How much of the predisposition to Hashimoto's thyroiditis can be explained based on previously reported associations?

PURPOSE: Our insight in the genetics of Hashimoto's thyroiditis (HT) has become clearer through information provided by genome-wide association studies and candidate gene studies, but remains still not fully understood. Our aim was to assess how many different genetic risk variants contribute to the development of HT. METHODS: 147 HT cases (10.2% men) and 147 controls (13.6% men) were qualified for the analysis. Intrinsic and environmental factors were controlled for. Polymorphisms (SNP) were chosen based on the literature and included markers of the genes PTPN22, CTLA4, TG, TPO among others, and of genomic regions pointed by GWAS studies. SNP were typed on a microarray. Variants in the HLA-DRB1 gene were identified by Sanger sequencing. RESULTS: Multivariate predisposition to HT was modeled. Based on the investigated group, a model of seven variables was obtained. The variability explained by this model was assessed at only 5.4821% (p = 2 × 10-6), which indicates that many dozens of factors are required simultaneously to explain HT predisposition. CONCLUSIONS: We analyzed genetic regions commonly and most significantly associated with autoimmune thyroid disorders in the literature, on a carefully selected cohort. Our results indicated a lack of possibility to predict the risk of HT development, even with a multivariate model. We therefore conclude that strong associations of single genetic regions with HT should be interpreted with great caution. We believe that a change in the attitude towards genetic association analyses of HT predisposition is necessary. Studies including multiple factors simultaneously are needed to unravel the intricacies of genetic associations with HT.

Search for an H-dibaryon with a mass near 2mΛ in Υ(1S) and Υ(2S) decays.

We report the results of a high-statistics search for H dibaryon production in inclusive Υ(1S) and Υ(2S) decays. No indication of an H dibaryon with a mass near the M(H)=2m(Λ) threshold is seen in either the H→Λpπ(-) or ΛΛ decay channels and 90% confidence level branching-fraction upper limits are set that are between one and two orders of magnitude below the measured branching fractions for inclusive Υ(1S) and Υ(2S) decays to antideuterons. Since Υ(1S,2S) decays produce flavor-SU(3)-symmetric final states, these results put stringent constraints on H dibaryon properties. The results are based on analyses of 102 million Υ(1S) and 158 million Υ(2S) events collected with the Belle detector at the KEKB e(+)e(-) collider.

Measurement of the CP-violation parameter sin2φ1 with a new tagging method at the Υ(5S) resonance.

We report a measurement of the CP-violation parameter sin2φ1 at the Υ(5S) resonance using a new tagging method, called "B-π tagging." In Υ(5S) decays containing a neutral B meson, a charged B, and a charged pion, the neutral B is reconstructed in the J/ψK(S)(0) CP-eigenstate decay channel. The initial flavor of the neutral B meson at the moment of the Υ(5S) decay is opposite to that of the charged B and may thus be inferred from the charge of the pion without reconstructing the charged B. From the asymmetry between B-π(+) and B-π(-) tagged J/ψK(S)(0) yields, we determine sin2φ1=0.57±0.58(stat)±0.06(syst). The results are based on 121 fb(-1) of data recorded by the Belle detector at the KEKB e(+)e(-) collider.

Observation of B(s)(0) → D(s)(*-) π+ and B(s)(0) → D(s)(*-) ρ+ and measurement of the B(s)(0) → D(s)(*-) ρ+ longitudinal polarization fraction.

