Therapist competence ratings in relation to clinical outcome in cognitive therapy of depression.

This study reports on the relationship of therapist competence to the outcome of cognitive-behavioral treatment in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Outpatients suffering from major depressive disorder were treated by cognitive-behavioral therapists at each of 3 U.S. sites using a format of 20 sessions in 16 weeks. Findings provide some support for the relationship of therapist competence (as measured by the Cognitive Therapy Scale) to reduction of depressive symptomatology when controlling for therapist adherence and facilitative conditions. The results are, however, not as strong or consistent as expected. The component of competence that was most highly related to outcome is a factor that reflects the therapist's ability to structure the treatment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tumor-Derived Small Extracellular Vesicles Induce Pro-Inflammatory Cytokine Expression and PD-L1 Regulation in M0 Macrophages via IL-6/STAT3 and TLR4 Signaling Pathways

Tumor-associated macrophages play a key role in promoting tumor progression by exerting an immunosuppressive phenotype associated with the expression of programmed cell death ligand 1 (PD-L1). It is well known that tumor-derived small extracellular vesicles (SEVs) affect the tumor microenvironment, influencing TAM behavior. The present study aimed to examine the effect of SEVs derived from colon cancer and multiple myeloma cells on macrophage functions. Non-polarized macrophages (M0) differentiated from THP-1 cells were co-cultured with SEVs derived from a colorectal cancer (CRC) cell line, SW480, and a multiple myeloma (MM) cell line, MM1.S. The expression of PD-L1, interleukin-6 (IL-6), and other inflammatory cytokines as well as of the underlying molecular mechanisms were evaluated. Our results indicate that SEVs can significantly upregulate the expressions of PD-L1 and IL-6 at both the mRNA and protein levels and can activate the STAT3 signaling pathway. Furthermore, we identified the TLR4/NF-kB pathway as a convergent mechanism for SEV-mediated PD-L1 expression. Overall, these preliminary data suggest that SEVs contribute to the formation of an immunosuppressive microenvironment.     

Impact of enzyme inactivation conditions during the generation of whey protein hydrolysates on their physicochemical and bioactive properties

The thermal inactivation conditions (75 °C × 35 min, 80 °C × 10 min, 85 °C × 5 min and 90 °C × 5 min) for Protamex? following bovine whey protein concentrate (WPC) hydrolysis was studied with the view to limiting WPC hydrolysate (WPH) aggregation while maintaining bioactivity. A decrease in the amount of large WPH aggregates formed was observed at inactivation temperatures ≤85 °C. However, the WPC appeared to be more hydrolysed on heating at 75 °C × 35 min, as Protamex? was active for longer under these heating conditions. Significantly (P < 0.05), higher WPH antioxidant (oxygen radical absorbance capacity – ORAC) activity was obtained on inactivation at temperatures ≤80 °C. In contrast, the dipeptidyl peptidase IV (DPP‐IV) inhibitory properties of all WPH samples were similar (P > 0.05). A reduction in thermal treatment from 90 °C × 5 min to 85 °C × 5 min was sufficient to decrease the amount of large aggregates formed in the hydrolysate without altering its bioactive properties.     

Impact assessment of push-pull pest management on incomes,productivity and poverty among smallholder households in Eastern Uganda

The paper evaluates the impact of adoption of push-pull technology (PPT) on household welfare in terms of productivity, incomes and poverty status measured through per-capita food consumption in eastern Uganda. Push-pull is a habitat management strategy for the integrated management of stemborers, striga weeds and poor soil fertility involving the use of a natural repellent (push) and an attractant (pull). This biological technology simultaneously reduces the impact of three major production constraints to cereal-livestock farming in Africa ? pests, weeds and poor soil. Cross sectional survey data were collected from 560 households in four districts in the region (Busia, Tororo, Bugiri and Pallisa), in November and December 2014. Generalized propensity scoring (GPS) was used to determine the intensity of adoption of the technology (i.e., land area allocated to PPT) and also to estimate the dose-response function (DRF) relating intensity of adoption and household welfare. Results revealed that with increased intensity of reported adoption of PPT, the probability of being poor declined through increased maize yield per unit area, incomes, and per capita food consumption. However, its impact varied with the intensity of adoption. With an increase in the area allocated to PPT from 0.025 to 1 acre, average maize yield per unit area increased from 27 kg to 1400 kg, average household income increased from 135 US$ (Uganda Shilling (USh) 370,000) to 273 US$ (USh 750,000) and per capita food consumption increased from 15 US$ (USh 40,000) to 27 US$ (USh 75,000). The average probability of a household being poor (below a rural poverty line of US$ 12.71) declined from 48% to 28%. These findings imply that increased investment in the dissemination and expansion of PPT is essential for poverty reduction among smallholder farmers in Uganda.     

