Burnsfinn3732

Maternal high-fat diet (HFD) often results in intrauterine and feto-placental inflammation, and increases the risks of fetal programming of metabolic diseases. Intake of prebiotic is reported beneficial. However, its effects on HFD during pregnancy and lactation is not known. We evaluated the maternal intake of fructooligosaccharide (FOS) and its impact on placental inflammation, offspring's adiposity, glucose, and lipid metabolism in their later life. Female Golden Syrian hamsters were fed with a control diet (CD, 26.4 % energy from fat) or HFD (60.7% energy from fat) in the presence or absence of FOS from preconception until lactation. All pups were switched over to CD after lactation and continued until the end. Placental inflammation was upregulated in HFD-fed dam, as measured by a high concentration of hsCRP in the serum and amniotic fluid. Neutrophil infiltration was significantly increased in the decidua through the chorionic layer of the placenta. The expression of pro-inflammatory cytokines such as COX2, NFκβ, IL-8, TGFβ mRNA was increased in the chorioamniotic membrane (P less then .05). The HFD/CD hamsters had more adiposity, higher triglyceride, and low HDL at 12 months of age compared to CD/CD (P less then .05). However, HFD+FOS/CD-fed hamsters prevented adverse effects such as placental inflammation, neutrophil infiltration, glucose, and lipid profiles in the offspring (P less then .05). Anti-inflammatory and lipid-lowering effects of FOS may reduce placental inflammation by lowering neutrophil infiltration and decreasing the production of pro-inflammatory cytokines. Intake of FOS during pregnancy may be beneficial in maintaining lipid metabolism and preventing excess adiposity for mother and their offspring.Amino acids can activate mTOR to promote milk synthesis in mammary epithelial cells (MECs), but the underlying molecular mechanism is still largely unknown. Angiogenesis inhibitor The objective is to investigate the regulatory mechanism of amino acids (Met and Leu) in stimulating mRNA expression of mTOR in MECs. We found that the protein abundance of AT-rich interaction domain 1A (ARID1A) was poorly expressed in mouse mammary gland tissues of lactating period. ARID1A knockdown and gene activation experiments detected whether ARID1A negatively regulated milk protein and fat synthesis in bovine MECs, cell proliferation and the expression and activation of mTOR. ChIP-PCR detected that ARID1A, H3K27ac, H3K27me3 and H3K4me3 all bound to the mTOR promoter at -548∼-793 nt. Knockdown or gene activation of ARID1A enhanced or weakened the binding of H3K27ac on the mTOR promoter, respectively. The stimulation of Met and Leu on mTOR expression and phosphorylation were eliminated by ARID1A gene activation. Furthermore, Met and Leu decreased the protein level of ARID1A through ubiquitination and proteasomal degradation. TRIM21 bound to ARID1A, and TRIM21 knockdown blocked the stimulation of Met and Leu on ARID1A degradation. In summary, these data reveal that ARID1A blocks Met and Leu signaling to mTOR gene transcription through inhibiting H3K27ac deposition on its promoter, and Met and Leu decrease ARID1A protein level through TRIM21-mediated ubiquitination and proteasomal degradation. Our findings uncover that Met and Leu promote mTOR expression for milk synthesis through the TRIM21-ARID1A signaling pathway, providing a novel theoretical basis for the application of amino acids in milk production.Zinc homeostasis is primarily maintained by zinc transporters that regulate zinc uptake and efflux in the small intestine; however, the relative contribution of the many zinc transporters identified (Slc39a1-14, Slc30a1-10) to dietary zinc absorption and utilization remains unknown. The objective of this study was to determine the expression of Slc39a1-14 and Slc30a1-10 in the small intestine and their relative contribution to dietary zinc absorption in mice. Five-week-old male C57BL/6J mice were fed modified AIN-93G diets containing .05). Liver and plasma appearance of 67Zn was greater in mice fed less then 1ppm compared to the 30ppm (P less then .0001) and 100ppm (P less then .0001) zinc diets. With the exception of Slc39a2, Slc39a12, Slc30a3, and Slc30a8, the remaining zinc transporters were expressed across all diets and intestinal segments. Expression of Slc39a4, Slc39a11, and Slc30a6 changed with diet (Pdiet less then .05 for all); expression of Slc39a5, Slc39a7, Slc39a11, Slc39a14, Slc30a1, Slc30a2, Slc30a4, Slc30a5, Slc30a7, and Slc30a10 changed by intestinal segment (Psegment less then .05 for all). Slc39a4 was the only transporter positively associated with liver (r2=0.316, P less then .001) and plasma (r2=0.189, P less then .01) 67Zn appearance. Although most zinc transporters are expressed in the small intestine, intestinal Slc39a4 predicts fractional zinc absorption and utilization in young mice.In recent years, methylation modification has been determined to be vital for the biological regulation of normal cells, tumor cells, and tumor microenvironment immune cells. Enhancer of zeste homology 2 (EZH2), a component of the Polycomb Repressive Complex 2 (PRC2), catalyzes the trimethylation of the downstream gene in the tri-methylates histone three lysine 27 (H3K27me3) position, which causes chromatin pyknosis, and thus, silences the expression of related genes. In this paper, we reviewed the role of EZH2 in regulating bone marrow mesenchymal stem cell differentiation and the immune cell function in tumor microenvironment, summarized all types of existing EZH2 inhibitors and the main clinical trials, and proposed relevant ideas for potential clinical applications.

