Onset Types Research Articles

Circadian Rhythm Disorders and Risk of Subsequent Depression: A Systematic Review and Meta-Analysis of Longitudinal Studies

Background: Patients with depression often suffer from circadian rhythm disruptions, such as insomnia and a lower amplitude of daily rhythms of locomotor activity. However, whether circadian disorders precede depression and act as a predictor for subsequent depression have not been unanimously approved. In light of increasing evidence of an association between disrupted circadian rhythms and affective symptoms, a meta-analysis was conducted to examine the effect of circadian disruptions on incident depression. Methods: A systematic search was performed in PubMed, Embase, Web of Science, PsycINFO, PsycArticles, CINAHL database. The search results were restricted to be published in English up to April 10, 2020.Reference lists from included studies and relevant reviews were also screened. We included longitudinal cohort studies that examined the predictive role of all various types of circadian disruption in incident depression. Two reviewers independently extracted information on study design, participants’ characteristics and diagnostic criteria for circadian disruption and depression. Study quality was assessed using the Newcastle-Ottawa Scale. Random-effect models were applied to all meta-analyses given potential heterogeneity. For insomnia, subgroup analyses were performed based on subject’s characteristics, insomnia symptom domains and numbers and the investigated methods. Pool-effect estimates of relative risks to develop incident depression in groups with circadian disruption compared to groups without. This study is registered with PROSPERO, CRD42020179135. Findings: A total of 49 studies were eligible for this meta-analysis. Of 49 eligible studies, included types of circadian disruption were sleep disturbances (n = 45), chronotype (n = 2), cortisol awakening response (n = 1) and rest - activity rhythm (n = 1). Insomnia, hypersomnia, excessive daytime sleepiness (EDS), short sleep duration, obstructive sleep apnea (OSA), restless legs syndrome (RLS), an evening preference, heightened levels of cortisol in awakening response and low robustness of rest - activity rhythm all acted as significant predictors of occurrence of depression. Among insomnia subtypes, difficulty initiating sleep (DIS) and difficulty maintaining sleep (DMS) predicted future depression. Of note, persistent insomnia (OR: 5.02) contributed to more than two - fold risk of incident depression compared to insomnia (OR: 2.34). Moreover, insomnia symptom numbers were associated with incident depression in a gradient trend. Interpretation: Different types of circadian disorders act as risk factors of onset of depression, which clinicians should be informed of. Future research should be aimed to determine the casual relationship between other types of circadian disorders and onset of depression, and moreover to further elucidate the underlying mechanisms. Funding Statement: This work was supported in part by the National Natural Science Foundation of China (no. 81871071 and 81171251) and Beijing Municipal Natural Science Foundation (no. 7162101). Declaration of Interests: All of the authors declare no conflict of interest.

Long-term outcomes of various pediatric short bowel syndrome in China.

The goal of this study was to analyze long-term outcome of various pediatric short bowel syndrome (SBS) at an intestinal rehabilitation center in China. One hundred and fifty-seven children with SBS were enrolled in this study from October 1988 to July 2019. Their long-term follow-up outcome was analyzed according to the age of disease onset, parenteral nutrition (PN) duration, and anatomic types of short bowel, respectively. The clinical characteristics, which included demographics, the length of residual small bowel, PN duration, PN dependence, SBS-related complications such as IF-related liver disease (IFALD), catheter-related bloodstream infection (CRBI), and mortality were compared among the groups. The main etiology for SBS were intestinal atresia, NEC, and volvulus. Five of 157 patients did not wean off PN. The incidence of IFALD and CRBI was 24.2 and 22.3%, respectively. Sixteen cases died because of infection and liver failure and eight patients lost to follow-up. The survival rate of the 157 patients was 84.7%. PN duration was longer in the infants and children group (284 ± 457d vs. 110 ± 64d, P = 0.021; R = 0.264, P = 0.001) and more patients did not wean off PN than in the neonates group (11.6% vs. 0, P = 0.001; R = 0.295, P < 0.001). Patients with PN with a duration of longer than 90days had more CRBIs (30.6%, P = 0.025; R = 0.236, P = 0.003). Additionally, the rate of CRBI was higher in patients with stoma (30.0%, P = 0.032). There was no difference in mortality among the groups. In five PN dependence patients, none was SBS onset in neonates. Pediatric patients with SBS could achieve favorable long-term survival and enteral autonomy. Different standards of SBS classification such as the age of disease onset, PN duration, and anatomic types of short bowel did not impact the overall mortality of pediatric SBS. Prolonged PN duration positively correlated with the age of disease onset and the incidence of CRBI. Patients with the complete continuity of intestinal tract suffered less from CRBI.

