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A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathologic responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis.
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Exocitosis , Técnicas de Preparación Histocitológica/métodos , Modelos Biológicos , Páncreas Exocrino/metabolismo , Pancreatitis/metabolismo , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Páncreas Exocrino/patología , Pancreatitis/patologíaRESUMEN
IMPORTANCE: Pre-operative hyperglycemia is associated with post-operative adverse outcomes in diabetic and non-diabetic patients. Current pre-operative screening includes random plasma glucose, yet plasma glycated hemoglobin (HbA1c) is a better measure of long-term glycemic control. It is not clear whether pre-operative HbA1c can identify non-diabetic patients at risk of post-operative complications. OBJECTIVE: The systematic review summarizes the evidence pertaining to the association of suboptimal pre-operative HbA1c on post-operative outcomes in adult surgical patients with no history of diabetes mellitus. EVIDENCE REVIEW: A detailed search strategy was developed by a librarian to identify all the relevant studies to date from the major online databases. FINDINGS: Six observational studies met all the eligibility criteria and were included in the review. Four studies reported a significant association between pre-operative HbA1c levels and post-operative complications in non-diabetic patients. Two studies reported increased post-operative infection rates, and two reported no difference. Of four studies assessing the length of stay, three did not observe any association with HbA1c level and only one study observed a significant impact. Only one study found higher mortality rates in patients with suboptimal HbA1c. CONCLUSIONS AND RELEVANCE: Based on the limited available evidence, suboptimal pre-operative HbA1c levels in patients with no prior history of diabetes predict post-operative complications and represent a potentially modifiable risk factor.
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Hemoglobina Glucada/análisis , Hiperglucemia/diagnóstico , Complicaciones Posoperatorias/sangre , Procedimientos Quirúrgicos Operativos/efectos adversos , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus/sangre , Humanos , Hiperglucemia/complicaciones , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Factores de RiesgoAsunto(s)
Bebidas , Colectomía , Carbohidratos de la Dieta/administración & dosificación , Resistencia a la Insulina , Laparoscopía , Complicaciones Posoperatorias/prevención & control , Administración Oral , Anciano , Método Doble Ciego , Recuperación Mejorada Después de la Cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de RiesgoRESUMEN
INTRODUCTION: Mental complications of diabetes are one of the main obstacles to the implementation of self -care behaviors that have been less studied. Therefore, this study was conducted to survey the effective factors in predicting burnout and self-care behaviors among patients with type 2 diabetes. METHODS: In this Path analysis, 1280 patients with type 2 diabetes were selected from Mashhad (Iran) in 2023 to 2024. Four scales, the mental health literacy (MHL) scale, diabetes burnout scale, diabetes distress scale, and self-care behavior scale were used for data gathering. AMOS software checked the direct and indirect paths between the variables. RESULTS: In the path analysis, variables of MHL and diabetes distress predicted 25% variance of diabetes burnout (R2 = 0.25), and diabetes distress (total effect = 0.491) had the greatest impact on predicting diabetes burnout. Variables of MHL, diabetes distress, and diabetes burnout predicted 12% variance of Self-care behaviors (R2 = 0.12) and MHL (total effect = -0.256), age of onset of diabetes (total effect = 0.199), and diabetes burnout (total effect = - 0.167) had the greatest impact on prediction of self-care behaviors. CONCLUSION: MHL could reduce diabetes distress and burnout and eventually promote self-care behaviors among patients with type 2 diabetes. Therefore, screening and identifying psychological problems (such as distress and burnout) and designing interventions to increase MHL can ultimately increase the health of patients with diabetes.
