Brain cortical maturation assessed by magnetic resonance imaging in unaffected or mildly affected fetuses with cytomegalovirus infection.

OBJECTIVES: To assess by magnetic resonance imaging (MRI) the cortical maturation pattern in fetuses with cytomegalovirus (CMV) infection with mild or no abnormalities on ultrasound (US) and MRI, and to establish possible differences compared with healthy controls. METHODS: This was a retrospective case-control study of consecutive pregnancies with a CMV-infected fetus undergoing prenatal MRI as a complementary diagnostic tool in two centers, and a control group of singleton low-risk pregnancies without fetal structural abnormalities, with normal fetal growth and with healthy newborns. CMV infection was confirmed by extraction of CMV-DNA from fetal and neonatal samples. Only fetuses with mild (mildly affected) or no (unaffected) neuroimaging abnormalities on US and MRI were included. MRI measurements of fetal parieto-occipital sulcus, cingulate sulcus and calcarine sulcus depth, Sylvian fissure depth and Sylvian fissure angles were performed and cortical development grading of specific cortical areas and sulci were assessed by one operator who was blinded to CMV infection status. Data were compared between controls and fetuses with CMV infection, using linear regression and non-parametric trend analysis. RESULTS: Twenty-four CMV-infected fetuses (seven unaffected and 17 mildly affected) and 24 healthy controls that underwent fetal MRI between 27 and 36 weeks' gestation were included. Compared with controls, CMV-infected fetuses showed significantly larger median lateral ventricular width (right side, 7.8 (interquartile range (IQR), 5.9-9.9) mm vs 3.9 (IQR, 2.6-5.3) mm; left side, 7.5 (IQR, 6.0-10.9) mm vs 4.2 (IQR, 3.2-5.3) mm), significantly decreased parieto-occipital sulcus depth (right side, 12.6 (IQR, 11.3-13.5) mm vs 15.9 (IQR, 13.5-17.3) mm; left side, 12.3 (IQR, 10.6-13.5) mm vs 16.0 (IQR, 13.3-17.5) mm) and calcarine sulcus depth (right side, 15.4 (IQR, 14.4-16.3) mm vs 17.5 (IQR, 16.1-18.7) mm; left side, 14.6 (IQR, 14.1-15.6) mm vs 16.7 (IQR, 15.6-18.9) mm) (P < 0.001 for all). Compared with controls, CMV-infected fetuses also had significantly smaller upper (right side, 42.8° (IQR, 35.8-45.8°) vs 48.9° (IQR, 38.4-64.7°); left side, 40.9° (IQR, 34.2-45.8°) vs 48.2° (IQR, 41.9-60.7°)) and lower (right side, 41.6° (IQR, 34.4-49.2°) vs 48.9° (IQR, 40.6-60.9°); left side, 42.2° (IQR, 38.8-46.9°) vs 48.9° (IQR, 39.5-57.5°)) Sylvian fissure angles (P < 0.05 for all). In addition, the mildly affected CMV-infected fetuses had a significantly lower cortical development grading in the temporal and parietal areas, and the parieto-occipital and calcarine sulci compared with healthy fetuses (P < 0.05). These differences persisted when adjusting for gestational age, ipsilateral atrium width, fetal gender and when considering small-for-gestational age as a confounding factor. CONCLUSIONS: Unaffected and mildly affected CMV-infected fetuses showed delayed cortical maturation compared with healthy controls. These results suggest that congenital CMV infection, even in non-severely affected fetuses that are typically considered of good prognosis, could be associated with altered brain cortical structure. Further research is warranted to better elucidate the correlation of these findings with neurodevelopmental outcomes. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Halo sign in fetal cytomegalovirus infection: cerebral imaging abnormalities and postmortem histopathology in 35 infected fetuses.