A computational approach to analyse the amino acid variants of GLB1 protein causing GM1 Gangliosidosis.

Lysosomal storage diseases comprise different forms of autosomal recessive disorders from which GM1 gangliosidosis has categorized by the accumulation of complex glycolipids associated with a range of progressive neurologic phenotypes. GM1 gangliosidosis is an inherited disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. GM1 has three main types of onsets, namely infantile (type I), juvenile (type II), and adult (type III) forms. This study provides a series of computational methods that examine the mutations that occurred in GLB1 protein. Initially, the mutational analysis started with 689 amino acid variants for a sequence-based screening and it was done with quite a few In-silico tools to narrow down the most significant variants by utilizing the standard tools; namely, Evolutionary analysis (77 variants), Pathogenicity prediction (44 variants), Stability predictions (30 variants), Biophysical functions (19 variants) and according to the binding site of protein structure with PDB ID 3THC, seven variants (Y83D, Y83H, Y270S, Y270D, W273R, W273D, and Y333H) were narrowed down. Structure based analysis was performed to understand the interacting profile of the native protein and variants with Miglustat; which is the currently used FDA drug as an alternative to enzyme replacement therapy. Molecular Docking study was done to analyze the protein interaction with Miglustat (ligand), as a result native (3THC) structure had a binding affinity of -8.18kcal/mol and two variant structures had an average binding affinities of -2.61kcal/mol (Y83D) and - 7.63kcal/mol (Y270D). Finally, Molecular Dynamics Simulation was performed to know the mutational activity of the protein structures on Miglustat for 50,000ps. The Y83D variant showed higher deviation than native protein and Y270D in all trajectory analysis. The analysis was done to the protein structures to check the structural variations happened through simulations. This study aids to understand the most deleterious mutants, the activity of the drug to the protein structure and also gives an insight on the stability of the drug with the native and selected variants.

Расстройства приема пищи у больных с ожирением и сахарным диабетом 2-го типа. Лекция для врачей

Obesity and type 2 diabetes mellitus (DM 2) that result from eating disorders (ED) which lead to weight gain are endocrine diseases provoked (caused) by psychopathology, and are psychosomatic diseases. The clinical features of ED in obesity and diabetes mellitus 2 are that they rarely occur as independent psychopathological units and are mainly represented by syndromic classification in the structure of other mental disorders. Preference of the predominant type of overeating for certain types of ED onset was revealed. Thus, fetal onset is characterized by permanent overeating, pubertal one – by compulsive overeating, psychogenic one – evening overeating and menopausal/age-related hypoandrogenic one – by polysyndromic overeating. Psychopharmacotherapy and psychotherapy combination is used to treat ED in patients with DM 2 and obesity. For prevention of obesity, it is recommended to diagnose early signs of ED which lead to weight gain, and to initiate psychiatric and psychotherapeutic care as soon as possible if ED occurred. Recent 2021 clinical guidelines for the treatment of obesity were updated with recommendation that all obese patients after secondary causes for weight gain were excluded, should be consulted by a psychiatrist-psychotherapist specializing in the general somatic network.