First observations of the B(s)(0) → D(s)(*-) π+, B(s)(0) → D(s)(-) ρ+ and B(s)(0) → D(s)(*-) ρ+ decays are reported together with measurements of their branching fractions: B(B(s)(0) → D(s)(*-) π+) = [2.4(-0.4)(+0.5)(stat) ± 0.3(syst) ± 0.4(f(s))]×10(-3), B(B(s)(0) → D(s)(-) ρ+) = [8.5(-1.2)(+1.3)(stat) ± 1.1(syst) ± 1.3(f(s))]×10(-3) and B(B(s)(0) → D(s)(*-) ρ+) = [11.9(-2.0)(+2.2)(stat) ± 1.7(syst) ± 1.8(f(s))]×10(-3) (f(s) = N(B(s)(*) B(s)(*))/N(bb)). From helicity-angle distributions, we measured the longitudinal polarization fraction in B(s)(0) → D(s)(*-) ρ+ decays to be f(L)(B(s)(0) → D(s)(*-) ρ+) = 1.05(-0.10)(+0.08)(stat)(-0.04)(+0.03)(syst). These results are based on a 23.6 fb(-1) data sample collected at the Υ(5S) resonance with the Belle detector at the KEKB e+ e- collider.

Search for a low mass particle decaying into µ+ µ- in B0 → K*0 X and B0 → ρ0 X at Belle.

We search for dimuon decays of a low mass particle in the decays B0→K*0 X and B0→ρ0 X using a data sample of 657×10(6)BB events collected with the Belle detector at the KEKB asymmetric-energy e+ e- collider. We find no evidence for such a particle in the mass range from 212 MeV/c2 to 300 MeV/c2 for lifetimes below 10(-12) s, and set upper limits on its branching fractions. In particular, we search for a particle with a mass of 214.3 MeV/c2 reported by the HyperCP experiment, and obtain upper limits on the products B(B0→K*0 X)×B(X→µ+ µ- )<2.26(2.27)×10(-8) and B(B0→ρ0 X)×B(X→µ+ µ-)<1.73(1.73)×10(-8) at 90% C.L. for a scalar (vector) X particle.

First measurement of inclusive B→Xsη decays.

We report a first measurement of inclusive B→Xsη decays, where Xs is a charmless state with unit strangeness. The measurement is based on a pseudoinclusive reconstruction technique and uses a sample of 657×10(6)BB pairs accumulated with the Belle detector at the KEKB e+e- collider. For MXs < 2.6 GeV/c2, we measure a branching fraction of [26.1±3.0(stat)-2.1+1.9(syst)-7.1+4.0(model)]×10(-5) and a direct CP asymmetry of ACP=-0.13±0.04-0.03+0.02. Over half of the signal occurs in the range MXs > 1.8 GeV/c2.

Search for CP violation in the decays D(s)+ --> KS0pi+ and D(s)+ --> KS0K+.

We have searched for CP violation in the charmed meson decays D((s))(+) --> K(S)(0)pi(+) and D((s))(+) --> K(S)(0)K(+) using 673 fb(-1) of data collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. No evidence for CP violation is observed. We report the most sensitive CP asymmetry measurements to date for these decays: A(CP)(D(+)-->K(S)(0)pi(+)) = (-0.71 +/- 0.19 +/- 0.20)%, A(CP)(D(s)(+) --> K(S)(0)pi(+)) = (+5.45 +/- 2.50 +/- 0.33)%, A(CP)(D(+) --> K(S)(0)K(+)) = (-0.16 +/- 0.58 +/- 0.25)%, and A(CP)(D(s)(+) --> K(S)(0)K(+)) = (+0.12 +/- 0.36 +/- 0.22)%, where the first uncertainties are statistical and the second are systematic.

Measurement of the differential branching fraction and forward-backward asymmetry for B --> K(*)l+l-.

We study B --> K(*)l+l- decays (l = e, mu) based on a data sample of 657 x 10(6) BB pairs collected with the Belle detector at the KEKB e+e- collider. We report the differential branching fraction, isospin asymmetry, K* polarization, and the forward-backward asymmetry (A(FB)) as functions of q2 = M(ll)(2)c2. The fitted A(FB) spectrum exceeds the standard model expectation by 2.7 standard deviations. The measured branching fractions are B(B --> K*l+l-) = (10.7(-1.0)(+1.1) +/- 0.9) x 10(-7) and B(B --> Kl+l-) = (4.8(-0.4)(+0.5) +/- 0.3) x 10(-7), where the first errors are statistical and the second are systematic, with the muon to electron ratios R(K*) = 0.83 +/- 0.17 +/- 0.08 and R(K) = 1.03 +/- 0.19 +/- 0.06.