OBJECTIVE: To evaluate the correlation of periventricular echogenic halo (halo sign) with histopathological findings and its association with other brain imaging abnormalities in fetuses with cytomegalovirus (CMV) infection. METHODS: This was a retrospective study of fetuses diagnosed with severe CMV infection based on central nervous system (CNS) abnormalities seen on ultrasound, which had termination of pregnancy (TOP) or fetal demise at a single center from 2006 to 2021. All included cases had been evaluated by conventional complete fetal autopsy. A maternal-fetal medicine expert reanalyzed the images from the transabdominal and transvaginal neurosonography scans, blinded to the histological findings. The halo sign was defined as the presence of homogeneous periventricular echogenicity observed in all three fetal brain orthogonal planes (axial, parasagittal and coronal). Cases were classified according to whether the halo sign was the only CNS finding (isolated halo sign) or concomitant CNS anomalies were present (non-isolated halo sign). An expert fetal radiologist reanalyzed magnetic resonance imaging (MRI) examinations when available, blinded to the ultrasound and histological results. Hematoxylin-eosin-stained histologic slides were reviewed independently by two experienced pathologists blinded to the neuroimaging results. Ventriculitis was classified into four grades (Grades 0-3) according to the presence and extent of inflammation. Brain damage was categorized into two stages (Stage I, mild; Stage II, severe) according to the histopathological severity and progression of brain lesions. RESULTS: Thirty-five CMV-infected fetuses were included in the study, of which 25 were diagnosed in the second and 10 in the third trimester. One fetus underwent intrauterine demise and TOP was carried out in 34 cases. The halo sign was detected on ultrasound in 32 (91%) fetuses (23 in the second trimester and nine in the third), and it was an isolated sonographic finding in six of these cases, all in the second trimester. The median gestational age at ultrasound diagnosis of the halo sign was similar between fetuses in which this was an isolated and those in which it was a non-isolated CNS finding (22.6 vs 24.4 weeks; P = 0.10). In fetuses with a non-isolated halo sign, the severity of additional ultrasound findings was not associated with the trimester at diagnosis, except for microencephaly, which was more frequent in the second compared with the third trimester (10/18 (56%) vs 1/8 (13%); P = 0.04). With respect to histopathological findings, ventriculitis was observed in all fetuses with an isolated halo sign, but this was mild (Grade 1) in the majority of cases (4/6 (67%)). Extensive ventriculitis (Grade 2 or 3) was more frequent in fetuses with a non-isolated halo sign (21/26 (81%)) and those without a periventricular echogenic halo (2/3 (67%); P = 0.032). All fetuses with an isolated halo sign were classified as histopathological Stage I with no signs of brain calcifications, white-matter necrosis or cortical injury. On the other hand, 25/26 fetuses with a non-isolated halo sign and all three fetuses without a periventricular echogenic halo showed severe brain lesions and were categorized as histopathological Stage II. Among fetuses with a non-isolated halo, histological brain lesions did not progress with gestational age, although white-matter necrosis was more frequent, albeit non-significantly, in fetuses diagnosed in the second vs the third trimester (10/15 (67%) vs 3/11 (27%); P = 0.06). CONCLUSIONS: In CMV-infected fetuses, an isolated periventricular echogenic halo was observed only in the second trimester and was associated with mild ventriculitis without signs of white-matter calcifications or necrosis. When considering pregnancy continuation, detailed neurosonographic follow-up complemented by MRI examination in the early third trimester is indicated. The prognostic significance of the halo sign as an isolated finding is still to be determined. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Increasing comparability among coral bleaching experiments.

Coral bleaching is the single largest global threat to coral reefs worldwide. Integrating the diverse body of work on coral bleaching is critical to understanding and combating this global problem. Yet investigating the drivers, patterns, and processes of coral bleaching poses a major challenge. A recent review of published experiments revealed a wide range of experimental variables used across studies. Such a wide range of approaches enhances discovery, but without full transparency in the experimental and analytical methods used, can also make comparisons among studies challenging. To increase comparability but not stifle innovation, we propose a common framework for coral bleaching experiments that includes consideration of coral provenance, experimental conditions, and husbandry. For example, reporting the number of genets used, collection site conditions, the experimental temperature offset(s) from the maximum monthly mean (MMM) of the collection site, experimental light conditions, flow, and the feeding regime will greatly facilitate comparability across studies. Similarly, quantifying common response variables of endosymbiont (Symbiodiniaceae) and holobiont phenotypes (i.e., color, chlorophyll, endosymbiont cell density, mortality, and skeletal growth) could further facilitate cross-study comparisons. While no single bleaching experiment can provide the data necessary to determine global coral responses of all corals to current and future ocean warming, linking studies through a common framework as outlined here, would help increase comparability among experiments, facilitate synthetic insights into the causes and underlying mechanisms of coral bleaching, and reveal unique bleaching responses among genets, species, and regions. Such a collaborative framework that fosters transparency in methods used would strengthen comparisons among studies that can help inform coral reef management and facilitate conservation strategies to mitigate coral bleaching worldwide.

