Development of quality indicators for pregnancy and childbirth in patients with systemic lupus erythematosus.

OBJECTIVES: A quality indicator for the treatment of systemic lupus erythematosus during pregnancy and childbirth that is useful for sharing standard treatment policies has not yet been developed. This study aimed to develop a quality indicator for systemic lupus erythematosus associated with pregnancy and childbirth. METHODS: To identify candidate quality indicators, we conducted a systematic literature review on the development of quality indicators for systemic lupus erythematosus related to pregnancy and childbirth and on clinical practice guidelines. Candidate quality indicator items were extracted from the final selected articles, and a first evaluation, panel meeting, and second evaluation were conducted to determine whether the candidate items were appropriate as quality indicators. Items for which all panel members reached a consensus were designated pregnancy and childbirth-related systemic lupus erythematosus quality indicators. RESULTS: Four articles on systemic lupus erythematosus-quality indicator development and 28 practice guidelines were listed through abstract/text screening. Based on these studies, 52 candidate quality indicators were extracted that were limited to items related to pregnancy and childbirth, and 41 items were selected on which all panel members agreed. CONCLUSION: We developed pregnancy-related systemic lupus erythematosus quality indicators using the RAND/UCLA method and selected 41 items, which could be used clinically.

Candidatus Mycoplasma haemohominis in Human, Japan.

Hemotropic mycoplasmas are common pathogens in animals, but it remains unclear what role these pathogens play in human infections. We report clinical and biologic characterization of Candidatus Mycoplasma haemohominis infection in a 42-year-old man in Japan. The patient had severe hemophagocytic syndrome 1 month after an accidental needlestick injury. Metagenomic deep sequencing identified Candidatus M. haemohominis and determined its draft genome for an isolate from serum of the patient. A high copy number of the Candidatus M. haemohominis genome was detected in serum and bone marrow samples. Electron microscopy examination showed morphologic characteristics of Candidatus M. haemohominis. Levofloxacin monotherapy induced resistance caused by a gyrase A gene mutation in the quinolone resistance-determining region, but a combination treatment with moxifloxacin and minocycline was effective. We identified Candidatus M. haemohominis in a patient who had life-threatening symptoms related to multiple organ infection. Human infection with this mycoplasma might occur more frequently than has been generally recognized.

Yellow Pea Pasta Enhances the Saltiness and Suppression of Postprandial Blood Glucose Elevation.

Salt and carbohydrates, two causes of elevated blood glucose, are essential components for survival; however, excessive intake of either is a known health risk. In a previous study, we reported the usefulness of pasta prepared from yellow pea (YPP) as a functional staple food that is beneficial for blood sugar control. In this study, we investigated the usefulness of YPP in reducing health risks by examining its effects on saltiness, postprandial satisfaction, and second meal. The results showed that YPP tasted saltier than conventional pasta made from semolina wheat when prepared with a 0.75% salt concentration. In addition, we examined blood glucose levels, insulin secretion, and postprandial hunger over a longer period than in previous studies. We observed that when the same amount of YPP and wheat pasta were eaten, the elevation in blood glucose and insulin secretion was lower after YPP consumption while maintaining a similar level of satiety. Furthermore, YPP was also observed to be able to suppress elevated insulin levels at the second meal.

Effect of short-term consumption of yellow peas as noodles on the intestinal environment: A single-armed pre-post comparative pilot study.

