High serum IgA levels in patients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, and favourable responses to treatments.

OBJECTIVES: Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels. METHODS: The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels. RESULTS: Of the 169 patients with IgG4-RD, 17 (10.1%) had elevated serum IgA levels. Those with elevated serum IgA levels showed higher serum C-reactive protein levels and lower prevalence of relapse than those without. Other clinical features did not differ significantly, including inclusion scores of the American College of Rheumatology/European League Against Rheumatism classification criteria. Cox regression analysis showed that elevated serum IgA levels were associated with a lower incidence of relapse. Moreover, patients with elevated serum IgA levels showed prompt improvement in response to glucocorticoids in the IgG4-RD responder index. CONCLUSIONS: Some patients diagnosed with IgG4-RD have high serum IgA levels. These patients may form a subgroup, characterized by good response to glucocorticoids, less frequent relapse, mildly elevated serum C-reactive protein levels, and possible complications of autoimmune diseases.

Systematic active environmental surveillance successfully identified and controlled the Legionella contamination in the hospital.

INTRODUCTION: Legionella disease can manifest as severe respiratory tract infection with a high mortality rate and is sometimes associated with a hospital outbreak by a contaminated water supply. A patient with breast cancer admitted about a month before. High fever was observed 18 days after admission and the Legionella antigen test showed the positive result. METHODS: Due to the incidence of Legionella infection, we demonstrated the active surveillance of Legionella contamination in the entire hospital. RESULTS: Cultures of her environmental samples revealed that hot water in two bathrooms were contaminated with Legionella. In our hospital, the hot water is heated and pumped up on the roof and distributed to each room. The contaminated bathrooms were related to the same plumbing. Therefore, we further collected samples throughout the hot water system. Legionella was not detected in the central part of the system. However, we detected Legionella in the hot water sampled from other five rooms, which were also associated with the same plumbing of the two bathrooms. The temperature and chlorine concentration of the hot water were not high enough to inactivate Legionella at the end of the plumbing. After the adjustment of the water temperature and chlorine concentration, Legionella became undetectable. Our prompt and active surveillance successfully identified the plumbing of the hot water system as the source of Legionella contamination and took precautions against future outbreaks. CONCLUSIONS: Monitoring of water temperature and chloride concentration at the end of the hot water circulation is important to prevent nosocomial Legionella disease.

De novo normotensive scleroderma renal crisis six years after living-donor renal transplantation in a patient with overlapping systemic sclerosis/systemic lupus erythematosus syndrome: a case report.

BACKGROUND: Scleroderma renal crisis (SRC) is a critical kidney involvement of systemic sclerosis (SSc), often resulting in end-stage renal disease. Although the recurrence of SRC in the allograft has been reported, the development of de novo SRC after kidney transplantation has not been reported. Furthermore, normotensive SRC, which rarely occurs, makes prompt diagnosis more challenging. This fact should be recognized widely among nephrologists. CASE PRESENTATION: We report a 37-year-old Japanese man with overlapping SSc/systemic lupus erythematous syndrome who developed normotensive SRC in the transplanted kidney shortly after glucocorticoid escalation. Six years prior to admission, he underwent an ABO-compatible living donor kidney transplantation because of lupus nephritis. He was admitted to our hospital for gradually worsening kidney dysfunction. A kidney biopsy showed idiopathic granulomatous interstitial nephritis and high-dose prednisolone was prescribed. Although renal function improved tentatively, it deteriorated again a week later. A secondary kidney biopsy revealed acute thrombotic microangiopathy, leading to the diagnosis of normotensive SRC because all other causes were excluded, and blood pressure was within normal range. Adding an angiotensin-converting enzyme inhibitor and tapering glucocorticoid slowed the speed of deterioration of his kidney function, but he finally required hemodialysis induction. CONCLUSIONS: SRC can newly develop even in the transplanted kidney, especially when high-dose glucocorticoid is administered. Normotensive SRC makes the diagnosis challenging, so nephrologists should carefully monitor patients with SSc and transplanted kidneys to treat SRC promptly.

Pharmacokinetics, pharmacodynamics, and safety of single-dose subcutaneous sarilumab with or without methotrexate in Japanese patients with rheumatoid arthritis: Two single-dose studies.

