Albergue agroturístico en el distrito de Limatambo – Cusco

El turismo es uno de los fenómenos sociales y económicos más importantes, siendo capaz de potenciar territorios y generar un progreso económico y social. El legado peruano está constituido por riquezas naturales, históricas y culturales incomparables; y es precisamente Cusco, uno de los departamentos que mejor representa toda la riqueza. En las zonas rurales, la principal fuente económica es la agropecuaria, sin embargo, esta actividad no se da abasto para incrementar el desarrollo de las mismas; a esto se suma un problema social que consiste en la falta de integración entre el medio rural y el urbano. Dicho esto, los pobladores en conjunto con las entidades gubernamentales, han encontrado en el turismo una alternativa potencial que incrementaría el desarrollo integral. Tal es el caso del distrito de Limatambo, ubicado en el departamento de Cusco, provincia de Anta, que forma parte de la red integral de turismo regional y conecta con dos de los atractivos turísticos más relevantes a nivel nacional: Santuario Histórico de Machu Picchu y el Parque Arqueológico de Choquequirao. La presente tesis pretende brindar un hospedaje de experiencia enriquecedora para los turistas nacionales e internacionales durante su estadía en el distrito; es por ello que surge la iniciativa de aplicar el agroturismo participativo, que permitiría que el visitante se involucre con la realidad del poblador y se sensibilice con sus necesidades, este proceso genera un gran vínculo poblador - turista y se convierte en una experiencia de integración social en la que ambos se enriquecen culturalmente en forma participativa. El perfil del turista que disfrutará del albergue es aquel que, alejándose de la dinámica urbana, se involucre participativamente con la naturaleza del lugar, pero sin dejar de contar con los servicios básicos para su comodidad

The effect of different volumes and temperatures of saline on the bladder pressure measurement in critically ill patients

INTRODUCTION: Intra-abdominal hypertension is common in critically ill patients and is associated with increased severity of organ failure and mortality. The techniques most commonly used to estimate intra-abdominal pressure are measurements of bladder and gastric pressures. The bladder technique requires that the bladder be infused with a certain amount of saline, to ensure that there is a conductive fluid column between the bladder and the transducer. The aim of this study was to evaluate the effect of different volumes and temperatures of infused saline on bladder pressure measurements in comparison with gastric pressure. METHODS: Thirteen mechanically ventilated critically ill patients (11 male; body mass index 25.5 +/- 4.6 kg/m2; arterial oxygen tension/fractional inspired oxygen ratio 225 +/- 48 mmHg) were enrolled. Bladder pressure was measured using volumes of saline from 50 to 200 ml at body temperature (35 to 37 degrees C) and room temperature (18 to 20 degrees C). RESULTS: Bladder pressure was no different between 50 ml and 100 ml saline (9.5 +/- 3.7 mmHg and 13.7 +/- 5.6 mmHg), but it significantly increased with 150 and 200 ml (21.1 +/- 10.4 mmHg and 27.1 +/- 15.5 mmHg). Infusion of saline at room temperature caused a significantly greater bladder pressure compared with saline at body temperature. The lowest difference between bladder and gastric pressure was obtained with a volume of 50 ml. CONCLUSION: The bladder acts as a passive structure, transmitting intra-abdominal pressure only with saline volumes between 50 ml and 100 ml. Infusion of a saline at room temperature caused a higher bladder pressure, probably because of contraction of the detrusor bladder muscl

Evaluation of a Portable Gynecological Examination Table on Increasing Access to Cervical Cancer Screenings

Introduction: Cervical cancer is a preventable disease affecting millions of women worldwide, with higher prevalence and mortality in developing countries. One explanation of this disparity is due to reduced access to screenings, especially in rural communities where mobile health clinics are limited by what medical equipment they can bring. To address these barriers, an engineering team called Project MESA (Making Examinations Safe and Accessible) designed a gynecological examination table that is portable, lightweight, and easily sanitizable. Objective: This study aims to (1) evaluate whether the implementation of this device improves the clinician’s ability to perform pap smears as opposed to alternative surfaces, and (2) investigate the impact on patients’ comfort with cervical cancer screening. Methods: Two gynecological exam tables are being used by a partner organization with clinics in Perú and Nicaragua. Since September of 2022, 42 responses have been recorded. Using clinician and patient questionnaires that were developed based on field observations, the team will perform a mixed methods analysis to compare clinician and patient preferences on the new device versus alternative surfaces. Results: Preliminary data may support greater clinician and patient satisfaction with the new device, but cannot be statistically confirmed yet due to ongoing data collection. Results that can be discussed are dynamic testing on the gynecological table which supported safety through 15,600 uses and positive feedback from many clinicians and international partners. Conclusion: This project provides a construct to address barriers to cervical cancer screenings, with more quantitative results becoming available soon

Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways

<p>Abstract</p> <p>Background</p> <p>Osteosarcoma (OS) is the most common primary bone tumour in children and young adults. Despite improved prognosis, metastatic or relapsed OS remains largely incurable and no significant improvement has been observed in the last 20 years. Therefore, the search for alternative agents in OS is mandatory.</p> <p>Results</p> <p>We investigated phospho-ERK 1/2, MCL-1, and phospho-Ezrin/Radixin/Moesin (P-ERM) as potential therapeutic targets in OS. Activation of these pathways was shown by immunohistochemistry in about 70% of cases and in all OS cell lines analyzed. Mutational analysis revealed no activating mutations in KRAS whereas BRAF gene was found to be mutated in 4/30 OS samples from patients. Based on these results we tested the multi-kinase inhibitor sorafenib (BAY 43-9006) in preclinical models of OS. Sorafenib inhibited OS cell line proliferation, induced apoptosis and downregulated P-ERK1/2, MCL-1, and P-ERM in a dose-dependent manner. The dephosphorylation of ERM was not due to ERK inhibition. The downregulation of MCL-1 led to an increase in apoptosis in OS cell lines. In chick embryo chorioallantoic membranes, OS supernatants induced angiogenesis, which was blocked by sorafenib and it was also shown that sorafenib reduced VEGF and MMP2 production. In addition, sorafenib treatment dramatically reduced tumour volume of OS xenografts and lung metastasis in SCID mice.</p> <p>Conclusion</p> <p>In conclusion, ERK1/2, MCL-1 and ERM pathways are shown to be active in OS. Sorafenib is able to inhibit their signal transduction, both <it>in vitro </it>and <it>in vivo</it>, displaying anti-tumoural activity, anti-angiogenic effects, and reducing metastatic colony formation in lungs. These data support the testing of sorafenib as a potential therapeutic option in metastatic or relapsed OS patients unresponsive to standard treatments.</p

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

The role of immune suppression in COVID-19 hospitalization: clinical and epidemiological trends over three years of SARS-CoV-2 epidemic

Specific immune suppression types have been associated with a greater risk of severe COVID-19 disease and death. We analyzed data from patients &gt;17 years that were hospitalized for COVID-19 at the “Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico” in Milan (Lombardy, Northern Italy). The study included 1727 SARS-CoV-2-positive patients (1,131 males, median age of 65 years) hospitalized between February 2020 and November 2022. Of these, 321 (18.6%, CI: 16.8–20.4%) had at least one condition defining immune suppression. Immune suppressed subjects were more likely to have other co-morbidities (80.4% vs. 69.8%, p &lt; 0.001) and be vaccinated (37% vs. 12.7%, p &lt; 0.001). We evaluated the contribution of immune suppression to hospitalization during the various stages of the epidemic and investigated whether immune suppression contributed to severe outcomes and death, also considering the vaccination status of the patients. The proportion of immune suppressed patients among all hospitalizations (initially stable at &lt;20%) started to increase around December 2021, and remained high (30–50%). This change coincided with an increase in the proportions of older patients and patients with co-morbidities and with a decrease in the proportion of patients with severe outcomes. Vaccinated patients showed a lower proportion of severe outcomes; among non-vaccinated patients, severe outcomes were more common in immune suppressed individuals. Immune suppression was a significant predictor of severe outcomes, after adjusting for age, sex, co-morbidities, period of hospitalization, and vaccination status (OR: 1.64; 95% CI: 1.23–2.19), while vaccination was a protective factor (OR: 0.31; 95% IC: 0.20–0.47). However, after November 2021, differences in disease outcomes between vaccinated and non-vaccinated groups (for both immune suppressed and immune competent subjects) disappeared. Since December 2021, the spread of the less virulent Omicron variant and an overall higher level of induced and/or natural immunity likely contributed to the observed shift in hospitalized patient characteristics. Nonetheless, vaccination against SARS-CoV-2, likely in combination with naturally acquired immunity, effectively reduced severe outcomes in both immune competent (73.9% vs. 48.2%, p &lt; 0.001) and immune suppressed (66.4% vs. 35.2%, p &lt; 0.001) patients, confirming previous observations about the value of the vaccine in preventing serious disease

