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AIMS: Patient satisfaction is associated with positive diabetes outcomes. However, there are no identified studies that evaluate both patient- and clinic-level predictors influencing diabetes care satisfaction longitudinally. METHODS: Data from the INtegrating DEPrEssioN and Diabetes treatmENT trial was used to perform the analysis. We used fixed and random effects models to assess whether and how changes in patient-level predictors (treatment assignment, depression symptom severity, systolic blood pressure, body mass index, LDL cholesterol, and haemoglobin A1C) from 0 to 24 months and clinic-level predictors (visit frequency, visit cost, number of specialists, wait time, time spent with healthcare provider, and receiving verbal reminders) measured at 24 months influence diabetes care satisfaction from 0 to 24 months. RESULTS: Model 1 (patient-level predictors) accounted for 7% of the change in diabetes satisfaction and there was a significant negative relationship between change in depressive symptoms and care satisfaction (ß = -0.23, SE = 0.12, p < 0.05). Within Model 1, 2% of the variance was explained by clinic-level predictors. Model 2 included both patient- and clinic-level predictors and accounted for 18% of the change in diabetes care satisfaction. Within Model 2, 9% of the variance was attributed to clinic-level predictors. There was also a cross-level interaction where the change in depression had less of an impact on the change in satisfaction for those who received a verbal reminder (ß = -0.11, SE = 0.21, p = 0.34) compared with those who did not receive a reminder (ß = -0.62, SE = 0.08, p < 0.01). CONCLUSIONS: Increased burden of depressive symptoms influences diabetes care satisfaction. Clinic-level predictors also significantly influence diabetes care satisfaction and can reduce dissatisfaction in primary care, specifically, reminder calls from clinic staff.
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Aim: To develop novel non-carbohydrate inhibitors of human galectin-1 (GAL-1), we have designed a series of coumarin-benzimidazole hybrids. Methods: We synthesized and characterized the coumarin-benzimidazole hybrids and further evaluated them using an in vitro GAL-1 enzyme-linked immunosorbent assay and in silico methods. Results: Among all, the compounds 6p and 6q were found to be potent, with GAL-1 inhibition of 37.61 and 36.92%, respectively, at 10 µM in GAL-1-expressed cell culture supernatant of MCF-7 cells. These two compounds are feasible for fluorine-18 radiolabeling to develop GAL-1 selective PET radiotracers. Computational studies revealed strong binding interactions of GAL-1 with these novel coumarin-benzimidazole hybrids. Conclusion: Coumarin-benzimidazole hybrids can serve as potential leads to develop selective non-carbohydrate GAL-1 inhibitors for cancer therapy.
[Box: see text].
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Bencimidazoles , Cumarinas , Diseño de Fármacos , Galectina 1 , Humanos , Galectina 1/antagonistas & inhibidores , Galectina 1/metabolismo , Cumarinas/química , Cumarinas/farmacología , Cumarinas/síntesis química , Bencimidazoles/química , Bencimidazoles/farmacología , Bencimidazoles/síntesis química , Células MCF-7 , Relación Estructura-Actividad , Simulación del Acoplamiento Molecular , Estructura MolecularRESUMEN
Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.
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Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes.
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Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.
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Water is being considered as an economical, safe and environmental friendly alternative solvent for dye lasers. However, the use of water in dye laser is restricted due to the formation of non-emissive aggregates of dye molecules. In the present study we have explored the possibility of the use of commercially available surfactant molecules for the water based laser of Pyrromethene 597 (PM597) dye, which has emerged as an alternative for more commonly used Rhodamine dyes in dye laser systems. Our studies show that in water, PM597 forms non-emissive aggregates which can be dissociated into monomeric dye molecules by adding common surfactants. Further, the high microviscosity in the micellar media retarded energy wasting ring puckering process in the excited state of the dye leading to the increase in its emission yield and excited state lifetime to a significant extent. It has been demonstrated that the emission yield and excited state lifetime in surfactant solution is relatively higher than in ethanol, the most commonly used organic solvent for dye lasers. Lasing action has been demonstrated in the aqueous solution of dye and lasing efficiency is found to be comparable to ethanol.
