Cervical dystonia incidence and diagnostic delay in a multiethnic population.

BackgroundCurrent cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is poorly characterized.ObjectivesTo determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.MethodsWe identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.ResultsCD incidence was 1.18/100,000 person-years (95% confidence interval [CI], 0.35-2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person-years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio [OR] 68.1; 95% CI, 28.2-164.5), cervical disc disease (OR 3.83; 95% CI, 2.8-5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99-3.62), anxiety (OR 2.24; 95% CI, 1.63-3.11) and depression (OR 1.94; 95% CI, 1.4-2.68).ConclusionsCD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society

Valores de referencia para leptina, cortisol, insulina y glucosa entre los adolescentes europeos y su asociación con adiposidad: Estudio Helena

Background and Objective: Adequate concentrations of leptin, cortisol, and insulin are important for a suitable metabolism and development during adolescence. These hormones jointly with glucose play a major role in fat metabolism and development of childhood obesity. Our main objective was to quantify biomarkers as leptin, cortisol, insulin and glucose status in European adolescents to contribute to establish reference ranges. Methods: A representative sample of 927 adolescents (45% males, 14.9±1.2 years for the overall population) from ten European cities of the HELENA study was used to obtain fasting blood samples for these biomarkers. The percentile distributions were computed by sex and age and percentiles were associated with BMI classification. Results: Serum leptin concentration in adolescents varied significantly according to BMI, sex and age (all p<0.001). Cortisol presented a tendency to increase with age, both for females and males, while insulin and glucose were stable with age. Leptin and insulin were highest in obese adolescents (p<0.001), whilst cortisol and glucose did not vary with BMI. Percentiles 5, 25, 50, 75 and 95, 26.70 and 65.33 ng/ml for leptin; 5.00, 8.11, 11.14, 15.00 and 24.51 μg/dl for cortisol and 3.65, 6.15, 8.52, 11.90 and 20.53 μlU/ml for insulin. Conclusions: In adolescents, leptin, cortisol, insulin and glucose concentrations are differently affected by age, sex and BMI. Establishment of reference ranges (percentiles) of these biomarkers would be of great interest when pediatricians have to assess the trend of an adolescent to develop obesity years after.Objetivo: Concentraciones adecuadas de leptina, cortisol e insulina son importantes para un metabolismo normal durante la adolescencia, puesto que valores alterados de estas hormonas, junto con la glucosa, se asocian con el desarrollo de la obesidad infantil. Nuestro principal objetivo fue cuantificar estos marcadores en adolescentes europeos con el fin de establecer rangos de referencia. Métodos: Muestras de sangre procedentes de 927 adolescentes en ayunas (14,9 ± 1,2 años, 45% varones, estudio HELENA), fueron analizadas para cuantificar la leptina, cortisol, insulina y glucosa. Las distribuciones de percentiles se determinaron teniendo en cuenta el sexo y la edad. También se estudió la asociación entre percentiles y la clasificación del IMC. Resultados: La concentración de leptina en suero variaba significativamente con el IMC, el sexo y la edad (todos p<0,001). El cortisol presentó una tendencia a aumentar con la edad, tanto para varones como mujeres, mientras que la insulina y la glucosa eran estables con la edad. La leptina y la insulina fueron más altas en los adolescentes obesos (p <0,001), mientras que el cortisol y glucosa no variaron con el IMC. Los percentiles 5, 25, 50, 75 y 95, para los valores de hormonas fueron, respectivamente: 1.27, 4.06, 11.54, 26.70 y 65.33 ng/ml para la leptina; 5.00, 8.11, 11.14, 15.00 y 24.51 μg/dl para el cortisol y 3.65, 6.15, 8.52, 11.90 y 20.53 μlU/ml de insulina.The HELENA study has taken place with the financial support of the European Community Sixth RTD Framework Programme (Contract FOODCT- 2005-007034). This study was also supported by a grant from the Spanish Ministry of Science and Innovation AGL2007-29784-E

Biogenesis and functions of bacterial S-layers.

