Surface parameters of stannic oxide in powder, ceramic, and gel form by nitrogen adsorption techniques Interim report

Surface parameters of stannic oxide in powder, ceramic, and gel form by nitrogen adsorption techniques - analysis of adsorption isotherm

Synthesis, x-ray structure and anion binding properties of a cryptand-like hybrid calixpyrrole

The novel cryptand in/out-3, containing two tripyrrolemethane units briged by three 1,3- diisopropylidenbenzene arms was readily synthesized by a convergent three-step synthesis. It binds fluoride by inclusion with excellent selectivity with respect to a number of other tested anions. The structure of the free receptor and that of its fluoride complex were investigated in solution by NMR spectroscopy. The solid state X-ray structure of the free cryptand 3 was also determined

Nutritional regulation of oligodendrocyte differentiation regulates perineuronal net remodeling in the median eminence

The mediobasal hypothalamus (MBH; arcuate nucleus of the hypothalamus [ARH] and median eminence [ME]) is a key nutrient sensing site for the production of the complex homeostatic feedback responses required for the maintenance of energy balance. Here, we show that refeeding after an overnight fast rapidly triggers proliferation and differentiation of oligodendrocyte progenitors, leading to the production of new oligodendrocytes in the ME specifically. During this nutritional paradigm, ME perineuronal nets (PNNs), emerging regulators of ARH metabolic functions, are rapidly remodeled, and this process requires myelin regulatory factor (Myrf) in oligodendrocyte progenitors. In genetically obese ob/ob mice, nutritional regulations of ME oligodendrocyte differentiation and PNN remodeling are blunted, and enzymatic digestion of local PNN increases food intake and weight gain. We conclude that MBH PNNs are required for the maintenance of energy balance in lean mice and are remodeled in the adult ME by the nutritional control of oligodendrocyte differentiation

Patient advocacy: barriers and facilitators

BACKGROUND: During the two recent decades, advocacy has been a topic of much debate in the nursing profession. Although advocacy has embraced a crucial role for nurses, its extent is often limited in practice. While a variety of studies have been generated all over the world, barriers and facilitators in the patient advocacy have not been completely identified. This article presents the findings of a study exploring the barriers and facilitators influencing the role of advocacy among Iranian nurses. METHOD: This study was conducted by grounded theory method. Participants were 24 Iranian registered nurses working in a large university hospital in Tehran, Iran. Semi-structured interviews were used for data collection. All interviews were transcribed verbatim and simultaneously Constant comparative analysis was used according to the Strauss and Corbin method. RESULTS: Through data analysis, several main themes emerged to describe the factors that hindered or facilitated patient advocacy. Nurses in this study identified powerlessness, lack of support, law, code of ethics and motivation, limited communication, physicians leading, risk of advocacy, royalty to peers, and insufficient time to interact with patients and families as barriers to advocacy. As for factors that facilitated nurses to act as a patient advocate, it was found that the nature of nurse-patient relationship, recognizing patients' needs, nurses' responsibility, physician as a colleague, and nurses' knowledge and skills could be influential in adopting the advocacy role. CONCLUSION: Participants believed that in this context taking an advocacy role is difficult for nurses due to the barriers mentioned. Therefore, they make decisions and act as a patient's advocate in any situation concerning patient needs and status of barriers and facilitators. In most cases, they can not act at an optimal level; instead they accept only what they can do, which we called 'limited advocacy' in this study. It is concluded that advocacy is contextually complex, and is a controversial and risky component of the nursing practice. Further research is needed to determine the possibility of a correlation between identified barriers/ facilitators and the use of advocacy

Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing

$\textbf{Objective}$ Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. $\textbf{Methods}$ Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. $\textbf{Results}$ Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (A$^{+}$P$_{+}$). Unbiased clustering analysis of P$^{+}$ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P$^{+}$ neurons expressed the leptin receptor ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively). $\textbf{Conclusion}$ These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.This work was supported by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1 & MRC_MC_UU_12012/5), a Wellcome Trust Strategic Award (100574/Z/12/Z), and the Helmholtz Alliance ICEMED

Activation of the hypothalamic-pituitary-adrenal axis by exogenous and endogenous GDF15.

