Anisotropic expansion of hepatocyte lumina enforced by apical bulkheads.

Lumen morphogenesis results from the interplay between molecular pathways and mechanical forces. In several organs, epithelial cells share their apical surfaces to form a tubular lumen. In the liver, however, hepatocytes share the apical surface only between adjacent cells and form narrow lumina that grow anisotropically, generating a 3D network of bile canaliculi (BC). Here, by studying lumenogenesis in differentiating mouse hepatoblasts in vitro, we discovered that adjacent hepatocytes assemble a pattern of specific extensions of the apical membrane traversing the lumen and ensuring its anisotropic expansion. These previously unrecognized structures form a pattern, reminiscent of the bulkheads of boats, also present in the developing and adult liver. Silencing of Rab35 resulted in loss of apical bulkheads and lumen anisotropy, leading to cyst formation. Strikingly, we could reengineer hepatocyte polarity in embryonic liver tissue, converting BC into epithelial tubes. Our results suggest that apical bulkheads are cell-intrinsic anisotropic mechanical elements that determine the elongation of BC during liver tissue morphogenesis.

Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9.

Despite their roles in intercellular communications, the different populations of extracellular vesicles (EVs) and their secretion mechanisms are not fully characterized: how and to what extent EVs form as intraluminal vesicles of endocytic compartments (exosomes), or at the plasma membrane (PM) (ectosomes) remains unclear. Here we follow intracellular trafficking of the EV markers CD9 and CD63 from the endoplasmic reticulum to their residency compartment, respectively PM and late endosomes. We observe transient co-localization at both places, before they finally segregate. CD9 and a mutant CD63 stabilized at the PM are more abundantly released in EVs than CD63. Thus, in HeLa cells, ectosomes are more prominent than exosomes. By comparative proteomic analysis and differential response to neutralization of endosomal pH, we identify a few surface proteins likely specific of either exosomes (LAMP1) or ectosomes (BSG, SLC3A2). Our work sets the path for molecular and functional discrimination of exosomes and small ectosomes in any cell type.

Localized Intercellular Transfer of Ephrin-As by Trans-endocytosis Enables Long-Term Signaling.

Ephrins can elicit either contact-mediated cell-cell adhesion or repulsion, depending on the efficiency of the removal of their ligand-receptor complexes from the cell surface, thus controlling tissue morphogenesis and oncogenic development. However, the dynamic of the turnover of newly assembled ephrin-Eph complexes during cell-cell interactions remains mostly unexplored. Here, we show that ephrin-A1-EphA2 complexes are locally formed at the tip of the filopodia, at cell-to-cell contacts. Clusters of ephrin-A1 from donor cells surf on filopodia associated to EphA2-bearing subdomains of acceptor cells. Full-length ephrin-A1 is transferred to acceptor cells by trans-endocytosis through a proteolysis-independent mechanism. Trans-endocytosed ephrin-A1 bound to its receptor enables signaling to be emitted from endo-lysosomes of acceptor cells. Localized trans-endocytosis of ephrin-A1 sustains contact-mediated repulsion on cancer cells. Our results uncover the essential role played by local concentration at the tip of filopodia and the trans-endocytosis of full-length ephrin to maintain long-lasting ephrin signaling.

Sexual and reproductive health for young adults in Colombia: teleconsultation using mobile devices.