Family and household structure are associated with acute type 1 diabetes complications: results of cross-sectional analyses.

AIM: To examine the association of family/household structure with short-term diabetes complications in adolescents and emerging adults with early-onset type 1 diabetes in more detail. METHODS: Data on 1690 11-21-year-olds with type 1 diabetes were used to estimate associations of family/household structure with self-reported severe hypoglycaemia, hospitalizations for severe hypoglycaemia or diabetic ketoacidosis, applying multiple negative binomial regression. RESULTS: Compared with living with both biological parents living with a single mother was associated with an increased rate of hospitalizations for ketoacidosis (incidence rate ratio 1.71, 95% CI 1.00-2.82). Incidence rate ratio of hospitalizations for ketoacidosis was similar (1.67, 95% CI 0.91-3.07) if the mother lived with a partner, however, hypoglycaemia-related hospitalizations increased (3.66, 95% CI 1.54-8.71). Participants living with a single father had 4.43 (95% CI 1.30-15.05) /10.42 (95% CI 1.55-70.22) times higher rates of severe hypoglycaemia and related hospitalizations, while living with a father and his partner was associated with an increased incidence rate ratio of hospitalizations for ketoacidosis (3.48, 95% CI 0.96-12.63) compared with living with both biological parents. CONCLUSIONS: Findings of our exploratory analyses point to different self-reported diabetes outcomes depending on the family/household structure. If confirmed in future studies, they may help to identify young people with diabetes at risk of short-term diabetes complications.

Diabetes distress in young adults with early-onset Type 1 diabetes and its prospective relationship with HbA1c and health status.

AIM: This study aimed to determine cross-sectional relationships between diabetes distress and health-related variables, and prospective associations between diabetes distress and future glycaemic control (HbA1c ) and health status among young adults with early-onset Type 1 diabetes. METHODS: Data were collected from a nationwide cohort study of adults whose Type 1 diabetes onset occurred from 0 to 4 years of age during 1993-2002. Questionnaire surveys were conducted in 2012-2013 and 2015-2016 (N = 584). Diabetes distress was assessed via the Problem Areas in Diabetes (PAID) scale (0-100 points), depressive symptoms via the Patient Health Questionnaire-9 (PHQ-9) and health status via the 12-Item Short Form Health Survey (SF-12) questionnaire. Multivariable linear regression analyses were applied to cross-sectional and longitudinal data. RESULTS: In the cross-sectional analyses, higher PAID scale total scores (representing higher distress levels) were observed in women than in men and in participants with more severe depressive symptoms. PAID scores were lower in individuals with better physical and mental health. A 1 mmol/mol increase in HbA1c was associated with a 0.28-point increase [95% confidence interval (95% CI) 0.20, 0.36] in diabetes distress. In longitudinal analyses adjusting for age, sex, socio-economic index and HbA1c at baseline, a 10-point higher PAID score at baseline was associated with a 1.82 mmol/mol higher HbA1c level (95% CI 0.43, 3.20) and a 2.48-point lower SF-12 mental health score (95% CI -3.55, -1.42) three years later. CONCLUSIONS: The cross-sectional and longitudinal analyses results suggest that diabetes distress impairs health-related outcomes in young adults with early-onset diabetes.

Correction to: Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

The authors regret that acknowledgment for Dr. Adrian Marchetti was omitted from the manuscript. The correct acknowledgment is written below.

Coral Symbiodinium Community Composition Across the Belize Mesoamerican Barrier Reef System is Influenced by Host Species and Thermal Variability.