An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic-pituitary-adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15 -/- mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies

Heterogeneity of hypothalamic pro-opiomelanocortin-expressing neurons revealed by single-cell RNA sequencing

$\textbf{Objective}$ Arcuate proopiomelanocortin (POMC) neurons are critical nodes in the control of body weight. Often characterized simply as direct targets for leptin, recent data suggest a more complex architecture. $\textbf{Methods}$ Using single cell RNA sequencing, we have generated an atlas of gene expression in murine POMC neurons. $\textbf{Results}$ Of 163 neurons, 118 expressed high levels of $\textit{Pomc}$ with little/no Agrp expression and were considered “canonical” POMC neurons (P$^{+}$). The other 45/163 expressed low levels of $\textit{Pomc}$ and high levels of $\textit{Agrp}$ (A$^{+}$P$_{+}$). Unbiased clustering analysis of P$^{+}$ neurons revealed four different classes, each with distinct cell surface receptor gene expression profiles. Further, only 12% (14/118) of P$^{+}$ neurons expressed the leptin receptor ($\textit{Lepr}$) compared with 58% (26/45) of A$^{+}$P$_{+}$ neurons. In contrast, the insulin receptor ($\textit{Insr}$) was expressed at similar frequency on P$^{+}$ and A$^{+}$P$_{+}$ neurons (64% and 55%, respectively). $\textbf{Conclusion}$ These data reveal arcuate POMC neurons to be a highly heterogeneous population. Accession Numbers: GSE92707.This work was supported by the UK Medical Research Council (MRC) Metabolic Disease Unit (MRC_MC_UU_12012/1 & MRC_MC_UU_12012/5), a Wellcome Trust Strategic Award (100574/Z/12/Z), and the Helmholtz Alliance ICEMED

Association of warfarin dose with genes involved in its action and metabolism

We report an extensive study of variability in genes encoding proteins that are believed to be involved in the action and biotransformation of warfarin. Warfarin is a commonly prescribed anticoagulant that is difficult to use because of the wide interindividual variation in dose requirements, the narrow therapeutic range and the risk of serious bleeding. We genotyped 201 patients for polymorphisms in 29 genes in the warfarin interactive pathways and tested them for association with dose requirement. In our study, polymorphisms in or flanking the genes VKORC1, CYP2C9, CYP2C18, CYP2C19, PROC, APOE, EPHX1, CALU, GGCX and ORM1-ORM2 and haplotypes of VKORC1, CYP2C9, CYP2C8, CYP2C19, PROC, F7, GGCX, PROZ, F9, NR1I2 and ORM1-ORM2 were associated with dose (P < 0.05). VKORC1, CYP2C9, CYP2C18 and CYP2C19 were significant after experiment-wise correction for multiple testing (P < 0.000175), however, the association of CYP2C18 and CYP2C19 was fully explained by linkage disequilibrium with CYP2C9*2 and/or *3. PROC and APOE were both significantly associated with dose after correction within each gene. A multiple regression model with VKORC1, CYP2C9, PROC and the non-genetic predictors age, bodyweight, drug interactions and indication for treatment jointly accounted for 62% of variance in warfarin dose. Weaker associations observed for other genes could explain up to ∼10% additional dose variance, but require testing and validation in an independent and larger data set. Translation of this knowledge into clinical guidelines for warfarin prescription will be likely to have a major impact on the safety and efficacy of warfarin. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00439-006-0260-8 and is accessible for authorized users

SLC6A3 and body mass index in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

<p>Abstract</p> <p>Background</p> <p>To investigate the contribution of the dopamine transporter to dopaminergic reward-related behaviors and anthropometry, we evaluated associations between polymorphisms at the dopamine transporter gene(<it>SLC6A3</it>) and body mass index (BMI), among participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.</p> <p>Methods</p> <p>Four polymorphisms (rs6350, rs6413429, rs6347 and the 3' variable number of tandem repeat (3' VNTR) polymorphism) at the <it>SLC6A3 </it>gene were genotyped in 2,364 participants selected from the screening arm of PLCO randomly within strata of sex, age and smoking history. Height and weight at ages 20 and 50 years and baseline were assessed by questionnaire. BMI was calculated and categorized as underweight, normal, overweight and obese (<18.5, 18.5–24.9, 25.0–29.9, or ≥ 30 kg/m², respectively). Odds ratios (ORs) and 95% confidence intervals (CIs) of <it>SLC6A3 </it>genotypes and haplotypes were computed using conditional logistic regression.</p> <p>Results</p> <p>Compared with individuals having a normal BMI, obese individuals at the time of the baseline study questionnaire were less likely to possess the <it>3' </it>VNTR variant allele with 9 copies of the repeated sequence in a dose-dependent model (** is referent; OR_*9= 0.80, OR₉₉= 0.47, p_trend= 0.005). Compared with individuals having a normal BMI at age 50, overweight individuals (A-C-G-* is referent; OR_A-C-G-9= 0.80, 95% CI 0.65–0.99, p = 0.04) and obese individuals (A-C-G-* is referent; OR_A-C-G-9= 0.70, 95% CI 0.49–0.99, p = 0.04) were less likely to possess the haplotype with the 3'variant allele (A-C-G-9).</p> <p>Conclusion</p> <p>Our results support a role of genetic variation at the dopamine transporter gene, <it>SLC6A3</it>, as a modifier of BMI.</p