Keeganbredahl4459

Pathologically, huNSGS spontaneously developed a disseminated histiocytosis with infiltrates of activated macrophages and hemophagocytosis predominantly affecting the liver, spleen, bone marrow, and pancreas. The infiltrates were chimeric with a mixture of human and mouse macrophages. Immunohistochemistry suggested activation of the inflammasome in both human and murine macrophages. Active Epstein-Barr virus infection was not a feature. Although the affected mice exhibited robust chimerism of the spleen and bone marrow, the phenotype often developed in the face of low chimerism of the peripheral blood. Given the high penetrance and early lethality associated with the MAS-like phenotype here described, we urge caution when considering the use of huNSGS mice for the development of long-term studies.There are no approved symptomatic treatments for vascular dementia (VaD). Rapamycin (RAPA) improves cognitive deficits in Alzheimer's disease rats. To explore whether RAPA improves cognitive impairment after VaD and its possible molecular mechanisms. Thirty Sprague Dawley rats were randomly divided into three groups sham (received sham-operation), VaD model (received permanent ligation of bilateral carotid arteries) and RAPA (7.5 mg/kg) treatment. Cognitive function was evaluated by Morris water maze test. Neuronal apoptosis was evaluated by TUNEL staining. Mitophagy was assessed by mitochondrial DNA (mtDNA), ATP level, transmission electron microscope and mitophagy-associated proteins. Proteins were quantified by Western blot and immunofluorescence. BV2 cells were exposed to RAPA or/and MHY1485 (mTOR activator) to verify in vivo results. Compared to VaD rats, the escape latency of RAPA-treated rats was significantly decreased, and time spent in target quadrant was longer. Pathologic changes, mitochondrial dysfunction, increase of neuronal apoptosis and related proteins in VaD rats were remarkably alleviated by RAPA. After RAPA treatment, an increase in number of autophagosomes was observed, along with up-regulation of mitophagy-related proteins. Overexpression of PI3K, AKT and mTOR were suppressed by RAPA treatment. click here In vitro experiments confirmed effects of RAPA, and demonstrated that MHY1485 addition reversed the RAPA-caused apoptosis inhibition and mitophagy enhancement. Overall, RAPA improved the cognitive impairment of VaD rats, alleviated neuronal injury and mitochondrial dysfunction. We proposed a potential mechanism that RAPA may play improving role by inhibiting neuronal apoptosis and enhancing mitophagy through PI3K/AKT/mTOR pathway. Findings provided an exciting possibility for novel treatment strategy of VaD.

patients with non-small-cell lung cancer (NSCLC) admitted to the intensive care unit have poor prognosis. There is limited data on cytotoxic chemotherapy in this setting. The standard of care for these patients is usually best supportive care.

60-year-old previously healthy female was admitted to the ICU with newly diagnosed mucinous adenocarcinoma of the lung. She received cisplatin and pemetrexed while intubated and mechanically ventilated. She was extubated a week later and discharged home after achieving an excellent radiographic and clinical response.

in select patients with NSCLC admitted to the ICU due to complications from their malignancy, a trial of cytotoxic chemotherapy may be reasonable. To our knowledge, this is the first case of mucinous NSCLC treated in the ICU.

in select patients with NSCLC admitted to the ICU due to complications from their malignancy, a trial of cytotoxic chemotherapy may be reasonable. To our knowledge, this is the first case of mucinous NSCLC treated in the ICU.

Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.

From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).

Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI) 2.34-4.66]. The median OS was 4.5 months (95%CI 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P = 0.030) and PFS (P = 0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).

Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.

AHEAD-G202 (NCT02668380).

AHEAD-G202 (NCT02668380).

Undocumented migrant women experience complex barriers to maternity services, are less likely to receive the recommended level of maternity care, and have poorer obstetric outcomes than non-migrant women. There are concerns increasing restrictions on entitlement to health services have a detrimental impact on access to services and obstetric outcomes, particularly among undocumented migrant women. The study aimed to investigate the experiences of undocumented migrant women who have been pregnant in England, and factors affecting access to care and health outcomes.

We conducted in-depth semi-structured interviews June-December 2017 with a purposive sample of migrant women born outside the UK (aged>18) who had experiences of pregnancy and undocumented status (without permission to reside) in the UK, recruited through Doctors of the World (DOTW) UK. Interpreting services were used on request. Interviews were recorded, transcribed, and analysed using thematic analysis. Ethical approval Imperial College London Research Ethics Committee (ICREC reference 17IC3924).