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ound the time of epilepsy diagnosis and better care coordination for epilepsy and comorbidities, to reduce hospitalization costs and the economic burden of epilepsy care.Transplant-associated thrombotic microangiopathy (TA-TMA) is a specific complication of allogeneic hematopoietic cell transplantation with a multifactorial etiology. There is little evidence published regarding the efficacy and factors influencing the outcome of substitution of calcineurin inhibitors (CNIs) with other agentsas a widely accepted practice in this disorder; however, there are limited data on the options for immunosuppression manipulation (ISM). In our study, we retrospectively analyzed outcomes of 45 patients with TA-TMA with ISM and substitution either with steroids (steroid group) or anmTOR inhibitor sirolimus (sirolimus group). In our study, sirolimus was associated with significantly better 1-year overall survival (HR 0.3, 95% CI 0.13-0.7, p = .004) and faster time to normalization of LDH (HR 2.2, 95% CI 0.99-4.99, p = .044). Replacing CNIs with sirolimus could be an effective option in patients with TA-TMA. A multicenter confirmatory study of CNIs replacement with sirolimus is justified.
Outcomes of ABO-incompatible living donor kidney transplantation (ABOi LDKT) in older individuals have not been established.
This multicentric observational study, using data from the Korean Organ Transplantation Registry database, included 634 older patients (≥60years) undergoing kidney transplantation. We compared clinical outcomes of ABOi LDKT (n=80) with those of ABO-compatible LDKT (ABOc LDKT, n=222) and deceased donor kidney transplantation (DDKT, n=332) in older patients.
Death-censored graft survival was similar between the three groups (P=0.141). Patient survival after ABOi LDKT was similar to that after ABOc LDKT (P=0.489) but higher than that after DDKT (P=0.038). In multivariable analysis, ABOi LDKT was not risk factor (hazard ratio [HR] 1.73, 95% confidence interval [CI] 0.29-10.38, P=0.548), while DDKT was significant risk factor (HR 3.49, 95% CI 1.01-12.23, P=0.049) for patient survival. Although ABOi LDKT showed higher biopsy-proven acute rejection than ABOc LDKT, the difference was not significant after adjustment with covariates. However, ABOi LDKT was significant risk factor for infection (HR 1.66, 95% CI 1.12-2.45, P=0.012).
In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.
In older patients, ABOi LDKT was not inferior to ABOc LDKT and was superior to DDKT for patient survival. ABOi LDKT can be recommended for older patients, rather than waiting for DDKT.
To assess seizure and cognitive outcomes and their predictors in children (<16years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers.
This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed-effect models corrected for multiple comparisons.
We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow-up (FU) was significantly higher in children (P=.006 and<.0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short- vs long-term FU. The only variables consistently associated with cltors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome.
To predict intrapartum fetal compromise (FC) and admission to neonatal intensive care unit (NICU) by cerebroplacental ratio (CPR) in term pregnancies.
A prospective observational study recruited women with singleton, term pregnancies. Ultrasound (US) was done for fetal biometry, umbilical and middle cerebral artery (UA, MCA) Doppler parameters, and CPR calculated. Intrapartum variables and neonatal data were recorded.
Mean interval from US to delivery was 2.21±2.71days. Rate of operative delivery for FC was 17.47%. Multivariate logistic regression analysis showed that UA pulsatility index (PI) multiples of median (MoM) (P=0.001), MCA PI MoM (P=0.001), and CPR MoM (P=0.001) were significantly and independently associated with operative delivery for FC. Similarly, UA PI MoM (P=0.004), MCA PI MoM (P=0.009), and CPR MoM (P=0.003) were also significantly and independently associated with admission to the NICU. Rate of operative delivery for presumed FC was higher in approprate-for-gestational-age fetuses with low CPR than in small-for-gestational-age fetuses with normal CPR (43.1% and 37.5%, respectively).
Lower mean CPR and CPR MoM were independently associated with the need for operative delivery for presumed FC and NICU admission at term. CPR is more likely to be associated with FC due to placental insufficiency than birth weight.
Lower mean CPR and CPR MoM were independently associated with the need for operative delivery for presumed FC and NICU admission at term. CPR is more likely to be associated with FC due to placental insufficiency than birth weight.Mentoring has experienced a tremendous upswing over the past decades, which has only recently slowed down somewhat. One possible factor explaining mentoring's popularity are numerous case studies suggesting that it is one of the most effective ways of helping individuals to develop. Meta-analyses indicating effect sizes for mentoring that are below what would theoretically be possible appear to contradict the success stories, however. This circumstance raises questions about the professionalization of mentoring practices. We focus on seven key issues for future efforts at professionalizing mentoring. Key issues 1 and 2 address observation of the state of the art within formal mentoring when programs are planned and implemented the consideration of recent research and of best practices. While both areas can overlap, they provide complementary sources of pertinent information for the professionalization of mentoring. Key issues 3-6 address the need to align mentoring activities to the specific context and goals of individual mentoring programs by observing idiographic program characteristics, mentoring dynamics, the orchestration of mentoring goals, and the provision of mentoring resources. Finally, key issue 7 highlights ongoing evaluation as the basis of the effective, continuous improvement of mentoring programs.