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Láseres de Colorantes , Tensoactivos , Etanol , Colorantes Fluorescentes , Porfobilinógeno/análogos & derivados , Solventes , AguaRESUMEN
BACKGROUND: Evaluation of peritoneal membrane permeability in patients on continuous ambulatory peritoneal dialysis (CAPD) is crucial in prescribing treatment regimens. This study evaluated peritoneal membrane characteristics in patients on CAPD using standard peritoneal equilibration test (PET) and fast PET. METHODS: A prospective observational longitudinal study included patients on CAPD with no symptoms of peritonitis for at least 4 weeks before the PET. Both, standard and fast PET were performed using 2.5% glucose-containing dialysate. The dialysate and plasma (D/P) creatinine ratios at each time point (i.e., 0 h, 2nd h, and 4th h) in standard and at 4th hour only in fast PET were determined. Patients were classified according to D/P creatinine value as high, high-average, low-average, low transporter. The follow-up period was 6 months and changes in membrane characteristics were compared again to revalidate the efficacy of fast PET. RESULTS: A total of 50 patients between 41 and 70 years of age were enrolled. The majority had diabetic nephropathy (40%) and chronic glomerulonephritis (28%). Based on transport type, a significant positive correlation was observed between the D/P creatinine ratio of baseline standard PET I and fast PET I (r = 0.992, P ≤ 0.05) and standard PET II and fast PET II (r = 0.969, P ≤ 0.05) done after 6 months. The results of the PET and transport category after 6 months were similar in 82% cases determined by fast PET and 98% cases determined by the standard pet. There was significant agreement between both the methods of PET (K value = 0.872, P < 0.001). A significant (P ≤ 0.001) correlation was observed between standard PET I and standard PET II transport status. CONCLUSION: Fast PET is a good alternative for assessing peritoneal membrane characteristics especially in the setting of less availability of resources and is a less cumbersome procedure as compared to standard PET.
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In this study, Bi3+ incorporation in NaYbF4 :Er lattice and its influence on upconversion luminescence properties have been investigated in detail using techniques such as temperature-dependent luminescence, Fourier transform infrared spectroscopy and X-ray diffraction (XRD). The study was carried out to develop phosphors with improved upconversion luminescence. From photoluminescence and lifetime measurements it is inferred that luminescence intensity from NaYbF4 :Er increases with Bi3+ addition. The sample containing 50 at.% Bi3+ ions exhibited optimum upconversion luminescence. Increased distance between Yb3+ -Yb3+ and Er3+ -Er3+ due to Bi3+ incorporation into the lattice and associated decrease in the extent of dipolar interaction/self-quenching are responsible for increase in lifetime values and luminescence intensities from Er3+ ions. Incorporation of Bi3+ into NaYbF4 :Er lattice reduced self-quenching among Yb3+ -Yb3+ ions and this facilitated energy transfer from Yb3+ to Er3+ . This situation also explains decrease in the extent of temperature-assisted quenching of emission from thermally coupled 2 H11/2 and 4 S3/2 levels of Er3+ . Based on Rietveld refinement of XRD patterns it was confirmed that a maximum of 10 at.% of Bi3+ added was incorporated into the NaYbF4 :Er lattice and the remaining complex co-exists as a BiOF phase. These results are of significant interest in the area of development of phosphors based on Yb3+ -Er3+ upconversion luminescence.
