Structure Of A Thionucleoside - 5'-Deoxy-5',6-Epithio-5,6-Dihydro-2',3'-Ortho-Isopropylidene-3-Methyluridine

C13HlsN205 S, M r = 314.35, orthorhombic, P212121 with a = 39.526 (4), b = 6.607 (2), c = 5.661 (2) A, Z = 4, V = 1478.36 A 3, D c = 1.412 Mg m -3, Cu Ka radiation. Final R = 0.073 for 1154 observed counter reflections. The sulphur atom is in a pseudo-equatorial position with respect to the dihydrouracil ring. The sugar pucker is predominantly O(l')-exo unlike the C(3')-exo,C(4')-endo observed for 2',3' O-isopropylideneuridine (ISPU). The fivemembered dioxolane ring has C(7) displaced by 0.497 (7)A from the best plane through atoms 0(2'), C(2'), C(3'), 0(3'), in contrast to ISPU where 0(3') shows the maximum deviation.

Anthropometric measures of obesity-their association with type 2 diabetes and hypertension across ethnic groups

Clinical trials have shown that weight reduction with lifestyles can delay or prevent diabetes and reduce blood pressure. An appropriate definition of obesity using anthropometric measures is useful in predicting diabetes and hypertension at the population level. However, there is debate on which of the measures of obesity is best or most strongly associated with diabetes and hypertension and on what are the optimal cut-off values for body mass index (BMI) and waist circumference (WC) in this regard. The aims of the study were 1) to compare the strength of the association for undiagnosed or newly diagnosed diabetes (or hypertension) with anthropometric measures of obesity in people of Asian origin, 2) to detect ethnic differences in the association of undiagnosed diabetes with obesity, 3) to identify ethnic- and sex-specific change point values of BMI and WC for changes in the prevalence of diabetes and 4) to evaluate the ethnic-specific WC cutoff values proposed by the International Diabetes Federation (IDF) in 2005 for central obesity. The study population comprised 28 435 men and 35 198 women, ≥ 25 years of age, from 39 cohorts participating in the DECODA and DECODE studies, including 5 Asian Indian (n = 13 537), 3 Mauritian Indian (n = 4505) and Mauritian Creole (n = 1075), 8 Chinese (n =10 801), 1 Filipino (n = 3841), 7 Japanese (n = 7934), 1 Mongolian (n = 1991), and 14 European (n = 20 979) studies. The prevalence of diabetes, hypertension and central obesity was estimated, using descriptive statistics, and the differences were determined with the χ2 test. The odds ratios (ORs) or  coefficients (from the logistic model) and hazard ratios (HRs, from the Cox model to interval censored data) for BMI, WC, waist-to-hip ratio (WHR), and waist-to-stature ratio (WSR) were estimated for diabetes and hypertension. The differences between BMI and WC, WHR or WSR were compared, applying paired homogeneity tests (Wald statistics with 1 df). Hierarchical three-level Bayesian change point analysis, adjusting for age, was applied to identify the most likely cut-off/change point values for BMI and WC in association with previously undiagnosed diabetes. The ORs for diabetes in men (women) with BMI, WC, WHR and WSR were 1.52 (1.59), 1.54 (1.70), 1.53 (1.50) and 1.62 (1.70), respectively and the corresponding ORs for hypertension were 1.68 (1.55), 1.66 (1.51), 1.45 (1.28) and 1.63 (1.50). For diabetes the OR for BMI did not differ from that for WC or WHR, but was lower than that for WSR (p = 0.001) in men while in women the ORs were higher for WC and WSR than for BMI (both p < 0.05). Hypertension was more strongly associated with BMI than with WHR in men (p < 0.001) and most strongly with BMI than with WHR (p < 0.001), WSR (p < 0.01) and WC (p < 0.05) in women. The HRs for incidence of diabetes and hypertension did not differ between BMI and the other three central obesity measures in Mauritian Indians and Mauritian Creoles during follow-ups of 5, 6 and 11 years. The prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others, given the same BMI or WC category. The  coefficients for diabetes in BMI (kg/m2) were (men/women): 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for Asian Indian, Chinese, Japanese, Mauritian Indian and European (overall homogeneity test: p > 0.05 in men and p < 0.001 in women). Similar results were obtained in WC (cm). Asian Indian women had lower  coefficients than women of other ethnicities. The change points for BMI were 29.5, 25.6, 24.0, 24.0 and 21.5 in men and 29.4, 25.2, 24.9, 25.3 and 22.5 (kg/m2) in women of European, Chinese, Mauritian Indian, Japanese, and Asian Indian descent. The change points for WC were 100, 85, 79 and 82 cm in men and 91, 82, 82 and 76 cm in women of European, Chinese, Mauritian Indian, and Asian Indian. The prevalence of central obesity using the 2005 IDF definition was higher in Japanese men but lower in Japanese women than in their Asian counterparts. The prevalence of central obesity was 52 times higher in Japanese men but 0.8 times lower in Japanese women compared to the National Cholesterol Education Programme definition. The findings suggest that both BMI and WC predicted diabetes and hypertension equally well in all ethnic groups. At the same BMI or WC level, the prevalence of diabetes was highest in Asian Indians, lowest in Europeans and intermediate in others. Ethnic- and sex-specific change points of BMI and WC should be considered in setting diagnostic criteria for obesity to detect undiagnosed or newly diagnosed diabetes.