Legumes contain dietary fiber and resistant starch, which are beneficial to the intestinal environment. Here, we investigated the effects of yellow pea noodle consumption on the gut microbiota and fecal metabolome of healthy individuals. This single-armed pre-post comparative pilot study evaluated eight healthy female participants who consumed yellow pea noodles for 4 weeks. The gut microbiota composition and fecal metabolomic profile of each participant were evaluated before (2 weeks), during (4 weeks), and after (4 weeks) daily yellow pea noodle consumption. 16S rRNA gene sequencing was performed on stool samples, followed by clustering of operational taxonomic units using the Cluster Database at High Identity with Tolerance and integrated QIIME pipeline to elucidate the gut microbiota composition. The fecal metabolites were analyzed using capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography time-of-flight mass spectrometry. Compared to day 0, the relative abundances of five bacterial genera (Bacteroides, Bilophila, Hungatella, Parabacteroides, and Streptococcus) in the intestinal microbiota significantly decreased, wherein those of Bifidobacterium longum and Ruminococcus bromii were increased on day 29 and decreased to the basal level (day 0) on day 57. Fecal metabolomic analysis identified 11 compounds showing significant fluctuations in participants on day 29 compared to day 0. Although the average levels of short-chain fatty acids in participants did not differ significantly on day 29 compared to those on day 0, the levels tended to increase in individual participants with >8% relative abundance of R. bromii in their gut microbiota. In conclusion, incorporating yellow peas as a daily staple may confer human health benefits by favorably altering the intestinal environment.

The use of mammalian cultured cells loaded with a fluorescent dye shows specific membrane penetration of undissociated acetic acid.

Acetic acid induces unique physiological responses in mammalian cells. Our previous study found that fura-2-loaded human embryonic kidney (HEK) 293T cells showed a robust intracellular fluorescence response immediately after stimulation with acetic acid, and no such response in the case of citric acid. In the present study, we aimed to identify the unique characteristics of acetic acid responsible for this phenomenon. We found that one such feature is its hydrophobicity. We also discovered that acetic acid induces cell responses by intracellular acidification. Of the components of acetic acid in solution (protons, acetate ions, and undissociated acetic acid), undissociated acetic acid might be the functional unit that penetrates the lipid bilayer of cell membranes to acidify the intracellular environment, thereby inducing cell responses. The method used in this study might be convenient in evaluating the intracellular acidification of cultured cells by acids in the external environment.

Acetic acid activates PKD1L3-PKD2L1 channel--a candidate sour taste receptor.

The polycystic kidney disease (PKD) 1L3-PKD2L1 channel is a candidate sour taste receptor expressed in mammalian taste receptor cells. Various acids are reported to activate PKD channels after the removal of the acid stimuli, but little information is available on the activation of these channels by acetic acid. It was difficult to analyze the PKD channel activation by acetic acid using Ca2+ imaging experiments because this acid induces a transient and nonspecific response in cultured cells. Here, we developed a novel method to evaluate PKD channel activation by acetic acid. Nonspecific responses were observed only over a short period after the application of acetic acid. In contrast, PKD channel activation evoked by acetic acid as well as citric acid was detected even at a later time point. This method revealed that PKD1L3-PKD2L1 channel activation by acetic acid was pH-dependent and occurred when the ambient pH was <3.1.

Pd-Catalyzed Dearomative Carboxylation of Indolylmethanol Derivatives.

By using a new catalytic system (PdCl2[P( n-Bu)3]2 in combination with ZnEt2), various 3-indolylmethanol derivatives were successfully carboxylated with CO2 (1 atm) via dearomatization of the indole nucleus, affording 3-methyleneindoline-2-carboxylates. In contrast, carboxylation of 2-indolylmethanol derivatives afforded unexpected doubly carboxylated products, which are useful synthetic precursors for biologically active compounds.

Correction to: ADAM-17 is expressed in the inflammatory myopathy and is involved with interstitial lung disease.

The original version of this article, unfortunately, contained errors. Figure citation, caption, image and updated sentence in the Result section are now presented correctly in this article.

ADAM-17 is expressed on rheumatoid arthritis fibroblast-like synoviocytes and regulates proinflammatory mediator expression and monocyte adhesion.

