Blueprinting extendable nanomaterials with standardized protein blocks.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies, in comparison, has been much more complex, largely owing to the irregular shapes of protein structures1. Here we describe extendable linear, curved and angled protein building blocks, as well as inter-block interactions, that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight 'train track' assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not previously been possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank three-dimensional canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to 'back of an envelope' architectural blueprints.

[Prevalence and gravity of depression and anxiety in patients with obesity and type 2 diabetes: a study in the population of Tabasco, Mexico]. / Prevalencia y gravedad de la depresión y la ansiedad en pacientes con obesidad y diabetes de tipo 2: estudio en población de Tabasco, México.

AIMS: The aim of this study was to assess the prevalence of anxiety and depression in groups of obese and normal-weight individuals with type 2 diabetes. Also, to analyze the severity of depression in type 2 diabetics by taking into account the body mass index in people with this condition. METHODS: This study included 702 patients with type 2 diabetes, 236 with normal weight, and 231 with obesity. All participants completed a demographic questionnaire, the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale. RESULTS: In patients with obesity, 48.48% (95% CI: 41.82-55.14) were positive for anxiety and 49.78% (95% CI: 43.11-56.44) for depression. A significant correlation existed between the Hamilton Depression Rating Scale and body mass index with a correlation coefficient of 0.11 (p = 0.003). Also, a significant correlation coefficient equal to 0.107 (p = 0.005) between the Hamilton Anxiety Rating Scale and body mass index was found. In addition, when we analyzed depression scores, significant differences were encountered for gender between normal-weight and obesity groups in the range of severe (p = 0.01) and very severe (p = 0.04) cases. CONCLUSION: In view of the existing relationships observed among obesity, depression, anxiety, and gender in type 2 diabetics, we consider that a psychological intervention is necessary for an integral management of these patients.

Directing polymorph specific calcium carbonate formation with de novo protein templates.

Biomolecules modulate inorganic crystallization to generate hierarchically structured biominerals, but the atomic structure of the organic-inorganic interfaces that regulate mineralization remain largely unknown. We hypothesized that heterogeneous nucleation of calcium carbonate could be achieved by a structured flat molecular template that pre-organizes calcium ions on its surface. To test this hypothesis, we design helical repeat proteins (DHRs) displaying regularly spaced carboxylate arrays on their surfaces and find that both protein monomers and protein-Ca2+ supramolecular assemblies directly nucleate nano-calcite with non-natural {110} or {202} faces while vaterite, which forms first in the absence of the proteins, is bypassed. These protein-stabilized nanocrystals then assemble by oriented attachment into calcite mesocrystals. We find further that nanocrystal size and polymorph can be tuned by varying the length and surface chemistry of the designed protein templates. Thus, bio-mineralization can be programmed using de novo protein design, providing a route to next-generation hybrid materials.

Blueprinting expandable nanomaterials with standardized protein building blocks.

A wooden house frame consists of many different lumber pieces, but because of the regularity of these building blocks, the structure can be designed using straightforward geometrical principles. The design of multicomponent protein assemblies in comparison has been much more complex, largely due to the irregular shapes of protein structures 1 . Here we describe extendable linear, curved, and angled protein building blocks, as well as inter-block interactions that conform to specified geometric standards; assemblies designed using these blocks inherit their extendability and regular interaction surfaces, enabling them to be expanded or contracted by varying the number of modules, and reinforced with secondary struts. Using X-ray crystallography and electron microscopy, we validate nanomaterial designs ranging from simple polygonal and circular oligomers that can be concentrically nested, up to large polyhedral nanocages and unbounded straight "train track" assemblies with reconfigurable sizes and geometries that can be readily blueprinted. Because of the complexity of protein structures and sequence-structure relationships, it has not been previously possible to build up large protein assemblies by deliberate placement of protein backbones onto a blank 3D canvas; the simplicity and geometric regularity of our design platform now enables construction of protein nanomaterials according to "back of an envelope" architectural blueprints.

Surgical treatment of acute cholecystitis in patients with confirmed COVID-19: Ten case reports and review of literature.