Patterns of grey and white matter changes differ between bulbar and limb onset amyotrophic lateral sclerosis

Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a high heterogeneity in patients’ disease course. Patients with bulbar onset of symptoms (b-ALS) have a poorer prognosis than patients with limb onset (l-ALS). However, neuroimaging correlates of the assumed biological difference between b-ALS and l-ALS may have been obfuscated by patients’ diversity in the disease course. We conducted Voxel-Based-Morphometry (VBM) and Tract-Based-Spatial-Statistics (TBSS) in a group of 76 ALS patients without clinically relevant cognitive deficits. The subgroups of 26 b-ALS and 52 l-ALS patients did not differ in terms of disease Phase or disease aggressiveness according to the D50 progression model. VBM analyses showed widespread ALS-related changes in grey and white matter, that were more pronounced for b-ALS. TBSS analyses revealed that b-ALS was predominantly characterized by frontal fractional anisotropy decreases. This demonstrates a higher degree of neurodegenerative burden for the group of b-ALS patients in comparison to l-ALS. Correspondingly, higher bulbar symptom burden was associated with right-temporal and inferior-frontal grey matter density decreases as well as fractional anisotropy decreases in inter-hemispheric and long association tracts. Contrasts between patients in Phase I and Phase II further revealed that b-ALS was characterized by an early cortical pathology and showed a spread only outside primary motor regions to frontal and temporal areas. In contrast, l-ALS showed ongoing structural integrity loss within primary motor-regions until Phase II. We therefore provide a strong rationale to treat both onset types of disease separately in ALS studies.

Clinical Pharmacology and Therapeutics of Antiepileptic Drugs

This article describes clinical antiepileptic drugs (AEDs) that are available for treatment of epilepsy. Epilepsy is characterized by repeated occurrence of seizures. Epileptic seizures are classified into focal onset (partial) and generalized onset (generalized) types. Around two-dozen AEDs are available for treating epilepsy. AEDs act on diverse molecular targets to selectively modify the abnormal excitability of neurons by reducing the focal seizure discharges or preventing spread of excitation. AEDs suppress seizures by blocking the voltage-gated sodium channels (phenytoin, carbamazepine, valproate, lamotrigine, oxcarbazepine, topiramate), voltage-activated calcium channels (ethosuximide, gabapentin), potentiation of GABA inhibition (barbiturates, benzodiazepines, tiagabine), and reduction of glutamate excitation (felbamate, parampanel). Carbamazepine, phenytoin, and valproate are the first-line agents for partial onset seizures and generalized onset seizures. Ethosuximide is the drug of choice for absence seizures. AEDs are orally-active and show unique PK features. Some AEDs cause enzyme induction and hence produce drug-drug interactions. Newer AEDs such as gabapentin, levetiracetam, tiagabine, and pregabalin do not cause enzyme induction. Despite many advances in AEDs, nearly 30% of people with epilepsy have drug-resistant or intractable seizures. Presently, there is no cure for epilepsy. Thus, newer and better AEDs that can better prevent refractory seizures and modify the disease are needed for curing epilepsy.

The Psychosocial Outcome of Conduct and Oppositional Defiant Disorder in Children With Attention Deficit Hyperactivity Disorder.

Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders diagnosed in children below the age of 12 years. It is characterized by hyperactivity, inattention, and impulsive behavior. ADHD affects the social, academic, and psychological aspects of children and adolescents. Children with ADHD struggle with school tasks and performance. They have lower grades than their peers and have difficulties interacting with their friends.Oppositional defiant disorder (ODD) is a mental disorder characterized by disruptive behavior, a pattern of angry and irritable mood, argumentative, and vindictive behavior. Children with ODD struggle with forming friendships and have problems at school. Conduct disorder (CD) is divided into the childhood onset and the adolescent onset types. The childhood onset is associated with poor outcomes in adulthood, an increase in criminal behavior, violence, and progression to antisocial behavior. Children with CD are at increased risk for substance use disorders (SUD) and antisocial personality disorder. The current literature review is aiming to provide an overview of the psychosocial impact of comorbid ODD and CD in children with ADHD. The results of this study review showed the comorbidity of ODD and CD is very strong. ODD is a strong predictor of CD in boys. The presence of comorbid ODD and ADHD in children is a significant predictor of adolescent onset CD. The comorbidity of ADHD with ODD and CD worsens symptom severity and is associated with high psychosocial dysfunction. Children with ADHD and comorbid ODD and CD have difficulties with school, friends, and trouble with the police.

