In the last decade, Internet usage has grown tremendously on a global scale. The increasing popularity and frequency of Internet use has led to an increasing number of reports highlighting the ...potential negative consequences of overuse. Over the last decade, research into Internet addiction has proliferated. This paper reviews the existing 68 epidemiological studies of Internet addiction that (i) contain quantitative empirical data, (ii) have been published after 2000, (iii) include an analysis relating to Internet addiction, (iv) include a minimum of 1000 participants, and (v) provide a full-text article published in English using the database Web of Science. Assessment tools and conceptualisations, prevalence, and associated factors in adolescents and adults are scrutinised. The results reveal the following. First, no gold standard of Internet addiction classification exists as 21 different assessment instruments have been identified. They adopt official criteria for substance use disorders or pathological gambling, no or few criteria relevant for an addiction diagnosis, time spent online, or resulting problems. Second, reported prevalence rates differ as a consequence of different assessment tools and cut-offs, ranging from 0.8% in Italy to 26.7% in Hong Kong. Third, Internet addiction is associated with a number of sociodemographic, Internet use, and psychosocial factors, as well as comorbid symptoms and disorder in adolescents and adults. The results indicate that a number of core symptoms (i.e., compulsive use, negative outcomes and salience) appear relevant for diagnosis, which assimilates Internet addiction and other addictive disorders and also differentiates them, implying a conceptualisation as syndrome with similar etiology and components, but different expressions of addictions. Limitations include the exclusion of studies with smaller sample sizes and studies focusing on specific online behaviours. Conclusively, there is a need for nosological precision so that ultimately those in need can be helped by translating the scientific evidence established in the context of Internet addiction into actual clinical practice.
Adolescents and young adults frequently experience mental disorders, yet tend not to seek help. This systematic review aims to summarise reported barriers and facilitators of help-seeking in young ...people using both qualitative research from surveys, focus groups, and interviews and quantitative data from published surveys. It extends previous reviews through its systematic research methodology and by the inclusion of published studies describing what young people themselves perceive are the barriers and facilitators to help-seeking for common mental health problems.
Twenty two published studies of perceived barriers or facilitators in adolescents or young adults were identified through searches of PubMed, PsycInfo, and the Cochrane database. A thematic analysis was undertaken on the results reported in the qualitative literature and quantitative literature.
Fifteen qualitative and seven quantitative studies were identified. Young people perceived stigma and embarrassment, problems recognising symptoms (poor mental health literacy), and a preference for self-reliance as the most important barriers to help-seeking. Facilitators were comparatively under-researched. However, there was evidence that young people perceived positive past experiences, and social support and encouragement from others as aids to the help-seeking process.
Strategies for improving help-seeking by adolescents and young adults should focus on improving mental health literacy, reducing stigma, and taking into account the desire of young people for self-reliance.
Adolescents and young adults experience a high level of mental disorders, yet tend not to seek help. Research indicates that there are many barriers and facilitators to help-seeking for young people ...in the general community. However there are limited data available for young elite athletes. This study aims to determine what young elite athletes perceive as the barriers and facilitators to help-seeking for common mental health problems.
Fifteen elite athletes aged 16-23 years each participated in one of three focus group discussions. In addition to written data, verbal responses were audio taped, transcribed and thematically analysed.
Participants' written and verbal data suggested that stigma was the most important perceived barrier to seeking help for young elite athletes. Other notable barriers were a lack of mental health literacy, and negative past experiences of help-seeking. Facilitators to help-seeking were encouragement from others, having an established relationship with a provider, pleasant previous interactions with providers, the positive attitudes of others, especially their coach, and access to the internet.
Intervention strategies for improving help-seeking in young elite athletes should focus on reducing stigma, increasing mental health literacy, and improving relations with potential providers.
Cytotoxic T lymphocytes (CTLs) use polarized secretion to rapidly destroy virally infected and tumor cells. To understand the temporal relationships between key events leading to secretion, we used ...high-resolution 4D imaging. CTLs approached targets with actin-rich projections at the leading edge, creating an initially actin-enriched contact with rearward-flowing actin. Within 1 min, cortical actin reduced across the synapse, T cell receptors (TCRs) clustered centrally to form the central supramolecular activation cluster (cSMAC), and centrosome polarization began. Granules clustered around the moving centrosome within 2.5 min and reached the synapse after 6 min. TCR-bearing intracellular vesicles were delivered to the cSMAC as the centrosome docked. We found that the centrosome and granules were delivered to an area of membrane with reduced cortical actin density and phospholipid PIP2. These data resolve the temporal order of events during synapse maturation in 4D and reveal a critical role for actin depletion in regulating secretion.
