Annals of medicine
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Review
The molecular basis of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum.
There is increasing evidence that frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) represent a continuum of neurodegenerative diseases. FTLD is complicated by ALS in a significant proportion of patients, and neuropsychological studies have demonstrated frontotemporal dysfunction in up to 50% of ALS patients. More recently, advances in neuropathology and molecular genetics have started to disclose the biological basis for the observed clinical concurrence. ⋯ Mutations in the TARDBP, FUS, and VCP genes had previously been associated with different phenotypes of the FTLD-ALS spectrum, although in these cases one end of the spectrum predominates. Whilst on the one hand providing evidence for overlap, these discoveries have also highlighted that FTLD and ALS are etiologically diverse. In this review, we review the recent advances that support the existence of an FTLD-ALS spectrum, with particular emphasis on the molecular genetic aspect.
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Review Meta Analysis Comparative Study
Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis.
This review compared the effect of high-dose nicotine replacement therapy (NRT) and combinations of NRT for increasing smoking abstinence rates compared to standard-dose NRT patch, varenicline, and bupropion on smoking abstinence. ⋯ All pharmacologic treatments were significantly more effective than inert controls. Varenicline was the only treatment demonstrating effects over other options. These results should be considered in the development of clinical practice guidelines.
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The (pro)renin receptor (PRR) was initially believed to be a contributor to the pathogenesis of cardiovascular diseases via the amplification of renin- or prorenin-induced angiotensin (Ang) formation. However, a recent paradigm shift suggests a new role for PRR, separate from the renin-angiotensin system (RAS), in contributing to cellular homeostasis. Specifically, PRR is thought to be essential for vacuolar H(+) -ATPase (V-ATPase) activity and acts as an adaptor between the V-ATPase and the Wnt signalling pathway. ⋯ Additionally, cleavage by furin at a single site within full-length PRR results in the production of a soluble form of the receptor, which is detectable in plasma. Soluble PRR is hypothesized to bind to specific ligands and receptors and mediate signal transduction pathways. Understanding the physiological function of full-length and soluble PRR will be important for establishing its role in pathology.
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Dietary salt intake is the most important factor contributing to hypertension, but the salt susceptibility of blood pressure (BP) is different in individual subjects. Although the pathogenesis of salt-sensitive hypertension is heterogeneous, it is mainly attributable to an impaired renal capacity to excrete sodium (Na(+) ). We recently identified two novel mechanisms that impair renal Na(+) -excreting function and result in an increase in BP. ⋯ Second, renospecific sympathoactivation may cause an increase in BP under conditions of salt excess. Renal beta2 adrenoceptor stimulation in the kidney leads to decreased transcription of the gene encoding WNK4, a negative regulator of Na(+) reabsorption through Na(+) -Cl (-) cotransporter in the distal convoluted tubules, resulting in salt-dependent hypertension. Abnormalities identified in these two pathways of Na(+) reabsorption in the distal nephron may present therapeutic targets for the treatment of salt-sensitive hypertension.
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Review Meta Analysis
A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials.
Current treatment of hyperglycemia in type 2 diabetes (T2DM) is often ineffective and has unwanted effects. Therefore, novel antidiabetic drugs are under development. ⋯ Pending confirmation from larger RCTs, this analysis shows SGLT2 inhibitors are safe and effective for hyperglycemia treatment in T2DM.