BACKGROUND: To examine the expression of ADAM-17 in rheumatoid arthritis (RA) biological fluids and the role it plays in monocyte adhesion to RA fibroblast-like synoviocytes (FLSs). METHODS: ADAM-17 expression was measured by enzyme-linked immunosorbent assays (ELISAs) in serum from normal (NL) subjects, osteoarthritis (OA) patients, and RA patients. We also analyzed the correlation between ADAM-17 and disease activity score 28 (DAS28) in RA. To determine expression of ADAM-17 in RA synovial tissues (STs) and RA FLS, we performed immunofluorescence analyses. To determine the role of ADAM-17 in RA, we transfected RA FLSs with small interfering RNA (siRNA) against ADAM-17. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was measured. Finally, adhesion molecules on ADAM-17 siRNA-transfected RA FLSs were measured using cell surface ELISAs. RESULTS: ADAM-17 in RA serum was significantly higher than that in NL and OA serum and correlated with DAS28. ADAM-17 in RA synovial fluids was higher than that in OA synovial fluids. ADAM-17 was expressed on RA cells lining STs and RA FLSs. THP-1 adhesion to ADAM-17 siRNA-transfected RA FLSs was decreased compared with that to control siRNA-transfected RA FLSs. ICAM-1 on TNF-α-stimulated ADAM-17 siRNA-transfected RA FLSs was significantly decreased compared with that on control siRNA-transfected RA FLSs. CONCLUSIONS: These data indicate that ADAM-17 is expressed on RA STs and plays a role in RA inflammation by regulating monocyte adhesion to RA FLSs. ADAM-17 might be an important inflammatory mediator in inflammatory diseases such as RA.

ADAM-17 is expressed in the inflammatory myopathy and is involved with interstitial lung disease.

The "A disintegrin and metalloprotease" (ADAM) family is thought to play an important role in tissue destruction and inflammatory reactions. ADAM-17 was first described as the protease responsible for tumor necrosis factor (TNF)-α shedding. Here, we have shown the expression of ADAM-17 in inflammatory myopathy and demonstrated the role of inflammation in interstitial lung diseases (ILD). ADAM-17 in inflammatory myopathy serum [polymyositis (n = 26), dermatomyositis (n = 34), and clinically amyopathic dermatomyositis (n = 10)] and healthy control (n = 19) was measured using enzyme-linked immunosorbent assay. The relationship between ADAM-17 and clinical data was examined. Finally, we performed immunohistological analysis to investigate the expression of ADAM-17 on the muscles of the inflammatory myopathy patients. ADAM-17 in inflammatory myopathy was significantly higher than that in healthy control (mean ± SEM, 1048 ± 312 and 36 ± 18 pg/ml, respectively; p < 0.05). ADAM-17 in post-treatment with corticosteroid and/or immunosuppressant serum was significantly decreased compared with that in pre-treatment serum (1465 ± 562 and 1059 ± 503 pg/ml, respectively; p < 0.01). ADAM-17 was significantly positively correlated with fractalkine/CX3CL1 and CXCL16. In addition, ADAM-17 in inflammatory myopathy with ILD patients (n = 46) was significantly higher than that in non-ILD patients (n = 24) (1379 ± 454 and 413 ± 226 pg/ml, respectively; p < 0.05). We found the expression of ADAM-17 on muscle biopsy tissue. ADAM-17 is expressed in inflammatory myopathies especially ILD, suggesting that ADAM-17 plays a role in lung fibrosis. ADAM-17 may be a potential target in inflammatory myopathies with ILD.

Sex Differences in the Effects of a Biological Drug for Rheumatoid Arthritis on Depressive State.