Maternal-perinatal outcome in pregnancies complicated by preeclampsia: Looking at early and late onset disorders

Background: Globally, preeclampsia; an idiopathic pregnancy-related proteinuric hypertensive disorder remains one of the major causes of maternal and perinatal morbidity and mortality, worst so in low resources settings. Accumulating evidence indicates that the outcome is influenced by the gestational age at onset of the disorder. Aim: We investigated the perinatal and maternal outcomes of pregnancies complicated by preeclampsia and in addition compared the early onset and late onset types. Materials and Methods: An analytical observational study was carried on all cases of preeclampsia managed in tertiary hospital between 2013 and 2019. The participants were comparatively studied for maternal and perinatal outcomes. Results: The incidence of preeclampsia was 7.1%. About a third 31.9% were early onset and 68.1% late onset disease. Maternal complications were frequent in preeclampsia; 24.5% eclampsia, an incidence of eclampsia of 56/3474 (1.61%), 74.2% cesarean section, 23.6% severe proteinuria, 12.2% anemia, 11.4% postpartum hemorrhage, 3.1% pulmonary edema, 1.7% thrombocytopenia, 0.9% hemolysis, elevated liver enzymes and low platelet syndrome and acute renal failure, respectively. These were more frequent in late preeclampsia but severer in early onset disease. Case fatality rate was 1.75% and maternal mortality ratio 117.7/100,000 live births. Mean gestational age at delivery in preeclampsia was 35.4 weeks with 51% preterm births and 28.8% small for gestational age neonates with early onset disease contributing more than twofold. The perinatal mortality was high at 21.4%; a perinatal mortality rate of 14.2/1000 total births with 6-fold among early onset disease mostly from iatrogenic prematurity. Conclusions: The incidence of preeclampsia was high, maternal morbidity though more common among late onset disease, was severer among the early onset disease which also had worse adverse perinatal outcomes.

Parallel Comparison of Major Sudden Stratospheric Warming Events in CESM1-WACCM and CESM2-WACCM

After the recent release of the historical runs by community Earth system model version 2–the whole atmosphere community climate model (CESM2-WACCM), the major sudden stratospheric warming (SSW) events in this model and in its previous version (CESM1-WACCM) are compared based on a modern reanalysis (JRA55). Using the World Meteorological Organization (WMO) definition of SSWs and a threshold-based classification method that can describe the polar vortex morphology, SSWs in models and the reanalysis are further classified into two types, vortex displacement SSWs and vortex split SSWs. The general statistical characteristics of the two types of SSW events in the two model versions are evaluated. Both CESM1-WACCM and CESM2-WACCM models are shown to reproduce the SSW frequency successfully, although the circulations differences between vortex displacement SSWs and vortex split SSWs in CESM2-WACCM are smaller than in CESM1-WACCM. Composite polar temperature, geopotential height, wind, and eddy heat flux anomalies in both the two models and the reanalysis show similar evolutions. In addition, positive Pacific–North America and negative Western Pacific patterns in the troposphere preceding vortex displacement and split SSWs are observed in both observations and the models. The strong negative North Atlantic oscillation-like pattern, especially after vortex split SSW onset, is also identified in models. The near-surface cold Eurasia–warm North America pattern before both types of SSW onset, the warm Eurasia–cold North America pattern after displacement SSW onset, and the cold Eurasia–cold North America pattern after split SSW onset are consistently identified in JRA55, CESM1-WACCM, and CESM2-WACCM, although the temperature anomalies after the split SSW onset in CESM2-WACCM are somewhat underestimated.

