Proposed carbohydrate antigen 19-9 (CA19-9) cut-off values for the detection of pancreatic cancer in patients with poorly controlled diabetes: a real-world study.

CA19-9 is a tumor marker for pancreatic cancer (PC), and the nondiabetic cut-off level is 37 U/mL. CA19-9 levels are said to rise in patients with tumors like PC and intraductal papillary mucinous neoplasm (IPMN). CA19-9 levels have also been shown to be related to HbA1c levels. We hypothesized that the CA19-9 cut-off levels would differ between patients with poorly controlled diabetes. This real-world trial was designed to test our hypotheses. This was a retrospective cohort study. All inpatients with poorly controlled diabetes had mean HbA1c levels of 10.0% and were divided into three groups: those with pancreatic cancer (PC group, N = 20), those with IPMN (IPMN group, N = 55), and those with neither (NC group, N = 985). Serum CA19-9 levels in the PC group were significantly higher than in the IPMN and NC groups (p < 0.001). CA19-9 levels did not differ statistically between the IPMN and NC groups. According to the receiver operating characteristic (ROC) analysis, serum CA19-9 levels of 98.4 U/mL had the highest sensitivity and specificity to detect PC, when comparing PC to IPMN + NC groups. Using this cut-off, the sensitivity and specificity of CA19-9 for PC were 70.0% and 96.5%, respectively, with a 0.81 area under the ROC curve. CA19-9 levels in two inpatients were >98.4 U/mL, most likely due to hepatocellular carcinoma and esophageal cancer. CA19-9 cut-off levels were thought to be 98.4 U/mL. However, we should keep in mind that the sensitivity and specificity were not 100%.

Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Negative impact of proteinuria on circulating myeloid dendritic cells.

BACKGROUND: A decrease in absolute numbers (abs.) of circulating dendritic cells (DCs) and recruitment into target organs has been reported, but whether the level of proteinuria associates with circulating DC abs. has not been clarified. METHODS: We conducted a cross-sectional study of 210 patients with kidney disease aged 21-96 years who were admitted to our hospital for kidney biopsy in 2007-2010. For accuracy, the level of proteinuria was thoroughly measured by 24-h urine collection from patients in their admitted condition. The abs. of total DCs (tDCs), myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) was measured by three-color fluorescence-activated cell sorting (FACS). Patients were divided into four groups based upon the quartile of each DC abs. and one-way ANOVA, and multivariable-adjusted regression analyses were performed. RESULTS: Quantile analysis showed that the level of daily proteinuria decreased with increasing blood mDC abs., with mean proteinuria levels (g/day) of 2.45, 1.68, 1.68, 1.10 for those in mDC abs. quartiles ≤ 445, < 686, < 907, ≥ 907 cells/102 µL (p = 0.0277), respectively. Multivariate-adjusted regression analysis revealed that the mDC abs. was negatively associated with proteinuria (95% CI - 57.0 to - 8.5) and positively associated with male gender (95% CI 66.2-250.5). Independent associations were also shown between pDCs abs. and estimated glomerular filtration rate (eGFR) (95% CI 0.14-2.67) and C-reactive protein (95% CI - 49.4 to - 9.9) and between tDCs abs. and male gender (95% CI 54.5-253.6) and C-reactive protein (95% CI - 80.5 to - 13.4). CONCLUSION: We first reported that circulating mDC abs. has a negative association with the level of proteinuria.

Association between chemical components of PM2.5 and children's primary care night-time visits due to asthma attacks: A case-crossover study.