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•4D imaging elucidates the order of events leading to secretion•Actin depletion initiates events leading to centrosome polarization and secretion•Lattice light-sheet imaging reveals a rearward flow of actin away from the synapse•Both centrosome and granules are delivered to an area of membrane depleted of actin
The key sequence of events by which cytotoxic T lymphocytes establish an immunological synapse to kill target cells remains unclear. Griffiths and colleagues have resolved this by using high-resolution 4D imaging, revealing a critical role for actin reorganization in initiating centrosome polarization and granule secretion.
The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) has proposed treatment ...targets in 2015 for adult patients with inflammatory bowel disease (IBD). We aimed to update the original STRIDE statements for incorporating treatment targets in both adult and pediatric IBD.
Based on a systematic review of the literature and iterative surveys of 89 IOIBD members, recommendations were drafted and modified in 2 surveys and 2 voting rounds. Consensus was reached if ≥75% of participants scored the recommendation as 7 to 10 on a 10-point rating scale.
In the systematic review, 11,278 manuscripts were screened, of which 435 were included. The first IOIBD survey identified the following targets as most important: clinical response and remission, endoscopic healing, and normalization of C-reactive protein/erythrocyte sedimentation rate and calprotectin. Fifteen recommendations were identified, of which 13 were endorsed. STRIDE-II confirmed STRIDE-I long-term targets of clinical remission and endoscopic healing and added absence of disability, restoration of quality of life, and normal growth in children. Symptomatic relief and normalization of serum and fecal markers have been determined as short-term targets. Transmural healing in Crohn’s disease and histological healing in ulcerative colitis are not formal targets but should be assessed as measures of the remission depth.
STRIDE-II encompasses evidence- and consensus-based recommendations for treat-to-target strategies in adults and children with IBD. This frameworkshould be adapted to individual patients and local resources to improve outcomes.
The interstellar medium of the Milky Way is multiphase, magnetized and turbulent. Turbulence in the interstellar medium produces a global cascade of random gas motions, spanning scales ranging from ...100 parsecs to 1,000 kilometres (ref. 4). Fundamental parameters of interstellar turbulence such as the sonic Mach number (the speed of sound) have been difficult to determine, because observations have lacked the sensitivity and resolution to image the small-scale structure associated with turbulent motion. Observations of linear polarization and Faraday rotation in radio emission from the Milky Way have identified unusual polarized structures that often have no counterparts in the total radiation intensity or at other wavelengths, and whose physical significance has been unclear. Here we report that the gradient of the Stokes vector (Q, U), where Q and U are parameters describing the polarization state of radiation, provides an image of magnetized turbulence in diffuse, ionized gas, manifested as a complex filamentary web of discontinuities in gas density and magnetic field. Through comparison with simulations, we demonstrate that turbulence in the warm, ionized medium has a relatively low sonic Mach number, M(s) ≲ 2. The development of statistical tools for the analysis of polarization gradients will allow accurate determinations of the Mach number, Reynolds number and magnetic field strength in interstellar turbulence over a wide range of conditions.
Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe ...plaque psoriasis.
In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).
The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept.
Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
Tezepelumab in Adults with Uncontrolled Asthma Corren, Jonathan; Parnes, Jane R; Wang, Liangwei ...
The New England journal of medicine,
09/2017, Letnik:
377, Številka:
10
Journal Article
Recenzirano
Odprti dostop
In some patients with moderate-to-severe asthma, particularly those with noneosinophilic inflammation, the disease remains uncontrolled. This trial evaluated the efficacy and safety of tezepelumab ...(AMG 157/MEDI9929), a human monoclonal antibody specific for the epithelial-cell-derived cytokine thymic stromal lymphopoietin (TSLP), in patients whose asthma remained uncontrolled despite treatment with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids.
In this phase 2, randomized, double-blind, placebo-controlled trial, we compared subcutaneous tezepelumab at three dose levels with placebo over a 52-week treatment period. The primary end point was the annualized rate of asthma exacerbations (events per patient-year) at week 52.
