The relationship between adult symptoms of Attention-Deficit/Hyperactivity Disorder and criminogenic cognitions:ADHD and Criminogenic Cognitions

The relationship between ADHD – in particular hyperactivity – and criminal behavior is well documented. The current study investigated the role of criminogenic cognitions in the explanation of this relationship by examining which symptoms of ADHD are associated with criminogenic cognitions. Community-recruited adults (N = 192) completed self-report questionnaires for symptoms of ADHD and criminogenic cognitions. Symptoms of inattention were consistently and strongly related to criminogenic cognitions. In particular, inattention was significantly related to cutoff, cognitive indolence, and discontinuity. There was also evidence that impulsivity was positively related to criminogenic cognitions, and specifically, to the power orientation subscale. In contrast, and contrary to expectations, symptoms of hyperactivity were not related to criminogenic cognitions. These results indicate that, in community-recruited adults, inattention rather than hyperactivity is related to criminogenic cognitions. We discuss the implications of these findings contrasting with those of previous studies that used forensic and clinical samples

Analyse von ZNS-Tumoren bezüglich ihres FGFR1 Mutationsstatus

Lowgrade-Gliome (LGG) und gemischte glioneuronale Tumore (MNGT) stellen eine heterogene Gruppe primärer Hirntumore dar und zeigen häufig Veränderungen im MAPK Signalweg. Nicht immer gelingt eine sichere Differenzierung allein durch die Histologie. Daher lag der Fokus dieser Arbeit auf der Untersuchung eines möglichen molekularen Diskriminators, in diesem Fall den zwei FGFR1-Hotspot-Mutationen c.546 (N546K) und c.656 (K656E). Über Mutationen der Tyrosinasekinase-Domäne des onkogenen Fibroblasten- Wachstumsfaktor-Rezeptors 1 (FGFR1) wurde in Gehirntumoren verschiedener histologischer Muster berichtet. Deshalb wurde in der vorliegenden Arbeit versucht, die Häufigkeit der FGFR1-Hotspot-Mutationen N546 und K656 in einer Gruppe LGG/MNGT ohne bekannte Treibermutation zu bestimmen. Dazu wurde die FGFR1-Immunhistochemie als potenzielles Instrument zum Nachweis dieser Veränderungen sowie die anschließende Pyrosequenzierung genutzt. Insgesamt wurden 476 LGG/MNGT-Tumoren auf die molekularen Veränderungen in BRAFV600E, IDH1/2, TERT-Promotor, NF1, H3F3A sowie auf eine KIAA-1549-BRAF Fusion untersucht. Die verbleibenden Fälle ohne bekannte Treibermutation wurden sodann auf ihre FGFR1-Immunoreaktivität und die FGFR1-Mutationshäufigkeit mittels Pyrosequenzierung untersucht. Hier wurden unter den 108 verbleibenden Fällen neun FGFR1 p.N546K- und 4 FGFR1 p.K656E Mutationen identifiziert. Fünf Tumore wurden als dysembryoplastischer neuroepithelialer Tumor (DNT), vier als pilozytisches Astrozytom (PA) und drei als rosettenbildender glioneuronaler Tumor (RGNT) klassifiziert. FGFR1-Mutationen waren mit einer Oligodendroglia-ähnlichen Histologie assoziiert, aber weder mit Alter noch Tumorlokalisation. Eine immunhistochemische Expression von FGFR1 wurde in 92/106 Fällen beobachtet. Der FGFR1-Immune Reactivity Score war insgesamt bei PA und DNT höher als bei diffusen Astrozytomen, aber es wurde keine Korrelation zwischen der FGFR1-Mutation in Tumoren und dem FGFR1-Expressionsniveau beobachtet. Als Resultat dieser Arbeit konnten wir zeigen, dass FGFR1- Hotspot-Mutationen die fünfthäufigste Veränderung bei LGG/MNGT ausmachen. Übertragen auf die Praxis kann die Durchführung einer FGFR1-Sequenzanalyse bei treiberunbekannten niedriggradigen Hirntumoren (LGG/MNGT) in bis zu 12 % der Fälle eine Veränderung in FGFR1 N546/K656 aufdecken. Für die nahe Zukunft könnte hieraus neben einer akkurateren Diagnosestellung ein Fundament für eine Therapie basierend auf den molekulargenetischen Eigenschaften des Tumors abgeleitet werden

Understanding Health Workers' Job Preferences to Improve Rural Retention in Timor-Leste: Findings from a Discrete Choice Experiment