DNA methylation analysis of negative pressure therapy effect in diabetic foot ulcers.

OBJECTIVE: Negative pressure wound therapy (NPWT) has been used to treat diabetic foot ulcerations (DFUs). Its action on the molecular level, however, is only partially understood. Some earlier data suggested NPWT may be mediated through modification of local gene expression. As methylation is a key epigenetic regulatory mechanism of gene expression, we assessed the effect of NPWT on its profile in patients with type 2 diabetes (T2DM) and neuropathic non-infected DFUs. METHODS: Of 36 included patients, 23 were assigned to NPWT and 13 to standard therapy. Due to ethical concerns, the assignment was non-randomized and based on wound characteristics. Tissue samples were obtained before and 8 ± 1 days after therapy initiation. DNA methylation patterns were checked by Illumina Methylation EPIC kit. RESULTS: In terms of clinical characteristics, the groups presented typical features of T2DM; however, the NPWT group had significantly greater wound area: 16.8 cm2 vs 1.4 cm2 (P = 0.0003). Initially only one region at chromosome 5 was differentially methylated. After treatment, 57 differentially methylated genes were found, mainly located on chromosomes 6 (chr6p21) and 20 (chr20p13); they were associated with DNA repair and autocrine signaling via retinoic acid receptor. We performed differential analyses pre treatment and post treatment. The analysis revealed 426 differentially methylated regions in the NPWT group, but none in the control group. The enrichment analysis showed 11 processes significantly associated with NPWT, of which 4 were linked with complement system activation. All but one were hypermethylated after NPWT. CONCLUSION: The NPWT effect on DFUs may be mediated through epigenetic changes resulting in the inhibition of complement system activation.

Prostaglandin E (dmPGE2) action in vitro on the activity of rat liver Golgi apparatus galactosyltransferase.

In vitro addition of 16,16'-dimethyl prostaglandin E2 to Golgi-rich membrane fraction in final concentration of 0.1 microgram/1 mg of protein increased generally the activity of galactosyltransferase in comparison with control. The percentage of phospholipids in the whole fraction was similar in both investigated groups, only the sum of phosphatidylethanolamine+phosphatidic acid was significantly lower after addition of dmPGE2 than in the control (0.001 < P < 0.01).

The influence of PGE1 and ethanol as PGE1 solvent on the activity of galactosyltransferase of rat liver Golgi fractions--in vitro experiments.

Addition in vitro of ethanol solution of PGE1 to isolated Golgi-rich membrane fraction caused great alterations in galactosyltransferase activity, marker enzyme of these membranes. Ethanol as a solvent of PGE1 has an influence on the activity of the enzyme as well as the membrane permeability, different drugs penetration and availability of substrates. Then, additional control with ethanol in identical concentration as in the investigated sample was performed. In a dose 1 microgram PGE1 per 1 mg of protein (and lower concentration of ethanol c. 0.09%) the stimulation of this enzyme activity (excluding 2 and 6 hours s after Golgi membrane isolation) was above 30% in comparison with the control.

Long-range assemblies on poly(dG-dC)2 and poly(dA-dT)2: phosphonium cationic porphyrins and the importance of the charge.

The present paper describes synthesis and spectroscopic properties of novel cationic meso-tetraphenylporphyrins bearing two (trans) (P2) or three (P3) triphenylphosphonium substituents. The porphyrin aggregation in aqueous solutions is discussed in detail. Porphyrin binding to and self-organization onto long-range assemblies on poly(dA-dT)2 or poly(dG-dC)2 were probed by combination of absorption, fluorescence, circular dichroism (CD), transient and resonance light-scattering (RLS) techniques. The higher hydrophobicity of P2 is manifested by more extensive self-organization. Induced CD and intensive RLS indicate binding to the chiral environment on the nucleic acids exterior and exciton coupling between adjacent porphyrin moieties. The CD spectra of P2 on poly(dG-dC), and poly(dA-dT)2 suggest that the binding geometry is essentially independent of the base sequence. The fluorescence lifetime of about 4 ns was attributed to the long-range assembly. In the case of P3 the distinctly different CD spectra induced by GC or AT base-pair regions reveal that the number of the substituents determines how closely the porphyrin can approach the specific electronic environment on the nucleic acid exterior. The fluorescence lifetime of the P3 assembly is about 2 ns.

