Braunschwegisches Adreßbuch für das Jahr 1938

This Note considers whether state regulations that restrict juvenile access to material that is obscene as to minors unconstitutionally encroach upon the first amendment rights of adults. Part I briefly describes the Court\u27s opinion in Ginsberg. Part II introduces the O\u27Brien analysis and discusses the aspects of juvenile access restrictions that tend to make O\u27Brien scrutiny applicable. In this context the frequently relaxed judicial review of governmental restrictions on sexually related material will be discussed. Having concluded that the O\u27Brien analysis is applicable to access restrictions, Part III applies the test and ultimately concludes that juvenile access restrictions survive O\u27Brien scrutiny

Overexpression of CDC25B, CDC25C and phospho-CDC25C (Ser216) in vulvar squamous cell carcinomas are associated with malignant features and aggressive cancer phenotypes

<p>Abstract</p> <p>Background</p> <p>CDC25 phosphatases are important regulators of the cell cycle. Their abnormal expression detected in a number of tumors implies that their dysregulation is involved in malignant transformation. However, the role of CDC25s in vulvar cancer is still unknown. To shed light on their roles in the pathogenesis and to clarify their prognostic values, expression of CDC25A, CDC25B and CDC25C in a large series of vulvar squamous cell carcinomas were examined.</p> <p>Methods</p> <p>Expression of CDC25A, CDC25B, CDC25C and phosphorylated (phospho)-CDC25C (Ser216) were examined in 300 vulvar carcinomas using immunohistochemistry. Western blot analysis was utilized to demonstrate CDC25s expression in vulvar cancer cell lines. Kinase and phosphatase assays were performed to exclude cross reactivity among CDC25s isoform antibodies.</p> <p>Results</p> <p>High nuclear CDC25A and CDC25B expression were observed in 51% and 16% of the vulvar carcinomas, respectively, whereas high cytoplasmic CDC25C expression was seen in 63% of the cases. In cytoplasm, nucleus and cytoplasm/nucleus high phospho-CDC25C (Ser216) expression was identified in 50%, 70% and 77% of the carcinomas, respectively. High expression of CDC25s correlated significantly with malignant features, including poor differentiation and infiltration of vessel for CDC25B, high FIGO stage, presence of lymph node metastases, large tumor diameter, poor differentiation for CDC25C and high FIGO stage, large tumor diameter, deep invasion and poor differentiation for phospho-CDC25C (Ser216). In univariate analysis, high expression of phospho-CDC25C (Ser216) was correlated with poor disease-specific survival (p = 0.04). However, such an association was annulled in multivariate analysis.</p> <p>Conclusions</p> <p>Our results suggest that CDC25C and phospho-CDC25C (Ser216) play a crucial role and CDC25B a minor role in the pathogenesis and/or progression of vulvar carcinomas. CDC25B, CDC25C and phospho-CDC25C (Ser216) were associated with malignant features and aggressive cancer phenotypes. However, the CDC25s isoforms were not independently correlated to prognosis.</p

Efficacy of a training intervention on the quality of practitioners' decision support for patients deciding about place of care at the end of life: A randomized control trial: Study protocol

<p>Abstract</p> <p>Background</p> <p>Most people prefer home palliation but die in an institution. Some experience decisional conflict when weighing options regarding place of care. Clinicians can identify patients' decisional needs and provide decision support, yet generally lack skills and confidence in doing so. This study aims to determine whether the quality of clinicians' decision support can be improved with a brief, theory-based, skills-building intervention.</p> <p>Theory</p> <p>The Ottawa Decision Support Framework (ODSF) guides an evidence based, practical approach to assist clinicians in providing high-quality decision support. The ODSF proposes that decisional needs [personal uncertainty, knowledge, values clarity, support, personal characteristics] strongly influence the quality of decisions patients make. Clinicians can improve decision quality by providing decision support to address decisional needs [clarify decisional needs, provide facts and probabilities, clarify values, support/guide deliberation, monitor/facilitate progress].</p> <p>Methods/Design</p> <p>The efficacy of a brief education intervention will be assessed in a two-phase study. In phase one a focused needs assessment will be conducted with key informants. Phase two is a randomized control trial where clinicians will be randomly allocated to an intervention or control group. The intervention, informed by the needs assessment, knowledge transfer best practices and the ODSF, comprises an online tutorial; an interactive skills building workshop; a decision support protocol; performance feedback, and educational outreach. Participants will be assessed: a) at baseline (quality of decision support); b) after the tutorial (knowledge); and c) four weeks after the other interventions (quality of decision support, intention to incorporate decision support into practice and perceived usefulness of intervention components). Between group differences in the primary outcome (quality of decision support scores) will be analyzed using ANOVA.</p> <p>Discussion</p> <p>Few studies have investigated the efficacy of an evidence-based, theory guided intervention aimed at assisting clinicians to strengthen their patient decision support skills. Expanding our understanding of how clinicians can best support palliative patients' decision-making will help to inform best practices in patient-centered palliative care. There is potential transferability of lessons learned to other care situations such as chronic condition management, advance directives and anticipatory care planning. Should the efficacy evaluation reveal clear improvements in the quality of decision support provided by clinicians who received the intervention, a larger scale implementation and effectiveness trial will be considered.</p> <p>Trial registration</p> <p>This study is registered as NCT00614003</p

