Efficacy and safety of tofacitinib for moderate-to-severe plaque psoriasis: a systematic review and meta-analysis of randomized controlled trials.

The effects of tofacitinib in treating moderate-to-severe plaque psoriasis were unclear. We aimed to assess the effects of tofacitinib in treating moderate-to-severe plaque psoriasis. We searched PubMed, Cochrane Central Register of Controlled Trials and EMBASE for relevant randomized controlled trials (RCTs) and conducted a systematic review and meta-analysis. Four RCTs with 2724 participants were included. Compared to placebo, tofacitinib significantly improved psoriasis {≥75% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: risk difference (RD) 0.32 [95% confidence interval (CI) 0.28-0.35], 10 mg BID: RD 0.51 (95% CI 0.43-0.58); ≥90% reduction in the Psoriasis Area and Severity Index score: 5 mg BID: RD 0.19 (95% CI 0.17-0.22), 10 mg BID: RD 0.36 (95% CI 0.31-0.42); Physician's Global Assessment 0/1: 5 mg BID: RD 0.31 (95% CI 0.27-0.35), 10 mg BID: RD 0.48 (95% CI 0.44-0.53)} and participants' life quality [Dermatology Life Quality Index 0/1: 5 mg BID: RD 0.24 (95% CI 0.20-0.2), 10 mg BID: RD 0.36 (95% CI 0.33-0.40)]. Tofacitinib was associated with an increase in minor adverse events [upper respiratory tract infection: 5 mg BID: RD 0.02 (95% CI 0.00-0.03), 10 mg BID: RD 0.02 (95% CI 0.00-0.04); hypercholesterolaemia: 5 mg BID: RD 0.02 (95% CI 0.01-0.04), 10 mg BID: RD 0.02 (95% CI 0.01-0.04)]. In conclusion, tofacitinib may be a treatment option for moderate-to-severe plaque psoriasis that is unresponsive to other therapies and patients who are intolerable to other therapies or prefer oral medications.

Medical and non-medical correlates of carpal tunnel syndrome in a Taiwan cohort of one million.

BACKGROUND: Carpal tunnel syndrome (CTS), with unclear etiology, is the most common entrapment neuropathy. Its occurrence is related to lots of medical and non-medical conditions with uncertain causality. With a large population, we characterized selected demographical and clinical factors to add more information on CTS-correlated factors and new insight into future CTS prevention. METHODS: A national insurance claim dataset of one million enrollees in Taiwan was used to identify 15 802 patients with CTS and 31 604 randomly selected controls, during a period of 7 years starting 1 January 2000. Statistical association with CTS was determined for five sociodemographic and nine medical factors. RESULTS: Patients were predominantly women (65.6% vs. 47.7% in the control group) and older (40 and above, 62.6% vs. 36.2%). Rheumatoid arthritis was found to be the most significant comorbidity associated with CTS, followed by gout, hypertension, diabetes, obesity, uremia, and acromegaly. For younger group age ≤39, the association of these comorbidities was stronger, and hypothyroidism and vitamin B(6) deficiency were additional comorbidities. Aging appears to reduce the relative impact of the diseases commonly associated with CTS as the possible risk factors. CONCLUSIONS: Identification of the CTS correlates in younger group would be of greater value in timely detection and treatment for these diseases. Correcting these disorders may aid in removing possible causes of CTS. This is the first report on the effect of aging on probable CTS risk factors. How factors associated with aging contribute to the development of CTS remains to be determined.

1-(3-Benzyl-4,6-dibenz-yloxy-2-hy-droxy-phen-yl)ethanone.

The title compound, C(29)H(26)O(4), is essentially planar in the acetophenone portion that includes both the hy-droxy and a benz-yloxy O atoms, with an r.m.s. deviation of 0.0311 Å. The other two substituents inter-sect the plane at 70.45 (3) and 59.55 (4)°. In the molecule there is an intramolecular O-H⋯O hydrogen bond. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, as well as C-H⋯π and π-stacking inter-actions, with centroid-centroid distances 3.6570 (2) Å.

Event-by-event fluctuations of azimuthal particle anisotropy in Au+Au collisions at square root(sNN) = 200 GeV.

