Isotactic rac-Lactide Polymerization with Copper Complexes: The Influence of Complex Nuclearity.

Diiminopyrrolide copper alkoxide complexes, LCuOR (OR(1)=N,N-dimethylamino ethoxide, OR(2)=2-pyridyl methoxide), are active for the polymerization of rac-lactide at ambient temperature in benzene to yield polymers with M(w)/M(n)=1.0-1.2. X-ray diffraction studies showed bridged dinuclear complexes in the solid state for both complexes. While LCuOR(1) provided only atactic polylactide, LCuOR(2) produced partially isotactic polylactide (P(m)=0.7). The difference in stereocontrol is attributed to a dinuclear active species for LCuOR(2) in contrast to a mononuclear species for LCuOR(1).

Effect of nateglinide on the incidence of diabetes and cardiovascular events.

BACKGROUND: The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS: In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS: After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS: Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)

Effect of valsartan on the incidence of diabetes and cardiovascular events.

BACKGROUND: It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS: In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS: The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS: Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)

Square-planar Cu(II) diketiminate complexes in lactide polymerization.

Cu(OiPr)2 was reacted with several ß-diketimine ligands, nacnac(R)H. Sterically undemanding ligands with N-benzyl substituents afforded the dimeric heteroleptic complexes [nacnac(Bn)Cu(µ-OiPr)]2 and [3-Cl-nacnac(Bn)Cu(µ-OiPr)]2 (Bn = benzyl). With sterically more demanding amines, dimerization was not possible, and the putative nacnacCuOiPr intermediate underwent ligand exchange to the homoleptic bisdiketiminate complexes Cu(nacnac(ipp))2 and Cu(nacnac(Naph))2 (ipp = 2-isopropylphenyl, Naph = 1-napthyl). Homoleptic complexes were also prepared with N-benzyl ligands to yield Cu(nacnac(Bn))2 and Cu(3-succinimido-nacnac(Bn))2. All complexes were characterized by single-crystal X-ray diffraction. Even bulkier ligands with N-anthrylmethyl, N-mesitylmethyl, or N-methylbenzyl substituents failed to react with Cu(OiPr)2. In the case of nacnac(dipp)CuOiPr, putative nacnac(dipp)CuOiPr decomposed by ß-hydride elimination. Heteroleptic complexes [nacnac(Bn)Cu(µ-OiPr)]2 and [3-Cl-nacnac(Bn)Cu(µ-OiPr)]2 are very highly active rac-lactide polymerization catalysts, with complete monomer conversion at ambient temperature in solution in 0.5-5 min. In the presence of free alcohol, the homoleptic complexes seem to be in equilibrium with small amounts of the respective heteroleptic complex, which are sufficient to complete polymerization in less than 60 min at room temperature. All catalysts show high control of the polymerization with polydispersities of 1.1 and below. The obtained polymers were essentially atactic, with a slight heterotactic bias at ambient temperature and at -17 °C.

Physical activity is strongly inversely related to post-challenge plasma glucose and glycemic spikes in a risk population for type 2 diabetes.

