Bryanmark6709

Few studies have focused on within-group heterogeneity about specific factors that make lesbian, gay, or bisexual (LGB) Latinx adolescents at greater odds than other LGB adolescents for suicide We take a unique mixture-modeling approach by creating profiles of Latinx LGB adolescents based on suicide risk factors used in previous investigations (bullying, alcohol, sleep, social media, and poor grades). We use these profiles in a logistic regression to investigate suicidality A sample of 686 LGB, Latinx adolescents were used in a latent profile analysis yielding four distinct profiles. Class 4 represented the highest risk, with high rates of bullying, alcohol, poor grades, and use of electronics, while class 3 represented the lowest risk with low rates of bullying and alcohol Results speak to the need to address suicidal ideation through multiple factors, noting the strong association that both bullying and alcohol have with suicidal ideation.This study assessed the relationship between immigration status, including recency, and unmet home care needs. Data from the 2015-2016 Canadian Community Health Survey (CCHS) was used to analyze the relationship between immigration status and unmet home care needs. Descriptive analyses and multivariable logistic regression controlling for age, sex, marital status, and education were calculated. Of the study sample of 5976 respondents, 34.5% had unmet home care needs. Prevalence of unmet needs was highest among recent immigrants (43.8%), compared with long-time immigrants (40.5%) and non-immigrants (32.7%). Adjusted odds of unmet needs was higher for both immigrant categories than non-immigrants, and stronger for long-time immigrants (OR = 1.58, 95% CI 1.14, 2.20) than recent immigrants (OR = 1.42, 95% CI 0.67, 3.00). The finding that immigrants are more likely to experience unmet home care needs, with a slight difference between recent and long-time immigrants, suggests home care access inequities exist between immigrants and non-immigrants, and among immigrants.Preschoolers' emotional development typically hinges on the family emotional climate and their interactions with caregivers. This study used a randomized controlled trial to examine the treatment efficacy of an emotion coaching parenting intervention culturally adapted from the Tuning in to Kids® (TIK) program in enhancing Chinese mothers' emotional responsiveness in parenting. A total of eighty-nine mothers with preschoolers were randomly assigned to either the intervention or waitlist control group. The TIK group received six weekly sessions of intervention on emotion coaching parenting training. The training significantly improved participating mothers' positive involvement and the use of emotion coaching in their parenting practices. More expressive encouragement and emotion-focused reactions to children's emotion expression, and less punitive parenting and emotional dismissing were also found in the mothers after training. Our findings provided the first evidence in a non-Western sample to support the effectiveness of such program in enhancing parents' efficacy in facilitating their children's emotional development.This study examined (1) adolescent mental health literacy (MHL) and stigma for depression, anxiety and obsessive-compulsive and related disorders (OCRDs), and (2) demographic moderators. Participants were 383 high school students (50.9% boys) aged 11-18 years (M = 14.12, SD = 1.91) in El Salvador. Participants read vignettes of adolescents with mental health problems and reported on their beliefs about (1) what was wrong with the young person, (2) expected recovery time, (3) help-seeking beliefs and recommendations, and (4) stigma and preferred social distance associated with each condition. Results suggested that recognition of mental health conditions, especially anxiety disorders and OCRDs, was limited, although one third could recognize depression in a peer. Help-seeking attitudes were favorable. Adolescents were only somewhat willing to be affiliated with someone experiencing a mental health problem. Girls showed better MHL and lower stigma than boys. Stigma was lower among those with exposure to mental health problems.Background Ulixertinib is the first-in-class ERK1/2 kinase inhibitor with encouraging clinical activity in BRAF- and NRAS-mutant cancers. Dermatologic adverse events (dAEs) are common with ulixertinib, so management guidelines like those established for epidermal growth factor receptor inhibitor (EGFRi)-associated dAEs are needed. Patients and Methods This was an open-label, multicenter, phase I dose escalation and expansion trial of ulixertinib evaluating data from 135 patients with advanced malignancies enrolled between March 2013 and July 2017. Histopathological features, management, and dAEs in 34 patients are also reported. Twice daily oral ulixertinib was administered at 10 to 900 mg in the dose escalation cohort (n = 27) and at 600 mg in 21-day cycles in the expansion cohort (n = 108). Results The incidence of ulixertinib-induced dAEs and combined rash were 79% (107/135) and 76% (102/135). The most common dAEs included acneiform rash (45/135, 33%), maculopapular rash (36/135, 27%), and pruritus (34/135, 25%). Grade 3 dAEs were observed in 19% (25/135) of patients; no grade 4 or 5 dAEs were seen. The presence of at least 1 dAE was associated with stable disease (SD) or partial response (PR) (OR = 3.64, 95% CI 1.52-8.72; P = .003). Acneiform rash was associated with a PR (OR = 10.19, 95% CI 2.67-38.91; P  less then  .001). Conclusion The clinical spectrum of ulixertinib-induced dAEs was similar to EGFR and MEK inhibitors; dAEs may serve as a surrogate marker of tumor response. We propose treatment algorithms for common ERK inhibitor-induced dAEs to maintain patients' quality of life and dose intensity for maximal clinical benefit. Clinical Trial Registration NCT01781429.Immunotherapy of HER2-overexpressing cancers by FDA approved