Estudio de la viabilidad comercial para la creación de un spa para hombres de 25 a 59 años en la ciudad de Chiclayo, 2015

La presente tesis tuvo como objetivo principal investigar la viabilidad comercial de implementar un Spa exclusivamente para hombres en la ciudad de Chiclayo, debido a que diversos estudios indicaron que en la actualidad los índices de estrés, ya sea laboral o psicológico, son elevados y se requiere desarrollar modelos de negocio que permitan atenuarlos. Por ello, la presente investigación, basándose en una segmentación que abarca hombres de 25 a 59 años, de estilos de vida sofisticados y progresistas, realizó mediante encuestas, entrevistas y grupos focales, un estudio para verificar la viabilidad de ejecución del spa masculino, del cual se obtuvo resultados positivos con respecto al crecimiento de éste sector, demostrando la aceptación del proyecto como parte del cuidado masculino, de modo que éste pueda brindar un servicio innovador, exclusivo y necesario, que ayude a mejorar la calidad de vida y satisfacción de los clientes, a través de las preferencias, características y sugerencias recolectadas en el estudio y análisis del mercado Chiclayano, por lo que se concluyó del estudio que sí es viable la creación de un spa para hombres en dicha ciudad.Tesi

Trend of electroconvulsive therapy use and its relationships with clinical characteristics from a large psychiatric center in China

BackgroundRecent studies on electroconvulsive therapy (ECT) have reported inconsistent frequencies of ECT use in various countries. Therefore, this study aimed to investigate the trends of ECT use in a large psychiatric center in China over 6 consecutive years.MethodsA total of 22,120 inpatients, aged 18–59 years, admitted during the period 2015–2020 to a large grade-A tertiary psychiatric center in Beijing were enrolled in this retrospective study. Demographic and clinical data including vital signs; daily living abilities(ADL); emergency referrals; psychiatric and physical prescriptions were collected from an electronic medical records system.ResultsIn all, 2,213 (10.0%) inpatients received ECT, with an average number of sessions of 10.3 ± 6.6. There were no significant differences between the ECT and non-ECT groups in terms of educational level, marital status, length of hospital stay, and blood pressure. After using the propensity score matching (PSM) method, Multiple logistic regression analysis revealed that ECT use was independently associated with married/cohabitating (OR = 1.21, 95% CI: 1.03-1.43); few hospitalizations (OR = 0.96, 95% CI: 0.93-0.99); unemployed (OR = 1.43, 95% CI: 1.16-1.76); emergency referral (OR = 1.62, 95% CI: 1.36-1.93); increased use of antipsychotics (OR = 2.63, 95% CI: 1.88-3.68), mood stabilizers (OR = 1.30, 95% CI: 1.01-1.67), antidepressants (OR = 1.40, 95% CI: 1.13-1.73), and trihexyphenidyl (OR = 1.30, 95% CI: 1.05-1.50); reduced use of hypoglycemic drugs (OR = 0.64, 95% CI: 0.45-0.83); fast heart rate (OR = 1.01, 95% CI: 1.01-1.02); and severe impairments in ADL. Compared with that in 2015 (13.2%), ECT use decreased annually from 2016 (12.4%) to 2019 (9.6%), especially in 2020 (5.7%), given the impact of the COVID-19 pandemic in China.ConclusionsThe ECT usage and year-by-year decrease in ECT use in this study were consistent with the recent trends in other regions. Patients with the married/cohabitating, unemployed, and emergency-referral, unstable vital signs, more severe disability received ECT for quick alleviation of their conditions

Phosphoproteomic Profiling of In Vivo Signaling in Liver by the Mammalian Target of Rapamycin Complex 1 (mTORC1)

Our understanding of signal transduction networks in the physiological context of an organism remains limited, partly due to the technical challenge of identifying serine/threonine phosphorylated peptides from complex tissue samples. In the present study, we focused on signaling through the mammalian target of rapamycin (mTOR) complex 1 (mTORC1), which is at the center of a nutrient- and growth factor-responsive cell signaling network. Though studied extensively, the mechanisms involved in many mTORC1 biological functions remain poorly understood.We developed a phosphoproteomic strategy to purify, enrich and identify phosphopeptides from rat liver homogenates. Using the anticancer drug rapamycin, the only known target of which is mTORC1, we characterized signaling in liver from rats in which the complex was maximally activated by refeeding following 48 hr of starvation. Using protein and peptide fractionation methods, TiO(2) affinity purification of phosphopeptides and mass spectrometry, we reproducibly identified and quantified over four thousand phosphopeptides. Along with 5 known rapamycin-sensitive phosphorylation events, we identified 62 new rapamycin-responsive candidate phosphorylation sites. Among these were PRAS40, gephyrin, and AMP kinase 2. We observed similar proportions of increased and reduced phosphorylation in response to rapamycin. Gene ontology analysis revealed over-representation of mTOR pathway components among rapamycin-sensitive phosphopeptide candidates.In addition to identifying potential new mTORC1-mediated phosphorylation events, and providing information relevant to the biology of this signaling network, our experimental and analytical approaches indicate the feasibility of large-scale phosphoproteomic profiling of tissue samples to study physiological signaling events in vivo

