RESUMEN
Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.
Asunto(s)
Medicamentos Herbarios Chinos , Ratas Sprague-Dawley , Sepsis , Animales , Sepsis/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacocinética , Masculino , Ratas , Administración IntravenosaRESUMEN
Although sodium and water reabsorption by the kidney plays a major role in maintaining body fluid homeostasis, the seasonal response of renal morphology and the factors involved in water and salt regulation are not well known, especially in reptiles. Eremias multiocellata is a typical desert-dwelling lizard. Here, we compared water and salt regulation of E. multiocellata in winter (hibernation), spring (emerging from hibernation), and summer (active) according to histomorphometry and the expression of genes such as those encoding aquaporins (AQP1, AQP2, AQP3), the Na+-Cl- cotransporter (NCC), the Na+-K+-2Cl- cotransporter (NKCC2), renin (Ren), angiotensin II receptor type 2 (AT2R), and endothelial nitric oxide synthase (eNOS) in the kidneys. The results showed that the area of Bowman's capsule and the glomerular density were lower in winter compared to summer and spring, and the lumen size of the DCT, PCT, and IS was greater in spring than in summer. Compared to summer and spring, the expression of AQP1, AQP3, NCC, NKCC2, Ren, and eNOS was significantly decreased in winter, whereas the expression of AQP2 and AT2R remained high. These results indicate that E. multiocellata balances its water budget via morpho-functional changes in different seasons. Although renal function was temporarily attenuated during winter, the regulation of aquaporins genes was not synchronous, indicating the complexity and particularity of water and salt regulation in desert lizards when facing the constraints of harsh environmental conditions, seasonal variations, and hibernation. These results will enrich the understanding of water and salt regulation mechanisms in desert reptiles.
Asunto(s)
Acuaporina 2 , Lagartos , Animales , Acuaporina 2/metabolismo , Riñón/metabolismo , Lagartos/metabolismo , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Receptores de Angiotensina/metabolismo , Renina/metabolismo , Estaciones del Año , Sodio/metabolismo , Cloruro de Sodio Dietético/metabolismo , Miembro 3 de la Familia de Transportadores de Soluto 12/metabolismo , Agua/metabolismoRESUMEN
PURPOSE: Approximately 20% of patients with lung nodules (LNs) have multiple LNs (MLNs). This meta-analysis was performed to assess the safety and efficacy of computed tomography (CT)-guided localization of MLNs in comparison with those of single LN (SLN) localization. MATERIAL AND METHODS: The PubMed, Embase, and Cochrane Library were searched to collect relevant articles published till February 2022. The meta-analysis was performed using the RevMan v5.3. RESULTS: In total, seven studies met the inclusion criteria for this meta-analysis. No significant difference was observed between patients with MLNs and SLN in terms of pooled successful localization rate based on LNs (p = 0.64) and patients (p = 0.06). The pooled duration of localization was significantly shorter and the pooled pneumothorax and lung hemorrhage rates were significantly lower in the SLN group than in the MLNs group (p < 0.00001 for all). The pooled duration of hospital stay was comparable between the MLNs and SLN groups (p = 0.96). Significant heterogeneity was observed in the endpoints of duration of localization (I2 = 75%) and pneumothorax (I2 = 53%). CONCLUSIONS: CT-guided simultaneous MLN localization is clinically safe and effective, despite requiring a longer procedural time and having higher incidence of pneumothorax and lung hemorrhage than SLN localization.