monoclonal antibodies (mAbs) such as trastuzumab and pertuzumab has shown promising results. We have recently produced a novel humanized anti-HER2 mAb, hersintuzumab, which did not sterically inhibit binding of trastuzumab and pertuzumab to HER2, thus recognizing a distinct epitope on subdomain I + II of HER2. In this study, we assessed the in vitro and in vivo anti-tumor activity of this mAb individually and in combination with trastuzumab. Different HER2-overexpressing human cancer cell lines, including SKOV3, NCI-N87 HCC1954 and BT-474 were cultured and binding reactivity of Hersintuzumab to these cell lines was analyzed by flow cytometry. In addition, the inhibitory effect of different concentrations of hersintuzumab, trastuzumab and their combination on tumor cells growth was assessed by XTT assay. For Assessment of tumor growth inhibition in xenograft model, Balb/c athymic nude mice were subcutaneously injected with NCI-N87 and SKOV3 tumor cells and then treated intravenously with these mAbs. Our results showed that hersintuzumab could bind to all HER2-overexpressing cell lines similar to trastuzumab. In vitro experiments showed that both hersintuzumab and trastuzumab individually and in combination inhibited growth of all cell lines with the exception of HCC-1954.Inhibitory effect of the combination of mAbs was significantly higher than that of each mAb alone. Similar results were obtained in the gastric (NCI-N87) and ovarian (SKOV-3) tumor xenograft models. Hersintuzumab in combination with trastuzumab induces synergic anti-tumor effects on HER2-overexpressing cells in vitro and in vivo and is potentially a therapeutic tool for treatment of HER2-overexpressing cancers.A selective RXR agonist, bexarotene, has been shown to have anti-inflammatory, anti-nociceptive, and neuroprotective effects in several models of numerous neurological diseases characterized by systemic inflammation. The mechanisms underlying these effects remains unknown. To elucidate these mechanisms, we investigated whether the TLR4/MyD88/TAK1/NF-κB/COX-2 signaling pathway in the CNS mediates the effect of bexarotene to prevent hyperalgesia in the LPS-induced inflammatory pain mouse model. The reaction time to thermal stimuli within 30 s was evaluated by the hot plate test in male mice treated with saline, LPS (10 mg/kg), DMSO, and/or bexarotene (0.1, 1, 3, or 10 mg/kg) after 6 h. The latency to the thermal stimulus (18.11 ± 1.36 s) in the LPS-treated mice was significantly decreased by 30% compared with saline-treated mice (25.84 ± 1.99 s). Treatment with bexarotene only at a dose of 10 mg/kg showed a significant increase in the latency by 22.49 ± 1.00 s compared with LPS-treated mice. Bexarotene also prevented the reduction in RXRα protein expression associated with a rise in the expression of TLR4, MyD88, phosphorylated TAK1, NF-κB p65, phosphorylated NF-κB p65, COX-2, and IL-1β proteins, in addition to COX-2 activity and levels of PGE2 and IL-1β in the brains and spinal cords of the LPS-treated animals. Likely, decreased activity of TLR4/MyD88/TAK1/NF-κB/COX-2 signaling pathway in addition to increased pro-inflammatory cytokine formation in the CNS of mice participates in the protective effect of bexarotene against hyperalgesia induced by LPS.Prenatal hypoxia is among leading causes of progressive brain pathologies in postnatal life. This study aimed to analyze the characteristics of the hippocampal glutamatergic system and behavior of rats in early (2 weeks), adult (3 months) and advanced (18 months) postnatal ontogenesis after exposure to prenatal severe hypoxia (PSH, 180 Torr, 5% O2, 3 h) during the critical period in the formation of the hippocampus (days 14-16 of gestation). We have shown an age-dependent progressive decrease in the hippocampal glutamate levels, a decrease of the neuronal cell number in the CA1 hippocampal region, as well as impairment of spatial long-term memory in the Morris water navigation task. The gradual decrease of glutamate was accompanied by decreased expression of the genes that mediate glutamate metabolism and recycling in the hippocampus. That deficiency apparently correlated with an increase of the metabotropic glutamate receptor type 1 (mGluR1) and synaptophysin expression. Generation of the lipid peroxidation products in the hippocampus of adult rats subjected to prenatal severe hypoxia (PSH rats) was not increased compared to the control animals when tested in a model of glutamate excitotoxicity induced by severe hypoxia. This demonstrates that excessive glutamate sensitivity in PSH rats does not compensate for glutamate deficiency. Our results show a significant contribution of the glutamate system dysfunction to age-associated decrease of this mediator, cognitive decline, and early neuronal loss in PSH rats.Neuroblastoma (NB) is a childhood malignancy of the sympathetic nervous system and is commonly studied using the SH-SY5Y cell line. Its neoplastic and neurodevelopmental manifestations are characterised by a high glucose demand which maintains its high proliferative capacity. This metabolic phenotype may be utilised in dietary therapies such as the ketone diet which alter substrate availability and thus starve NB cells of their preferred biosynthetic requirements. However, the effects of ketone metabolism on cancer growth remain poorly understood due to the involvement of other metabolic substrates in experimental paradigms and complexities underlying the Warburg effect. We investigated how the primary ketone body beta-hydroxybutyrate (βOHB) affects the growth of SH-SY5Y NB cells in the presence or absence of culture metabolic substrates. We demonstrated that while glucose deprivation reduced the growth and viability of SH-SY5Y cells, they proliferated and were initially unaffected by the addition of βOHB. However, a growth response to βOHB was subsequently revealed in media containing low levels of glucose, as well as in glucose and pyruvate deprived conditions.