OBJECTIVES: To assess the safety and pharmacokinetics (PK) of single-dose subcutaneous (SC) sarilumab or tocilizumab SC ± methotrexate (MTX) and to assess the pharmacodynamics (PD) of sarilumab SC or tocilizumab SC monotherapy in Japanese rheumatoid arthritis (RA) patients. METHODS: TDU13402 was a randomized, double-blind, placebo-controlled, single-ascending dose Phase 1 study (NCT01850680). Twenty-four patients (6 per treatment group) received sarilumab 50, 100, or 200 mg plus MTX or placebo (2 per cohort) on Day (D) 1; PK and safety were assessed through D57. PDY14191 was a randomized, open-label, single-dose study (NCT02404558). Thirty patients (15 per arm) received sarilumab 150 mg or tocilizumab 162 mg on D1; PK, PD, and safety were assessed through D43. RESULTS: TDU13402: mean serum sarilumab exposure increased in a greater than dose proportional manner from 50 to 200 mg dose with no clinically meaningful increase in treatment-emergent adverse events (TEAEs). PDY14191: PK profiles of single-dose sarilumab 150 mg or tocilizumab 162 mg were similar; some numerical differences in PD profiles and TEAEs were observed. Neutrophil count decrease/neutropenia was the most frequently reported TEAE with sarilumab treatment in both studies. CONCLUSIONS: PK, PD, and safety profiles of single-dose sarilumab SC with/without MTX were consistent with results anticipated in Japanese patients with RA.

A Japanese Case of COVID-19 Caused by Omicron Strain with Y453F Substitution.

Frequent mutations of SARS-CoV-2 change the strain more transmissible, leading to the pandemic in worldwide. We detected Y453F substitution on Omicron strain, isolated from a Japanese patient in July 2022. While Y453F substitution was identified B1.1.298 lineage in Netherlands and Denmark in 2020, the substitution has not been reported in Omicron strain especially in Japan. Y453F substitution is associated with higher viral infectivity because it is sited in the receptor-binding domain (RBD), and Y453F substitution contributes to increase binding affinity to angiotensin converting enzyme 2 (ACE2). Additionally, Y453F substitution has been reported to escape human leukocyte antigen (HLA), which is known to recognize non-self-antigens in virus-infected cells as cellular immunity, so it should be closely monitored.

Dupilumab efficacy in chronic rhinosinusitis with nasal polyps from SINUS-52 is unaffected by eosinophilic status.

BACKGROUND: The human monoclonal antibody dupilumab blocks interleukin (IL)-4 andIL-13, key and central drivers of type 2 inflammation. Dupilumab, on background mometasone furoate nasal spray (MFNS), improved outcomes in the phase III SINUS-52 study (NCT02898454) in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). This posthoc analysis of SINUS-52 examined whether eosinophilic status of CRSwNP was a predictor of dupilumab efficacy. METHODS: Patients were randomized 1:1:1 to dupilumab 300 mg every 2 weeks (q2w) until week 52; dupilumab 300 mg q2w until Week 24, then 300 mg every 4 weeks until week 52; or placebo (MFNS) until week 52. Coprimary endpoints were change from baseline in nasal polyps score (NPS), nasal congestion (NC), and Lund-Mackay score assessed by CT (LMK-CT) at week 24. Patients (n = 438) were stratified by eosinophilic chronic rhinosinusitis (ECRS) status according to the Japanese Epidemiological Survey of Refractory Eosinophilic Rhinosinusitis algorithm. RESULTS: Dupilumab significantly improved NPS, NC, and LMK-CT scores versus placebo at week 24 in all ECRS subgroups (p < 0.001), with improvements maintained or increased at week 52 (p < 0.001). There was no significant interaction between ECRS subgroup (non-/mild or moderate/severe) and dupilumab treatment effect for all endpoints at weeks 24 and 52 (p > 0.05), except LMK-CT at week 24 (p = 0.0275). Similar results were seen for the secondary endpoints. Dupilumab was well tolerated across all ECRS subgroups. CONCLUSION: Dupilumab produced consistent improvement in symptoms of severe CRSwNP irrespective of ECRS status. Therefore, blood eosinophil level may not be a suitable biomarker for dupilumab efficacy in CRSwNP.