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Naringenin Promotes Thermogenic Gene Expression in Human White Adipose Tissue

© 2018 The Obesity Society Objective: Naringenin, a citrus flavonoid, prevents diet-induced weight gain and improves glucose and lipid metabolism in rodents. There is evidence that naringenin activates brown fat and increases energy expenditure in mice, but little is known about its effects in humans. The goal of this study was to examine the effects of naringenin on energy expenditure in adipose tissue. Methods: Human white adipocyte cultures (hADSC) and abdominal subcutaneous adipose tissue (pWAT) were treated with naringenin for 7 to 14 days. Expression (quantitative real-time polymerase chain reaction, immunoblotting) of candidate genes involved in thermogenesis and glucose metabolism was measured. Oxygen consumption rate was measured in hADSC using a Seahorse flux analyzer. Results: In hADSC, naringenin increased expression of the genes associated with thermogenesis and fat oxidation, including uncoupling protein 1 and adipose triglyceride lipase, and key factors associated with insulin sensitivity, including glucose transporter type 4, adiponectin, and carbohydrate-responsive element-binding protein (P \u3c 0.01). Similar responses were observed in pWAT. Basal, ATP-linked, maximal and reserve oxygen consumption rate increased in the naringenin-treated hADSC (P \u3c 0.01). Conclusions: Naringenin increases energy expenditure in hADSC and stimulates expression of key enzymes involved in thermogenesis and insulin sensitivity in hADSC and pWAT. Naringenin may promote conversion of human white adipose tissue to a brown/beige phenotype

Mortality in infantile spasms: A hospital-based study.

OBJECTIVE: To determine risk factors and causes for mortality during childhood in patients with infantile spasms (IS). We describe the overall goals of care for those who died. METHODS: This is a retrospective chart review of IS patients born between 2000 and 2011. We examined potential risk factors for mortality, including etiology, neurologic impairment, medication use, persistence of epileptic spasms, and comorbid systemic involvement (requirement for G-tube feedings, respiratory interventions). For patients who died, we describe cause of death and resuscitation status or end-of-life care measures. RESULTS: We identified 150 IS patients with median follow-up of 12 years. During the study period, 25 (17%) patients died, 13 before 5 years of age. Univariate analysis demonstrated that developmental delay, identifiable etiology, hormonal use for IS, persistence of epileptic spasms, polypharmacy with antiseizure medications, refractory epilepsy, respiratory system comorbidity, and the need for a G-tube were significant risk factors for mortality. In a multivariate analysis, mortality was predicted by persistence of epileptic spasms (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 1.11-16.67, P = .035) and significant respiratory system comorbidity (OR = 12.75, 95% CI = 2.88-56.32, P = .001). Mortality was epilepsy-related in one-third of patients who died with sudden unexpected death in epilepsy (SUDEP), accounting for 88% of epilepsy-related deaths. Most deaths before age 5 years were related to respiratory failure, and SUDEP was less common (17%) whereas SUDEP was more common (45%) with deaths after 5 years. For the majority (67%) of patients with early mortality, an end-of-life care plan was in place (based on documentation of resuscitation status, comfort measures, or decision not to escalate medical care). SIGNIFICANCE: Mortality at our single-center IS cohort was 17%, and persistence of epileptic spasms and comorbid respiratory system disorders were the most important determinants of mortality. Early deaths were related to neurological impairments/comorbidities. SUDEP was more common in children who died after 5 years of age than in those who died younger than 5 years