Ambient temperature and risk of cardiovascular hospitalization: An updated systematic review and meta-analysis

The association between temperatures and risk of cardiovascular mortality has been recognized but the association drawn from previous meta-analysis was weak due to the lack of sufficient studies. This paper presented a review with updated reports in the literature about the risk of cardiovascular hospitalization in relation to different temperature exposures and examined the dose–response relationship of temperature-cardiovascular hospitalization by change in units of temperature, latitudes, and lag days. The pooled effect sizes were calculated for cold, heat, heatwave, and diurnal variation using random-effects meta-analysis, and the dose–response relationship of temperature-cardiovascular admission was modelled using random-effect meta-regression. The Cochrane Q-test and index of heterogeneity (I2) were used to evaluate heterogeneity, and Egger's test was used to evaluate publication bias. Sixty-four studies were included in meta-analysis. The pooled results suggest that for a change in temperature condition, the risk of cardiovascular hospitalization increased 2.8% (RR, 1.028; 95% CI, 1.021–1.035) for cold exposure, 2.2% (RR, 1.022; 95% CI, 1.006–1.039) for heatwave exposure, and 0.7% (RR, 1.007; 95% CI, 1.002–1.012) for an increase in diurnal temperature. However no association was observed for heat exposure. The significant dose–response relationship of temperature — cardiovascular admission was found with cold exposure and diurnal temperature. Increase in one-day lag caused a marginal reduction in risk of cardiovascular hospitalizations for cold exposure and diurnal variation, and increase in latitude was associated with a decrease in risk of cardiovascular hospitalizations for diurnal temperature only. There is a significant short-term effect of cold exposure, heatwave and diurnal variation on cardiovascular hospitalizations. Further research is needed to understand the temperature-cardiovascular relationship for different climate areas.

8-13 Hz fluctuations in rectal pressure are an objective marker of clitorally-induced orgasm in women

Orgasm is a subjective experience accompanied by involuntary muscle contractions. We hypothesized that orgasm in women would be distinguishable by frequency analysis of a perineal muscle-derived signal. Rectal pressure, an index of perineal muscle activity, was measured continuously in 23 healthy women during different sexual tasks: receiving clitoral stimulation, imitation of orgasm, and attempt to reach orgasm, in which case the women were asked to report whether orgasm had been reached ("orgasm") or not ("failed orgasm attempt"). We performed spectral analysis on the rectal pressure data and calculated the spectral power in the frequency bands delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), and beta (13-25 Hz). The most significant and most important difference in spectral power between orgasm and both control motor tasks (imitation of orgasm and failed orgasm attempt) was found in the alpha band. An objective rule based on spectral power in the alpha band recognized 94% (29/31) of orgasms and correctly labeled 69% (44/64) of all orgasm attempts as either successful or failed. Because outbursts of alpha fluctuations in rectal pressure only occurred during orgasm and not during voluntary imitation of orgasm or failed attempts, we propose that they represent involuntary contractions of muscles in the rectal vicinity. This is the first objective and quantitative measure that has a strong correspondence with the subjective experience of orgasm.

Activities of daily living in children with developmental coordination disorder: Performance, learning, and participation

Background Children with developmental coordination disorder (DCD) face evident motor difficulties in daily functioning. Little is known, however, about their difficulties in specific activities of daily living (ADL). Objective The purposes of this study were: (1) to investigate differences between children with DCD and their peers with typical development for ADL performance, learning, and participation, and (2) to explore the predictive values of these aspects. Design. This was a cross-sectional study. Methods In both a clinical sample of children diagnosed with DCD (n=25 [21 male, 4 female], age range=5-8 years) and a group of peers with typical development (25 matched controls), the children’s parents completed the DCDDaily-Q. Differences in scores between the groups were investigated using t tests for performance and participation and Pearson chi-square analysis for learning. Multiple regression analyses were performed to explore the predictive values of performance, learning, and participation. Results Compared with their peers, children with DCD showed poor performance of ADL and less frequent participation in some ADL. Children with DCD demonstrated heterogeneous patterns of performance (poor in 10%-80% of the items) and learning (delayed in 0%-100% of the items). In the DCD group, delays in learning of ADL were a predictor for poor performance of ADL, and poor performance of ADL was a predictor for less frequent participation in ADL compared with the control group. Limitations A limited number of children with DCD were addressed in this study. Conclusions This study highlights the impact of DCD on children’s daily lives and the need for tailored intervention.