BACKGROUND: Sexual risk behaviors associated with poor information on sexuality have contributed to major public health problems in the area of sexual and reproductive health in teenagers and young adults in Colombia. OBJECTIVE: To report our experience with the use of DoctorChat Mobile to provide sexual education and information among university students in Bogota, Colombia, and knowledge about the sexual risk factors detected among them. METHODS: A mobile app that allows patients to ask about sexual and reproductive health issues was developed. Sexual and reproductive risk behaviors in a sample of young adults were measured before and after the use of the app through the validated survey Family Health International (FHI) Behavioral Surveillance Survey (BSS) for Use With Adults Between 15 and 49 Years. A nonprobabilistic convenience recruitment was undertaken through the study´s webpage. After completing the first survey, participants were allowed to download and use the app for a 6-month period (intervention), followed by completion of the same survey once again. For the inferential analysis, data was divided into 3 groups (dichotomous data, discrete quantitative data, and ordinal data) to compare the results of the questions between the first and the second survey. The study was carried out with a sample of university students between 18 and 29 years with access to mobile phones. Participation in the study was voluntary and anonymous. RESULTS: A total of 257 subjects met the selection criteria. The preintervention survey was answered by 232 subjects, and 127 of them fully answered the postintervention survey. In total, 54.3% (69/127) of the subjects completed the survey but did not use the app, leaving an effective population of 58 subjects for analysis. Of these subjects, 53% (31/58) were women and 47% (27/58) were men. The mean age was 21 years, ranging between 18 and 29 years. The differences between the answers from both surveys were not statistically significant. The main sexual risk behaviors identified in the population were homosexual intercourse, nonuse of condoms, sexual intercourse with nonregular and commercial partners, the use of psychoactive substances, and lack of knowledge on symptoms of sexually transmitted diseases and HIV transmission. CONCLUSIONS: Although there were no differences between the pre- and postintervention results, the study revealed different risk behaviors among the participating subjects. These findings highlight the importance of promoting high-impact educational strategies on this matter and the importance of providing teenagers and young adults with easily accessible tools with reliable health information, regardless of their socioeconomic status.

Encefalomielitis aguda diseminada en el adulto Caso de asociación con infección por el virus de la hepatitis A / Acute disseminated encephalomyelitis in adults Association with infection by hepatitis A virus

Resumen La encefalomielitis aguda diseminada (ADEM) es una enfermedad desmielinizante monofásica, queusualmente sigue a una infección o vacunación, principalmente por el virus del sarampión, y ocurre principalmente en niños y adultos jóvenes. Su asociación con la infección por el virus de la hepatitis A es rara, y se halla poco documentada. Se presenta el caso de una paciente femenina de 53 años con ADEM e infección por hepatitis A. Se resalta la inclusión de la hepatitis A dentro del tamiz causal de pacientes adultos con ADEM. (Acta Med Colomb 2014; 39: 64-68).

Abstract Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease that usually follows an infection or vaccination, mainly by the measles virus and occurring primarily in children and young adults. His association with infection by hepatitis A virus is rare, and is poorly documented. The case of a 53 years old female patient with ADEM and infection by hepatitis A is presented. The inclusion of hepatitis A within the causal screening of adult patients with ADEM is highlighted. (Acta Med Colomb 2014; 39: 64-68).

Síndrome de Blesovsky Pseudotumor pulmonar infrecuente y subdiagnosticado / Blesovsky syndrome Uncommon and underdiagnosed pulmonary pseudotumor

Resumen Se presenta el caso de un hombre de 68 años inmunosuprimido, en periodo tardío postrasplante hepático por cirrosis alcohólica en quien se encuentra de manera incidental atelectasia redonda del pulmón en estudios imagenológicos. El paciente cursaba asintomático y como único hallazgo positivo al examen físico presentaba estertores finos basales. No fue posible encontrar factores etiológicos relacionados, por lo que se categorizó como un caso idiopático. (Acta Med Colomb 2013; 38: 258-261).

Abstract We present the case of a 68 year old immunosuppressed man, in the late period after liver transplant for alcoholic cirrhosis and in whom incidentally imaging studies showed a lung round atelectasis. The patient was asymptomatic and the only positive finding on physical examination was fine basal rales. It was impossible to find related etiological factors, so the case was categorized as idiopathic. (ActaMed Colomb 2013; 38: 258-261).

Endoplasmic reticulum sorting and kinesin-1 command the targeting of axonal GABAB receptors.