Asunto(s)
Nódulos Pulmonares Múltiples , Tomografía Computarizada por Rayos X , Humanos , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/cirugía , Neumotórax/epidemiología , Neumotórax/etiología , Tomografía Computarizada por Rayos X/efectos adversos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a treatment-refractory malignancy with poor prognosis. It is urgent to identify novel and valid biomarkers to predict the progress and prognosis of PDAC. The S100A family have been identified as being involved in cell proliferation, migration and differentiation progression of various cancer types. However, the expression patterns and prognostic values of S100As in PDAC remain to be analyzed. METHODS: We investigated the transcriptional expressions, methylation level and prognostic value of S100As in PDAC patients from the Oncomine, GEPIA2, Linkedomics and cBioPortal databases. Real-time PCR was used to detect the expressions of S100A2/4/6/10/14/16 in four pancreatic cancer cell lines and pancreatic cancer tissues from PDAC patients undergoing surgery. To verify the results further, immunohistochemistry was used to measure the expression of S100A2/4/6/10/14/16 in 43 PDAC patients' tissue samples. The drug relations of S100As were analyzed by using the Drugbank database. RESULTS: The results suggested that, the expression levels of S100A2/4/6/10/14/16 were elevated to PDAC tissues than in normal pancreatic tissues, and the promoter methylation levels of S100A S100A2/4/6/10/14/16 in PDAC (n = 10) were lower compared with normal tissue (n = 184) (P < 0.05). In addition, their expressions were negatively correlated with PDAC patient survival. CONCLUSIONS: Taken together, these results suggest that S100A2/4/6/10/14/16 might be served as prognostic biomarkers for survivals of PDAC patients.
Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas S100/metabolismo , Adenocarcinoma/mortalidad , Anexina A2/metabolismo , Proteínas de Unión al Calcio/metabolismo , Carcinoma Ductal Pancreático/mortalidad , Proteínas de Ciclo Celular/metabolismo , Línea Celular Tumoral , Factores Quimiotácticos/metabolismo , Bases de Datos Genéticas , Progresión de la Enfermedad , Humanos , Páncreas/metabolismo , Neoplasias Pancreáticas/mortalidad , Pronóstico , ARN Mensajero/metabolismo , Proteína A6 de Unión a Calcio de la Familia S100/metabolismo , Proteína de Unión al Calcio S100A4/metabolismo , Proteínas S100/genética , Transcripción GenéticaRESUMEN
OBJECTIVES: To evaluate the impact of providing personalized depression risk information on self-help and help-seeking behaviors among individuals who are at high risk of having a major depressive episode (MDE). MATERIALS AND METHODS: In a mixed methods randomized controlled trial, participants who were at high risk of having a MDE, were recruited from across Canada, and were randomized into intervention (n = 358) and control (n = 354) groups. Participants in the intervention group received their personalized depression risk estimated by sex-specific risk prediction models for MDE. All participants were assessed at baseline, 6 and 12 months. RESULTS: Repeated measure mixed effects modeling showed significant between group differences in self-help scores. In the complete case analysis, the between group difference in mean self-help change score was 1.13 at 12 months (effect size = 0.16). Among participants who reported "fair" or "poor health," the between group difference in mean self-help change score was 2.78 at 12 months (effect size = 0.35). The qualitative data revealed three themes and the findings are consistent with the quantitative results. CONCLUSIONS: Providing personalized depression risk information has a positive impact on self-help in high-risk individuals, particularly in those with poor health.
Asunto(s)
Trastorno Depresivo Mayor , Conducta de Búsqueda de Ayuda , Canadá , Depresión , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Knowledge is limited regarding the longitudinal course and predictors of mental health problems, suicide, and physical health outcomes among military and veterans. Statistics Canada, in collaboration with researchers at the University of Manitoba and an international team, conducted the Canadian Armed Forces Members and Veterans Mental Health Follow-Up Survey (CAFVMHS). Herein, we describe the rationale and methods of this important survey. METHOD: The CAFVMHS is a longitudinal survey design with 2 time points (2002 and 2018). Regular Force military personnel who participated in the first Canadian Community Health Survey Cycle 1.2-Mental Health and Well-Being, Canadian Forces Supplement (CCHS-CFS) in 2002 (N = 5,155) were reinterviewed in 2018 (n = 2,941). The World Mental Health Survey-Composite International Diagnostic Interview was used with the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria. RESULTS: The CAFVMHS includes 2,941 respondents (66% veterans; 34% active duty) and includes data on mental disorder diagnoses, physical health conditions, substance use, medication use, general health, mental health services, perceived need for care, social support, moral injury, deployment experiences, stress, physical activity, military-related sexual assault, childhood experiences, and military and sociodemographic information. CONCLUSIONS: The CAFVMHS provides a unique opportunity to further understand the health and well-being of military personnel in Canada over time to inform intervention and prevention strategies and improve outcomes. The data are available through the Statistics Canada Research Data Centres across Canada and can be used cross-sectionally or be longitudinally linked to the 2002 CCHS-CFS data.
