Gestión de inventario para incrementar el nivel de satisfacción del cliente en una empresa biofarmacéutica, en Lima, 2022

El presente estudio de investigación tuvo por finalidad determinar cómo la implementación de la gestión de inventarios incrementa el nivel de satisfacción del cliente en una empresa biofarmacéutica en Lima en el año 2022. Mediante el tipo de investigación aplicada, nivel descriptivo y diseño pre experimental, de pre test y pos test. La población son 10 reportes de los indicadores de las variables medidos cada 2 semanas. La muestra es igual que la población, por tanto, censal. Para recolectar información se empleó la técnica de observación y las fichas de registros de datos como instrumentos. Se concluyó que la aplicación de la gestión de inventarios incrementa significativamente el nivel de satisfacción del cliente en 33.14%, ya que antes se registró un puntaje de 56.97% y después 90.11%; esta diferencia es significativa, según lo comprueba el valor estadístico de Sig.= 0,540<0,05

A Novel Gene Required for Male Fertility and Functional CATSPER Channel Formation in Spermatozoa

Summary Calcium signaling is critical for successful fertilization. In spermatozoa, capacitation, hyperactivation of motility, and the acrosome reaction are all mediated by increases in intracellular Ca2+. Cation channels of sperm proteins (CATSPERS1-4) form an alkalinization-activated Ca2+-selective channel required for the hyperactivated motility of spermatozoa and male fertility. Each of the CatSper1-4 genes encodes a subunit of a tetramer surrounding a Ca2+-selective pore, in analogy with other six-transmembrane ion channel α subunits. In addition to the pore-forming proteins, the sperm Ca2+ channel contains auxiliary subunits, CATSPERβ and CATSPERγ. Here, we identify the Tmem146 gene product as a novel subunit, CATSPERδ, required for CATSPER channel function. We find that mice lacking the sperm tail-specific CATSPERδ are infertile and their spermatozoa lack both Ca2+ current and hyperactivated motility. We show that CATSPERδ is an essential element of the CATSPER channel complex and propose that CATSPERδ is required for proper CATSPER channel assembly and/or transport

The Cation Selectivity Filter of the Bacterial Sodium Channel, NaChBac

The Bacillus halodurans voltage-gated sodium-selective channel (NaChBac) (Ren, D., B. Navarro, H. Xu, L. Yue, Q. Shi, and D.E. Clapham. 2001b. Science. 294:2372–2375), is an ideal candidate for high resolution structural studies because it can be expressed in mammalian cells and its functional properties studied in detail. It has the added advantage of being a single six transmembrane (6TM) orthologue of a single repeat of mammalian voltage-gated Ca2+ (CaV) and Na+ (NaV) channels. Here we report that six amino acids in the pore domain (LESWAS) participate in the selectivity filter. Replacing the amino acid residues adjacent to glutamatic acid (E) by a negatively charged aspartate (D; LEDWAS) converted the Na+-selective NaChBac to a Ca2+- and Na+-permeant channel. When additional aspartates were incorporated (LDDWAD), the mutant channel resulted in a highly expressing voltage-gated Ca2+-selective conductance

Simultaneous knockout of Slo3 and CatSper1 abolishes all alkalization- and voltage-activated current in mouse spermatozoa