AIM: To examine the relationship between physical activity (PA) and various cardiometabolic risk factors during an oral glucose tolerance test (OGTT), including glycemic spikes (PGS) in individuals at risk for type 2 diabetes. SUBJECTS AND METHODS: A total of 949 middle-aged subjects from the Risk factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) trial aged 40-70 years were included in the present cross-sectional analysis. Standard 75 g OGTT was performed and blood was collected every 30 min for 2 hours for measurements of plasma glucose (PG) and other cardiometabolic risk factors. PA was assessed using interviewer-administered questionnaire. RESULTS: Post-challenge PGS and maximal PG (PGmax) during OGTT were significantly lower in individuals with high PA vs. individuals with low PA even after body mass index (BMI) adjustment (p = 0.026 and p = 0.035, respectively). In univariate analysis post-challenge PG 30, 60, 90, and 120 minutes, PGS and PGmax during OGTT were significantly inversely correlated to PA. This correlation was attenuated but remained significant after adjustment for BMI. Fasting PG and glycosylated hemoglobin were not correlated to PA. Significantly higher fasting and post-challenge insulin levels were found among subjects with low vs. subjects with medium (p < 0.05) and high PA (p < 0.05). Post-challenge C-peptide and proinsulin levels were significantly lower in participants with high vs. participants with low PA (p < 0.05 for all). The relationship between 2-h PG and PA was observed also in lean subjects and in subjects with normal fasting glucose. In multivariate analysis PA was a significant independent determinant of 2-h PG. CONCLUSION: We found a strong inverse relationship between PA and various post-challenge cardiometabolic parameters during OGTT, including glycemic spikes, in a population at risk for diabetes. This relationship was only partially dependent on BMI.

Formation and reactivity of 3-diazopyridinium cations and influence on their reductive electrografting on glassy carbon.

The in situ generation of 3-diazonium cations from 3-aminopyridine and their subsequent stability under experimental conditions used for electrografting of pyridine groups were investigated by spectroscopy and electrochemistry. UV spectroscopy revealed the rapid kinetics for the reaction of 3-aminopyridine with sodium nitrite in HCl to form the 3-diazopyridinium cation with a second-order rate constant of 550 ± 20 L mol(-1) s(-1) at 22 °C. UV spectroscopy showed that the 3-diazopyridinium ion was relatively unstable and its transformation into 3-hydroxypyridine was proven by (1)H NMR. Its hydrolytic decomposition was investigated by NMR and followed first-order kinetics with a rate constant of (53 ± 5) × 10(-3) s(-1) at 22 °C. These results enable us to establish the appropriate conditions for the electrografting of pyridine from the corresponding diazonium cations generated in situ. The electrochemical modification of glassy carbon electrodes with pyridine was characterized by cyclic voltammetry and the resulting grafted layer by electrochemical impedance spectroscopy in the presence of Fe(CN)(6)(3-/4-) as redox probes. The effect of diazotization time before electrochemical reduction on the blocking effect of the grafted layer was investigated and showed that an increase of the diazotization time led to less efficient grafting. The presence of immobilized pyridine on the electrode surface was demonstrated by X-ray photoelectron spectroscopy measurements, and a surface coverage of 8.8 × 10(-10) mol cm(-2) was estimated for the grafted pyridine groups. The significance of these results for researchers using the in situ generation approach for electrochemical and chemical grafting is discussed.

Association of physical activity with insulin resistance, subclinical inflammation, coagulation, and fibrinolytic biomarkers among population at high risk for type 2 diabetes.

OBJECTIVE: TO investigate the association of physical activity with insulin resistance and biomarkers of inflammation, coagulation, and fibrinolysis in a population at high risk for type 2 diabetes. PATIENTS AND METHODS: A total of 778 subjects from the Risk factors in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study aged 40-70 years were included in the present cross-sectional analysis. RESULTS: Participants classified as having low physical activity (PA) were more insulin resistant in comparison to participants with medium (P = 0.042) and high PA (P = 0.015). Individuals with high physical activity had a significantly lower leucocytes count than individuals with low PA (P = 0.027) and significantly lower hs-CRP and fibrinogen concentrations than individuals with medium (P = 0.011 and P = 0.021) and low physical activity (P = 0.04 and P = 0.007). Although a trend towards a decrease in plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (tPA) levels with increasing physical activity was present, significant differences were observed only between subjects with high and medium physical activity (P = 0.045 and P = 0.033). In multivariate regression analyses physical activity was an independent determinant of insulin resistance, leucocytes count, hs-CRP, and fibrinogen concentrations. CONCLUSIONS: Physical activity was independently associated with insulin resistance and biomarkers of inflammation, whereas only a tendency towards decreased concentrations of coagulation and fibrinolytic biomarkers with increasing physical activity was observed.