[Return to work of professional drivers after cardiac rehabilitation]. / Reprise du travail après réadaptation cardiaque chez les chauffeurs professionnels.

This study analysed the possibilities of returning to work of professional drivers after a cardiac event and rehabilitation. The population comprised 94 consecutive patients, all men, average age 48.8 years (range 30 to 63 years) referred after coronary bypass surgery (N = 39), myocardial infarction (N = 38), angina (N = 4) or valve replacement surgery (N = 13). Advice on professional reinsertion was given after the rehabilitation program, authorization to drive being given in the absence of cardiac symptoms, residual myocardial ischaemia, severe left ventricular dysfunction and serious ventricular arrhythmias. After 35 months, 4 patients were lost to follow-up; of the 90 remaining patients, the frequency of return to work (maximal at the 9th month) was 65.6% with 84.7% obtaining a renewal of their driving licence. In this series, 81% of patients were asymptomatic, 2 died, 16.7% had further cardiovascular complications. The morbidity and mortality were significantly greater in the group who had to stop driving (N = 40) (32.5% vs 8%, p < 0.001). Non complications occurred during work in those who resumed driving. This study confirms the safety of allowing low risk professional drivers, identified during cardiac rehabilitation by simple, reliable clinical and paraclinical criteria, to return to work.

[Injectable and oral propafenone in nodal reentry and pathways of ventricular preexcitation]. / Etude de la propafénone injectable et orale dans les rentrées nodales et les voies de préexcitation ventriculaire.

Propafenone, an antiarrhythmic drug of IC type, was applied to 10 patients with supraventricular tachycardia (SVT) produced by intranodal reentry (group I) and in 14 patients with reentry by an accessory atrioventricular (AV) pathway (group II), 10 of them suffering from orthodromic SVT. Propafenone given intravenously depresses or blocks the antegrade or retrograde conduction in the AV node and in the accessory AV pathway. The same effect is observed with orally given propafenone: 66% of antegrade blocking and 54% of retrograde blocking of the accessory conduction pathway. Intravenously given propafenone reduces within 2 to 3 min by antegrade or retrograde blocking 70% of SVT produced by intranodal reentry and by 85% of SVT produced by reentry by the accessory pathway. After injection it becomes impossible to induce intranodal SVT in 60% of cases and SVT by the accessory pathway reentry in 28% of cases. With oral treatment (600 mg/day) reinduction of intranodal SVT becomes impossible in 66% of cases and of SVT produced by reentry by the accessory pathway in 42% of cases. Long-term oral administration (17 +/- 3.7 months) of the same dose prevents 88% of SVT produced by internodal reentry and 80% of spontaneous SVT produced by reentry by the accessory pathway. Cardiologic tolerance is satisfactory: one case of atrioventricular and intraventricular dysrhythmia is observed. The same holds true for general tolerance: in 2 cases drug administration is discontinued and 11 patients present neurologic and digestive troubles improving after lowering the dosage or increasing the fractionation.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sinoatrial and atrioventricular conduction disorders in Lyme disease. Apropos of 2 case reports]. / Troubles conductifs sino-auriculaires et auriculo-ventriculaires de la maladie de Lyme. A propos de deux observations.

Lyme's disease due to Borrelia Burgdorferii is a rare cause of acute atrioventricular block (AVB) which is the commonest cardiac complication. Cutaneous, neurological and articular involvement complete the clinical picture of this condition. These two cases, confirmed by serology, support previously reported data describing the favourable prognosis of these conduction defects (suprahisian and/or hisian in our 2 cases) which regress completely, irrespective of their degree of severity. The authors also describe AVB occurring without extracardiac manifestations of this condition and a documented case of sinoatrial block, indicating a new zone of infestation.