OBJECTIVE: Sex-specific medicine has attracted attention in recent years, but no report on rheumatoid arthritis (RA) has examined sex differences in the effectiveness of biologics on activities of daily living (ADL), quality of life (QOL), or depressive state. METHODS: The study subjects were 161 RA patients (female: 138; male: 23) attending regular doctor visits at our hospital. We compared the changes in disease activity, which was evaluated using the simplified disease activity index (SDAI), ADL (using the modified health assessment questionnaire; mHAQ), QOL (using short form-36; SF-36), and the Hamilton Depression Rating Scale (HAM-D) for RA patients between each sex over a six-month observation period while administering biologic treatment. RESULTS: The female patients reported significant improvements in the following metrics: SDAI: from 22.1 ± 11.9 to 8.9 ± 7.8 (p < 0.001); mHAQ: from 0.46 ± 0.50 to 0.32 ± 0.45 (p < 0.001); and HAM-D: from 6.2 ± 4.8 to 3.8 ± 4.1 (p < 0.001). Moreover, all eight items of the SF-36 were significantly improved (p < 0.01). In contrast, the male patients improved on the SDAI (from 27.9 ± 11.7 to 12.7 ± 8.6 (p < 0.001)), but we did not observe significant improvements in the mHAQ or HAM-D scores or in any items on the SF-36. CONCLUSION: Both male and female patients with RA improved when using a biological drug. Sex differences in the improvement of depressive state were observed.

Influence of renal complications on the efficacy and adverse events of tacrolimus combination therapy in patients with systemic lupus erythematosus (SLE) during a maintenance phase: a single-centre, prospective study.

OBJECTIVES: The study investigated whether renal complications affected the efficacy and safety of tacrolimus combination therapy in patients with systemic lupus erythematosus (SLE) during a maintenance phase. METHODS: Fifty-seven patients with SLE (A: 30 cases with renal complication, B: 27 cases without renal complications) were included. The presence of renal complications was defined as proteinuria ≥0.5 g/day and lupus nephritis on renal biopsy. Major outcome measures included SLE disease activity index (SLEDAI), steroid dose, serum anti-dsDNA Ab, C3 and creatinine (Cr) levels and estimated glomerular filtration rate (eGFR). The patient's background factors included age, gender, disease duration and ACE-I/angiotensin II receptor blocker and statin therapies. We compared these outcome measures pre treatment and after 1 year of treatment. RESULTS: The SLEDAI and serum C3 levels improved in both groups from pretreatment period to post-treatment period: from 7.2±5.0 to 2.8±2.3 in A and 6.4±3.8 to 2.4±2.2 in B, p<0.001, and from 65.9±24.6 to 77.7±18.2 mg/dL in A and 81.8±23.0 to 90.6±19.4 mg/dL in B, p=0.002, respectively. The anti-dsDNA antibody level was reduced, and the serum Cr and eGFR levels were slightly elevated. No patients developed end-stage renal failure that required artificial dialysis. CONCLUSIONS: Tacrolimus combination therapy had additive beneficial effects on reduced proteinuria and increased serum C3 levels in patients with SLE with renal complications during a maintenance phase.

A disintegrin and metalloprotease-10 is correlated with disease activity and mediates monocyte migration and adhesion in rheumatoid arthritis.

A disintegrin and metalloproteases (ADAMs) are a family of proteins that have been reported to be involved in several inflammatory conditions. We examined the secretion of ADAM-10 in biological fluids from patients with rheumatoid arthritis (RA) and the role it plays in monocyte migration. ADAM-10 levels were measured using enzyme-linked immunosorbent assays and immunofluorescence. To examine the role of ADAM-10 in RA synovial fluids (SFs), we studied THP-1 (human acute monocyte leukemia cell line) and monocyte chemotaxis. To determine whether ADAM-10 plays a role in cell proliferation in the RA synovium, we assayed the proliferation of ADAM-10 small interfering RNA (siRNA)-transfected RA fibroblast-like synoviocytes (FLSs). The ADAM-10 level in RA serum was significantly higher than that in normal serum and was correlated with a disease activity score of 28. ADAM-10-depleted RA SFs showed a decrease in THP-1 and monocyte migratory activity compared with that of sham-depleted controls. ADAM-10 siRNA inhibited monocyte adhesion to RA FLSs. Finally, blocking ADAM-10 secretion in RA FLSs resulted in decreased production of fractalkine/CX3CL1 and vascular endothelial cell growth factor. These data indicate that ADAM-10 plays a role in monocyte migration in RA and suggest that targeting ADAM-10 may provide a method of decreasing inflammation and potentially treating other inflammatory diseases.