This Letter presents the first measurement of event-by-event fluctuations of the elliptic flow parameter v(2) in Au+Au collisions at square root(s(NN))=200 GeV as a function of collision centrality. The relative nonstatistical fluctuations of the v(2) parameter are found to be approximately 40%. The results, including contributions from event-by-event elliptic flow fluctuations and from azimuthal correlations that are unrelated to the reaction plane (nonflow correlations), establish an upper limit on the magnitude of underlying elliptic flow fluctuations. This limit is consistent with predictions based on spatial fluctuations of the participating nucleons in the initial nuclear overlap region. These results provide important constraints on models of the initial state and hydrodynamic evolution of relativistic heavy ion collisions.

High transverse momentum triggered correlations over a large pseudorapidity acceptance in Au + Au collisions at square root(s(NN)) = 200 GeV.

A measurement of two-particle correlations with a high transverse momentum trigger particle (p(T)(trig) > 2.5 GeV/c) is presented for Au+Au collisions at square root(s(NN)) = 200 GeV over the uniquely broad longitudinal acceptance of the PHOBOS detector (-4 < Delta eta < 2). A broadening of the away-side azimuthal correlation compared to elementary collisions is observed at all Delta eta. As in p+p collisions, the near side is characterized by a peak of correlated partners at small angle relative to the trigger particle. However, in central Au+Au collisions an additional correlation extended in Delta eta and known as the "ridge" is found to reach at least |Delta eta| approximately = 4. The ridge yield is largely independent of Delta eta over the measured range, and it decreases towards more peripheral collisions. For the chosen (p(T)(trig) cut, the ridge yield is consistent with zero for events with less than roughly 100 participating nucleons.

Electromechanical characterization of cinnamophilin, a natural thromboxane A2 receptor antagonist with anti-arrhythmic activity, in guinea-pig heart.

BACKGROUND AND PURPOSE: Cinnamophilin, a thromboxane A(2) receptor antagonist, has been identified as a prominent anti-arrhythmic agent in rat heart. This study aimed to determine its electromechanical and anti-arrhythmic effects in guinea-pig hearts. EXPERIMENTAL APPROACH: Microelectrodes were used to study action potentials in ventricular papillary muscles. Fluo-3 fluorimetric ratio and whole-cell voltage-clamp techniques were used to record calcium transients and membrane currents in single ventricular myocytes, respectively. Intracardiac electrocardiograms were obtained and the anti-arrhythmic efficacy was determined from isolated perfused hearts. KEY RESULTS: In papillary muscles, cinnamophilin decreased the maximal rate of upstroke (V(max)) and duration of action potential, and reduced the contractile force. In single ventricular myocytes, cinnamophilin reduced Ca(2+) transient amplitude. Cinnamophilin decreased the L-type Ca(2+) current (I(Ca,L))(IC(50)=7.5 microM) with use-dependency, induced a negative shift of the voltage-dependent inactivation and retarded recovery from inactivation. Cinnamophilin also decreased the Na(+) current (I(Na)) (IC(50)=2.7 microM) and to a lesser extent, the delayed outward (I(K)), inward rectifier (I(K1)), and ATP-sensitive (I(K,ATP)) K(+) currents. In isolated perfused hearts, cinnamophilin prolonged the AV nodal conduction interval and Wenckebach cycle length and the refractory periods of the AV node, His-Purkinje system and ventricle, while shortening the ventricular repolarization time. Additionally, cinnamophilin reduced the occurrence of reperfusion-induced ventricular fibrillation. CONCLUSIONS AND IMPLICATIONS: These results suggest that the promising anti-arrhythmic effect and the changes in the electromechanical function induced by cinnamophilin in guinea-pig heart can be chiefly accounted for by inhibition of I(Ca,L) and I(Na).

Molecular cloning and gene expression of the gonadotropin-releasing hormone receptor in the orange-spotted grouper, Epinephelus coioides.

The objective of this study was to investigate the molecular mechanisms of gonadotropin-releasing hormone receptor (GnRH-R) involved in the endocrine regulation of reproduction in the orange-spotted grouper, Epinephelus coioides. The full-length cDNA encoding GnRH-R type I was successfully cloned from the pituitary by reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) methods in the grouper. The complete GnRH-R type I cDNA is 1607 bp, which includes an open reading frame of 1092 bp encoding a protein of 364 amino acids, a seven-alpha helix transmembrane domain, a N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The expression of GnRH-R type I was found to be highest in the pituitary. An intramuscular injection of various GnRH types in vivo was attempted. The expression of GnRH-R type I was stimulated by a single injection of salmon GnRH, while in the case of chicken GnRH II treatment, the expression of GnRH-R type I was inhibited. This suggests that the action of chick GnRH II is probably enhanced through the GnRH receptor of different forms. Furthermore, none of them were expressed by an injection of seabream GnRH, and this is likely attributed to the injection dose being below the threshold level, and this remains to be further examined. In conclusion, GnRHs of various types are effective in stimulating the expression of gonadotropins through various forms of the GnRH-R, and multiple forms of the receptor gene likely exist in teleosts.