BACKGROUND: Few papers have examined the association between the chemical components of PM2.5 and health effects. The existence of an association is now under discussion. METHODS: This case-crossover study aimed to examine the association between the chemical components of PM2.5 and night-time primary care visits (PCVs) due to asthma attacks. The subjects were 1251 children aged 0-14 years who received medical care for asthma at a municipal emergency clinic. We measured daily average concentrations of hydrogen ion, sulfate ion, nitrate ion and water-soluble organic compounds (WSOCs), which are components of PM2.5. We estimated the odds ratios (ORs) of PCVs per unit increment (inter quartile ranges) in each chemical component of PM2.5 for the subgroups of warmer months and colder months separately. RESULTS: No association was seen between PCVs and PM2.5 mass concentrations the day before the PCVs in either warmer or colder months. In the warmer months, an association was seen with the concentrations of WSOCs and hydrogen ion the day before the PCVs (OR = 1.33; 95% CI: 1.00-1.76, OR = 1.18; 95% CI: 1.02-1.36, respectively). Furthermore, a negative association was seen between sulfate ion and PCVs (OR = 0.85; 95%CI: 0.74-0.98). No associations were observed in the colder months. CONCLUSIONS: We observed a positive association between PCVs and certain concentrations of WSOCs and hydrogen ions in warmer months. In contrast, sulfate ion showed a negative association.

Association between PM2.5 and primary care visits due to asthma attack in Japan: relation to Beijing's air pollution episode in January 2013.

AIM: In January 2013, extremely high concentrations of fine particles (PM2.5) were observed around Beijing, China. In Japan, the health effects of transboundary air pollution have been a matter of concern. We examined the association between the levels of outdoor PM2.5 and other air pollutants with primary care visits (PCVs) at night due to asthma attack in Himeji City, western Japan. METHODS: A case-crossover study was conducted in a primary care clinic in Himeji City, Japan, involving 112 subjects aged 0-80 years who visited the clinic due to an asthma attack between 9 p.m. and 6 a.m. during the period January-March, 2013. Daily concentrations of particulate matter, ozone, nitrogen dioxide, and some meteorological elements were measured, and a conditional logistic regression model was used to estimate the odds ratios (OR) of PCVs per unit increment in air pollutants or meteorological elements. RESULTS: Of the 112 subjects, 76 (68 %) were aged <15 years. We did not note any association between daily PM2.5 levels and PCVs due to asthma attack at night. A positive relation between ozone and PCVs due to asthma attack was detected. The OR per 10 ppb increment in daily mean ozone the day before the visit was 2.31 (95 % confidence interval 1.16-4.61). CONCLUSION: These findings do not support an association between daily mean concentration of PM2.5 and PCVs at night. However, we did find evidence suggesting that ozone is associated with PCVs.

Patient Satisfaction Survey on Portable Infusion Pumps for Colorectal Cancer Chemotherapy: Hard-Shelled or Soft-Shelled?

Purpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types. Patients and Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump. The respondents used a numerical rating scale (0-10) to rate their comfort when using each pump, their ease of carrying it, the pump size and shape, its weight, their ease of reading its memory, and their overall satisfaction with it. They were then asked to determine which pump they would ultimately prefer. Results: In terms of comfort, significantly higher user satisfaction was reported for the soft-shelled pump during the daytime and when going out (P < 0.001, P < 0.001, respectively). For pump portability, size, shape, and weight, the soft-shelled type also outperformed the hard-shelled one (P < 0.001, P=0.0011, P < 0.001, respectively). However, the hard-shelled pump scored significantly better in terms of ease of viewing memory (P < 0.001). Overall satisfaction was significantly higher for the soft-shelled pump than the hard-shelled type (P=0.0095). Finally, 13 patients (65%) indicated that they would prefer a soft-shelled pump for their next treatment, while only one patient (5%) preferred a hard-shelled alternative. A preference for soft-shelled pump was observed, particularly in female patients and those with a body mass index of < 22 kg/m2. Conclusion: The selection of portable elastomeric infusion pumps should consider the preferences of patients with colorectal cancer, as these devices have the potential to enhance their quality of life.

Growth-phase dependent variation in photosynthetic activity and cellular protein expression profile in the harmful raphidophyte Chattonella antiqua.

