Neurodevelopment and ages of onset in depressive disorders

How and why do clinical depressive disorders emerge in adolescence? In this Personal View, we present a neurodevelopmental theory to address causes for adolescent onsets of clinical depressive disorders. We argue that theories should account for three perplexing aspects of depressive disorders in adolescence: the episodic nature of depression; differences between sexes in rates of depression across development; and age-differentiated onsets. We consider how theories such as psychosocial acceleration, heterochronic brain development, dual-process models, glucocorticoid vulnerability hypothesis linked to early life stress, and epigenetic and genetic susceptibility might explain some aspects of adolescent depressive disorders. We argue that some synthesis between existing theories might be needed to establish a sufficient neurodevelopmental theoretical framework to explain onsets of depressive disorders in adolescence

Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland

background:  Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland. methods:  Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined. results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001). conclusions:  Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer

Defining the structure of the NF-ĸB pathway in human immune cells using quantitative proteomic data

The NF-ĸB transcription factor is a critical regulator of immune homeostasis and inflammatory responses and is a critical factor in the pathogenesis of inflammatory disease. The pathways to NF-ĸB activation are paradigms for signal-induced ubiquitination and proteasomal degradation, control of transcription factor function by subcellular localisation, and the control of gene transcription and physiological processes by signal transduction mechanisms. Despite the importance of NF-ĸB in disease, the NF-ĸB pathway remains unexploited for the treatment of inflammatory disease. Our understanding of NF-ĸB comes mostly from studies of transgenic mice and cell lines where components of the pathway have been deleted or over expressed. Recent advances in quantitative proteomics offer new opportunities to understand the NF-ĸB pathway using the absolute abundance of individual pathway components. We have analysed available quantitative proteomic datasets to establish the structure of the NF-ĸB pathway in human immune cells under both steady state and activated conditions. This reveals a conserved NF-κB pathway structure across different immune cell lineages and identifies important differences to the current model of the NF-ĸB pathway. These include the findings that the IKK complex in most cells is likely to consist predominantly of IKKβ homodimers, that the relative abundancies of IκB proteins show strong cell type variation, and that the components of the non-canonical NF-ĸB pathway are significantly increased in activated immune cells. These findings challenge aspects of our current view of the NF-κB pathway and identify outstanding questions important for defining the role of key components in regulating inflammation and immunity

Mechanical Stress Inference for Two Dimensional Cell Arrays

Many morphogenetic processes involve mechanical rearrangement of epithelial tissues that is driven by precisely regulated cytoskeletal forces and cell adhesion. The mechanical state of the cell and intercellular adhesion are not only the targets of regulation, but are themselves likely signals that coordinate developmental process. Yet, because it is difficult to directly measure mechanical stress {\it in vivo} on sub-cellular scale, little is understood about the role of mechanics of development. Here we present an alternative approach which takes advantage of the recent progress in live imaging of morphogenetic processes and uses computational analysis of high resolution images of epithelial tissues to infer relative magnitude of forces acting within and between cells. We model intracellular stress in terms of bulk pressure and interfacial tension, allowing these parameters to vary from cell to cell and from interface to interface. Assuming that epithelial cell layers are close to mechanical equilibrium, we use the observed geometry of the two dimensional cell array to infer interfacial tensions and intracellular pressures. Here we present the mathematical formulation of the proposed Mechanical Inverse method and apply it to the analysis of epithelial cell layers observed at the onset of ventral furrow formation in the {\it Drosophila} embryo and in the process of hair-cell determination in the avian cochlea. The analysis reveals mechanical anisotropy in the former process and mechanical heterogeneity, correlated with cell differentiation, in the latter process. The method opens a way for quantitative and detailed experimental tests of models of cell and tissue mechanics

Fast versus gradual adaptation of soft daily disposable contact lenses in neophyte wearers

