International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

International Hackathon as a Tool to Augment Education, Collaboration, and Innovation in Global Neurosurgery.

BACKGROUND AND OBJECTIVES: Health care providers' exposure to global surgical disparities is limited in current nursing and/or medical school curricula. For instance, global health is often associated with infectious diseases or maternal health without acknowledging the growing need for surgical care in low- and middle-income countries (LMICs). We propose an international virtual hackathon based on neurosurgical patient cases in under-resourced settings as an educational tool to bring awareness to global surgical disparities and develop relationships among trainees in different countries. METHODS: Participants were recruited through email listservs, a social media campaign, and prize offerings. A 3-day virtual hackathon event was administered, which included workshops, mentorship, keynote panels, and pitch presentations to judges. Participants were presented with real patient cases and directed to solve a barrier to their care. Surveys assessed participants' backgrounds and event experience. The hackathon was executed through Zoom at Harvard Innovation Lab in Boston, MA, on March 25 to 27, 2022. Participants included medical students, with additional participants from business, engineering, or current health care workers. RESULTS: Three hundred seven applications were submitted for 100 spots. Participants included medical students, physicians, nurses, engineers, entrepreneurs, and undergraduates representing 25 countries and 82 cities. Fifty-one participants previously met a neurosurgeon, while 39 previously met a global health expert, with no difference between LMIC and high-income countries' respondents. Teams spent an average of 2.75 hours working with mentors, and 88% of postevent respondents said the event was "very" or "extremely conducive" to networking. Projects fell into 4 categories: access, language barriers, education and training, and resources. The winning team, which was interdisciplinary and international, developed an application that analyzes patient anatomy while performing physical therapy to facilitate remote care and clinical decision-making. CONCLUSION: An international virtual hackathon can be an educational tool to increase innovative ideas to address surgical disparities in LMICs and establish early collaborative relationships with medical trainees from different countries.

Functional roles of microRNAs in vasculogenic mimicry and resistance to therapy in human cancers: an update.

INTRODUCTION: Vasculogenic mimicry (VM) alludes to the ability of cancer cells to organize on three-dimensional channel-like structures to obtain nutrients and oxygen. This mechanism confers an aggressive phenotype, metastatic potential, and resistance to chemotherapy resulting in a poor prognosis. Recent studies have been focused on the identification of microRNAs (miRNAs) that regulate the VM representing potential therapeutic targets in cancer. AREAS COVERED: An overview of the roles of miRNAs on VM development and their functional relationships with tumor microenvironment. The functions of cancer stem-like cells in VM, and resistance to therapy are also discussed. Moreover, the modulation of VM by natural compounds is explored. The clinical significance of deregulated miRNAs as potential therapeutic targets in tumors showing VM is further highlighted. EXPERT OPINION: The miRNAs are regulators of protein-encoding genes involved in VM; however, their specific expression signatures with clinical value in large cohorts of patients have not been established yet. We considered that genomic profiling of miRNAs could be useful to define some hallmarks of tumors such as stemness, drug resistance, and VM in cancer patients. However, additional studies are needed to establish the relevant role of miRNAs as effective therapeutic targets in tumors that have developed VM.

Benzo[a]pyrene promotes an epithelial-to-mesenchymal transition process in MCF10A cells and mammary tumor growth and brain metastasis in female mice.

Breast cancer is the most frequent neoplasia in developed countries and the leading cause of death in women worldwide. Epithelial-to-mesenchymal transition (EMT) is a cellular process through which epithelial cells decrease or lose their epithelial characteristics and gain mesenchymal properties. EMT mediates tumor progression, because tumor cells acquire the capacity to execute the multiple steps of invasion and metastasis. Benzo[a]pyrene (B[a]P) is an environmental organic pollutant generated during the burning of fossil fuels, wood, and other organic materials. B[a]P exposition increases the incidence of breast cancer, and induces migration and/or invasion in MDA-MB-231 and MCF-7 breast cancer cells. However, the role of B[a]P in the induction of an EMT process and metastasis of mammary carcinoma cells has not been studied in detail. In this study, we demonstrate that B[a]P induces an EMT process in MCF10A mammary non-tumorigenic epithelial cells. In addition, B[a]P promotes the formation of larger tumors in Balb/cJ mice inoculated with 4T1 cells than in untreated mice and treated with dimethyl sulfoxide (DMSO). B[a]P also increases the number of mice with metastasis to brain and the total number of brain metastatic nodules in Balb/cJ mice inoculated with 4T1 cells compared with untreated mice and treated with DMSO. In conclusion, B[a]P induces an EMT process in MCF10A cells and the growth of mammary tumors and metastasis to brain in Balb/cJ mice inoculated with 4T1 cells.