Low-density lipoprotein cholesterol goal attainment in Germany: Results from the DA VINCI study.

Background and aims: Cardiovascular mortality is high in Germany. For patients with high or very high cardiovascular risk, the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT). This study aimed to assess dyslipidaemia management and achievement of the ESC/EAS guideline-recommended low-density lipoprotein cholesterol (LDL-C) goals. Methods: This European 18-country, cross-sectional, observational DA VINCI study (EUPAS22075) collected data during a single visit between June 2017 and November 2018 and included LLT in the preceding 12 months and the patients' most recent LDL-C measurement. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL-C goals while receiving stabilized LLT was assessed. Data from the German cohort are presented here. Results: Seven German sites enrolled a total of 421 primary and secondary prevention patients, 327 were receiving stabilized LLT at the time of LDL-C measurement, i.e. statin monotherapy of high (16%; n = 53), moderate (49%; n = 160) or low (7%; n = 24) intensity, ezetimibe combination (18%; n = 58), proprotein convertase subtilisin/kexin type 9 antibody combination (3%; n = 9), and other LLT (7%; n = 23). The 2016 and 2019 risk-based LDL-C goals were attained by 46% (n = 149) and 28% (n = 92) of patients, respectively. Conclusions: There is a large gap between ESC/EAS recommendations and LDL-C goal achievement in routine clinical practice in high and very high-risk patients in Germany. Low-to-moderate-intensity statin monotherapy was the most frequently used LLT; use of high-intensity statins and combination therapy was limited. In addition to optimizing statin intensity, combination with non-statin LLT may be needed in most of these patients.

Correlation of SHOX2 gene amplification and DNA methylation in lung cancer tumors.

BACKGROUND: DNA methylation in the SHOX2 locus was previously used to reliably detect lung cancer in a group of critical controls, including 'cytologically negative' samples with no visible tumor cell content, at a high specificity based on the analysis of bronchial lavage samples. This study aimed to investigate, if the methylation correlates with SHOX2 gene expression and/or copy number alterations. An amplification of the SHOX2 gene locus together with the observed tumor-specific hypermethylation might explain the good performance of this marker in bronchial lavage samples. METHODS: SHOX2 expression, gene copy number and DNA methylation were determined in lung tumor tissues and matched morphologically normal adjacent tissues (NAT) from 55 lung cancer patients. Quantitative HeavyMethyl (HM) real-time PCR was used to detect SHOX2 DNA methylation levels. SHOX2 expression was assayed with quantitative real-time PCR, and copy numbers alterations were measured with conventional real-time PCR and array CGH. RESULTS: A hypermethylation of the SHOX2 locus in tumor tissue as compared to the matched NAT from the same patient was detected in 96% of tumors from a group of 55 lung cancer patients. This correlated highly significantly with the frequent occurrence of copy number amplification (p < 0.0001), while the expression of the SHOX2 gene showed no difference. CONCLUSIONS: Frequent gene amplification correlated with hypermethylation of the SHOX2 gene locus. This concerted effect qualifies SHOX2 DNA methylation as a biomarker for lung cancer diagnosis, especially when sensitive detection is needed, i.e. in bronchial lavage or blood samples.

Development and evaluation of an educational intervention for general practitioners and staff caring for people with dementia living in residential facilities.