Early diagnosis of Cryptococcus neoformans var. grubii meningitis using multiplex PCR assay in an immunocompetent patient.

Cryptococcosis is an invasive fungal infection that mainly affects the lungs and central nervous system. While patients with cell-mediated immunodeficiency are at high risk of developing cryptococcosis, there have been increasing reports of cryptococcosis in immunocompetent individuals with no underlying conditions. Herein, we report a case of cryptococcal meningitis in a 55-year-old apparently immunocompetent man with a history of heavy alcohol consumption. Although the patient was initially treated for tuberculous meningitis and varicella-zoster virus induced vasculopathy due to a history of exposure to tuberculosis and a presence of stroke, a multiplex polymerase chain reaction (PCR) assay of cerebrospinal fluid (CSF) identified Cryptococcus species unexpectedly, enabling swift treatment and a favorable clinical outcome. The multiplex PCR assay, which can identify multiple pathogens simultaneously and instantly, may lead to early diagnosis and treatment by detecting unanticipated pathogens. Furthermore, the strain was identified through multilocus sequence typing (MLST) analysis as Cryptococcus neoformans var. grubii, Sequence Type 5, molecular type: VNI. Although simplified microbial identification techniques such as mass spectrometry have recently been developed, molecular biological assays are still essential for the accurate identification of infectious strains.

Involvement of two or more sets of lacrimal glands and/or major salivary glands is related to greater systemic disease activity due to multi-organ involvement in IgG4-related dacryoadenitis/sialadenitis.

OBJECTIVES: In IgG4-related dacryoadenitis and/or sialadenitis (IgG4-DS), involvement of two or more sets of lacrimal glands (LGs) and/or major salivary glands (MSGs) is regarded as a specific finding with diagnostic significance. This study aimed to clarify the influence of this factor on the overall clinical picture of IgG4-DS. METHODS: We retrospectively reviewed the medical records of 130 patients with IgG4-related disease, 97 of whom were diagnosed with IgG4-DS. We determined their clinical features according to the presence/absence of involvement of ≥2 sets of LGs and/or MSGs and compared the results with those obtained in 33 DS-limited patients. RESULTS: The IgG4-DS patients comprised 60 men and 37 women (median age 65 years). The median serum IgG4 level at diagnosis was 548 mg/dL. The patients with involvement of ≥2 sets (n = 44) had significantly more affected organs, lower serum C3 and C4 levels, and a tendency to have higher serum IgG levels and IgG4-RD responder index than did those without it (n = 53). In the 33 DS-limited patients, these two groups had no significant differences in clinical features. CONCLUSIONS: Involvement of ≥2 sets of LGs and/or MSGs suggests greater systemic disease activity mainly reflected by involvement of more organs.

Time-resolved FRET and NMR analyses reveal selective binding of peptides containing the LC3-interacting region to ATG8 family proteins.

Selective autophagy sequesters cytoplasmic cargo for lysosomal degradation via the binding of autophagy receptors to Atg8 (autophagy-related 8) family proteins on the autophagic membrane. The sole yeast Atg8 gene has six mAtg8 (mammalian Atg8) homologs, including the MAP1LC3 (microtubule-associated protein-1 light chain 3) family and the GABA receptor-associated proteins. Selective autophagy receptors interact with two conserved hydrophobic pockets (termed the W-site and L-site) of mATG8 proteins through a linear motif called the LC3-interacting region (LIR) with the general composition (W/F/Y)XX(I/L/V). To address a lack in our knowledge regarding LIR peptide specificity toward each mATG8 homolog, here we used competitive time-resolved FRET to sensitively and quantitatively characterize the interactions between LIRs and mAtg8. We report that 14 representative LIR-containing peptides display differential binding affinities toward the mAtg8 proteins and identified the LIR domain peptide of TP53INP1 as exhibiting high affinity for all six mATG8 proteins. Using peptide truncation studies, we found that both N- and C-terminal acidic residues, as well as the C-terminal Cys residue of the TP53INP1 LIR peptide, are required for its high-affinity binding to LC3A and LC3B, whereas binding to the GABARAP subfamily proteins was facilitated by residues either N-terminal or C-terminal to the core motif. Finally, we used NMR chemical shift perturbation analysis to gain molecular insights into these findings. Collectively, our results may aid in the development of molecules that selectively disrupt specific mATG8-LIR interactions to dissect the biological roles of the six mATG8 homologs for potential therapeutic applications.

