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1.
PLoS Genet ; 20(2): e1011164, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38416769

RESUMO

TOP2 inhibitors (TOP2i) are effective drugs for breast cancer treatment. However, they can cause cardiotoxicity in some women. The most widely used TOP2i include anthracyclines (AC) Doxorubicin (DOX), Daunorubicin (DNR), Epirubicin (EPI), and the anthraquinone Mitoxantrone (MTX). It is unclear whether women would experience the same adverse effects from all drugs in this class, or if specific drugs would be preferable for certain individuals based on their cardiotoxicity risk profile. To investigate this, we studied the effects of treatment of DOX, DNR, EPI, MTX, and an unrelated monoclonal antibody Trastuzumab (TRZ) on iPSC-derived cardiomyocytes (iPSC-CMs) from six healthy females. All TOP2i induce cell death at concentrations observed in cancer patient serum, while TRZ does not. A sub-lethal dose of all TOP2i induces limited cellular stress but affects calcium handling, a function critical for cardiomyocyte contraction. TOP2i induce thousands of gene expression changes over time, giving rise to four distinct gene expression response signatures, denoted as TOP2i early-acute, early-sustained, and late response genes, and non-response genes. There is no drug- or AC-specific signature. TOP2i early response genes are enriched in chromatin regulators, which mediate AC sensitivity across breast cancer patients. However, there is increased transcriptional variability between individuals following AC treatments. To investigate potential genetic effects on response variability, we first identified a reported set of expression quantitative trait loci (eQTLs) uncovered following DOX treatment in iPSC-CMs. Indeed, DOX response eQTLs are enriched in genes that respond to all TOP2i. Next, we identified 38 genes in loci associated with AC toxicity by GWAS or TWAS. Two thirds of the genes that respond to at least one TOP2i, respond to all ACs with the same direction of effect. Our data demonstrate that TOP2i induce thousands of shared gene expression changes in cardiomyocytes, including genes near SNPs associated with inter-individual variation in response to DOX treatment and AC-induced cardiotoxicity.


Assuntos
Antraciclinas , Cardiotoxicidade , Humanos , Feminino , Antraciclinas/efeitos adversos , Antraciclinas/metabolismo , Cardiotoxicidade/genética , Cardiotoxicidade/metabolismo , Antibióticos Antineoplásicos/efeitos adversos , Antibióticos Antineoplásicos/metabolismo , Inibidores da Topoisomerase II/metabolismo , Inibidores da Topoisomerase II/farmacologia , Doxorrubicina/efeitos adversos , Doxorrubicina/metabolismo , Mitoxantrona/efeitos adversos , Mitoxantrona/metabolismo , Miócitos Cardíacos/metabolismo , Daunorrubicina/metabolismo , Daunorrubicina/farmacologia , Epirubicina/metabolismo , Epirubicina/farmacologia , DNA Topoisomerases Tipo II/genética , Expressão Gênica
2.
Front Oncol ; 13: 1187268, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397374

RESUMO

The therapy of children with acute lymphoblastic leukemia (ALL) in limited resource geospaces is challenging and must balance safety, efficacy, availability, and affordability. We modified the control arm of the St. Jude Total XI protocol for outpatient delivery including once-weekly daunorubicin and vincristine in initial therapy, postponing intrathecal chemotherapy until day 22, prophylactic oral antibiotics/antimycotics, use of generic drugs, and no central nervous system (CNS) radiation. Data were interrogated from 104 consecutive children ≤12 years (median, 6 years [interquartile range (IQR), 3, 9 years]. All therapies were given in an outpatient setting in 72 children. Median follow-up is 56 months (IQR 20, 126 months). A total of 88 children achieved a hematological complete remission. Median event-free survival (EFS) is 87 months [95% confidence interval (CI), 39, 60], 7.6 years in low-risk children (3.4, 8 years) whereas 2.5 years (1, 10 years) in high-risk children. The 5-year cumulative incidence of relapse (CIR) is 28% (18, 35%), 26% (14, 37%) in low-risk children and 35% (14, 52%) in high-risk children. Median survival for all subjects is not reached but must exceed 5 years. A total of 36 children relapsed at a median of 12 months (5, 23 months). Outcomes were comparable to those reported in the control arm of the Total Therapy XI study, but inferior to current treatment protocols in high-income countries. The average cost of the first 2 years of therapy was $28,500 USD compared with an average cost of approximately $150,000 USD in the US, an 80% saving. In conclusion, using an outpatient-based modification of the St. Jude Total XI protocol, we obtained good results with relatively few hospitalizations or adverse events and at a substantial saving. This model can be applied in other resource-poor geospaces.