Asunto(s)
Personal Militar , Veteranos , Canadá , Estudios de Seguimiento , Humanos , Salud Mental , Encuestas y CuestionariosRESUMEN
Heat shock protein 90α (HSP90α) has been confirmed to be upregulated in the blood in various types of tumors and may therefore serve as a potential tumor marker. However, whether HSP90α exists in nipple discharge remains unknown, and its expression and diagnostic value in nipple discharge remain unclear. In this study, the expression of HSP90α, carcinoembryonic antigen (CEA), and cancer antigen 153 in nipple discharge and blood from 128 patients was measured. Receiver operating characteristic curve was used to assess the diagnostic value of HSP90α. Further, its relationship with clinicopathological parameters of patients with breast cancer was analyzed. The results showed that the expression of HSP90α in nipple discharge was significantly higher in patients with breast cancer than in those with benign disease, and its diagnostic value was better than that of CEA. Combination of HSP90α and CEA showed better diagnostic efficacy than HSP90α or CEA alone. Moreover, the expression of HSP90α displayed a stepwise increase from benign lesions, followed by carcinoma in situ to invasive ductal carcinoma. HSP90α was positively correlated with Ki67 expression. However, there was no significant difference in the expression of HSP90α in blood between patients with breast cancer and benign disease. Further, the expression of HSP90α was higher in nipple discharge than in blood. In summary, HSP90α was upregulated in the nipple discharge of patients with breast cancer, and it may be related to the occurrence and progression of breast cancer. HSP90α in nipple discharge may serve as a potential diagnostic marker for breast cancer.
Asunto(s)
Neoplasias de la Mama , Proteínas HSP90 de Choque Térmico/genética , Secreción del Pezón , Biomarcadores de Tumor , Neoplasias de la Mama/diagnóstico , Femenino , HumanosRESUMEN
Myocardial ischaemia reperfusion (I/R) injury is one of the leading causes of coronary artery disease-associated morbidity and mortality. While different strategies have been used to limit I/R injuries, cardiac functions often do not recover to the normal level as anticipated. Recent studies have pointed to important roles of long noncoding RNAs (lncRNAs) in the development of myocardial I/R injury. LncRNA is a class of RNA molecules of more than 200 nucleotides in length which are not translated into proteins. I/R causes dysregulation of lncRNA expression in cardiomyocytes, thereby affecting multiple cellular functions including mitochondrial homeostasis, apoptosis, necrosis and autophagy, suggesting that manipulating lncRNAs may be of great potential in counteracting I/R injury-induced myocardial dysfunctions. In this review, we provide an updated summary on our knowledge about contributions of lncRNAs to the development of I/R injury, with an emphasis on the functional links between several well established cardiac lncRNAs and regulation of cellular outcomes post I/R.
Asunto(s)
Terapia Molecular Dirigida , Daño por Reperfusión Miocárdica , ARN Largo no Codificante , Animales , Humanos , Mitocondrias/metabolismo , Transducción de Señal/genéticaRESUMEN
PURPOSE: We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). METHODS: The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. RESULTS: Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). CONCLUSION: Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.