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Bismuto/química , Erbio/química , Fluoruros/química , Luminiscencia , Itrio/química , Mediciones Luminiscentes , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
Although aqueous dye lasers are much sought after, they have been of no practical use, as laser dyes show a strong tendency for aggregation in water, thus diminishing their optical output. Contributing towards this shortcoming, we studied the noncovalent interactions of two prominent laser dyes, namely, rhodamine 6G and rhodamine B, with a water soluble macrocyclic host, sulfobutylether-ß-cyclodextrin (SBE7 ßCD). Spectral changes in the absorption and fluorescence behavior of dyes in presence of the SBE7 ßCD host indicated adequate complex formation between dye and host (Kâ¼104 â M-1 ). A combination of various photophysical parameters evaluated from measurements such as Job plot, changes in the fluorescence lifetime/anisotropy values, and favorable thermodynamic parameters from isothermal titration calorimetric measurements adjudicated a 1 : 1 stoichiometric complex formation between dye and SBE7 ßCD host. Consequently, SBE7 ßCD prevents dye aggregation/adsorption and present rhodamine dyes in their monomeric forms with enhanced fluorescence yield and brightness. These vital parameters were utilized to optimize and demonstrate cost-effective supramolecular broad-band and narrow-band aqueous dye laser systems with improved lasing efficiencies (â¼25 % higher for the SBE7 ßCD : RhB system and â¼10 % higher for SBE7 ßCD : Rh6G system), better beam profile, and enhanced durability compared to the respective dyes in optically matched ethanol solutions.
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Colorantes Fluorescentes/química , Láseres de Colorantes , Sustancias Macromoleculares/química , Rodaminas/química , beta-Ciclodextrinas/química , Adsorción/efectos de los fármacos , Fluorescencia , Colorantes Fluorescentes/efectos de la radiación , Tecnología Química Verde , Sustancias Macromoleculares/efectos de la radiación , Modelos Químicos , Estructura Molecular , Rodaminas/efectos de la radiación , Agua/químicaRESUMEN
Hemidesmus indicus (L.) R. Br. was extensively used as hypoglycaemic agent and significance of this plant on secondary complications of diabetes remained unknown. The present study was to investigate the anti-cataractous activity of H. indicus against streptozotocin (STZ)-induced diabetic cataract in rodent model. Root extracts have been prepared and tested for inhibition of rat lens aldose reductase (AR) activity. In addition, its pharmacological potential has been investigated in STZ-induced diabetic cataract. Methanol extract of H. indicus-inhibited AR activity in vitro decreased the blood glucose levels, inhibited the AR activity and delayed the onset and progression of cataract in a dose-dependent manner in in vivo and the antioxidant markers have been normalised. Our results demonstrate that H. indicus has decrease the osmotic stress by inhibiting the AR activity and prevented the loss of antioxidants and delayed the progression of diabetic cataract in STZ-induced diabetic rats.
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Catarata/prevención & control , Diabetes Mellitus Experimental/tratamiento farmacológico , Hemidesmus/química , Hipoglucemiantes/farmacología , Aldehído Reductasa/antagonistas & inhibidores , Aldehído Reductasa/metabolismo , Animales , Antioxidantes/metabolismo , Catarata/etiología , Diabetes Mellitus Experimental/complicaciones , Enzimas/metabolismo , Cristalino/efectos de los fármacos , Cristalino/metabolismo , Masculino , Presión Osmótica/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Raíces de Plantas/química , Ratas Sprague-Dawley , EstreptozocinaRESUMEN
The prevalence of both Alzheimer's disease (AD) and vascular dementia (VaD) is increasing with the aging of the population. Studies from the last several years have shown that people with diabetes have an increased risk for dementia and cognitive impairment. Therefore, the authors of this consensus review tried to elaborate on the role of diabetes, especially diabetes type 2 (T2DM) in both AD and VaD. Based on the clinical and experimental work of scientists from 18 countries participating in the International Congress on Vascular Disorders and on literature search using PUBMED, it can be concluded that T2DM is a risk factor for both, AD and VaD, based on a pathology of glucose utilization. This pathology is the consequence of a disturbance of insulin-related mechanisms leading to brain insulin resistance. Although the underlying pathological mechanisms for AD and VaD are different in many aspects, the contribution of T2DM and insulin resistant brain state (IRBS) to cerebrovascular disturbances in both disorders cannot be neglected. Therefore, early diagnosis of metabolic parameters including those relevant for T2DM is required. Moreover, it is possible that therapeutic options utilized today for diabetes treatment may also have an effect on the risk for dementia. T2DM/IRBS contribute to pathological processes in AD and VaD.
