Nonmalignant Features Associated with Inherited Colorectal Cancer Syndromes-Clues for Diagnosis

Simple Summary: Familiarity with nonmalignant features and comorbidities of cancer predisposition syndromes may raise awareness and assist clinicians in the diagnosis and interpretation of molecular test results. Genetic predisposition to colorectal cancer (CRC) should be suspected mainly in young patients, in patients with significant family histories, multiple polyps, mismatch repair-deficient tumors, and in association with malignant or nonmalignant comorbidities. The aim of this review is to describe the main nonmalignant comorbidities associated with selected CRC predisposition syndromes that may serve as valuable diagnostic clues for clinicians and genetic professionals.& nbsp;Genetic diagnosis of affected individuals and predictive testing of their at-risk relatives, combined with intensive cancer surveillance, has an enormous cancer-preventive potential in these families. A lack of awareness may be part of the reason why the underlying germline cause remains unexplained in a large proportion of patients with CRC. Various extracolonic features, mainly dermatologic, ophthalmic, dental, endocrine, vascular, and reproductive manifestations occur in many of the cancer predisposition syndromes associated with CRC and polyposis. Some are mediated via the WNT, TGF-beta, or mTOR pathways. However the pathogenesis of most features is still obscure. Here we review the extracolonic features of the main syndromes, the existing information regarding their prevalence, and the pathways involved in their pathogenesis. This knowledge could be useful for care managers from different professional disciplines, and used to raise awareness, enable diagnosis, and assist in the process of genetic testing and interpretation

Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety

<p>Background: Melatonin is extensively used in the USA in a non-regulated manner for sleep disorders. Prolonged release melatonin (PRM) is licensed in Europe and other countries for the short term treatment of primary insomnia in patients aged 55 years and over. However, a clear definition of the target patient population and well-controlled studies of long-term efficacy and safety are lacking. It is known that melatonin production declines with age. Some young insomnia patients also may have low melatonin levels. The study investigated whether older age or low melatonin excretion is a better predictor of response to PRM, whether the efficacy observed in short-term studies is sustained during continued treatment and the long term safety of such treatment.</p> <p>Methods: Adult outpatients (791, aged 18-80 years) with primary insomnia, were treated with placebo (2 weeks) and then randomized, double-blind to 3 weeks with PRM or placebo nightly. PRM patients continued whereas placebo completers were re-randomized 1:1 to PRM or placebo for 26 weeks with 2 weeks of single-blind placebo run-out. Main outcome measures were sleep latency derived from a sleep diary, Pittsburgh Sleep Quality Index (PSQI), Quality of Life (World Health Organzaton-5) Clinical Global Impression of Improvement (CGI-I) and adverse effects and vital signs recorded at each visit.</p> <p>Results: On the primary efficacy variable, sleep latency, the effects of PRM (3 weeks) in patients with low endogenous melatonin (6-sulphatoxymelatonin [6-SMT] ≤8 μg/night) regardless of age did not differ from the placebo, whereas PRM significantly reduced sleep latency compared to the placebo in elderly patients regardless of melatonin levels (-19.1 versus -1.7 min; P = 0.002). The effects on sleep latency and additional sleep and daytime parameters that improved with PRM were maintained or enhanced over the 6-month period with no signs of tolerance. Most adverse events were mild in severity with no clinically relevant differences between PRM and placebo for any safety outcome.</p> <p>Conclusions: The results demonstrate short- and long-term efficacy and safety of PRM in elderly insomnia patients. Low melatonin production regardless of age is not useful in predicting responses to melatonin therapy in insomnia. The age cut-off for response warrants further investigation.</p&gt

Diagnosis and treatment of muscle pain according to Tipaldos (literature review)

This review contents the information on the theory of the structure and mechanisms of damage to the body fascial system, proposed by American osteopath S. Tipaldos and named by him the Fascial Distortion Model (FDM), as well as on the original method of diagnosis and treatment of muscle pain syndromes associated with fascial damage (distortion). The author describes classifications of connective tissue and fascial structures, created by S.  Tipaldos, which are based on anatomical and functional features that determine the role of each type of fascia in compensating for various types of external influences. The conditions, mechanisms of formation and characteristics of six types of fascial lesions identified by S. Tipaldos are considered in detail: triggerband, herniated triggerpoint, continuum distortion, folding distortion, cylinder distortion, tectonic fixation. All elements of the fascial distortions diagnosis are discussed in detail, including the specification of complaints (characteristics of pain syndrome), anamnesis (history of the pain onset and its development) and an objective examination (the actual diagnostic techniques). At the same time, the special role of the patient’s description of his own painful sensations with the help of specific gestures and movements, called «body language», is emphasized. The principles and some methods of therapeutic effects used in FDM-therapy, indications and contraindications for the use of the considered manual techniques, possible side reactions that may occur during manipulation or after a session of FDMtherapy are presented. Particular attention is paid to  the evidence base of FDM therapy effectiveness in comparison with traditional methods of myofascial pain syndromes manual treatment: the results of controlled studies by foreign authors, confirming the new technique effectiveness in the treatment of certain muscle algic phenomena types, are considered