Rare and serious types of central nervous system demeylinating diseases and MS types

Multiple sclerosis (MS) is an inflammatory condition causing demyelination and axonal loss in the central nervous system (brain and spinal cord). The primary brain insult (“sclerosis”) and its clinical features are “dissemination in space”, affecting different anatomical sites, and “dissemination in time”, appearing episodically over time. The common types of MS includes-Relapsing and remitting type (RRMS)-Secondary progressive MS (SPMS)-Primary progressive MS ( PPMS) The sub-division is based more on clinical characteristics and not specific biological pathophysiology. Nonetheless, they provide an organized framework for diagnosis and long-term management. Multiple Sclerosis was initially thought to be a rare condition in countries close to the equator such as India. However that has changed now and we do see cases of Multiple Sclerosis in this part of the world. And occasionally we do also come across patients with evidence of demyelination in the CNS which is resistant to treatment and has a rapidly progressive course which even leads to death. These rare types of MS includes Marburg variety and tumefactive MS. We have three such patients who presented with rapidly progressive neurological deficits and showed such a rampant course, in spite of various anti-inflammatory agents used including Rituximab. This presentation is to highlight the fact that demyelinating disease of the CNS could be quite dangerous from the onset and rare types of MS should be considered early in such cases.

Intractable seizures, prediction, prognostic factors, intractability: A systematic review

It is my honour to be here and share our systematic review results about intercatable seizures prognostic studies with you. About 30 percent of epileptic patients have medically intractable epilepsy. Traditionally, therapeutic failure of three antiepileptic drugs defined intractability. With many new antiseizure drugs available in recent years, it might have been expected that more, rather than fewer, drug trials would be recommended before determining intractability. A task force of the International League Against Epilepsy (ILAE) proposed that drug-resistant be defined as the failure of adequate trials of two tolerated, appropriately chosen and administered antiseizure drugs to achieve seizure control. Our aim of this review is to evaluate the evidence for independent prognostic factors of intractability in patients with epilepsy. MEDLINE and EMBASE from 2010 to 2017 were searched for cohort studies reporting on prognostic factors for medically intractable epilepsy. After selection the valued studies, their quality was assessed by using the QUIPS checklist .In these studies, some of the prognostic factors were independent such as symptomatic etiology, poorly control in the first year, abnormal EEG, and age at seizure onset and mixed seizure types. Early response to treatment is an important positive predictor of long‐term prognosis, while the history of a high number of seizures at the time of diagnosis, intellectual disability, and symptomatic etiology are negative predictors. In childhood studies, logistic regression analysis revealed that a previous history of epilepticus status, abnormal electroencephalogram results, and multiple seizures in 1 day comprise independent predictors of medically intractable childhood epilepsy.

Diabetes mellitus types: Key genetic determinants and risk assessment

The characteristic symptom of diabetes is consistently elevated levels of blood sugar. This is instigated either by complete lack of insulin production (type 1 diabetes), reduced level of insulin production (type 2 diabetes) or insulin resistance (inability of body cells to take up glucose). Other types of diabetes include maturity onset of diabetes of the young (MODY), a form of type 2 diabetes and gestational diabetes which affects pregnant women mostly in second or third trimester. The term type-3-diabetes is now being used for insulin resistance in brain. Apart from environmental and dietary causes which pose the risk of diabetes, genetic constitution and gene mutations execute the manifestation of diabetes. So far, several hundreds of genes having genomic, metabolic and immunological functions have been associated with different forms of diabetes. Due to complexity in diabetes etiology, involvement of multiple genetic factors and overlap between phenotypes, the treatment for diabetes remains a major challenge. Single gene mutations can be potentially targeted therapeutically; however, the prevalence of single gene mutations in diabetic condition is rare. Comprehensive analysis of genes and genetic variants relevant to diabetes enables development of effective treatment or interventional strategies. The current literature survey was conducted and reviewed to identify studies that proposed the genetic basis for specific subtypes of diabetes and related complications. In addition, this review emphasizes the role of genome wide association studies and epigenetic factors. In the present review, we have identified some of the most significant protein encoding genes whose mutations have great impact in the development of diabetic condition. The characteristic features of these genes such as the risk level associated with the genes and inter-genic associations both in terms of position and functional proximity have been discussed. Additionally, genomic studies and epigenetic aspects have also been highlighted for wider comprehension of the diabetic condition from a genetic perspective. The present review would be of significance in prevention, screening, diagnosis, treatment and management of different forms of diabetes.