Reef-building corals maintain a symbiotic relationship with dinoflagellate algae of the genus Symbiodinium, and this symbiosis is vital for the survival of the coral holobiont. Symbiodinium community composition within the coral host has been shown to influence a coral's ability to resist and recover from stress. A multitude of stressors including ocean warming, ocean acidification, and eutrophication have been linked to global scale decline in coral health and cover in recent decades. Three distinct thermal regimes (highTP, modTP, and lowTP) following an inshore-offshore gradient of declining average temperatures and thermal variation were identified on the Belize Mesoamerican Barrier Reef System (MBRS). Quantitative metabarcoding of the ITS-2 locus was employed to investigate differences and similarities in Symbiodinium genetic diversity of the Caribbean corals Siderastrea siderea, S. radians, and Pseudodiploria strigosa between the three thermal regimes. A total of ten Symbiodinium lineages were identified across the three coral host species. S. siderea was associated with distinct Symbiodinium communities; however, Symbiodinium communities of its congener, S. radians and P. strigosa, were more similar to one another. Thermal regime played a role in defining Symbiodinium communities in S. siderea but not S. radians or P. strigosa. Against expectations, Symbiodinium trenchii, a symbiont known to confer thermal tolerance, was dominant only in S. siderea at one sampled offshore site and was rare inshore, suggesting that coral thermal tolerance in more thermally variable inshore habitats is achieved through alternative mechanisms. Overall, thermal parameters alone were likely not the only primary drivers of Symbiodinium community composition, suggesting that environmental variables unrelated to temperature (i.e., light availability or nutrients) may play key roles in structuring coral-algal communities in Belize and that the relative importance of these environmental variables may vary by coral host species.

Evolution of sex chromosomes prior to speciation in the dioecious Phoenix species.

Understanding the driving forces and molecular processes underlying dioecy and sex chromosome evolution, leading from hermaphroditism to the occurrence of male and female individuals, is of considerable interest in fundamental and applied research. The genus Phoenix, belonging to the Arecaceae family, consists uniquely of dioecious species. Phylogenetic data suggest that the genus Phoenix has diverged from a hermaphroditic ancestor which is also shared with its closest relatives. We have investigated the cessation of recombination in the sex-determination region within the genus Phoenix as a whole by extending the analysis of P. dactylifera SSR sex-related loci to eight other species within the genus. Phylogenetic analysis of a date palm sex-linked PdMYB1 gene in these species has revealed that sex-linked alleles have not clustered in a species-dependent way but rather in X and Y-allele clusters. Our data show that sex chromosomes evolved from a common autosomal origin before the diversification of the extant dioecious species.

Mapping coral calcification strategies from in situ boron isotope and trace element measurements of the tropical coral Siderastrea siderea.

Boron isotopic and elemental analysis of coral aragonite can give important insights into the calcification strategies employed in coral skeletal construction. Traditional methods of analysis have limited spatial (and thus temporal) resolution, hindering attempts to unravel skeletal heterogeneity. Laser ablation mass spectrometry allows a much more refined view, and here we employ these techniques to explore boron isotope and co-varying elemental ratios in the tropical coral Siderastrea siderea. We generate two-dimensional maps of the carbonate parameters within the calcification medium that deposited the skeleton, which reveal large heterogeneities in carbonate chemistry across the macro-structure of a coral polyp. These differences have the potential to bias proxy interpretations, and indicate that different processes facilitated precipitation of different parts of the coral skeleton: the low-density columella being precipitated from a fluid with a carbonate composition closer to seawater, compared to the high-density inter-polyp walls where aragonite saturation was ~ 5 times that of external seawater. Therefore, the skeleton does not precipitate from a spatially homogeneous fluid and its different parts may thus have varying sensitivity to environmental stress. This offers new insights into the mechanisms behind the response of the S. siderea skeletal phenotype to ocean acidification.

A Molecular Reporter for Monitoring Autophagic Flux in Nervous System In Vivo.

The relevance of autophagy in neuronal health has been extensively reported in a plethora of conditions affecting the nervous system, such as neurodegenerative diseases, cancer, diabetes, and tissue injury, where altered autophagic activity may contribute to the pathological process. Autophagy is a dynamic pathway involving the formation of a membrane surrounding and enclosing cargoes that are delivered to lysosomal compartments for degradation. Cargoes can include large protein aggregates, organelles, or even pathogens. Traditionally, autophagy assessment relies on the measurement of LC3-II protein levels or the visualization of LC3-positive puncta. However, these approaches represent a static measurement of autophagy markers, making difficult the dissection of the actual changes in the autophagy process (activation, inhibition, or no effects), due to the dynamic regulation of LC3 viral levels. To circumvent this limitation, we previously developed an adeno-associated vector (AAV) to deliver a molecular autophagy sensor to the neuronal compartment in vivo. Here, we describe the detailed design and methods to use an engineered AAV harboring the monomeric tandem mCherry-GFP-LC3 to determine autophagic fluxes in the nervous system. Key methodological details to succeed in the use of this reporter are provided.