Benno Strauss with unidentified family members; Edel-Str. 6, Würzburg.

Verso: handwritten correspondence

Genome-wide association study identifies a locus at 7p15.2 associated with endometriosis

Endometriosis is a common gynecological disease associated with pelvic pain and subfertility. We conducted a genome-wide association study (GWAS) in 3,194 individuals with surgically confirmed endometriosis (cases) and 7,060 controls from Australia and the UK. Polygenic predictive modeling showed significantly increased genetic loading among 1,364 cases with moderate to severe endometriosis. The strongest association signal was on 7p15.2 (rs12700667) for 'all' endometriosis (P = 2.6 x 10(-)(7), odds ratio (OR) = 1.22, 95% CI 1.13-1.32) and for moderate to severe disease (P = 1.5 x 10(-)(9), OR = 1.38, 95% CI 1.24-1.53). We replicated rs12700667 in an independent cohort from the United States of 2,392 self-reported, surgically confirmed endometriosis cases and 2,271 controls (P = 1.2 x 10(-)(3), OR = 1.17, 95% CI 1.06-1.28), resulting in a genome-wide significant P value of 1.4 x 10(-)(9) (OR = 1.20, 95% CI 1.13-1.27) for 'all' endometriosis in our combined datasets of 5,586 cases and 9,331 controls. rs12700667 is located in an intergenic region upstream of the plausible candidate genes NFE2L3 and HOXA10.

Human herpesvirus 6 in multiple sclerosis and encephalitis

Human herpesvirus 6 (HHV-6) was identified from patients with HIV and lymphoproliferative diseases in 1986. It is a β-herpesvirus and is divided into two subgroups, variants A and B. HHV-6 variant B is the cause of exanthema subitum, while variant A has not yet definitely proven to cause any disease. HHV-6, especially variant A, is a highly neurotropic virus and has been associated with many diseases of the central nervous system (CNS) such as encephalitis and multiple sclerosis (MS). The present studies were aimed to elucidate the role of HHV-6 and its two variants in neurological infections. Special attention was given to study the possible role of HHV-6 in the pathogenesis of MS. We studied the expression of HHV-6 antigens using immunohistochemistry in brain autopsy samples from patients with MS and controls. HHV-6 antigen was identified in 70% of MS specimens whereas 30% of control specimens expressed HHV-6 antigen. Serum and cerebrospinal fluid (CSF) samples were collected from patients with MS and patients with other neurological diseases (OND) from patients visiting Helsinki University Central Hospital Neurological Outpatient Clinic during the years 2003 and 2004. In addition, we studied 53 children with suspected encephalitis. We developed an immunofluorescence IgG-avidity assay for the detection of primary HHV-6A and HHV-6B infection. For HHV-6B antibodies, no differences were observed between patients with MS and OND. For HHV-6A both seroprevalence and mean titers were significantly higher in MS compared to OND. HHV-6A low-avidity IgG antibodies, suggestive of primary infection, were found in serum of two, three and one patient with definite MS, possible MS and OND, respectively. From pediatric patients with suspected encephalitis, six serum samples (11.3%) contained low-avidity antibodies, indicating a temporal association between HHV-6A infection and onset of encephalitis. Three out of 26 patients with CDMS and four out of 19 patients with CPMS had HHV-6 antibodies in their CSF compared to none of the patients with OND (p=0.06 and p=0.01, respectively). Two patients with CDMS and three patients with CPMS appeared to have specific intrathecal synthesis of HHV-6A antibodies. In addition, oligoclonal bands (OCB) were observed in the CSF of five out of nine MS patients tested, and in two the OCBs reacted specifically with HHV-6 antigen, which is a novel finding. These results indicate HHV-6 specific antibody production in the CNS and suggest that there is a subset of MS patients with an active or chronic HHV-6A infection in the CNS that might be involved in the pathogenesis of MS. Our studies suggest that HHV-6 is an important causative or associated virus in some neurological infections, such as encephalitis and it might contribute to the development of MS, at least in some cases. In conclusion, HHV-6 is a neurotropic virus that should be taken into consideration when studying acute and chronic CNS diseases of unknown origin.

