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The L-type calcium channel (LTCC) is an important determinant of cardiac contractility. Therefore, changes in LTCC activity or protein levels could be expected to affect cardiac function. Several studies describing LTCC regulation are available, but only a few examine LTCC protein stability. Polycystin-1 (PC1) is a mechanosensor that regulates heart contractility and is involved in mechanical stretch-induced cardiac hypertrophy. PC1 was originally described as an unconventional Gi/o protein-coupled receptor in renal cells. We recently reported that PC1 regulates LTCC stability in cardiomyocytes under stress; however, the mechanism underlying this effect remains unknown. Here, we use cultured neonatal rat ventricular myocytes and hypo-osmotic stress (HS) to model mechanical stretch. The model shows that the Cavß2 subunit is necessary for LTCC stabilization in cardiomyocytes during mechanical stretch, acting through an AKT-dependent mechanism. Our data also shows that AKT activation depends on the G protein-coupled receptor activity of PC1, specifically its G protein-binding domain, and the associated Gßγ subunit of a heterotrimeric Gi/o protein. In fact, over-expression of the human PC1 C-terminal mutant lacking the G protein-binding domain blunted the AKT activation-induced increase in Cav1.2 protein in cardiomyocytes. These findings provide novel evidence that PC1 is involved in the regulation of cardiac LTCCs through a Gißγ-AKT-Cavß2 pathway, suggesting a new mechanism for regulation of cardiac function.

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Background: Age plays a crucial role in women fertility and is related with a decreased oocyte quality and quantity. The evidence for this asseveration comes from data obtained in infertile women. However there is a paucity of studies in patients with proven fertility evaluating ovarian reserve and its decline with time. Aim: To measure antral follicle count (AFC) in probed fertile patients and to create a distribution chart based on variables that may affect its natural decline. Material and Methods: Observational prospective study. A transvaginal ultrasound was made between menstrual cycle days 3 and 5, evaluating AFC in 100 patients, followed during a year. Results: Median antral follicle count media was 14.5 (interval 3 to 26). There was a lineal decline of AFC with age. Women with hypertension and type 2 diabetes mellitus had significantly less follicles. However, a multiple regression analysis showed that only women's age was a significant predictor of AFC (R2 = 0.84). Conclusions: There was a lineal relationship between AFC and age in women with probed fertility.

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Background: Live Donor Laparoscopic Nephrectomy (LDLN) has substantial benefits when compared with open nephrectomy such as shorter hospital stay, prompt return to work, less post-operative pain, better cosmetic results, less blood loss and less surgical wound infections. It is the mode of choice for safely harvesting a kidney for organ transplantation. Aim: To describe the surgical results of LDLN in a pioneer renal transplant center in Chile. Material and Methods: Review of clinical records of 75 subjects aged 27 to 60 years (37 males) subjected to a LDLN in a public hospital between 1998 and 2013. Information about clinical and surgical data and perioperative complications was retrieved. Results: No subject died. All kidneys were satisfactorily implanted in their receptors. The mean operative time was 116 minutes. Mean hospital stay was 1.6 days, warm ischemia time was 6.8 minutes, and cold ischemia time was 31.5 minutes. Operative adverse events occurred in 8 percent. The conversion and reoperation rates were 4 and 1.3 percent, respectively. Among receptors, 1.5 percent evolved with Acute Tubular Necrosis and 2.2 percent required graft excision. Conclusions: LDLN is a safe and pioneering surgical technique in Chile. Its results are satisfactory and comparable to those obtained with classic lumbotomy.

Introducción: El trasplante renal es en la actualidad el tratamiento de elección de la Insuficiencia Renal Crónica Terminal. La Nefrectomía Laparoscópica del Donante Vivo (NLDV) tiene ventajas sustanciales en relación a la Nefrectomía Clásica. Entre estas se destacan una menor estancia hospitalaria, pronto regreso a la actividad laboral, disminución del dolor post-operatorio, mejores resultados cosméticos, menor pérdida de volumen sanguíneo y una disminución de infecciones de heridas operatorias, consolidándose como la primera prioridad como forma de obtener un órgano para trasplante renal. El presente trabajo tiene como objetivo mostrar la casuística y complicaciones en el Hospital Barros Luco-Trudeau (HBLT), como centro pionero en NLDV en nuestro país. Material y Método: Estudio retrospectivo de corte transversal. Se realiza una revisión de registros clínicos de 75 NLDV realizadas entre 1998-2013, seleccionando datos demográficos, clínicos y quirúrgicos de donantes y receptores, con un especial énfasis en relación a complicaciones peri-operatorias. Resultados: Sin mortalidad. Todos los riñones fueron implantados satisfactoriamente en sus respectivos receptores. Cirugía con duración promedio de 116 min, estadía hospitalaria promedio de 1,6 días, isquemia caliente promedio de 6,8 min e isquemia fría promedio de 31,5 min. Incidentes operatorios 8 por ciento y 4 por ciento conducentes a conversión. Tasa de reoperación de 1,3 por ciento. En cuanto a receptores, un 1,5 por ciento desarrolla Necrosis Tubular Aguda. 2,2 por ciento requiere transplantectomía. Discusión: La NLDV representa una técnica segura, que ha llegado a constituir el 100 por ciento de las nefrectomías de donantes vivos realizadas durante los últimos tres años. Los resultados son satisfactorios y plenamente comparables a los resultados obtenidos por lumbotomía clásica y de otros centros de alto volumen laparoscópico a nivel internacional.