BACKGROUND: Despite high levels of participation in dementia education, general practitioners (GPs) and residential care facility (RCF) staff report perceived learning needs. Small group education, which is flexible, individualized, practical and case-based, is sought. We aimed to develop educational interventions for GPs and RCF staff tailored to meet their perceived educational needs. METHODS: We used a consultative process to develop education programs. A flexible program for RCF staff was developed in 30-minute blocks, which could be combined in sessions of different lengths. The RCF program aimed to facilitate sustainable change by engaging local "Dementia Champions". For GPs, face-to-face and self-directed packages were developed. We collected participant feedback to evaluate the program. RESULTS: GPs and RCF staff were recruited as part of a larger intervention study. Sixteen of the 27 GPs who were offered the dementia education participated. Two of the 16 GPs participated in both learning packages. A total of 45 GP feedback responses were received from 16 GPs: 28 out of 45 GPs (62%) reported that the participants' learning needs were entirely met. Eighteen of 19 facilities offered the intervention participated and 326 RCF staff attended one or more of the 94 RCF education sessions. Feedback was collected from 93 sessions: 1013 out of 1067 RCF staff feedback responses (95%) reported that the session met the participants' learning needs. Qualitative feedback was also strongly positive. CONCLUSION: Participants perceived the education programs as meeting their needs. Despite explicit attempts to provide flexible delivery options, overall participation rates remained low.

'Gotta be sit down and worked out together': views of Aboriginal caregivers and service providers on ways to improve dementia care for Aboriginal Australians.

INTRODUCTION: Dementia is five-fold more prevalent among Aboriginal than non-Aboriginal Australians. Despite this, the quality of care available to people living with dementia in remote Aboriginal communities is poor. The objective of this study was to determine ways to overcome factors affecting the successful delivery of services to Aboriginal people with dementia living in remote communities, and to their families and communities. METHODS: This qualitative research took place in the Kimberley Region of Western Australia. Data collection occurred in three stages: (1) interviews with service providers to identify the services available; (2) interviews with the caregivers of Aboriginal people living with dementia and community-based care workers; and (3) focus groups with community representatives and community care staff. Each stage was concluded when no new themes emerged. At each stage the transcribed information was analysed and joint interpretation identified common themes. RESULTS: In total, 42 service providers, 31 caregivers and community-based care workers were interviewed and 3 focus groups were conducted. Obstacles to accessing quality care were mentioned and recommendations on ways to improve care were made. The key themes that emerged were caregiver role, perspectives of dementia, community and culturally-appropriate care, workforce, education and training, issues affecting remote communities and service issues. Detailed information on how each theme affects the successful delivery of dementia care is provided. CONCLUSIONS: These research findings indicate that people living with dementia and their caregivers in remote Aboriginal communities are struggling to cope. They are requesting and require better community care. Implementing a culturally safe model of dementia care for remote Aboriginal communities that encompasses the recommendations made and builds on the strengths of the communities could potentially deliver the required improvements to dementia care for this population.

Current experiences and educational preferences of general practitioners and staff caring for people with dementia living in residential facilities.

BACKGROUND: Residential care is important for older adults, particularly for those with advanced dementia and their families. Education interventions that achieve sustainable improvement in the care of older adults are critical to quality care. There are few systematic data available regarding the educational needs of Residential Care Facility (RCF) staff and General Practitioners (GPs) relating to dementia, or the sustainability of educational interventions. We sought to determine participation in dementia education, perceived levels of current knowledge regarding dementia, perceived unmet educational needs, current barriers, facilitators and preferences for dementia education. METHODS: A mixed methods study design was utilised. A survey was distributed to a convenience sample of general practitioners, and staff in 223 consecutive residential care facilities in Perth, Western Australia. Responses were received from 102 RCF staff working in 10 facilities (out of 33 facilities who agreed to distribute the survey) and 202 GPs (19% of metropolitan GPs). Quantitative survey data were summarised descriptively and chi squared statistics were used to analyse the distribution of categorical variables. Qualitative data were collected from general practitioners, staff in residential care facilities and family carers of people with dementia utilizing individual interviews, surveys and focus groups. Qualitative data were analysed thematically. RESULTS: Among RCF staff and GPs attending RCF, participation in dementia education was high, and knowledge levels generally perceived as good. The individual experiences and needs of people with dementia and their families were emphasised. Participants identified the need for a person centred philosophy to underpin educational interventions. Limited time was a frequently mentioned barrier, especially in relation to attending dementia care education. Perceived educational needs relating to behaviours of concern, communication, knowledge regarding dementia, aspects of person centred care, system factors and the multidisciplinary team were consistently and frequently cited. Small group education which is flexible, individualized, practical and case based was sought. CONCLUSION: The effectiveness and sustainability of an educational intervention based on these findings needs to be tested. In addition, future interventions should focus on supporting cultural change to facilitate sustainable improvements in care.