In neuronal cells the intracellular trafficking machinery controls the availability of neurotransmitter receptors at the plasma membrane, which is a critical determinant of synaptic strength. Metabotropic γ amino-butyric acid (GABA) type B receptors (GABA(B)Rs) are neurotransmitter receptors that modulate synaptic transmission by mediating the slow and prolonged responses to GABA. GABA(B)Rs are obligatory heteromers constituted by two subunits, GABA(B)R1 and GABA(B)R2. GABA(B)R1a and GABA(B)R1b are the most abundant subunit variants. GABA(B)R1b is located in the somatodendritic domain whereas GABA(B)R1a is additionally targeted to the axon. Sushi domains located at the N-terminus of GABA(B)R1a constitute the only difference between both variants and are necessary and sufficient for axonal targeting. The precise targeting machinery and the organelles involved in sorting and transport have not been described. Here we demonstrate that GABA(B)Rs require the Golgi apparatus for plasma membrane delivery but that axonal sorting and targeting of GABA(B)R1a operate in a pre-Golgi compartment. In the axon GABA(B)R1a subunits are enriched in the endoplasmic reticulum (ER), and their dynamic behavior and colocalization with other secretory organelles like the ER-to-Golgi intermediate compartment (ERGIC) suggest that they employ a local secretory route. The transport of axonal GABA(B)R1a is microtubule-dependent and kinesin-1, a molecular motor of the kinesin family, determines axonal localization. Considering that progression of GABA(B)Rs through the secretory pathway is regulated by an ER retention motif our data contribute to understand the role of the axonal ER in non-canonical sorting and targeting of neurotransmitter receptors.

RNA interference of Marlin-1/Jakmip1 results in abnormal morphogenesis and migration of cortical pyramidal neurons.

The formation of the nervous systems requires processes that coordinate proliferation, differentiation and migration of neuronal cells, which extend axons, generate dendritic branching and establish synaptic connections during development. The structural organization and dynamic remodeling of the cytoskeleton and its association to the secretory pathway are critical determinants of cell morphogenesis and migration. Marlin-1 (Jakmip1) is a microtubule-associated protein predominantly expressed in neurons and lymphoid cells. Marlin-1 participates in polarized secretion in lymphocytes, but its functional association with the neuronal cytoskeleton and its contribution to brain development have not been explored. Combining in vitro and in vivo approaches we show that Marlin-1 contributes to the establishment of neuronal morphology. Marlin-1 associates to the cytoskeleton in neurites, is required for the maintenance of an intact Golgi apparatus and its depletion produces the down-regulation of kinesin-1, a plus-end directed molecular motor with a central function in morphogenesis and migration. RNA interference of Marlin-1 in vivo results in abnormal migration of newborn pyramidal neurons during the formation of the cortex. Our results support the involvement of Marlin-1 in the acquisition of the complex architecture and migration of pyramidal neurons, two fundamental processes for the laminar layering of the cortex.

Costo-efectividad de la colecistectomía laparoscópica y de la abierta en una muestra de población colombiana / Cost-effectiveness of laparoscopic versus open cholecystectomy

Introducción. La colecistectomía ha sido objeto de varios estudios clínicos y de costos a nivelmundial. Objetivo. Evaluar el costo-efectividad de la colecistectomía abierta y de la laparoscópica desde laperspectiva del tercer pagador. Materiales y métodos. Se llevó a cabo un estudio de costo-efectividad en dos hospitales de Bogotá. Se obtuvieron los datos de efectividad de las cirugías a partir de un estudio de cohortes, y se obtuvo enforma retrospectiva el tipo de colecistectomía y en forma prospectiva, el resultado. Se incluyeron 376 pacientes intervenidos por colecistitis o litiasis de mayo de 2005 a junio de 2006; 156 pacientes fueron intervenidos por colecistectomía abierta y 220 por laparoscopia. Los resultados que se analizaron fueron los siguientes: frecuencia de complicaciones, estancia hospitalaria, reincorporación a las labores cotidianas y duración de la cirugía. Los costos se recolectaron según el tipo de estudio económico y sólo se incluyeron los costos directos. Posteriormente, se planteó un estudio de costo-efectividad a un año desde la perspectiva del tercer pagador; se propuso un modelo de árbol de decisiones y se calcularon las razones de incremento de costo-efectividad para cada uno de los desenlaces propuestos. Resultados. Los resultados de la colecistectomía abierta frente a la laparoscópica fueron: OR ajustado de complicaciones: 2,02 (IC95% 0,94-4,37); conversión quirúrgica (tasa): 3,2%; estancia: 2,2 Vs. 1,6,p=0,003; reincorporación a cotidianidad: 32,5 Vs. 9,6, p<0,001; duración quirúrgica: 22 minutos (p<0,001) menor en la colecistectomía abierta; desde la perspectiva del tercer pagador, costo promedio: US$995 Vs. US$ 1.048; incremento del costo-efectividad: US$ 7,4 favoreciendo la laparoscópica; desde la perspectiva paciente, costo promedio: US$ 53.2 Vs. US$ 104,8; incremento del costo-efectividad: US$-7.3 favoreciendo la laparoscópica; cero mortalidad. La variable que más impactó tiene en la toma de decisiones en términos de costos es el costo del procedimiento quirúrgico. Conclusiones. Hubo mayor estancia hospitalaria en la colecistectomía abierta frente a la mayor duración quirúrgica en la laparoscópica; en el costo directo de la laparoscópica: menor para IPS y pacientes; y en costo-efectividad equiparable para ambos procedimientos.

