Roles of binding elements, FOXL2 domains, and interactions with cJUN and SMADs in regulation of FSHβ.

We previously identified FOXL2 as a critical component in FSHβ gene transcription. Here, we show that mice deficient in FOXL2 have lower levels of gonadotropin gene expression and fewer LH- and FSH-containing cells, but the same level of other pituitary hormones compared to wild-type littermates, highlighting a role of FOXL2 in the pituitary gonadotrope. Further, we investigate the function of FOXL2 in the gonadotrope cell and determine which domains of the FOXL2 protein are necessary for induction of FSHβ transcription. There is a stronger induction of FSHβ reporter transcription by truncated FOXL2 proteins, but no induction with the mutant lacking the forkhead domain. Specifically, FOXL2 plays a role in activin induction of FSHβ, functioning in concert with activin-induced SMAD proteins. Activin acts through multiple promoter elements to induce FSHβ expression, some of which bind FOXL2. Each of these FOXL2-binding sites is either juxtaposed or overlapping with a SMAD-binding element. We determined that FOXL2 and SMAD4 proteins form a higher order complex on the most proximal FOXL2 site. Surprisingly, two other sites important for activin induction bind neither SMADs nor FOXL2, suggesting additional factors at work. Furthermore, we show that FOXL2 plays a role in synergistic induction of FSHβ by GnRH and activin through interactions with the cJUN component of the AP1 complex that is necessary for GnRH responsiveness. Collectively, our results demonstrate the necessity of FOXL2 for proper FSH production in mice and implicate FOXL2 in integration of transcription factors at the level of the FSHβ promoter

Niveles de glucosa y triglicéridos en plasma seminal y motilidad espermática en COBAYOS alimentadas con 10% más en energÍa digestible

The objective the study was to determine the levels of glucose and triglycerides in seminal plasma of 10 guinea pigs, which were fed for a period of 2 months with a diet containing 10% more ED. The level of glucose found in seminal plasma was 11.59 ± 0.5 mg/dL and triglyceride value was 55.95 ± 3.2 mg/dL, while the motility was 97% on average. We conclude that in guinea pigs the levels both glucose and triglycerides were increased by major level of ED in feed, but the spermatic motility was not.El objetivo del presente estudio fue determinar los niveles de los componentes energéticos (glucosa y triglicéridos) en el plasma seminal y la motilidad espermática de 10 cobayos, los cuales fueron alimentados por un período de 2 meses con una dieta 10% mayor en energía digestible (ED). El nivel de glucosa encontrado en plasma seminal fue de 11.59 ± 0.5 mg/dL y el valor de triglicéridos fue de 55.95 ± 3.2 mg/dL, mientras que la motilidad promedio fue de 95%. Concluimos que en cobayos los niveles de glucosa y triglicéridos se incrementan al aumentar el nivel de ED en dieta sin producir alteraciones en la motilidad espermática

Correlaciones entre la infección por microquistes de S. lamacanis y CK-MB, Ast y LDH alpacas

El presente estudio tuvo objetivo determinar la correlación entre el número de microquistes de S. lamacanis en miocardio (N°Mq) y los niveles en sangre de las enzimas CK-MB, AST y LDH en alpacas, a fin de usarlos como predictores de salud o grado de infección por sarcocystiosis. Se utilizaron 41 alpacas de 3-5 años de edad del matadero Municipal Ninacaca, Pasco-Perú, las muestras de sangre se colectaron ante-mortem y las de miocardio post-mortem. El 100 % de los animales presentaron microquistes de S. Lamacanis, y los coeficientes de correlación entre el N°Mq y CK-MB fue de 0.17, AST 0.04 y para LDH 0.06. Se concluye que la correlación es muy baja o casi nula, por lo que las enzimas evaluadas no tendrían mayor importancia para determinar daño cardiaco por infección de microquistes de S. Lamacanis en alpacas

