Although cognitive behavioural therapy (CBT) is claimed to be effective in schizophrenia, major depression and bipolar disorder, there have been negative findings in well-conducted studies and ...meta-analyses have not fully considered the potential influence of blindness or the use of control interventions.
We pooled data from published trials of CBT in schizophrenia, major depression and bipolar disorder that used controls for non-specific effects of intervention. Trials of effectiveness against relapse were also pooled, including those that compared CBT to treatment as usual (TAU). Blinding was examined as a moderating factor.
CBT was not effective in reducing symptoms in schizophrenia or in preventing relapse. CBT was effective in reducing symptoms in major depression, although the effect size was small, and in reducing relapse. CBT was ineffective in reducing relapse in bipolar disorder.
CBT is no better than non-specific control interventions in the treatment of schizophrenia and does not reduce relapse rates. It is effective in major depression but the size of the effect is small in treatment studies. On present evidence CBT is not an effective treatment strategy for prevention of relapse in bipolar disorder.
Regulation of respiratory mucosal immunity by microbial-derived metabolites has been a proposed mechanism that may provide airway protection. Here we examine the effect of oral Lactobacillus ...johnsonii supplementation on metabolic and immune response dynamics during respiratory syncytial virus (RSV) infection. L. johnsonii supplementation reduced airway T helper type 2 cytokines and dendritic cell (DC) function, increased regulatory T cells, and was associated with a reprogrammed circulating metabolic environment, including docosahexanoic acid (DHA) enrichment. RSV-infected bone marrow-derived DCs (BMDCs) from L. johnsonii-supplemented mice had altered cytokine secretion, reduced expression of co-stimulatory molecules, and modified CD4+ T-cell cytokines. This was replicated upon co-incubation of wild-type BMDCs with either plasma from L. johnsonii-supplemented mice or DHA. Finally, airway transfer of BMDCs from L. johnsonii-supplemented mice or with wild-type derived BMDCs pretreated with plasma from L. johnsonii-supplemented mice reduced airway pathological responses to infection in recipient animals. Thus L. johnsonii supplementation mediates airway mucosal protection via immunomodulatory metabolites and altered immune function.
Periglacial soils are one of the least studied ecosystems on Earth, yet they are widespread and are increasing in area due to retreat of glaciers worldwide. Soils in these environments are cold and ...during the brief summer are exposed to high levels of UV radiation and dramatic fluctuations in moisture and temperature. Recent research suggests that these environments harbor immense microbial diversity. Here we use sequencing of environmental DNA, culturing of isolates, and analysis of environmental variables to show that members of the Chytridiomycota (chytrids) dominate fungal biodiversity and perhaps decomposition processes in plant-free, high-elevation soils from the highest mountain ranges on Earth. The zoosporic reproduction of chytrids requires free water, yet we found that chytrids constituted over 70% of the ribosomal gene sequences of clone libraries from barren soils of the Himalayas and Rockies; by contrast, they are rare in other soil environments. Very few chytrids have been cultured, although we were successful at culturing chytrids from high-elevation sites throughout the world. In a more focused study of our sites in Colorado, we show that carbon sources that support chytrid growth (eolian deposited pollen and microbial phototrophs) are abundant and that soils are saturated with water for several months under the snow, thus creating ideal conditions for the development of a chytrid-dominated ecosystem. Our work broadens the known biodiversity of the Chytridomycota, and describes previously unsuspected links between aquatic and terrestrial ecosystems in alpine regions.
Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) have previously shown that dietary patterns are observable by 3 years. However, it is not clear when dietary patterns emerge. We ...aimed to describe dietary patterns in early life and their associations with maternal and infant sociodemographic characteristics.
Principal component analysis was applied to diet questionnaires of ALSPAC participants at 6 months (n = 7052) and 15 months (n = 5610) to extract dietary patterns. The sociodemographic factors associated with dietary patterns were investigated using regression analyses.
Four dietary patterns were extracted at both 6 and 15 months. A traditional-style pattern characterized by home-prepared meats, vegetables and desserts, a second pattern characterized by ready-prepared baby foods and a third pattern characterized by discretionary foods such as biscuits, sweets and crisps were identified at both ages. At 6 months, the fourth pattern was characterized predominantly by breastfeeding and at 15 months, by contemporary-style foods including herbs, legumes, nuts, raw fruit and vegetables. Higher maternal age and education, number of siblings and lower body mass index (BMI) was associated with higher scores on the breastfeeding or meat, vegetables and desserts patterns, whereas higher discretionary food pattern scores were associated with younger maternal age, lower education, higher BMI and more siblings. Associations between sociodemographic factors and the ready-prepared baby food pattern scores were inconsistent across ages.
