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Visfatin is found in adipose tissue and is referred to as nicotinamide phosphoribosyltransferase (Nampt). Visfatin has anti-apoptotic, proliferative, and metastatic properties and may mediate its effects via ERK and PI3K/Akt signaling. Studies have yet to determine whether inhibition of kinase signaling will suppress visfatin-induced liver cancer. The purpose of this study was to determine which signaling pathways visfatin may promote liver cancer progression.
HepG2 and SNU-449 liver cancer cells were exposed to visfatin with or without ERK or PI3K/Akt inhibitor, or both inhibitors combined. These processes that were assessed proliferation, reactive oxygen species (ROS), lipogenesis, invasion, and matrix metalloproteinase (MMP).
Inhibition of PI3K/Akt and combination of inhibitors suppressed visfatin-induced viability. ERK inhibition in HepG2 cells decreased visfatin-induced proliferation. ERK inhibitor alone or in combination with PI3K inhibitors effectively suppressed MMP-9 secretion and invasion in liver cancer cells. PI3K and ERK inhibition and PI3K inhibition alone blocked visfatin's ROS production in SNU-449cells. These results corresponded with a decrease in phosphorylated Akt and ERK, β-catenin, and fatty acid synthase.
Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.
Akt and ERK inhibition differentially regulated physiological changes in liver cancer cells. Inhibition of Akt and ERK signaling pathways suppressed visfatin-induced invasion, viability, MMP-9 activation, and ROS production.
The study was conducted to assess patterns of prescribed drug therapy and clinical predictors of need for therapy escalation in outpatients with diabetes mellitus (DM).
This was a prospective cohort study, conducted at an apex tertiary care teaching hospital in central India for a period of 18months. The demographic, clinical, and treatment details on the baseline and follow up visits were collected from the patients' prescription charts. Glycemic control, adherence, pill burdens along with pattern of antidiabetic therapy escalation, and deescalations were analyzed.
A total of 1,711 prescriptions of 925 patients of diabetes with a mean age of 53.81±10.42years and duration of disease of 9.15±6.3years were analyzed. Approximately half of the patients (n=450) came for≥1 follow up visits. Hypertension (59.35%) was the most common comorbidity followed by dyslipidemia and hypothyroidism. The mean total daily drugs and pills per prescription were 4.03±1.71 and 4.17±1.38, respectively. Metformin (30.42%) followd poor medication adherence may be the predictors of therapy escalation independent of glycemic control and such patients should be more closely monitored.
Disease and therapy patterns are reflective of diabetes care as expected at a tertiary care center. Higher BMI, age, pill burden, duration of diabetes, presence of comorbidities, and poor medication adherence may be the predictors of therapy escalation independent of glycemic control and such patients should be more closely monitored.
We investigated the associations between health-related quality of life (HRQoL) and health, pain and lifestyle factors, as well as motivation for lifestyle changes, in adults living with chronic pain referred to a Danish pain centre.
A total of 144 outpatients completed a questionnaire on HRQoL (EQ-5D-5L), health, pain, lifestyle factors (Body Mass Index [BMI], physical activity, smoking, alcohol, physical fitness, eating, sleep and stress) and motivation for lifestyle changes. We used multiple linear regression analyses to assess associations between HRQoL and the independent variables.
The participants (age mean 50years, 81% females) had≥2 body pain sites (93%), BMI≥25 (64%), sedentary lifestyle (43%) and multiple (n≥2) elevated metabolic risk factors (58%). Navitoclax molecular weight Most considered lifestyle important for HRQoL (72%) and expressed moderate to very high motivation for changing lifestyle (92%). Poorer HRQoL in the study population was significantly associated with higher pain intensity in the most painful body lthy eating, are needed to estimate the effect of a lifestyle-oriented approach on health and quality of life in people living with chronic pain. The results of this study will inform the research project reg. SJ-703, the Danish the Research Ethics Committee for Region Zealand, Denmark.
Hypothyroidism is the most common disorder arising from hormone deficiency. It frequently affects women than men. The prevalence of overall hypothyroidism has been reported to be 4.8-11%. Levothyroxine is the treatment of choice for all types of hypothyroidism. The purpose of this pilot study was to evaluate the efficacy and safety of Barg-e-Sahajna (Leaves of
Lam.) among diagnosed patients of primary hypothyroidism.
This study was an open observational study. A total of 22 patients were screened, out of which 10 were excluded (did not meet inclusion criteria) and 2 refused to consent to be part of the study, rest 10 participants were enrolled after obtaining written informed consent finally 8 subjects completed the study and 2 are dropout in last follow up. The drug was given in the form of decoction at the dose of 5g fresh leaves twice a day after meal for 45days.