High surface laser-induced damage threshold of SrB4O7 single crystals under 266-nm (DUV) laser irradiation.

Under 266-nm (deep ultraviolet, DUV) laser irradiation, an SrB4O7 (SBO) single crystal has been found to exhibit a surface laser-induced damage threshold (LIDT) of ∼ 16.4 J/cm2, which is higher than those of a synthetic silica glass (4.8 J/cm2) and a calcium fluoride (CaF2) crystal (11.4 J/cm2). By catalyst-referred etching (CARE), the LIDT of an SBO crystal can also be improved to around 24.1 J/cm2, which is 1.4 and 6.0 times higher compared to an unetched crystal and a silica glass, respectively. With high surface LIDTs, SBO single crystals can then be used as optical window materials for high-power DUV laser systems.

Dupilumab efficacy and safety in Japanese patients with uncontrolled, moderate-to-severe asthma in the phase 3 LIBERTY ASTHMA QUEST study.

BACKGROUND: In the LIBERTY ASTHMA QUEST (ClinicalTrials.gov: NCT02414854) study, dupilumab 200 mg and 300 mg every 2 weeks vs matched-volume placebo reduced severe asthma exacerbations and improved lung function (FEV1), asthma control, and quality of life in patients with uncontrolled, moderate-to-severe asthma (N = 1902). Here, we examine the safety and efficacy of dupilumab in the subpopulation of Japanese patients who participated in QUEST (n = 114; 6%). METHODS: Endpoints assessed were annualized severe exacerbation rates and the effect of treatment over the 52-week treatment period on FEV1, asthma control, asthma-related quality of life, and markers of type 2 inflammation. RESULTS: In Japanese patients, dupilumab 200 and 300 mg every 2 weeks vs matched placebo reduced severe asthma exacerbation rates by 44% (P = 0.33) and 75% (P = 0.03), respectively, and improved FEV1 at Week 12 by 0.20 L (P = 0.05) and 0.17 L (P = 0.12). FEV1 improvements were rapid (by Week 2) and sustained throughout treatment. Significant and/or numerical improvements vs placebo in asthma control and quality of life were also observed throughout treatment. For each endpoint, greater efficacy was observed in patients with elevated baseline levels of type 2 inflammatory biomarkers (blood eosinophils or FeNO). Dupilumab treatment significantly reduced levels of FeNO and total IgE, but not blood eosinophils. CONCLUSIONS: In this subanalysis of QUEST, the efficacy and safety of dupilumab in Japanese patients was comparable to that observed in the overall intention-to-treat population, suggesting no variability in efficacy on the basis of Japanese ethnicity. (Funded by Sanofi and Regeneron Pharmaceuticals, Inc.; ClinicalTrials.gov number: NCT02414854).

Sarilumab monotherapy or in combination with non-methotrexate disease-modifying antirheumatic drugs in active rheumatoid arthritis: A Japan phase 3 trial (HARUKA).

Objectives: To determine long-term safety and efficacy of sarilumab as monotherapy or with non-methotrexate (MTX) conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) in Japanese patients with active rheumatoid arthritis (RA).Methods: In this double-blind, randomized study (NCT02373202), patients received subcutaneous sarilumab 150 mg q2w (S150) or 200 mg q2w (S200) as monotherapy or with non-MTX csDMARDs for 52 weeks. The primary endpoint was safety.Results: Sixty-one patients received monotherapy (S150, n = 30; S200, n = 31) and 30 received combination therapy (S150 + csDMARDs, n = 15; S200 + csDMARDs, n = 15). Rates of treatment-emergent adverse events (TEAEs) were 83.3%/90.3%/93.3%/86.7% for S150/S200/S150 + csDMARDs/S200 + csDMARDs, respectively. Nasopharyngitis and neutropenia were the most frequently reported TEAEs. One serious infection was reported in each monotherapy group and in the S200 + csDMARDs group. There were no cases of grade 4 neutropenia; no patients with grade 3 neutropenia experienced associated serious infection. Improvements in ACR20/50/70 response rates were generally similar between the two monotherapy groups and between the two combination groups; improvements in physical function (Health Assessment Questionnaire-Disability Index, HAQ-DI) and DAS28-CRP were observed at weeks 24 and 52 (all groups).Conclusion: The safety profile of sarilumab was consistent with known class effects of interleukin-6 signaling blockade therapeutics. Sarilumab as mono- or combination therapy improved clinical signs/symptoms and physical function in Japanese RA patients.