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Encéfalo/patología , Disfunción Cognitiva , Diabetes Mellitus Tipo 2 , Enfermedad de Alzheimer/epidemiología , Enfermedad de Alzheimer/etiología , Enfermedad de Alzheimer/patología , Encéfalo/metabolismo , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , HumanosRESUMEN
INTRODUCTION: Depression and diabetes are highly prevalent worldwide and often co-exist, worsening outcomes for each condition. Barriers to diagnosis and treatment are exacerbated in low and middle-income countries with limited health infrastructure and access to mental health treatment. The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) study tests the sustained effectiveness and cost-effectiveness of a multi-component care model for individuals with poorly-controlled diabetes and depression in diabetes clinics in India. MATERIALS AND METHODS: Adults with diabetes, depressive symptoms (Patient Health Questionnaire-9 score≥10), and ≥1 poorly-controlled cardiometabolic indicator (either HbA1c≥8.0%, SBP≥140mmHg, and/or LDL≥130mg/dl) were enrolled and randomized to the intervention or usual care. The intervention combined collaborative care, decision-support, and population health management. The primary outcome is the between-arm difference in the proportion of participants achieving combined depression response (≥50% reduction in Symptom Checklist score from baseline) AND one or more of: ≥0.5% reduction in HbA1c, ≥5mmHg reduction in SBP, or ≥10mg/dl reduction in LDL-c at 24months (12-month intervention; 12-month observational follow-up). Other outcomes include control of individual parameters, patient-centered measures (i.e. treatment satisfaction), and cost-effectiveness. RESULTS: The study trained seven care coordinators. Participant recruitment is complete - 940 adults were screened, with 483 eligible, and 404 randomized (196 to intervention; 208 to usual care). Randomization was balanced across clinic sites. CONCLUSIONS: The INDEPENDENT model aims to increase access to mental health care and improve depression and cardiometabolic disease outcomes among complex patients with diabetes by leveraging the care provided in diabetes clinics in India (clinicaltrials.gov number: NCT02022111).
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Manejo de Caso/organización & administración , Depresión/epidemiología , Depresión/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Autocuidado/métodos , Adulto , Anciano , Presión Sanguínea , Manejo de Caso/economía , LDL-Colesterol/sangre , Análisis Costo-Beneficio , Femenino , Hemoglobina Glucada , Humanos , India , Masculino , Persona de Mediana Edad , Entrevista Motivacional/métodos , Educación del Paciente como Asunto/métodos , Proyectos de Investigación , Método Simple CiegoRESUMEN
AIMS: Depression and diabetes are highly comorbid, adversely affecting treatment adherence and resulting in poor outcomes. To improve treatment and outcomes for people dually-affected by diabetes and depression in India, we aimed to develop and test an integrated care model. In the formative phase of this INtegrated DEPrEssioN and Diabetes TreatmENT (INDEPENDENT) study, we sought stakeholder perspectives to inform culturally-sensitive adaptations of the intervention. METHODS: At our Delhi, Chennai, and Vishakhapatnam sites, we conducted focus groups for patients with diabetes and depression and interviewed healthcare workers, family members, and patients. These key informants were asked about experiences with diabetes and depression and for feedback on intervention materials. Data were analyzed using a grounded theory approach. RESULTS: Three major themes emerged that have bearing on adaptation of the proposed intervention: importance of family assistance, concerns regarding patient/family understanding of diabetes, and feedback regarding the proposed intervention (e.g. adequate time needed for implementation; training program and intervention should address stigma). CONCLUSIONS: Based on our findings, the following components would add value when incorporated into the intervention: 1) engaging families in the treatment process, 2) clear/simple written information, 3) clear non-jargon verbal explanations, and 4) coaching to help patients cope with stigma.