During passage through the female reproductive tract, mammalian sperm undergo a maturation process termed capacitation that renders sperm competent to produce fertilization. Capacitation involves a sequence of changes in biochemical and electrical properties, the onset of a hyperactivated swimming behavior, and development of the ability to undergo successful fusion and penetration with an egg. In mouse sperm, the development of hyperactivated motility is dependent on cytosolic alkalization that then results in an increase in cytosolic Ca2+. The elevation of Ca2+ is thought to be primarily driven by the concerted interplay of two alkalization-activated currents, a K+ current (KSPER) composed of pore-forming subunits encoded by the Kcnu1 gene (also termed Slo3) and a Ca2+ current arising from a family of CATSPER subunits. After deletion of any of four CATSPER subunit genes (CATSPER1–4), the major remaining current in mouse sperm is alkalization-activated KSPER current. After genetic deletion of the Slo3 gene, KSPER current is abolished, but there remains a small voltage-activated K+ current hypothesized to reflect monovalent flux through CATSPER. Here, we address two questions. First, does the residual outward K+ current present in the Slo3 −/− sperm arise from CATSPER? Second, can any additional membrane K+ currents be detected in mouse sperm by patch-clamp methods other than CATSPER and KSPER? Here, using mice bred to lack both SLO3 and CATSPER1 subunits, we show conclusively that the voltage-activated outward current present in Slo3 −/− sperm is abolished when CATSPER is also deleted. Any leak currents that may play a role in setting the resting membrane potential in noncapacitated sperm are likely smaller than the pipette leak current and thus cannot be resolved within the limitation of the patch-clamp technique. Together, KSPER and CATSPER appear to be the sole ion channels present in mouse sperm that regulate membrane potential and Ca2+ influx in response to alkalization

Family history of breast and ovarian cancer and triple negative subtype in hispanic/latina women.

Familial breast and ovarian cancer prevalence was assessed among 1150 women of Mexican descent enrolled in a case-only, binational breast cancer study. Logistic regression was conducted to compare odds of triple negative breast cancer (TNBC) to non-TNBC according to family history of breast and breast or ovarian cancer among 914 of these women. Prevalence of breast cancer family history in a first- and first- or second-degree relative was 13.1% and 24.1%, respectively; that for breast or ovarian cancer in a first-degree relative was 14.9%. After adjustment for age and country of residence, women with a first-degree relative with breast cancer were more likely to be diagnosed with TNBC than non-TNBC (OR=1.98; 95% CI, 1.26-3.11). The odds of TNBC compared to non-TNBC were 1.93 (95% CI, 1.26-2.97) for women with a first-degree relative with breast or ovarian cancer. There were non-significant stronger associations between family history and TNBC among women diagnosed at age &lt;50 compared to ≥50 years for breast cancer in a first-degree relative (P-interaction = 0.14) and a first- or second-degree relative (P-interaction = 0.07). Findings suggest that familial breast cancers are associated with triple negative subtype, possibly related to BRCA mutations in Hispanic/Latina women, which are strongly associated with TNBC. Family history is an important tool to identify Hispanic/Latina women who may be at increased risk of TNBC, and could benefit from prevention and early detection strategies

Hypothesized role of pregnancy hormones on HER2+breast tumor development

Breast cancer incidence rates have declined among older but not younger women; the latter are more likely to be diagnosed with breast cancers carrying a poor prognosis. Epidemiological evidence supports an increase in breast cancer incidence following pregnancy with risk elevated as much as 10 years post-partum. We investigated the association between years since last full-term pregnancy at the time of diagnosis (10 years) and breast tumor subtype in a case series of premenopausal Hispanic women (n = 627). Participants were recruited in the United States, Mexico, and Spain. Cases with known estrogen receptor (ER), progesterone receptor (PR), and HER2 status, with one or more full-term pregnancies >/=1 year prior to diagnosis were eligible for this analysis. Cases were classified into three tumor subtypes according to hormone receptor (HR+ = ER+ and/or PR+; HR- = ER- and PR-) expression and HER2 status: HR+/HER2-, HER2+ (regardless of HR), and triple negative breast cancer. Case-only odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for HER2+ tumors in reference to HR+/HER2- tumors. Participants were pooled in a mixed-effects logistic regression model with years since pregnancy as a fixed effect and study site as a random effect. When compared to HR+/HER2- cases, women with HER2+ tumors were more likely be diagnosed in the post-partum period of 45 years) did not materially alter our results (OR = 1.78; 95 % CI, 1.08-2.93). These findings support the novel hypothesis that factors associated with the post-partum breast, possibly hormonal, are involved in the development of HER2+ tumors

