Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 μg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson’s disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding

Nonuniform Spin Triplet Superconductivity due to Antisymmetric Spin-Orbit Coupling in Noncentrosymmetric Superconductor CePt3_3Si

We show that the nonuniform state (Fulde-Ferrel-Larkin-Ovchinnikov (FFLO) state) of the spin triplet superconductivity in noncentrosymmetric systems is stabilized by antisymmetric spin-orbit coupling even if the magnetic field is absent. The transition temperature of the spin triplet superconductivity is reduced by the antisymmetric spin-orbit coupling in general. This pair breaking effect is shown to be similar to the Pauli pair breaking effect due to magnetic field for the spin singlet superconductivity, in which FFLO state is stabilized near the Pauli limit (or Chandrasekhar-Clogston limit) of external magnetic field. Since there are gapless excitations in nonuniform superconducting state, some physical quantities such as specific heat and penetration depth should obey the power low temperature-dependences. We discuss the possibility of the realization of nonuniform state in CePt$_3$Si.Comment: 8 pages, 6 figure

Unconventional Charge Ordering in Na0.70CoO2 below 300 K

We present the results of measurements of the dc-magnetic susceptibility chi(T) and the 23Na-NMR response of Na_{0.70}CoO_{2} at temperatures between 50 and 340 K. The chi(T) data suggest that for T > 75 K, the Co ions adopt an effective configuration of Co^{3.4+}. The 23Na-NMR response reveals pronounced anomalies near 250 and 295 K, but no evidence for magnetic phase transitions is found in chi(T). Our data suggest the onset of a dramatic change in the Co 3d-electron spin dynamics at 295 K. This process is completed at 230 K. Our results maybe interpreted as evidence for either a tendency to electron localization or an unconventional charge-density wave phenomenon within the cobalt oxide layer, CoO_2, 3d electron system near room temperature.Comment: 4 pages, 4 figures, re-submitted to Physical Review Letters. The manuscript has been revised following the recommendations of the referees. The discussion section contains substantial change

Theory of Fulde-Ferrell-Larkin-Ovchinnikov state of superconductors with and without inversion symmetry: Hubbard model approach

We study Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state of superconductors with and without inversion symmetry based on the Hubbard model on the square lattice near half-filling, using the random phase approximation. We show that center of mass momentum $Q$ tends to be parallel to $x$- or y-axis in the presence of inversion symmetry, while $Q$ vector is likely to be perpendicular to the magnetic field in the absence of inversion symmetry. We also clarify that $d+f$-wave pairing is favored and the hetero spin triplet $f$-wave state is present in the FFLO state unlike state in the superconductors only with the Rashba type spin-orbit coupling (RSOC) originating from the broken inversion symmetry. The triplet $f$-wave state is enhanced by magnetic field and the RSOC. This stems from the reduction of the spin susceptibilities by the magnetic field and the RSOC.Comment: 9 pages, 15 figures, 1 tabl

Clinical association of serum interleukin 17 levels in systemic sclerosis: Is systemic sclerosis a Th17 disease?

金沢大学医薬保健研究域医学

The degree of microRNA-34b/c methylation in serum-circulating DNA is associated with malignant pleural mesothelioma

Objectives: Malignant pleural mesothelioma (MPM) is an aggressive tumor with a poor prognosis. microRNA-34b/c (miR-34b/c), which plays an important role in the pathogenesis of MPM, is frequently downregulated by DNA methylation in approximately 90% of MPM cases. In this study, we estimated the degree of miR-34b/c methylation in serum-circulating DNA using a digital methylation specific PCR assay (MSP). Materials and methods: A real-time MSP assay was performed using the SYBR Green method. The melting temperature (Tm) of each PCR product was examined using a melting curve analysis. For a digital MSP assay, 40 wells were analyzed per sample. A total of 110 serum samples from 48 MPM cases, 21 benign asbestos pleurisy (BAP) cases, and 41 healthy volunteers (HVs) were examined. Results: Positive range of Tm value for miR-34b/c methylation was defined as 77.71-78.79 degrees C which was the mean 3 standard deviations of 40 wells of a positive control. The number of miR-34b/c methylated wells was counted per sample according to this criterion. The number of miR-34b/c methylated wells in MPM cases was significantly higher than that in BAP cases (P = 0.03) or HVs (P < 0.001). Advanced MPM cases tended to have higher number of miR-34b/c methylated wells than early MPM cases. Receiver-operating characteristic (ROC) curve analysis revealed that three number of miR-34b/c methylated wells per sample was the best cut-off of positivity of MPM with a 67% of sensitivity and a 77% specificity for prediction. The area under the ROC curve was 0.77. Conclusions: Our digital MSP assay can quantify miR-34b/c methylation in serum-circulating DNA. The degree of miR-34b/c methylation in serum-circulating DNA is associated with MPM, suggesting that this approach might be useful for the establishment of a new detection system for MPM

Critical amino acids in human DNA polymerases η and κ involved in erroneous incorporation of oxidized nucleotides

Oxidized DNA precursors can cause mutagenesis and carcinogenesis when they are incorporated into the genome. Some human Y-family DNA polymerases (Pols) can effectively incorporate 8-oxo-dGTP, an oxidized form of dGTP, into a position opposite a template dA. This inappropriate G:A pairing may lead to transversions of A to C. To gain insight into the mechanisms underlying erroneous nucleotide incorporation, we changed amino acids in human Polη and Polκ proteins that might modulate their specificity for incorporating 8-oxo-dGTP into DNA. We found that Arg61 in Polη was crucial for erroneous nucleotide incorporation. When Arg61 was substituted with lysine (R61K), the ratio of pairing of dA to 8-oxo-dGTP compared to pairing of dC was reduced from 660:1 (wild-type Polη) to 7 : 1 (R61K). Similarly, Tyr112 in Polκ was crucial for erroneous nucleotide incorporation. When Tyr112 was substituted with alanine (Y112A), the ratio of pairing was reduced from 11: 1 (wild-type Polκ) to almost 1: 1 (Y112A). Interestingly, substitution at the corresponding position in Polη, i.e. Phe18 to alanine, did not alter the specificity. These results suggested that amino acids at distinct positions in the active sites of Polη and Polκ might enhance 8-oxo-dGTP to favor the syn conformation, and thus direct its misincorporation into DNA