Cambios en los parámetros fisiológicos por diarrea neonatal en crías de alpaca

Alpacas in the pre-weaning stage often present neonatal diarrhoea, usually of infectious type, causing high mortality. This study determined the physiological parameters and their changes in animals with diarrhoea. In total, 79 neonate alpacas less than 60 days of age from Pasco and Junín regions, Peru, were used. Of them, 60 had clinical diarrhoea lasting 1 to 3 days, and 19 were healthy (controls). Heart and respiratory rate, peripheral capillary oxygen saturation, body temperature, capillary refill time, and mucous color were determined. A significant increase in heart rate in crias with diarrhea compared to healthy ones was found (p<0.05). Besides, no differences in other physiological parameters between diseased and apparently healthy offspring was found.Las crías de alpaca en la etapa pre-destete cursan con frecuencia con cuadros diarreicos, por lo general de tipo infeccioso, causantes de alta mortalidad. El presente estudio determinó los parámetros fisiológicos y sus cambios en animales con diarrea. Se utilizaron 79 alpacas neonatas menores de 60 días de edad de las zonas de Pasco y Junín, Perú. De ellas, 60 cursaban con cuadros de diarrea entre 1 a 3 días y 19 estaban sanas (controles). Se determinó la frecuencia cardiaca y respiratoria, saturación de la sangre por la presión parcial de oxígeno, temperatura corporal, tiempo de llenado capilar y coloración de las mucosas. Se encontró un aumento significativo de la frecuencia cardiaca (p<0.05) en crías con diarrea en comparación a las sanas, no habiendo diferencias en los demás parámetros fisiológicos entre crías enfermas y aparentemente sanas

Serum cytokine levels as predictive biomarkers of benefit from ipilimumab in small cell lung cancer

Background. Immunotherapy has shown efficacy in small cell lung cancer (SCLC), but only a subset of patients benefits. Surrogate biomarkers are urgently needed. Our aim was to evaluate serum Th1, Th2, and proinflammatory cytokines in two cohorts of SCLC patients before and during treatment with chemotherapy with or without ipilimumab and to correlate them with survival. Patients and methods. Two cohorts of SCLC patients were studied: patients treated with chemotherapy (n = 47), and patients treated with chemotherapy plus ipilimumab (n = 37). Baseline, on-treatment and after-treatment serum samples were evaluated for the presence of IL-1beta, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IFN-gamma, TNF-alpha, GM-CSF, and Mip-1alpha using a Luminex assay. Differential changes in cytokines between cohorts were analyzed. Associations between cytokine levels and their changes with overall survival were evaluated. Results. Patients treated with ipilimumab showed a global increase of all cytokines after treatment initiation. A high level of IL-8 at baseline was associated with worse prognosis regardless of treatment. Baseline increased IL-2 levels predicted sensitivity to ipilimumab, while high IL-6 and TNF-alpha predicted resistance. An on-treatment increase in IL-4 levels in patients treated with immune-chemotherapy was associated with a better overall survival. Conclusions. The addition of ipilimumab to standard chemotherapy in SCLC modulates the serum levels of cytokines. Baseline levels and their change over time relate to overall survival. Blood-based biomarkers are convenient for patients, and our results support prospective validation of cytokines as predictive biomarkers for ipilimumab in SCLC

Análisis retrospectivo de agentes bacterianos y patrones de susceptibilidad antibiótica en casos de infecciones del tracto urinario en caninos domésticos (2012-2017)