The association of chronic kidney disease and dialysis treatment with foot ulceration and major amputation

Objective The objective of this study was to investigate the risk of chronic kidney disease (CKD) stage 4-5 and dialysis treatment on incidence of foot ulceration and major lower extremity amputation in comparison to CKD stage 3. Methods In this retrospective study, all individuals who visited our hospital between 2006 and 2012 because of CKD stages 3 to 5 or dialysis treatment were included. Medical records were reviewed for incidence of foot ulceration and major amputation. The time from CKD 3, CKD 4-5, and dialysis treatment until first foot ulceration and first major lower extremity amputation was calculated and analyzed by Kaplan-Meier curves and multivariate Cox proportional hazards model. Diabetes mellitus, peripheral arterial disease, peripheral neuropathy, and foot deformities were included for potential confounding. Results A total of 669 individuals were included: 539 in CKD 3, 540 in CKD 4-5, and 259 in dialysis treatment (individuals could progress from one group to the next). Unadjusted foot ulcer incidence rates per 1000 patients per year were 12 for CKD 3, 47 for CKD 4-5, and 104 for dialysis (P < .001). In multivariate analyses, the hazard ratio for incidence of foot ulceration was 4.0 (95% confidence interval [CI], 2.6-6.3) in CKD 4-5 and 7.6 (95% CI, 4.8-12.1) in dialysis treatment compared with CKD 3. Hazard ratios for incidence of major amputation were 9.5 (95% CI, 2.1-43.0) and 15 (95% CI, 3.3-71.0), respectively. Conclusions CKD 4-5 and dialysis treatment are independent risk factors for foot ulceration and major amputation compared with CKD 3. Maximum effort is needed in daily clinical practice to prevent foot ulcers and their devastating consequences in all individuals with CKD 4-5 or dialysis treatment.

Short and long term mortality rates after a lower limb amputation

Objective To determine mortality rates after a first lower limb amputation and explore the rates for different subpopulations. Methods Retrospective cohort study of all people who underwent a first amputation at or proximal to transtibial level, in an area of 1.7 million people. Analysis with Kaplan-Meier curves and Log Rank tests for univariate associations of psycho-social and health variables. Logistic regression for odds of death at 30-days, 1-year and 5-years. Results 299 people were included. Median time to death was 20.3 months (95%CI: 13.1; 27.5). 30-day mortality = 22%; odds of death 2.3 times higher in people with history of cerebrovascular disease (95%CI: 1.2; 4.7, P = 0.016). 1 year mortality = 44%; odds of death 3.5 times higher for people with renal disease (95%CI: 1.8; 7.0, P < 0.001). 5-years mortality = 77%; odds of death 5.4 times higher for people with renal disease (95%CI: 1.8; 16.0,P = 0.003). Variation in mortality rates was most apparent in different age groups; people 75–84 years having better short term outcomes than those younger and older. Conclusions Mortality rates demonstrated the frailty of this population, with almost one quarter of people dying within 30-days, and almost half at 1 year. People with cerebrovascular had higher odds of death at 30 days, and those with renal disease and 1 and 5 years, respectively.

Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile: Synthesis of 4-cyano-3-ethoxy-1-hydroxy-5,6,7,8-tetrahydroisoquinoline, an isomer of the abnormal product

The structure of the abnormal product 1a formed in the Knoevenagel condensation of 2-carbethoxycyclohexanone and malononitrile has been further confirmed. Oxidation of the tetrahydroisoquinoline 3b using Na2Cr2O-AcOH-H2SO4 gave the keto isoquinoline 3d and the isoquinoline-1-carboxylic acid 5a. The acid chloride of 5a was condensed with diethyl ethoxymagnesiomalonate to afford after decarbethoxylation the methyl ketone 5d which on Baeyer-Villiger oxidation gave a mixture of the acetate 1g and the title compound 1b. The unambiguous synthesis of 1b confirms the structure assigned earlier to the title compound also formed during the partial hydrolysis of the diethoxy compound 1c. Condensation of 2-acetylcyclohexane-1,3-dione with malononitrile gave the quinoline derivative 4c which on ethylation yielded the ketoquinoline 4d. The present studies have confirmed that the quinoline compound 4a is also formed in the condensation of 2-acetylcyclohexanone and cyanoacetamide.