1H and 13C NMR spectral studies of C-2 substituted isomeric exo- and endo-5-methyl-bicyclo[3.2.1]octane-6,8-diones

A detailed analysis of the 1H and 13C NMR spectra of C-2 aryl and alkyl/desalkyl substituted isomeric exo- and endo-5-methylbicyclo[3.2.1]octane-6,8-diones is presented. The chemical shift of the C-5 angular methyl, the C-2 alkyl/olefinic (C-10)/C-2 methine protons, the aromatic proton shieldings and the characteristic AMX and ABX spectral pattern of the ketomethylene and bridgehead protons were found to be sensitive to the phenyl ring orientation (anisotropy). These distinctive features could be used for configurational distinction for this class of compounds. With increasing ortho-methoxy substitution on the phenyl ring, considerable deshilelding of the bridgehead proton was observed (ca. 0.6 ppm). Absence of the C-2 alkyl group in the desalkyl isomers resulted in substantial changes in the chemical shifts of different protons. A study of the NMR spectra of the corresponding bicyclic compounds with C-2 methoxy/hydroxy substitution instead of the aryl group revealed that the anisotropy of the phenyl ring and the electronegative oxygen substituents have opposite effects. The 13C NMR spectral assignment of each carbon resonance of C-2 aryl and alkyl/desalkyl substituted isomeric exo- and endo-5-methylbicyclo[3.2.1]octane-6,8-diones and the corresponding C-2 methoxy/hydroxy/chloro and methyl bicyclic compounds are reported. Additional ortho-methoxy substitution on the phenyl ring was found to produce considerable high field shifts of the C-10 and C-1 carbon resonances. A high-field shift was observed for the C-6 and C-8 carbonyl carbons, presumably due to 1,3-dicarbonyl interactions. The chemical shifts of C-1 aromatic, C-10 alkyl and C-2 carbons, which are sensitive to exo/endo isomerism, could be utilized in differentiating a pair of isomers.

Polypharmacy among inpatients aged 70 years or older in Australia

Objectives To investigate medication changes for older patients admitted to hospital and to explore associations between patient characteristics and polypharmacy. Design Prospective cohort study. Participants and setting Patients aged 70 years or older admitted to general medical units of 11 acute care hospitals in two Australian states between July 2005 and May 2010. All patients were assessed using the interRAI assessment system for acute care. Main outcome measures Measures of physical, cognitive and psychosocial functioning; and number of regular prescribed medications categorised into three groups: non-polypharmacy (0–4 drugs), polypharmacy (5–9 drugs) and hyperpolypharmacy (≥ 10 drugs). Results Of 1220 patients who were recruited for the study, medication records at admission were available for 1216. Mean age was 81.3 years (SD, 6.8 years), and 659 patients (54.2%) were women. For the 1187 patients with complete medication records on admission and discharge, there was a small but statistically significant increase in mean number of regular medications per day between admission and discharge (7.1 v 7.6), while the prevalence of medications such as statins (459 [38.7%] v 457 [38.5%] patients), opioid analgesics (155 [13.1%] v 166 [14.0%] patients), antipsychotics (59 [5.0%] v 65 [5.5%] patients) and benzodiazepines (122 [10.3%] v 135 [11.4%] patients) did not change significantly. Being in a higher polypharmacy category was significantly associated with increase in comorbidities (odds ratio [OR], 1.27; 95% CI, 1.20–1.34), presence of pain (OR, 1.31; 1.05–1.64), dyspnoea (OR, 1.64; 1.30–2.07) and dependence in terms of instrumental activities of daily living (OR, 1.70; 1.20–2.41). Hyperpolypharmacy was observed in 290/1216 patients (23.8%) at admission and 336/1187 patients (28.3%) on discharge, and the proportion of preventive medication in the hyperpolypharmacy category at both points in time remained high (1209/3371 [35.9%] at admission v 1508/4117 [36.6%] at discharge). Conclusions Polypharmacy is common among older people admitted to general medical units of Australian hospitals, with no clinically meaningful change to the number or classification (symptom control, prevention or both) of drugs made by treating physicians.