Pulse pressure is a strong predictor of cardiovascular risk: Data of the risk factors in impaired glucose tolerance for atherosclerosis and diabetes and the Sofia Metabolic Syndrome studies.

UNLABELLED: The aim of the present study was to examine the relationship between pulse pressure (PP), cardiovascular risk factors and intima-media thickness (IMT) in a population at risk for type 2 diabetes and atherosclerosis in Saxony, and to assess the association between PP and history of myocardial infarction in the general population of Bulgaria. MATERIAL AND METHODS: The Risk factors in IGT for Atherosclerosis and Diabetes (RIAD) study included 1139 subjects, aged 40-70 years, with a family history of type 2 diabetes, obesity and/or hyper/dyslipoproteinemia. The SMS study included 1018 subjects (> 14 years of age) from the general population of Bulgaria. RESULTS: In RIAD study, PP was significantly correlated with age, plasma glucose, body mass index, microalbuminuria, triglycerides, waist-to-hip ratio, plasminogen activator inhibitor, total cholesterol, free fatty acids, leucocytes count and HDL-cholesterol (inversely). PP was also significantly correlated with carotid IMT. In multivariate analysis PP was an independent determinant of IMT. In the Sofia Metabolic Syndrome (SMS) study PP was significantly correlated with age, body mass index, waist circumference and fasting glucose and was an independent significant determinant of history of myocardial infarction. CONCLUSIONS: PP was an important cardiovascular risk factor both in a risk population for type 2 diabetes and atherosclerosis in Saxony and in the general population of Bulgaria.

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.

We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4+/-6.5 years; body mass index [BMI] 29.2+/-4.1 kg/m2; mean +/- SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator (t-PA) and blood lipids were monitored over six months. Atorvastatin treatment, alone and in combination with pioglitazone, revealed a significant regression in IMT (0.923+/-0.013 to 0.874+/-0.012 mm and 0.921+/-0.015 to 0.882+/-0.015 mm; mean +/- SEM; p<0.05 respectively) and Aix@75 (27.3+/-1.2 to 25.9+/-1.4; and 25.6+/-1.4 to 24.8+/-1.7%; p<0.05). The endothelial response to acetylcholine as measured by laser Doppler fluximetry (LDF) improved during combined treatment (373+/-57 to 576+/-153 AU; p<0.05). Addition of pioglitazone to atorva-statin resulted in significant further effects on high-sensitivity C-reactive protein (hsCRP), t-PA, P-selectin, adiponectin, triglycerides and high-density lipoprotein (HDL) cholesterol (p<0.05 respectively). Atorvastatin significantly improved IMT and vascular elasticity. Co-administration of pioglitazone provided additional effects on endothelial function, lipid profile and laboratory markers of inflammation.

Dinuclear iminophenoxide copper complexes in rac-lactide polymerisation.

Dinuclear bis(R'-(R''-iminomethyl)phenoxide) copper complexes L2Cu2(µ-OR)2 were prepared from the reaction of copper methoxide with ROH and LH (ROH = dimethylaminoethanol or pyridylmethanol, R' = H, 4,6-tBu, 1,3-Cl, R'' = benzyl, cyclohexyl, diphenylmethyl and 2,6-dimethylphenyl). Preparation was complicated by formation of homoleptic L2Cu and only 9 of the 24 possible combinations could be prepared. All complexes were characterized by single crystal X-ray diffraction studies and crystallized as dinuclear penta-coordinated complexes. Homoleptic complexes L2Cu were inactive in lactide polymerization at room temperature. Most heteroleptic complexes showed modest to good activities with full conversion in less than 6 h at room temperature. Complexes with R' = H showed poor molecular weight control, complexes with R' = Cl were inactive in polymerization. In pyridylmethoxide-containing complexes, only one alkoxide initiated chain growth. All complexes produced atactic polymer.

