Johansenslater8106

Telomerase reverse transcriptase (TERT) is the catalytic subunit of telomerase, an enzyme that elongates telomeres at the ends of chromosomes during DNA replication. Recently, it was shown that TERT has additional roles in cell survival, mitochondrial function, DNA repair, and Wnt signaling, all of which are unrelated to telomeres. Here, we demonstrate that TERT is enriched in Purkinje neurons, but not in the granule cells of the adult mouse cerebellum. TERT immunoreactivity in Purkinje neurons is present in the nucleus, mitochondria, and cytoplasm. Furthermore, TERT co-localizes with mitochondrial markers, and immunoblot analysis of protein extracts from isolated mitochondria and synaptosomes confirmed TERT localization in mitochondria. TERT expression in Purkinje neurons increased significantly in response to two stressors a sub-lethal dose of X-ray radiation and exposure to a high glutamate concentration. While X-ray radiation increased TERT levels in the nucleus, glutamate exposure elevated TERT levels in mitochondria. Our findings suggest that in mature Purkinje neurons, TERT is present both in the nucleus and in mitochondria, where it may participate in adaptive responses of the neurons to excitotoxic and radiation stress.

Modafinil is a wake-promoting drug with FDA approval for the treatment of excessive daytime sleepiness that has been prescribed for ADHD and recently assessed as a potential treatment for psychostimulant dependence. Previous research indicates that modafinil modestly increases locomotor activity and produces similar discriminative stimulus effects to psychostimulants in rodents, although the subjective effects of modafinil are reportedly distinct from those of cocaine or amphetamine in humans with a history of psychostimulant abuse.

The current study employed drug discrimination procedures in rats to examine the pharmacological actions contributing to modafinil's discriminative stimulus functions.

Eight male Sprague-Dawley rats were trained to discriminate intragastric administration of 256 mg/kg modafinil from vehicle (5% arabic gum) under a FR 20 schedule of food reinforcement. Substitution tests were conducted with various dopaminergic agents (d-amphetamine, cocaine, PNU-91356A, GBR 12909, methylphencontribution of other neurotransmitter systems to these effects should be continued. The findings are discussed in light of clinical research efforts with modafinil as a treatment for psychostimulant dependence.Embolectomy with stentriever devices is the newest treatment for acute stroke. Since 1995, treatment of acute stroke has been limited to a 4.5-h window with the use of intravenous tissue plasminogen activator (tPA). Five articles have been published in 2015 with the results supporting the paired treatment of tPA and embolectomy. This has also expanded the treatment window to greater than 4.5 h and produced evidence which will guide selection of patients that will benefit most from this therapy. This article will compare and contrast this most recent evidence.To maximize the risk benefit ratio of blood pressure control in people with chronic kidney diseases (CKD), a number of guidelines provide recommendations on optimal blood pressure (BP) targets in CKD. This review examines these guidelines, their supporting evidence base, and generalizability and limitations of current standards of care. this website Over the years, the BP targets are liberalized. They now focus on the usual BP target of 300 mg/g creatinine, low-quality evidence suggests targeting BP to less then 130/90 mmHg. Individualization of BP lowering is a key based on comorbid conditions, response to treatment, and level of kidney function. Consideration of out of clinic BP monitoring either implemented by home BP recordings or ambulatory BP measurements may enhance BP control.Amyloidosis is a disease in which proteins misfold, aggregate into fibrils, and deposit extracellularly disrupting organ architecture and function. There are two main types which affect the heart light chain (AL) amyloidosis and transthyretin cardiac amyloidosis (ATTR). There is a misconception that cardiac amyloidosis has no effective treatment options. However, over the past decade, there has been extensive research and drug development. Outcomes are improving in AL amyloidosis with evolving chemotherapeutic regimens and novel monoclonal antibodies. In ATTR, therapies that decrease protein production, prevent dissociation, and promote clearance have the potential to slow or even halt a disease which is uniformly fatal. Selected patients may be candidates for heart and/or stem cell transplant and should be promptly referred to an experienced amyloid program. Herein, we discuss the emerging advances for the treatment of cardiac amyloidosis.

The chemokine CXCL12 and its receptor CXCR4 can affect tumor growth, recurrence, and metastasis. We tested the hypothesis that the CXCL12 and CXCR4 expression influences the prognosis of patients with inoperable head and neck cancer treated with definite radiotherapy or chemoradiotherapy.

Formalin-fixed paraffin-embedded pretreatment tumor tissue from 233 patients with known HPV/p16(INK4A) status was analyzed. CXCL12 and CXCR4 expressions were correlated with pretreatment parameters and survival data by univariate and multivariate Cox regression.