Violets of the section Melanium, their colonization by arbuscular mycorrhizal fungi and their occurrence on heavy metal heaps.

Violets of the sections Melanium were examined for their colonization by arbuscular mycorrhizal fungi (AMF). Heartsease (Viola tricolor) from several heavy metal soils was AMF-positive at many sites but not at extreme biomes. The zinc violets Viola lutea ssp. westfalica (blue zinc violet) and ssp. calaminaria (yellow zinc violet) were always AMF-positive on heavy metal soils as their natural habitats. As shown for the blue form, zinc violets germinate independently of AMF and can be grown in non-polluted garden soils. Thus the zinc violets are obligatorily neither mycotrophs nor metalophytes. The alpine V. lutea, likely ancestor of the zinc violets, was at best poorly colonized by AMF. As determined by atomic absorption spectrometry, the contents of Zn and Pb were lower in AMF colonized plants than in the heavy metal soils from where the samples had been taken. AMF might prevent the uptake of toxic levels of heavy metals into the plant organs. Dithizone staining indicated a differential deposition of heavy metals in tissues of heartsease. Leaf hairs were particularly rich in heavy metals, indicating that part of the excess of heavy metals is sequestered into these cells.

Observation of the doubly cabibbo-suppressed decay D_{s};{+}-->K;{+}K;{+}pi;{-}.

We report the first observation of the doubly Cabibbo-suppressed decay D_{s};{+}-->K;{+}K;{+}pi;{-} using 605 fb;{-1} of data collected with the Belle detector at the KEKB asymmetric-energy e;{+}e;{-} collider. The branching ratio with respect to its Cabibbo-favored counterpart B(D_{s};{+}-->K;{+}K;{+}pi;{-})/B(D_{s};{+}-->K;{+}K;{-}pi;{+}) is (0.229+/-0.028+/-0.012)%, where the first uncertainty is statistical and the second is systematic. We also report a significantly improved measurement of the doubly Cabibbo-suppressed decay D;{+}-->K;{+}pi;{+}pi;{-}, with a branching ratio B(D;{+}-->K;{+}pi;{+}pi;{-})/B(D;{+}-->K;{-}pi;{+}pi;{+})=(0.569+/-0.018+/-0.014)%.

Observation of B_(s)(0)-->phigamma and search for B_(s)(0)-->gammagamma decays at Belle.

We search for the radiative penguin decays B_{s}{0}-->varphigamma and B_{s}{0}-->gammagamma in a 23.6 fb{-1} data sample collected at the Upsilon(5S) resonance with the Belle detector at the KEKB e{+}e{-} asymmetric-energy collider. We observe for the first time a radiative penguin decay of the B_{s}{0} meson in the B_{s}{0}-->varphigamma mode and we measure B(B_{s}{0}-->varphigamma)=(57_{-15}{+18}(stat)-11+12(syst))x10{-6}. No significant B_{s}{0}-->gammagamma signal is observed and we set a 90% confidence level upper limit of B(B_{s}{0}-->gammagamma)<8.7x10{-6}.

Production of new charmoniumlike states in e+e- -->J/psiD*D[over](*) at sqrt[s] approximately 10.6 GeV.

We report a study of the processes e+e- -->J/psiD*D[over](*). In J/psiD*D[over]* we observe a significant enhancement in the D*D[over]* invariant mass spectrum, which we interpret as a new charmoniumlike state and denote X(4160). The X(4160) parameters are M=(4156(-20)+25+/-15) MeV/c2 and Gamma=(139(-61)+111+/-21) MeV. We also report a new measurement of the X(3940) mass and width: M=(3942(-6)+7+/-6) MeV/c2 and Gamma=(37(-15)+26+/-8) MeV. The analysis is based on a 693 fb(-1) data sample recorded near the Upsilon(4S) resonance by the Belle detector at the KEKB asymmetric-energy collider.