The use of tezepelumab at a dose of 70 mg every 4 weeks (low dose; 145 patients), 210 mg every 4 weeks (medium dose; 145 patients), or 280 mg every 2 weeks (high dose; 146 patients) resulted in annualized asthma exacerbation rates at week 52 of 0.26, 0.19, and 0.22, respectively, as compared with 0.67 in the placebo group (148 patients). Thus, exacerbation rates in the respective tezepelumab groups were lower by 61%, 71%, and 66% than the rate in the placebo group (P<0.001 for all comparisons). Similar results were observed in patients regardless of blood eosinophil counts at enrollment. The prebronchodilator forced expiratory volume in 1 second at week 52 was higher in all tezepelumab groups than in the placebo group (difference, 0.12 liters with the low dose P=0.01, 0.11 liters with the medium dose P=0.02, and 0.15 liters with the high dose P=0.002). A total of 2 patients in the medium-dose group, 3 in the high-dose group, and 1 in the placebo group discontinued the trial regimen because of adverse events.
Among patients treated with long-acting beta-agonists and medium-to-high doses of inhaled glucocorticoids, those who received tezepelumab had lower rates of clinically significant asthma exacerbations than those who received placebo, independent of baseline blood eosinophil counts. (Funded by MedImmune a member of the AstraZeneca Group and Amgen; PATHWAY ClinicalTrials.gov number, NCT02054130 .).
Thymic stromal lymphopoietin (TSLP), an epithelial cytokine (alarmin), is a central regulator of the immune response to inhaled environmental insults such as allergens, viruses and pollutants, ...initiating a cascade of downstream inflammation. There is compelling evidence that TSLP plays a major role in the pathology of asthma, and therapies that aim to block its activity are in development.
We review studies conducted in humans and human cells, largely published in PubMed January 2010-October 2019, that investigated the innate and adaptive immune mechanisms of TSLP in asthma relevant to type 2-driven (eosinophilic/allergic) inflammation and non-type 2-driven (non-eosinophilic/non-allergic) inflammation, and the role of TSLP as a mediator between immune cells and structural cells in the airway. Clinical data from studies evaluating TSLP blockade are also discussed.
The position of TSLP at the top of the inflammatory cascade makes it a promising therapeutic target in asthma. Systemic anti-TSLP monoclonal antibody therapy with tezepelumab has yielded positive results in clinical trials to date, reducing exacerbations and biomarkers of inflammation in patients across the spectrum of inflammatory endotypes. Inhaled anti-TSLP is an alternative route currently under evaluation. The long-term safety and efficacy of TSLP blockade need to be evaluated.
Abnormal composition of intestinal bacteria—“dysbiosis”—is characteristic of Crohn’s disease. Disease treatments include dietary changes and immunosuppressive anti-TNFα antibodies as well as ...ancillary antibiotic therapy, but their effects on microbiota composition are undetermined. Using shotgun metagenomic sequencing, we analyzed fecal samples from a prospective cohort of pediatric Crohn’s disease patients starting therapy with enteral nutrition or anti-TNFα antibodies and reveal the full complement and dynamics of bacteria, fungi, archaea, and viruses during treatment. Bacterial community membership was associated independently with intestinal inflammation, antibiotic use, and therapy. Antibiotic exposure was associated with increased dysbiosis, whereas dysbiosis decreased with reduced intestinal inflammation. Fungal proportions increased with disease and antibiotic use. Dietary therapy had independent and rapid effects on microbiota composition distinct from other stressor-induced changes and effectively reduced inflammation. These findings reveal that dysbiosis results from independent effects of inflammation, diet, and antibiotics and shed light on Crohn disease treatments.
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•Inflammation, antibiotics, and diet independently affect microbiota in Crohn’s disease•Antibiotics are associated with bacterial dysbiosis and increased fungi•Dysbiosis decreases with reduction in intestinal inflammation•Diet has an independent and rapid effect on gut microbiota composition
Intestinal microbiota dysbiosis is characteristic of Crohn’s disease, but the contributing factors remain unclear. By examining pediatric Crohn’s disease patients, Lewis et al. show that dysbiosis is independently associated with antibiotics, inflammation, and diet and decreases with reduced intestinal inflammation. These results may facilitate biomarker discovery and therapeutic interventions.
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