15 research outputs found
Profound Pathogen-Specific Alterations in Intestinal Microbiota Composition Precede Late-Onset Sepsis in Preterm Infants:A Longitudinal, Multicenter, Case-Control Study
BACKGROUND: The role of intestinal microbiota in the pathogenesis of late-onset sepsis (LOS) in preterm infants is largely unexplored but could provide opportunities for microbiota-targeted preventive and therapeutic strategies. We hypothesized that microbiota composition changes before the onset of sepsis, with causative bacteria that are isolated later in blood culture. METHODS: This multicenter case-control study included preterm infants born under 30 weeks of gestation. Fecal samples collected from the 5 days preceding LOS diagnosis were analyzed using a molecular microbiota detection technique. LOS cases were subdivided into 3 groups: gram-negative, gram-positive, and coagulase-negative Staphylococci (CoNS). RESULTS: Forty LOS cases and 40 matched controls were included. In gram-negative LOS, the causative pathogen could be identified in at least 1 of the fecal samples collected 3 days prior to LOS onset in all cases, whereas in all matched controls, this pathogen was absent (P = .015). The abundance of these pathogens increased from 3 days before clinical onset. In gram-negative and gram-positive LOS (except CoNS) combined, the causative pathogen could be identified in at least 1 fecal sample collected 3 days prior to LOS onset in 92% of the fecal samples, whereas these pathogens were present in 33% of the control samples (P = .004). Overall, LOS (expect CoNS) could be predicted 1 day prior to clinical onset with an area under the curve of 0.78. CONCLUSIONS: Profound preclinical microbial alterations underline that gut microbiota is involved in the pathogenesis of LOS and has the potential as an early noninvasive biomarker
New genetic loci link adipose and insulin biology to body fat distribution.
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
Diagnosing ADHD during active substance use:Feasible or flawed?
Background: Attention Deficit Hyperactivity Disorder (ADHD) is highly prevalent in patients with a substance use disorder (SUD). Because of possible problems with validity, diagnostic assessment of ADHD is usually postponed until after a period of abstinence, which may jeopardize adequate and timely treatment. The aim of this study is to investigate how a diagnostic assessment of ADHD in patients who are actively using substances compares to the results of a second assessment after a period of full or partial abstinence. Methods: Prospective test-retest study in a SUD treatment center among 127 treatment seeking adult SUD patients with a comorbid diagnosis of adult ADHD. Conners' Adult ADHD Diagnostic Interview for DSM-IV was administered at intake and after four SUD treatment sessions. Results: The mean time interval between intake and retest assessment was 78 days (SD = 32; range 31-248). At the second ADHD assessment, substance use had decreased to about 50% of baseline consumption. Of the 127 patients with an initial diagnosis of ADHD, 121 patients (95.3%) still fulfilled DSM-IV adult ADHD criteria at re diagnosis. Subtyping of ADHD was less stable (Cohen's Kappa = 0.53). Agreement on the number of childhood and adult ADHD symptoms between both assessments was good (intraclass correlation coefficient of 0.69 and 0.65, respectively). Sensitivity analyses in subgroups of patients who were fully abstinent during the second assessment yielded very similar results. Conclusions: These findings strongly suggest that a pragmatic approach, in which patients are evaluated for ADHD even when they are not (yet) abstinent, is feasible and justifiabl
Integrated cognitive behavioral therapy for ADHD in adult substance use disorder patients: Results of a randomized clinical trial
BACKGROUND: Attention Deficit Hyperactivity Disorder (ADHD) frequently co-occurs with Substance Use Disorders (SUDs). Standard ADHD pharmacotherapies are not effective in patients with this comorbidity and cognitive behavioral therapy (CBT) has not been tested in this population. This RCT aimed to compare the efficacy of Integrated CBT (CBT/Integrated) directed at adult ADHD and SUD with CBT directed at SUD only (CBT/SUD) in patients with SUD and ADHD (SUD + ADHD). METHODS: Randomized clinical trial among 119 SUD + ADHD patients in a SUD treatment center. CBT/Integrated consisted of 15 individual sessions of motivational therapy, coping skills training and relapse prevention for SUD, and training of planning skills, problem-solving skills and dealing with emotions for ADHD. CBT/SUD consisted of 10 individual SUD treatment sessions only. Primary outcome was ADHD symptom severity according to the ADHD rating scale (ARS) at post-treatment. Secondary outcomes included ADHD symptom severity after