Background Timor-Leste built its health workforce up from extremely low levels after its war of independence, with the assistance of Cuban training, but faces challenges as the first cohorts of doctors will shortly be freed from their contracts with government. Retaining doctors, nurses and midwives in remote areas requires a good understanding of health worker preferences. Methods The article reports on a discrete choice experiment (DCE) carried out amongst 441 health workers, including 173 doctors, 150 nurses and 118 midwives. Qualitative methods were conducted during the design phase. The attributes which emerged were wages, skills upgrading/specialisation, location, working conditions, transportation and housing. Findings One of the main findings of the study is the relative lack of importance of wages for doctors, which could be linked to high intrinsic motivation, perceptions of having an already highly paid job (relative to local conditions), and/or being in a relatively early stage of their career for most respondents. Professional development provides the highest satisfaction with jobs, followed by the working conditions. Doctors with less experience, males and the unmarried are more flexible about location. For nurses and midwives, skill upgrading emerged as the most cost effective method. Conclusions The study is the first of its kind conducted in Timor-Leste. It provides policy-relevant information to balance financial and non-financial incentives for different cadres and profiles of staff. It also augments a thin literature on the preferences of working doctors (as opposed to medical students) in low and middle income countries and provides insights into the ability to instil motivation to work in rural areas, which may be influenced by rural recruitment and Cuban-style training, with its emphasis on community service.Our Research Report for 2000-2002 reflects an outstanding level of achievement throughout the institution and demonstrates once again our high level of commitment to strategic and applied research particularly in areas that enhance the quality of life.Funding: The authors thank the Australian Department of Foreign Affairs and Trade and the European Commission for their financial support.sch_iih11pub4608pub1

Immunodeficiency, autoimmune thrombocytopenia and enterocolitis caused by autosomal recessive deficiency of PIK3CD-encoded phosphoinositide 3-kinase δ.

Phosphoinositide 3-kinase δ (PI3Kδ), a lipid kinase consisting of a catalytic (p110δ, encoded by PIK3CD) and a regulatory subunit (p85, encoded by PIK3R1), generates the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP3) in the plasma membrane of leukocytes downstream of antigen and cytokine receptors.1 Signaling via PDK1, AKT, mTOR and downstream targets such as FOXO1, contributes to the metabolic and transcriptional changes required for the expansion, differentiation and effector function of lymphocytes. Activating germline mutations in PIK3CD cause the immune dysregulatory disease activated PI3Kδ syndrome (APDS), usually presenting with recurrent sinopulmonary infections in childhood, herpesvirus infections and CD4+ lymphopenia, underscoring the important role of balanced p110δ activity in human adaptive immunity. Ablation of p110δ in mice leads to aberrant T cell responses and intestinal inflammation. In humans, immune dysregulation including severe colitis is present in many cancer patients who are treated with the p110δ-specific inhibitor Idelalisib. Recently, one patient with autosomal recessive deficiency of p85α and two patients with loss-of function mutations in p110δ have been described who developed humoral immunodeficiency and colitis

Телемедицина: перспективы развития

Необходимость развития в условиях цифровой экономики такого направления как телемедицина кажется необходимостью, однако существует противоречие между существующими проблемами в системе организации здравоохранения Российской Федерации и возможностями доступности к услугам телемедицины. Анализ показал, что данное направление востребовано, необходимо, существует ряд сервисов, предлагающих услуги по телемедицине, однако нормативно-правовая база не позволяет в полной мере организовать полноценную работу по предоставлению телемедицинских услуг, в том числе, бесплатных

What do health workers in Timor-Leste want, know and do? Findings from a national health labour market survey

Background The objectives of this study were to understand the labour market dynamics among health workers, including their preferences and concerns, and to assess the skills, competence and performance (i.e. the 'know-do gap') of doctors working in Timor-Leste. Methods This cross-sectional survey was implemented in all 13 districts of Timor-Leste in 2014. We surveyed 443 health workers, including 175 doctors, 150 nurses and 118 midwives (about 20% of the health workers in the country). We also observed 632 clinical consultations with doctors, including 442 direct clinical observations, and tested 190 vignettes. Results The study highlights some positive findings, including the gender balance of health workers overall, the concentration of doctors in rural areas, the high overall reported satisfaction of staff with their work and high motivation, the positive intention to stay in the public sector, the feeling of being well prepared by training for work, the relatively frequent and satisfactory supervisions, and the good attitudes towards patients as identified in observations and vignettes. However, some areas require more investigations and investments. The overall clinical performance of the doctors was very good in terms of attitude and moderate in regard to history taking, health education and treatment. However, the average physical examination performance score was low. Doctors performed better with simulated cases than the real cases in general, which means they have better knowledge and skills than they actually demonstrated. The factors that were significantly associated with the clinical performance of doctors were location of the health facility (urban doctors were better) and consultation time (cases with more consultation time were better). Regression analysis suggests that lack of knowledge was significantly associated with lack of performance, while lack of motivation and equipment were not significant. Conclusions The survey provides essential information for workforce planning and for developing training policies and terms and conditions that will attract and retain health workers in rural service. Improving the work environment and performance of doctors working in rural health facilities and ensuring compliance with clinical protocols are two priority areas needed to improve the performance of doctors in Timor-Leste.sch_iih14pub4622pub

Defective Leukocyte Adhesion and Chemotaxis Contributes to Combined Immunodeficiency in Humans with Autosomal Recessive MST1 Deficiency.