This study investigated temporal variations in the potential maximum quantum yield of photosystem II (F(v)/F(m) ratio) and growth-phase dependent cellular protein expressions of Chattonella antiqua under laboratory conditions. Despite the culture conditions, significant positive correlations between the F(v)/F(m) ratio and daily growth rate were observed. Threshold F(v)/F(m) ratios associated with positive cell growth were calculated to be >0.44, >0.44, and >0.37, and those associated with active cell growth (growth rate >0.5 div. d(-1)) were >0.58, >0.60, and >0.49 under control culture, low nutrient and intense light conditions, respectively. Proteome profiles obtained by two-dimensional gel electrophoresis (2-DE) indicated that 42 protein spots were differentially expressed at various growth phases of C. antiqua, which indicates changes in cellular physiological status throughout the growth cycle, and suggests that oxygen evolving enhancer 1 and 2-cysteine peroxiredoxin play roles in maintaining the positive growth of C. antiqua.

Association of ambient air pollution and meteorological factors with primary care visits at night due to asthma attack.

AIM: The association of outdoor air pollution and meteorological elements with primary care visits at night due to asthma attack was studied. METHODS: A case-crossover study was conducted in a primary care clinic in Himeji City, Japan. The subjects were 956 children aged 0-14 years who visited the clinic with an asthma attack between the hours of 9 p.m. and 6 a.m. Daily concentrations of particulate matter, ozone, nitrogen dioxide, and a number of meteorological elements were measured, and a conditional logistic regression model was used to estimate odds ratios (ORs) of primary care visits per unit increment of air pollutants or meteorological elements. The analyses took into consideration the effects of seasonality. RESULTS: Of the 956 children, 73 (7.6 %) were aged <2 years and 417 (43.6 %) were aged 2-5 years. No association between daily ozone levels and primary care visits due to asthma attack at night in the spring or summer was found. An inverse relation between suspended particulate matter and primary care visits due to asthma attack was detected in the winter. ORs in the summer per degree increment in daily mean temperature was 1.31 [95 % confidential interval (CI) 1.09-1.56], and ORs in the autumn per hourly increment in daily hours of sunshine was 0.94 (95 % CI 0.90-0.99). CONCLUSION: The findings of our study fail to support any association between daily mean concentration of air pollutant and primary care visits at night. However, we did find evidence indicating that certain meteorological elements may be associated with primary care visits.

Validity and reliability of the Japanese version of the diabetes knowledge test among in-patients with type 2 diabetes.

AIMS/INTRODUCTION: The diabetes knowledge test (DKT) is unavailable in Japan. In this study, we developed and evaluated a Japanese version of the DKT (J-DKT) for in-patients with type 2 diabetes before and after receiving diabetes education. MATERIALS AND METHODS: The J-DKT contains 12 questions (0-12 points) to assess knowledge regarding diabetes, its complications, and diabetic nutrition therapy. During the median 10 days of hospitalization, 107 patients with type 2 diabetes received diabetes education (20 min private lessons every day from physicians, two nutrition counselling programs from dietitians, and a 2 h group session conducted by physicians, dietitians, and nurses). The J-DKT was administered on admission and before discharge. To confirm the J-DKT's reliability, we assessed the internal consistency using Cronbach's α (≥0.70 was considered acceptable). To evaluate its validity, we investigated changes in the J-DKT total scores after the education programs and examined the differences in the scores among groups classified based on patient characteristics such as age, diabetes-related hospitalization history, and hospitalization duration. RESULTS: The J-DKT total scores increased from 5 to 8 (P ˂ 0.01) after the education programs. The J-DKT before and after the program showed a Cronbach's α of 0.48 and 0.73, respectively. Except for age, baseline characteristics such as history and period of hospitalization for diabetes were not associated with the J-DKT scores after the education program. CONCLUSIONS: The validity and reliability of the J-DKT after the diabetes education program were acceptable in this study.

Augmented antihypertensive effect of a fixed combination formula of candesartan and hydrochlorothiazide combined with furosemide in a patient on peritoneal dialysis.