two-month follow-up, and treatment response (≥30% ADHD symptom reduction), substance use, depressive or anxiety symptoms, and quality of life at post-treatment and follow-up. RESULTS: CBT/Integrated was more effective than CBT/SUD in the reduction of ADHD symptoms post-treatment: ARS = 28.1 (SD 9.0) vs. 31.5 (SD 11.4) (F = 4.739, df = 1, 282, p = .030; d = 0.34). At follow-up, CBT/Integrated still resulted in lower ARS scores than CBT/SUD, but the difference was not significant at the 0.05 level. For other secondary outcomes, including substance use, no significant between-group differences were present. CONCLUSIONS: Compared to regular SUD cognitive behavioral therapy, integrated cognitive behavioral therapy resulted in a significant extra improvement in ADHD symptoms in SUD + ADHD patients
Supervisory dyads' communication and alignment regarding the use of workplace-based observations:a qualitative study in general practice residency
BACKGROUND: In medical residency, performance observations are considered an important strategy to monitor competence development, provide feedback and warrant patient safety. The aim of this study was to gain insight into whether and how supervisor-resident dyads build a working repertoire regarding the use of observations, and how they discuss and align goals and approaches to observation in particular. METHODS: We used a qualitative, social constructivist approach to explore if and how supervisory dyads work towards alignment of goals and preferred approaches to performance observations. We conducted semi-structured interviews with supervisor-resident dyads, performing a template analysis of the data thus obtained. RESULTS: The supervisory dyads did not frequently communicate about the use of observations, except at the start of training and unless they were triggered by internal or external factors. Their working repertoire regarding the use of observations seemed to be primarily driven by patient safety goals and institutional assessment requirements rather than by providing developmental feedback. Although intended as formative, the institutional test was perceived as summative by supervisors and residents, and led to teaching to the test rather than educating for purposes of competence development. CONCLUSIONS: To unlock the full educational potential of performance observations, and to foster the development of an educational alliance, it is essential that supervisory dyads and the training institute communicate clearly about these observations and the role of assessment practices of- and for learning, in order to align their goals and respective approaches
Muramyl dipeptide–induced differential gene expression in NOD2 mutant and wild-type crohnʼs disease patient–derived dendritic cells
A synthesis of radial growth patterns preceding tree mortality
Tree mortality is a key factor influencing forest functions and dynamics, but our understanding of the mechanisms leading to mortality and the associated changes in tree growth rates are still limited. We compiled a new pan-continental tree-ring width database from sites where both dead and living trees were sampled (2970 dead and 4224 living trees from 190 sites, including 36 species), and compared early and recent growth rates between trees that died and those that survived a given mortality event. We observed a decrease in radial growth before death in ca. 84% of the mortality events. The extent and duration of these reductions were highly variable (1–100 years in 96% of events) due to the complex interactions among study species and the source(s) of mortality. Strong and long-lasting declines were found for gymnosperms, shade- and drought-tolerant species, and trees that died from competition. Angiosperms and trees that died due to biotic attacks (especially bark-beetles) typically showed relatively small and short-term growth reductions. Our analysis did not highlight any universal trade-off between early growth and tree longevity within a species, although this result may also reflect high variability in sampling design among sites. The intersite and interspecific variability in growth patterns before mortality provides valuable information on the nature of the mortality process, which is consistent with our understanding of the physiological mechanisms leading to mortality. Abrupt changes in growth immediately before death can be associated with generalized hydraulic failure and/or bark-beetle attack, while long-term decrease in growth may be associated with a gradual decline in hydraulic performance coupled with depletion in carbon reserves. Our results imply that growth-based mortality algorithms may be a powerful tool for predicting gymnosperm mortality induced by chronic stress, but not necessarily so for angiosperms and in case of intense drought or bark-beetle outbreaks