Introduction. Cholecystectomy has been the subject of several clinical and cost comparison studies. Objective. The results of open or laparoscopy cholecystectomy were compared in terms of cost and effectiveness from the perspective of health care institutions and from that of the patients. Materials and methods. The cost-effectiveness study was undertaken at two university hospitals in Bogotá, Colombia. The approach was to select the type of cholecystectomy retrospectively and then assess the result prospectively. The cost analysis used the combined approach of micro-costs and daily average cost. Patient resource consumption was gathered from the time of surgery room entry to time of discharge. A sample of 376 patients with cholelithiasis/cystitis (May 2005-June 2006) was selected--156 underwent open cholecystectomy and 220 underwent laparoscopic cholecystectomy. The following data were tabulated: (1) frequency of complications and mortality, post-surgical hospital stay, (2) reincorporation to daily activities, (3) surgery duration, (4) direct medical costs, (5) costs to the patient, and (6) mean and incremental cost-effectiveness ratios. Results. Frequency of complications was 13.5% for open cholecystectomy and 6.4% for laparoscopic cholecystectomy (p=0.02); hospital stay was longer in open cholecystectomy than in laparoscopic cholecystectomy (p=0.003) as well as the reincorporation to daily activities reported by the patients (p<0.001). The duration of open cholecystectomy was 22 min longer than laparoscopic cholecystectomy (p<0.001). The average cost of laparoscopic cholecystectomy was lower than open cholecystectomyand laparoscopic cholecystectomy was more cost-effective than open cholecystectomy (US$ 995 vs. US$ 1,048, respectively). The patient out-of-pocket expenses were greater in open cholecystectomy compared to laparoscopic cholecystectomy (p=0.015). Mortality was zero. Conclusions: The open laparoscopy procedure was associated with longer hospital stays, where asthe cholecystectomy procedure required a longer surgical duration. The direct cost of the latter was lower for both for the health care institution and patients. The cost-effectiveness for both procedures was comparable.

Neuronal protein trafficking: emerging consequences of endoplasmic reticulum dynamics.

The highly polarized morphology and complex geometry of neurons is determined to a great extent by the structural and functional organization of the secretory pathway. It is intuitive to propose that the spatial arrangement of secretory organelles and their dynamic behavior impinge on protein trafficking and neuronal function, but these phenomena and their consequences are not well delineated. Here we analyze the architecture and motility of the archetypal endoplasmic reticulum (ER), and their relationship to the microtubule cytoskeleton and post-translational modifications of tubulin. We also review the dynamics of the ER in axons, dendrites and spines, and discuss the role of ER dynamics on protein mobility and trafficking in neurons.

A telephone survey of patient satisfaction with realtime telemedicine in a rural community in Colombia.

We conducted a telephone survey of all patients referred to a realtime telemedicine consultation at the Centre for Telehealth in Bogotá. Over a six-month period, 281 teleconsultations were conducted, and we were able to retrieve telephone numbers for 156 patients. Of these, 121 patients (78%) agreed to answer the questionnaire. Eighty percent of the respondents were satisfied or very satisfied with the teleconsultation and 63% would use telemedicine again. Sixty-five percent thought that telemedicine improved their medical care. More than 50% believed that telemedicine had a positive effect in terms of medical care improvement, time- and cost-savings. Twenty-seven percent felt that teleconsultation was not as good as a traditional face-to-face consultation. Lack of familiarity with ICT did not appear to act as a major barrier to telemedicine, and cognitive factors may be more important in acceptability to patients and their satisfaction. The results of the present study may also be relevant to the poorest countries of the world, where two-thirds of the population live in rural areas.

[Cost-effectiveness of laparoscopic versus open cholecystectomy]. / Costo-efectividad de la colecistectomía laparoscópica y de la abierta en una muestra de población colombiana.