A 38-year-old female patient on peritoneal dialysis (PD) due to type 1 diabetic nephropathy with a well-preserved residual renal function did not respond well to the conventional antihypertensive therapy consisting of candesartan, furosemide, and bunazosin. Switching candesartan for a fixed combination formula of candesartan plus hydrochlorothiazide (HCTZ) while the rest of the other two agents remained unchanged led to the remarkable reduction in both systolic and diastolic blood pressure (BP) without significant changes in the cardiothoracic ratio (CTR), body weight (BW), and residual renal function. This case suggests that when used in combination, diuretics acting on different functional segment of the nephron hold greater potential for enhanced antihypertensive effect, especially in patients on PD whose residual renal function is well preserved. A small dose of HCTZ with an angiotensin II receptor blocker (ARB) may partially explain the therapeutic benefit of this combination therapy in terms of a reliable hypotensive effect, a better adherence, and fewer side effects.

Risk factors for wheezing, eczema and rhinoconjunctivitis in the previous 12 months among six-year-old children in Himeji City, Japan: food allergy, older siblings, day-care attendance and parental allergy history.

BACKGROUND: The aim of this study was to clarify whether some environmental and genetic factors (food allergy, older siblings, early day-care attendance and parents' allergy history) are related to the development of allergic symptoms (wheezing in the previous 12 months [WP], eczema symptoms in the previous 12 months [EP], and rhinoconjunctivitis symptoms in the previous 12 months [RP]) in Japanese children. METHODS: Using the modified version of the International Study on Asthma and Allergies in Childhood (ISSAC) questionnaire, we studied the prevalence of WP, EP and RP among six-year-old children attending 72 primary schools throughout Himeji City, Japan, during the two years from 2005 to 2006. RESULTS: Food allergy and parents' history of allergy showed a significant relationship with the prevalence of WP, EP and RP. Day-care attendance in the first two years of life and presence of older siblings showed a significant inverse relationship with the prevalence of RP. However, neither day-care attendance nor presence of older siblings was related to the development of W and ER. CONCLUSIONS: Among Japanese children, food allergy and parents' history of allergy are risk factors for WP, ES or RS. However, early day-care attendance and presence of older siblings might be protective factors against RS. Infections in early life may affect the prevalence of rhinoconjunctivitis in six-year-old children.

Comparison of Structural Properties Between Postnatal and Adult Tendon Insertion with FIB/SEM Tomography in Rat.

OBJECTIVE: The repaired tendon-bone interface after rotator cuff (RC) repair has been identified as a mechanical weak point, which may contribute to re-tearing. Analyzing the postnatal development of a normal tendon insertion in detail may be useful in helping to promote the regeneration of a normal tendon insertion. We verified the morphological differences between postnatal and adult tendon insertions in terms of the cellular structural properties using FIB/SEM tomography. MATERIALS AND METHOD: SPostnatal and adult Sprague-Dawley rats were used as a model of tendon insertion. The morphological structure of the insertion was evaluated using hematoxylin and eosin (HE) staining, and the 3D ultrastructure of the cells in the insertion was evaluated using FIB/SEM tomography. Additionally, the volume of the cell bodies, nuclei, and cytoplasm were measured and compared in a quantitative analysis. RESULTS: On conventional histology, the boundary line between the fibrocartilage and mineralized cartilage was flat in the adult insertions; however, the boundary line between the mineralized cartilage and bone formed deep interdigitations. The morphology of the cells among the collagen bundles in the adult insertions was completely different from those in the postnatal insertions at the 3D ultrastructural level. The cellular structural properties were statistically different between the postnatal and adult insertions. CONCLUSIONS: In the present study, the morphological differences between postnatal and adult tendon insertion in terms of the ultrastructural cellular properties were clarified. These findings may aid in determining how to regenerate a clinically stable tendon insertion at the tendon-bone interface after RC repair.

A case of an elderly patient with insulin-dependent diabetes and dementia receiving one basal insulin plus one bolus insulin injections a day for 6 months.