3.
Lancet Reg Health Am ; 24: 100552, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37457139

RESUMO

Background: Reliable national estimations for blindness and vision impairment are fundamental to assessing their burden and developing public health policies. However, no comprehensive analysis is available for Mexico. Therefore, in this observational study we describe the national burden of blindness and vision loss by cause and severity during 2019. Methods: Using public data from the Global Burden of Disease (GBD) study 2019, we present national prevalence and years lived with disability (YLDs) counts and crude and age-standardized rates (per 100,000 people) of total, severity- and cause-specific blindness and vision impairment with 95% uncertainty intervals (UIs) by sex and age group. Findings: In Mexico, the burden of blindness and vision impairment was estimated at 11.01 million (95% UI, 9.25-13.11) prevalent cases and 384.96 thousand (259.57-544.24) YLDs during 2019. Uncorrected presbyopia caused the highest burden (6.06 million cases, 4.36-8.08), whereas severe vision loss and blindness affected 619.40 thousand (539.40-717.73) and 513.84 thousand (450.59-570.98) people, respectively. Near vision loss and refraction disorders caused 78.7% of the cases, whereas neonatal disorders and age-related macular degeneration were among the least frequent. Refraction disorders were the main cause of moderate and severe vision loss (61.44 and 35.43%), and cataracts were the second most frequent cause of blindness (26.73%). Females suffered an overall higher burden of blindness and vision impairment (54.99% and 52.85% of the total cases and YLDs), and people >50 years of age suffered the highest burden, with people between 70 and 74 years being the most affected. Interpretation: Vision loss represents a public health problem in Mexico, with women and older people being the most affected. Although the causes of vision loss contribute differentially to the severity of visual impairment, most of the impairment is avoidable. Consequently, a concerted effort at different levels is needed to alleviate this burden. Funding: This study received no funding.

4.
Cancers (Basel) ; 16(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38201576

RESUMO

The global burden of cancer is on the rise, with varying national patterns. To gain a better understanding and control of cancer, it is essential to provide national estimates. Therefore, we present a comparative description of cancer incidence and mortality rates in Mexico from 1990 to 2019, by age and sex for 29 different cancer groups. Based on public data from the Global Burden of Disease Study 2019, we evaluated the national burden of cancer by analyzing counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and trends using the annual percentage change from 1990 to 2019. In 2019, cancer resulted in 222,060 incident cases and 105,591 deaths. In 2019, the highest incidence of cancer was observed in non-melanoma skin cancer, prostate cancer, and breast cancer. Additionally, 53% of deaths were attributed to six cancer groups (lung, colorectal, stomach, prostate, breast, and pancreatic). From 1990 to 2019, there was an increasing trend in incidence and mortality rates, which varied by 10-436% among cancer groups. Furthermore, there were cancer-specific sex differences in crude and age-standardized rates. The results show an increase in the national cancer burden with sex-specific patterns of change. These findings can guide national efforts to reduce health loss due to cancer.

5.
Salud Publica Mex ; 64(5, sept-oct): 464-470, 2022 Aug 19.
Artigo em Espanhol | MEDLINE | ID: mdl-36130363

RESUMO

OBJECTIVE: Determine the proportion of vaccinated patients in a private hematology and internal medicine outpatient clinic and potential factors in adherence in at-risk patients (due to onco-hematological diseases). MATERIALS AND METHODS: This is a cross-sectional study of outpatients from a private clinic. We applied a non-validated instrument to all patients attending the outpatient clinic from May to October 2021. According to the primary diagnosis, we classified patients into onco-hematological and non-onco-hematological patients. Since national authorities exclusively executed and planned the rollout of vaccines, the order and eligibility defined by authorities of vaccination was considered when conducting the analysis and patients were classified according to the their corresponding group. RESULTS: 397 participants were accrued, 269 (68%) had an onco-hematological condition. In the whole group, 73 (18.3%) had a history of infection. Vaccination history was present in 286 persons (72%); 82% had two doses. In the subset of 269 persons with an onco-hematological condition, 191 (71%) were vaccinated, whereas 95 participants with non-hematological conditions (73%) had received the vaccine. Vaccination status was associated with age (OR 1.07, 95%CI: 1.03,1.10, p<0.0001) and body mass index (OR 1.11, 95%CI: 1.04,1.17, p<0.0001). CONCLUSIONS: According to our study, vaccination adherence at our center is significantly different from the nationwide proportion of vaccines.