INTRODUCTION: Cholecystectomy has been the subject of several clinical and cost comparison studies. OBJECTIVE: The results of open or laparoscopy cholecystectomy were compared in terms of cost and effectiveness from the perspective of health care institutions and from that of the patients. MATERIALS AND METHODS: The cost-effectiveness study was undertaken at two university hospitals in Bogotá, Colombia. The approach was to select the type of cholecystectomy retrospectively and then assess the result prospectively. The cost analysis used the combined approach of micro-costs and daily average cost. Patient resource consumption was gathered from the time of surgery room entry to time of discharge. A sample of 376 patients with cholelithiasis/cystitis (May 2005-June 2006) was selected--156 underwent open cholecystectomy and 220 underwent laparoscopic cholecystectomy. The following data were tabulated: (1) frequency of complications and mortality, post-surgical hospital stay, (2) reincorporation to daily activities, (3) surgery duration, (4) direct medical costs, (5) costs to the patient, and (6) mean and incremental cost-effectiveness ratios. RESULTS: Frequency of complications was 13.5% for open cholecystectomy and 6.4% for laparoscopic cholecystectomy (p=0.02); hospital stay was longer in open cholecystectomy than in laparoscopic cholecystectomy (p=0.003) as well as the reincorporation to daily activities reported by the patients (p<0.001). The duration of open cholecystectomy was 22 min longer than laparoscopic cholecystectomy (p<0.001). The average cost of laparoscopic cholecystectomy was lower than open cholecystectomy and laparoscopic cholecystectomy was more cost-effective than open cholecystectomy (US$ 995 vs. US$ 1,048, respectively). The patient out-of-pocket expenses were greater in open cholecystectomy compared to laparoscopic cholecystectomy (p=0.015). Mortality was zero. CONCLUSIONS: The open laparoscopy procedure was associated with longer hospital stays, where as the cholecystectomy procedure required a longer surgical duration. The direct cost of the latter was lower for both for the health care institution and patients. The cost-effectiveness for both procedures was comparable.

Web-based asynchronous teleconsulting for consumers in Colombia: a 2-year follow up.

BACKGROUND: Remote consultation was implemented in 2006 in our institution, through an open-access Web-based Teleconsulting service: Doctor Chat. This tool was created with the aim of improving access to health care services in Colombia, especially in underserved areas. OBJECTIVE: The aim of this paper is to report our experience with the free Web-based application for teleconsultation. METHODS: After validating the tool, we analyzed the queries submitted between May 2007 and June 2009. Requests were classified into three axes: purpose of the query, specialty, and geographic area of origin. Descriptive statistics were gathered for each category (name, email, city, country, age, gender). RESULTS: We received 1624 consultations, with an average of 59 requests per month. 52.7% of the users were aged 18 to 29 years. Users asked mainly about sexual and reproductive health issues. 79.2% of consultations came from Colombia and 32.91% of the users were students. CONCLUSIONS: Doctor Chat is an innovative tool to deliver health care information, but advertising, preventive and technical strategies must be implemented to improve its impact on Colombia's health system.

Prevalence of suicide risk factors and suicide-related outcomes in the National Mental Health Study, Colombia.

A community survey in 4,426 adults was undertaken as part of the World Mental Health Survey Initiative reporting the prevalence and risk factors for suicide-related outcomes in Colombia. Lifetime prevalence estimates of suicide ideation, plans, attempts, and risk factors for suicide-related outcomes were assessed. Retrospective reports of disorders age-of-onset were used to study associations between primary mental disorders and first onset of suicide-related outcomes. Risks of plans and attempts were highest with ideation early age-of-onset and within the first year. The highest risk for ideation and attempt among ideators occurred in the 18-29 age group. After first employment (defined as the first paid job accepted by the respondent) and presence of mental disorders constituted risk factors. Impulse-control disorders were strongest diagnostic predictors.

[Health care workers' perception of the Internet and mobile technologies in Colombia]. / Percepciones de los trabajadores del sector salud frente a Internet y las tecnologías móviles en Colombia.

