisar implica promover en la formación del psicólogo una actitud ética e investigativa, capaz de trascender la teoría y ejercer su praxis sosteniendo una postura crítica y un permanente aprendizaje del saber hacer. Se presentan modalidades de entrenamiento de habilidades clínicas básicas para realizar entrevistas psicológicas, por ser esta la técnica fundamental para la formación de psicólogos en las diferentes áreas de ejercicio profesional.

Abstract: This article reports a self-strangulation suicide in which a double complex group of ligatures was used. Although similar cases have been referenced in forensic literature, this case is notable because of the unusual method used by the victim. A 61-year-old man was found in a locked room with a double elaborate ligature comprising six wire clothes hangers completely encircling the neck and a black rubber band in a double loop. Autopsy also documented parallel superficial cut lesions in proximal forearm interpreted as hesitation marks. It stresses the importance of characteristics such as analysis of number of ligatures, position of the knots, number of knots and turns of ligature marks and the absence of any defense and relevant internal injuries inherent to suicide ligature strangulation cases. Resumen: Este artículo reporta un suicidio de auto-estrangulación en el que se utilizó un grupo doble de ligaduras. Aunque casos similares se han referenciado en la literatura forense, este caso es notable debido al método inusual utilizado por la víctima. Un hombre de 61 años de edad fue encontrado en una habitación cerrada con un muy elaborado conjunto de doble ligadura que constaba de seis perchas de ropa de alambre que rodean completamente el cuello y una banda de goma negra de doble lazada. La autopsia también documentó lesiones paralelas de corte superficial en el antebrazo proximal interpretadas como heridas de vacilación. El artículo destaca la importancia de características tales como el análisis del número de ligaduras, la posición de los nudos, el número de nudos y giros de las ligaduras, la ausencia de signos de defensa y las lesiones internas relevantes en los casos de suicidio por estrangulación con ligadura.

Abstract: Trypanosomes are unicellular early divergent eukaryotic microorganisms that cause sleeping sickness and Chagas disease. Genome sequencing has revealed that these parasites lack most of the highly conserved proteins involved in chromosome segregation. However, kinetochore-associated chromosome segregation has been proposed to occur in Trypanosoma brucei and the existence of centromeres, the locus that interacts with the kinetochores, has been inferred in T. brucei and Trypansoma cruzi. This work aimed to characterise, at a structural and functional level, the centromeres of Trypanosoma sp. Centromeres in T. brucei have been localised to chromosomal loci that contain an array of ~147 bp AT-rich tandem repeats. Using a long-range restriction endonuclease mapping approach, we found that the sizes of the arrays in T. brucei chromosomes 1-8 vary from 20 to 110 kb and present length heterogeneity between chromosome homologues. Topoisomerase II-? (TOP2?) plays a major role in sister chromatid segregation. TOP2? specific centromeric activity has been demonstrated in trypanosomes. In this project, we systematically evaluated through different approaches, regulatory mechanisms for the TOP2? activity/recruitment to trypanosome centromeres. In other eukaryotes, the Small Ubiquitin-like MOdifier (SUMO) interaction with TOP2? is required for it to be recruited to centromeres during mitosis. In independent experiments, we found no evidence for this association in bloodstream form (BSF) T. brucei . Modifications to the carboxyl terminal region (CTR) of TOP2?, other than SUMOylation, have been described that affect cell cycle specific localisation on chromosomes. Here, we undertook experiments to further delineate regions of the CTR of trypanosome TOP2?. Using a sequential deletion approach, we found that amino acids 1223-1312 in the CTR of enzyme are not required for its centromeric-specific activity. Finally, we found that the condensin unit SMC2 is essential for growth of T. brucei BSFs and not for TOP2? specific centromeric activity.

Abstract: Stress is a physiological response that promotes maintenance of balance against harmful stim- uli. Unfortunately, chronic activation of stress systems facilitates the development of psychi- atric disorders. A stress-mediated hypercholinergic state could underlie this facilitation, as cholinergic mechanisms have been suggested to play a role in anxiety, depression, and sub- stance use disorder (SUD). Stimulation by stress hormones, urocortin (Ucn1) or corticotropin- releasing factor (CRF), of the CRF receptor type 1 (CRFR1) of acetylcholine-containing neurons of the laterodorsal tegmental nucleus (LDT) could be involved in modulation of cholinergic transmission during periods of stress hormone activation, which could play a role in psychiatric disorders as cholinergic LDT neurons project to, and control activity in, mood-, arousal- and SUD-controlling regions. The present study investigated for the first time the membrane effects and intracellular outcomes of CRFR1 activation by endogenous stress hormones on LDT neurons. Patch clamp recordings of immunohistochemically- identified cholinergic and non-cholinergic LDT neurons with concurrent calcium imaging were used to monitor cellular responses to CRFR1 stimulation with Ucn1 and CRF. Postsynaptically-mediated excitatory currents were elicited in LDT cholinergic neurons, accompanied by an enhancement in synaptic events. In addition, CRFR1 activation resulted in rises in intracellular calcium levels. CRFR1 stimulation recruited MAPK/ERK and SERCA-ATPase involved pathways. The data presented here provide the first evidence that Ucn1 and CRF exert pre and postsynaptic excitatory membrane actions on LDT cholinergic neurons that could underlie the hypercholinergic state associated with stress which could play a role in the heightened risk of psychiatric disorders associated with a chronic stress state. Resumen: El estrés es una respuesta fisiológica que promueve el mantenimiento del equilibrio frente a los estímulos dañinos. Desafortunadamente, la activación crónica de los sistemas de estrés facilita el desarrollo de trastornos psiquiátricos. Un estado hipercolinérgico mediado por estrés podría ser la base de esta facilitación, ya que se ha sugerido que los mecanismos colinérgicos desempeñan un papel en la ansiedad, la depresión y el trastorno por consumo de sustancias (TUS). La estimulación por hormonas del estrés, urocortina (Ucn1) o factor liberador de corticotropina (CRF), del receptor CRF tipo 1 (CRFR1) de neuronas que contienen acetilcolina del núcleo tegmental laterodorsal (LDT) podría estar involucrado en la modulación de la transmisión colinérgica durante los períodos. de activación de la hormona del estrés, que podría desempeñar un papel en los trastornos psiquiátricos, ya que las neuronas LDT colinérgicas proyectan y controlan la actividad en las regiones que controlan el estado de ánimo, la excitación y el SUD. El presente estudio investigó por primera vez los efectos de la membrana y los resultados intracelulares de la activación de CRFR1 por las hormonas del estrés endógenas en las neuronas LDT. Se utilizaron registros de pinza de parche de neuronas LDT colinérgicas y no colinérgicas identificadas inmunohistoquímicamente con imágenes de calcio concurrentes para controlar las respuestas celulares a la estimulación de CRFR1 con Ucn1 y CRF. Las corrientes excitadoras mediadas postsinápticamente se provocaron en las neuronas colinérgicas de LDT, acompañadas de una mejora en los eventos sinápticos. Además, la activación de CRFR1 dio como resultado aumentos en los niveles de calcio intracelular. La estimulación de CRFR1 reclutó las vías involucradas MAPK / ERK y SERCA-ATPasa. Los datos presentados aquí proporcionan la primera evidencia de que Ucn1 y CRF ejercen acciones de la membrana excitadora pre y postsináptica sobre las neuronas colinérgicas LDT que podrían ser la base del estado hipercolinérgico asociado con el estrés que podría desempeñar un papel en el mayor riesgo de trastornos psiquiátricos asociados con un estado de estrés crónico.