Asunto(s)
Sulfuro de Hidrógeno/sangre , Hipertensión/sangre , Apnea Obstructiva del Sueño/sangre , Adulto , Anciano , Asociación , Presión Sanguínea/fisiología , Estudios de Casos y Controles , Presión de las Vías Aéreas Positiva Contínua , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/epidemiología , Hipertensión/terapia , Modelos Lineales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polisomnografía , Factores de Riesgo , Apnea Obstructiva del Sueño/epidemiología , Apnea Obstructiva del Sueño/terapiaRESUMEN
BACKGROUND: Self-help may reduce the risk of depression, and risk perception of depression may influence initiating self-help. It is unknown how risk perception is associated with self-help behaviours. The objectives of this study are to (1) describe the self-help strategies used by high-risk Canadians in relation to the accuracy of perceived depression risk, by sex, and (2) identify demographic and clinical factors associated with self-help behaviours. METHODS: Baseline data from a randomized controlled trial including 358 men and 356 women at high-risk of developing depression were used. Following methods used in cancer research, risk perception accuracy was determined by comparing the participant's self-perceived and objective risk of developing depression and classifying as accurate, over-estimation and under-estimation based on a ± 10% threshold. The participant's objective depression risk was assessed using sex-specific multivariable risk predictive algorithms. Frequency of using 14 self-help strategies was assessed. One-way ANOVA testing was used to detect if differences in risk perception accuracy groups existed, stratified by sex. Linear regression was used to investigate the clinical and demographic factors associated with self-help behaviours, also stratified. RESULTS: Compared to accurate-estimators, male over-estimators were less likely to "leave the house daily," and "participate in activities they enjoy." Male under-estimators were also less likely to "participate in activities they enjoy." Both male 'inaccurate' perception groups were more likely to 'create lists of strategies which have worked for feelings of depression in the past and use them'. There were no significant differences between self-help behaviours and risk perception accuracy in women. Regression modeling showed negative relationships between self-rated health and self-help scores, irrespective of sex. In women, self-help score was positively associated with age and educational attainment, and negatively associated with perceived risk. In men, a positive relationship with unemployment was also seen. CONCLUSIONS: Sex differences exist in the factors associated with self-help. Risk perception accuracy, work status, and self-rated health is associated with self-help behaviours in high-risk men. In women, factors related to self-help included age, education, self-rated health status, and perceived risk. More research is needed to replicate findings. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov (NCT02943876) as of 10/21/16.
Asunto(s)
Depresión/psicología , Conductas Relacionadas con la Salud , Conducta de Reducción del Riesgo , Autoimagen , Factores Sexuales , Adulto , Análisis de Varianza , Canadá , Estudios Transversales , Depresión/etiología , Autoevaluación Diagnóstica , Femenino , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Quassinoids, one kind of triterpenoids with multiple bioactivities such as anti-cancer, anti-malarial, anti-oxidative, anti-microbial, anti-diabetic, anti-viral, and anti-inflammatory effects, have drawn much attention in recent years. Between 2004 and 2018, the structural characteristics and plant sources of 190 quassinoids were reported. Herein, the structure-activity relationships (SARs) of quassinoids along with the anti-cancer mechanisms of four representative quassinoids, eurycomanone, bruceine D, dehydrobruceine B, and brusatol are discussed. This review might be useful for further research and development of quassinoids.
Asunto(s)
Antineoplásicos Fitogénicos/química , Cuassinas/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Antiprotozoarios/química , Antiprotozoarios/aislamiento & purificación , Antiprotozoarios/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Antivirales/farmacología , Supervivencia Celular/efectos de los fármacos , Humanos , Plantas/química , Plantas/metabolismo , Plasmodium falciparum/efectos de los fármacos , Cuassinas/aislamiento & purificación , Cuassinas/farmacología , Relación Estructura-Actividad , Virus del Mosaico del Tabaco/efectos de los fármacosRESUMEN
BACKGROUND: Most mental disorders begin in adolescence; however, there are gaps in our understanding of youth mental health. Clinical and policy gaps arise from our current inability to predict, from amongst all youth who experience mild behavioural disturbances, who will go on to develop a mental illness, what that illness will be, and what can be done to change its course and prevent its worsening to a serious mental illness (SMI). There are also gaps in our understanding of how known risk factors set off neurobiological changes that may play a role in determining who will develop a SMI. Project goals are (i) to identify youth at different stages of risk of SMI so that intervention can begin as soon as possible and (ii) to understand the triggers of these mental illnesses. METHOD: This 2-site longitudinal study will recruit 240 youth, ages 12-25, who are at different stages of risk for developing a SMI. The sample includes (a) healthy individuals, (b) symptom-free individuals who have a first-degree relative with a SMI, (c) youth who are experiencing distress and may have mild symptoms of anxiety or depression, and (d) youth who are already demonstrating attenuated symptoms of SMI such as bipolar disorder or psychosis. We will assess, every 6 months for one year, a wide range of clinical and psychosocial factors to determine which factors can be used to predict key outcomes. We will also assess neuroimaging and peripheral markers. We will develop and validate a prediction algorithm that includes demographic, clinical and psychosocial predictors. We will also determine if adding biological markers to our algorithm improves prediction. DISCUSSION: Outcomes from this study include an improved clinical staging model for SMI and prediction algorithms that can be used by health care providers as decision-support tools in their practices. Secondly, we may have a greater understanding of clinical, social and cognitive factors associated with the clinical stages of development of a SMI, as well as new insights from neuroimaging and later neurochemical biomarker studies regarding predisposition to SMI development and progression through the clinical stages of illness.