ALPPS monosegmento, una variante de hepatectomía extrema para resección de metástasis hepáticas de cáncer colorrectal

La resección quirúrgica con márgenes negativos de las metástasis hepáticas de cáncer colorectal, representa la única opción de tratamiento con potencial curativo, sin embargo, el 85% de estos pacientes son considerados irresecables a la evaluación inicial, ya sea por número, tamaño y localización de las metástasis o por un remanente hepático futuro insuficiente. ALPPS es una técnica quirúrgica compleja, que permite en dos tiempos operatorios, la resección de extensas porciones de parénquima hepático tras un periodo de incremento volumétrico del remanente, que alcanza el 80% en un periodo de 9 días, lo que supera ampliamente a otras técnicas como la embolización/ligadura portal preoperatoria. Pese a cuestionamientos iniciales relativos a la morbimortalidad asociada, la significativa ganancia de masa hepatocelular lograda con ALPPS, ha permitido el tratamiento exitoso de pacientes con alta carga tumoral metastásica hepática, tensionando principios fundamentales clásicamente considerados para la realización de hepatectomías mayores en forma segura. El objetivo de este trabajo es presentar la experiencia inicial con la aplicación de la técnica de ALPPS llevado al extremo de dejar un remanente hepático constituido por un único segmento.

R0 resection of colorectal liver metastases is the main curative treatment option; however, 85% of patients are considered initially unresectable, either due to number, size and location of metastases or insufficient future liver remnant. ALPPS is a complex surgical technique, which allows, in two operative times, the resection of extensive portions of liver parenchyma after a period of volumetric remnant increase, which reaches 80% in 9 days, far exceeding other techniques as well as preoperative portal embolization / ligation. Despite initial doubts regarding the associated morbidity and mortality, the significant gain in hepatocellular mass achieved with ALPPS has allowed the successful treatment of patients with high hepatic metastatic tumor burden, questioning fundamental principles classically considered for safely performing major hepatectomies. The aim of this article is to show the initial experience with the ALPPS technique application taken to the extreme of leaving a liver remnant made up of a single segment.

Meal composition is a determinant of lispro-induced hypoglycemia in IDDM.

OBJECTIVE: Lispro is a newly FDA-approved analog of human insulin that will be widely used in patients with IDDM. This insulin, however, may have an increased potential for hypoglycemia because of its very rapid subcutaneous absorption, especially in a setting of decreased carbohydrate intake. Using a short-term prospective randomized parallel group-study design, we studied the incidence of hypoglycemia when lispro was given before breakfast compared with regular human insulin. Since carbohydrate intake is a determinant of postprandial glycemia, we administered three isocaloric meals characterized by low, average, and high carbohydrate content. RESEARCH DESIGN AND METHODS: Two groups of six IDDM subjects were randomized to receive 0.15 U/kg of lispro or regular human insulin subcutaneously before the ingestion of three 500-kcal breakfast meals of differing carbohydrate content on separate days. Lispro was administered at mealtime, and regular insulin was administered 30 min before mealtime. RESULTS: Postprandial plasma glucose concentrations were decreased in the lispro group compared with the regular-insulin group for all three meal types (P < 0.05), and hypoglycemia developed more frequently and rapidly in the lispro group, compared with the regular-insulin group by survival analysis. Additionally, peak insulin concentrations were higher (P < 0.001) and peaked more rapidly (P < 0.05) in the lispro group, compared with the regular-insulin group. CONCLUSIONS: We conclude that lispro has a tendency for early postprandial hypoglycemia compared with regular insulin in the setting of reduced carbohydrate intake. This fact should be told to patients who decide to switch from regular insulin to lispro. Health care professionals should instruct their IDDM patients to monitor glucose levels frequently after switching to lispro since adjustments in their carbohydrate intake and/or their lispro dosage may be necessary to avoid hypoglycemia.