Bif-1/Endophilin B1/SH3GLB1 regulates bone homeostasis.

Skeletal tissue homeostasis is maintained via the balance of osteoclastic bone resorption and osteoblastic bone formation. Autophagy and apoptosis are essential for the maintenance of homeostasis and normal development in cells and tissues. We found that Bax-interacting factor 1 (Bif-1/Endophillin B1/SH3GLB1), involving in autophagy and apoptosis, was upregulated during osteoclastogenesis. Furthermore, mature osteoclasts expressed Bif-1 in the cytosol, particularly the perinuclear regions and podosome, suggesting that Bif-1 regulates osteoclastic bone resorption. Bif-1-deficient (Bif-1 -/- ) mice showed increased trabecular bone volume and trabecular number. Histological analyses indicated that the osteoclast numbers increased in Bif-1 -/- mice. Consistent with the in vivo results, osteoclastogenesis induced by receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) was accelerated in Bif-1 -/- mice without affecting RANKL-induced activation of RANK downstream signals, such as NF-κB and mitogen-activated protein kinases (MAPKs), CD115/RANK expression in osteoclast precursors, osteoclastic bone-resorbing activity and the survival rate. Unexpectedly, both the bone formation rate and osteoblast surface substantially increased in Bif-1 -/- mice. Treatment with ß-glycerophosphate (ß-GP) and ascorbic acid (A.A) enhanced osteoblastic differentiation and mineralization in Bif-1 -/- mice. Finally, bone marrow cells from Bif-1 -/- mice showed a significantly higher colony-forming efficacy by the treatment with or without ß-GP and A.A than cells from wild-type (WT) mice, suggesting that cells from Bif-1 -/- mice had higher clonogenicity and self-renewal activity than those from WT mice. In summary, Bif-1 might regulate bone homeostasis by controlling the differentiation and function of both osteoclasts and osteoblasts (235 words).

Endophilin B2 facilitates endosome maturation in response to growth factor stimulation, autophagy induction, and influenza A virus infection.

Endocytosis, and the subsequent trafficking of endosomes, requires dynamic physical alterations in membrane shape that are mediated in part by endophilin proteins. The endophilin B family of proteins contains an N-terminal Bin/amphiphysin/Rvs (N-BAR) domain that induces membrane curvature to regulate intracellular membrane dynamics. Whereas endophilin B1 (SH3GLB1/Bif-1) is known to be involved in a number of cellular processes, including apoptosis, autophagy, and endocytosis, the cellular function of endophilin B2 (SH3GLB2) is not well understood. In this study, we used genetic approaches that revealed that endophilin B2 is not required for embryonic development in vivo but that endophilin B2 deficiency impairs endosomal trafficking in vitro, as evidenced by suppressed endosome acidification, EGFR degradation, autophagic flux, and influenza A viral RNA nuclear entry and replication. Mechanistically, although the loss of endophilin B2 did not affect endocytic internalization and lysosomal function, endophilin B2 appeared to regulate the trafficking of endocytic vesicles and autophagosomes to late endosomes or lysosomes. Moreover, we also found that despite having an intracellular localization and tissue distribution similar to endophilin B1, endophilin B2 is dispensable for mitochondrial apoptosis. Taken together, our findings suggest that endophilin B2 positively regulates the endocytic pathway in response to growth factor signaling, autophagy induction, and viral entry.

Mice overexpressing latent matrix metalloproteinase-2 develop lung emphysema after short-term exposure to cigarette smoke extract.