Assuntos
COVID-19 , Hematologia , Instituições de Assistência Ambulatorial , Vacinas contra COVID-19 , Estudos Transversais , Humanos , SARS-CoV-2 , Vacinação
6.
Leuk Res ; 121: 106935, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36037624

RESUMO

The results of treatment of adolescents and adults with acute lymphoblastic leukemia (ALL) remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. 126 adolescent and adult patients with ALL were treated in a 37-year period with a pediatric inspired combined chemotherapy (PICC) schedule, delivered on an outpatient basis and based on the St. Jude´s TOTAL XI pediatric protocol employing vincristine, prednisone, asparaginase, daunorubicin, etoposide, cytarabine, methotrexate, mercaptopurine and triple intrathecal therapy. 80 % of patients were able to receive the initial seven-week period of induction / consolidation fully as outpatients and 77 % achieved a complete remission. In adolescents and young adults (AYAs) the median probability of overall survival (OS) was 44 months, whereas the 5-year OS was 48 %. In adults, the median probability of OS was 24 months, and the 5-year OS was 32 %. Patients with T-cell ALL did significantly worse than those with a B cell phenotype (OS at 5 years 17 versus 40 %, respectively). These figures are better than those informed in our country employing more aggressive, in-hospital schedules such as the hyper-CVAD. We found that, in AYAs and adult patients with ALL, the use of an asparaginase-containing PICC delivered on an outpatient basis renders acceptable results, better than those obtained in similar socioeconomic circumstances employing adult-oriented schedules. Additional studies are needed to assess the usefulness of these PICC treatments in adult individuals with ALL treated in underprivileged circumstances, such as those prevailing in LMIC.


Assuntos
Asparaginase , Leucemia-Linfoma Linfoblástico de Células Precursoras , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida , Citarabina , Daunorrubicina , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Mercaptopurina , Metotrexato/uso terapêutico , Pacientes Ambulatoriais , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prednisona , Vincristina/uso terapêutico
7.
Cancers (Basel) ; 14(13)2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35804962

RESUMO

In 2019, the Global Burden of Disease (GBD) estimated that prostate cancer (PC) was the 16th most common cause of death globally in males. In Mexico, PC epidemiology has been studied by a number of metrics and over various periods, although without including the most up-to-date estimates. Herein, we describe and compare the burdens and trends of PC in Mexico and its 32 states from 2000 to 2019. For this study, we extracted online available data from the GBD 2019 to estimate the crude and age-standardized rates (ASR per 100,000 people) of the incidence and mortality of PC. In Mexico, PC caused 27.1 thousand (95% uncertainty intervals, 20.6-36.0 thousand) incident cases and 9.2 thousand (7.7-12.7 thousand) deaths in males of all ages in 2019. Among the states, Sinaloa had the greatest ASR of incidence, and Guerrero had the highest mortality. The burden of PC showed an increasing trend, although the magnitude of change differed between metrics and locations. We found both an increasing national trend and subnational variation in the burden of PC. Our results confirm the need for updated and timely estimates to design effective diagnostic and treatment campaigns in locations where the burden of PC is the highest.