Analysis of phonological processes in the acquisition of complex onset in children with typical phonological development

ABSTRACT Objective: description and analysis of the phonological processes in the acquisition of complex onset by children with typical phonological development in the age ranges of 3;0 and 5;11. Methods: thirty-one students of a public day-care center in Maceió-AL, having no auditory, cognitive, or motor impairment, participated in this study. The data were collected using the ABFW Child Language Test (WERTZNER, 2004); spontaneous speech was also collected. Inferential statistical analysis of the data was performed, and the phonological processes were analyzed in the production of complex onset. Results: we found evidence for late acquisition of this syllabic component in the age range of 5;0-5;11 for both types of complex onsets. In relation to the prevalence of phonological processes, a statistically significant difference was observed between the different processes, with a prevalence of the simplified phonological process for C1V, when taking the two types of complex onset into consideration; however, the 5-year age group, in which there was a prevalence of liquid substitution, was an exception. Conclusion: the most observed phonological processes in children's speech were: simplification of C1V and liquid substitution. These results will contribute to the selection of the lexicon for evaluation and treatment of cases of atypical development.

Sham-Controlled Study of Optokinetic Stimuli as Treatment for Mal de Debarquement Syndrome.

Introduction: Mal de Debarquement Syndrome (MdDS) is a condition characterized by a perception of self-motion in the absence of a stimulus, with two onset types: Motion-Triggered and Spontaneous. Currently, the pathophysiology is unknown and consequently, the therapeutic options are limited. One proposed treatment protocol, developed by Dai and colleagues is based on optokinetic stimulation, which aims to re-adapt the vestibular ocular reflex. This study aimed to reproduce the treatment protocol developed by Dai and colleagues and to assess if a placebo effect is present in the treatment protocol and lastly, aimed to further investigate the treatment on MdDS patient outcomes.Method: Twenty-five MdDS patients (13 Motion-Triggered and 12 Spontaneous) were exposed to 5 consecutive days of optokinetic treatment (consisting of exposure to optokinetic stimuli with head movements). Eleven of these 25 patients were also exposed to 2 days of a sham treatment prior to the OKN treatment. Posturography measurements and reported symptoms [e.g., using the visual analog scale (VAS)] of patients were assessed throughout the treatment. Posturography data of the patients was compared with the data of 20 healthy controls.Results: No placebo effect was recorded with any changes in postural data and VAS scale. After the optokinetic treatment, a significant improvement in postural control was observed in 48% of patients, of whom 70% were of the Motion-Triggered subtype (p-values: Area under the Curve—Anterior Posterior < 0.001; Area under the Curve—Medio Lateral p < 0.001, Confidence Ellipse Area (CEA) < 0.001, Velocity < 0.001).Conclusion: The protocol was effective in approximately half of the MdDS patients that took part in the study, with no placebo effect recorded. The Motion-Triggered group responded better to treatment than the Spontaneous group. In addition to this, this study indicates that the greatest postural changes occur within the first 3 days of treatment, suggesting that a shorter protocol is possible. Overall, these findings support what was previously observed in Dai's studies, that optokinetic stimulation can reduce and ease self-motion perception in those with MdDS. Thus, validating the reproducibility of this protocol, suggesting that a consistent and uncomplicated implementation across treatment centers is possible.

Patient-reported outcomes are worse for progressive-onset multiple sclerosis than relapse-onset multiple sclerosis, particularly early in the disease process.