BACKGROUND: Research concerning postoperative outcomes of confirmed coronavirus disease 2019 (COVID-19) patients revealed unfavorable postoperative results with increased morbidity, pulmonary complications and mortality. Case reports have suggested that COVID-19 is associated with more aggressive presentation of acute cholecystitis. The aim of the present study is to describe the perioperative assessment and postoperative outcomes of ten patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with concomitant acute cholecystitis who underwent cholecystectomy. CASE SUMMARY: We report a total of 10 SARS-CoV-2 positive patients with concomitant acute cholecystitis that underwent cholecystectomy. Six patients were males, the mean age was 47.1 years. Nine patients had moderate acute cholecystitis, and one patient had severe acute cholecystitis. All patients were treated with urgent/early laparoscopic cholecystectomy. Regarding the Parkland grading scale, two patients received a Parkland grade of 3, two patients received a Parkland grade of 4, and six patients received a Parkland grade of 5. Eight patients required a bail-out procedure. Four patients developed biliary leakage and required endoscopic retrograde cholangiopancreatography with biliary sphincterotomy. After surgery, five patients developed acute respiratory distress syndrome (ARDS) and required intensive care unit (ICU) admission. One patient died after cholecystectomy due to ARDS complications. The mean total length of stay (LOS) was 18.2 d. The histopathology demonstrated transmural necrosis (n = 5), vessel obliteration with ischemia (n = 3), perforation (n = 3), and acute peritonitis (n = 10). CONCLUSION: COVID-19 patients with acute cholecystitis had difficult cholecystectomies, high rates of ICU admission, and a prolonged LOS.

Role of the DLL4-NOTCH system in PGF2alpha-induced luteolysis in the pregnant rat.

We investigated the expression and cell localization of NOTCH1, NOTCH4, and the delta-like ligand DLL4 in corpus luteum (CL) from pregnant rats during prostaglandin F2alpha (PGF2alpha)-induced luteolysis. We also examined serum progesterone (P(4)) and CL proteins related to apoptosis after local administration of the notch inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT). Specific staining for NOTCH1 and NOTCH4 receptors was detected predominantly in large and small luteal cells. Furthermore, in line with the fact that the notch intracellular domain is translocated to the nucleus, where it regulates gene expression, staining was evident in the nuclei of luteal cells. In addition, we detected diffuse cytoplasmic immunostaining for DLL4 in small and large luteal cells, in accordance with the fact that DLL4 undergoes proteolytic degradation after receptor binding. The mRNA expression of Notch1, Notch4, and Dll4 in CL isolated on Day 19 of pregnancy decreased significantly after administration of PGF2alpha. Consistent with the mRNA results, administration of PGF2alpha to pregnant rats on Day 19 of pregnancy decreased the protein fragment corresponding to the cleaved forms of NOTCH1/4 CL receptors. In contrast, no significant changes were detected in protein levels for the ligand DLL4. The local intrabursal administration of DAPT decreased serum P(4) levels and increased luteal levels of active caspase 3 and the BAX:BCL2 ratio 24 h after the treatment. These results support a luteotropic role for notch signaling to promote luteal cell viability and steroidogenesis, and they suggest that the luteolytic hormone PGF2alpha may act in part by reducing the expression of some notch system members.

Altered expression of Bcl-2 and Bax in follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

PCOS (polycystic ovary syndrome) is a heterogeneous disease characterized by hyperandrogenaemia, hirsutism, oligo- or amenorrhea, insulin resistance and anovulation. The aim of the present study was to evaluate if the balance between the ovarian expression of Bax (proapoptotic protein) and Bcl-2 (antiapoptotic protein) is altered in a PCOS model developed in rats by DHEA (dehydroepiandrosterone) administration. In addition, the ovarian morphology and the circulating progesterone levels were evaluated. Histological studies confirmed the presence of follicular cysts, atretic follicles and the absence of corpora lutea in the ovaries from the PCOS group and a significant decrease in circulating progesterone levels. Immunohistochemical studies showed that the expression of Bcl-2 and Bax were mainly localized in granulosa cells of AFs (antral follicles) in both groups. Bax expression was greater in preantral and AFs from PCOS ovarian sections than in the controls. In contrast, intense Bcl-2 immunostaining was observed in the control AFs, while Bcl-2 protein was either absent in PFs (preantral follicles) or weakly expressed in AFs from PCOS rats. These results were partially confirmed by Western studies. Data revealed that the ovarian level of Bcl-2 protein was lower in PCOS than in the control and that there were no differences in Bax ovarian levels between groups. However, Bax/Bcl-2 ratio was significantly higher in PCOS group than in the control group. In conclusion, an increase in ovarian apoptosis through an imbalance among the Bcl-2 family members may be involved in the transformation of growing follicles in cystic follicles in the ovaries from DHEA-induced PCOS rats.

Comparing perceptions of professionalism by pharmacy students, faculty, and staff during didactic education.

