Josephgunter7596
Reduced-intensity conditioning regimens using fludarabine (Flu) and cyclophosphamide (Cy) have been widely used in hematopoietic cell transplantation (HCT) recipients. The optimal exposure of these agents remains to be determined. We aimed to delineate the exposure-outcome associations of Flu and Cy separately and then both combined on HCT outcomes. This is a single-center, observational, pharmacokinetic (PK)-pharmacodynamic (PD) study of Flu and Cy in HCT recipients age ≥18 years who received Cy (50 mg/kg in a single dose), Flu (150 to 200 mg/m2 given as 5 daily doses), and total body irradiation (TBI; 200 cGy). We measured trough concentrations of 9-β-D-arabinosyl-2-fluoradenine (F-ara-A), an active metabolite of Flu, on days -5 and -4 (F-ara-ADay-5 and F-ara-ADay-4, respectively), and measured phosphoramide mustard (PM), the final active metabolite of Cy, and estimated the area under the curve (AUC). The 89 enrolled patients had a nonrelapse mortality (NRM) of 9% (95% confidence interval [CI], 3% to 15%) at day +100 and 15% (95% CI, 7% to 22%) at day +180, and an overall survival (OS) of 73% (95% CI, 63% to 81%) at day +180. Glesatinib nmr In multivariate analysis, higher PM area under the curve (AUC) for 0 to 8 hours (PM AUC0-8 hr) was an independent predictor of worse NRM (P 16-fold higher NRM. These results warrant further investigation to optimize reduced-intensity regimens based on better PK-PD understanding and possible adaptation to predictable factors influencing drug clearance.Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice. MLIF administration down-regulated systemic inflammatory mediators such as IFN-γ, TNF-α, IL-6, CXCL2, and CCL2, as well as the in situ expression of TNF-α in the brain. In the same way, MLIF reduced the expression of CD31, CD36, CD54, and CD106 in the cerebral endothelium of infected animals and prevented the sequestration of iRBC and leucocytes in the brain microvasculature. Furthermore, MLIF inhibited the activation of astrocytes and microglia and preserved the integrity of the blood-brain barrier (BBB). In conclusion, our results demonstrated that the administration of MLIF increased survival and conferred neuroprotection by decreasing neuroinflammation in murine CM.
Electroconvulsive therapy is an important somatic treatment for severe mental disorders with established efficacy and safety. However, data on the relationship between ECT and the readmission rate of patients with schizophrenia are scarce. This study will explore the association between the administration of ECT and readmission rates using a machine learning method.
Inpatient medical records from the year of 2016 in one large psychiatric hospital in Beijing, China, were analyzed using a machine learning algorithm to determine the most important variables affecting readmission of patients with schizophrenia.
The medical records of 2131 inpatients with schizophrenia were reviewed. 1099 patients were followed up within 3 months of their index admission (642 ECT cases and 457 non-ECT cases) and 1032 patients were followed up within 6 months (596 ECT cases and 436 non-ECT cases) after discharge. The 3- and 6-month readmission rates in the ECT group (11.37% and 17.94%, respectively) were significantly lower than that of the patients who did not receive ECT (18.79% and 29.36%, respectively, both p<0.001). The risk of readmission was significantly associated with male sex, older age, being married, having a lower income, a shorter inpatient length of stay, and receiving specific antipsychotic medications including olanzapine, paliperidone, clozapine, and haloperidol during the index admission. In the ECT group, patients who received 9 or more treatments were significantly less likely to be readmitted.
Receiving ECT may be associated with a lower risk of readmission in patients with schizophrenia.
Receiving ECT may be associated with a lower risk of readmission in patients with schizophrenia.The insect renal (Malpighian) tubules are functionally homologous to the mammalian kidney. Accumulating evidence indicates that renal tubule crystals form in a manner similar to mammalian kidney stones. In Drosophila melanogaster, crystals can be induced by diet, toxic substances, or genetic mutations that reflect circumstances influencing or eliciting kidney stones in mammals. Incredibly, many mammalian proteins have distinct homologs in Drosophila, and the function of most homologs have been demonstrated to recapitulate their mammalian and human counterparts. Here, we discuss the present literature establishing Drosophila as a nephrolithiasis model. This insect model may be used to investigate and understand the etiology of kidney stone diseases, especially with regard to calcium oxalate, calcium phosphate and xanthine or urate crystallization.
A strong association of obesity and insulin resistance with increased circulating levels of branched-chain and aromatic amino acids and decreased glycine levels has been recognized in human subjects for decades.
More recently, human metabolomics and genetic studies have confirmed and expanded upon these observations, accompanied by a surge in preclinical studies that have identified mechanisms involved in the perturbation of amino acid homeostasis- how these events are connected to dysregulated glucose and lipid metabolism, and how elevations in branched-chain amino acids (BCAA) may participate in the development of insulin resistance, type 2 diabetes (T2D), and other cardiometabolic diseases and conditions.
