European guideline for the diagnosis and treatment of insomnia

This European guideline for the diagnosis and treatment of insomnia was developed by a task force of the European Sleep Research Society, with the aim of providing clinical recommendations for the management of adult patients with insomnia. The guideline is based on a systematic review of relevant meta-analyses published till June 2016. The target audience for this guideline includes all clinicians involved in the management of insomnia, and the target patient population includes adults with chronic insomnia disorder. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) system was used to grade the evidence and guide recommendations. The diagnostic procedure for insomnia, and its co-morbidities, should include a clinical interview consisting of a sleep history (sleep habits, sleep environment, work schedules, circadian factors), the use of sleep questionnaires and sleep diaries, questions about somatic and mental health, a physical examination and additional measures if indicated (i.e. blood tests, electrocardiogram, electroencephalogram; strong recommendation, moderate- to high-quality evidence). Polysomnography can be used to evaluate other sleep disorders if suspected (i.e. periodic limb movement disorder, sleep-related breathing disorders), in treatment-resistant insomnia, for professional at-risk populations and when substantial sleep state misperception is suspected (strong recommendation, high-quality evidence). Cognitive behavioural therapy for insomnia is recommended as the first-line treatment for chronic insomnia in adults of any age (strong recommendation, high-quality evidence). A pharmacological intervention can be offered if cognitive behavioural therapy for insomnia is not sufficiently effective or not available. Benzodiazepines, benzodiazepine receptor agonists and some antidepressants are effective in the short-term treatment of insomnia (≤4 weeks; weak recommendation, moderate-quality evidence). Antihistamines, antipsychotics, melatonin and phytotherapeutics are not recommended for insomnia treatment (strong to weak recommendations, low- to very-low-quality evidence). Light therapy and exercise need to be further evaluated to judge their usefulness in the treatment of insomnia (weak recommendation, low-quality evidence). Complementary and alternative treatments (e.g. homeopathy, acupuncture) are not recommended for insomnia treatment (weak recommendation, very-low-quality evidence).

Cognitive impairment in early-stage non-demented Parkinson's disease patients.

OBJECTIVES: In Parkinson's disease (PD), Parkinson's disease dementia (PDD) and Parkinson's disease-mild cognitive impairment (PD-MCI) are common. PD-MCI is a risk factor for developing PDD. Knowledge of cognition in early-stages PD is essential in understanding and predicting the dementia process. MATERIALS AND METHODS: We describe the cognitive profile in early-stage PD patients with no prior clinical suspicion of cognitive impairment, depression or psychiatric disturbances, and investigate possible features distinguishing patients with cognitive deficits, defining a PD-MCI risk-profile. Single Photon Emission Computerized Tomography (SPECT) DaT-scan and neurological examination confirmed the diagnosis. Mini-mental state examination-, Addenbrooke's Cognitive Examination, Unified Parkinson's Disease Rating Scale scoring, Hoehn &Yahr/Activity of Daily Living staging and a neuropsychological test battery were applied. Mild cognitive impairment patients were identified according to modified criteria by Troster necessarily omitting subjective cognitive complaints. 80 patients, mean age 61.0 years (SD 6.6), mean duration of disease 3.4 years (SD 1.2) were included. 76 patients were neuropsychologically tested. RESULTS: 26 (34%) patients fulfilled modified PD-MCI criteria, 18 (69%) of these showed episodic memory deficits, 14 (54%) executive dysfunction, 13 (50%) language/praxis deficits, 12 (46%) visuospatial/constructional deficits and 9 (35%) attention/working memory deficits. Cognitive impairment was associated with higher Unified Parkinson's Disease Rating scale (UPDRS)-, bradykinesia- and rigidity scores and more symmetric distribution of symptoms, but not tremor scores. Patients with cognitive impairment were less educated. Other demographic and clinical variables were comparable. CONCLUSIONS: 34% of early-stage PD patients without prior clinical suspicion of cognitive impairment exhibit cognitive impairment, which is associated to disease severity, especially bradykinesia, rigidity, axial symptoms and less asymmetry of motor symptoms, even at early disease stages and when cognitive symptoms are mild.

Hansenula polymorpha as a novel yeast system for the expression of heterologous genes.

The advantages of Hansenula polymorpha as a new yeast expression system are discussed in terms of the powerful and regulatable methanol oxidase promoter and the organism's ability to grow on cheap carbon sources. The development of techniques for conventional genetic analysis is described. A total of 218 mutants have been assigned to 62 complementation groups, three genes have been found to be linked forming the first linkage group in this organism. Methods for molecular transformation have been developed allowing the expression of heterologous genes. The disruptive integration and expression of the neomycin phosphotransferase is described.