Caspase-1 Inhibition Impacts the Formation of Chondrogenic Nodules,and the Expression of Markers Related to Osteogenic Differentiation and Lipid Metabolism

Caspase-1, as the main pro-inflammatory cysteine protease, was investigated mostly with respect to inflammation-related processes. Interestingly, caspase-1 was identified as being involved in lipid metabolism, which is extremely important for the proper differentiation of chondrocytes. Based on a screening investigation, general caspase inhibition impacts the expression of Cd36 in chondrocytes, the fatty acid translocase with a significant impact on lipid metabolism. However, the engagement of individual caspases in the effect has not yet been identified. Therefore, the hypothesis that caspase-1 might be a candidate here appears challenging. The primary aim of this study thus was to find out whether the inhibition of caspase-1 activity would affect Cd36 expression in a chondrogenic micromass model. The expression of Pparg, a regulator Cd36, was examined as well. In the caspase-1 inhibited samples, both molecules were significantly downregulated. Notably, in the treated group, the formation of the chondrogenic nodules was apparently disrupted, and the subcellular deposition of lipids and polysaccharides showed an abnormal pattern. To further investigate this observation, the samples were subjected to an osteogenic PCR array containing selected markers related to cartilage/bone cell differentiation. Among affected molecules, Bmp7 and Gdf10 showed a significantly increased expression, while Itgam, Mmp9, Vdr, and Rankl decreased. Notably, Rankl is a key marker in bone remodeling/homeostasis and thus is a target in several treatment strategies, including a variety of fatty acids, and is balanced by its decoy receptor Opg (osteoprotegerin). To evaluate the effect of Cd36 downregulation on Rankl and Opg, Cd36 silencing was performed using micromass cultures. After Cd36 silencing, the expression of Rankl was downregulated and Opg upregulated, which was an inverse effect to caspase-1 inhibition (and Cd36 upregulation). These results demonstrate new functions of caspase-1 in chondrocyte differentiation and lipid metabolism-related pathways. The effect on the Rankl/Opg ratio, critical for bone maintenance and pathology, including osteoarthritis, is particularly important here as well.     

Long-Term Efficacy of Intranasal Esketamine in Treatment-Resistant Major Depression: A Systematic Review

Esketamine (ESK) has been approved as a rapid-acting intranasal treatment for treatment-resistant depression (TRD). Although existing studies have investigated the efficacy of ESK in the 4-week induction phase, our knowledge about long-term ESK efficacy remains poor. The aim of this systematic review was to summarize the available data on long-term ESK efficacy for TRD. A systematic search was performed including articles in English, up to 31 March 2021. The search found 7 relevant studies, involving 1024 adult TRD patients. Continuing treatment with ESK after the 4-week induction phase may be associated with stable efficacy in relapse prevention among TRD patients. Conversely, the long-term antidepressant effectiveness upon discontinuation of ESK might be limited, although data from three studies had a moderate to high risk of bias. Overall, the results on the effectiveness of this compound in the long term are mixed. According to our findings, ESK treatment should be continued following the induction phase to reach a stable efficacy in relapse prevention, while the long-term antidepressant and anti-suicidal effects of ESK after discontinuation are inconsistent. Currently, the level of proof of ESK efficacy in long-term TRD treatment remains low and more RCTs with larger sample sizes and active comparators are needed.     

Comparison of Mono- and Di-Saccharides Release in Aqueous Solutions by Raw or Fried Dice of Onion (Allium Cepa L.) Bulbs using Quantitative Nuclear Magnetic Resonance (qNMR)

ABSTRACT:  Although onion bulb tissues, either raw or thermally processed, are widely used as culinary ingredients in homes, in restaurants, and in the food industry, especially for sauces, little is known about the chemical constituents released from such systems. To get a straightforward and fast analysis of sugars released from onion dice soaked in model aqueous solutions, quantitative nuclear magnetic resonance (qNMR) spectroscopy was applied, and the effect of a preliminary thermal processing in oil was investigated. Soaking of raw or fried onion bulb dice at room temperature was followed for 11 d as a model of long-term storage. For the Armstrong cultivar, the extracted dry matter (in milligrams per gram of fresh weight) as well as the content in 3 sugars (glucose, fructose, and sucrose) increased up to a maximum after about 48 h of soaking. Frying induces no measurable new water-soluble compounds. However, extraction kinetics are different (about 3 times faster with frying). Using additional microscopic studies, a possible extraction mechanism is proposed: compounds from sap—including sugars—would diffuse through conductive tissue channels.     

Atomic force microscopy with nanoscale cantilevers resolves different structural conformations of the DNA double helix

Structural variability and flexibility are crucial factors for biomolecular function. Here we have reduced the invasiness and enhanced the spatial resolution of atomic force microscopy (AFM) to visualize, for the first time, different structural conformations of the two polynucleotide strands in the DNA double helix, for single molecules under near-physiological conditions. This is achieved by identifying and tracking the anomalous resonance behavior of nanoscale AFM cantilevers in the immediate vicinity of the sample.     

Why CCR5 is chosen as the target for stem cell gene therapy for HIV infection?

Since the first case reported in 1981, more than 60 million individuals have succumbed to HIV worldwide. Although great efforts have been put forth in developing therapeutic drugs and effective vaccines for the treatment and prevention of HIV infection, these efforts are not correlated to the reported case of cured HIV infection. The first case of cured HIV infection, from allogenic stem cell transplantation, may shed light on future prevention and therapy of HIV infection. The choice of gene target, however, must first be evaluated regarding stem cell based gene therapy for HIV infection. Out of the tens of genes that had shown anti-HIV infection potentials, CCR5 was described to be effective in stem cell based gene therapy in 2005. Here, we appreciate the clinical observations that directly led to the choice of CCR5, rather than other genes for stem cell gene therapy.