Configurationally flexible zinc complexes as catalysts for rac-lactide polymerisation.

Zn(N(SiMe3)2)2 was reacted with pyridinemethanol and R,R-N,N'-di(methylbenzyl)-2,5-diiminopyrrole (L1H) to afford the dimeric complex (L1)2Zn2(µ-OR)2. The complex showed moderate activity in rac-lactide polymerization to heterotactic polymer (Pr = 0.75). 2,4-Di-tert-butyl-6-aminomethyl-phenol ligands with amino = N,N,N',N'-tetramethyldiethylenetriamine (L2H) or di-(2-picoly)amine (L3H) were reacted with ZnEt2 to form (L2)ZnEt and with Zn(N(SiMe3)2)2 to form the respective amide complexes. All complexes, including (L1)2Zn2(µ-OR)2 were characterised by X-ray diffraction studies. (L2)ZnEt was unreactive toward ethanol, but the amide complexes afforded (L2)ZnOEt and (L3)ZnOEt upon reaction with ethanol, which were used in rac-lactide polymerization without isolation. All complexes racemise readily at room temperature and show apparent Cs-symmetry in their NMR spectra. The ethoxide complexes were highly active in lactide polymerization, with (L3)ZnOEt reaching full conversion in 15 min at 0.5 mM catalyst concentration at room temperature. In both cases, introduction of a second donor arm on the central nitrogen introduced a slight bias for isotactic monomer enchainment (Pm = 0.55-0.60), which for (L3)ZnOEt was dependent on catalyst concentration.

Physical disability contributes to caregiver stress in dementia caregivers.

BACKGROUND: Previous findings of studies on the impact of physical illness on caregiver health have been inconsistent. The authors wanted to determine whether physical disability, as determined by the SF-12 survey that provides information on both physical and mental health problems, contributes to caregiver stress. METHODS: The authors interviewed 91 primary caregivers (aged 38-85 years) of persons with dementia who had been referred by their family physicians for the first time for formal support services or memory evaluation. Caregivers completed the SF-12 version of the Medical Outcomes Study Short Form Health Survey that generates Mental Component Summary (MCS) and Physical Component Summary (PCS) scores and reported on caregiver stress and concurrent medical conditions and medications. RESULTS: Most caregivers reported stress (76.9%), having medical conditions (72.4%), or taking medications (67%). The MCS but not the PCS scores were significantly lower than community norms, indicating an excess of disability due to mental health problems. Nevertheless, 40.7% had PCS scores indicating some degree of physical disability. Using multiple logistic regression analysis, PCS scores but not the presence of medical problems were independently associated with caregiver stress. CONCLUSIONS: Chronic disability as assessed by SF-12 PCS scores is independently associated with caregiver stress. These data suggest that caregivers of persons with dementia should be assessed for disabling physical conditions and mental health problems. In addition, reducing the impact of physical disability could ameliorate caregiver stress.

Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes study.