Asunto(s)
Algoritmos , Familia/psicología , Trastornos Mentales/diagnóstico por imagen , Trastornos Mentales/psicología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Ansiedad/diagnóstico por imagen , Ansiedad/epidemiología , Ansiedad/psicología , Trastorno Bipolar/diagnóstico por imagen , Trastorno Bipolar/epidemiología , Trastorno Bipolar/psicología , Canadá/epidemiología , Niño , Depresión/diagnóstico por imagen , Depresión/epidemiología , Depresión/psicología , Femenino , Humanos , Estudios Longitudinales , Masculino , Trastornos Mentales/epidemiología , Trastornos Psicóticos/diagnóstico por imagen , Trastornos Psicóticos/epidemiología , Trastornos Psicóticos/psicología , Factores de Riesgo , Adulto JovenRESUMEN
In this paper, a novel semi-supervised segmentation framework based on a spot-divergence supervoxelization of multi-sensor fusion data is proposed for autonomous forest machine (AFMs) applications in complex environments. Given the multi-sensor measuring system, our framework addresses three successive steps: firstly, the relationship of multi-sensor coordinates is jointly calibrated to form higher-dimensional fusion data. Then, spot-divergence supervoxels representing the size-change property are given to produce feature vectors covering comprehensive information of multi-sensors at a time. Finally, the Gaussian density peak clustering is proposed to segment supervoxels into sematic objects in the semi-supervised way, which non-requires parameters preset in manual. It is demonstrated that the proposed framework achieves a balancing act both for supervoxel generation and sematic segmentation. Comparative experiments show that the well performance of segmenting various objects in terms of segmentation accuracy (F-score up to 95.6%) and operation time, which would improve intelligent capability of AFMs.
RESUMEN
OBJECTIVE: To determine whether there is an association between latitude and annual major depressive episode (MDE) prevalence in Canada. METHODS: Data from 2 national survey programs (the National Population Health Survey and the Canadian Community Health Survey) were used, providing 10 data sets collected between 1996 and 2013, together including 922,260 respondents, of whom 495,739 were assessed for MDE using 1 of 2 versions of the Composite International Diagnostic Interview, a short-form version (8 studies), and a Canadian adaptation of the World Mental Health version (2 studies). Approximate latitude was determined by linkage to postal code data. Data were analyzed using logistic regression and pooled across surveys using individual-level meta-analytic methods. RESULTS: In models including latitude as a continuous variable, a statistically significant association was observed, with prevalence increasing with increasing latitude. This association persisted after adjustment for a set of known risk factors. The latitude gradient was modest in magnitude, a 1% to 2% increase in the prevalence odds of MDE per degree of latitude was observed. Due to sparse data, this gradient cannot be confidently generalized beyond major population centres, which tend to occur at less than 55° latitude in Canada. CONCLUSION: A latitude gradient has not previously been reported. If replicated, the gradient may have implications for the planning of services and generation of aetiological hypotheses. However, this cross-sectional analysis cannot confirm aetiology and could not evaluate the potential contributions of variables such as light exposure, weather patterns, or social determinants.