Si-C bond cleavage by hydride complexes of rhodium and iridium: comparison of Si-C(sp(2)) and Si-C(sp(3)) activation.

Single Si-C(R) (R = Ph, Me, Et) bond activation in {o-(Ph(2)P)C(6)H(4)}(2)Si(Me)(R) induced by Rh(H)(CO)(PPh(3))(3) was developed. The efficiency of Si-C(R) bond breaking reactions increased at 60 °C in the order Si-C(Et) < Si-C(Me) < Si-C(Ph) and strongly depended on the reaction temperature. Elevating the reaction temperature promoted Si-C(Me) over Si-C(Ph) bond activation, demonstrating that Si-C(Me) cleavage is entropically favored but enthalpically unfavored in comparison with Si-C(Ph) bond cleavage.

Facile synthesis of rhodium and iridium complexes bearing a [PEP]-type ligand (E = Ge or Sn) via E-C bond cleavage.

Rhodium and iridium complexes bearing a tridentate [PEP] type ligand ([PEP] = {o-(Ph(2)P)C(6)H(4)}(2)E(Me); E = Ge or Sn) were synthesized through the phosphine exchange reaction accompanied by selective E-C bond cleavage. The ligand precursors {o-(Ph(2)P)C(6)H(4)}(2)EMe(2) (E = Ge or Sn) were readily obtained in excellent yields by treating {o-(Ph(2)P)C(6)H(4)}(2)Li with 0.5 equivalents of Me(2)ECl(2). Tris(triphenylphosphine)rhodium(I) carbonyl hydride M(H)(CO)(PPh(3))(3) (M = Rh, Ir) cleaved one of the E-Me bonds of {o-(Ph(2)P)C(6)H(4)}(2)EMe(2) exclusively to afford the trigonal bipyramidal (TBP) complexes, [PEP]M(CO)(PPh(3)). Square-planar rhodium complexes [PEP]Rh(PPh(3)) were also prepared from the reactions of tetrakis(triphenylphosphine)rhodium(I) hydride Rh(H)(PPh(3))(4) with {o-(Ph(2)P)C(6)H(4)}(2)EMe(2). Further, the trans influence of group 14 elements E (E = Si, Ge, Sn) in [PEP]Rh(PPh(3)) is discussed in terms of the (1)J(Rh-P) coupling constants, indicating that E exhibited a stronger trans labilizing effect in the order Sn < Ge < Si.

Synthesis of iridium complexes bearing {o-(Ph2P)C6H4}(3)E type (E = Si, Ge, and Sn) ligand and evaluation of electron donating ability of group 14 elements E.

Trigonal bipyramidal (TBP) iridium(i) complexes {o-(Ph(2)P)C(6)H(4)}(3)EIr(CO) (E = Si: 1-Ir, Ge: 2-Ir, Sn: 3-Ir) comprising group 14 element E were synthesized and converted into the corresponding cationic iridium(III) complexes [{o-(Ph(2)P)C(6)H(4)}(3)EIr(H)(CO)][BF(4)] (E = Si: 4, Ge: 5, Sn: 6) bearing octahedral geometry by protonation using (Et(2)OH)(BF(4)). The origin of trans-labilizing abilities of E was investigated through structural analysis, IR and NMR spectroscopic analysis, and density functional theory calculations. Further, the electron-donating abilities of E were investigated through proton transfer reactions.

The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs.