Chromogenic, Biochemical and Proteomic Identification of Yeast and Yeast-like Microorganisms Isolated from Clinical Samples from Animals of Costa Rica.

Yeast infections are challenging human and animal medicine due to low rates of detection and the emergence of unknown ecology isolates. The aim of this study was to verify the biochemical identification of yeasts and yeast-like microorganisms obtained from animals comparing the results with chromogenic media and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS). Between January and August 2023, yeast and yeast-like isolates from samples of animals with suspicion of mycosis were identified using Vitek® 2 Compact, Brilliance® Candida Agar and MALDI Biotyper® MSP. A total of 39 cases were included, and 45 isolations were obtained. Cryptococcus neoformans (15.5%, 7/45), Meyerozyma guilliermondii (13.3%, 6/45), Candida parapsilosis (11.1%, 5/45), Candida albicans and Candida tropicalis (8.9%, each one 4/45) were the most identified organisms. There was full agreement with the three identification methods in 71.1% (32/45) of the isolates, disagreement on species in 17.8% (8/45), disagreement on genus and species in 6.7% (3/45) and, in 4.4% (2/45), there was no matched pattern in MALDI-TOF to compare the results. Biochemical methods are a good option in laboratories where proteomics are not available, and chromogenic media enhances diagnostics by detecting mixed infections. Surveillance must be implemented to improve the detection of agents shared between humans and animals.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico.

Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

MicroRNA-204 Regulates Angiogenesis and Vasculogenic Mimicry in CD44+/CD24- Breast Cancer Stem-like Cells.

Tumors have high requirements in terms of nutrients and oxygen. Angiogenesis is the classical mechanism for vessel formation. Tumoral vascularization has the function of nourishing the cancer cells to support tumor growth. Vasculogenic mimicry, a novel intratumoral microcirculation system, alludes to the ability of cancer cells to organize in three-dimensional (3D) channel-like architectures. It also supplies the tumors with nutrients and oxygen. Both mechanisms operate in a coordinated way; however, their functions in breast cancer stem-like cells and their regulation by microRNAs remain elusive. In the present study, we investigated the functional role of microRNA-204 (miR-204) on angiogenesis and vasculogenic mimicry in breast cancer stem-like cells. Using flow cytometry assays, we found that 86.1% of MDA-MB-231 and 92% of Hs-578t breast cancer cells showed the CD44+/CD24- immunophenotype representative of cancer stem-like cells (CSCs). The MDA-MB-231 subpopulation of CSCs exhibited the ability to form mammospheres, as expected. Interestingly, we found that the restoration of miR-204 expression in CSCs significantly inhibited the number and size of the mammospheres. Moreover, we found that MDA-MB-231 and Hs-578t CSCs efficiently undergo angiogenesis and hypoxia-induced vasculogenic mimicry in vitro. The transfection of precursor miR-204 in both CSCs was able to impair the angiogenesis in the HUVEC cell model, which was observed as a diminution in the number of polygons and sprouting cells. Remarkably, miR-204 mimics also resulted in the inhibition of vasculogenic mimicry formation in MDA-MB-231 and Hs-578t CSCs, with a significant reduction in the number of channel-like structures and branch points. Mechanistically, the effects of miR-204 were associated with a diminution of pro-angiogenic VEGFA and ß-catenin protein levels. In conclusion, our findings indicated that miR-204 abrogates the angiogenesis and vasculogenic mimicry development in breast cancer stem-like cells, suggesting that it could be a potential tool for breast cancer intervention based on microRNA replacement therapies.