The present study aimed to describe and analyse the results of bacterial isolates and their antibiograms in canine patients with a diagnosis of urinary tract infection, which were treated at the Small Animal Clinic of the Faculty of Veterinary Medicine of Universidad de San Marcos between 2012 and 2017. In total, 97 medical records of patients who had urine cultures and antibiograms exams were identified. The bacterial agents isolated were Escherichia coli (36.9%), Staphylococcus sp (28.7%), Proteus sp (27.9%), Pseudomonas sp (3.3%), Klebsiella sp (1.6%), Streptococcus sp (0.8%) and Citrobacter sp (0.8%) These evidenced a high antibiotic resistance due possibly to the inappropriate use of antibiotics in the country, so it is not possible to recommend a safe initial treatment in canine patients with presumptive diagnosis of this disease.El presente estudio tuvo como objetivo describir y analizar los resultados de los aislados bacterianos y sus antibiogramas en pacientes caninos con diagnóstico de infección del tracto urinario, que fueron atendidos en la Clínica de Animales Menores de la Facultad de Medicina Veterinaria de la Universidad Nacional Mayor de San Marcos entre 2012 y 2017. Se identificaron 97 historias clínicas de pacientes que contaban con exámenes de urocultivos y antibiogramas. Los agentes bacterianos aislados fueron Escherichia coli (36.9%), Staphylococcus sp (28.7%), Proteus sp (27.9%), Pseudomonas sp (3.3%), Klebsiella sp (1.6%), Streptococcus sp (0.8%) y Citrobacter sp (0.8%). Estos evidenciaron una alta resistencia antibiótica debido posiblemente al uso inadecuado de los antibióticos en el medio, por lo que no permite recomendar un tratamiento inicial seguro en pacientes caninos con diagnóstico presuntivo de esta enfermedad

Inflammatory breast cancer: dynamic contrast-enhanced MR in patients receiving bevacizumab. Initial experience

To retrospectively compare three dynamic contrast material-enhanced magnetic resonance (MR) imaging (dynamic MR imaging) analytic methods to determine the parameter or combination of parameters most strongly associated with changes in tumor microvasculature during treatment with bevacizumab alone and bevacizumab plus chemotherapy in patients with inflammatory or locally advanced breast cancer. MATERIALS AND METHODS: This study was conducted in accordance with the institutional review board of the National Cancer Institute and was compliant with the Privacy Act of 1974. Informed consent was obtained from all patients. Patients with inflammatory or locally advanced breast cancer were treated with one cycle of bevacizumab alone (cycle 1) followed by six cycles of combination bevacizumab and chemotherapy (cycles 2-7). Serial dynamic MR images were obtained, and the kinetic parameters measured by using three dynamic analytic MR methods (heuristic, Brix, and general kinetic models) and two region-of-interest strategies were compared by using two-sided statistical tests. A P value of .01 was required for significance. RESULTS: In 19 patients, with use of a whole-tumor region of interest, the authors observed a significant decrease in the median values of three parameters measured from baseline to cycle 1: forward transfer rate constant (Ktrans) (-34% relative change, P=.003), backflow compartmental rate constant extravascular and extracellular to plasma (Kep) (-15% relative change, P<.001), and integrated area under the gadolinium concentration curve (IAUGC) at 180 seconds (-23% relative change, P=.009). A trend toward differences in the heuristic slope of the washout curve between responders and nonresponders to therapy was observed after cycle 1 (bevacizumab alone, P=.02). The median relative change in slope of the wash-in curve from baseline to cycle 4 was significantly different between responders and nonresponders (P=.009). CONCLUSION: The dynamic contrast-enhanced MR parameters Ktrans, Kep, and IAUGC at 180 seconds appear to have the strongest association with early physiologic response to bevacizumab. Clinical trial registration no. NCT0001654

Design of 280 GHz feedhorn-coupled TES arrays for the balloon-borne polarimeter SPIDER