PURPOSE: To investigate the clinical and functional aspects of MST1 (STK4) deficiency in a profoundly CD4-lymphopenic kindred with a novel homozygous nonsense mutation in STK4. Although recent studies have described the cellular effects of murine Mst1 deficiency, the phenotype of MST1-deficient human lymphocytes has yet to be fully explored. Patient lymphocytes were therefore investigated in the context of current knowledge of murine Mst1 deficiency. METHODS: Genetic etiology was identified by whole exome sequencing of genomic DNA from two siblings, combined with linkage analysis in the wider family. MST1 protein expression was assessed by immunoblotting. The ability of patient lymphocytes to adhere to ICAM-1 under flow conditions was measured, and transwell assays were used to assess chemotaxis. Chemokine receptor expression was examined by flow cytometry and receptor signalling by immunoblotting. RESULTS: A homozygous nonsense mutation in STK4 (c.442C > T, p.Arg148Stop) was found in the patients, leading to a lack of MST1 protein expression. Patient leukocytes exhibited deficient chemotaxis after stimulation with CXCL11, despite preserved expression of CXCR3. Patient lymphocytes were also unable to bind effectively to immobilised ICAM-1 under flow conditions, in keeping with a failure to develop high affinity binding. CONCLUSION: The observed abnormalities of adhesion and migration imply a profound trafficking defect among human MST1-deficient lymphocytes. By analogy with murine Mst1 deficiency and other defects of leucocyte trafficking, this is likely to contribute to immunodeficiency by impairing key aspects of T-cell development and function such as positive selection in the thymus, thymic egress and immune synapse formation in the periphery.This is thepublished version. It first appeared at http://link.springer.com/article/10.1007%2Fs10875-016-0232-2

New and recurrent gain-of-function STAT1 mutations in patients with chronic mucocutaneous candidiasis from Eastern and Central Europe

Background: Chronic mucocutaneous candidiasis disease (CMCD) may result from various inborn errors of interleukin (IL)-17-mediated immunity. Twelve of the 13 causal mutations described to date affect the coiled-coil domain (CCD) of STAT1. Several mutations, including R274W in particular, are recurrent, but the underlying mechanism is unclear. Objective: To investigate and describe nine patients with CMCD in Eastern and Central Europe, to assess the biochemical impact of STAT1 mutations, to determine cytokines in supernatants of Candida-exposed blood cells, to determine IL-17-producing T cell subsets and to determine STAT1 haplotypes in a family with the c.820C>T (R274W) mutation. Results: The novel c.537C>A (N179K) STAT1 mutation was gain-of-function (GOF) for γ-activated factor (GAF)-dependent cellular responses. In a Russian patient, the cause of CMCD was the newly identified c.854 A>G (Q285R) STAT1 mutation, which was also GOF for GAF-dependent responses. The c.1154C>T (T385M) mutation affecting the DNA-binding domain (DBD) resulted in a gain of STAT1 phosphorylation in a Ukrainian patient. Impaired Candida-induced IL-17A and IL-22 secretion by leucocytes and lower levels of intracellular IL-17 and IL-22 production by T cells were found in several patients. Haplotype studies indicated that the c.820C>T (R274W) mutation was recurrent due to a hotspot rather than a founder effect. Severe clinical phenotypes, including intracranial aneurysm, are presented. Conclusions: The c.537C>A and c.854A>G mutations affecting the CCD and the c.1154C>T mutation affecting the DBD of STAT1 are GOF. The c.820C>T mutation of STAT1 in patients with CMCD is recurrent due to a hotspot. Patients carrying GOF mutations of STAT1 may develop multiple intracranial aneurysms by hitherto unknown mechanisms

Imbalanced Lignin Biosynthesis Promotes the Sexual Reproduction of Homothallic Oomycete Pathogens

Lignin is incorporated into plant cell walls to maintain plant architecture and to ensure long-distance water transport. Lignin composition affects the industrial value of plant material for forage, wood and paper production, and biofuel technologies. Industrial demands have resulted in an increase in the use of genetic engineering to modify lignified plant cell wall composition. However, the interaction of the resulting plants with the environment must be analyzed carefully to ensure that there are no undesirable side effects of lignin modification. We show here that Arabidopsis thaliana mutants with impaired 5-hydroxyguaiacyl O-methyltransferase (known as caffeate O-methyltransferase; COMT) function were more susceptible to various bacterial and fungal pathogens. Unexpectedly, asexual sporulation of the downy mildew pathogen, Hyaloperonospora arabidopsidis, was impaired on these mutants. Enhanced resistance to downy mildew was not correlated with increased plant defense responses in comt1 mutants but coincided with a higher frequency of oomycete sexual reproduction within mutant tissues. Comt1 mutants but not wild-type Arabidopsis accumulated soluble 2-O-5-hydroxyferuloyl-l-malate. The compound weakened mycelium vigor and promoted sexual oomycete reproduction when applied to a homothallic oomycete in vitro. These findings suggested that the accumulation of 2-O-5-hydroxyferuloyl-l-malate accounted for the observed comt1 mutant phenotypes during the interaction with H. arabidopsidis. Taken together, our study shows that an artificial downregulation of COMT can drastically alter the interaction of a plant with the biotic environment