8.
Hematology ; 27(1): 449-455, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35413225

RESUMO

INTRODUCTION: High-dose melphalan (HD-Mel) has been successfully employed in autografting patients with multiple myeloma. An advantage of this regimen is that the total dose of Mel can be delivered in a single day, being particularly useful when non-frozen hematopoietic stem cells are employed in the autograft. MATERIAL AND METHODS: All consecutive patients with R/R lymphomas, both HL and NHL studied and treated at two different centers were prospectively included in a study of ASCT employing a single dose of HD-Mel (200 mg/m2). A group of R/R HL or NHL autografted employing BEAM-like preparative regimens was constructed matched by diagnosis and age. The primary endpoint of the study was overall survival (OS), the secondary endpoint was event-free survival (EFS). RESULTS: Twenty-five R/R HL/NHL patients were prospectively accrued in the study. There were 8 (32%) females, 13 (52%) patients had at least 1 adverse effect: 7 (28%) developed mucositis, 5 (20%) neutropenic fever, and 6 (24%) grade IV nausea. In the HD-Mel group, median overall survival (OS) was not achieved and OS at 36 months was 71%, the transplant-related mortality being 0%. In the control group, median OS was not achieved and the 36-month OS was 76%, results not statistically significant (p 0.5). The EFS was also similar in both groups (p 0.5). CONCLUSION: HD-Mel alone is non-inferior to a BEAM-like regimen as a preparative regimen for autografting patients with R/R HL and NHL. The regimen is adequate to graft persons with non-frozen stem cells.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Linfoma/tratamento farmacológico , Melfalan/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Autólogo
9.
IEEE Trans Med Imaging ; 40(6): 1687-1701, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33684035

RESUMO

Is it possible to find deterministic relationships between optical measurements and pathophysiology in an unsupervised manner and based on data alone? Optical property quantification is a rapidly growing biomedical imaging technique for characterizing biological tissues that shows promise in a range of clinical applications, such as intraoperative breast-conserving surgery margin assessment. However, translating tissue optical properties to clinical pathology information is still a cumbersome problem due to, amongst other things, inter- and intrapatient variability, calibration, and ultimately the nonlinear behavior of light in turbid media. These challenges limit the ability of standard statistical methods to generate a simple model of pathology, requiring more advanced algorithms. We present a data-driven, nonlinear model of breast cancer pathology for real-time margin assessment of resected samples using optical properties derived from spatial frequency domain imaging data. A series of deep neural network models are employed to obtain sets of latent embeddings that relate optical data signatures to the underlying tissue pathology in a tractable manner. These self-explanatory models can translate absorption and scattering properties measured from pathology, while also being able to synthesize new data. The method was tested on a total of 70 resected breast tissue samples containing 137 regions of interest, achieving rapid optical property modeling with errors only limited by current semi-empirical models, allowing for mass sample synthesis and providing a systematic understanding of dataset properties, paving the way for deep automated margin assessment algorithms using structured light imaging or, in principle, any other optical imaging technique seeking modeling. Code is available.


Assuntos
Neoplasias da Mama , Algoritmos , Neoplasias da Mama/diagnóstico por imagem , Calibragem , Feminino , Humanos , Redes Neurais de Computação , Imagem Óptica
10.
Biomed Opt Express ; 11(1): 133-148, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32010505

RESUMO

Many well-known algorithms for the color enhancement of hyperspectral measurements in biomedical imaging are based on statistical assumptions that vary greatly with respect to the proportions of different pixels that appear in a given image, and thus may thwart their application in a surgical environment. This article attempts to explain why this occurs with SVD-based enhancement methods, and proposes the separation of spectral enhancement from analysis. The resulting method, termed affinity-based color enhancement, or ACE for short, achieves multi- and hyperspectral image coloring and contrast based on current spectral affinity metrics that can physically relate spectral data to a particular biomarker. This produces tunable, real-time results which are analogous to the current state-of-the-art algorithms, without suffering any of their inherent context-dependent limitations. Two applications of this method are shown as application examples: vein contrast enhancement and high-precision chromophore concentration estimation.

11.
Sensors (Basel) ; 19(7)2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30970657

RESUMO

Prototyping hyperspectral imaging devices in current biomedical optics research requires taking into consideration various issues regarding optics, imaging, and instrumentation. In summary, an ideal imaging system should only be limited by exposure time, but there will be technological limitations (e.g., actuator delay and backlash, network delays, or embedded CPU speed) that should be considered, modeled, and optimized. This can be achieved by constructing a multiparametric model for the imaging system in question. The article describes a rotating-mirror scanning hyperspectral imaging device, its multiparametric model, as well as design and calibration protocols used to achieve its optimal performance. The main objective of the manuscript is to describe the device and review this imaging modality, while showcasing technical caveats, models and benchmarks, in an attempt to simplify and standardize specifications, as well as to incentivize prototyping similar future designs.