Asunto(s)
Trastorno Depresivo Mayor/epidemiología , Ambiente , Canadá , Clima Frío/efectos adversos , Humanos , PrevalenciaRESUMEN
Type 2 diabetes mellitus (T2DM) is a complex and multifactorial disease that is generally characterized by insulin resistance and loss of ß-cell function that develops in adulthood. To date, more than 6% of the world's population is affected by T2DM. The main treatments of T2DM are dietary and lifestyle changes. However, only dependent on behaviour modification and oral hypoglycemics, many patients are unable to maintain glycemic control. Emerging evidence indicates that up to 80% of patients with T2DM undergoing Roux-en-Y gastric bypass (RYGB) experience complete remission of their T2DM and the majority of remissions occur almost immediately following the operation. Obestatin is a 23-amino-acid peptide, which is not only thought to suppress food intake and decrease gastric emptying but also found to exert survival effects in pancreatic ß cells, increase glucose-stimulated insulin secretion, and reduce insulin resistance and inflammation. In addition, some researchers demonstrated that obestatin is a nutritional marker reflecting body adiposity and insulin resistance. Although results from previous studies were conflicting, the peripheral blood concentrations of obestatin were changed after RYGB. Therefore, regulation of obestatin level may be another mechanism for RYGB-induced remission of T2DM. In this article, we review briefly the effect of RYGB on T2DM in humans and offer an overview of the published data on the effects of RYGB on obestatin level in patients with T2DM. Furthermore, the possible roles of obestatin in the remission of T2DM following RYGB are also reviewed. Copyright © 2015 John Wiley & Sons, Ltd.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirugía , Derivación Gástrica , Ghrelina/metabolismo , Humanos , Inducción de RemisiónRESUMEN
BACKGROUND: Gastric bypass restricts food intake, with a limited component of malabsorption. Gut and brain hormone changes also facilitate improvements in weight and comorbidities. Patients' perception of taste and smell also change, along with reduced appetite for savory meals. Data on how changes in gastrointestinal physiology affect brain centers of perception and reward are sparse. METHODS: With IRB approval, we recruited 13 patients to undergo pre- and postoperative taste testing and functional MRI (fMRI) in response to sweet and salty solutions. A delivery system to the tongue was used, and patients rated intensity and pleasantness. They then underwent fMRI scanning. Sensory and reward areas of the brain were evaluated for activation. Subjects were then compared to non-obese non-surgical controls with the same taste paradigm and scanning twice, at 1 month apart. RESULTS: All subjects experienced significant weight loss at 1 month and at 1 year after surgery. As expected, after surgery brain activation in the reward center of the brain was significantly decreased in response to sweet solutions, but this effect was also seen in non-surgical controls, making this result inconclusive. In contrast, surgical patients had significantly increased activation in the reward center to salty taste compared both to their preoperative scans and to healthy controls. CONCLUSIONS: After GBS, brain activation in the reward system of obese patients responding to palatable tastes may be significantly changed, and such changes can be detected using fMRI. They do not always correlate with subjective reports of intensity and pleasantness. To verify that such taste-related activation changes are caused specifically by the GBS, taste function of a control group of obese patients should be studied during the same period of time without GBS intervention but with similar weight loss.
Asunto(s)
Encéfalo/patología , Derivación Gástrica/efectos adversos , Obesidad Mórbida/cirugía , Complicaciones Posoperatorias/epidemiología , Trastornos del Gusto/epidemiología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Proyectos Piloto , Complicaciones Posoperatorias/etiología , Trastornos del Gusto/etiología , Trastornos del Gusto/patologíaRESUMEN
OBJECTIVE: Major depressive episodes (MDE) make an important contribution to disease burden in Canada. The epidemiology of MDE in the national population has been examined in 2 mental health surveys, one conducted in 2002 and the other in 2012. Our objective was to compare selected variables from the 2 surveys to determine whether changes have occurred in the prevalence, treatment, and impact of MDE. METHOD: The World Health Organization World Mental Health Composite International Diagnostic Interview was used in both surveys and the MDE module (which was not modified) was scored using the same algorithm. Some variables assessing impact and management of MDE were also identical in the 2 surveys. The analysis was based on frequency estimates and associated 95% confidence intervals. RESULTS: The annual prevalence of MDE was 4.7% (95% CI 4.3% to 5.1%) in 2012, nearly identical to 4.8% (95% CI 4.5% to 5.1%) in 2002. Receipt of potentially adequate treatment (defined as taking an antidepressant or 6 or more visits to a health professional for mental health reasons) increased from 41.3% in 2002 to 52.2% in 2012, mostly due to an increase in respondents reporting 6 or more visits. Use of second generation antipsychotics also increased. There was no evidence of diminishing prevalence or impact (as assessed by symptoms of distress). CONCLUSIONS: There appears to have been an increase in receipt of treatment for people with MDE and a changing pattern of management. However, it was not possible to confirm that the impact of MDE is diminishing as a result.