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BACKGROUND: Dissatisfaction with appearance is most pronounced in rhinoplasty patients compared to candidates for other aesthetic procedures. We aimed to test and introduce the Body Image Concern Inventory (BICI) as a self-report screening tool for identifying body dysmorphic disorder (BDD) among patients seeking rhinoplasty. METHODS: The surgeon completed a two-point defect severity scale in which a score of 1 represented no defect or one defect and a score of 2 represented more than one defect. Each of the 117 subjects with a score of 1 answered a questionnaire that was designed to obtain demographic data and completed the Persian version of the BICI. The psychiatrist, considering the patient's demographic data and blind to the BICI score, interviewed him/her using a semistructured diagnostic tool for BDD based on DSM-IV. RESULTS: The validity of the Persian version of the BICI was calculated at 85%. The reliability of the Persian BICI items was tested and Cronbach's alpha was 0.90. The results of ROC analysis for the ideal cutoff point of the Persian BICI, based on the Youden index method and optimum sensitivity and specificity, revealed that the ideal cutoff point for positive or negative criterion of that questionnaire's result may be the total score of 42 (sensitivity, 93.5%; specificity, 80.8%) The diagnostic accuracy of the Persian BICI in comparison with the gold standard (psychiatric interview), according to the area under the ROC curve (AUC), was 91.4% (95% CI = 86-97%, P < 0.0001). The agreement of the results of the Persian BICI questionnaire with the psychiatric interview for diagnosis of BDD, according to kappa index, was 61.7% (P < 0.001), and the odds ratio (OR) of being diagnosed with BDD in a psychiatric interview for those with overall scores ≥42 for the Persian BICI was 47.7 (95% CI = 43-52). CONCLUSION: The results of the present study emphasize the high rate of BDD (12.2%) in subjects seeking rhinoplasty. The BICI appears to be an internally consistent and valid brief multiple-choice instrument for assessing dysmorphic concern. To our knowledge, this is the first time that this measure has ever been used for identifying BDD patients in a rhinoplasty setting; it is also the first time that ROC analysis has been used for calculating and analyzing the results of BICI. Our study suggests that rhinoplasty surgeons could rely on the scores of the BICI to identify subjects with probable BDD among their consultants with no or one slight defect.
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Trastorno Dismórfico Corporal/diagnóstico , Imagen Corporal , Rinoplastia , Encuestas y Cuestionarios , Femenino , Humanos , Masculino , Traducciones , Adulto JovenRESUMEN
To assess the effect of two different combinations of alar cartilage-modifying techniques on the degree of nasal tip projection and rotation, a prospective trial was performed using preoperative and postoperative photos. The patients were seen in private practice. Sixty patients who had underprojected with/without underrotated nasal tips, primarily due to alar cartilage malformities, were randomly divided into two equal groups (A, B). All patients were operated using an external rhinoplasty approach. The techniques of narrowing transdomal sutures and placing a collumellar strut were used in both groups; in addition, lateral crural steal (LCS) was used only in group B. The patients were reevaluated after a minimum period of 6 months. The nasofacial angle and the Goode ratio were measured to assess tip projection and the nasolabial angle was used to assess tip rotation. The patients of both groups showed significant increase in tip projection and rotation (P < 0.001). Additionally, the use of LCS in patients of group B resulted in significantly more increase in tip projection and rotation in comparison with group A (P < 0.05). The LCS along with placement of a columellar strut and a transdomal suture is more beneficial in patients suffering from underprojection with/without underrotated nasal tips.
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Cartílago/cirugía , Rinoplastia/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Nariz , Adulto JovenRESUMEN
Up until the date of this research, studies have examined poststroke cognitive impairments in attention, memory, and executive functions. In this study, we investigated the occurrence of memory problems in various patterns of memory in ischemic stroke patients in an attempt to determine specific memory profiles of the patients. The goal was to determine the severity and patterns of memory impairments in ischemic stroke patients and to identify specific profiles of memory impairments in stroke patients, in order to help therapists to develop more appropriate memory rehabilitation programs for the patients. The sample consisted of 35 patients with ischemic stroke. Thirty-five individuals who were matched with the patients were selected as the control group. Demographic questionnaires, subscales of the Wechsler Memory Scale-III (WMS-III), including logical memory I and II and visual reproduction I and II, digit span from the Wechsler Adult Intelligence Scale-R (WAIS-R), and the Corsi span test were administered to both of the patients and control groups. Multivariate analysis of covariance (MANCOVA) was carried out to unveil possible differences in memory between the two groups. The mean scores of different memory patterns were significantly higher in the control group comparing to the patient group (p < 0.05). Among different aspects of memory, visual long-term memory and visual short-term memory had the largest effect sizes. Substantial impairments were also found in visual short-term memory, visuospatial short-term memory, and visual long-term memory. The findings suggest that the stroke patients have identifiable patterns of memory impairment.