Molecular cloning of a cold-shock domain protein, zfY1, in zebrafish embryo(1).

Cold-shock domain proteins in vertebrates contain a highly conserved domain which is related to the Escherichia coli cold-shock proteins. Here we report the cloning of a cold-shock domain protein from zebrafish embryo. Using the combination of PCR techniques with degenerate primers, 5'RACE and 3'RACE, the full length cDNA of a cold-shock domain protein in the zebrafish embryo was successfully cloned without constructing and screening a library. Determined from the deduced amino acid sequence, this protein is most similar to Xenopus, FRGY1, and this newly cloned zebrafish gene was therefore designated as zfY1.

In silico analysis of crustacean hyperglycemic hormone family.

Through multiple sequence alignment and phylogenetic analysis, the subgrouping of the crustacean hyperglycemic hormone (CHH) family was updated using the most complete, nonredundant sequence data set. All sequences from insects were clustered into a distinct subbranch with characters closer to CHH subfamily I. Several sequences that are controversial in their nomenclature and classification are discussed. The motif configuration of CHHs differs from that of molt-inhibiting hormone or gonad-inhibiting hormone in both N and C termini. These two motifs approach each other in tertiary structure models, and the motif preference reveals the critical roles of these regions in functional specificity. Two types of exon organizations of the CHH family genes were observed. Four-exon Chh genes were found in a wide range of pan-crustacean (crustacean and hexapod) taxa, except for the penaeid species, from which the 3-exon Chh genes were reported. Meanwhile, the 3-exon structure was found in the Mih gene and Moih genes from one brachyuran species. Combining gene scan skill and exon splicing rules found in this study, we define three more novel sequences from two insect genomes. The pattern of the exon-exon junction within the mature peptide segment is preserved in all CHH family members.

Stearoyl-CoA desaturase expression and fatty acid composition in milkfish (Chanos chanos) and grass carp (Ctenopharyngodon idella) during cold acclimation.

Desaturation of fatty acids is an important adaptation mechanism for fish to maintain membrane fluidity under thermal stress. To comprehend the temperature adaptation mechanism in fish, we investigated the difference in the changes of stearoyl-CoA desaturase expression and fatty acid composition between milkfish and grass carp under cold acclimation. We find that in both fish the proportions of unsaturated fatty acids at 15 degrees C are all higher than those at 25 degrees C. In milkfish Delta(9)-desaturation index (ratios of 16:1/16:0 and 18:1/18:0) increases significantly in the beginning of cold acclimation at 15 degrees C and decreases afterward, but in grass carp it increases slightly in the beginning of cold acclimation followed by a sustained dramatic increase. Similarly, activity of stearoyl-CoA desaturase in milkfish increases significantly in the beginning, peaks at day 4, and then decreases constantly, but in grass carp it increases gradually in the first week, rises dramatically afterward, and then maintains a very high level. The change of stearoyl-CoA desaturase activity is parallel to the change of Delta(9)-desaturation index in both milkfish and grass carp, but it is one day earlier than Delta(9)-desaturation index in milkfish. The difference of adaptation capability between milkfish and grass carp under cold stress is further evidenced by RT-PCR and Northern blot analysis of stearoyl-CoA desaturase gene expression.

Recycling rates of waste home appliances in Taiwan.

The objective of this study is to provide a calculation of recycling rates of waste home appliances in Taiwan, for the EPA to amend these rates in order to increase the recycling efficiency. The recycling rate is calculated by a formula according to the statistical results obtained through: (1) an estimation of domestic use of home appliances using time series analysis with multiplicative seasonal ARIMA model, (2) a further estimation of generated waste home appliances based upon the estimated domestic use and the corresponding distribution of lifetime span, and (3) a cost analysis of recycling home appliances based on a sampling survey with stratified systematic sampling conducted among collectors and a survey on five recycling plants of waste home appliances. The suggested recycling rates in this study finally used by the EPA show that all of the recycling rates have increased compared with the rates in previous years. This study also implies that amending the recycling rates may only solve some recycling problems temporarily; however, the recycling system of waste home appliances in Taiwan has to be reformed to increase the recycling efficiency for the long term.

