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pioid consumption without causing respiratory depression and may be used to treat postoperative restlessness, agitation, and pain in geriatric patients. However, hemodynamic effects of dexmedetomidine may require close observation for 3 hours following administration in older adult patients.Accumulating evidence strongly indicates that the presence of cancer stem cells (CSCs) leads to the emergence of worse clinical scenarios, such as chemo- and radiotherapy resistance, metastasis, and cancer recurrence. CSCs are a highly tumorigenic population characterized by self-renewal capacity and differentiation potential. Thus, CSCs establish a hierarchical intratumor organization that enables tumor adaptation to evade the immune response and resist anticancer therapy. YY1 functions as a transcription factor, RNA-binding protein, and 3D chromatin regulator. Thus, YY1 has multiple effects and regulates several molecular processes. Emerging evidence indicates that the development of lethal YY1-mediated cancer phenotypes is associated with the presence of or enrichment in cancer stem-like cells. Therefore, it is necessary to investigate whether and to what extent YY1 regulates the CSC phenotype. Since CSCs mirror the phenotypic behavior of stem cells, we initially describe the roles played by YY1 in embryonic and adult stem cells. Next, we scrutinize evidence supporting the contributions of YY1 in CSCs from a number of various cancer types. Finally, we identify new areas for further investigation into the YY1-CSCs axis, including the participation of YY1 in the CSC niche.Pseudomonas aeruginosa is a ubiquitous bacterium, which is able to change its physiological characteristics in response to different habitats. Environmental strains are presumably less pathogenic than clinical strains and whether or not the clinical strains originate from the environment or through inter-host transmission remains poorly understood. To minimize the risk of infection, a better understanding of proteomic profiling of P. aeruginosa is necessary for elucidating the correlation between environmental and clinical strains. Based on antimicrobial susceptibility and patterns of virulence, we selected 12 clinical and environmental strains (i) environmental, (ii) multidrug resistant (MDR) clinical and (iii) susceptible clinical strains. Whole-cell protein was extracted from each strain and subjected to two-dimensional differential gel electrophoresis (2-D DIGE) and liquid chromatography tandem mass spectrometry quadrupole time-of-flight (LC-MS QTOF). All 12 strains were clustered into 3 distinct groups based on their variance in protein expression. A total of 526 matched spots were detected and four differentially expressed protein spots (p less then 0.05) were identified and all differential spots were downregulated in MDR strain J3. Upregulation of chitin binding and BON domain proteins was present in the environmental and some MDR strains, whereas the clinical strains exhibited distinct proteomic profiles with increased expression of serine protein kinase and arginine/ornithine transport ATP-binding proteins. Significant difference in expression was observed between susceptible clinical and MDR strains, as well as susceptible clinical and environmental strains. Transition from an environmental saprophyte to a clinical strain could alter its physiological characteristics to further increase its adaptation.Although advances have been made in facilitating the implementation of evidence-based treatments, little is known about the most effective way to sustain their use over time. The current study examined the sustainability of one evidence-based treatment, Parent-Child Interaction Therapy (PCIT), following a statewide implementation trial testing three training methods Cascading Model, Learning Collaborative, and Distance Education. Participants included 100 clinicians and 50 administrators from 50 organizations across Pennsylvania. Clinicians and administrators reported on sustainability at 24-months, as measured by the number of clients receiving PCIT and the continued use of the PCIT protocol. Multi-level path analysis was utilized to examine the role of training on sustainability. Clinicians and administrators reported high levels of sustainability at 24-months. Clinicians in the Cascading Model reported greater average PCIT caseloads at 24-months, whereas clinicians in the Learning Collaborative reported greater full use of the PCIT protocol at 24-months. Attending consultation calls was associated with delivering PCIT to fewer families. Implications for the sustainable delivery of PCIT beyond the training year as well as for the broader field of implementation science are discussed.To examine the agreement between patient and psychiatrist ratings of subjective well-being in people with schizophrenia using three well-being measurements Satisfaction with Life, Subjective Happiness, and Subjective Well-being under Neuroleptic Treatment (SWN), including the SWN-subscale, and to investigate whether the psychiatrist's judgement or the psychiatrist-rated SWN is better at defining patient well-being. Patients with schizophrenia (n = 150) completed the three well-being measurements, then met psychiatrists, and their well-being was judged as either 'poor' or 'adequate' via the usual clinical assessment before being assessed again by the psychiatrist using the same measurements. Intra-class correlation was used to analyze the absolute agreement between 'patient-rated' and 'psychiatrist-rated' scores. Agreements on 'adequate' well-being