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Trastornos de la Memoria/etiología , Accidente Cerebrovascular/complicaciones , Adulto , Anciano , Análisis de Varianza , Isquemia Encefálica/complicaciones , Isquemia Encefálica/diagnóstico por imagen , Femenino , Humanos , Pruebas de Inteligencia , Irán/epidemiología , Imagen por Resonancia Magnética , Masculino , Trastornos de la Memoria/diagnóstico , Persona de Mediana Edad , Pruebas Neuropsicológicas , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Aprendizaje Verbal/fisiología , Escalas de WechslerRESUMEN
OBJECTIVE: Pancreatic beta-cells express three Munc18 isoforms. Much is known about the roles of Munc18a (pre-docked secretory granules-SGs) and Munc18b (newcomer SGs and SG-SG fusion) in insulin exocytosis. Although shown to influence glucose-stimulated insulin secretion (GSIS) in rodents the precise role of Munc18c in insulin SG exocytosis has not been elucidated. We here examined the role of Munc18c in human pancreatic beta-cells. METHODS: Munc18c-shRNA/RFP lenti-virus (versus control virus) was used to knock down the expression level of Munc18c in human islets or single beta-cells. Insulin secretion and granule exocytosis were measured by performing islets perifusion, single-cell patch clamp capacitance measurements and total internal reflection fluorescence microscopy (TIRFM). RESULTS: Munc18c is most abundant in the cytosol of human beta-cells. Endogenous function of Munc18c was assessed by knocking down (KD) its islet expression by 70% employing lenti-shRNA virus. Munc18c-KD caused reduction in cognate syntaxin-4 islet expression but not in other exocytotic proteins, resulting in the reduction in GSIS in first- (by 42%) and second phases (by 35%). Single cell analyses of RFP-tagged Munc18c-KD beta-cells by patch clamp capacitance measurements showed inhibition in both readily-releasable pool (by 52%) and mobilization from the reserve pool (by 57%). TIRFM to assess single SG behavior showed that Munc18c-KD inhibition of first phase GSIS was attributed to reduction in exocytosis of pre-docked and newcomer SGs, and second phase inhibition attributed entirely to reduction in newcomer SG fusion (SGs that undergo minimal residence or docking time at the plasma membrane before fusion). CONCLUSION: Munc18c is involved in the distinct molecular machineries that affect exocytosis of both predocked and newcomer SG pools that underlie Munc18c's role in first and second phases of GSIS, respectively.
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Early-stage type 1 diabetes (T1D) exhibits hyperglucagonemia by undefined cellular mechanisms. Here we characterized α-cell voltage-gated ion channels in a streptozotocin (STZ)-induced diabetes model that lead to increased glucagon secretion mimicking T1D. GYY mice expressing enhanced yellow fluorescence protein in α cells were used to identify α cells within pancreas slices. Mice treated with low-dose STZ exhibited hyperglucagonemia, hyperglycemia, and glucose intolerance, with 71% reduction of ß-cell mass. Although α-cell mass of STZ-treated mice remained unchanged, total pancreatic glucagon content was elevated, coinciding with increase in size of glucagon granules. Pancreas tissue slices enabled in situ examination of α-cell electrophysiology. α cells of STZ-treated mice exhibited the following: 1) increased exocytosis (serial depolarization-induced capacitance), 2) enhanced voltage-gated Na(+) current density, 3) reduced voltage-gated K(+) current density, and 4) increased action potential (AP) amplitude and firing frequency. Hyperglucagonemia in STZ-induced diabetes is thus likely due to increased glucagon content arising from enlarged glucagon granules and increased AP firing frequency and amplitude coinciding with enhanced Na(+) and reduced K(+) currents. These alterations may prime α cells in STZ-treated mice for more glucagon release per cell in response to low glucose stimulation. Thus, our study provides the first insight that STZ treatment sensitizes release mechanisms of α cells.