Assuntos
Processamento de Imagem Assistida por Computador/métodos , Imagem Molecular/instrumentação , Óptica e Fotônica/instrumentação , Pesquisa Biomédica/tendências , Humanos
12.
J Vet Pharmacol Ther ; 42(3): 300-308, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30714169

RESUMO

The pharmacokinetics, PK/PD ratios, and Monte Carlo modeling of enrofloxacin HCl-2H2 O (Enro-C) and its reference preparation (Enro-R) were determined in cows. Fifty-four Jersey cows were randomly assigned to six groups receiving a single IM dose of 10, 15, or 20 mg/kg of Enro-C (Enro-C10 , Enro-C15 , Enro-C20 ) or Enro-R. Serial serum samples were collected and enrofloxacin concentrations quantified. A composite set of minimum inhibitory concentrations (MIC) of Leptospira spp. was utilized to calculate PK/PD ratios: maximum serum concentration/MIC (Cmax /MIC90 ) and area under the serum vs. time concentration of enrofloxacin/MIC (AUC0-24 /MIC90 ). Monte Carlo simulations targeted Cmax /MIC = 10 and AUC0-24 /MIC = 125. Mean Cmax obtained were 6.17 and 2.46 µg/ml; 8.75 and 3.54 µg/ml; and 13.89 and 4.25 µg/ml, respectively for Enro-C and Enro-R. Cmax /MIC90 ratios were 6.17 and 2.46, 8.75 and 3.54, and 13.89 and 4.25 for Enro-C and Enro-R, respectively. Monte Carlo simulations based on Cmax /MIC90  = 10 indicate that only Enro-C15 and Enro-C20 may be useful to treat leptospirosis in cows, predicting a success rate ≥95% when MIC50  = 0.5 µg/ml, and ≥80% when MIC90  = 1.0 µg/ml. Although Enro-C15 and Enro-C20 may be useful to treat leptospirosis in cattle, clinical trials are necessary to confirm this proposal.


Assuntos
Antibacterianos/farmacocinética , Enrofloxacina/farmacocinética , Leptospira/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/microbiologia , Relação Dose-Resposta a Droga , Enrofloxacina/administração & dosagem , Enrofloxacina/sangue , Feminino , Injeções Intramusculares , Leptospirose/tratamento farmacológico , Leptospirose/veterinária , Testes de Sensibilidade Microbiana/veterinária , Método de Monte Carlo
13.
Biomed Opt Express ; 9(12): 6283-6301, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31065429

RESUMO

Early detection and diagnosis is a must in secondary prevention of melanoma and other cancerous lesions of the skin. In this work, we present an online, reservoir-based, non-parametric estimation and classification model that allows for this functionality on pigmented lesions, such that detection thresholding can be tuned to maximize accuracy and/or minimize overall false negative rates. This system has been tested in a dataset consisting of 116 patients and a total of 124 hyperspectral images of nevi, raised nevi and melanomas, detecting up to 100% of the suspicious lesions at the expense of some false positives.

14.
Comunidad salud ; 13(1): 46-55, jun. 2015. tab
Artigo em Espanhol | LILACS | ID: lil-783068

RESUMO

EL síndrome metabólico es un conjunto de factores de riesgo de origen metabólico que pueden aparecer de manera simultánea o secuencial en un mismo individuo, el SM es causado por la combinación de factores genéticos y factores asociados al estilo de vida, especialmente la sobrealimentación y la ausencia de actividad física, que promueven a su vez el desarrollo de enfermedades cardiovasculares (ECV) y otras patologías como la diabetes, enfermedad coronaria y cerebro vascular.. Entre los factores indirectos del síndrome metabólico, se ha establecido recientemente los niveles bajos de te stosterona como factor desencadenante en hombres. De allí que se desarrolló la presente investigación con el objeto de relacionar los niveles séricos de testosterona total y libre con el síndrome metabólico y sus criterios, en la población masculina. Para ello se determinaron los parámetros clínicos (presión arterial, circunferencia abdominal) y bioquímicos (glucemia basal, HDL-Colesterol, Triglicéridos ) que evalúan el síndrome metabólico asi como los niveles de Testosterona Total y Ligada . Resultados: los niveles de testosterona total y libre, son inferiores en el grupo de pacientes con síndrome metabólico, sin embargo al determinar la significancia estadística mediante la t de Student, no se aprecia diferencia en los valores promedio de testosterona total (sig 0,08) más si en los valores promedio de testosterona libre (sig 0,000). Ambas (testosterona total y libre) se correlacionan significativamente de manera inversa con la obesidad abdominal. Los niveles de testosterona libre se relacionan inversa y significativamente con la edad.