Cirugía laparoscópica con imagen 3D: indicaciones, resultados y evaluación subjetiva y objetiva de cirujanos participantes / Laparoscopic surgery with 3D image: indications, results and subjective and objective evaluation of participating surgeons

Resumen Introducción El uso del sistema de visión 3D en cirugía laparoscópica puede significar una mejor performance de los procedimientos quirúrgicos de mayor complejidad. Objetivo Reportar las indicaciones, los resultados y la valoración de un grupo de cirujanos de diferentes especialidades en el uso de visión 3D. Materiales y Método: Se analizan las indicaciones quirúrgicas y los resultados subjetivos y objetivos del uso del sistema óptico 3D (n = 155 pacientes) en cirugía laparoscópica compleja. Para evaluación subjetiva se aplicó a una encuesta de percepción cualitativa a los cirujanos participantes tipo Likert. Para la evaluación objetiva, se registran los tiempos quirúrgicos empleados en los diferentes procedimientos efectuados y las complicaciones postoperatorias y se comparan con los pacientes operados con sistema 2D (n = 783 pacientes) en el mismo periodo. Resultados el 70,6% concuerda tener mejor imagen con la técnica 3D, el 64,7% de los cirujanos refieren que se puede reducir el tiempo operatorio, el 58,8% considera que se puede reducir el error quirúrgico, el 92% y 100% respectivamente afirman que el confort del cirujano es mejor con el uso de óptica 3D y que esta técnica es recomendable para los procedimientos complejos. El tiempo operatorio se redujo en algunos procedimientos, especialmente urológicos. No se encontró diferencias sustanciales al comparar los resultados con el uso de sistema 3D versus 2D en cuanto a complicaciones postoperatorias. En la 3D no se encontró mortalidad postoperatoria, probablemente por el menor número de pacientes de ese grupo. Conclusión La laparoscopia 3D posee una buena valoración por los cirujanos que la emplearon, principalmente en calidad de imagen, reducción del tiempo operatorio y confort del cirujano en comparación con la laparoscopía 2D convencional. No se encontró diferencias sustanciales al comparar los resultados con el uso de sistema 3D versus 2D en cuanto a tiempo operatorio ni complicaciones postoperatorias.

Introduction The use of the 3D vision system in laparoscopic surgery can mean better performance in more complex surgical procedures. Aim Report the indications, results and assessment of a group of surgeons of different specialties in the use of 3D vision. Materials and Method Surgical indications and subjective and objective results of the use of 3D optical system in patients (n = 155) submitted to complex laparoscopic surgery are analyzed. Subjective evaluation based on a survey of qualitative perception (Likert) was applied to the participating surgeons. For objective evaluation, the operatory times and postoperative complications were recorded and compared with the results observed with the use of the 2D system (783 patients) in the same period. Results 70.6% agree to have a better image with the 3D technique, 64.7% of surgeons report that the operative time can be reduced, 58.8% consider that it can be reduced the surgical error, 92% and 100% respectively considered that the comfort of the surgeon is better with the use of 3D optics and that this technique is recommended for complex procedures. No substantial differences were found when comparing the results with the use of 3D versus 2D system by the same surgical teams in terms of operative times and postoperative complications. In 3D, postoperative mortality was probably not found due to the lower number of patients in this group. Conclusion 3D laparoscopy has a good evaluation by the surgeons who used it, mainly in image quality, reduction of operative time and comfort of the surgeon compared to conventional 2D laparoscopy. No substantial differences were found when comparing the results with the use of 3D versus 2D system in terms of operative times or postoperative complications.

Diagnostic gene expression biomarkers of coral thermal stress.

Gene expression biomarkers can enable rapid assessment of physiological conditions in situ, providing a valuable tool for reef managers interested in linking organism physiology with large-scale climatic conditions. Here, we assessed the ability of quantitative PCR (qPCR)-based gene expression biomarkers to evaluate (i) the immediate cellular stress response (CSR) of Porites astreoides to incremental thermal stress and (ii) the magnitude of CSR and cellular homeostasis response (CHR) during a natural bleaching event. Expression levels largely scaled with treatment temperature, with the strongest responses occurring in heat-shock proteins. This is the first demonstration of a 'tiered' CSR in a coral, where the magnitude of expression change is proportional to stress intensity. Analysis of a natural bleaching event revealed no signature of an acute CSR in normal or bleached corals, indicating that the bleaching stressor(s) had abated by the day of sampling. Another long-term stress CHR-based indicator assay was significantly elevated in bleached corals, although assay values overall were low, suggesting good prospects for recovery. This study represents the first step in linking variation in gene expression biomarkers to stress tolerance and bleaching thresholds in situ by quantifying the severity of ongoing thermal stress and its accumulated long-term impacts.