INTRODUCTION: The objectives were to describe pharmacy students' perceptions of professionalism and to compare students and faculty/staff perceptions of professionalism during the didactic years at Touro University California College of Pharmacy in California (TUC COP). METHODS: A two-part online survey was administered to the TUC COP faculty/staff and first-year (P1) and second-professional year (P2) students in May 2016. The first part of the survey collected demographic information, assessment of faculty/staff and students' overall opinions on behavior and conduct displayed by P1 and P2 students, students' responses about the average of missed lectures per month, and the average number of days of late arrival to lecture per week. The second part assessed professionalism perceptions responses to 20 scenarios using a 4-point Likert rating. RESULTS: The study included 37 (88.4%) faculty/staff and 181 (96.4%) P1 and P2 students, for a 98% response rate. Of the faculty/staff, 59.5% perceived the students' overall behaviors and conduct as acceptable whereas 35.3% of students perceived the overall behavior of P1 and P2 students as acceptable, with the majority of students self-reporting missing on average fewer than five lectures per month (65.2%) and arriving late to lecture fewer than one day each week (71.8%). There were statistically significant differences between faculty/staff and students' responses in 9 of the 20 scenarios. CONCLUSIONS: Differences in responses between faculty/staff and students regarding what is considered professional suggest that there is a gap in professionalism perceptions that should be addressed during didactic years.

Effect of Elicitation on Polyphenol and Carotenoid Metabolism in Butterhead Lettuce (Lactuca sativa var. capitata).

The effect of elicitation in butterhead lettuce on carotenoid and polyphenol metabolism was evaluated. Different concentrations of arachidonic acid (AA), salicylic acid (SA), methyl jasmonate (MJ) (15, 45, and 90 µM) and Harpin protein (HP) (30, 60, and 120 mg/L) were applied on red and green butterhead lettuces. Total phenolic and flavonoid content were incremented by MJ (90 µM) in green and red lettuce. Carotenoids were increased in red lettuce (AA; 45 µM). Green lettuce modifies their phenolic acid profile after elicitation with AA and MJ; meanwhile, red lettuce incremented mainly in hydroxycinnamic acids and flavonols, MJ being the elicitor with the highest effect. There was an impact on secondary metabolite enzyme gene transcript concentration. Phenylalanine ammonia-lyase (PAL) and lycopene beta cyclase (LBC) increased in both varieties after elicitation. A relationship between phytochemical increase and the activation of the metabolic pathways after elicitation in butterhead lettuce was observed.

Spatiotemporal analysis of the protein expression of angiogenic factors and their related receptors during folliculogenesis in rats with and without hormonal treatment.

This study investigated the protein expression and cellular localization of ANGPT1, ANGPT2, and their receptor TEK, as well as vascular endothelial growth factor A (VEGFA) and its receptor KDR (VEGFR2) during folliculogenesis. To obtain follicles at different stages for immunochemistry and western analyses, we used prepubertal untreated, diethylstilbestrol- and equine chorionic gonadotropin-treated rats. To confirm that these hormonal treatments reflect physiological change, we used non-treated adult rats. No expression of ANGPT1 was observed in granulosa cells (Gc) from immature hormone-treated and non-treated rats at any follicular stage. By contrast, ANGPT1 expression in theca cells (Tc) increased with follicular maturation. ANGPT2 protein was either absent or weakly expressed in Gc at all follicular stages. In Tc, minimal expression of ANGPT2 protein was detected in the preantral follicle (PF), whereas it was stronger in the early antral follicle (EAF) and preovulatory follicle (POF). TEK staining was absent in Gc but was intense in Tc at every follicular stage. Staining for VEGFA was either absent or weakly present in Gc and Tc in PF and EAF, although in POF it was stronger in Gc and Tc. Staining for KDR was absent in Gc and very low in Tc from PF. Gc and Tc of EAF showed positive staining for KDR and in POF the staining was stronger. These results were confirmed by western immunoblot. A similar pattern of expression of these proteins was observed in cycling rats. In conclusion, we observed that the protein expression of ANGPT1, ANGPT2, VEGFA and their receptors increased during follicular development in rats.

Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat.

Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2alpha). On day 19 of pregnancy, 2 hr before systemic PGF-2alpha administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2alpha injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-alpha) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2alpha injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2alpha, but not caspase-9 activity. In contrast, expression of pAKT and TNF-alpha decreased significantly. Administration of S1P suppressed (P < 0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-alpha expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2alpha. PGF-2alpha treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2alpha by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-alpha expression.