The study effects on objective parameter thyroid stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were found extremesafety parameters (serum-glutamic-oxaloacetic-transaminase [SGOT], serum glutamic-pyruvic transaminase [SGPT], blood urea, and serum creatinine) was observed. Therefore, it may be concluded that the Barg-e-Sahajna is preliminarily safe and effective in the management of primary hypothyroidism.Introduction To evaluate the effect of therapeutic plasma exchange(TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome(aHUS). Additionally, to examine the reliability of discontinuation of eculizumab treatment.Methods This was an observational and retrospective study of 18 patients diagnosed with aHUS.Results The median age of the study population was 30(22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient in the died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3(66%) patients for TPE and 5 of 9(56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS, developed disease relapse after Eculizumab discontinuation.Conclusion Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.
Pre-analytical plasma glucose (PG) sampling methodology may significantly affect gestational diabetes mellitus (GDM) incidence, but no studies directly examined the impact on perinatal outcomes. We compared the effect on oral glucose tolerance test (OGTT) results of using for blood sampling the traditional sodium fluoride (NaF) tubes, batched at controlled temperature, and the more effective citrate-buffered tubes, in terms of GDM diagnosis and related outcomes.
We evaluated 578 pregnant women performing OGTT between 24- and 28-weeks' gestation. Paired NaF and citrate blood samples were drawn and analyzed for PG. GDM diagnosis was made by applying the 'one-step' American Diabetes Association strategy. Data on perinatal outcomes were collected in a subset of 330 women who delivered in our hospital network.
Using the standard NaF approach, 69 (11.9%) GDM women were detected. Using citrate PG values, 90 women were additionally identified as GDM, increasing the GDM prevalence to 27.5%. Perinatal outcomes were analyzed according to the different diagnostic allocation (NaF-diagnosed GDM, additional citrate-diagnosed GDM, and no GDM). NaF-diagnosed GDM showed a higher incidence of large for gestational age (LGA) (p=0.034), and of cesarean and preterm delivery (p<0.01) vs. no GDM. The only outcome remaining more frequent in the additional citrate diagnosed GDM when compared with no GDM group was LGA (17.2 vs. 6.8%, p=0.025).
If a health care system plans to use citrate tubes for GDM diagnosis, considerations about clinical implications are mandatory by balancing higher sensitivity in detecting a poor glycemic control with effects on outcomes to avoid "overdiagnosis".
If a health care system plans to use citrate tubes for GDM diagnosis, considerations about clinical implications are mandatory by balancing higher sensitivity in detecting a poor glycemic control with effects on outcomes to avoid "overdiagnosis".Mycotoxins are fungal metabolites that can cause various diseases in humans and animals. The adverse health effects of mycotoxins such as liver failure, immune deficiency, and cancer are well-described. However, growing evidence suggests an additional link between these fungal metabolites and neurodegenerative diseases. Despite the wealth of these initial reports, reliable conclusions are still constrained by limited access to human patients and availability of suitable cell or animal model systems. This review summarizes knowledge on mycotoxins associated with neurodegenerative diseases and the assumed underlying pathophysiological mechanisms. The limitations of the common in vivo and in vitro experiments to identify the role of mycotoxins in neurotoxicity and thereby in neurodegenerative diseases are elucidated and possible future perspectives to further evolve this research field are presented.Statins inhibit β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase, an enzyme involved in cholesterol synthesis, and are widely used for primary and secondary prevention of cardiovascular events. They are generally well tolerated but may cause muscle symptoms ranging from myalgias, myopathy, myositis to rhabdomyolysis. More recently, studies have reported autoimmune necrotizing myopathy associated with statin use, characterized by progressive symmetric weakness even after discontinuation of statins, often warranting immunosuppressive treatment. We describe the spectrum of statin associated muscle adverse effects for primary care physician including the clinical presentation, etiology, diagnostic workup, and appropriate management.
The Summer Program for Undergraduate Research in Addiction (SPURA) at the University of South Dakota provides research opportunities to better understand substance use and related mental health disorders. The program was initiated in 2014 from funding from the National Institute on Drug Abuse with a mission to provide high-quality mentorship and research experiences for undergraduate students, including those underrepresented in science, technology, engineering, and math.
Students from the University of South Dakota were recruited to participate in this program. Survey responses and demographic information were collected from the students.
During the first five years, 37 students completed the program. Many of these students were underrepresented in science. Of the students that had completed their undergraduate degree at the time of the last survey, most students either continued their education in a health professional or graduate program, or were employed in a career related to mental health or substance use.
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