Measurement of autophagy flux in the nervous system in vivo.

Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings.

Opciones terapéuticas actuales en el manejo de la coledocolitiasis asociada a colecistolitiasis / Current therapeutic options in the management of choledocholithiasis associated with cholecyllithiasis

The term Choledocholithiasis refers to the presence of biliary stones in the extrahepatic bile ducts, which are found in 5 to 10% of patients undergoing cholecystectomy for gallstones. Nowadays, with the adoption of the laparoscopic cholecystectomy(LC) as a standard, multiple minimally invasive treatment options for bile duct stones are feasible, with no consensus to date on the procedure of choice. The two stage endoscopic techniques involve the use of Endoscopic Retrograde Cholangiopancreatography(ERCP) before or after performing a LC, which has the main advantage of separating the bile duct procedure from the LC. However, the need for two separate anesthesia times, the possibility of blank or failed ERCP, and the chance for calculi migration between procedures increase the length of hospital stay and associated costs. The single stage procedures include the Laparoscopic Bile Duct Exploration (LBDE), and more recently, the performance of a laparoscopy guided intraoperative ERCP(Rendez Vous). The LBDE, when performed by an experienced surgical team, is an effective and safe technique. Nonetheless, it is considered a technically demanding procedure, whose results cannot be extrapolated to the general surgical community. Recently, the Rendez Vous has become a treatment alternative that simplifies both the surgical and the endoscopic procedures, decreases morbidity, and requires a single anesthesia time. On the downside, Rendez Vous technique involves complex operating room (OR) logistics, requiring both a trained surgical and endoscopic team at the same time. (AU)

Cáncer temprano de la vesícula biliar: tratamiento y sobrevida a largo plazo / Survival of patients with early gallbladder cancer

Background: Advanced gallbladder cancer has a high mortality. Therefore, this tumor should be diagnosed and treated in early stages. Aim: To analyze the survival rates of patients with an early gallbladder cancer. Material and Methods: Retrospective analysis of medical records of patients with early gallbladder cancer diagnosed until 2003. From that date, all patients with gastrointestinal cancer were registered in a prospective record. Patients with early gallbladder cancer defined as Tis (Carcinoma in situ), T1A (Tumor invades lamina propia) and T1B (Tumor invades muscular layer), were included in this analysis. Results: Eighty patients aged 31 to 87 years (74 percent women) were analyzed. The diagnosis was made during surgery in two patients and during the pathological study in the rest. All 24 patients with Tis tumors were alive after 96 months of follow up. Only one of 16 patients with T1A tumors died of unknown causes. Among the 40 patients with T1B tumors, 24 were re-operated and survival was over 90 percent. Conclusions: This group of patients with early gallbladder cancer had a five years survival over 90 percent. In patients with muscle involvement does not seem necessary to extend the surgery.

Introducción: Dada la elevada mortalidad del cáncer vesicular en etapas avanzadas, lo ideal es diagnosticarlo y tratarlo en una etapa temprana de la enfermedad. Objetivo: Analizar la sobrevida de pacientes con carcinoma temprano de la vesícula biliar y el impacto de una eventual re-operación. Material y Método: Se incluyen en el estudio 80 pacientes con cáncer temprano, siendo la mayoría (65 pacientes) parte de un estudio prospectivo desde mayo de 2004 hasta febrero de 2013. Fueron divididos en 3 grupos: a) carcinoma in situ T1s; b) carcinoma mucoso T1a; c) carcinoma muscular I1b. Seguimiento en el 100 por ciento de los casos. Resultados: El diagnóstico de carcinoma temprano se hizo en 2 pacientes durante la cirugía, en el resto fue un hallazgo del estudio histo-patológico. Los 24 pacientes con carcinoma in situ estaban vivos a los 96 meses de seguimiento. De los 16 pacientes con carcinoma mucoso, sólo 1 (6 por ciento) falleció sin conocerse la causa. Entre los 40 pacientes con cáncer muscular, hubo 24 que no se reoperaron y 16 reoperados. Los resultados anatomo patológicos fueron similares y la sobrevida de ambos grupos fue superior al 90 por ciento. Conclusión: En pacientes con carcinoma de la vesícula biliar in situ y hasta la mucosa, la colecistectomía logra sobrevida mayor del 95 por ciento a largo plazo. En pacientes con carcinoma muscular, ésta se acompaña de una sobrevida mayor a 90 por ciento a 5 años y no parece justificarse ampliar la cirugía.