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Diabetes Mellitus Experimental/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Células Secretoras de Glucagón/fisiología , Glucagón/metabolismo , Canales de Potasio con Entrada de Voltaje/fisiología , Canales de Sodio Activados por Voltaje/fisiología , Potenciales de Acción/fisiología , Animales , Células Cultivadas , Diabetes Mellitus Tipo 1/inducido químicamente , Fenómenos Electrofisiológicos , Exocitosis/fisiología , Glucagón/análisis , Glucagón/sangre , Células Secretoras de Glucagón/patología , Intolerancia a la Glucosa/fisiopatología , Hiperglucemia/sangre , Hiperglucemia/fisiopatología , Ratones , Vesículas Secretoras/fisiologíaRESUMEN
Impaired counterregulation during hypoglycemia in type 1 diabetes (T1D) is partly attributable to inadequate glucagon secretion. Intra-islet somatostatin (SST) suppression of hypoglycemia-stimulated α-cell glucagon release plays an important role. We hypothesized that hypoglycemia can be prevented in autoimmune T1D by SST receptor type 2 (SSTR2) antagonism of α-cells, which relieve SSTR2 inhibition, thereby increasing glucagon secretion. Diabetic biobreeding diabetes-prone (BBDP) rats mimic insulin-dependent human autoimmune T1D, whereas nondiabetic BBDP rats mimic prediabetes. Diabetic and nondiabetic rats underwent a 3-h infusion of vehicle compared with SSTR2 antagonist (SSTR2a) during insulin-induced hypoglycemia clamped at 3 ± 0.5 mmol/L. Diabetic rats treated with SSTR2a needed little or no glucose infusion compared with untreated rats. We attribute this effect to SSTR2a restoration of the attenuated glucagon response. Direct effects of SSTR2a on α-cells was assessed by resecting the pancreas, which was cut into fine slices and subjected to perifusion to monitor glucagon release. SSTR2a treatment enhanced low-glucose-stimulated glucagon and corticosterone secretion to normal levels in diabetic rats. SSTR2a had similar effects in vivo in nondiabetic rats and promoted glucagon secretion from nondiabetic rat and human pancreas slices. We conclude that SST contributes to impaired glucagon responsiveness to hypoglycemia in autoimmune T1D. SSTR2a treatment can fully restore hypoglycemia-stimulated glucagon release sufficient to attain normoglycemia in both diabetic and prediabetic stages.
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Diabetes Mellitus Tipo 1/metabolismo , Células Secretoras de Glucagón/efectos de los fármacos , Glucagón/metabolismo , Páncreas/efectos de los fármacos , Estado Prediabético/metabolismo , Receptores de Somatostatina/antagonistas & inhibidores , Animales , Catecolaminas/metabolismo , Corticosterona/metabolismo , Células Secretoras de Glucagón/metabolismo , Técnica de Clampeo de la Glucosa , Humanos , Insulina/metabolismo , Secreción de Insulina , Masculino , Páncreas/metabolismo , Péptidos Cíclicos/farmacología , Ratas , Somatostatina/metabolismoRESUMEN
OBJECTIVE: To report a rare presentation of Swyer syndrome in a woman with pure 46,XY gonadal dysgenesis. DESIGN: Case report. SETTING: Academic gynecology and obstetrics department. PATIENT(S): A 28-year-old woman with primary amenorrhea. INTERVENTION(S): Laparoscopic gonadectomy. MAIN OUTCOME MEASURE(S): Age at diagnosis, risk of gonadal malignancy, bone mineral density, uterus size, height. RESULT(S): The patient had pure 46,XY gonadal dysgenesis with hypoplastic uterus, which is a rare finding in Swyer syndrome. She had developed no gonadal malignancies and, despite receiving estrogen, had remained amenorrheic. CONCLUSION(S): Further studies should be done on this rare chromosomal condition to find the exact factors affecting the uterus size and to improve the ways of inducing puberty in such patients by considering the age of diagnosis in order to help them have a normal sex life and also the ability to carry a fetus in their immature uteruses.