The Metabolic syndrome is a cluster of risk factors of metabolic origin that may occur simultaneously or sequentially in the same individual, the SM is caused by a combination of genetic factors and factors related to lifestyle, especially overeating and lack physical activity, which in turn promote the development of cardiovascular disease (CVD) and other diseases such as diabetes, heart disease and cerebrovascular .. Indirect factors of metabolic syndrome, was recently established low levels of testosterone as a factor trigger in men. Hence, this research was conducted in order to relate the serum total and free testosterone with metabolic syndrome and its criteria in the male population. For this clinical parameters (blood pressure, abdominal circumference) and biochemical (fasting glucose, HDL-cholesterol, triglycerides) evaluating the metabolic syndrome as well as Total Testosterone levels were determined and Bound. Results: The levels of total and free testosterone are lower in the group of patients with metabolic syndrome, however to determine statistical significance using Student's t, no difference was seen in the average values of total testosterone (sig 0.08 ) more if in the mean values of free testosterone (sig 0.000). Both (total and free testosterone) was significantly inversely correlated with abdominal obesity. Free testosterone levels are associated inversely and significantly with age.

15.
Aging Cell ; 11(2): 284-96, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22221695

RESUMO

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes (T2DM). In this study, we have evaluated the role of PTP1B in the development of aging-associated obesity, inflammation, and peripheral insulin resistance by assessing metabolic parameters at 3 and 16 months in PTP1B(-/-) mice maintained on mixed genetic background (C57Bl/6J × 129Sv/J). Whereas fat mass and adipocyte size were increased in wild-type control mice at 16 months, these parameters did not change with aging in PTP1B(-/-) mice. Increased levels of pro-inflammatory cytokines, crown-like structures, and hypoxia-inducible factor (HIF)-1α were observed only in adipose tissue from 16-month-old wild-type mice. Similarly, islet hyperplasia and hyperinsulinemia were observed in wild-type mice with aging-associated obesity, but not in PTP1B(-/-) animals. Leanness in 16-month-old PTP1B(-/-) mice was associated with increased energy expenditure. Whole-body insulin sensitivity decreased in 16-month-old control mice; however, studies with the hyperinsulinemic-euglycemic clamp revealed that PTP1B deficiency prevented this obesity-related decreased peripheral insulin sensitivity. At a molecular level, PTP1B expression and enzymatic activity were up-regulated in liver and muscle of 16-month-old wild-type mice as were the activation of stress kinases and the expression of p53. Conversely, insulin receptor-mediated Akt/Foxo1 signaling was attenuated in these aged control mice. Collectively, these data implicate PTP1B in the development of inflammation and insulin resistance associated with obesity during aging and suggest that inhibition of this phosphatase by therapeutic strategies might protect against age-dependent T2DM.


Assuntos
Envelhecimento , Resistência à Insulina , Obesidade/enzimologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Animais , Metabolismo Energético , Hipóxia/enzimologia , Inflamação/enzimologia , Células Secretoras de Insulina/enzimologia , Camundongos , Camundongos Knockout , Proteína Tirosina Fosfatase não Receptora Tipo 1/deficiência , Transdução de Sinais , Estresse Fisiológico
16.
Rev cienc méd pinar río ; 15(4)dic, 2011.
Artigo em Espanhol | CUMED | ID: cum-48483

RESUMO

La Extensión Universitaria se enmarca en una perspectiva estratégica en su correspondiente expresión dentro de la planeación, tanto a nivel del sistema de la Educación Médica Superior como en el de las propias instituciones y sus estructuras. La Universalización de la Educación Médica Superior en Cuba es una realidad, se impone la necesidad de una estrategia que fortalezca desde la Atención Primaria a través de la promoción de salud, la labor extensionista de la universidad médica con la comunidad y para la comunidad. Mediante el método de revisión bibliográfica, el método comparativo e histórico lógico, así como la aplicación de encuestas, se presentan preceptos teóricos que tributan a la concepción de la estrategia antes mencionada. La promoción de salud es el eje central de la labor extensionista en la Universidad Médica Cubana, coadyuvando a elevar el nivel de conciencia y la capacidad de acción, tanto individual como colectiva a través de sus proyectos en vertientes fundamentales como la comunidad universitaria y extrauniversitaria, con la identificación de las principales necesidades de salud...(AU)