In human cohorts, BCAA and related metabolites are now well established as among the strongest biomarkers of obesity, insulin resistance, T2D, and cardiovascular diseases. Lowering of BCAA and branched-chain ketoacid (BCKA) levels by feeding BCAA-restricted diet or by the activation of the rate-limid (BCKA) levels by feeding BCAA-restricted diet or by the activation of the rate-limiting enzyme in BCAA catabolism, branched-chain ketoacid dehydrogenase (BCKDH), in rodent models of obesity have clear salutary effects on glucose and lipid homeostasis, but BCAA restriction has more modest effects in short-term studies in human T2D subjects. Feeding of rats with diets enriched in sucrose or fructose result in the induction of the ChREBP transcription factor in the liver to increase expression of the BCKDH kinase (BDK) and suppress the expression of its phosphatase (PPM1K) resulting in the inactivation of BCKDH and activation of the key lipogenic enzyme ATP-citrate lyase (ACLY). These and other emergent links between BCAA, glucose, and lipid metabolism motivate ongoing studies of possible causal actions of BCAA and related metabolites in the development of cardiometabolic diseases.
To determine the utility of a 3D vulvar model for teaching pediatric straddle injury repair.
Prospective study.
Two academic hospitals.
Twenty obstetrics and gynecology residents INTERVENTIONS AND MAIN OUTCOME MEASURES Knowledge score on the basis of a 7-question pre/post test. Likert scale questions evaluated the 3D model as a teaching tool.
Twenty residents participated; 2 (10%) had ever repaired a straddle injury. Knowledge scores increased after model use and didactic session from 3.05 of possible 7 to 6.35; P=.001. Only 2/20 (10%) residents "agreed" or "strongly agreed" with the statement, "I am comfortable repairing a straddle injury" before the intervention, compared with 19/20 (95%) afterward (P < .001). Of 20 residents, 19 (95%) believed that it simulated surgical experience "very well" or "well."
The use of a 3D pediatric vulvar model can simulate surgical experience and can be an effective teaching tool when combined with a didactic session on pediatric straddle injury.
The use of a 3D pediatric vulvar model can simulate surgical experience and can be an effective teaching tool when combined with a didactic session on pediatric straddle injury.
The aim of this study was to compare the characteristics of adolescents with and without adnexal mass who were diagnosed with ovarian torsion (OT).
Retrospective cross-sectional study.
Gynecology Department at Tepecik Education and Reseach Hospital, Izmir, Turkey.
Adolescent girls who received surgery for OT between March 2012 and October 2020 in our institution.
The patients were divided into 2 groups according to the presence or absence of an ovarian mass and compared. Demographic and clinical characteristics, imaging findings, surgery, and pathology reports of the patients were obtained. Differences in initial symptoms, ultrasound findings, the diagnostic process, and the degree of torsion in patients with and without ovarian mass.
Seventy-six patients were diagnosed with OT. Of the 76 patients, 41/76 (53.9%) had an ovarian mass (OTwM), and 35/76 (46.1%) had no pathology (OTnP). The admission to surgery interval was longer in the OTnP group (P=.03). Ultrasound findings of ovarian edema and the appearance of free fluid were significant in the OTnP group (P=.001). The largest dimension of the nontorsion ovary in the OTnP group was greater than in the OTwM group (P=.03). In addition, it was found that torsion more than 360° was more common in the OTnP group than in the OTwM group (24/35, 68.5% vs 41/18, 43.9%; P=.03).
In symptomatic adolescents without an ovarian mass, the presence of follicle peripheralization suggesting ovarian edema on ultrasound and the presence of free fluid in the abdomen are important in terms of suspicion of torsion for clinicians. In addition, the degree of torsion was increased in these patients.
In symptomatic adolescents without an ovarian mass, the presence of follicle peripheralization suggesting ovarian edema on ultrasound and the presence of free fluid in the abdomen are important in terms of suspicion of torsion for clinicians. In addition, the degree of torsion was increased in these patients.
Atypical ductal hyperplasia (ADH) is a benign epithelial proliferative lesion with histologic features resembling those seen in low grade ductal carcinoma in situ (DCIS). Surgical excision of the biopsy site is the standard management approach. The objective of this study was to determine the upgrade rate from ADH on stereotactic breast biopsies to DCIS or invasive carcinoma (IC) in our institution. We also sought to identify clinical, pathologic and radiologic predictive factors associated with risk of upgrade.
Clinical charts, mammograms and pathology reports were reviewed for all women with a stereotactic breast biopsy showing ADH and subsequent surgery at our institution between 2008 and 2018. When available, mammograms were re-reviewed by a radiologist for this study.
295 biopsies were analyzed in 290 patients. Mean age was 56 y old. Upgrade rate was 10.5% of which 7.5% were DCIS and 3.1% IC. Mammograms were reviewed by a radiologist in 161 patients from 2013 to 2018. In this subset of patients, the rate of upgrade was 8.