Más allá de la violencia física y sexual contra la mujer / Going further than physical and sexual violence against women

Hemos leído el artículo titulado Violencia extrema contra la mujer y feminicidio en el Perú publicado en la Revista Cubana de Salud Pública 2018;44(2), donde se menciona que la violencia extrema contra la mujer ha aumentado y el feminicidio es mayor en zonas rurales,1 por lo que queremos dar un enfoque más allá de la violencia física y sexual. La violencia contra la mujer constituye un problema social y una violación de los derechos humanos que repercute de manera importante en la salud y el bienestar de la mujer.2 Los datos actuales nos indican que las medidas adoptadas por el gobierno son insuficientes para lograr controlar este problema de salud pública.3,4 A nivel mundial se estima que alrededor de una de cada tres mujeres han sufrido violencia física y sexual; y que el agresor generalmente es su propia pareja.5 Los casos más severos llegan a feminicidio, que es definido como la muerte de mujeres a causa de la discriminación de género, lo cual constituye la manifestación más cruel que adopta la violencia contra la mujer. Según el Instituto Nacional de Estadísticas e Informática (INEI) entre los años 2011 y 2015, en el Perú se había registrado la muerte de 556 mujeres como tipificación de feminicidio.6 La violencia hacia la mujer no solo implica el ámbito físico y sexual, sino que incluyen también el psicológico, emocional y social que repercuten en el desenvolvimiento adecuado de la mujer en su entorno. Esto ha sido tomado en cuenta en la Declaración de las Naciones Unidas, donde define la violencia contra la mujer como todo acto de violencia de género que...(AU)

Psychosocial triggers or facilitators and burnout syndrome in workers of grocery stores in Guadalajara, Mexico / Desencadenantes o facilitadores psicosociales y síndrome de burnout en trabajadores de tiendas de abarrotes en Guadalajara, México

Abstract Objective: To analyze the relationship among the triggers and facilitators variables of the influential psychosocial type with Burnout Syndrome in grocery store workers, in Guadalajara, Mexico. Material and methods: The study was cross-sectional and applied to 321 people working in grocery stores located in the municipality of Guadalajara, Jalisco. A sociodemographic and labor data questionnaire was applied for the evaluation of psychosocial variables and the Maslach Burnout Inventory scale (MBI-HSS) for the presence of Burnout Syndrome. Both descriptive and inferential analysis were included. Under informed consent the respondents accepted their participation voluntarily. Results: 64.2% of the population presented Burnout Syndrome. Emotional exhaustion was the most affected (59.9%). Several triggers and / or facilitators were associated with more than one burned dimension, specifically with the Emotional exhaustion dimension. Conclusions: Grocery stores are usually a family business. The people who work in them, depend on them to survive. They are a source of employment, tranquility and protection. Thus, working safely affirms a better life quality and customer service.

Resumen Objetivo: Analizar la relación entre las variables desencadenantes y facilitadores del tipo psicosocial influyente con el síndrome de Burnout en los trabajadores de las tiendas de abarrotes en Guadalajara, México. Material y métodos: El estudio fue transversal y aplicado a 321 personas que trabajaban en supermercados ubicados en el municipio de Guadalajara, Jalisco. Se aplicó un cuestionario sociodemográfico y de datos laborales para la evaluación de variables psicosociales y la escala de inventario de Maslach Burnout (MBI-HSS) para la presencia de síndrome de Burnout. Se incluyeron análisis tanto descriptivos como inferenciales. Bajo consentimiento informado los encuestados aceptaron su participación voluntariamente. Resultados: 64,2% de la población presentó síndrome de Burnout. El agotamiento emocional fue el más afectado (59,9%). Varios disparadores y/o facilitadores se asociaron con más de una dimensión quemada, específicamente con la dimensión de agotamiento emocional. Conclusión: Las tiendas de abarrotes suelen ser una empresa familiar. Las personas que trabajan en ellas dependen de ellos para sobrevivir. Son una fuente de empleo, tranquilidad y protección. Por lo tanto, trabajar con seguridad afirma una mejor calidad de vida y servicio al cliente.

Sensitivity of MRI of the spine compared with CT myelography in orthostatic headache with CSF leak.

OBJECTIVE: To investigate the sensitivity of MRI of the spine compared with CT myelography (CTM) in detecting CSF leaks. METHODS: Between July 1998 and October 2010, 12 patients with orthostatic headache and a CTM-confirmed spinal CSF leak underwent an MRI of the spine with and without contrast. Using CTM as the gold standard, we retrospectively investigated the sensitivity of spinal MRI in detecting a CSF leak. RESULTS: Eleven of 12 patients with a CSF leak documented by CTM also had extradural fluid collections on spinal MRI (sensitivity 91.7%). Six patients with extradural fluid collections on spinal MRI also had spinal dural enhancement. CONCLUSION: When compared with the gold standard of CTM, MRI of the spine appears to be a sensitive and less invasive imaging modality for detecting a spinal CSF leak, suggesting that MRI of the spine should be the imaging modality of first choice for the detection of spinal CSF leaks.