A clinical tool for predicting survival in ALS.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and usually fatal neurodegenerative disease. Survival from diagnosis varies considerably. Several prognostic factors are known, including site of onset (bulbar or limb), age at symptom onset, delay from onset to diagnosis and the use of riluzole and non-invasive ventilation (NIV). Clinicians and patients would benefit from a practical way of using these factors to provide an individualised prognosis. METHODS: 575 consecutive patients with incident ALS from a population-based registry in South-East England register for ALS (SEALS) were studied. Their survival was modelled as a two-step process: the time from diagnosis to respiratory muscle involvement, followed by the time from respiratory involvement to death. The effects of predictor variables were assessed separately for each time interval. FINDINGS: Younger age at symptom onset, longer delay from onset to diagnosis and riluzole use were associated with slower progression to respiratory involvement, and NIV use was associated with lower mortality after respiratory involvement, each with a clinically significant effect size. Riluzole may have a greater effect in younger patients and those with longer delay to diagnosis. A patient's survival time has a roughly 50% chance of falling between half and twice the predicted median. INTERPRETATION: A simple and clinically applicable graphical method of predicting an individual patient's survival from diagnosis is presented. The model should be validated in an independent cohort, and extended to include other important prognostic factors.

Motor Neuron Disease Register for England, Wales and Northern Ireland-an analysis of incidence in England.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) has a reported incidence of 1-2/100,000 person-years. It is estimated that there are 5000 people with ALS in the UK at any one time; however, the true figure and geographical distribution, are unknown. In this study, we describe the establishment of a population register for England, Wales, and Northern Ireland and report-estimated incidence. Methods: People with a diagnosis of ALS given by a consultant neurologist and whose postcode of residence is within England, Wales, or Northern Ireland were eligible. The catchment area was based on six data contributors that had been participating since 2016. All centres included in this analysis were in England, and therefore Wales and Northern Ireland are not included in this report. Crude age- and sex-specific incidence rates were estimated using population census records for the relevant postcodes from Office of National Statistics census data. These rates were standardized to the UK population structure using direct standardization. Results: There were 232 people in the database with a date of diagnosis between 2017 and 2018, when missing data were imputed there were an estimated 287-301 people. The denominator population of the catchment area is 7,251,845 according to 2011 UK census data. Age- and sex-adjusted incidence for complete cases was 1.61/100,000 person-years (95% confidence interval 1.58, 1.63), and for imputed datasets was 2.072/100,000 person-years (95% CI 2.072, 2.073). Discussion: We found incidence in this previously unreported area of the UK to be similar to other published estimates. As the MND Register for England, Wales, and Northern Ireland grows we will update incidence estimates and report on further analyses.

[Sexual disorders in schizophrenia--overview of research literature]. / Zaburzenia seksualne w schizofrenii--przeglad badan.

There are relatively few systematic investigations concerning sexual disorders in schizophrenia. In the paper, the most important set of symptoms of sexual disorders in schizophrenia, such as weaker libido, erection and ejaculation disturbances in men, and lubrication and orgasm disturbances in women are described. The lacking of satisfactory partner and sexual relationships is emphasized in the article. In the case of women, the most significant are the problems related to the period of pregnancy, childbirth and care giving. The overview of research literature is focused on differences between females and males in relation to sexual disorders determinants as well as clinical, mental and social effects in the course of schizophrenia.

The benefit of evolving multidisciplinary care in ALS: a diagnostic cohort survival comparison.

BACKGROUND: Care for people with amyotrophic lateral sclerosis (ALS) has altered at King's College Hospital over the last 20 years. The clinic has been a multidisciplinary, specialist, tertiary referral centre since 1995 with a large team with integrated palliative and respiratory care since 2006. We hypothesised that these changes would improve survival. METHODS: In this retrospective observational study, patients diagnosed with El Escorial definite, probable and possible ALS between 1995-1998 and 2008-2011 were followed up. The primary outcome measure was a chi-square test for the proportion of each cohort surviving. Kaplan-Meier survival analysis and Cox multivariate regression were secondary analyses. RESULTS: There was low reporting of some interventions. Five hundred and forty-seven people were included. Survival between the cohorts was significantly different (p = 0.022) with a higher proportion surviving during 2008-2011. Survival time was 21.6 (95% CI 19.2-24.0) months in the 2008-2011 cohort compared to 19.2 years (15.6-21.6) in the 1995-1998 cohort (log rank p = 0.018). Four hundred and ninety-three cases were included in the Cox regression. Diagnostic cohort was a significant predictor variable (HR 0.79 (0.64-0.97) p = 0.023). CONCLUSIONS: These results support the hypothesis that integrated specialist clinics with multidisciplinary input improve survival in ALS.

Procaine-induced enhancement of fluid-phase endocytosis and inhibition of exocytosis in human skin fibroblasts.

Local anaesthetics are often applied directly onto the skin, and for this reason the effect of some local anaesthetics upon morphology and cytoskeleton organisation in human skin fibroblasts was investigated. In this paper the authors report that procaine (p-aminobenzoic acid diethylamino-etyl ester hydrochloride) induced vacuolisation of cytoplasm and great enhancement of neutral red accumulation in human skin fibroblasts cultured in vitro. Procaine-induced vacuolisation of cell's cytoplasm was observed to be associated with the enhanced uptake and inhibited release of fluid taken by endocytosis. All these effects appeared fully reversible. The cell vacuolisation cannot be prevented by 3-methyadenine, brefeldine A, and cytochalasine D. On the other hand, nocodazole and caffeine prevent cytoplasm vacuolisation induced by procaine. These observations suggest that procaine-induced formation of great vacuoles is due to an impairment of membrane traffic between endosomes. The authors' results also demonstrate that neutral red uptake assay, if used as a cell viability test, must be interpreted with great caution.

Exercising during learning improves vocabulary acquisition: behavioral and ERP evidence.

Numerous studies have provided evidence that physical activity promotes cortical plasticity in the adult brain and in turn facilitates learning. However, until now, the effect of simultaneous physical activity (e.g. bicycling) on learning performance has not been investigated systematically. The current study aims at clarifying whether simultaneous motor activity influences verbal learning compared to learning in a physically passive situation. Therefore the learning behavior of 12 healthy subjects (4 male, 19-33 years) was monitored over a period of 3 weeks. During that time, behavioral and electrophysiological responses to memorized materials were measured. We found a larger N400 effect and better performance in vocabulary tests when subjects were physically active during the encoding phase. Thus, our data indicate that simultaneous physical activity during vocabulary learning facilitates memorization of new items.