Although salvage surgery (SS) is considered the best curative choice in recurrent head and neck cancer, the identification of patients who can benefit the most from this treatment is challenging.

We systematically reviewed the prognostic role of pre- and post-surgery factors in patients undergoing SS for recurrent head and neck cancer (oral cavity, oropharynx, hypopharynx, and larynx).

Twenty-five studies met the inclusion criteria out of 1280 screened citations. Pre-surgery factors significantly associated with worse overall survival were age>60 years, advanced initial stage, early recurrence, and regional recurrence; no heterogeneity between study emerged. Among post- surgery factors, worse survival emerged for positive surgical margins, extracapsular extension and perineural invasion.

The identification of pre-surgery factors associated with poor outcomes may help the selection of the best candidate to SS; alternative treatments should be considered for high-risk patients. Post-surgery predictors of worse prognosis may guide clinicians in tailoring patients' surveillance.

The identification of pre-surgery factors associated with poor outcomes may help the selection of the best candidate to SS; alternative treatments should be considered for high-risk patients. Post-surgery predictors of worse prognosis may guide clinicians in tailoring patients' surveillance.This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI(1.29,2.86); HR = 2.25, 95 %CI(1.73,2.92)) and KRAS mutations (HR = 1.88, CI1.22,2.92,); HR = 1.52, 95 %CI(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.The Accreditation Council for Graduate Medical Education (ACGME) requirements for child and adolescent psychiatry training require that child and adolescent psychiatry fellows demonstrate competence in psychodynamic psychotherapy.1 Child and adolescent psychiatry educators may turn to JAACAP to find up-to-date advances in psychodynamic psychotherapy to teach. However, the term psychodynamic appears to be hard to find, literally. A search on https//www.jaacap.org/ of past issues for psychodynamic2 resulted in 4 articles published in the past year, but none have the word psychodynamic in the title. Three articles describe newer evidence-based forms of psychotherapy brief focused parent-infant psychotherapy, adolescent-focused therapy, and mentalization-based treatment. These are are described in their respective articles as "psychodynamic-based," as "psychodynamically informed," and having "historical roots in psychodynamic psychotherapy." As none are specifically titled psychodynamic therapy, it is unclear whether teaching these modalities would satisfy the ACGME requirement of competence in psychodynamic psychotherapy. Comparatively, this linguistic dilution does not seem to affect cognitive-behavioral therapy (CBT), another psychotherapy required by the ACGME1 specialized branches such as trauma-focused CBT, CBT for psychosis, and CBT for insomnia all retain the parent name of CBT. Therefore, it is important to define psychodynamic.Asian American and Pacific Islanders (AAPI) are the fastest growing racial minority in the United States. With more than 40 subgroups in the diaspora, 1 in 10 American youths will be of Asian origin by 2060. Racism-defined as prejudice, discrimination or antagonism on the basis of membership in a particular racial or ethnic group-is increasingly recognized as a public health crisis.1 Anti-AAPI racism, such as unequal resource distribution in housing, education, employment, and health care, exclusionary naturalization policies and violence1,2 (eg, Pacific coast riots, Japanese Americans' internment during World War II, recent Atlanta shootings) is well documented. Anti-AAPI microaggressions-that is, the subtle, sometimes unintentional forms of racism such as characterizations as perpetual foreigners, ascriptions of intelligence, oversexualization of women, invalidated interethnic differences, and model minority myth-are common. The model minority stereotype dismisses real struggles1 and pits AAPIs against other racial minorities. Despite the proud tradition of AAPI activism , discrimination is often endured in silence, probably stemming from cultural values of stoicism and harmony, and tacit societal acceptance of racism.3.Tigecycline is commonly used for infections by multidrug-resistant bacteria. However, it is not approved for ventilator-associated pneumonia (VAP) as increased mortality has been reported in VAP patients treated with conventional doses. The purpose of this study was to prospectively evaluate the intrapulmonary pharmacokinetics of off-label high-dose tigecycline in patients with VAP. Nine mechanically ventilated patients received tigecycline intravenously (loading dose 200 mg followed by 100 mg every 12 h). After ≥5 doses, two bronchoscopies were performed in each patient on consecutive days and eight blood samples were collected. Tigecycline concentrations in plasma and bronchoalveolar lavage fluid were determined by liquid chromatography. The urea dilution method was used to calculate epithelial lining fluid (ELF) concentrations. A two-compartmental pharmacokinetic (PK) model with linear elimination was used to estimate PK parameters. Mean patient age was 69 ± 11.86 years and mean APACHE II score was 21. The estimated population mean PK parameters (relative standard error) were clearance, 11.