Psychological distress and related work attendance among small-to-medium enterprise owner/managers: literature review and research agenda

Small-to-medium enterprises (SMEs) may experience the antecedents and consequences of depression more acutely than larger organizations. Managing depression-related sickness absenteeism and presenteeism, and associated productivity loss may also be more challenging because the SME's size and structure make administration, finance, and responsibilities of human resources difficult. This may diminish the growth and long-term sustainability of SME. However, the mental health of the SME workforce is a neglected sector in occupational health research and practice, despite the contribution it makes to developed economies worldwide. This study aims to review the literature on current stress, burnout, and depression, and uses existing knowledge of SME structure and characteristics to propose a theory as to why this may be the case. Further, using the information garnered, it developed a model to guide future research designed to test these assumptions, and inform the development of workplace mental health promotion programmes tailored to the needs of the SME sector.     

Anti-infliximab antibodies in inflammatory bowel disease: prevalence, infusion reactions, immunosuppression and response, a meta-analysis

Infliximab is a chimeric monoclonal antibody directed against tumour necrosis factor-α. When used in inflammatory bowel disease, primary nonresponse is found in at least 10% of patients, with secondary loss of response occurring in a further 10-15% per year. It has been suggested that this may in part be a result of the development of anti-infliximab antibodies (ATIs). The aim of the study was to determine in patients receiving infliximab the prevalence of ATIs, the effect of immunosuppressants on the prevalence of ATI, the effect of ATIs on the prevalence of infusion reactions and the effect of ATIs on the rates of remission. MEDLINE and EMBASE databases were searched from 1948 and 1980, respectively, to October 2011. Eighteen studies involving 3326 patients were included. The prevalence of ATIs was 45.8% when episodic infusions of infliximab were given and 12.4% when maintenance infliximab was given. The rates of infusion reactions were significantly higher in patients with ATIs (relative risk: 2.07; 95% confidence interval, 1.61-2.67). Immunosuppressants resulted in a 50% reduction in the risk of developing ATIs (P<0.00001). However, the presence or absence of ATIs did not affect the rates of clinical remission. The prevalence of ATIs depends on the regimen of infliximab administration and the use of immunosuppressants. Patients who test positive for ATIs are at an increased risk of infusion reactions, but have similar rates of remission compared with patients who test negative for ATIs. Further analysis is required to determine whether loss of response is dependent on the titre of ATIs.     

Ventricular resynchronization is the principle mechanism of benefit with cardiac resynchronization therapy

Although there is little debate over the fact that cardiac resynchronization therapy (CRT) can benefit the majority of patients selected with routine indications, the precise mechanism for improvement may be considered controversial. Among patients selected with New York Heart Association functional class III or IV symptoms, left ventricular ejection fraction ≤35% and electrocardiographic QRS widening of at least 120-130?ms, approximately 60-80% of patients improved depending on the definition of response used. Although a reasonable assumption is that electrocardiographic QRS widening is a surrogate for delays in regional ventricular mechanical activation, a large volume of data has demonstrated that there is a subset of patients with widened QRS complexes who have no significant mechanical dyssynchrony. The reason for dissociation of electrical dispersion and mechanical dyssynchrony is unknown presently, but many studies have demonstrated the association of dyssynchrony with favorable outcome following CRT. Perhaps more importantly, several imaging studies (principally by echocardiography) have shown the lack of baseline mechanical dyssynchrony to be as a marker for a less favorable outcome after CRT. Recently, the lack of dyssynchrony before CRT has been shown to be associated with a significantly lower long-term probability of freedom from death, heart transplantation, or left ventricular assist device placement. As further mechanistic evidence for the relationship of mechanical dyssynchrony and LV functional response to CRT, it has been suggested that patients who failed to improve their tissue Doppler measures of dyssynchrony after CRT have a lower chance of reverse remodeling. This topic has been muddled by technical difficulties in measurement of mechanical dyssynchrony by all imaging approaches, the confounding variable of scar in ischemic disease, and the widely variable definitions of response used by different investigators. However, the weight of evidence from a pathophysiological basis to the recent long-term patient outcome data strongly support the notion that resynchronization is the principle mechanism of benefit from CRT.     