Purpose Despite the widespread practice of gradually adapting all new soft contact lens wearers (neophytes), there is little evidence-based research underpinning such practice. This work determined if a gradual adaptation period is necessary for neophytes when fitted with modern hydrogel or silicone-hydrogel daily disposable contact lenses. Method At four sites, neophytes (19–32 years) were randomly assigned to an adaptation schedule: fast (10 h wear from the first day) or gradual (4 h on the first day, increasing their wear-time by 2 h on each subsequent day until they had reached 10 h) with hydrogel (n = 24 fast; n = 21 gradual) or silicone-hydrogel (n = 10 fast; n = 10 gradual) contact lenses. Masked investigators graded ocular surface physiology and non-invasive tear breakup time (NIBUT). A range of subjective scores (using 0–100 visual analogue scales) were recorded at the initial visit and after 10 h of lens wear, 4–6 days and 12–14 days after initial fitting. Subjective scores were also repeated after 7 days. Results There was no difference (p > 0.05) in ocular surface physiology between the fast and gradual adaptation groups at any time point in either lens type. NIBUT was similar at all time points for both adaptation groups in both lens types with the exception that the gradual adaptation silicone-hydrogel wearers had a slightly longer NIBUT (p = 0.007) than the fast adaptation group at 12-14 days. Subjective scores were also similar across the visits and lens types with the exception of ‘lens awareness’ and ‘ease of lens removal’ which were better (p < 0.05) in the fast compared with the gradual adaptation hydrogel lens group at day 7. Additionally, ‘end-of-day discomfort’ was better (p = 0.02) in the fast compared with the gradual adaptation hydrogel lens group at 12–14 days. Conclusion There appears to be no benefit in daily disposable soft contact lens adaptation for neophytes with modern contact lens materials

Primary care patients reporting concerns about their gambling frequently have other co-occurring lifestyle and mental health issues

BACKGROUND: Problem gambling often goes undetected by family physicians but may be associated with stress-related medical problems as well as mental disorders and substance abuse. Family physicians are often first in line to identify these problems and to provide a proper referral. The aim of this study was to compare a group of primary care patients who identified concerns with their gambling behavior with the total population of screened patients in relation to co-morbidity of other lifestyle risk factors or mental health issues. METHODS: This is a cross sectional study comparing patients identified as worrying about their gambling behavior with the total screened patient population for co morbidity. The setting was 51 urban and rural New Zealand practices. Participants were consecutive adult patients per practice (N = 2,536) who completed a brief multi-item tool screening primary care patients for lifestyle risk factors and mental health problems (smoking, alcohol and drug misuse, problem gambling, depression, anxiety, abuse, anger). Data analysis used descriptive statistics and non-parametric binomial tests with adjusting for clustering by practitioner using STATA survey analysis. RESULTS: Approximately 3/100 (3%) answered yes to the gambling question. Those worried about gambling more likely to be male OR 1.85 (95% CI 1.1 to 3.1). Increasing age reduced likelihood of gambling concerns – logistic regression for complex survey data OR = 0.99 (CI 95% 0.97 to 0.99) p = 0.04 for each year older. Patients concerned about gambling were significantly more likely (all p < 0.0001) to have concerns about their smoking, use of recreational drugs, and alcohol. Similarly there were more likely to indicate problems with depression, anxiety and anger control. No significant relationship with gambling worries was found for abuse, physical inactivity or weight concerns. Patients expressing concerns about gambling were significantly more likely to want help with smoking, other drug use, depression and anxiety. CONCLUSION: Our questionnaire identifies patients who express a need for help with gambling and other lifestyle and mental health issues. Screening for gambling in primary care has the potential to identify individuals with multiple co-occurring disorders

Determination of composition and structure of spongy bone tissue in human head of femur by Raman spectral mapping

Biomechanical properties of bone depend on the composition and organization of collagen fibers. In this study, Raman microspectroscopy was employed to determine the content of mineral and organic constituents and orientation of collagen fibers in spongy bone in the human head of femur at the microstructural level. Changes in composition and structure of trabecula were illustrated using Raman spectral mapping. The polarized Raman spectra permit separate analysis of local variations in orientation and composition. The ratios of ν2PO43−/Amide III, ν4PO43−/Amide III and ν1CO32−/ν2PO43− are used to describe relative amounts of spongy bone components. The ν1PO43−/Amide I ratio is quite susceptible to orientation effect and brings information on collagen fibers orientation. The results presented illustrate the versatility of the Raman method in the study of bone tissue. The study permits better understanding of bone physiology and evaluation of the biomechanical properties of bone

Inter-rater agreement of comorbid DSM-IV personality disorders in substance abusers

<p>Abstract</p> <p>Background</p> <p>Little is known about the inter-rater agreement of personality disorders in clinical settings.</p> <p>Methods</p> <p>Clinicians rated 75 patients with substance use disorders on the DSM-IV criteria of personality disorders in random order, and on rating scales representing the severity of each.</p> <p>Results</p> <p>Convergent validity agreement was moderate (range for r = 0.55, 0.67) for cluster B disorders rated with DSM-IV criteria, and discriminant validity was moderate for eight of the ten personality disorders. Convergent validity of the rating scales was only moderate for antisocial and narcissistic personality disorder.</p> <p>Discussion</p> <p>Dimensional ratings may be used in research studies and clinical practice with some caution, and may be collected as one of several sources of information to describe the personality of a patient.</p