status between patient-rated SWN (≥ 80; gold standard), psychiatrist-rated SWN, and psychiatrist's judgement were calculated using Kappa coefficients. We also calculated the sensitivity and specificity of the psychiatrist's judgement and the psychiatrist-rated SWN to define adequate well-being. SWN showed the strongest absolute agreement between patient-psychiatrist ratings (ICC = 0.7, p = 0.005), with physical functioning yielding the highest and self-control the lowest coefficients. The psychiatrist-rated SWN showed a better Kappa coefficient (0.4, p less then 0.001) than the psychiatrist's judgement. Clinical judgement showed a 67% sensitivity and a 64% specificity, whereas the psychiatrist-rated SWN (score 93, AUC 81.4%) showed a 74% sensitivity and a 74% specificity for well-being prediction. The use of SWN by psychiatrists yielded a better alignment of well-being than the psychiatrist's judgement alone. The SWN subscale could help fill the gap between clinician and patient views on well-being. Psychiatrists should upskill in assessing patient wellbeing for appropriate treatment provision.Although some studies have suggested the effectiveness of hyperbaric oxygen (HBO) therapy for hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the role of HBO has not been established. We compared the treatment outcomes of 8 patients with viral HC (adenovirus [ADV], n = 2; BK virus [BKV], n = 6) treated with HBO (HBO[+]) and 8 patients (ADV, n = 2; BKV, n = 6) treated with conventional therapy (HBO[-]), such as urinary catheterization and intravenous cidofovir. HBO therapy was performed at 2.1 atmospheres for 90 min/day until clinical improvement was achieved. The median number of HBO treatments was 10 (range 8-12). The median duration of HBO treatment was 19.5 days (range 10-23 days). All 8 HBO(+) patients achieved complete remission (CR) at a median of 14.5 days (range 5-25 days). Of the 8 HBO(-) patients, 5 (62.5%) obtained CR and 3 remained symptomatic for 2-6 months. learn more The cumulative incidence of transplant-related mortality at day 100 after allogeneic HSCT was significantly higher in the HBO(-) patients than in the HBO(+) patients (14.2 vs. 0%, P less then 0.05). No severe HBO-related adverse effects were observed. In conclusion, HBO is a feasible option for treating viral HC after allogeneic HSCT.
The risk of contrast-induced nephropathy (CIN) is high in patients with chronic kidney disease (CKD). However, the mechanism of CIN in CKD is not fully understood. Here, we prepared a clinically relevant model of CIN and examined the role of necroptosis, which potentially cross-talks with autophagy, in CIN.
In Sprague-Dawley rats, CKD was induced by subtotal nephrectomy (SNx, 5/6 nephrectomy) 4weeks before induction of CIN. CIN was induced by administration of a contrast medium (CM), iohexol, following administration of indomethacin and N-omega-Nitro-L-arginine methyl ester. Renal function and tissue injuries were assessed 48h after CM injection.
Serum creatinine (s-Cre) and BUN were increased from 0.28 ± 0.01 to 0.52 ± 0.02mg/dl and from 15.1 ± 0.7 to 29.2 ± 1.2mg/dl, respectively, after SNx alone. CM further increased s-Cre and BUN to 0.69 ± 0.03 and 37.2 ± 2.1, respectively. In the renal tissue after CM injection, protein levels of receptor-interacting serine/threonine-protein kinase (RIP) 1, RIP3, cleaved caspase 3, and caspase 8 were increased by 64 ~ 212%, while there was reduction in LC3-II and accumulation of p62. Necrostatin-1, an RIP1 inhibitor, administered before and 24h after CM injection significantly suppressed elevation of s-Cre, BUN and urinary albumin levels, kidney injury molecule-1 expression and infiltration of CD68-positive macrophages in renal tissues after CM injection.
The results suggest that necroptosis of proximal tubular cells contributes to CIN in CKD and that suppression of protective autophagy by pro-necroptotic signaling may also be involved.
The results suggest that necroptosis of proximal tubular cells contributes to CIN in CKD and that suppression of protective autophagy by pro-necroptotic signaling may also be involved.
Fatigue is a distressing symptom commonly reported among pediatric patients with primary immunodeficiency (PID). However, the relationship between fatigue and disease activity is currently unknown.
In this cross-sectional study, we examined the prevalence of severe fatigue, the effect of fatigue on health-related quality of life (HRQoL), and the effects of disease activity and comorbidity on fatigue severity among pediatric patients 2-18years of age with PID. Fatigue and HRQoL were assessed using the pediatric quality of life inventory multidimensional fatigue scale (PedsQL MFS) and generic core scales (PedsQL GCS), respectively. Linear regression analyses and an analysis of covariance were used to compare the fatigue scores with the scores obtained from a healthy control group. Data were adjusted for age and sex.
Of the 91 eligible patients, 79 were assessed (87% participation rate), with a mean age of 10.4 ± 4.4years. Pediatric patients with PID reported significantly higher fatigue levels compared toof pediatric patients with PID reported experiencing severe fatigue, and fatigue was reported among a wide range of PID subcategories. In addition, severe fatigue negatively affected the patient's quality of life and daily functioning, but was not associated with disease activity or comorbidity. Thus, targeting severe fatigue might be a promising strategy for improving the overall well-being and quality of life of pediatric patients with PID.
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