USP7 small-molecule inhibitors interfere with ubiquitin binding

The ubiquitin system regulates essential cellular processes in eukaryotes. Ubiquitin is ligated to substrate proteins as monomers or chains and the topology of ubiquitin modifications regulates substrate interactions with specific proteins. Thus ubiquitination directs a variety of substrate fates including proteasomal degradation. Deubiquitinase enzymes cleave ubiquitin from substrates and are implicated in disease; for example, ubiquitin-specific protease-7 (USP7) regulates stability of the p53 tumour suppressor and other proteins critical for tumour cell survival. However, developing selective deubiquitinase inhibitors has been challenging and no co-crystal structures have been solved with small-molecule inhibitors. Here, using nuclear magnetic resonance-based screening and structure-based design, we describe the development of selective USP7 inhibitors GNE-6640 and GNE-6776. These compounds induce tumour cell death and enhance cytotoxicity with chemotherapeutic agents and targeted compounds, including PIM kinase inhibitors. Structural studies reveal that GNE-6640 and GNE-6776 non-covalently target USP7 12 Å distant from the catalytic cysteine. The compounds attenuate ubiquitin binding and thus inhibit USP7 deubiquitinase activity. GNE-6640 and GNE-6776 interact with acidic residues that mediate hydrogen-bond interactions with the ubiquitin Lys48 side chain, suggesting that USP7 preferentially interacts with and cleaves ubiquitin moieties that have free Lys48 side chains. We investigated this idea by engineering di-ubiquitin chains containing differential proximal and distal isotopic labels and measuring USP7 binding by nuclear magnetic resonance. This preferential binding protracted the depolymerization kinetics of Lys48-linked ubiquitin chains relative to Lys63-linked chains. In summary, engineering compounds that inhibit USP7 activity by attenuating ubiquitin binding suggests opportunities for developing other deubiquitinase inhibitors and may be a strategy more broadly applicable to inhibiting proteins that require ubiquitin binding for full functional activity.</p

Enhanced integration methods for the peridynamic theory.

Doctor of PhilosophyDepartment of Mechanical and Nuclear EngineeringKevin B. LeaseXiao J. XinPeridynamics is a non-local continuum theory that formulates problems in terms of integration of interactions between the material points. Because the governing equation of motion in the peridynamic theory involves only integrals of displacements, rather than derivatives of displacements, this new theory offers great advantages in dealing with problems that contain discontinuities. Integration of the interaction force plays an important role in the formulation and numerical implementation of the peridynamic theory. In this study two enhanced methods of integration for peridynamics have been developed. In the first method, the continuum is discretized into cubic cells, and different geometric configurations over the cell and the horizon of interaction are categorized in detail. Integration of the peridynamic force over different intersection volumes are calculated accurately using an adaptive trapezoidal integration scheme with a combined relative-absolute error control. Numerical test examples are provided to demonstrate the accuracy of this new adaptive integration method. The bond-based peridynamic constitutive model is used in the calculation but this new method is also applicable to state-based peridynamics. In the second method, an integration method with fixed Gaussian points is employed to accurately calculate the integration of the peridynamic force. The moving least square approximation method is incorporated for interpolating the displacement field from the Gaussian points. A compensation factor is introduced to correct the soft boundary effect on the nodes near the boundaries. This work also uses linear viscous damping to minimize the dynamic effect in the solution process. Numerical results show the accuracy and effectiveness of this Gaussian integration method. Finally current research progress and prospective directions for several topics are discussed

Isolation of phosphopeptides by immobilized metal ion affinity chromatography.

The identification of protein phosphorylation sites from cell-derived proteins is crucial to the understanding of signal transduction pathways. While determining the modified sites on individual proteins can present a significant challenge, recent progress in the rapid, large-scale identification of phosphopeptides from complex protein mixtures by combinations of affinity chromatography and mass spectrometry provides a powerful tool to decipher the phosphoproteome. A set of protocols is described for sample preparation, fractionation, immobilized metal ion affinity chromatography (IMAC), and mass spectrometric analysis of phosphorylation sites. Parts of the protocols can be combined in different ways to adapt to sample amounts, complexity, and available equipment. Up to thousands of unique phosphopeptides can be sequenced from a single sample in a day, revealing a unique snapshot of global cellular phosphorylation sites on proteins and facilitating in-depth study of the identified phosphoproteins