Dietary patterns emerge from infancy and are associated with sociodemographic characteristics.
Background: High resolution computed tomography (HRCT) has an important diagnostic role in idiopathic interstitial pneumonia (IIP). We hypothesised that the HRCT appearance would have an impact on ...survival in patients with IIP. Methods: HRCT scans from patients with histological usual interstitial pneumonia (UIP; n=73) or histological non-specific interstitial pneumonia (NSIP; n=23) were characterised as definite UIP, probable UIP, indeterminate, probable NSIP, or definite NSIP. Cox regression analysis examined the relationships between histopathological and radiological diagnoses and mortality, controlling for patient age, sex, and smoking status. Results: All 27 patients with definite or probable UIP on HRCT had histological UIP; 18 of 44 patients with probable or definite NSIP on HRCT had histological NSIP. Patients with HRCT diagnosed definite or probable UIP had a shorter survival than those with indeterminate CT (hazards ratio (HR) 2.43, 95% CI 1.06 to 5.58; median survival 2.08 v 5.76 years) or HRCT diagnosed definite or probable NSIP (HR 3.47, 95% CI 1.58 to 7.63; median survival 2.08 v 5.81 years). Patients with histological UIP with no HRCT diagnosis of probable or definite UIP fared better than patients with histological UIP and an HRCT diagnosis of definite or probable UIP (HR 0.49, 95% CI 0.25 to 0.98; median survival 5.76 v 2.08 years) and worse than those with a histological diagnosis of NSIP (HR 5.42, 95% CI 1.25 to 23.5; median survival 5.76 v >9 years). Conclusions: Patients with a typical HRCT appearance of UIP experience the highest mortality. A surgical lung biopsy is indicated for patients without an HRCT appearance of UIP to differentiate between histological UIP and NSIP.
The intensity of major storm events generated within the Atlantic Basin is projected to rise with the warming of the oceans, which is likely to exacerbate coastal erosion. Nature-based flood defence ...has been proposed as a sustainable and effective solution to protect coastlines. However, the ability of natural ecosystems to withstand major storms like tropical hurricanes has yet to be thoroughly tested. Seagrass meadows both stabilise sediment and attenuate waves, providing effective coastal protection services for sandy beaches. To examine the tolerance of Caribbean seagrass meadows to extreme storm events, and to investigate the extent of protection they deliver to beaches, we employed a combination of field surveys, biomechanical measurements and wave modelling simulations. Field surveys of seagrass meadows before and after a direct hit by the category 5 Hurricane Irma documented that established seagrass meadows of
Thalassia testudinum
remained unaltered after the extreme storm event. The flexible leaves and thalli of seagrass and calcifying macroalgae inhabiting the meadows were shown to sustain the wave forces that they are likely to experience during hurricanes. In addition, the seagrass canopy and the complex biogeomorphic landscape built by the seagrass meadows combine to significantly dissipate extreme wave forces, ensuring that erosion is minimised within sandy beach foreshores. The persistence of the Caribbean seagrass meadows and their coastal protection services during extreme storm events ensures that a stable coastal ecosystem and beach foreshore is maintained in tropical regions.
The objective of the study was to characterize the timing and trends of select mitigation policies, changes in community mobility, and coronavirus disease 2019 (COVID-19) epidemiology in Australia, ...Japan, Hong Kong, and Singapore.
Prospective abstraction of publicly available mitigation policies obtained from media reports and government websites.
Data analyzed include seven kinds of mitigation policies (mass gathering restrictions, international travel restrictions, passenger screening, traveler isolation/quarantine, school closures, business closures, and domestic movement restrictions) implemented between January 1 and April 26, 2020, changes in selected measures of community mobility assessed by Google Community Mobility Reports data, and COVID-19 epidemiology in Australia, Japan, Hong Kong, and Singapore.
During the study period, community mobility decreased in Australia, Japan, and Singapore; there was little change in Hong Kong. The largest declines in mobility were seen in places that enforced mitigation policies. Across settings, transit-associated mobility declined the most and workplace-associated mobility the least. Singapore experienced an increase in cases despite the presence of stay-at-home orders, as migrant workers living in dormitories faced challenges to safely quarantine.