Bromination of Intermolecular Chelate Linkage Isomers of 3-Oximino-4,9-Dimethyl (or 4,7,9-Trimethyl)-5,8-Diazadodeca-4,8-Diene-2,11-Dionato Nickel(II)

The reaction of the title complexes (FIG. 1) with N-bromosuccinimide or bromine in chloroform yields isomeric bromo complexes on substitution of the γ-CH carbon proton by bromine. The brominated products have been characterised by ir, pmr, electronic absorption spectra, conductivity and magnetic susceptibility measurements. The linkage isomerisation of the brominated products in chloroform has been shown to depend on the diamine residue.

Photocytotoxic 3d-Metal Scorpionates with a 1,8-Naphthalimide Chromophore Showing Photoinduced DNA and Protein Cleavage Activity

Ternary 3d-metal complexes of formulation [M(Tp(Ph))(py-nap)](ClO4)(1-3), where M is Co(II) (1), Cu(II) (2), and Zn(II) (3); Tp(Ph) is anionic tris (3-phenylpyrazolyl)borate; and py-nap is a pyridyl ligand with a conjugated 1,8-naphthalimide moiety, have been prepared from the reaction of metal perchlorate with KTp(Ph) and py-nap in CH2Cl2. The complexes have been characterized from analytical and physicochemical data. The complexes are stable in solution as evidenced from the electrospray ionization mass spectrometry data. The complexes show good binding propensity with calf thymus (CT) DNA, giving binding constant (K-b) values of similar to 10(5) M-1 and a molecular ``light-switch'' effect that results in an enhancement of the emission intensity of the naphthalimide chromophore on binding to CT DNA. The complexes do not show any hydrolytic cleavage of DNA. They show poor chemical nuclease activity in the presence of 3-mercaptopropionic acid or hydrogen peroxide (H2O2). The Co(II) and Cu(II) complexes exhibit oxidative pUC19 DNA cleavage activity in UV-A light of 365 rim. The Zn(II) complex shows moderate DNA photocleavage activity at 365 nm. The Cu(II)complex 2 displays photoinduced DNA cleavage activity in red light of 647.1 nm and 676 rim and near-IR light of >750 rim. A mechanistic studyin UV-A and visible light suggests the involvement of the hydroxyl radical as the reactive species in the DNA photocleavage reactions. The complexes also show good bovine serum albumin (BSA) protein binding propensity, giving K-BSA values of similar to 10(5) M-1. Complexes 1 and 2 display significant photoinduced BSA cleavage activity in UV-A light. The Co(II) complex 1 shows a significant photocytotoxic effect in HeLa cervical cancer cells on exposure to UV-A light of 365 nm, giving an IC50 value of 32 mu M. The IC50 value for the py-nap ligand alone is 41.42 mu m in UV-A light. The IC50 value is >200 mu M in the dark, indicating poor dark toxicity of 1. The Cu(II) complex 2 exhibits moderate photocytotoxicity and significant dark toxicity, giving IC50 values of 18.6 mu m and 29.7 mu m in UV-A light and in the dark, respectively.

Tasa-arvo ja muutoksen rajat : Sukupuolten tasa-arvo poliittisena ongelmana Ranskan parité- ja Suomen kiintiökeskusteluissa

The study looks at the debates on gender equality in political decision-making in Finland and France in the 1990s and 2000s by analysing the argumentation for parité and quotas and the ways in which gender equality was constructed as a political problem. The focus of the study is on the parliamentary debates on the amendment of the electoral law in France in 2000 and the introduction of quota regulations into the Act on Equality in Finland in 1994 - 1995. The debates ended in the adoption of quota regulations in the electoral lists (France) and in the executive and preparatory bodies at the national and the local level (Finland). Apart from the analysis of the parliamentary debates, the study explores the political processes preceding the adoption of legislation as well as the debates on quotas and parity in Finnish and French societies in the 1980s and 1990s. The debates on gender equality are analysed as the sites of struggle and change with regard to the normative boundaries of gender equality, as well as of politics and citizenship. The cross-cultural perspective gives room to explore the ways in which gender equality and change can be imagined in different national contexts, and which kinds of discursive resources are available for the politicization of gender equality. Specific attention is paid to the discursive frames and agenda settings in the debates and how these set the limits of the imaginable and the possible in the promotion of gender equality. In both Finland and France, the promotion of equality was constructed as a national project, in which the main beneficiary was the society or the nation as a whole. In France, gender equality was an inherent part of the promotion of French democracy; in Finland, gender equality was regarded as a means to bring the expertise of both women and men to the benefit of the whole society. Furthermore, in both countries the promotion of gender equality was based on the harmonious cooperation of women and men and the temporal dimension of "nearly achieved" gender equality. In this kind of a context, gender equality served as a means towards the wider national ends, and there was little room to discuss the aspects of power and agency with regard to gender equality. However, the internationalisation of equality politics, as well as the conflicting interpretations of gender equality in the national political arenas, calls into question the existence of clearly defined and immutable boundaries of "Finnish" and "French" gender equality. At the same time, the rules of the game in politics, including the meaning of French republicanism and Finnish "expert oriented" politics were contested. In this way, the new equality legislation and the preceding political processes played a part in the transformation of the limits of gender equality, politics and citizenship.