Asunto(s)
Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/terapia , Servicios de Salud Mental/estadística & datos numéricos , Adulto , Canadá/epidemiología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
BACKGROUND: Women have a higher prevalence of major depressive episodes (MDE) than men, and the annual prevalence of MDE declines with age. Age by sex interactions may occur (a weakening of the sex effect with age), but are easily overlooked since individual studies lack statistical power to detect interactions. The objective of this study was to evaluate age by sex interactions in MDE prevalence. METHODS: In Canada, a series of 10 national surveys conducted between 1996 and 2013 assessed MDE prevalence in respondents over the age of 14. Treating age as a continuous variable, binomial and linear regression was used to model age by sex interactions in each survey. To increase power, the survey-specific interaction coefficients were then pooled using meta-analytic methods. RESULTS: The estimated interaction terms were homogeneous. In the binomial regression model I (2) was 31.2 % and was not statistically significant (Q statistic = 13.1, df = 9, p = 0.159). The pooled estimate (-0.004) was significant (z = 3.13, p = 0.002), indicating that the effect of sex became weaker with increasing age. This resulted in near disappearance of the sex difference in the 75+ age group. This finding was also supported by an examination of age- and sex-specific estimates pooled across the surveys. CONCLUSIONS: The association of MDE prevalence with sex becomes weaker with age. The interaction may reflect biological effect modification. Investigators should test for, and consider inclusion of age by sex interactions in epidemiological analyses of MDE prevalence.
Asunto(s)
Trastorno Depresivo Mayor/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Canadá/epidemiología , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Distribución por Sexo , Adulto JovenRESUMEN
PURPOSE: To establish the relationship between ALS histopathology and quantitative MRI metrics. MATERIALS AND METHODS: ALS patients (N = 8) in advanced stages of the disease were enrolled and, immediately after death, the brain of each patient was removed. Freshly excised ALS tissue was imaged at 3.0 Tesla with T1 and T2 mapping protocols and subsequently stained with astrocyte, myelin, and neuronal markers. Measures of ALS histological stains were compared with the internal control (primary visual cortex) and longitudinal parametric maps. RESULTS: Post-mortem T1 -weighted images demonstrate diminished contrast between gray and white matter and alterations in T1 relaxation within the primary motor cortex. An increase in astrocyte number and reactivity as well as evident neuronal loss, a decrease in axonal density, and unraveling of the myelin sheaths in subcortical white matter were found in the ALS primary motor cortex exhibiting significant T1 relaxation and contrast changes. CONCLUSION: This study provides a histopathological basis for differences in MR T1 contrast and relaxation seen in the ALS brain.
Asunto(s)
Esclerosis Amiotrófica Lateral/patología , Imagen por Resonancia Magnética , Corteza Motora/patología , Anciano , Anciano de 80 o más Años , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/ultraestructuraRESUMEN
Surfactant-free CuAgSe nanoparticles were successfully synthesized on a large scale within a short reaction time via a simple environmentally friendly aqueous approach under room temperature. The nanopowders obtained were consolidated into pellets for investigation of their thermoelectric properties between 3 and 623 K. The pellets show strong metallic characteristics below 60 K and turn into an n-type semiconductor with increasing temperature, accompanied by changes in the crystal structure (i.e., from the pure tetragonal phase into a mixture of tetragonal and orthorhombic phases), the electrical conductivity, the Seebeck coefficient, and the thermal conductivity, which leads to a figure of merit (ZT) of 0.42 at 323 K. The pellets show further interesting temperature-dependent transition from n-type into p-type in electrical conductivity arising from phase transition (i.e., from the mixture phases into cubic phase), evidenced by the change of the Seebeck coefficient from -28 µV/K into 226 µV/K at 467 K. The ZT value increased with increasing temperature after the phase transition and reached 0.9 at 623 K. The sintered CuAgSe pellets also display excellent stability, and there is no obvious change observed after 5 cycles of consecutive measurements. Our results demonstrate the potential of CuAgSe to simultaneously serve (at different temperatures) as both an n-type and a p-type thermoelectric material.