University extension must be in the line of the strategic perspective and its respective expression within the strategic planning toward Higher Medical Education, institutions and their structures. Currently, the Universalization of Higher Medical Education is a reality in Cuba, and the need of a strategy to strengthen primary health care by means of health promotion is imperative; as well as the university extension within the community and to the community. Methods such as: Literature reviews, comparative and historical-logical, surveys together with theoretical precepts which respond to the conception of the mentioned strategy were used. Health promotion is the Axis of the university extension in Cuban Medical Universities, contributing to the development of individual and collective awareness with the capacity of action simultaneously, and through projects into the main aspects: university and extra-university activities to identify the most important health needs in the community...(AU)


Assuntos
Humanos , Educação Médica , Atenção Primária à Saúde
17.
Rev cienc méd pinar río ; 15(4)dic, 2011. tab
Artigo em Espanhol | CUMED | ID: cum-48476

RESUMO

Se realizó un estudio descriptivo y retrospectivo sobre el impacto socio-económico y extensionista del ingreso domiciliario en la Atención Primaria de Salud. El universo estuvo constituido por todos los ingresos domiciliarios de los grupos básicos 1 y 2 del Policlínico Universitario Hermanos Cruz de Pinar de Río, durante el año 2008. Se determinaron las principales enfermedades que causaron ingreso domiciliario y se aplicó una encuesta para recoger los datos individuales y generales de los pacientes a quienes se les brindó este servicio. Se realizó la revisión de las historias clínicas individuales en los Consultorios Médicos de pertenencia, que los que reportaron como ingresos en este período. Se exploró sobre el papel y conocimiento de los estudiantes sobre el ingreso en el hogar y su labor extensionista a través de la promoción de salud y las actividades asistenciales. Se aplicaron los métodos de la estadística descriptiva. Las principales causas fueron: las afecciones del embarazo, la existencia de mayor satisfacción para la familia y el paciente con esta modalidad de atención, así como la labor extensionista de los estudiantes de medicina que rotaban por esos consultorios. Se demostró el costo-beneficio de 27 780,00 pesos diarios y 194 460,00 pesos semanales en relación al ingreso hospitalario además, existencia de una buena satisfacción en la comunidad por esta oferta de servicios médicos en la atención primaria de salud, que trae consigo la elevación de la resolutividad local y una mejor competencia y desempeño del Médico y Enfermera de la familia. Se concluye sobre la viabilidad del sistema y la aceptación y beneficios económicos para la familia y el estado...(AU)


A retrospective and descriptive study was conducted at Hermanos Cruz Outpatient Clinic, Pinar del Rio during January 2008-2009 aimed at determining the socio-economic and extensional impact of domiciliary admissions. The target group was comprised of the total of this kind of admissions for number 1 and 2 basic working groups. The 10 main pathologies causing domiciliary admissions were determined, and a survey was applied to collect individual and general data of the patients under this medical care service. Individual Clinical Histories in the Doctors Offices having domiciliary admissions during the period under study were revised. The role of medical students was explored, as well as their level of knowledge regarding domiciliary admissions, extensional doings through health promotion and medical care activities. One of the main causes was pregnancy-associated illnesses; verifying a greater familial and patient agreement with this type of admission. Extensional activities of medical students during the training period at the doctors offices were considered satisfactory. The cost-benefit reached a figure of 27780.00 Cuban pesos daily and 194460.00 Cuban pesos weekly compared with hospital admissions; as well as the level of satisfaction in the community regarding this modality of medical services in Primary Health Care. Higher local solutions to health problems are achieved, together with better competence and performance of the Family Doctors and Nurses...(AU)


Assuntos
Humanos , Atenção Primária à Saúde , Impacto Psicossocial , Custos de Cuidados de Saúde
18.
Rev. cienc. med. Pinar Rio ; 15(4): 102-115, oct.-dic. 2011.
Artigo em Espanhol | LILACS | ID: lil-739754