The Crystal and Molecular Structure of 4-Aza-5-oxo-tricyclo[4.4.0.03,8]decane (Aza-twistanone)

Die kristalline Struktur von Aza-twistanon wurde durch eine Röntgenstruktur-analyse untersucht. Die Kristalle gehören zur monoklinen Raumgruppe P21/n mit den Zelldimensionen a = 6,662(6), b = 13,36(2), c = 8,606(9) Å, = 98,97(2)°, V = 757 Å3, Z = 4. Die Struktur wurde mit Direktmethoden gelöst und bis zu R = 0,035 verfeinert (mittlere (c) = 0,003 Å3).Die cis-Amidgruppe ist relativ stark deformiert und hat einen Torsionswinkel C -C -N-C von 14,5(4)° (Deformation aus der Ebene c = 5,0(5)° und N = 13,5(4,0)°). Die gegenüberliegende äthylenbrücke weist einen Torsionswinkel von 25,1(5)° auf. Die entsprechenden Winkel in Twistan betragen je 20°. Das tricyclische Gerüst von Aza-twistanon hat approximative.

Structural studies of analgesics and their interactions. Part 4. Crystal structures of phenylbutazone and a 2 : 1 complex between phenylbutazone and piperazine

The X-ray crystal structures of 4-butyl-1,2-diphenylpyrazolidine-3,5-dione (phenylbutazone)(I). and its 2 : 1 complex (II) with piperazine have been determined by direct methods and the structures refined to R 0.096 (2 300 observed reflections measured by diffractometer) and 0.074 (2 494 observed reflections visuallyestimated). Crystals are monoclinic, space group P21/c; for (I)a= 21.695(4), b= 5.823(2), c= 27.881(4)Å, = 108.06 (10)°, Z= 8, and for (II)a= 8.048(4), b= 15.081(4), c= 15.583(7)Å, = 95.9(3)°, Z= 2. The two crystallographically independant molecules in the structure of (I) are similar except for the conformation of the butyl group, which is disordered in one of the molecules. In the pyrazolidinedione group, the two C–C bonds are single and the two C–O bonds double. The two nitrogen atoms in the five-membered ring are pyramidal with the attached phenyl groups lying on the opposite sides of the mean plane of the ring. The phenylbutazone molecule in (II) exists as a negative ion owing to deprotonation of C-4. C-4 is therefore trigonal and the orientation of the Bu group with respect to the pyrazolidinedione group is considerably different from that in (I); there is also considerable electron delocalization along the C–O and C–C bonds. These changes in geometry and electronic structure may relate to biological activity. The doubly charged cationic piperazine molecule exists in the chair form with the nitrogen atoms at the apices. The crystal structure of (II) is stabilized by ionic interactions and N–H O hydrogen bonds.

Molecular dynamics simulations of CXCL-8 and its interactions with a receptor peptide, heparin fragments, and sulfated linked cyclitols