Quantification of CD4+ T Cell Alloreactivity and Its Control by Regulatory T Cells Using Time‐Lapse Microscopy and Immune Synapse Detection

Assays designed to select transplant recipients for immunosuppression withdrawal have met with limited success, perhaps because they measure events downstream of T cell–alloantigen interactions. Using in vitro time‐lapse microscopy in a mouse transplant model, we investigated whether transplant outcome would result in changes in the proportion of CD4⁺ T cells forming prolonged interactions with donor dendritic cells. By blocking CD4–MHC class II and CD28–B7 interactions, we defined immunologically relevant interactions as those ≥500 s. Using this threshold, T cell–dendritic cell (T‐DC) interactions were examined in rejection, tolerance and T cell control mediated by regulatory T cells. The frequency of T‐DC contacts ≥500 s increased with T cells from mice during acute rejection and decreased with T cells from mice rendered unresponsive to alloantigen. Regulatory T cells reduced prolonged T‐DC contacts. Importantly, this effect was replicated with human polyclonally expanded naturally occurring regulatory T cells, which we have previously shown can control rejection of human tissues in humanized mouse models. Finally, in a proof‐of‐concept translational context, we were able to visualize differential allogeneic immune synapse formation in polyclonal CD4⁺ T cells using high‐throughput imaging flow cytometry.     

Anticonvulsant Activity of Diospyros Fischeri Root Extracts

Diospyros fischeri Gurke (Ebenaceae) is used in traditional medicine for the treatment of epilepsy. Dichloromethane, ethylacetate, and ethanol extracts of the roots, at doses between 100 and 1600 mg/kg BW, inhibited convulsions induced by the γ-aminobutyric acid type A (GABAa) receptor antagonist, pentylenetetrazole (PTZ), in a dose dependent manner. The extracts also exhibited low toxicity against brine shrimps giving LC₅₀ values between 45.4 and 95.4 µg/ml. These results provide evidence for the potential of D. fischeri extracts to treat absence seizures, especially given their seemingly innocuous nature.     

Mycobacterium avium subspecies paratuberculosis infection in cases of irritable bowel syndrome and comparison with Crohn's disease and Johne's disease: common neural and immune pathogenicities

Mycobacterium avium subsp. paratuberculosis causes Johne's disease, a systemic infection and chronic inflammation of the intestine that affects many species, including primates. Infection is widespread in livestock, and human populations are exposed. Johne's disease is associated with immune dysregulation, with involvement of the enteric nervous system overlapping with features of irritable bowel syndrome in humans. The present study was designed to look for an association between Mycobacterium avium subsp. paratuberculosis infection and irritable bowel syndrome. Mucosal biopsy specimens from the ileum and the ascending and descending colon were obtained from patients with irritable bowel syndrome attending the University of Sassari, Sassari, Sardinia, Italy. Crohn's disease and healthy control groups were also included. Mycobacterium avium subsp. paratuberculosis was detected by IS900 PCR with amplicon sequencing. Data on the potential risk factors for human exposure to these pathogens and on isolates from Sardinian dairy sheep were also obtained. Mycobacterium avium subsp. paratuberculosis was detected in 15 of 20 (75%) patients with irritable bowel syndrome, 3 of 20 (15%) healthy controls, and 20 of 23 (87%) people with Crohn's disease (P = 0.0003 for irritable bowel syndrome patients versus healthy controls and P = 0.0000 for Crohn's disease patients versus healthy controls). One subject in each group had a conserved single-nucleotide polymorphism at position 247 of IS900 that was also found in isolates from seven of eight dairy sheep. There was a significant association (P = 0.0018) between Mycobacterium avium subsp. paratuberculosis infection and the consumption of hand-made cheese. Mycobacterium avium subsp. paratuberculosis is a candidate pathogen in the causation of a proportion of cases of irritable bowel syndrome as well as in Crohn's disease.