The rs1477196 SNP of the FTO Gene is Associated with Primary Knee Osteoarthritis in a Female Population from Northern Mexico

ABSTRACT Background: Osteoarthritis is a frequent rheumatic disease. Some single-nucleotide polymorphisms of the gene associated with fat mass and obesity are associated with increased body mass index and knee osteoarthritis. Objective: The objective of this study was to analyze the association of single nucleotide polymorphism rs1477196 of the fat mass and obesity gene with primary knee osteoarthritis. Methods: This observational and cross-sectional study included 347 Mexican participants. We performed the genotypification analysis with TaqMan® probe C_2031262_10 for rs1477196 (Thermo Fisher Scientific). Multivariate analysis included covariables such as age, type 2 diabetes, obesity, and postmenopause. Results: Type 2 diabetes, obesity, and postmenopause were associated with primary knee osteoarthritis in female participants. We did not find an association between rs1477196 and obesity. In the codominant and dominant genetic models, rs1477196 was significantly associated with primary knee osteoarthritis only in the female group, including in the model adjusted by other covariables (odds ratio = 2.517; 1.035-6.123; p = 0.042 and odds ratio = 2.387; 1.054-5.407; p = 0.037, respectively). The interaction between rs1477196 and obesity was significantly associated with primary knee osteoarthritis in female participants (p = 0.039 and p = 0.043). Conclusions: Our findings suggest that the rs1477196 variant of the fat and obesity mass gene may be associated with the risk of primary knee osteoarthritis in women.

Multiparity favors same-sex partner preference in male rats.

Same-sex partner preference is present in many mammals, including rodents. Several possible causal factors have been proposed for the establishment of this preference. The Fraternal Birth Order effect refers to the observation that older brothers increase the probability of homosexuality in men, but no experiment has analyzed this possibility. In this study, partner preference (tested in a three compartments box) and female and male sexual behavior (studied in a cylindrical arena) were evaluated in young male rats (3 months) born to multiparous mothers that had 4-6 previous gestations and around 12 months of age. Control groups were young male rats born to primiparous young (4 months) or aged (12 months) mothers. In the partner preference test, the males born to multiparous dams spent less time interacting with the receptive female and more time interacting with the sexually active male, and a 39% exhibited same-sex partner preference. This high percentage seems related to multiparity of their mothers and not to maternal age, because the males born to primiparous aged females (12 months) showed a similar low proportion of same-sex partner preference than the males born to young (4 months) primiparous females (4%). In the sexual behavior tests, no male born of a multiparous dam and with same-sex preference ejaculated and 54% displayed proceptivity and lordosis. Present results suggest that the fraternal birth order effect may occur also in rats.

Coverage error and shade-match accuracy in three ceramic gingival systems.

STATEMENT OF PROBLEM: Research into the coverage error (CE) of gingival systems that have been expanded by using ceramic specimens created by mixing basic colors is lacking. PURPOSE: The purpose of this in vitro study was to compare the CEs of 3 ceramic gingival color systems that have been expanded with basic-color mixtures from a sample of 360 White participants and to classify the participants according to the accuracy of the shade match achieved with each system. MATERIAL AND METHODS: L*a*b* color coordinates were recorded in 3 zones of attached gingiva for 360 White participants with healthy gingival tissue (187 men and 173 women). The CEs were calculated for 3 ceramic gingival systems that had been expanded with specimens obtained by mixing the basic colors in consecutive order, the color percentages in each mixture having been altered by 10% increments. The systems were Heraceram (Kulzer GmbH) (n=51); Vita VM9 (Vita-Zahnfabrik) (n=41); and IPS Style (Ivoclar AG) (n=41). The participants were classified into 3 groups according to how well the selected shade matched their gingival color (excellent, acceptable, or poor). The data were analyzed using a 1-way ANOVA with a randomized block design and the homogeneity of proportions test (α=.05). RESULTS: Statistically significant differences were found between the CEs of the 3 expanded gingival systems in the 3 zones where gingival color was measured (P<.001). The expanded Heraceram system had the smallest CE (ΔE00: minimum 2.66 in the middle zone and maximum 2.95 at the mucogingival line). In the 3 gingival zones, the expanded IPS Style system produced the largest percentage of participants with a poor shade match (ΔE00: minimum 71.4% at the mucogingival line and maximum 75.8% at the free gingival margin), while the expanded Heraceram system had the lowest percentage of participants with a poor shade match (ΔE00: minimum 33.3% in the middle zone and maximum 41.7% at the mucogingival line). CONCLUSIONS: The CEs calculated for the expanded Vita VM9 and IPS Style ceramic gingival color systems exceeded the clinical acceptability thresholds in the 3 zones examined. According to the ΔE00 formula, the gingival color of at least 33% of participants matched poorly with the expanded systems studied.