We describe 280 GHz bolometric detector arrays that instrument the balloon-borne polarimeter SPIDER. A primary science goal of SPIDER is to measure the large-scale B-mode polarization of the cosmic microwave background in search of the cosmic-inflation, gravitational-wave signature. 280 GHz channels aid this science goal by constraining the level of B-mode contamination from galactic dust emission. We present the focal plane unit design, which consists of a 16$\times$16 array of conical, corrugated feedhorns coupled to a monolithic detector array fabricated on a 150 mm diameter silicon wafer. Detector arrays are capable of polarimetric sensing via waveguide probe-coupling to a multiplexed array of transition-edge-sensor (TES) bolometers. The SPIDER receiver has three focal plane units at 280 GHz, which in total contains 765 spatial pixels and 1,530 polarization sensitive bolometers. By fabrication and measurement of single feedhorns, we demonstrate 14.7$^{\circ}$ FHWM Gaussian-shaped beams with $<$1% ellipticity in a 30% fractional bandwidth centered at 280 GHz. We present electromagnetic simulations of the detection circuit, which show 94% band-averaged, single-polarization coupling efficiency, 3% reflection and 3% radiative loss. Lastly, we demonstrate a low thermal conductance bolometer, which is well-described by a simple TES model and exhibits an electrical noise equivalent power (NEP) = 2.6 $\times$ 10$^{-17}$ W/$\sqrt{\mathrm{Hz}}$, consistent with the phonon noise prediction.Comment: Proceedings of SPIE Astronomical Telescopes + Instrumentation 201

Cambios en la Bioquímica Sérica en Crías de Alpaca con Diarrea

El objetivo del presente estudio fue determinar las alteraciones que ocurren en los parámetros bioquímicos sanguíneos en crías de alpaca que cursan con diarrea infecciosa. Se utilizaron 80 animales de las regiones Pasco y Junín, Perú. Los animales fueron distribuidos de acuerdo a su edad: menores de 1 mes de edad (10 controles y 40 enfermos) y 1-2 meses de edad (10 controles y 20 enfermos). La diarrea clínica tenía 2-3 días de presentación en el momento de la toma de muestras. Se hicieron determinaciones de glucosa, triglicéridos, colesterol, proteína total, albúmina, calcio, bilirrubina total, bilirrubina directa y fosfatasa alcalina. Los parámetros bioquímicos, excepto glucosa, cambiaron significativamente en los animales enfermos con respecto a los controles. En los animales enfermos los niveles de proteína total, albúmina y calcio disminuyeron significativamente (p&lt;0.05), mientras que los niveles de fosfatasa alcalina, bilirrubina, colesterol y triglicéridos se incrementaron significativamente (p&lt;0.05)

Assessment of neuronal autoantibodies in patients with small cell lung cancer treated with chemotherapy with or without ipilimumab

Small-cell lung cancer (SCLC) is often associated with paraneoplastic syndromes. To assess the role of anti-neuronal autoantibodies (NAAs) as biomarkers of treatment outcome, we assessed NAAs in serial samples from SCLC patients treated with chemoimmunotherapy compared to chemotherapy alone. We evaluated 2 cohorts: in cohort 1 (C1), 47 patients received standard platinum/etoposide, and in cohort 2 (C2), 38 patients received ipilimumab, carboplatin and etoposide. Serum samples at baseline and subsequent time points were analyzed for the presence of NAAs. NAAs were detected at baseline in 25 patients (53.2%) in C1 and in 20 patients (52.6%) in C2 (most frequently anti-Sox1). NAA at baseline was associated with limited disease (75% vs 50%; p: 0.096) and better overall survival (15.1 m vs 11.7 m; p: 0.032) in C1. Thirteen patients (28.9%) showed 2 or more reactivities before treatment; this was associated with worse PFS (5.5 m vs 7.3 m; p: 0.005) in patients treated with chemoimmunotherapy. NAA titers decreased after therapy in 68.9% patients, with no differential patterns of change between cohorts. Patients whose NAA titer decreased after treatment, showed longer OS [18.5 m (95% CI: 15.8 – 21.2)] compared with those whose NAA increased [12.3 m (95% CI: 8.1 – 16.5; p 0.049)], suggesting that antibody levels correlate to tumor load. Our findings reinforce the role of NAAs as prognostic markers and tumor activity/burden in SCLC, warrant further investigation in their predictive role for immunotherapy and raise concern over the use of immunotherapy in patients with more than one anti-NAA reactivity