Polycystic kidney disease (PKD) 2L1 protein is a member of the transient receptor potential (TRP) ion channel family. In circumvallate and foliate papillae, PKD2L1 is coexpressed with PKD1L3. PKD2L1 and PKD1L3 interact through their transmembrane domain and the resulting heteromer PKD1L3/PKD2L1 owns a unique channel property called 'off-responses' to acid stimulation, although PKD2L1 does not own this property by itself. To define the pharmacological properties of the PKD1L3/PKD2L1 channel, we developed a new method to effectively evaluate channel activity using human embryonic kidney 293T cells in which the channel was heterologously expressed. This method was applied to screen substances that potentially regulate it. We found that capsaicin and its analogs, which are TRPV1 agonists, inhibited the response to acid stimuli and that the capsaicin inhibition was reversible with an IC(50) of 32.5 µm. Capsaicin and its analogs are thus useful tools for physiological analysis of PKD1L3/PKD2L1 function.

Methyl syringate, a low-molecular-weight phenolic ester, as an activator of the chemosensory ion channel TRPA1.

Transient receptor potential channel ankryn 1 (TRPA1) and transient receptor potential channel vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and are often coexpressed in sensory neurons. Extracts of the first leaves of Kalopanax pictus Nakai (Araliaceae) have been shown to activate hTRPA1 and hTRPV1. Therefore, the effects of six commercially available chemicals (methyl syringate, coniferyl alcohol, protocatechuic acid, hederacoside C, α-hederin, and eleutheroside B) found in K. pictus were investigated on cultured cells expressing hTRPA1 and hTRPV1. Of the six compounds, methyl syringate selectively activated hTRPA1 (EC(50) = 507.4 µM), but not hTRPV1. Although methyl syringate had a higher EC(50) compared with allyl isothiocyanate (EC(50) = 7.4 µM) and cinnamaldehyde (EC(50) = 22.2 µM), the present study provides evidence that methyl syringate from K. pictus is a specific and selective activator of hTRPA1.

Radiographic method to measure the inclination angle of the acetabulum.

BACKGROUND: Various attempts have been made to assess the inclination angle of the acetabulum utilizing new imageprocessing technologies to enable three-dimensional reconstruction of the acetabulum. However, reliability of these methods has not been estimated in comparison with anatomical measurements. This study developed a geometric method for measuring the acetabular inclination with radiograms and evaluated the reliability of this method by comparing the anatomically measured acetabular inclination angle of the same dry pelvic bone. METHODS: One hundred and ten acetabulums from 55 human pelvis specimens were used. The uppermost, most frontal, and posterior lowermost points of the acetabular rim were determined, and an axis perpendicular to the triangular plane formed by these three points was defined as the anatomical inclination axis of the acetabulum. The anatomical lateral and anterior opening angles were directly measured using a tool we devised for this purpose. Posteroanterior and lateral radiograms of each pelvis were taken concurrently and three points were marked by small metal plates. Based on projections of these three points onto the posteroanterior and lateral images, we geometrically measured and calculated the lateral and anterior opening angles of the acetabulum. RESULTS: Anatomical measurements of the lateral opening angles ranged from 38 degrees to 63 degrees (mean 51.0 degrees ), and anterior opening angles from 10 degrees to 36 degrees (mean 20.8 degrees ). Geometric measurements of the lateral opening angles ranged from 40 degrees to 61 degrees (mean 50.5 degrees ), and anterior opening angles ranged from 7 degrees to 35 degrees (mean 20.8 degrees ). Geometrically measured acetabular inclination angles were highly correlated with the anatomically measured ones for both the lateral and anterior opening angles, with correlation coefficients of 0.803 and 0.822, respectively. CONCLUSIONS: Our geometric measurement method of the acetabular inclination angle enabled us to calculate the lateral and anterior opening angles, which were very close to the corresponding anatomical measurements. This method allows three-dimensional evaluation of the anatomical structure of the hip and may be useful in predicting progression of coxarthrosis by measuring the femoral neck shaft and anteversion angles.