Genetic Variant HLA-DRB1*0403 and Therapeutic Response to Disease-Modifying Therapies in Multiple Sclerosis: A Case-Control Study.

Multiple sclerosis (MS) is a chronic and demyelinating disease with an autoimmune origin, which leads to neurodegeneration and progressive disability. Approximately 30 to 50% of patients do not respond optimally to disease-modifying therapies (DMTs), and therapeutic response may be influenced by genetic factors such as genetic variants. Therefore, our study aimed to investigate the association of the HLA-DRB1*0403 genetic variant and therapeutic response to DMTs in MS. We included 105 patients with MS diagnosis. No evidence of disease activity based on the absence of clinical relapse, disability progression or radiological activity (NEDA-3) was used to classify the therapeutic response. Patients were classified as follows: (a) controls: patients who achieved NEDA-3; (b) cases: patients who did not achieve NEDA-3. DNA was extracted from peripheral blood leukocytes. HLA-DRB1*0403 genetic variant was analyzed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. NEDA-3 was achieved in 86.7% of MS patients treated with DMTs. Genotype frequencies were GG 50.5%, GA 34.3%, and AA 15.2%. No differences were observed in the genetic variant AA between patients who achieved NEDA-3 versus patients who did not achieve NEDA-3 (48.7% vs. 43.1%, p = 0.6). We concluded that in Mexican patients with MS, HLA-DRB1*0403 was not associated with the therapeutic response to DMTs.

Degree of Standardisation in Ceramic Gingival Systems.

No gingival shade guide exists that can be used as a 'gold standard' in gingival shade selection. This research, therefore, aimed to determine whether comparable results in subjective gingival shade selection can be achieved using basic gingival colours produced by distinct manufacturers. It also aimed to explore how coverage of the colour space is affected by mixing these basic colours to create additional shades. To achieve these objectives, the basic gingival colours of three ceramic systems (Heraceram, Kulzer, Madrid, Spain; Vita VM9, Vita Zahnfabrik, Bad Säckingen, Germany; IPS Style, Ivoclar, Schaan, Liechtenstein) were analysed. The colour systems were expanded by creating porcelain gingival samples, whose colours were obtained by mixing the basic colours, altering each mixture by increments of 10%, and respecting the numerical order used by manufacturers to identify the colours. The colour coordinates of the basic and additional colours were recorded using spectrophotometry, and the intra- and inter-system colour differences were calculated using the Euclidean (ΔEab) and CIEDE2000 (ΔE00) formulae. None of the basic colours in the three systems, despite their similar nomenclature, were found to be interchangeable (the colour differences exceeded the gingival acceptability threshold: ΔE00 2.9 units). The expanded gingival colour systems, with mixtures altered by 10% increments, notably increased the gingival colour space covered by the original systems. The authors concluded that there are clear differences between the basic gingival colours produced by distinct manufacturers using the same nomenclature. Ceramic samples produced by mixing basic gingival colours are a resource with the potential to improve subjective gingival shade matching.

Nephrologists' perspectives on the impact of COVID-19 on caring for patients undergoing dialysis in Latin America: a qualitative study.

