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.

Epidemiological data of seasonal variation in mood and behaviour

The aim of this study was to measure seasonal variation in mood and behaviour. The dual vulnerability and latitude effect hypothesis, the risk of increased appetite, weight and other seasonal symptoms to develop metabolic syndrome, and perception of low illumination in quality of life and mental well-being were assessed. These variations are prevalent in persons who live in high latitudes and need balancing of metabolic processes to adapt to environmental changes due to seasons. A randomized sample of 8028 adults aged 30 and over (55% women) participated in an epidemiological health examination study, The Health 2000, applying the probability proportional to population size method for a range of socio-demographic characteristics. They were present in a face-to-face interview at home and health status examination. The questionnaires included the modified versions of the Seasonal Pattern Assessment Questionnaire (SPAQ) and Beck Depression Inventory (BDI), the Health Related Quality of Life (HRQoL) instrument 15D, and the General Health Questionnaire (GHQ). The structured and computerized Munich Composite International Diagnostic Interview (M-CIDI) as part of the interview was used to assess diagnoses of mental disorders, and, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria were assessed using all the available information to detect metabolic syndrome. A key finding was that 85% of this nationwide representative sample had seasonal variation in mood and behaviour. Approximately 9% of the study population presented combined seasonal and depressive symptoms with a significant association between their scores, and 2.6% had symptoms that corresponded to Seasonal Affective Disorder (SAD) in severity. Seasonal variations in weight and appetite are two important components that increase the risk of metabolic syndrome. Other factors such as waist circumference and major depressive disorder contributed to the metabolic syndrome as well. Persons reported of having seasonal symptoms were associated with a poorer quality of life and compromised mental well-being, especially if indoors illumination at home and/or at work was experienced as being low. Seasonal and circadian misalignments are suggested to associate with metabolic disorders, and could be remarked if individuals perceive low illumination levels at home and/or at work that affect the health-related quality of life and mental well-being. Keywords: depression, health-related quality of life, illumination, latitude, mental well-being, metabolic syndrome, seasonal variation, winter.

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

Verso: handwritten correspondence

Mutation analysis of TGF-β signaling pathway genes among Finnish patients with primary pulmonary hypertension and hereditary hemorrhagic telangiectasia

Primary pulmonary hypertension (PPH), or according to the recent classification idiopathic pulmonary hypertension (IPAH), is a rare, progressive disease of pulmonary vasculature leading to pulmonary hypertension and right heart failure. Most of the patients are sporadic but in about 6% of cases the disease is familial (FPPH). In 2000 two different groups identified the gene predisposing to PPH. This gene, Bone morphogenetic protein receptor type 2 (BMPR2), encodes a subunit of transforming growth factor β (TGF-β) receptor complex. There is a genetic connection between PPH and hereditary hemorrhagic telangiectasia (HHT), a bleeding disorder characterized by local telangiectasias and sometimes with pulmonary hypertension. In HHT, mutations in ALK1 (activin like kinase type 1) and Endoglin, another members of the TGF-β signaling pathway are found. In this study we identified all of the Finnish PPH patients for the years 1986-1999 using the hospital discharge registries of Finnish university hospitals. During this period we found a total of 59 confirmed PPH patients: 55 sporadic and 4 familial representing 3 different families. In 1999 the prevalence of PPH was 5.8 per million and the annual incidence varied between 0.2-1.3 per million. Among 28 PPH patients studied, heterozygous BMPR2 mutations were found in 12% (3/26) of sporadic patients and in 33% of the PPH families (1/3). All the mutations found were different. Large deletions of BMPR2 were excluded by single-stranded chain polymomorphism analysis. As a candidate gene approach we also studied ALK1, Endoglin, Bone Morphogenetic Receptor Type IA (BMPR1A or ALK3), Mothers Against Decapentaplegic Homolog 4 (SMAD4) and Serotonine Transporter Gene (SLC6A4) using single-strand conformational polymorphism (SSCP) analysis and direct sequencing. Among patients and family members studied, we found two mutations in ALK1 in two unrelated samples. We also identified all the HHT patients treated at the Department of Otorhinolaryngology at Helsinki University Central Hospital between the years of 1990-2005 and 8 of the patients were studied for Endoglin and ALK1 mutations using direct sequencing. A total of seven mutations were found and all the mutations were different. The absence of a founder mutation in the Finnish population in both PPH and HHT was somewhat surprising. This suggests that the mutations of BMPR2, ALK1 and Endoglin are quite young and the older mutations have been lost due to repetitive genetic bottlenecks and/or negative selection. Also, other genes than BMPR2 may be involved in the pathogenesis of PPH. No founder mutations were found in PPH or HHT and thus no simple genetic test is available for diagnostics.