Treatments for progressive-onset multiple sclerosis (MS) are lacking. To improve the disease management for progressive-onset MS, the differences between relapse-onset MS and progressive-onset MS in patient-reported disability, progression and symptoms were examined. A total of 1985 participants of the Australian Multiple Sclerosis Longitudinal Study were included. Associations between onset type and outcomes were assessed with negative binomial regression. The severity of 17 of the 19 outcomes was significantly higher for progressive-onset MS patients than relapse-onset MS patients, including perspectives from disability, progression over the last year, fatigue, sensory, walking difficulties, pain, balance, spasticity, sexual dysfunction, bladder, bowel, anxiety, depression and the European quality of life (EQ-5D) (P<0.05; adjusted mean ratio ranged from 1.11 to 1.52). The differences between the two onset types were most pronounced early in the disease process and reduced with increasing MS duration, and the interaction was significant for disability, progression over the last year, walking difficulties, bladder problems, bowel problems and spasticity. Participants with progressive-onset MS were significantly worse off on nearly all patient-reported outcomes than relapse-onset MS participants, and the differences were most pronounced early in the disease course, highlighting the importance of early intervention for those with progressive-onset MS.

Association of the novel susceptible locus rs9266150 with clinical features of psoriasis vulgaris in the Chinese Han population.

Psoriasis is a chronic multifactorial disease and is considered to be strongly associated with the major histocompatibility complex (MHC) region. We have discovered an independent, novel and susceptible psoriasis risk HLA loci, rs9266150; P=4.52×10-9 for the first time. In this study, we aimed to verify the relationship between the susceptible locus and the subphenotypes of psoriasis vulgaris (PV), including geographic location, gender, age of onset, family history and present skin lesion types (chronic plaque and guttate). To investigate the distribution and association of the rs9266150 gene with clinical phenotypes of PV in Chinese Han population, we conducted an analysis in case-control and case-only subjects in the 9906 controls and 8744 cases by MHC targeted sequencing stratified analysis in this study. Significant associations were found with a northern geographic location in the case-only (P=1.97×10-4 ) and the subphenotype-control analyses (P=5.57×10-5 ), males in the case-only (P=4.77×10-3 ) and the subphenotype-control analyses (P=7.31×10-4 ), and guttate psoriasis in the case-only (P=4.08×10-3 ) and the subphenotype-control analyses (P=1.27×10-3 ). There were no significant differences observed between the age of onset (OR=1.062, 95% CI: 0.9725-1.16, P=1.8×10-1 ) and the family history of psoriasis (OR=0.981, 95% CI: 0.9048-1.064, P=6.43×10-1 ). The recessive model provided the best fit for rs9266150 (P=4.38×10-7 ). Our results implied that rs9266150 might not only play an important role in the development of psoriasis, but also be positively associated with the geographic location, gender and present skin lesion in the Chinese population.

Evaluation of Children with SMA Type 1 Under Treatment with Nusinersen within the Expanded Access Program in Germany.

Background:Spinal muscular atrophy (SMA) is a neuromuscular disorder characterized by muscle weakness and muscle atrophy. Nusinersen acts as a splicing modifier and has recently been approved for intrathecal treatment of SMA.Objective:Prior to approval, nusinersen was provided to patients with SMA type 1 in Germany within an Expanded Access Program (EAP). In contrast to previous clinical trials, children of different age groups and different stages of the disease were treated with nusinersen.Methods:We conducted a prospective, longitudinal data collection of patients treated with nusinersen within the EAP in seven neuromuscular centers in Germany. Standardized assessments including CHOP-INTEND and HINE-2 motor milestones were performed at baseline and 60 and 180 days after start of treatment.Results:Data from 61 SMA type 1 patients (mean age 21.08 months, range 1–93) were available for analysis. After six months of treatment, 47 children (77.0%) improved by ≥4 points in CHOP INTEND score. Mean change in CHOP INTEND score was 9.0±8.0 points. Nineteen patients (31.1%) improved by ≥2 points in HINE-2 motor milestones. Regression analysis revealed age at onset of treatment as major determinant of change in CHOP INTEND from baseline.Conclusion:When analyzing a broad spectrum of SMA type 1 patients, many children showed an improvement of motor function after six months of treatment with nusinersen, which is generally not expected within the natural course of the disease. Long-term observation and follow-up of patients with later onset types of SMA are crucial to understand the clinical impact of treatment with nusinersen.