OBJECTIVE: To describe the experiences of nephrologists on caring for patients undergoing in-centre haemodialysis during the COVID-19 pandemic in Latin America. DESIGN: Twenty-five semistructured interviews were conducted by Zoom videoconference in English and Spanish languages during 2020 until data saturation. Using thematic analysis, we conducted line-by-line coding to inductively identify themes. SETTING: 25 centres across nine countries in Latin America. PARTICIPANTS: Nephrologists (17 male and 8 female) were purposively sampled to include diverse demographic characteristics and clinical experience. RESULTS: We identified five themes: shock and immediate mobilisation for preparedness (overwhelmed and distressed, expanding responsibilities to manage COVID-19 infection and united for workforce resilience); personal vulnerability (being infected with COVID-19 and fear of transmitting COVID-19 to family); infrastructural susceptibility of dialysis units (lacking resources and facilities for quarantine, struggling to prevent cross-contamination, and depletion of personal protective equipment and cleaning supplies); helplessness and moral distress (being forced to ration life-sustaining equipment and care, being concerned about delayed and shortened dialysis sessions, patient hesitancy to attend to dialysis sessions, being grieved by socioeconomic disparities, deterioration of patients with COVID-19, harms of isolation and inability to provide kidney replacement therapy); and fostering innovative delivery of care (expanding use of telehealth, increasing uptake of PD and shifting focus on preventing syndemics). CONCLUSION: Nephrologists felt personally and professionally vulnerable and reported feeling helpless and morally distressed because they doubted their capacity to provide safe care for patients undergoing dialysis. Better availability and mobilisation of resources and capacities to adapt models of care, including telehealth and home-based dialysis, are urgently needed.

Endothelial activation impairs the function of small extracellular vesicles.

Small extracellular vesicles are nanosized vesicles (30-200 nm) that can ferry proteins, nucleic acids, and lipids between cells and therefore, have significant potential as biomarkers, drug delivery tools or therapeutic agents. SEVs of endothelial origin have been shown to -among other functions-reduce in vitro ischemia/reperfusion (I/R) injury in cardiomyocytes, but whether a pro-inflammatory state of the endothelium impairs the functionality of these SEVs remains to be elucidated. To test this, human umbilical vein endothelial cells cells were treated with TNF-α 10 ng/mL and the expression of the pro-inflammatory parameters VCAM-1, ICAM-1 and eNOS were determined by Western blot. SEVs were isolated from endothelial cells treated with or without TNF-α 10 ng/mL using size exclusion chromatography. The size and concentration of SEVs was measured by Nanoparticle Tracking Analysis. The expression of the surface marker CD81 was determined by immunoassay, whereas their morphology was assessed by electron microscopy. The function of endothelial SEVs was assessed by evaluating their cardioprotective effect in an ex vivo model of global I/R using isolated hearts from adult C57BL/6 mice. Treatment of HUVECs with TNF-α induced the expression of VCAM-1 and ICAM-1, whereas eNOS levels were decreased. TNF-α did not affect the production, size, morphology, or expression of CD81. SEVs significantly reduced the infarct size as compared with untreated mice hearts, but SEVs isolated from TNF-α treated cells were unable to achieve this effect. Therefore, a pro-inflammatory state induced by TNF-α does not alter the production of endothelial SEVs but impairs their function in the setting of I/R injury.

Metastatic breast tumors downregulate miR-145 regulating the hypoxia-induced vasculogenic mimicry.

Tumor cells grow in three-dimensional (3D) channels-like structures denoted as vasculogenic mimicry (VM), which provides a route for nutrients and oxygen acquisition. VM is activated by hypoxia and associated with metastasis and poor prognosis. MetastamiRs are microRNAs regulating metastasis, however, if they control VM in breast cancer remains poorly understood. The aim of this study was to evaluate the expression of VM-associated microRNAs in tumors of metastatic breast cancer patients. Firstly, we constructed microRNAs/mRNAs coregulation networks using expression data from TCGA databases. Dozens of microRNAs regulating genes involved in VM and metastasis were found. Of these, we selected 10 microRNAs for further characterization. The presence of VM in histological samples from patients with or without metastasis was evaluated using CD31-/PAS+ immunophenotyping. Remarkably, data showed that VM was significantly increased in tumors from patients with metastasis in comparison with no-metastatic group. Gene expression analysis indicated that miR-145, miR-142-3p, miR-31, miR-148a, miR-200b-3p and miR-526b were downregulated in primary tumors from patients with metastatic disease and positive for VM. Moreover, modulated microRNAs showed a predictive clinical value in overall survival in a cohort (n=1262) of breast cancer patients. Of these, we evaluated the role of miR-145 in formation of hypoxia-induced 3D channels-like using an in vitro model that recapitulates the early stages of VM. Data showed that miR-145 mimics was able to abolish the VM development in both metastatic Hs578t and MDA-MB-231 breast cancer cells. In conclusion, manipulation of miR-145 levels may represent a therapeutic approach in metastatic breast cancer patients that developed VM.