In July 2007 in Medellín, Colombia, 1,200 health care professionals were asked to complete a questionnaire: of the 493 who participated, the mean age was 31.2 years; 58.8% were physicians; and 97.6% had Internet access, 60.5% on a daily basis and 27.7%, weekly. The preferred place to access the Internet was from home (58%) or from the work place (12.5%); 98% reported having a cell phone, and of those, 80% were interested in using health education tools via cell phone. These are the first data published regarding Internet and cellular phone penetration among health care workers in Colombia. Acceptance of the Internet and mobile systems as health information tools is gaining, and as such, creating a new opportunity for training and harnessing of these new technologies.

Percepciones de los trabajadores del sector salud frente a Internet y las tecnologías móviles en Colombia / Health care workers' perception of the Internet and mobile technologies in Colombia

In July 2007 in Medellín, Colombia, 1 200 health care professionals were asked to complete a questionnaire: of the 493 who participated, the mean age was 31.2 years; 58.8 percent were physicians; and 97.6 percent had Internet access, 60.5 percent on a daily basis and 27.7 percent, weekly. The preferred place to access the Internet was from home (58 percent) or from the work place (12.5 percent); 98 percent reported having a cell phone, and of those, 80 percent were interested in using health education tools via cell phone. These are the first data published regarding Internet and cellular phone penetration among health care workers in Colombia. Acceptance of the Internet and mobile systems as health information tools is gaining, and as such, creating a new opportunity for training and harnessing of these new technologies.

Web-based asynchronous teleconsulting for consumers in Colombia: a case study.

BACKGROUND: Fourteen years after the reform to Colombia's health system, the promises of universality, improved equity, efficiency, and better quality of care have not materialized. Remote areas remain underserved and access to care very limited. Recognizing teleconsultation as an effective way to improve access to health care and health information, a noncommercial open-access Web-based application for teleconsultation called Doctor Chat was developed. OBJECTIVE: The objective was to report the experience of the Center for Virtual Education and Simulation eHealth (Centro de Educación Virtual y Simulación e-Salud) with open-access Web-based asynchronous teleconsultation for consumers in Colombia. METHODS: A teleconsultation service in Spanish was developed and implemented in 2006. Teleconsultation requests were classified on three axes: (1) the purpose of the query, (2) the specialty, and (3) the geographic area of the query. Content analysis was performed on the free-text queries submitted to Doctor Chat, and descriptive statistics were gathered for each of the data categories (name, email, city, country, age, and gender). RESULTS: From September 2006 to March 2007, there were 270 asynchronous teleconsultations documented from 102 (37.8%) men and 168 (62.2%) women. On average, 1.4 requests were received per day. By age group, the largest number of requests (n = 80; 30%) were from users 24-29 years, followed by users (n = 66; 24%) 18-23 years. Requests were mainly from Colombia (n = 204; 75.6%) but also from Spain (n = 17; 6.3%), Mexico (n = 11; 4.1%), and other countries. In Colombia, 137 requests (67.2%) originated in Bogotá, the nation's capital, 25 (12.4%) from other main cities of the country, 40 (19.7%) from intermediate cities, and 2 (0.7%) from remote areas. The purpose of the majority of requests was for information about symptoms, health-related problems, or diseases (n = 149; 55.2%) and medications/treatments (n = 70; 25.9%). By specialty, information was most requested for gynecology and obstetrics (n = 71; 26%), dermatology (n = 28; 10%), urology (n = 22; 8%), and gastroenterology (n = 18; 7%), with anesthesiology, critical care, physical medicine and rehabilitation, and pathology being the least requested (n = 0; 0%). Overall, sexual and reproductive health (n = 93; 34%) issues constituted the main query subject. The average time to deliver a response was 120 hours in 2006 and 59 hours in 2007. Only 19 out of 270 users (7%) completed a survey with comments and perceptions about the system, of which 18 out of 19 (95%) corresponded to positive perceptions and 1 out of 19 (5%) expressed dissatisfaction with the service. CONCLUSION: The implementation of a Web-based teleconsulting service in Colombia appeared to be an innovative way to improve access to health care and information in the community and encouraged open and explicit discussion. Extending the service to underserved areas could improve access to health services and health information and could potentially improve economic indicators such as waiting times for consultations and the rate of pregnancy among teenagers; however, cultural, infrastructural, and Internet connectivity barriers are to be solved before successful implementation can derive population-wide positive impacts.