Public policies may have different impacts on mobility and transmission of severe acute respiratory coronavirus-2 transmission. When enacting mitigation policies, decision makers should consider the possible impact of enforcement measures, the influence on transmission of factors other than movement restrictions, and the differential impact of mitigation policies on subpopulations.
Patients with idiopathic interstitial pneumonias (IIPs) can be subdivided into groups based on the histological appearance of lung tissue obtained by surgical biopsy. The quantitative impact of ...histological diagnosis, baseline factors and response to therapy on survival has not been evaluated. Surgical lung biopsy specimens from 168 patients with suspected IIP were reviewed according to the latest diagnostic criteria. The impact of baseline clinical, physiological, radiographic and histological features on survival was evaluated using Cox regression analysis. The predictive value of honeycombing on high-resolution computed tomography (HRCT) as a surrogate marker for usual interstitial pneumonia (UIP) was examined. The response to therapy and survival of 39 patients treated prospectively with high-dose prednisone was evaluated. The presence of UIP was the most important factor influencing mortality. The risk ratio of mortality when UIP was present was 28.46 (95% confidence interval (CI) 5.5-148.0; p=0.0001) after controlling for patient age, duration of symptoms, radiographic appearance, pulmonary physiology, smoking history and sex. Honeycombing on HRCT indicated the presence of UIP with a sensitivity of 90% and specificity of 86%. Patients with nonspecific interstitial pneumonia were more likely to respond or remain stable (9 of 10) compared to patients with UIP (14 of 29) after treatment with prednisone. Patients remaining stable had the best prognosis. The risk ratio of mortality for stable patients compared to nonresponders was 0.32 (95% CI 0.11-0.93; p=0.04) in all patients and 0.33 (95% CI 0.12-0.96; p=0.04) in patients with UIP. The histological diagnosis of usual interstitial pneumonia is the most important factor determining survival in patients with suspected idiopathic interstitial pneumonia. The presence of honeycombing on high-resolution computed tomography is a good surrogate for usual interstitial pneumonia and could be utilized in patients unable to undergo surgical lung biopsy. Patients with nonspecific interstitial pneumonia are more likely to respond or remain stable following a course of prednisone. Patients remaining stable following prednisone therapy have the best prognosis.
Epithelial cells must adhere to the extracellular matrix (ECM) for survival, as detachment from matrix triggers apoptosis or anoikis. Integrins are major mediators of adhesion between cells and ECM ...proteins, and transduce signals required for cell survival. Recent evidence suggests that integrin receptors are coupled to growth factor receptors in the regulation of multiple biological functions; however, mechanisms involved in coordinate regulation of cell survival are poorly understood and mediators responsible for anoikis have not been well characterized. Here, we identify the pro-apoptotic protein Bim as a critical mediator of anoikis in epithelial cells. Bim is strongly induced after cell detachment and downregulation of Bim expression by RNA interference (RNAi) inhibits anoikis. Detachment-induced expression of Bim requires a lack of β1-integrin engagement, downregulation of EGF receptor (EGFR) expression and inhibition of Erk signalling. Overexpressed EGFR was uncoupled from integrin regulation, resulting in the maintenance of Erk activation in suspension, and a block in Bim expression and anoikis. Thus, Bim functions as a key sensor of integrin and growth factor signals to the Erk pathway, and loss of such coordinate regulation may contribute to tumour progression.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Immunosuppressant drugs such as cyclosporin have allowed widespread organ transplantation, but their utility remains limited
by toxicities, and they are ineffective in chronic management of ...autoimmune diseases such as multiple sclerosis. In contrast,
the immune modulating drug FTY720 is efficacious in a variety of transplant and autoimmune models without inducing a generalized
immunosuppressed state and is effective in human kidney transplantation. FTY720 elicits a lymphopenia resulting from a reversible
redistribution of lymphocytes from circulation to secondary lymphoid tissues by unknown mechanisms. Using FTY720 and several
analogs, we show now that FTY720 is phosphorylated by sphingosine kinase; the phosphorylated compound is a potent agonist
at four sphingosine 1-phosphate receptors and represents the therapeutic principle in a rodent model of multiple sclerosis.
Our results suggest that FTY720, after phosphorylation, acts through sphingosine 1-phosphate signaling pathways to modulate
chemotactic responses and lymphocyte trafficking.
PDF