Association of the STAT4 Gene rs7574865 Polymorphism with IFN-γ Levels in Patients with Systemic Lupus Erythematosus.

STAT4 plays an important role in disease activity in SLE patients. STAT4 particles have the capacity to activate the transcription of genes associated with the production of TH1 and Th17 lymphocytes, with a greater predominance on the production of IFN-γ and IL-17A. The presence of variants in STAT4 genes has a major impact on the generation of autoimmunity. However, there are few studies evaluating the impact of these variants on the production of proinflammatory cytokines such as IFN-γ and IL-17A. Methods-A case-control study was carried out with 206 Mexican mestizo patients residing in Western Mexico with a diagnosis of SLE and a group of 80 patients without autoimmune diseases was captured to determine the cut-off point for high IFN-γ levels. In this study, SLE patients with high IFN-γ levels were considered as cases (cut-off > 15.6 pg/mL), and SLE patients with normal IFN-γ levels were considered as controls (cut-off ≤ 15.6 pg/mL). Disease activity was identified from the systemic lupus erythematosus disease activity index (SLEDAI). For the determination of levels of cytokines IFN-γ, IL-12, and IL17A, commercial ELISA kits were used. Genotyping of STAT4 rs7574865 (G > T) was performed by quantitative polymerase chain reaction (qPCR) using TaqMan probes. Results-The patients with SLE had a median age of 45 years with a range of disease duration from 4 years to 18 years; 45.6% were identified as having disease activity. In this sample, we identified a high IFN-γ prevalence of 35.4%. The levels of IFN-γ were higher in the patients with genotype TT than GG. We found that TT genotype conferred a higher risk of high IFN-γ when compared to the GG and GT genotypes. Conclusions-In this study, we identified that the polymorphic genotype TT of the STAT4 gene rs7574865 polymorphism is associated with increased levels of IFN-γ. However, its strength of association was weak, so complementary studies are needed to evaluate its impact on SLE patients.

[Frequency of food allergy in students of human medicine of a private university]. / Frecuencia de alergia alimentaria en estudiantes de medicina humana de una universidad privada.

OBJECTIVE: Determine the frequency of total food allergy, and to Peruvian products, in Human Medicine students. METHODS: A study design is observational, descriptive and retrospective was made. Human medicine students, aged 18-25 from a private Peruvian university were included in a type of snowball sampling via electronic messaging. The sample size was calculated using the OpenEpi v3.0 program and the prevalence formula. RESULTS: We registered 355 students, with a mean age of 20.87 years (SD ± 5.01). A frequency of food allergy was also found in 9.3% of the total participants in terms of native products and common in other countries, the highest percentage are seafood 2.24%, spices and condiments 2.24%, allergy to fruits 1.4%, milk 1.4%, red meat 0.84%. CONCLUSIONS: The frequencies of self-reported food allergy produced was 9.3% by native Peruvian products and commonly consumed nationwide.

OBJECTIVO: Determinar la frecuencia de alergia alimentaria en general, y de productos de consumo común oriundos del Perú, en estudiantes de medicina humana. MÉTODOS: Estudio observacional, descriptivo y retrospectivo, al que se incluyeron estudiantes de medicina humana de 18-25 años, de una universidad privada del Perú, seleccionados mediante muestreo tipo "bola de nieve" a través de mensajería electrónica. El tamaño de la muestra se calculó con el programa OpenEpi v3.0 y la fórmula de prevalencia. RESULTADOS: Se registraron 355 estudiantes, con edad media de 20.9 años (SD ± 5,01). La frecuencia de alergia alimentaria fue de 9.3% del total de la muestra; y la frecuencia de alergia a productos de consumo común (oriundos del país) reportó: mariscos 2.24%, especias y condimentos 2.24%, frutas 1.4%, leche 1.4% y carnes rojas 0.84%. CONCLUSIONES: Existe una frecuencia de 9.3% de alergia alimentaria autorreportada, producida por productos de consumo común (oriundos del Perú) a nivel nacional.

Caveolae Microdomains Mediate STAT5 Signaling Induced by Insulin in MCF-7 Breast Cancer Cells.