Polarized ethylenes: structures of (1,3-dimethyl-2-imidazolidinylidene)malononitrile and (1,3-dimethyl-2-perhydropyrimidinylidene)malononitrile

Crystal structures of the title compounds, (I) and (II), have been determined by three-dimensional diffraction methods. Crystals of CsHIoN 4 (I) are monoclinic, space group P21/a with Z = 4, Mr= 162, a = 7.965 (1), b = 16.232 (2), c = 7.343 (1) A, fl = 113.54 (1) °, V = 890.7 A 3, D,n = 1.218, D x = 1.208 gcm -3, g(Cu Ka, 2 = 1.5418/~) = 6.47 em -1, F(000) = 344. The crystals of C9H12N4 (II) are orthorhombic, space group P21en, with Z = 4, Mr = 176, a = 7.983 (3), b = 8.075 (2), c = 14.652 (3) ./k, V = 944.43/~3, Dm= 1.219, D x = 1.237 g cm -3, #(Mo Ka, ). = 0.7107 ,/k) = 0.868 cm -1, F(000) = 376. Both structures were solved by direct methods and refined to R = 5.8% for (I) and 5.3 % for (II). The C-C double-bond distances are 1.407 (3) in (I) and 1.429 (6)/~ in (II), appreciably longer than normal. The steric and push-pull effects result in rotation about the C=C bond, the rotation angles being 20.2 (3) in (I) and 31.5 (6) o in (II).

Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations

Elevated serum uric acid levels cause gout and are a risk factor for cardiovascular disease and diabetes. To investigate the polygenetic basis of serum uric acid levels, we conducted a meta-analysis of genome-wide association scans from 14 studies totalling 28,141 participants of European descent, resulting in identification of 954 SNPs distributed across nine loci that exceeded the threshold of genome-wide significance, five of which are novel. Overall, the common variants associated with serum uric acid levels fall in the following nine regions: SLC2A9 (p = 5.2x10(-201)), ABCG2 (p = 3.1x10(-26)), SLC17A1 (p = 3.0x10(-14)), SLC22A11 (p = 6.7x10(-14)), SLC22A12 (p = 2.0x10(-9)), SLC16A9 (p = 1.1x10(-8)), GCKR (p = 1.4x10(-9)), LRRC16A (p = 8.5x10(-9)), and near PDZK1 (p = 2.7x10(-9)). Identified variants were analyzed for gender differences. We found that the minor allele for rs734553 in SLC2A9 has greater influence in lowering uric acid levels in women and the minor allele of rs2231142 in ABCG2 elevates uric acid levels more strongly in men compared to women. To further characterize the identified variants, we analyzed their association with a panel of metabolites. rs12356193 within SLC16A9 was associated with DL-carnitine (p = 4.0x10(-26)) and propionyl-L-carnitine (p = 5.0x10(-8)) concentrations, which in turn were associated with serum UA levels (p = 1.4x10(-57) and p = 8.1x10(-54), respectively), forming a triangle between SNP, metabolites, and UA levels. Taken together, these associations highlight additional pathways that are important in the regulation of serum uric acid levels and point toward novel potential targets for pharmacological intervention to prevent or treat hyperuricemia. In addition, these findings strongly support the hypothesis that transport proteins are key in regulating serum uric acid levels.

Gottschalk residence; Ruehmkorffstrasse 6, Hannover, Germany.

The house the Gottschalk family lived in after 1934; Hans and Elizabeth Krakauer were married on the third floor in 1936

Implementing sustainable farming practices in the Herbert: The Oakleigh Farming Company experience

The Oakleigh Farming Company has been progressively changing its farming practices on its property at Cordelia in the Herbert River District. During the last ten years the changes have included the adoption of raised beds at 1.8m row spacing, controlled traffic and dual row planting using double disc opener planters. This paper describes some of the changes that have been made to the farming system and examines their impact on farm productivity and economic performance. Since changing to the current farming system, the farm gross margin has increased from $789/ha to $897/ha. In addition to the numerous cost savings, the new farming system has reduced the time spent on tractors by 54% across the whole farm. Return on investment on the 1997 farming system was 1.6% versus 2.7% on their current farming system. The farming company is continually looking for new ways to improve profitability and believes that innovation is critical for the long term sustainability of the sugar industry.

3-Acetyl-6-chloro-1-ethyl-4-phenylquinolin-2(1H)-one

In the title compound, C19H16ClNO2, the dihedral angle between the plane of the phenyl substituent and 3-acetylquinoline unit is 75.44 (5)degrees. The crystal structure is stabilized by intermolecular C-H center dot center dot center dot O hydrogen bonds.

Tombstone of Adolf Molling and his wife Henriette (Henny) nee Meyerhof in the Jewish cemetery An der Strangriede Str. 54. 7; Hannover, Germany. Cemeteries Tombs

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Tombstone of Adolf Molling and his wife Henriette (Henny) nee Meyerhof; Strangriede Cemetery Str.54.7; Hannover Cemeteries Tombs

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