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.

α-Synuclein pathology in very elderly Finns : A population-based clinico-neuropathologic and molecular genetic study of Dementia with Lewy bodies

Populations in developed countries are ageing fast. The elderly have the greatest incidence of de-mentia, and thus the increase in the number of demented individuals, increases the immediate costs for the governments concerning healthcare and hospital treatment. Attention is being paid to disorders behind cognitive impairment with behavioural and psychological symptoms, which are enormous contributors to the hospital care required for the elderly. The highest dreams are in prevention; however, before discovering the tools for preventing dementia, the pathogenesis behind dementia disorders needs to be understood. Dementia with Lewy bodies (DLB), a relatively recently discovered dementia disorder compared to Alzheimer’s disease (AD), is estimated to account for up to one third of primary degenerative dementia, thus being the second most common cause of dementia in the elderly. Nevertheless, the impact of neuropathological and genetic findings on the clinical syndrome of DLB is not fully established. In this present series of studies, the frequency of neuropathological findings of DLB and its relation to the clinical findings was evaluated in a cohort of subjects with primary degenerative dementia and in a population-based prospective cohort study of individuals aged 85 years or older. α-synuclein (αS) immunoreactive pathology classifiable according to the DLB consensus criteria was found in one fourth of the primary degenerative dementia subjects. In the population-based study, the corresponding figure was one third of the population, 38% of the demented and one fifth of the non-demented very elderly Finns. However, in spite of the frequent discovery of αS pathology, its association with the clinical symptoms was quite poor. Indeed, the common clinical features of DLB, hypokinesia and visual hallucinations, associated better with the severe neurofibrillary AD-type pathology than with the extensive (diffuse neocortical) αS pathology when both types of pathology were taken into account. The severity of the neurofibrillary AD-type pathology (Braak stage) associated with the extent of αS pathology in the brain. In addition, the genetic study showed an interaction between tau and αS; common variation in the αS gene (SNCA) associated significantly with the severity of the neurofibrillary AD-type pathology and nominally significantly with the extensive αS pathology. Further, the relevance and temporal course of the substantia nigra (SN) degeneration and of the spinal cord αS pathology were studied in relation to αS pathology in the brain. The linear association between the extent of αS pathology in the brain and the neuron loss in SN suggests that in DLB the degeneration of SN proceeds as the αS pathology extends from SN to the neocortex instead of early destruction of SN seen in Parkinson’s disease (PD). Furthermore, the extent of αS pathology in the brain associated with the severity of αS pathology in the thoracic and sacral autonomic nuclei of the spinal cord. The thoracic αS pathology was more common and more severe compared to sacral cord, suggesting that the progress of αS pathology proceeds downwards from the brainstem towards the sacral spinal cord.

Ternary metal complexes of anionic and neutral pyridoxine (vitamin B6) with 2,2'-bipyridine. Syntheses and x-ray structures of (pyridoxinato)bis(2,2'-bipyridyl)cobalt(III) perchlorate and chloro(2,2'-bipyridyl)(pyridoxine)copper(II) perchlorate hydrate

