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BACKGROUND This study aims to investigate effectiveness of a 6-week, transdiagnostic cognitive behavioral therapy (CBT) for anxiety and depression in adolescents, the Structured Material for Therapy (SMART), in naturalistic settings of child and adolescent mental health outpatient services (CAMHS). METHODS A randomized controlled trial with waiting list control (WLC) was performed at three community CAMHS in Norway. Referred adolescents (N = 163, age = 15.72, 90.3% girls) scoring 6 or more on the emotional disorders subscale of the Strengths and Difficulties Questionnaire (SDQ) were randomly assigned to SMART or to WLC. RESULTS In the treatment group (CBT), 32.9% improved in the main outcome measure (SDQ), compared to 11.6% in the WLC. Clinically significant and reliable change was experienced by 17.7% in the CBT condition, compared to 5.8% in the WLC. No patients deteriorated. Statistically significant treatment effects were achieved for internalization symptoms, anxiety symptoms and general functioning. CONCLUSIONS These promising findings indicate that SMART may be considered as a first step in a stepped care model for anxiety and/or depression treatment in CAMHS. The recovery rates imply that further investigations into the effectiveness of brief treatments should be made. Furthermore, there is a need for more comprehensive second-stage treatments for some of these patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT02150265. First registered May 292,014.BACKGROUND Medical specialty is a critical choice in a physician's life because it determines their professional future and medical practice. While some are motivated to choose a specific specialty based on the monetary gain it can provide, others are inspired by seeing the work performed by a physician or by a patient's recovery. It is common to stereotype doctors' personalities by their specialty. METHODS This was a cross-sectional survey study in which we administered the 100-item HEXACO Personality Inventory-Revised to 292 medical students between September 2018 and March 2019. We evaluated six different domains of personality traits. We also included questions about their medical specialty of choice, their least preferred specialty, and the motivation behind these choices. The participants included 175 women (59.9%) and 117 men (40.1%). RESULTS When the participants were asked about their preferred type of medical specialty, 52.4% indicated a preference for surgical specialties (surgical group) vs 47.6% who preferred clinical specialties (clinical group). We found that the surgical group showed significantly higher scores for Extraversion and Organization domains, while the clinical group showed significantly higher scores on the Honesty-Humility, Emotionality, and Agreeableness domains. We identified critical differences within the overall group of medical students by their medical specialty preference. CONCLUSIONS Some classical stereotypes were confirmed by our results, such as surgical specialists tending to be more extroverted and organized, whereas clinical specialists were prone to being more introverted, anxious, and more emotionally attached to their patients.BACKGROUND Insecticide resistance is a growing concern for malaria control and vector control effectiveness relies on assessing it distribution and understanding its evolution. METHODS We assessed resistance levels and the frequencies of two major target-site mutations, L1014F-VGSC and G119S-ace-1, conferring resistance to pyrethroids (PYRs) and carbamates/organophosphates (CXs/OPs) insecticides. These data were compared to those acquired between 2006 and 2010 to follow resistance evolutionary trends over ten years. RESULTS We report the results of a 3-year survey (2013-2015) of insecticide resistance in 13 localities across the whole country of Benin. Permethrin (PYR) resistance was found in all populations tested, L1014F-VGSC being almost fixed everywhere, while bendiocarb resistance was limited to a few localities, G119S-ace-1 remaining rare, with very limited variations during surveyed period. Interestingly, we found no effect of the type of insecticide pressure on the dynamics of these mutations. CONCLUSIONS These results confirm both the high prevalence of PYR resistance and the potential of CXs/OPs as short- to medium-term alternatives in Benin. They also underline the need for regular resistance monitoring and informed management in their usage, as the G119S-ace-1 mutation is already present in Benin and surrounding countries. Their unwise usage would rapidly lead to its spread, which would jeopardize PYR-resistant Anopheles control.BACKGROUND Skin fibrosis is the clinical hallmark of systemic sclerosis (SSc), where collagen deposition and remodeling of the dermis occur over time. The most widely used outcome measure in SSc clinical trials is the modified Rodnan skin score (mRSS), which is a semi-quantitative assessment of skin stiffness at seventeen body sites. However, the mRSS is confounded by obesity, edema, and high inter-rater variability. In order to develop a new histopathological outcome measure for SSc, we applied a computer vision technology called a deep neural network (DNN) to stained sections of SSc skin. We tested the hypotheses that DNN analysis could reliably assess mRSS and discriminate SSc from normal skin. METHODS We analyzed biopsies from two independent (primary and secondary) cohorts. One investigator performed mRSS assessments and forearm biopsies, and trichrome-stained biopsy sections were photomicrographed. We used the AlexNet DNN to generate a numerical signature of 4096 quantitative image features (QIFs) for 1icantly correlated with mRSS (R = 0.70 [training], 0.55 [test]). The DNN-derived Fibrosis Score significantly correlated with 4S (R = 0.69, p = 3 × 10- 17). CONCLUSIONS DNN analysis of SSc biopsies is an unbiased, quantitative, and reproducible outcome that is associated with validated SSc outcomes.BACKGROUND Oral squamous cell carcinoma (OSCC) is associated with high morbidity and ranks sixth among malignancies worldwide. Increasing evidence suggests that microRNAs (miRNAs or miRs) play a critical role in regulating cancer stem cells (CSCs), which drive the proliferation and spread of OSCC. Therefore, based on the alteration of aberrantly expressed miR-495 and homeobox C6 (HOXC6) by Gene Expression Omnibus (GEO) analysis, we subsequently explore the potential effect of miR-495 on the progression of CSCs in OSCC. METHODS After the isolation of CSCs from the clinical tissue samples of OSCC patients, the expression of miR-495 and HOXC6 was determined, followed by the validation of the relationship between miR-495 and HOXC6. Subsequently, gain- and loss-function approach was performed to detect the role of miR-495 and HOXC6 in cell proliferation, migration, invasion, cell cycle entry, apoptosis, and epithelial-mesenchymal transition (EMT) of CSCs in OSCC, as well as the tumor growth in vivo. RESULTS HOXC6 was highly expressed while miR-495 was poorly expressed in OSCC. HOXC6 was verified to be a target gene of miR-495, and miR-495 could inhibit the activation of the TGF-β signaling pathway. CSCs with miR-495 overexpression or HOXC6 silencing exhibited reversed EMT process; reduced abilities of proliferation, migration, and invasion; and promoted cell apoptosis in vitro. Moreover, inhibited tumor growth was observed in vivo after injection with miR-495 agomir or sh-HOXC6. In contrast, the downregulation of miR-495 showed an induced role in the progression of OSCC. CONCLUSION These findings suggest that miR-495 may suppress HOXC6 to inhibit EMT, proliferation, migration, and invasion while promoting apoptosis of CSCs in OSCC by inhibiting the TGF-β signaling pathway.BACKGROUND Generalized anxiety disorder (GAD) is a persistent and common mental disorder that entails significant impairments in role functioning and quality of life. Currently available effective interventions include psychological therapies, self-help approaches, and pharmacological treatments, which do not quite meet clinical needs, and the ideal anxiolytic is still being sought. Shu-gan-qing-re (SGQR) formula, a Chinese patent medicine, has been well received by patients with GAD in Chinese clinical practice for years. The present prospective, double-blind, double-dummy, randomized controlled trial is designed to investigate the efficacy and safety of SGQR formula for GAD. METHODS/DESIGN A total of 200 eligible participants will be recruited from four hospitals in different parts of China. They will be randomly assigned to either the study group or the control group in a ratio of 11. Participants allocated to the study group will receive SGQR formula and buspirone placebo, while buspirone and SGQR placebo will be applied in the control group. Six scheduled visits will be conducted over the course of 8 weeks. Outcome measurements include Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale-17 (HAMD-17), Clinical Global Impression-Improvement Scale (CGI-I), Traditional Chinese Medicine Syndrome Scale for GAD, and pro-inflammatory cytokine tests interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha. Ruxotemitide Adverse reactions will be evaluated by using the Treatment Emergent Symptom Scale (TESS). Safety outcomes and adverse events will also be recorded. DISCUSSION The study will provide scientific and objective assessments for the efficacy and safety of SGQR formula for patients with GAD, hopefully offering clinicians an alternative approach to GAD. TRIAL REGISTRATION Chinese Clinical Trial Registry, ID ChiCTR-IPR-17013058. Registered on October 20, 2017.BACKGROUND Proving that specific genes are essential for the intracellular viability of Leishmania parasites within macrophages remains a challenge for the identification of suitable targets for drug development. This is especially evident in the absence of a robust inducible expression system or functioning RNAi machinery that works in all Leishmania species. Currently, if a target gene of interest in extracellular parasites can only be deleted from its genomic locus in the presence of ectopic expression from a wild type copy, it is assumed that this gene will also be essential for viability in disease-promoting intracellular parasites. However, functional essentiality must be proven independently in both life-cycle stages for robust validation of the gene of interest as a putative target for chemical intervention. METHODS Here, we have used plasmid shuffle methods in vivo to provide supportive genetic evidence that N-myristoyltransferase (NMT) is essential for Leishmania viability throughout the parasite life-cycle. Following confirmation of NMT essentiality in vector-transmitted promastigotes, a range of mutant parasites were used to infect mice prior to negative selection pressure to test the hypothesis that NMT is also essential for parasite viability in an established infection. RESULTS Ectopically-expressed NMT was only dispensable under negative selection in the presence of another copy. Total parasite burdens in animals subjected to negative selection were comparable to control groups only if an additional NMT copy, not affected by the negative selection, was expressed. CONCLUSIONS NMT is an essential gene in all parasite life-cycle stages, confirming its role as a genetically-validated target for drug development.

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