This study aimed to assess the levels of fear and uncertainty regarding the spread of coronavirus disease 2019among Jouf University students and to explore the factors influencing those fears and uncertainties.
This was a cross-sectional study of 416 undergraduate students who used an electronic questionnaire. Fear and intolerance of uncertainty scales were used to assess students' fear and uncertainty.
Results indicated a positive correlation between fear and intolerance of uncertainty, and a negative correlation between the level of knowledge and fear. Gender, age, and type of college emerged as significant predictors of fear.
Developing strategies to respond positively to students' worries and fears and proactively help them to solve their problems and guide them in preparing a plan for the future.
Developing strategies to respond positively to students' worries and fears and proactively help them to solve their problems and guide them in preparing a plan for the future.Investigations in the area of tumor-derived extracellular vesicles (EVs) open a new horizon in developing cancer biology and its potential as cancer biomarkers. Following this prospect, we aimed to identify that the role of successfully isolated EVs from drug-resistance cells in the progression of non-small-cell lung cancer (NSCLC). P-EVs and R-EVs secreted by A549 cells and drug-resistant A549-R cells respectively were extracted and characterized. The targeting relationship between miR-425 and MED1 was verified. Cell proliferation, invasion, migration and apoptosis after treatment of P-EVs, R-EVs, miR-425 inhibitor, miR-425 mimic, pcDNA-MED1, or phosphatidylinositol-3-kinase (PI3K)/AKT inhibitor LY294002 were detected. Furthermore, xenograft tumor in nude mice was established for further confirming our in vitro findings. P-EVs and R-EVs were successfully extracted and could be internalized by A549 cells. A549-R cells and R-EVs showed higher miR-425 expression compared with A549 cells and P-EVs, respectively. miR-425 delivered by R-EVs could promote the proliferation, migration, and invasion, while inhibit apoptosis of NSCLC cells. MED1 was the target gene of miR-425. EVs-encapsulated miR-425-derived from A549-R cells could promote the progression of NSCLC in vivo through regulating DAPK1-medicated PI3K/AKT pathway. Moreover, miR-425 delivered by R-EVs promoted tumorigenesis in vivo. https://www.selleckchem.com/products/homoharringtonine.html Taken together, the result suggested that EVs-delivered miR-425-derived from A549-R cells promoted the progression of NSCLC through regulating DAPK1-medicated PI3K/AKT signaling pathway.A variety of findings from in vitro experiments and animal models support the hypothesis that one contribution to pathogenesis in Alzheimer's disease (AD) is enhanced phosphorylation of tau protein, which may be triggered by amyloid β (Aβ) and mediated by impaired activity of the PI3K/Akt signaling pathway. A number of tyrosine phosphatases act to reduce PI3K/Akt activity, and inhibition of tyrosine phosphatases is protective against Aβ toxicity in cell cultures and whole animals. Results from analysis of exome sequenced late onset AD cases and controls similarly show that rare coding variants predicted to damage PI3K functioning increase AD risk, whereas those which are predicted to damage genes for tyrosine phosphatase genes are protective. Taken together, these results support the proposition that tyrosine phosphatase antagonists might be trialed as therapeutic agents to protect against the development of AD.
An objective of the phase 3 HELP Study was to investigate the effect of lanadelumab on health-related quality of life (HRQoL) in patients with hereditary angioedema (HAE).
Patients with HAE-1/2 received either lanadelumab 150mg every 4weeks (q4wks; n=28), 300mg q4wks (n=29), 300mg every 2weeks (q2wks; n=27), or placebo (n=41) for 26weeks (days 0-182). The Angioedema Quality of Life Questionnaire (AE-QoL) was administered monthly, consisting of four domain (functioning, fatigue/mood, fears/shame, nutrition) and total scores. The generic EQ-5D-5L questionnaire was administered on days 0, 98, and 182. Comparisons were made between placebo and (a) all lanadelumab-treated patients and (b) individual lanadelumab groups for changes in scores (day 0-182) and proportions achieving the minimal clinically important difference (MCID, -6) in AE-QoL total score.
Compared with the placebo group, the lanadelumab total group demonstrated significantly greater improvements in AE-QoL total and domain scores (mean change, -13.