Ternary metal complexes involving vitamin B6 with formulas [CO",(PN-H)](anCdI [OC)'(bpy)(PN)Cl]C10(.bpHy 0 = 2,2'-bipyridine, PN = neutral pyridoxine, PN-H = anionic pyridoxine) have been prepared for the first time and characterized by means of magnetic and spectroscopic measurements. The crystal structures of the compounds have also been determined. [CO(PN-H)](CcryIsOta,l)lize s in the space group P2,/c with a = 18.900 (3) A, b = 8.764 (1) A, c = 20.041 (2) A,p = 116.05 (l)', and Z = 4 and [Cu(bpy)(PN)C1]C104-H20in the space group Pi with a = 12.136 (5) A, b = 13.283 (4) A,c = 7.195 (2) A, a = 96.91 (Z)', 0 = 91.25 (3)', y = 71.63 (3)', and Z = 2. The structures were solved by the heavy-atom method and refined by least-squares techniques to R values of 0.080 and 0.042 for 3401 and 2094 independent reflections, respectively. Both structures consist of monomeric units. The geometry around Co(II1) is octahedral and around Cu(I1) is distorted square pyramidal. In [CO(PN-H)]t(wCo IoxOy~ge)n~s ,fro m phenolic and 4-(hydroxymethyl) groups of PN-H and two nitrogens from each of two bpy's form the coordination sphere. In [Cu(bpy)(PN)C1]C104.H20o ne PN and one bpy, with the same donor sites, act as bidentate chelates in the basal plane, with a chloride ion occupying the apical position. In both structures PN and PN-H exist in the tautomeric form wherein pyridine N is protonated and phenolic 0 is deprotonated. However, a novel feature of the cobalt compound is that PN-H is anionic due to the deprotonation of the 4-(hydroxymethyl) group. The packing in both structures is governed by hydrogen bonds, and in the copper compound partial stacking of bpy's at a distance of -3.55 also adds to the stability of the system. Infrared, NMR, and ligand field spectroscopic results and magnetic measurements are interpreted in light of the structures.

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.

Fisheries Queensland Long Term Monitoring Program Underwater Visual Census of twenty-four reefs on the Great Barrier Reef between 1999 and 2004.

In 1999, the Department of Employment, Economic Development and Innovation (DEEDI), Fisheries Queensland undertook a new initiative to collect long term monitoring data of various important stocks including reef fish. This data and monitoring manual for the reef fish component of that program which was based on Underwater Visual Census methodology of 24 reefs on the Great Barrier Reef between 1999 and 2004. Data was collected using six 50m x 5m transects at 4 sites on 24 reefs. Benthic cover type was also recorded for 10m of each transect. The attached Access Database contains 5 tables being: SITE DETAILS TABLE Survey year Data entry complete REF survey site ID Site # (1-4) Location (reef name) Site Date (date surveyed) Observer 1 (3 initials to identify who estimated fish lengths and recorded benthic cover) TRANSECT DETAILS Survey ID Transect Number (1-6) Time (the transect was surveyed) Visibility (in metres) Minimum Depth surveyed (m) Maximum Depth surveyed (m) Percent of survey completed (%) Comments SUBSTRATE Survey ID Transect Number (1-6) then % cover of each of eth following categories of benthic cover types Dead Coral Live Coral Soft Coral Rubble Sand Sponge Algae Sea Grass Other COORDINATES (over survey sites) from -14 38.792 to -19 44.233 and from 145 21.507 to 149 55.515 SIGHTINGS ID Survey ID Transect Number (1-6) CAAB Code Scientific Name Reef Fish Length (estimated Fork Length of fish; -1 = unknown or not recorded) Outside Transect (if a fish was observed outside a transect -1 was recorded) Morph Code (F = footballer morph for Plectropomus laevis, S = Spawning colour morph displayed)

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

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.

Study of internal motions through N.Q.R. in 6-Chloropyridin-2-ol

Chlorine-35 n.q.r, has been observed for the first time in 6-chloropyridin-2-ol and its temperature dependence has been studied from 77 K to room temperature. The torsional frequencies and their temperature dependences have been calculated by using Bayer's theory with and without Tatsuzaki's modification.

Tombstones of Frederike Benjamin nee Salamon and her husband David Benjamin; Strangriede Cemetery (R 84.6 and R 84.7); Hannover Cemeteries; Tombs

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