CXCL-8 (Interleukin 8) is a CXC chemokine with a central role in the human immune response. We have undertaken extensive in silico analyses to elucidate the interactions of CXCL-8 with its various binding partners, which are crucial for its biological function. Sequence and structure analyses showed that residues in the thirdq β-sheet and basic residues in the heparin binding site are highly variable, while residues in the second β-sheet are highly conserved. Molecular dynamics simulations in aqueous solution of dimeric CXCL-8 have been performed with starting geometries from both X-ray and NMR structures showed shearing movements between the two antiparallel C-terminal helices. Dynamic conservation analyses of these simulations agreed with experimental data indicating that structural differences between the two structures at quaternary level arise from changes in the secondary structure of the N-terminal loop, the 310-helix, the 30s, 40s, and 50s loops and the third β-sheet, resulting in a different interhelical separation. Nevertheless, the observation of these different states indicates that CXCL-8 has the potential to undergo conformational changes, and it seems likely that this feature is relevant to the mode of binding of glycosaminoglycan (GAG) mimetics such as cyclitols. Simulations of the receptor peptide fragment−CXCL-8 complex identified several specific interactions of the receptor peptide with CXCL-8 that could be exploited in the structure-based design of competitive peptides and nonpeptidic molecules targeting CXCL-8 for combating inflammatory diseases. Simulations of the CXCL-8 dimer complexed with a 24-mer heparin fragment and of the CXCL-8−receptor peptide complex revealed that Arg60, Lys64, and Arg68 in the dimer bind to cyclitols in a horseshoe pattern, defining a region which is spatially distinct from the receptor binding site. There appears to be an optimum number of sulfates and an optimum length of alkyl spacers required for the interaction of cyclitol inhibitors with the dimeric form of CXCL-8. Calculation of the binding affinities of cyclitol inhibitors reflected satisfactorily the ranking of experimentally determined inhibitory potencies. The findings of these molecular modeling studies will help in the search for inhibitors which can modulate various CXCL-8 biological activities and serve as an excellent model system to study CXC-inhibitor interactions.

X-ray studies on crystalline complexes involving amino acids and peptides. XXIII. Variability in ionization state, conformation and molecular aggregation in the complexes of succinic acid with DL- and L-lysine

Crystalline complexes of succinic acid with DL- and L-lysine have been prepared and analysed by X-ray diffraction. DL-Lysine complex: C6HIsN202 + 1 2- 1 ~C4H404 .~C4H604, Mr -- 264"2, PI, a = 5"506 (4), =8.070(2), c=14.089(2) A,, a=92.02(1), /3= 100"69 (3), y = 95"85 (3) ~>, Z = 2, Dx = 1"44 g cm -3, R = 0.059 for 2546 observed reflections. Form I of the e-lysine complex: C6HIsN20-, ~ .C4H504, Mr = 264.2, P1, a = 5" 125 (2), b = 8"087 (1), c = 8"689 (1) A,, a = 112.06 (1), /3 = 99.08 (2), y = 93"77(2) °, Z--l, D,,,=1"34(3), Dx=l"34gcm 3 R = 0.033 for 1475 observed reflections. Form II of + I 2- the e-lysine complex: C6H15N202 .,iC4H404 .- 1 I ") 4C4H604.4(C4HsO4""H'"CaH404)" , Mr = 264"2, P1, a = 10.143 (4), b = 10.256 (2), c = 12"916 (3) A,, a = 105.00 (2),/3 = 99-09 (3), y = 92"78 (3)::, Z = 4, Dm= 1"37(4), D,.= 1.38gcm 3, R=0.067 for 2809 observed reflections. The succinic acid molecules in the structures exhibit a variety of ionization states. Two of the lysine conformations found in the complexes have been observed for the first time in crystals containing lysine. Form II of the L-lysine complex is highly pseudosymmetric. In all the complexes, unlike molecules aggregate into separate alternating layers. The basic element of aggregation in the lysine layer in the complexes is an S2-type head-to-tail sequence. This element combines in different ways in the three structures. The basic element of aggre gation in the succinic acid layer in the complexes is a hydrogen-bonded ribbon. The ribbons are interconnected indirectly through amino groups in the lysine layer.

High pressure clamp for electrical measurements up to 8 GPa and temperature down to 77 K

A compact clamp-type high pressure cell for carrying out electrical conductivity measurements on small solid samples of size 1 mm or less at pressures upto 8 GPa (i.e., 80 kbar) and for use down to 77 K has been designed and fabricated. The pressure generated in the sample region has been calibrated at room temperature against the polymorphic phase transitions of Bismuth and Ytterbium. The pressure relaxation of the clamp at low temperatures has been estimated by monitoring the electrical conductivity behavior of lead. Review of Scientific Instruments is copyrighted by The American Institute of Physics.

Aspects of tautomerism. 8. Solvolysis of some pseudo and normal acid chlorides

Pseudo acid chlorides derived from levulinic acid ando-benzoyl-benzoic acid, solvolyse in aqueous acetone, aqueous dioxane and aqueous dimethylformamide by aS Nl process. Their reaction pattern is distinct from that of typical normal acid chlorides, viz.,p-benzoylbenzoyl chloride and fluorene-9-one-1-carboxylic acid chloride, which solvolyse by aS N2 pathway. No evidence for tautomerism could be obtained either between the normal and pseudo forms of the acid chlorides or the derived ion pairs.