The Klotho protein deficiency is known to participate in premature aging. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity. Due to many reasons, the insulin/insulin-like growth factor-1 (IGF-1) has been considered as a key pathway in aging research. The Klotho gene is closely related to this pathway. The Klotho gene encodes a transmembrane protein that after cleavage is also found as a secreted protein. Importantly, its overexpression suppresses insulin/IGF-1 signaling and thus extends the lifespan. In addition, Klotho participates in the regulation of several other intracellular signaling pathways, including regulation of FGF23 signaling, cAMP, PKC, transforming growth factor-β (TGF-β), p53/p21, and Wnt signaling. The aim of this review is to summarize current literature that shows the involvement of Klotho in the regulation of several intracellular pathways. The results of our review clearly indicate that Klotho participates in several intracellular signaling pathways, and by regulating them, Klotho is involved in aging and longevity.
Background: There are few epidemiological studies on neurological disorders in Albania. Methods: A door-to-door survey was undertaken in two geographical areas (Tirana and Saranda) with different socioeconomic backgrounds. Two random samples of the local population underwent a structured interview to ascertain headache, epilepsy, dementia, parkinsonism, multiple sclerosis, polyneuropathy, stroke and cerebral palsy. Each diagnosis was made using standard criteria for epidemiological studies and was confirmed by history, neurological examination and, where available, the review of personal medical records. Lifetime prevalence ratios with 95% confidence intervals were calculated. Results: Of the 9,869 individuals screened (Tirana 4,953; Saranda 4,916), 4,867 were males aged 1–91 years (median 39 years) and 5,002 were females aged 1–96 years (median 37 years). Crude prevalence ratios (per 1,000) were: headache 241.9 (233.5–250.3), polyneuropathy 32.5 (29.0–36.0), epilepsy 14.2 (11.7–16.3), stroke 12.4 (10.2–14.6), dementia 9.6 (7.7–11.5), parkinsonism 8.0 (6.2–9.8), cerebral palsy 4.8 (3.4–6.2), and multiple sclerosis 0.3 (0.0–0.6). Prevalence varied with age and gender, with differences across diseases. Except for polyneuropathy (Tirana 39.8; Saranda 25.2), ratios were not different in the two study areas. Conclusions: The prevalence of selected neurological disorders in Albania is higher than in other countries. Differences may be explained by study design, population structure and/or genetic and environmental factors.
BackgroundThe Albanian medical system and Albanian health legislation have adopted a paternalistic position with regard to individual decision making. This reflects the practices of a not-so-remote past when state-run facilities and a totalitarian philosophy of medical care were politically imposed. Because of this history, advance directives concerning treatment refusal and do-not-resuscitate decisions are still extremely uncommon in Albania. Medical teams cannot abstain from intervening even when the patient explicitly and repeatedly solicits therapeutic abstinence. The Albanian law on health care has no provisions regarding limits or withdrawal of treatment. This restricts the individual's healthcare choices.DiscussionThe question of 'medically futile' interventions and pointless life-prolonging treatment has been discussed by several authors. Dutch physicians call such interventions 'medisch zinloos' (senseless), and the Netherlands, as one of the first states to legislate on end-of-life situations, actually regulates such issues through appropriate laws. In contrast, leaving an 'advance directive' is not a viable option for Albanian ailing individuals of advanced age. Verbal requests are provided during periods of mental competence, but unfortunately such instructions are rarely taken seriously, and none of them has ever been upheld in a legal or other official forum.SummaryEnd-of-life decisions, treatment refusal and do-not-resuscitate policies are hazardous options in Albania, from the legal point of view. Complying with them involves significant risk on the part of the physician. Culturally, the application of such instructions is influenced from a mixture of religious beliefs, death coping-behaviors and an immense confusion concerning the role of proxies as decision-makers. Nevertheless, Albanian tradition is familiar with the notion of 'amanet', a sort of living will that mainly deals the property and inheritance issues. Such living wills, verbally transmitted, may in certain cases include advance directives regarding end-of-life decisions of the patient including refusal or termination of futile medical treatments. Since these living wills are never formally and legally validated, their application is impossible and treatment refusal remains still non practicable. Tricks to avoid institutional treatment under desperate conditions are used, aiming to provide legal coverage for medical teams and relatives that in extreme situations comply with the advice of withholding senseless treatment.
The main objective is to assess the benefits and harms of rituximab compared to placebo or another DMT for people with multiple sclerosis. Specific comparisons include:• rituximab compared with placebo or other DMTs as first choice treatment for relapsing forms of MS;• rituximab when switching from another DMT compared with placebo or other DMTs for relapsing forms of MS;• rituximab compared with placebo or other DMTs as first choice treatment for progressive forms of MS; and • rituximab when switching from another DMT compared with placebo or other DMTs for progressive forms of MS.
BACKGROUND:Lightning injuries may produce a variety of medical conditions, and specific neurological complications have been identified, with the character of immediate aftershock effects or even long-term consequences.AIM:The authors describe the incidental finding following a routine unenhanced brain MRI performed to a young female patient, suffering from a headache.CASE REPORT:Diffuse white matter changes with the character of a leukoencephalopathy were seen, which strictly interested only the right cerebral hemisphere. The parents referred that she suffered from an indoor lightning strike at age of seven months, although she survived with almost no external burns or signs, and recovered uneventfully at that time. A discussion over the effects of electrocution and lightning strike on the human body in general, and over the nervous system, is made. Particular attention must be shown when making the differential diagnosis of leukoencephalopathies with a strictly one-hemisphere extension since several other conditions might resemble each other under the radiological aspect, here including brain viral infections, genetic disorders, and so on.CONCLUSION:The particularity of the long-term aftershock effects of the lightning strike on the central nervous system raise again the necessity of collecting data and duly reporting every electrical accident, lightning events included.
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