CXCL12 was expressed in 43.3 % and CXCR4 in 66.1 % of the samples and both were correlated with HPV/p16(INK4A) positivity. A high CXCL12 expression was associated with increased overall survival (p = 0.036), while a high CXCR4 expression was associated with decreased metastasis-free survival (p = 0.034).

A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis.

A high CXCR4 expression could be regarded as a negative prognostic factor in head and neck cancer because it may foster metastatic spread. This may recommend CXCR4 as therapeutic target for combating head and neck cancer metastasis.

Genome-wide-association studies have identified numerous body mass index (BMI)-associated variants, but it is unclear how these relate to weight gain in adults at different ages.

We examined the association of a genetic risk score (GRS), consisting of 31 BMI-associated variants, with an annual weight change (AWC) and a substantial weight gain (SWG) of 10% by comparing self-reported weight at 20 years (y) with baseline weight (mean 58 y; s.d. 8 y) in 21407 participants from the Malmö Diet and Cancer Study (MDCS), and comparing baseline weight to weight at follow-up (mean 73 y; s.d. 6 y) among 2673 participants. Association between GRS and AWG and SWG was replicated in 4327 GLACIER (Gene x Lifestyle interactions And Complex traits Involved in Elevated disease Risk) participants (mean 45 y; s.d. 7 y) with 10 y follow-up. Cohort-specific results were pooled by fixed-effect meta-analyses.

In MDCS, the GRS was associated with increased AWC (β 0.003; s.e 0.01; P 7 × 10(-8)) and increased odds for SWG (odds ratdence for a paradoxical inversed relationship between a high number of BMI-associated risk-alleles and less weight gain during and after middle-age, in contrast to the expected increased weight gain seen in younger age.Within the past 15 years, the endocannabinoid system (ECS) has emerged as a lipid signaling system critically involved in the regulation of energy balance, as it exerts a regulatory control on every aspect related to the search, the intake, the metabolism and the storage of calories. An overactive endocannabinoid cannabinoid type 1 (CB1) receptor signaling promotes the development of obesity, insulin resistance and dyslipidemia, representing a valuable pharmacotherapeutic target for obesity and metabolic disorders. However, because of the psychiatric side effects, the first generation of brain-penetrant CB1 receptor blockers developed as antiobesity treatment were removed from the European market in late 2008. Since then, recent studies have identified new mechanisms of action of the ECS in energy balance and metabolism, as well as novel ways of targeting the system that may be efficacious for the treatment of obesity and metabolic disorders. These aspects will be especially highlighted in this review.

Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans.

Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to either gain 5% of body weight by 8 weeks of overfeeding (n=34) or maintain weight (n=10). Modest weight gain of 3.8±1.2 kg resulted in increased adiponectin level (P=0.03), whereas weight maintenance resulted in no changes in adiponectin. Further, changes in adiponectin correlated positively with changes in leptin (P=0.0085). In-vitro experiments using differentiated human white preadipocytes showed that leptin increased adiponectin mRNA and protein expression, whereas a leptin antagonist had opposite effects. To undersn signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

Modest weight gain in healthy individuals is associated with increases in adiponectin levels, which correlate positively with changes in leptin. In vitro, leptin induces adiponectin expression, which is attenuated by increased caveolin-1 expression. In addition, the adipose tissue from obese subjects shows increased caveolin-1 expression and impaired leptin signaling. This leptin signal impairment may prevent concordant increases in adiponectin levels in obese subjects despite their high levels of leptin. Therefore, impaired leptin signaling may contribute to low adiponectin expression in obesity and may provide a target for increasing adiponectin expression, hence improving insulin sensitivity and cardio-metabolic profile in obesity.

To assess changes in perceptions of confidence and preparedness for practice of preregistration nursing students before and after the introduction of a capstone subject, and factors associated with perceptions of preparedness.

Preregistration nursing student 'readiness' or 'preparedness' for practice has been highlighted in the literature in recent years, along with employer concerns that university graduate nurses are not work ready. Few studies have examined Australian preregistration nursing students' perceptions of preparedness for clinical practice following their final clinical placement or assessed whether preregistration student nurses' perceptions of preparedness change as the result of undertaking a capstone subject.

A capstone subject was introduced at a regional northern Australian university in 2013. Perceptions of preparedness were assessed in two different cohorts of final year nursing students; one of which undertook a capstone subject.

Two separate cohorts of third year nursing students were surveyed regarding their perceptions of preparedness for practice at the conclusion of their final 240hour clinical placement.