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Infectious salmon anemia virus (ISAV) infection is a constant major threat to farmed and wild Atlantic salmon worldwide. Many epidemics have recently been reported in the most important salmon farming regions of the world, including Chile (2007-2009), where ISAV generated the most important disease and economic crisis in history of the salmon industry of the country. The spread of ISAV within a region is most likely by local or neighborhood spread from an infected farm; however, there is evidence that anthropogenic activities, such as movement of live or harvested fish or their byproduct, may have played a more important role than environmental or passive transmission in the 2007-2009 outbreak. Atlantic salmon farms (n=421) were retrospectively followed from stocking to harvesting in southern Chile at the time of the ISAV epidemic (2007-2009). The effect of husbandry and spatial risk factors, in addition to contact-network risk factors, which were obtained from the social network analyses, on time to first ISAV infection was estimated using a multivariable Cox proportional hazards model. Five variables were retained in the final fitted model: co-existing multiple generations on a farm (hazard ratio [HR]=2.585), mean smolt weight at stocking greater than 120g (HR=1.165), farm area (perkm(2)) (HR=1.005), and increased number of shipments entering a farm, i.e. the farm input degree (HR=1.876) were associated with reduced time to infection; whereas time-to-infection was longer for farms located farther from an ongoing ISAV outbreak (HR=0.943). It was demonstrated that movements of latently infected fish resulted in approximately 7 outbreaks, and potentially explain about 6% of the total number of cases during the epidemic. Results from this study provide new information about the mechanisms of spread of ISAV in one the largest documented ISAV epidemics in the world. Findings may be used to support the design and implementation of risk-based surveillance and control programs that may help to prevent, detect and control future ISAV outbreaks.

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Spread of infectious salmon anemia virus (ISAV) at the cage level was quantified using a subset of data from 23 Atlantic salmon Salmo salar farms located in southern Chile. Data collected from official surveillance activities were systematically organized to obtain detailed information on infectious salmon anemia (ISA) outbreaks. Descriptive statistics for outbreak duration, proportion of infected fish, and time to secondary infection were calculated to quantify the magnitude of ISAV incursions. Linear and multiple failure time (MFT) regression models were used to determine factors associated with the cage-level reproduction number (Rc) and hazard rate (HR) for recurrent events, respectively. In addition, the Knox test was used to assess if cage-to-cage transmissions were clustered in space and time. Findings suggest that within farms, ISA outbreaks, on average, lasted 30 wk (median = 26 wk, 95% CI = 24 to 37 wk) and affected 57.3% (95% CI = 47.7 to 67.0%) of susceptible cages. The median time to secondarily diagnosed cages was 23 d. Occurrence of clinical ISAV outbreaks was significantly associated with increased Rc, whereas increased HR was significantly associated with clinical outbreaks and with a large number of fish. Spatio-temporal analysis failed to identify clustering of cage cases, suggesting that within-farm ISAV spread is independent of the spatial location of the cages. Results presented here will help to better understand ISAV transmission, to improve the design of surveillance programs in Chile and other regions in which salmon are intensively farmed, and to examine the economic impact of ISAV and related management strategies on various cost and demand shifting factors.

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Infectious salmon anaemia virus (ISAV) caused a large epidemic in farmed Atlantic salmon in Chile in 2007-2009. Here, we assessed co-infection patterns of ISAV and sea lice (SL) based on surveillance data collected by the fish health authority. ISAV status and SL counts in all Atlantic salmon farms located in the 10th region of Chile were registered monthly from July 2007 through December 2009. Each farm was categorized monthly according to its ISAV and SL status. A multinomial time-space scan test using a circular window was applied to identify disease clusters, and a multivariate regression model was fitted to quantify the association between disease-clustering and farm-management factors. Most of the identified clusters (9/13) were associated with high SL burdens. There were significant associations (P < 0.05) between management factors and ISAV/SL status. Areas in which good management practices were associated with a reduced disease risk were identified. The findings of this study suggest that certain management practices can effectively reduce the risk of SL and ISAV in the face of an epidemic and will be helpful towards creating an effective disease control programme in Chile.