A New Kid on the Block: Sacituzumab Govitecan for the Treatment of Breast Cancer and Other Solid Tumors

Human trophoblast cell-surface antigen-2 (Trop-2) is a membrane glycoprotein involved in cell proliferation and motility, frequently overexpressed in epithelial tumors. Thus, it represents an attractive target for anticancer therapies. Sacituzumab govitecan (SG) is a third-generation antibody-drug conjugate, consisting of an anti-Trop-2 monoclonal antibody (hRS7), a hydrolyzable linker, and a cytotoxin (SN38), which inhibits topoisomerase 1. Specific pharmacological features, such as the high antibody to payload ratio, the ultra-toxic nature of SN38, and the capacity to kill surrounding tumor cells (the bystander effect), make SG a very promising drug for cancer treatment. Indeed, unprecedented results have been observed with SG in patients with heavily pretreated advanced triple-negative breast cancer and urothelial carcinomas, and the drug has already received approval for these indications. These results are coupled with a manageable toxicity profile, with neutropenia and diarrhea as the most frequent adverse events, mainly of grades 1&ndash;2. While several trials are exploring SG activity in different tumor types and settings, potential biomarkers of response are under investigation. Among these, Trop-2 overexpression and the presence of BRCA1/2 mutations seem to be the most promising. We review the available literature concerning SG, with a focus on its toxicity spectrum and possible biomarkers of its response

Open Access The effect of different volumes and temperatures of saline on the bladder pressure measurement in critically ill patients

Abstract Introduction Intra-abdominal hypertension is common in critically ill patients and is associated with increased severity of organ failure and mortality. The techniques most commonly used to estimate intra-abdominal pressure are measurements of bladder and gastric pressures. The bladder technique requires that the bladder be infused with a certain amount of saline, to ensure that there is a conductive fluid column between the bladder and the transducer. The aim of this study was to evaluate the effect of different volumes and temperatures of infused saline on bladder pressure measurements in comparison with gastric pressure

Trophism and Homeostasis of Liver Sinusoidal Endothelial Graft Cells during Preservation, with and without Hypothermic Oxygenated Perfusion

The aim of the present study was to evaluate the homeostasis and trophism of liver sinusoidal endothelial cells (LSECs) in vivo in different stages of liver graft donation, in order to understand the effects of graft ischemia and perfusion on LSEC activity in liver grafts. Special attention was paid to grafts that underwent hypothermic oxygenated perfusion (HOPE). Forty-seven donors were prospectively enrolled, and two distinct biopsies were performed in each case: one allocation biopsy (at the stage of organ allocation) and one post-perfusion biopsy, performed after graft implant in the recipients. In all biopsies, immunohistochemistry and RT-PCR analyses were carried out for the endothelial markers CD34, ERG, Nestin, and VEGFR-2. We observed an increase in CD34 immunoreactivity in LSEC during the whole preservation/perfusion period (p &lt; 0.001). Nestin and ERG expression was low in allocation biopsies, but increased in post-perfusion biopsies, in both immunohistochemistry and RT-PCR (p &lt; 0.001). An inverse correlation was observed between ERG positivity and donor age. Our results indicate that LSEC trophism is severely depressed in liver grafts, but it is restored after reperfusion in standard conditions. The execution of HOPE seems to improve this recovery, confirming the effectiveness of this machine perfusion technique in restoring endothelial functions

Inhibition of FGF23 is a therapeutic strategy to target hematopoietic stem cell niche defects in β-thalassemia

Clinical evidence highlights a relationship between the blood and the bone, but the underlying mechanism linking these two tissues is not fully elucidated. Here, we used beta-thalassemia as a model of congenital anemia with bone and bone marrow (BM) niche defects. We demonstrate that fibroblast growth factor 23 (FGF23) is increased in patients and mice with beta-thalassemia because erythropoietin induces FGF23 overproduction in bone and BM erythroid cells via ERK1/2 and STAT5 pathways. We show that in vivo inhibition of FGF23 signaling by carboxyl-terminal FGF23 peptide is a safe and efficacious therapeutic strategy to rescue bone mineralization and deposition in mice with beta-thalassemia, normalizing the expression of niche factors and restoring hematopoietic stem cell (HSC) function. FGF23 may thus represent a molecular link connecting anemia, bone, and the HSC niche. This study provides a translational approach to targeting bone defects and rescuing HSC niche interactions, with potential clinical relevance for improving HSC transplantation and gene therapy for hematopoietic disorders