Chronic obstructive pulmonary disease is the major growing cause of mortality and morbidity worldwide, and it is going to become the third most common cause of death by 2020. Chronic obstructive pulmonary disease is pathologically characterized by lung emphysema and small airway inflammation. Animal models are very important to get insights into the disease pathogenesis but current models of chronic obstructive pulmonary disease take a long time to develop. The need of a new model is compelling. In the present study we focus on the role of matrix metalloproteinases in the pathogenesis of chronic obstructive pulmonary disease and hypothesized that lung overexpression of latent matrix metalloproteinases-2 would allow the development of emphysema after short-term exposure to cigarette smoke extract inhalation. Human latent matrix metalloproteinases-2 transgenic mouse expressing high level of the protein in the lungs and wild type mouse were exposed to aerosolized cigarette smoke extract for two weeks. Transgenic mice showed significant lung emphysematous changes, increased infiltration of inflammatory cells and enhanced lung concentrations of inflammatory cytokines in the lungs compared to their wild type counterparts after inhalation of cigarette smoke extract. This novel mouse model will be a very useful tool for evaluating the mechanistic pathways and for development of novel therapies in cigarette smoke-associated lung emphysema.

Inhibition of Cell Apoptosis and Amelioration of Pulmonary Fibrosis by Thrombomodulin.

Pulmonary fibrosis is the terminal stage of a group of idiopathic interstitial pneumonias, of which idiopathic pulmonary fibrosis is the most frequent and fatal form. Recent studies have shown that recombinant human thrombomodulin (rhTM) improves exacerbation and clinical outcome of idiopathic pulmonary fibrosis, but the mechanism remains unknown. This study evaluated the mechanistic pathways of the inhibitory activity of rhTM in pulmonary fibrosis. Transgenic mice overexpressing human transforming growth factor-ß1 that develop spontaneously pulmonary fibrosis, and wild-type mice treated with bleomycin were used as models of lung fibrosis. rhTM was administered to mice by i.p. injection or by the intranasal route. Therapy with rhTM significantly decreased the concentration of high mobility group box1, interferon-γ, and fibrinolytic markers, the expression of growth factors including transforming growth factor-ß1, and the degree of lung fibrosis. rhTM significantly suppressed apoptosis of lung epithelial cells in in vivo and in vitro experiments. The results of the present study demonstrated that rhTM can inhibit bleomycin-induced pulmonary fibrosis and transforming growth factor-ß1-driven exacerbation and progression of pulmonary fibrosis, and that apart from its well-recognized anticoagulant and anti-inflammatory properties, rhTM can also suppress apoptosis of lung epithelial cells.

Glycaemic control, hypoglycaemia, and weight change with insulin glargine 300 U/mL versus insulin glargine 100 U/mL in Japanese adults with type 2 diabetes: A 12-month comparison by concomitant sulphonylurea and/or glinide use.

AIM: To explore if clinical effects and hypoglycaemia risks associated with insulin glargine 300 U/mL (Gla-300) and 100 U/mL (Gla-100) differed by sulphonylurea and/or glinide (SU/G) treatment. METHODS: A post hoc subgroup analysis of 12-month treatment data from the EDITION Japan 2 trial, a randomized, open-label, phase 3 study of Japanese people with type 2 diabetes receiving once-daily Gla-300/Gla-100 + oral antihyperglycaemic drugs. Participants previously receiving SU/G (+SU/G) were compared with those not taking SU/G (-SU/G). Endpoints included HbA1c, hypoglycaemia and body weight. RESULTS: For +SU/G (n = 152, 63%), HbA1c was reduced from baseline to month 12 for Gla-300 (8.1% to 7.6%) and Gla-100 (8.2% to 7.8%). For -SU/G (n = 89, 37%), reductions were 7.8% to 7.4%, and 7.9% to 7.5% for Gla-300 and Gla-100, respectively. A lower annualized rate of hypoglycaemia with Gla-300 versus Gla-100 was observed at night (00:00-05:59 hours; p = 0.0001) and any time of day (24 hour; p = 0.0015). Irrespective of the insulin used, the incidence and rate of confirmed (≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia appeared higher in +SU/G versus -SU/G; overall, a reduced incidence of nocturnal hypoglycaemia, and rate of hypoglycaemia at any time, was observed in -SU/G versus +SU/G. In the -SU/G subgroup, body weight gain differences were observed between Gla-300 and Gla-100 (p < 0.0001). CONCLUSIONS: Participants with prior and continued SU/G use had similar therapeutic responses with basal insulin but greater risk of hypoglycaemia than those not using SU/G; hypoglycaemia risk was lower with Gla-300 than Gla-100 in both subgroups.

Prognostic value of dynamic MRI positive enhancement integral color mapping in osteosynthesis of undisplaced femoral neck fractures.

AIMS: The common treatment for an undisplaced femoral neck fracture is osteosynthesis. Two major complications of osteosynthesis are non-union and late collapse of the femoral head. We speculated that femoral head perfusion is one of the most important factors that affect the outcome of osteosynthesis after femoral neck fracture. We have preoperatively estimated femoral head perfusion by dynamic MRI positive enhancement integral color mapping (PEICM). The purpose of this study was to evaluate the outcomes of undisplaced femoral neck fractures based on PEICM. PATIENTS AND METHODS: Sixty-eight patients participated in this prospective study. All patients underwent PEICM in a 1.5-Tesla MRI machine using coronal fast spoiled gradient echo imaging sequences with gadopentetate dimeglumine as the contrast agent. Femoral head perfusion was displayed via color mapping using PEICM. Three types were distinguished. For type A, the color was identical to unaffected side indicated normal perfusion. For type B, the color was darker than unaffected side indicated decreased perfusion. For type C, the color was black indicated complete absence of perfusion. All patients underwent osteosynthesis with three cannulated screws. The rates of non-union and late collapse for each type were calculated. RESULTS: Sixteen patients were classified as Type A, 43 as Type B, and 6 as Type C. The non-union rates were 0% for Type A, 6.7% for Type B, and 50.0% for Type C. The late collapse rates were 0% for Type A, 4.4% for Type B, and 0% for Type C. CONCLUSION: PEICM precisely detected femoral head perfusion. Primary prosthetic replacement should be considered for older patients with Type C to minimize the chances of revision surgery, even in undisplaced femoral neck fractures.

Development of a new measurement scale for interprofessional collaborative competency: The Chiba Interprofessional Competency Scale (CICS29).

The purpose of this study was to refine the items on a scale measuring interprofessional collaborative competency that was developed by the authors in an earlier pilot study. A questionnaire-based study was conducted with a sample of 2133 health professionals using the reformulated questionnaire. Construct validity was tested by comparing the survey results with a covariance structure analysis and the domains of interprofessional collaboration competencies presented in previous studies. A second survey was conducted 2 weeks later with a sample of 571 nursing professionals, using the same survey form to test its reliability. We constructed a model comprising 29 observed variables and six latent variables (the Chiba Interprofessional Competency Scale: CICS29), and obtained the following values for the model's goodness of fit: GFI = 0.925, AGFI = 0.908, CFI = 0.950, RMSEA = 0.049. With regard to reliability, we obtained scores ranging from 0.65 to 0.77 for the intraclass correlation coefficients of the six domains. Compared with the interprofessional collaboration scales indicated in previous studies, the CICS29 was found to have subsumed the key concepts that should be configured as interprofessional collaboration competencies. The CICS29 appeared to have satisfactory levels of reliability and validity and is recommended as a scale for measuring competencies of interprofessional practice.

Picosecond high-power 355-nm UV generation in CsLiB6O10 crystal.

We report third-harmonic generation (THG) at 355 nm in CsLiB6O10 (CLBO) by using sum-frequency mixing process. As a fundamental laser source, we employ a hybrid master oscillator power amplifier (MOPA) system seeded by a gain-switched laser diode (GS-LD) at 1064 nm to produce narrow spectral picosecond pulses. Both CLBO and walk-off compensated prism-coupled CLBO device generate over 30-W output of 355-nm UV lights, which means walk-off effect in CLBO is negligible in the picosecond laser system. The maximum THG conversion efficiency from the fundamental reaches about 48%, which is 1.2 times higher than that of LiB3O5 (LBO). Theoretical THG outputs with CLBO and LBO are numerically calculated in order to verify the validity of these experimental results in detail.