Resección de metástasis hepáticas en cáncer gástrico: experiencia preliminar / Excision of liver metastases in gastric cancer: preliminary experience

Introduction: The benefits of liver metastasis excision in gastric cancer are not clearly demonstrated. Aim: To communicate preliminary experience concerning excision of hepatic metastasis and simultaneously performing gastrectomy in patients with gastric cancer. Material and Methods: In a prospective study, 3 of 397 patients treated for gastric cancer that met certain criteria, underwent hepatic metastasis excision. Results: Three patients with gastric cancer and liver metastases. A 58 years old male in whom one liver metastasis was excised and two were treated with radiofrequency ablation, who is alive after 40 months of follow up. A 26 years old female subjected to the excision of one liver metastasis. Eight months later, the lesion relapsed and a right hepatectomy was carried out. The patient died after 19 months of follow up. A 56 years old female subjected to the excision of one liver metastasis, who died 9 months later...

Introducción: En pacientes con cáncer gástrico y metástasis hepáticas sincrónicas, la posibilidad de tener sólo 1 a 3 metástasis es cerca de 2 por ciento, ya que, en la inmensa mayoría, corresponde a una enfermedad sistémica. Objetivos: Comunicar una experiencia preliminar que se refiere a realizar metastasectomía hepática simultánea a la gastrectomía en pacientes con cáncer gástrico. Material y Método: En estudio prospectivo, 3 de 397 pacientes tratados por cáncer gástrico que cumplían algunos criterios, fueron sometidos además a metatasectomía hepática. Resultados: Se incluye a 3 pacientes, 2 con sólo metástasis hepáticas y 1 paciente con metástasis hepáticas y peritoneales, en los que se realizó metastasectomía. La evolución postoperatoria en los 3 fue sin incidentes. En 2 pacientes la metástasis era única y en otro se realizó además radiofrecuencia de 3 pequeñas metástasis, siendo el único paciente vivo a 40 meses; los otros fallecen a los 19 y 9 meses...

Causas de mortalidad por colecistectomía tradicional y laparoscópica 1991-2010 / Mortality associated with open and laparoscopic cholecystectomy

Background: Laparoscopic cholecystectomy is nowadays the standard surgical treatment for cholelithiasis. Aim: To determine surgical mortality of laparoscopic cholecystectomy as compared with the open procedure. Material and Methods: Review of medical records of all patients subjected to open or laparosco-pic surgery in a surgical service of a clinical hospital, in a period of 20 years. Results: The records of 26.441 patients were reviewed. The figures for overall, open and laparoscopic surgery mortality were 0.16, 0.39 and 0.07 percent respectively. Only two of the 43 deceased patients, died as a direct complication of the surgical procedure. In the rest, the causes of mortality were underlying severe medical conditions. Conclusions: La-paroscopic cholecystectomy has a very low mortality that depends mostly on underlying medical conditions and advanced age.

Introducción: La colecistectomía laparoscópica se ha convertido en el gold standard de la cirugía biliar y se emplea masivamente en todo Chile. Objetivos: Determinar la mortalidad operatoria en 4 períodos de 5 años de la colecistectomía laparoscópica comparada con la colecistectomía tradicional. Material y Método: Se incluyó a todos los pacientes sometidos a colecistectomía, ya sea laparotómica o laparoscópica, entre enero de 1991 y diciembre de 2010 (20 años). Se analizó las causas de mortalidad, el grupo etario en que ocurrió y el tipo de abordaje quirúrgico. Resultados: Se operaron un total de 26.441 pacientes, con un promedio de 1.322 operados por año. La mortalidad global de la colecistectomía laparotómica fue de 0,39 por ciento y de la laparoscópica de 0,07 por ciento, con un promedio general de 0,16 por ciento. Las principales causas de mortalidad fueron patologías médica severas. Sólo 2 pacientes de los 43 fallecidos (5 por ciento) tuvieron una complicación directamente derivada de la cirugía como causa de la mortalidad. Conclusiones: La colecistectomía laparoscópica es una operación de muy baja mortalidad (7 de 10.000 operados). Esta complicación se presenta principalmente en pacientes con grave patología biliar, de edad avanzada y con múltiples complicaciones médicas.