The outer surface of many archaea and bacteria is coated with a proteinaceous surface layer (known as an S-layer), which is formed by the self-assembly of monomeric proteins into a regularly spaced, two-dimensional array. Bacteria possess dedicated pathways for the secretion and anchoring of the S-layer to the cell wall, and some Gram-positive species have large S-layer-associated gene families. S-layers have important roles in growth and survival, and their many functions include the maintenance of cell integrity, enzyme display and, in pathogens and commensals, interaction with the host and its immune system. In this Review, we discuss our current knowledge of S-layer and related proteins, including their structures, mechanisms of secretion and anchoring and their diverse functions

Urological cancer care pathways: development and use in the context of systematic reviews and clinical practice guidelines

Background: Making healthcare treatment decisions is a complex process involving a broad stakeholder base including patients, their families, health professionals, clinical practice guideline developers and funders of healthcare. Methods: This paper presents a review of a methodology for the development of urological cancer care pathways (UCAN care pathways), which reflects an appreciation of this broad stakeholder base. The methods section includes an overview of the steps in the development of the UCAN care pathways and engagement with clinical content experts and patient groups. Results: The development process is outlined, the uses of the urological cancer care pathways discussed and the implications for clinical practice highlighted. The full set of UCAN care pathways is published in this paper. These include care pathways on localised prostate cancer, locally advanced prostate cancer, metastatic prostate cancer, hormone-resistant prostate cancer, localised renal cell cancer, advanced renal cell cancer, testicular cancer, penile cancer, muscle invasive and metastatic bladder cancer and non-muscle invasive bladder cancer. Conclusion: The process provides a useful framework for improving urological cancer care through evidence synthesis, research prioritisation, stakeholder involvement and international collaboration. Although the focus of this work is urological cancers, the methodology can be applied to all aspects of urology and is transferable to other clinical specialties.11 page(s

Effects of lay support for pregnant women with social risk factors on infant development and maternal psychological health at 12 months postpartum

Background The ELSIPS (Evaluation of Lay Support in Pregnant Women with Social Risk) RCT showed that lay support for women with social risk had a positive effect on maternal mental health and mother-infant bonding. This exploratory study examined whether these observed benefits would impact infant development at 1 year. Methods A sub-sample of women whose infants were under one year who had participated in the ELSIPS RCT which randomised women to receive either standard care or the services of a Pregnancy Outreach Worker (POW), and who were contactable, were eligible to participate in the follow up. At home visits, the Bayley Scales of Infant Development (3rd Edition) and standardised measures of depression, self efficacy, mind-mindedness and bonding were completed. Results 486 women were eligible for follow up, of whom 154 agreed to participate. 61/273 were successfully followed up in the standard maternity care arm and 51/213 in the POW arm. Women who completed follow up were less depressed and had higher selfefficacy scores at 8–12 weeks postpartum than those who did not complete follow up. There were no significant differences in maternal outcomes, infant cognitive development, receptive communication, expressive communication, fine motor development or social/emotional functioning between groups at 12 month follow up. Infants of mothers who received the POW intervention had significantly better gross motor development than infants whose mothers received standard care (p<0.03)

Promotion, prevention and protection: interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries

Background In addition to services within the health system, interventions at the population and community levels are also important for the promotion of mental health, primary prevention of mental, neurological and substance use (MNS) disorders, identification and case detection of MNS disorders; and to a lesser degree treatment, care and rehabilitation. This study aims to identify “best practice” and “good practice” interventions that can feasibly be delivered at these population- and community-levels in low- and middle-income countries (LMICs), to aid the identification of resource efficiencies and allocation in LMICs. Methods A narrative review was conducted given the wide range of relevant interventions. Expert consensus was used to identify “best practice” at the population-level on the basis of existing quasi-experimental natural experiments and cost effectiveness, with small scale emerging and promising evidence comprising “good practice”. At the community-level, using expert consensus, the ACE (Assessing Cost-Effectiveness in Prevention Project) grading system was used to differentiate “best practice” interventions with sufficient evidence from “good practice” interventions with limited but promising evidence. ResultsAt the population-level, laws and regulations to control alcohol demand and restrict access to lethal means of suicide were considered “best practice”. Child protection laws, improved control of neurocysticercosis and mass awareness campaigns were identified as “good practice”. At the community level, socio-emotional learning programmes in schools and parenting programmes during infancy were identified as “best practice”. The following were all identified as “good practice”: Integrating mental health promotion strategies into workplace occupational health and safety policies; mental health information and awareness programmes as well as detection of MNS disorders in schools; early child enrichment/preschool educational programs and parenting programs for children aged 2–14 years; gender equity and/or economic empowerment programs for vulnerable groups; training of gatekeepers to identify people with MNS disorders in the community; and training non-specialist community members at a neighbourhood level to assist with community-based support and rehabilitation of people with mental disorders. Conclusion Interventions provided at the population- and community-levels have an important role to play in promoting mental health, preventing the onset, and protecting those with MNS disorders. The importance of inter-sectoral enga

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Minimal information for studies of extracellular vesicles 2018 (MISEV2018):a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points