Comparison of millimeter-wave cloud radar measurements for the Fall 1997 Cloud IOP

One of the primary objectives of the Fall 1997 IOP was to intercompare Ka-band (350Hz) and W-band (95GHz) cloud radar observations and verify system calibrations. During September 1997, several cloud radars were deployed at the Southern Great Plains (SOP) Cloud and Radiation Testbed (CART) site, including the full time operation 35 GHz CART Millimeter-wave Cloud Radar (MMCR), the University of Massachusetts (UMass) single antenna 33GHz/95 GHz Cloud Profiling Radar System (CPRS), the 95 GHz Wyoming Cloud Radar (WCR) flown on the University of Wyoming King Air, the University of Utah 95 GHz radar and the dual-antenna Pennsylvania State University 94 GHz radar. In this paper the authors discuss several issues relevant to comparison of ground-based radars, including the detection and filtering of insect returns. Preliminary comparisons of ground-based Ka-band radar reflectivity data and comparisons with airborne radar reflectivity measurements are also presented

Effect of multidisciplinary rehabilitation on sleep outcomes in individuals with preclinical Huntington disease: An exploratory study

Dear Editor Sleep disturbances are an early feature of Huntington disease (HD), which worsen as the disease progresses. Studies have documented increased sleep fragmentation, decreased rapid eye-movement (REM) sleep, reduced sleep efficiency, insomnia and an increase in periodic leg movements (PLMs) in individuals with HD [1], [2]. Disturbances in sleep are thought to exacerbate cognitive impairments and may hasten subcortical neurodegeneration [3], [4]. Hence, management of sleep disturbances in individuals with HD is imperative

The effects of melatonin versus placebo on delirium in hip fracture patients: study protocol of a randomised, placebo-controlled, double blind trial

<p>Abstract</p> <p>Background</p> <p>With an ageing population, older persons become a larger part of the hospital population. The incidence of delirium is high in this group, and experiencing delirium has major short- and long-term sequelae, which makes prevention crucial. During delirium, a disruption of the sleep-wake cycle is frequently observed. Melatonin plays an important role in the regulation of the sleep-wake cycle, so this raised the hypothesis that alterations in the metabolism of melatonin might play an important role in the development of delirium. The aim of this article is to describe the design of a randomised, placebo controlled double-blind trial that is currently in progress and that investigates the effects of melatonin versus placebo on delirium in older, postoperative hip fracture patients.</p> <p>Methods/Design</p> <p>Acutely hospitalised patients aged 65 years or older admitted for surgical repair of hip fracture are randomised (n = 452) into a treatment or placebo group. Prophylactic treatment consists of orally administered melatonin (3 mg) at 21:00 h on five consecutive days. The primary outcome is the occurrence of delirium, to be diagnosed according to the Confusion Assessment Method, within eight days after start of the study medication. Secondary outcomes are delirium severity, measured by the Delirium Rating Scale; duration of delirium; differences in subtypes of delirium; differences in total length of hospital stay; total dose of antipsychotics and/or benzodiazepine use during delirium; and in-hospital complications. In the twelve-month follow up visit, cognitive function is measured by a Mini-Mental state examination and the Informant Questionnaire on Cognitive Decline in the Elderly. Functional status is assessed with the Katz ADL index score (patient and family version) and grip strength measurement. The outcomes of these assessments are compared to the outcomes that were obtained during admission.</p> <p>Discussion</p> <p>The proposed study will contribute to our knowledge because studies on the prophylactic treatment of delirium with long term follow up remain scarce. The results may lead to a prophylactic treatment for frail older persons at high risk for delirium that is safe, effective, and easily implementable in daily practice.</p> <p>Trial registration</p> <p>Dutch Clinical Trial Registry: <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1576">NTR1576</a></p