Liver abscess in patients with cirrhosis of the liver: a 12-year experience.

PURPOSE: Liver abscess is rare in patients with cirrhosis of the liver. The aim of this retrospective study was to investigate the incidence, clinical presentation, causal pathogens, and outcome of liver abscess in cirrhotic patients. METHODS: We collected 21 liver abscess specimens (from 14 male patients and 7 female patients; Child A: B: C, 4: 7: 10) from 22,731 admissions of 6450 cirrhotic patients, from 1986 through 1998. RESULTS: The common clinical symptoms and signs included fever, chills, and abdominal tenderness. The major predisposing factors were biliary tract disease (52%) and diabetes mellitus (48%). The diagnosis rate with abdominal ultrasonography was 79%. Gram-negative aerobes were the predominant pathogens (Klebsiella pneumoniae, 66.7%; Escherichia coli, 23.8%), and occurred in 80% and 69% of blood and pus cultures, respectively, while 38% of cases showed polymicrobial pathogens. The location of the abscess was predominantly in the right lobe (71.4%), and 47.6% of patients had multiple abscesses. Six patients died (all with Child C cirrhosis). The overall mortality rate was 28.6% (6/21). CONCLUSIONS: The incidence of liver abscess in the cirrhotic patients was low, at 0.09% (21/22,731 admissions). The clinical presentations and pathogens were not different from those in noncirrhotic patients, except that in our cirrhotic patients, there was no significant difference in mortality between those with monomicrobial and those with polymicrobial abscess: nor was there a significant difference in mortality between those with single and those with multiple abscesses. The Child C patients were the high-risk group.

Molecular cloning and sequence analysis of stearoyl-CoA desaturase in milkfish, Chanos chanos.

Stearoyl-CoA desaturase (EC 1.14.99.5) is a key enzyme in the biosynthesis of polyunsaturated fatty acids and the maintenance of the homeoviscous fluidity of biological membranes. The stearoyl-CoA desaturase cDNA in milkfish (Chanos chanos) was cloned by RT-PCR and RACE, and it was compared with the stearoyl-CoA desaturase in cold-tolerant teleosts, common carp and grass carp. Nucleotide sequence analysis revealed that the cDNA clone has a 972-bp open reading frame encoding 323 amino acid residues. Alignments of the deduced amino acid sequence showed that the milkfish stearoyl-CoA desaturase shares 79% and 75% identity with common carp and grass carp, and 63%-64% with other vertebrates such as sheep, hamsters, rats, mice, and humans. Like common carp and grass carp, the deduced amino acid sequence in milkfish well conserves three histidine cluster motifs (one HXXXXH and two HXXHH) that are essential for catalysis of stearoyl-CoA desaturase activity. However, RT-PCR analysis showed that stearoyl-CoA desaturase expression in milkfish is detected in the tissues of liver, muscle, kidney, brain, and gill, and more expression sites were found in milkfish than in common carp and grass carp. Phylogenic relationships among the deduced stearoyl-CoA desaturase amino acid sequence in milkfish and those in other vertebrates showed that the milkfish stearoyl-CoA desaturase amino acid sequence is phylogenetically closer to those of common carp and grass carp than to other higher vertebrates.

Molecular cloning of the common carp (Cyprinus carpio) rhodopsin cDNA.

A recombinant phage clone containing a 1584 nucleotides rhodopsin cDNA was screened from a carp retinal cDNA library. The inserted DNA consisting of a single open reading frame of 1062 nucleotides at positions 72 to 1133 encodes a 354 amino acid polypeptide. The deduced amino acid sequence of carp rhodopsin showed 95.7, 85.5 and 74.4% identity with that of goldfish, sand goby and lamprey, respectively. The sites of palmitoylation, glycosylation, disulfide bond formation and Schiff base formation in the putative rhodopsin are all conserved.

The zeta protein kinase C isoform from the testis of the grey mullet Mugil cephalus with a specific reaction protein of M(r) 48,000 on oolemma.

The zeta protein kinase C isoform (PKC-zeta) was purified from the testis of the grey mullet Mugil cephalus and has relative masses (M(r)) of 65,000 and 63,000. The subunits of PKC-zeta from spermatozoa degenerated to M(r) 58,000 and 53,000 after continuous freezing and thawing. Proteins of M(r) 48,000 on the oolemma of the grey mullet Mugil cephalus were found to be the reaction proteins of the PKC-zeta from spermatozoa.