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BACKGROUND: Thrombotic events (TEs) are serious adverse events that can occur following administration of clotting factors (CFs). OBJECTIVES: To evaluate occurrence of same-day TEs for different CF products and potential risk factors. METHODS: A retrospective cohort study of individuals exposed to CF products during 2008-2013 was conducted using a large commercial insurance database. CF products were identified by procedure codes, and TEs were ascertained via diagnosis codes. Crude same-day TE rates (per 1000 persons exposed) were estimated overall and by congenital factor deficiency (CFD) status, CF products, age and gender. Multivariable logistic regression analyses were used to control for confounding. Laboratory analysis was used to compare the procoagulant activities of FIX products. RESULTS: Of 3801 individuals exposed to CFs, 117 (30.8 per 1000) had same-day TEs recorded. The crude same-day TE rate was higher for CF users without CFD, 70.2 (102 of 1452), as compared with those with CFD, 6.4 (15 of 2349) (RR, 11.0; 95% CI, 6.4-18.9). For individuals without CFD, a significantly increased same-day TE risk was identified for factor IX complex (OR, 6.92; 95% CI, 3.11-15.40), factor VIIa (OR, 9.42; 95% CI, 4.99-17.78) and other products when compared with fibrin sealant. An increased risk of a TE was found with older age (≥ 45 years), history of TEs and underlying health conditions. The laboratory identified elevated procoagulant activity in Profilnine(®) and Benefix(®) . CONCLUSIONS: The study shows an increased same-day TE risk for CF users without CFD and suggests substantial off-label CF use. The study findings also show elevated same-day TE rates for different CF products and suggest the importance of product properties and patient factors.
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Coagulantes/efectos adversos , Factor IX/efectos adversos , Trombosis/inducido químicamente , Adolescente , Adulto , Anciano , Distribución de Chi-Cuadrado , Coagulantes/administración & dosificación , Comorbilidad , Bases de Datos Factuales , Esquema de Medicación , Contaminación de Medicamentos , Factor IX/administración & dosificación , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Uso Fuera de lo Indicado , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Trombosis/diagnóstico , Trombosis/epidemiología , Factores de Tiempo , Estados Unidos/epidemiología , Adulto JovenRESUMEN
The title mol-ecular salt, C15H22N(+)·Cl(-), arose as an unexpected product of the reaction between aniline and melanol in the presence of HCl. The central heterocyclic ring has a half-chair conformation and the five-membered ring has an envelope conformation, with the C atom linked to the N atom as the flap. In the crystal, the ions are linked by N-Hâ¯Cl hydrogen bonds, generating chains propagating in the [100] direction. The crystal studied was a merohedral twin with a 0.64â (3):0.36â (3) domain ratio.
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Recurrence of FSGS in renal allo grafts is a major cause of graft loss. In this context, we tried to diagnose and classify FSGS in renal allografts. Indications for biopsy included graft dysfunction and/or proteinuria. Three hundred and sixty-three graft biopsies were studied over a period of 2 years. We classified FSGS into recurrent FSGS, new-onset primary FSGS and FSGS secondary to chronic humoral rejection, calcineurin inhibitor toxicity, and nephron loss and hyperfiltration injury. Twenty-four cases were diagnosed as FSGS, constituting 6.6%. Secondary FSGS was the most common FSGS in grafts in our study. Incidence of recurrent FSGS may not be accurate as pretransplant biopsy is available in very few cases.
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Thrombotic microangiopathy (TMA) is a serious complication of renal transplantation. It is a morphological expression of various etiological factors. In a renal allograft, TMA can occur de novo or be a recurrent disease. The aim of this study was to analyze the etiological factors and observe the changing trends of TMA with respect to emerging new etiological factors. We evaluated 131 graft biopsies over a period of 2½ years (2010-2012). All the renal biopsies were formalin fixed, paraffin embedded. Twenty serial sections were studied. Stains routinely used were Hematoxylin and Eosin, Periodic Acid Schiff, Massons Trichrome and Silver Methenamine stains. C4d by immunohistochemical method was done on all graft biopsies. Incidence of TMA in our series was 9.1%. Out of the 12 cases, five were associated with calcineurin inhibitor toxicity, three were diagnosed as acute antibody-mediated rejection, and two were recurrent haemolytic uremic syndrome. One patient developed haemolytic uremic syndrome on treatment with sirolimus and one patient was cytomegalovirus positive on treatment with ganciclovir, developed haemolytic uremic syndrome during treatment course. This study describes a spectrum of etiological factors for thrombotic mciroangiopathy ranging from common cause like calcineurin inhibitor toxicity to rare cause like ganciclovir induced TMA.