Treatment adherence in adolescent psychiatric inpatients with severe disruptive behaviour

ObjectiveTo examine pre‐treatment characteristics associated with dropout in 224 adolescent psychiatric inpatients (mean age 17.1 years) with severe disruptive behaviour. To date, little is known about the factors predicting dropout among adolescents treated for severe disruptive behaviour. This is surprising, as dropout is a major problem in this specific group.MethodDropouts (n = 77) and completers (n = 147) were compared on known risk factors for dropout, such as severity of externalising problems and disorders, ethnic minority status, male gender, and lower academic functioning, as well as on other factors considered relevant: behavioural characteristics, including age of onset and different types of disruptive behaviour. Within dropout, withdrawal (termination against the advice of the therapist; n = 40) and pushout (termination against the wish of the client; n = 37) were distinguished.ResultsTwo characteristics significantly predicted dropout: early onset of disruptive behaviour and cannabis usage prior to treatment. Within the dropout group no differences were found between withdrawals and pushouts.ConclusionsPredicting dropout among adolescent psychiatric inpatients with severe disruptive behaviour is difficult. The two predictors found were already present at the time of admission and are therefore considered unalterable. However, they can be used to pinpoint individuals with higher chance at dropout, who in turn can be offered tailored interventions aimed at improving the therapeutic relationship.

Comparing the adoption of protective behaviors: The framing effects of national culture and hazard onset type

ABSTRACTOn the basis of framing effect and protective action decision model, this study examines the differences in people's response to diverse hazard onset types (sudden or gradual) under different cultural frameworks (China and the United States) and the framing effects of culture and hazard onset type on people's perception and behavioral response. The data are derived from three questionnaire surveys on people's behavioral response to H7N9 and smog emergency in China and H1N1 in the United States. Results indicate that people with different cultures and diverse contexts of hazard onset type present substantial differences in risk perception, protective action perception, stakeholder perception, and behavioral expectations. Furthermore, culture and hazard onset type exert significant framing effects on people's three types of perception, reliance on official information sources, and intention to adopt protective actions. This research empirically verifies the existence of framing effect in culture and decision scenarios, thereby helping in developing different emergency communication strategies.

Sensitive periods for the effect of childhood interpersonal violence on psychiatric disorder onset among adolescents.

BackgroundAlthough childhood adversity is a strong determinant of psychopathology, it remains unclear whether there are 'sensitive periods' when a first episode of adversity is most harmful.AimsTo examine whether variation in the developmental timing of a first episode of interpersonal violence (up to age 18) associates with risk for psychopathology.MethodUsing cross-sectional data, we examined the association between age at first exposure to four types of interpersonal violence (physical abuse by parents, physical abuse by others, rape, and sexual assault/molestation) and onset of four classes of DSM-IV disorders (distress, fear, behaviour, substance use) (n = 9984). Age at exposure was defined as: early childhood (ages 0-5), middle childhood (ages 6-10) and adolescence (ages 11-18).ResultsExposure to interpersonal violence at any age period about doubled the risk of a psychiatric disorder (odds ratios (ORs) = 1.51-2.52). However, few differences in risk were observed based on the timing of first exposure. After conducting 20 tests of association, only three significant differences in risk were observed based on the timing of exposure; these results suggested an elevated risk of behaviour disorder among youth first exposed to any type of interpersonal violence during adolescence (OR = 2.37, 95% CI 1.69-3.34), especially being beaten by another person (OR = 2.44; 95% CI 1.57-3.79), and an elevated risk of substance use disorder among youth beaten by someone during adolescence (OR = 2.77, 95% CI 1.94-3.96).ConclusionsChildren exposed to interpersonal violence had an elevated risk of psychiatric disorder. However, age at first episode of exposure was largely unassociated with psychopathology risk.