System size, energy, and centrality dependence of pseudorapidity distributions of charged particles in relativistic heavy-ion collisions.

We present the first measurements of the pseudorapidity distribution of primary charged particles in Cu+Cu collisions as a function of collision centrality and energy, sqrt[s_{NN}]=22.4, 62.4, and 200 GeV, over a wide range of pseudorapidity, using the PHOBOS detector. A comparison of Cu+Cu and Au+Au results shows that the total number of produced charged particles and the rough shape (height and width) of the pseudorapidity distributions are determined by the number of nucleon participants. More detailed studies reveal that a more precise matching of the shape of the Cu+Cu and Au+Au pseudorapidity distributions over the full range of pseudorapidity occurs for the same N{part}/2A rather than the same N_{part}. In other words, it is the collision geometry rather than just the number of nucleon participants that drives the detailed shape of the pseudorapidity distribution and its centrality dependence at RHIC energies.

System size, energy, pseudorapidity, and centrality dependence of elliptic flow.

This Letter presents measurements of the elliptic flow of charged particles as a function of pseudorapidity and centrality from Cu-Cu collisions at 62.4 and 200 GeV using the PHOBOS detector at the Relativistic Heavy Ion Collider. The elliptic flow in Cu-Cu collisions is found to be significant even for the most central events. For comparison with the Au-Au results, it is found that the detailed way in which the collision geometry (eccentricity) is estimated is of critical importance when scaling out system-size effects. A new form of eccentricity, called the participant eccentricity, is introduced which yields a scaled elliptic flow in the Cu-Cu system that has the same relative magnitude and qualitative features as that in the Au-Au system.

Involvement of norepinephrine in the hyperglycemic responses of the freshwater giant prawn, Macrobrachium rosenbergii, under cold shock.

Hyperglycemic response of freshwater giant prawn, Macrobrachium rosenbergii, under acute cold shock was investigated, and the involvement and stimulatory pathways of norepinephrine (NE) on induced-glycemia were further examined. Remarkable elevations in hemolymph glucose at comparable magnitude were observed in both intact and eyestalkless prawn under cold treatments, suggesting that hyperglycemic response of this species is not solely mediated through the actions of crustacean hyperglycemic hormone released from X-organ sinus gland complex on the target tissues, but NE is involved. Positive and significant correlations were noted between the hemolymph glucose titers and NE contents in both thoracic ganglia and the hemolymph, suggesting that NE plays a significant role in the hyperglycemic responses of this species under cold. Depressive effects of various adrenoceptor antagonists monitored in vivo and in vitro further suggest that the action of NE is primarily mediated through both alpha1- and beta1-adrenoceptors.

Energy dependence of directed flow over a wide range of pseudorapidity in Au + Au collisions at the BNL Relativistic Heavy Ion Collider.

We report on measurements of directed flow as a function of pseudorapidity in Au + Au collisions at energies of square root of SNN = 19.6, 62.4, 130 and 200 GeV as measured by the PHOBOS detector at the BNL Relativistic Heavy Ion Collider. These results are particularly valuable because of the extensive, continuous pseudorapidity coverage of the PHOBOS detector. There is no significant indication of structure near midrapidity and the data surprisingly exhibit extended longitudinal scaling similar to that seen for elliptic flow and charged particle pseudorapidity density.

System size and centrality dependence of charged hadron transverse momentum spectra in Au + Au and Cu + Cu collisions at square root of SNN = 62.4 and 200 GeV.

We present transverse momentum distributions of charged hadrons produced in Cu + Cu collisions at square root of SNN = 62.4 and 200 GeV. The spectra are measured for transverse momenta of 0.25 < pT < 5.0 GeV/c at square root of SNN = 62.4 GeV and 0.25 < pT < 7.0 GeV/c at square root of SNN = 200 GeV, in a pseudorapidity range of 0.2 < eta < 1.4. The nuclear modification factor R(AA) is calculated relative to p + p data at both collision energies as a function of collision centrality. At a given collision energy and fractional cross section, R(AA) is observed to be systematically larger in Cu + Cu collisions compared to Au + Au. However, for the same number of participating nucleons, R(AA) is essentially the same in both systems over the measured range of pT, in spite of the significantly different geometries of the Cu + Cu and Au + Au systems.