Caveolae are small plasma membrane invaginations constituted for membrane proteins namely caveolins and cytosolic proteins termed cavins, which can occupy up to 50% of the surface of mammalian cells. The caveolae have been involved with a variety of cellular processes including regulation of cellular signaling. Insulin is a hormone that mediates a variety of physiological processes through activation of insulin receptor (IR), which is a tyrosine kinase receptor expressed in all mammalian tissues. Insulin induces activation of signal transducers and activators of transcription (STAT) family members including STAT5. In this study, we demonstrate, for the first time, that insulin induces phosphorylation of STAT5 at tyrosine-694 (STAT5-Tyr(P)694), STAT5 nuclear accumulation and an increase in STAT5-DNA complex formation in MCF-7 breast cancer cells. Insulin also induces nuclear accumulation of STAT5-Tyr(P)694, caveolin-1, and IR in MCF-7 cells. STAT5 nuclear accumulation and the increase of STAT5-DNA complex formation require the integrity of caveolae and microtubule network. Moreover, insulin induces an increase and nuclear accumulation of STAT5-Tyr(P)694 in MDA-MB-231 breast cancer cells. In conclusion, results demonstrate that caveolae and microtubule network play an important role in STAT5-Tyr(P)694, STAT5 nuclear accumulation and STAT5-DNA complex formation induced by insulin in breast cancer cells.

Association of personal, behavioral and positive psychological variables with somatization and number of diseases in Mexican general population: the influence of gender.

The objective of the study is to determine the personal, behavioral and psychological variables associated with somatization and the number of diseases in each gender from a sample of Mexican general population. They answered a questionnaire of behavioral and psychological variables including somatization and the sum of 16 different diseases and any additional one, finally the body mass index (BMI) was measured. A total of 164 participants (women = 90, men = 74) were included. We observed that women had more somatization and number of diseases than men and that more variables (mainly psychological) were associated with somatization and with the number of diseases in women than in men. Among the variables most negatively correlated in women with both variables were sleep quality (r = -0.525 and r = -0.536, p < 0.001), self-acceptance (r = -0.460 and r = -0.501, p < 0.001), positive relations with others (r = -0.447 and r = -0.441 p < 0.001), environmental mastery (r = -0.414, p < 0.001, for both variables), purpose in life and optimism; while men only showed a low negative correlation between emotion regulation and the number of diseases (r = -0.289, p < 0.05). The positive associated variables in women were anxiety, negative emotions and depression; while men showed a lower correlation between these three variables only with somatization. The somatization and age were positively related to the number of diseases in both genders and the BMI was significantly associated with the number of diseases only in men. In conclusion, women had more somatization and number of diseases than men and also had more relation between psychological variables and the two dependent variables than men, which could in part explains the higher values of somatization and the number of diseases in women, considering that they usually present higher values of psychopathological variables.

Androgen receptors immunoreactivity in the rat brain of males with same-sex preference.

Androgen receptors (AR) are crucial in the control of male sexual behavior and sex preference. AR are particularly concentrated in areas related with the neuroendocrine control of sex preference including the medial amygdala (MeA), the ventromedial nucleus of the hypothalamus (VMH), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA), the nucleus accumbens (Acb), the suprachiasmatic (SCh) and supraoptic (SO) nuclei, but also seem to be important for the control of reproductive processes in the hippocampus (CA1-CA4 and dentate gyrus, DG). In the present study we analyzed the density of AR in these brain areas of adult male rats with sexual preference (established in a three-compartment box). Same-sex preference was produced in male rats by the prenatal administration of the aromatase inhibitor, letrozole (0.56 µg/kg/ml s.c. G10-22) that usually produces 1-2 animals per litter with same sex preference, while the others retain a female sex preference. We also included a group of proestrus females that had a clear preference for a sexually active male. AR were analyzed by immunocytochemistry using PG21 as primary antibody. We also measured total plasma testosterone concentrations by radioimmunoassay. In males with same sex preference there was a specific AR overexpression in CA3 and CA4 that suggests a feminized pattern because females in proestrus trend to show a higher density of AR in these hippocampal areas. Sex differences in AR density were found in the anterior cingulate cortex (ACg) and frontoparietal cortex (FrPa). Serum levels of testosterone did not differ between groups. Data are discussed based on the role of AR in the hippocampus.