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An epidemic of infectious salmon anemia virus (ISAV) has greatly impacted salmon production in Chile with devastating social and economic consequences. The epidemic is analyzed here and is likely the largest ISAV outbreak reported affecting one of the most productive regions for salmon farming activities in the world. After re-emerging in 2007, ISAV rapidly expanded the following two years, both in magnitude and geographic range, affecting about 65% and 50% of salmon farms located at the 10th and 11th regions of Chile, respectively. A useful metric for the control of infectious diseases that quantifies the progression of an epidemic is the reproduction number at the farm level (R(f)), which describes the mean number of secondary cases generated by an infectious farm. The parameter in this study was estimated for individual farms (R(fi)), specific phases (R(tf)), and for the entire epidemic (R(f)) by using several analytical approaches based on the characterization of the epidemic curves for the two regions. For the initial spread and the epidemic growth phase, initial and intrinsic growth rates were used to estimate R(tf). In addition, two approaches (epidemic final size and nearest neighbor analyses) were used to obtain an individual (R(fi)) and overall estimate of R(f) for the complete epidemic. In general, two distinct regional patterns of spread were identified. In the 10th region, after an explosive initial spread of ISAV in which R(tf) reached 12.0-16.9, a smaller epidemic growth of 1.6≤R(tf)≥2.5 and a final burnout with R(tf)<1 were observed. For the 11th region, R(tf) only reached 2.4 during the initial spread phase, ranged from 1.6≤R(tf)≥4.4 during the epidemic growth phases and ended when R(tf) was <1.0. The epidemic was characterized by clustering of ISAV 'superspreaders' farms i.e., farms with statistically significantly (P<0.047) higher R(fi) values. Distances between pairs of infected farms were statistically significantly (P=0.003) shorter in the 10th compared to the 11th region. Overall, R(f) ranged from 1.6 to 2.5 and 1.3 to 1.7 in the 10th and 11th regions, respectively. Our findings suggest that control efforts were able to protect 38-60% and 23-41% of the farms in the 10th and 11th regions, respectively, and may have resulted in the epidemic not spreading further. In addition, control strategies in highly populated areas using a control zone of at least 10km radius may be more effective than the 5km zone recommended by the World Animal Health Organization.

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El desarrollo y uso masivo de técnicas de fecundación asistida desde hace 30 años ha permitido el nacimiento de más de 3 millones de niños en el mundo; sin embargo, estos procedimientos no están exentos de riesgos. La complicación más frecuente es el embarazo múltiple determinado por el desarrollo de múltiples folículos en la inseminación intrauterina y la transferencia de 2 ó más embriones en la fecundación in-vitro. El síndrome de hiperestimulación ovárica constituye una complicación menos frecuente, pero potencialmente grave para la cual detallamos las estrategias de prevención y manejo clínico. Se discuten además las complicaciones derivadas de la aspiración folicular tales como hemorragia e infección entre otras.

The widespread use of fertility treatments such as in-vitro fertilization has determined the birth of more than 3 million babies worldwide, however, these procedures can derive into medical complications. The most frequent complication of assisted reproductive techniques is multiple pregnancy. Single embryo transfer has been avdocated as the best strategy to prevent this complication. Ovarian hyperstimulation syndrome constitutes a life threathening complication of ovarian stimulation. Detailed information on prevention and treatment strategies are given. Other complications after oocyte retrieval such as bleeding and infection are also discussed.

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Our objective was to establish which is the best sperm retrieval technique in non-obstructive azoospermia based on the available evidence. To date, no randomized controlled trial has compared the efficiency of these strategies and thus current recommendations are based on cumulative evidence provided by descriptive, observational and controlled studies. Three outcome measures were assessed for the sperm retrieval techniques: sperm retrieval rate (SRR), complications and live birth rate. Twenty-four descriptive studies reporting on the results of testicular sperm extraction (TESE) were encountered. Seven controlled studies that compared microdissection (MD) TESE with conventional TESE and seven controlled studies comparing fine needle testicular aspiration (FNA) with TESE were identified. The mean SRR for TESE was 49.5% (95% CI 49.0-49.9). TESE with multiple biopsies results in a higher SRR than FNA especially in cases of Sertoli-cell-only (SCO) syndrome and maturation arrest. Current evidence suggests that MD performs better than conventional TESE only in cases of SCO where tubules containing active focus of spermatogenesis can be identified. MD appears to be the safest technique regarding post-operative complications followed by FNA. Only three studies could be identified concerning the influence of the sperm retrieval technique on clinical pregnancy and live birth rate, hence no definitive conclusions can be made. However, so far there appears to be no impact of the technique itself on success rates.

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