OBJECTIVE: Isolated impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are two risk categories for type 2 diabetes. This study compared both categories with respect to the degree of insulin secretion abnormalities and insulin resistance. RESEARCH DESIGN AND METHODS: This is a crossover comparison of a population at high risk for type 2 diabetes. The subjects were recruited from the Risk Factor in Impaired Glucose Tolerance for Atherosclerosis and Diabetes (RIAD) study. They underwent a 75-g oral glucose tolerance test, with measurement of specific insulin, C-peptide, proinsulin, and free fatty acids at baseline and every 30 min after load for 2 h. Factor analysis was performed to evaluate the importance of insulin resistance and secretion abnormalities in both categories. RESULTS: All categories of prediabetic hyperglycemia had a higher cardiovascular risk factor level when adjusted for sex, age, and BMI compared to control subjects with normal glucose tolerance. Subjects with isolated IFG were more insulin resistant than those with IGT. By contrast, subjects with isolated IGT exhibited a more severe deficit in early- and late-phase insulin secretion versus IFG subjects. As shown with factor analysis, in IFG the insulin resistance factor explained 28.4% of the variance, whereas in IGT the insulin secretion factor was dominant, explaining 31.1% of the total variance. CONCLUSIONS: Our cross-sectional data from the RIAD study demonstrate that isolated IFG and isolated IGT are different with respect to the degree of insulin resistance and anomalies in insulin secretion, and that subjects with IGT exhibit a deficit in the early and late phases of insulin secretion. This finding may be important for a differential approach in primary prevention of type 2 diabetes.

Exploring the reactivity of manganese(III) complexes with diphenolate-diamino ligands in rac-lactide polymerization.

Manganese(III) complexes of tetradentate diphenolate-diamino (NNOO(2-)) ligands were prepared from aerobic reaction of MnCl2 with the respective ligands in basic methanolic solution. Methoxide complexes (NNOO)Mn(OMe)(MeOH)0-1 were obtained for three ligands, while others only provided the respective chloride complexes (NNOO)Mn(Cl)(MeOH). Complexes were analyzed by X-ray diffraction studies and octahedral complexes showed evidence of Jahn-Teller distortions. Magnetic moments determined in MeOD were indicative of high-spin Mn(III)-d(4) complexes (µeff = 4.2-4.6µB). Methoxide complexes were active in the coordination-insertion polymerization of rac-lactide (130 °C, 0.33-1.0 mol% catalyst loading) to yield atactic polylactic acid with moderate molecular weight control. Polymerization activity was reduced, but not suppressed by the presence of protic impurities. Chloride complexes showed less activity and only in the presence of external alcohol, indicative of an activated-monomer mechanism.

Parallel screening for ALK, MET and ROS1 alterations in non-small cell lung cancer with implications for daily routine testing.

OBJECTIVES: ALK, MET and ROS1 are prognostic and predictive markers in NSCLC, which need to be implemented in daily routine. To evaluate different detection approaches and scoring systems for optimal stratification of patients eligible for mutation testing in the future, we screened a large and unselected cohort of NSCLCs for all three alterations. MATERIAL AND METHODS: Using tissue microarrays, 473 surgically resected NSCLCs were tested for ALK and MET expression by IHC and genomic alterations in the ALK, MET and ROS1 gene by FISH. For MET IHC, two different criteria (MetMAb and H-score), for MET FISH, three different scoring systems (UCCC, Cappuzzo, PathVysion) were investigated. RESULTS: ALK and ROS1 positivity was seen in 2.6% and 1.3% of all ADCs, respectively, but not in pure SCCs. One ROS1 translocated tumor showed additional ROS1 amplification. MET IHC+/FISH+ cases were found in both histological subtypes (8.6% in all NSCLCs; 10.6% in ADCs; 5.0% in SCCs) and were associated with pleural invasion, lymphatic vessel invasion and lymph node metastasis. MET altered ADCs more frequently showed a papillary growth pattern. Whereas ALK testing revealed homogenous results in IHC and FISH, we saw discordant results for MET in about 10% of cases. Both METIHC scoring systems revealed almost identical results. We did not encounter any combined FISH positivity for ALK, MET or ROS1. However, three ALK positive cases harbored MET overexpression. CONCLUSION: In daily routine, IHC could support FISH in the identification of ALK altered NSCLCs. Further research is needed to assess the role of discordant MET results by means of IHC and FISH as well as the relevance of tumors with an increased ROS1 gene copy number.