Estandarización de modelo de perfusión renal en ratones

La técnica de riñón ex vivo permite valorar la respuesta renal intrínseca permitiendo que las variables experimentales puedan ser controladas por el investigador. En los laboratorios del CIPFAR trabajamos para poner a punto el modelo de riñón aislado y perfundido, para lo cual empleamos ratones C57BL/6 y CD-1 machos. Realizamos laparatomía abdominal, localizamos y ligamos la sección aórtica, seguidamente, realizamos una incisión en la arteria renal izquierda e introdujimos una cánula acoplada a un microtubo de polietileno. A través de la cánula, los riñones aislados son conectados a un sistema de perfusión y expuestos a los contracturantes KCl (80mM) y fenilefrina (FE 10-5 M). También obtuvimos curvas concentración respuesta frente a acetilcolina (ACh 10-8–10-4M). Nuestros resultados revelan valores de presión basal de 36.8 ± 4.8 mmHg y 30.7 ± 14.2 mmHg para las cepas CD-1 y C57BL/6, respectivamente. La despolarización con KCl desarrolló un efecto contracturante máximo de 25.7 ± 16.0 mmHg para CD-1 y 63.8 ± 34.8 mmHg en ratones C57BL/6. El agente adrenérgico FE, produjo contracciones máximas de 53.0 ± 29.6 mmHg en CD-1 y 66.1 ± 4.7 mmHg en C57BL/6. El efecto vasodilatador máximo inducido por ACh fue de 35.7 % ± 3.5 y 46.9 % ± 18.7 en CD-1 y C57BL/6, respectivamente.A la luz de este resultado, tanto el tiempo de exposición, la manipulación excesiva, la perfusión inadvertida de burbujas y la formación de coágulos, pueden ser factores que disminuyan la viabilidad del endotelio renal. En cualquier caso, los datos de perfusión basal, así como la reactividad frente a agentes contracturantes son pruebas de la viabilidad del tejido en ambos grupos de animales

Influencia del gen CRELD1 en las cardiopatías congénitas de pacientes con síndrome de Down durante la pandemia por COVID -19.: Influence of the CRELD1 gene on congenital heart disease in patients with Down syndrome during the COVID -19 pandemic.

Down syndrome is a pathology that, according to WHO, has a high worlwide and national incidence, frequently associated with congenital heart defects. It affects the human genetic material and it is caused by the nondisjunction of chromosome 21 (XY, + 21 or XX, + 21) or other alterations associated with the same chromosome (mosaicism, translocation). It manifests itself with peculiar characteristics in various areas of the body, among which congenital heart disease stands out, mainly atrioventricular septal defects (AVSD), caused by mutations in the CRELD1 gene. This gene contains 9 exons, encodes cell adhesion molecules and at the same time acts as a regulator of the calcineurin / NFATc1 signaling pathway, thus allowing correct cardiac morphogenesis. On the other hand,&nbsp; DS&nbsp; brings&nbsp; with&nbsp; it&nbsp; defects in&nbsp; the&nbsp; immune&nbsp; and&nbsp; respiratory system,&nbsp; with&nbsp; vital importance today, given that deficiencies in their functioning increase vulnerability to Covid-19.El síndrome de Down es una patología que, según la OMS, presenta una alta incidencia a nivel mundial y nacional, encontrándose frecuentemente asociada a defectos cardíacos congénitos. Afecta al material genético del ser humano y se origina por la no disyun ción del cromosoma 21 (XY, + 21 o XX, + 21) u otras alteraciones asociadas a este mismo cromosoma (mosaicismo, translocación). Se manifiesta con características peculiares en diversas áreas del organismo, entre las cuales destacan las cardiopatías congénit as, principalmente los defectos del tabique auriculoventricular (AVSD), causados por mutaciones en el gen CRELD1. Este gen contiene 9 exones, codifica moléculas de adhesión celular y la vez actúa como regulador de la vía de señalización de la calcineurina/ NFATc1, permitiendo así la correcta morfogénesis cardiaca. Por otra parte, el SD trae consigo defectos en el sistema inmune y respiratorio, de vital importancia hoy en día, dado que, deficiencias en su funcionamiento incrementan la vulnerabilidad frente a la Covid-19

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations