Weak Interactions between Salmonella enterica FlhB and Other Flagellar Export Apparatus Proteins Govern Type III Secretion Dynamics

The bacterial flagellum contains its own type III secretion apparatus that coordinates protein export with assembly at the distal end. While many interactions among export apparatus proteins have been reported, few have been examined with respect to the differential affinities and dynamic relationships that must govern the mechanism of export. FlhB, an integral membrane protein, plays critical roles in both export and the substrate specificity switching that occurs upon hook completion. Reported herein is the quantitative characterization of interactions between the cytoplasmic domain of FlhB (FlhBC) and other export apparatus proteins including FliK, FlhAC and FliI. FliK and FlhAC bound with micromolar affinity. KD for FliI binding in the absence of ATP was 84 nM. ATP-induced oligomerization of FliI induced kinetic changes, stimulating fast-on, fast-off binding and lowering affinity. Full length FlhB purified under solubilizing, nondenaturing conditions formed a stable dimer via its transmembrane domain and stably bound FliH. Together, the present results support the previously hypothesized central role of FlhB and elucidate the dynamics of protein-protein interactions in type III secretion

Effects of canagliflozin on WBC counts

Aims/Introduction: Clinical evidence is lacking about the influence of sodium–glucose cotransporter 2 inhibitors on white blood cell (WBC) counts, a commonly used and widely available marker of inflammation. The aim of the present analysis was to assess the effect of canagliflozin relative to glimepiride on WBC counts. Materials and Methods: This was a post-hoc subanalysis of the CANDLE trial (Effects of Canagliflozin in Patients with Type 2 Diabetes and Chronic Heart Failure: A Randomized Trial; UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. A total of 233 patients with type 2 diabetes and concomitant heart failure were randomly assigned to either canagliflozin (n = 113) or glimepiride (n = 120) treatment for 24 weeks. Overall, patient baseline characteristics were as follows: mean ± standard deviation age, 68.6 ± 10.1 years; hemoglobin A1c, 7.0 ± 0.9%; left ventricular ejection fraction, 56.7 ± 14.4%; and median N-terminal pro-brain natriuretic peptide, 252 pg/mL (interquartile range 96–563 pg/mL). The mean baseline WBC counts were 6704 cells/μL (95% confidence interval 6,362–7,047) in the canagliflozin group and 6322 cells/μL (95% confidence interval 5,991–6,654) in the glimepiride group. There were no significant differences between treatment groups in terms of changes in WBC counts from baseline to weeks 4 and 12. In contrast, a group difference (canagliflozin minus glimepiride) from baseline to week 24 was significant (mean difference − 456 cells/μL [95% confidence interval −774 to −139, P = 0.005]). Conclusions: Our findings suggest that 24 weeks of treatment with canagliflozin, relative to glimepiride, reduced WBC counts in patients with type 2 diabetes and heart failure

2型糖尿病入院患者の食後血糖値に影響を及ぼす栄養素等の要因

本研究は2型糖尿病患者の食後血糖値に影響する栄養素について明らかにすることを目的とした。対象は入院中の2型糖尿病患者で、食前および食後の血糖測定を実施した22名であった。分析は食後血糖値を従属変数に、エネルギー、たんぱく質、脂質、炭水化物、食物繊維、年齢、BMI、HbA1c、食前血糖値を独立変数とした重回帰分析を用いた。結果は全体としては食後血糖に影響する有意な要因は認められなかった。一方、朝食においてHbA1cと食物繊維に有意な値が認められた。すなわち、2型糖尿病入院患者において、食後血糖値を抑制する栄養素として最も影響を及ぼすのは食物繊維であると考えられる

The impact of cardiac rehabilitation for older adults with heart failure who underwent invasive cardiac treatment eligible for long‐term care needs certification: A retrospective cohort study

Abstract Background This study aimed to assess the usefulness of cardiac rehabilitation (CR) for older adults with heart failure (HF) who need nursing care and investigate the effect of CR on cognitive function (CF) and basic activities of daily living (BADL). Methods This was a retrospective cohort study. The study included older adults with HF eligible for long‐term care insurance in fiscal year 2014 (FY2014) as the baseline and followed them up until March 2018. Patients were divided into two groups, CR (+) and CR (−), and the changes in their CF and BADL scores over time for 3 years were investigated. Results Of the 765 patients included in the study, 36.5% performed CR. BADL scores in the CR (+) and CR (−) groups (mean (SE)) were 5.81 (0.26) vs. 5.87 (0.20) in FY2014, 5.6 (0.28) vs. 5.92 (0.21) in FY2015, 5.72 (0.31) vs. 6.15 (0.22) in FY2016, and 5.64 (0.33) vs. 6.40 (0.25) in FY2017, respectively. BADL scores worsened over time in the CR (−) group but had a trend to inhibit decline in the CR (+) group, and a significant difference was observed between both groups (p = 0.04). Multivariate analysis showed a significant difference in CR as a factor suppressing ADL decline after 1 year (adjusted odds ratios: 0.54, 95% confidence intervals: 0.36–0.82; p = 0.004). However, no significant difference in the CF scores was observed. Conclusion CR for older adults with HF eligible for long‐term care needs certification does not affect CF and may suppress ADL decline

Effect of canagliflozin on white blood cell counts in patients with type 2 diabetes and heart failure: A subanalysis of the randomized CANDLE trial

ABSTRACT Aims/Introduction Clinical evidence is lacking about the influence of sodium–glucose cotransporter 2 inhibitors on white blood cell (WBC) counts, a commonly used and widely available marker of inflammation. The aim of the present analysis was to assess the effect of canagliflozin relative to glimepiride on WBC counts. Materials and Methods This was a post‐hoc subanalysis of the CANDLE trial (Effects of Canagliflozin in Patients with Type 2 Diabetes and Chronic Heart Failure: A Randomized Trial; UMIN000017669), an investigator‐initiated, multicenter, open‐label, randomized, controlled trial. A total of 233 patients with type 2 diabetes and concomitant heart failure were randomly assigned to either canagliflozin (n = 113) or glimepiride (n = 120) treatment for 24 weeks. Overall, patient baseline characteristics were as follows: mean ± standard deviation age, 68.6 ± 10.1 years; hemoglobin A1c, 7.0 ± 0.9%; left ventricular ejection fraction, 56.7 ± 14.4%; and median N‐terminal pro‐brain natriuretic peptide, 252 pg/mL (interquartile range 96–563 pg/mL). The mean baseline WBC counts were 6704 cells/μL (95% confidence interval 6,362–7,047) in the canagliflozin group and 6322 cells/μL (95% confidence interval 5,991–6,654) in the glimepiride group. There were no significant differences between treatment groups in terms of changes in WBC counts from baseline to weeks 4 and 12. In contrast, a group difference (canagliflozin minus glimepiride) from baseline to week 24 was significant (mean difference − 456 cells/μL [95% confidence interval −774 to −139, P = 0.005]). Conclusions Our findings suggest that 24 weeks of treatment with canagliflozin, relative to glimepiride, reduced WBC counts in patients with type 2 diabetes and heart failure