Treating the "Not-Invented-Here Syndrome" in Medical Leadership: Learning From the Insights of Outside Disciplines.

Physicians are being increasingly called upon to engage in leadership at all levels of modern health organizations, leading many to call for greater research and training interventions regarding physician leadership development. Yet, within these calls to action, the authors note a troubling trend toward siloed, medicine-specific approaches to leadership development and a broad failure to learn from the evidence and insight of other relevant disciplines, such as the organizational sciences. The authors describe how this trend reflects what has been called the "not-invented-here syndrome" (NIHS)-a commonly observed reluctance to adopt and integrate insights from outside disciplines-and highlight the pitfalls of NIHS for effective physician leadership development. Failing to learn from research and interventions in the organizational sciences inhibits physician leadership development efforts, leading to redundant rediscoveries of known insights and reinventions of existing best practices. The authors call for physician leaders to embrace ideas that are "proudly developed elsewhere" and work with colleagues in outside disciplines to conduct collaborative research and develop integrated training interventions to best develop physician leaders who are prepared for the complex, dynamic challenges of modern health care.

Kinin B1 receptor deficiency leads to leptin hypersensitivity and resistance to obesity.

OBJECTIVE: Kinins mediate pathophysiological processes related to hypertension, pain, and inflammation through the activation of two G-protein-coupled receptors, named B(1) and B(2). Although these peptides have been related to glucose homeostasis, their effects on energy balance are still unknown. RESEARCH DESIGN AND METHODS: Using genetic and pharmacological strategies to abrogate the kinin B(1) receptor in different animal models of obesity, here we present evidence of a novel role for kinins in the regulation of satiety and adiposity. RESULTS: Kinin B(1) receptor deficiency in mice (B(1)(-/-)) resulted in less fat content, hypoleptinemia, increased leptin sensitivity, and robust protection against high-fat diet-induced weight gain. Under high-fat diet, B(1)(-/-) also exhibited reduced food intake, improved lipid oxidation, and increased energy expenditure. Surprisingly, B(1) receptor deficiency was not able to decrease food intake and adiposity in obese mice lacking leptin (ob/ob-B(1)(-/-)). However, ob/ob-B(1)(-/-) mice were more responsive to the effects of exogenous leptin on body weight and food intake, suggesting that B(1) receptors may be dependent on leptin to display their metabolic roles. Finally, inhibition of weight gain and food intake by B(1) receptor ablation was pharmacologically confirmed by long-term administration of the kinin B(1) receptor antagonist SSR240612 to mice under high-fat diet. CONCLUSIONS: Our data suggest that kinin B(1) receptors participate in the regulation of the energy balance via a mechanism that could involve the modulation of leptin sensitivity.

Composition, irregular terpenoids, chemical variability and antibacterial activity of the essential oil from Santolina corsica Jordan et Fourr.

A detailed analysis of Santolina corsica essential oil was carried out by combination of GC (RI), GC-MS and 13C NMR spectroscopy. After fractionation by column chromatography, 50 components were identified, accounting for 88.2% of the total amount of the oil. The chemical composition was dominated by monoterpene hydrocarbons, myrcene (34.6%), santolina triene (13.5%) and beta-phellandrene (11.7%). Beside the main compounds, we noted the occurrence of irregular mono and sesquiterpenes belonging to five families: santolinane, artemisane, chrysanthemane, lavandulane and sesquilavandulane. Three compounds, lyratyl butyrate, isolyratone and epi-isolyratol were isolated and their structure elucidated by 2D NMR. Antibacterial activity was tested against six bacteria strains. The essential oil was effective against Staphylococcus aureus and C. jejuni. Lyratol was identified as main responsive of the antibacterial activity. The content of lyratol was measured in 33 oil samples isolated from individual plants.

Direct identification and quantitative determination of costunolide and dehydrocostuslactone in the fixed oil of Laurus novocanariensis by 13C-NMR spectroscopy.

The fixed oil of Laurus novocanariensis (previously L. azorica) contains mostly glycerides together with minor non-saponifiable compounds. The direct identification and quantitative determination of costunolide and dehydrocostuslactone, two sesquiterpene lactones components of the oil that exhibit biological activities, is described. The analysis was carried out using 13C-NMR spectroscopy (signal acquisition with inverse gated decoupling of protons; diglyme as internal standard) without separation, derivatisation or any sample preparation.

Two new irregular acyclic sesquiterpenes aldehydes from Santolina corsica essential oil.

Two isomeric irregular sesquiterpene aldehydes, namely 3,9-dimethyl-6-isopropyl-2(E),7(E),9-decatrienal and 3,9-dimethyl-6-isopropyl-2(Z),7(E),9-decatrienal, were isolated from the essential oil of Santolina corsica and their structures were elucidated by 1D and 2D NMR spectroscopy.

SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride], a new nonpeptide antagonist of the bradykinin B1 receptor: biochemical and pharmacological characterization.

The biochemical and pharmacological properties of a novel non-peptide antagonist of the bradykinin (BK) B(1) receptor, SSR240612 [(2R)-2-[((3R)-3-(1,3-benzodioxol-5-yl)-3-[[(6-methoxy-2-naphthyl)sulfonyl]amino]propanoyl)amino]-3-(4-[[2R,6S)-2,6-dimethylpiperidinyl]methyl]phenyl)-N-isopropyl-N-methylpropanamide hydrochloride] were evaluated. SSR240612 inhibited the binding of [(3)H]Lys(0)-des-Arg(9)-BK to the B(1) receptor in human fibroblast MRC5 and to recombinant human B(1) receptor expressed in human embryonic kidney cells with inhibition constants (K(i)) of 0.48 and 0.73 nM, respectively. The compound selectivity for B(1) versus B(2) receptors was in the range of 500- to 1000-fold. SSR240612 inhibited Lys(0)-desAr(9)-BK (10 nM)-induced inositol monophosphate formation in human fibroblast MRC5, with an IC(50) of 1.9 nM. It also antagonized des-Arg(9)-BK-induced contractions of isolated rabbit aorta and mesenteric plexus of rat ileum with a pA(2) of 8.9 and 9.4, respectively. Antagonistic properties of SSR240612 were also demonstrated in vivo. SSR240612 inhibited des-Arg(9)-BK-induced paw edema in mice (3 and 10 mg/kg p.o. and 0.3 and 1 mg/kg i.p.). Moreover, SSR240612 reduced capsaicin-induced ear edema in mice (0.3, 3 and 30 mg/kg p.o.) and tissue destruction and neutrophil accumulation in the rat intestine following splanchnic artery occlusion/reperfusion (0.3 mg/kg i.v.). The compound also inhibited thermal hyperalgesia induced by UV irradiation (1 and 3 mg/kg p.o.) and the late phase of nociceptive response to formalin in rats (10 and 30 mg/kg p.o.). Finally, SSR240612 (20 and 30 mg/kg p.o.) prevented neuropathic thermal pain induced by sciatic nerve constriction in the rat. In conclusion, SSR240612 is a new, potent, and orally active specific non-peptide bradykinin B(1) receptor antagonist.