RESUMO

Objetivo: se realizó un estudio descriptivo y retrospectivo sobre el impacto socio-económico y extensionista del ingreso domiciliario en la Atención Primaria de Salud. Método: el universo estuvo constituido por todos los ingresos domiciliarios de los grupos básicos 1 y 2 del Policlínico Universitario "Hermanos Cruz" de Pinar de Río, durante el año 2008. Se determinaron las principales enfermedades que causaron ingreso domiciliario y se aplicó una encuesta para recoger los datos individuales y generales de los pacientes a quienes se les brindó este servicio. Se realizó la revisión de las historias clínicas individuales en los Consultorios Médicos de pertenencia, que los que reportaron como ingresos en este período. Se exploró sobre el papel y conocimiento de los estudiantes sobre el ingreso en el hogar y su labor extensionista a través de la promoción de salud y las actividades asistenciales. Se aplicaron los métodos de la estadística descriptiva. Resultados: las principales causas fueron: las afecciones del embarazo, la existencia de mayor satisfacción para la familia y el paciente con esta modalidad de atención, así como la labor extensionista de los estudiantes de medicina que rotaban por esos consultorios. Se demostró el costo-beneficio de 27 780,00 pesos diarios y 194 460,00 pesos semanales en relación al ingreso hospitalario además, existencia de una buena satisfacción en la comunidad por esta oferta de servicios médicos en la atención primaria de salud, que trae consigo la elevación de la resolutividad local y una mejor competencia y desempeño del Médico y Enfermera de la familia. Conclusión: sobre la viabilidad del sistema y la aceptación y beneficios económicos para la familia y el estado.


A retrospective and descriptive study was conducted at "Hermanos Cruz" Outpatient Clinic, Pinar del Rio during January 2008-2009 aimed at determining the socio-economic and extensional impact of domiciliary admissions. The target group was comprised of the total of this kind of admissions for number 1 and 2 basic working groups. The 10 main pathologies causing domiciliary admissions were determined, and a survey was applied to collect individual and general data of the patients under this medical care service. Individual Clinical Histories in the Doctor's Offices having domiciliary admissions during the period under study were revised. The role of medical students was explored, as well as their level of knowledge regarding domiciliary admissions, extensional doings through health promotion and medical care activities. One of the main causes was pregnancy-associated illnesses; verifying a greater familial and patient agreement with this type of admission. Extensional activities of medical students during the training period at the doctor's offices were considered satisfactory. The cost-benefit reached a figure of 27780.00 Cuban pesos daily and 194460.00 Cuban pesos weekly compared with hospital admissions; as well as the level of satisfaction in the community regarding this modality of medical services in Primary Health Care. Higher local solutions to health problems are achieved, together with better competence and performance of the Family Doctors and Nurses.

19.
Rev. cienc. med. Pinar Rio ; 15(4): 218-230, oct.-dic. 2011.
Artigo em Espanhol | LILACS | ID: lil-739761

RESUMO

La Extensión Universitaria se enmarca en una perspectiva estratégica en su correspondiente expresión dentro de la planeación, tanto a nivel del sistema de la Educación Médica Superior como en el de las propias instituciones y sus estructuras. La Universalización de la Educación Médica Superior en Cuba es una realidad, se impone la necesidad de una estrategia que fortalezca desde la Atención Primaria a través de la promoción de salud, la labor extensionista de la universidad médica con la comunidad y para la comunidad. Mediante el método de revisión bibliográfica, el método comparativo e histórico lógico, así como la aplicación de encuestas, se presentan preceptos teóricos que tributan a la concepción de la estrategia antes mencionada. La promoción de salud es el eje central de la labor extensionista en la Universidad Médica Cubana, coadyuvando a elevar el nivel de conciencia y la capacidad de acción, tanto individual como colectiva a través de sus proyectos en vertientes fundamentales como la comunidad universitaria y extrauniversitaria, con la identificación de las principales necesidades de salud.


University extension must be in the line of the strategic perspective and its respective expression within the strategic planning toward Higher Medical Education, institutions and their structures. Currently, the Universalization of Higher Medical Education is a reality in Cuba, and the need of a strategy to strengthen primary health care by means of health promotion is imperative; as well as the university extension within the community and to the community. Methods such as: Literature reviews, comparative and historical-logical, surveys together with theoretical precepts which respond to the conception of the mentioned strategy were used. Health promotion is the Axis of the university extension in Cuban Medical Universities, contributing to the development of individual and collective awareness with the capacity of action simultaneously, and through projects into the main aspects: university and extra-university activities to identify the most important health needs in the community.

20.
Rev. cienc. med. Pinar Rio ; 15(2): 1-2, abr.-jun. 2011.
Artigo em Espanhol | LILACS | ID: lil-739662
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