Multiple daily injections of insulin, referred to basal-bolus regimen, are generally essential in achieving glycemic control and preventing ketosis in insulin-dependent diabetes, such as type 1 diabetes (T1D). A 75-year-old man with T1D receiving basal-bolus insulin therapy exhibited symptoms of dementia after hospitalization due to pyelonephritis and failed to continue insulin self-injection. Given that his social and familial circumstances allowed insulin injection once a day during the morning, bolus insulin injections needed to be discontinued. Ketonuria was observed the day following discontinuation of bolus insulin. Although increasing the basal insulin dose (degludec) from 10 to 15 units improved ketonuria, his preprandial glucose levels increased to ≥ 500 mg/dL before lunch and ≥ 400 mg/dL before dinner. Hence, another bolus insulin injection was simultaneously added to the basal insulin dose before breakfast, which, subsequently, decreased his preprandial glucose levels to ≤ 220 mg/dL before lunch and ≤ 350 mg/dL before dinner. For half a year after discharge, ketonuria or hypoglycemia had not been detected. After 6 months, he was able to restart intensive insulin therapy with familial support. Hence, in cases where elderly patients with diabetes exhibit symptoms of dementia and can receive insulin injection once a day due to their social circumstances, short-term one basal plus one bolus insulin injections a day might be considered to prevent life-threatening diabetes complications among those who are insulin-dependent.

Generation and maintenance of acentric stable double minutes from chromosome arms in inter-species hybrid cells.

BACKGROUND: Extrachromosomal acentric double minutes (DMs) contribute to human malignancy by carrying amplified oncogenes. Recent cancer genomics revealed that the pulverization of defined chromosome arms (chromothripsis) may generate DMs, however, nobody had actually generated DMs from chromosome arm in culture. Human chromosomes are lost in human-rodent hybrid cells. RESULTS: We found that human acentric DMs with amplified c-myc were stable in human-rodent hybrid cells, although the degree of stability depended on the specific rodent cell type. Based on this finding, stable human-rodent hybrids were efficiently generated by tagging human DMs with a plasmid with drug-resistance gene. After cell fusion, human chromosomes were specifically pulverised and lost. Consistent with chromothripsis, pulverization of human chromosome arms was accompanied by the incorporation into micronuclei. Such micronucleus showed different replication timing from the main nucleus. Surprisingly, we found that the hybrid cells retained not only the original DMs, but also new DMs without plasmid-tag and c-myc, but with human Alu. These DMs were devoid of telomeres and centromeres, and were stable in culture for more than 3 months. Microarray analysis showed that the new DMs were generated from several human chromosomal regions containing genes advantageous for cellular growth. Such regions were completely different from the original DMs. CONCLUSIONS: The inter-species hybrid mimics the chromothripsis in culture. This is the first report that experimentally demonstrates the generation of multiple stable acentric DMs from the chromosome arm.

Gcm2 regulates the maintenance of parathyroid cells in adult mice.

Glial cells missing homolog 2 (GCM2), a zinc finger-type transcription factor, is essential for the development of parathyroid glands. It is considered to be a master regulator because the glands do not form when Gcm2 is deficient. Remarkably, Gcm2 expression is maintained throughout the fetal stage and after birth. Considering the Gcm2 function in embryonic stages, it is predicted that Gcm2 maintains parathyroid cell differentiation and survival in adults. However, there is a lack of research regarding the function of Gcm2 in adulthood. Therefore, we analyzed Gcm2 function in adult tamoxifen-inducible Gcm2 conditional knockout mice. One month after tamoxifen injection, Gcm2-knockout mice showed no significant difference in serum calcium, phosphate, and PTH levels and in the expressions of calcium-sensing receptor (Casr) and parathyroid hormone (Pth), whereas Ki-67 positive cells were decreased and terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) positive cell number did not change, as compared with those of controls. Seven months after tamoxifen injection, Gcm2-knockout mice showed shrinkage of the parathyroid glands and fewer parathyroid cells. A significant decrease was noted in Casr- and Pth-expressing cells and serum PTH and Ca levels, whereas serum phosphate levels increased, as compared with those of controls. All our results concluded that a reduction of Gcm2 expression leads to a reduction of parathyroid cell proliferation, an increase in cell death, and an attenuation of parathyroid function. Therefore, we indicate that Gcm2 plays a prominent role in adult parathyroid cell proliferation and maintenance.

Valsartan in a Japanese population with hypertension and other cardiovascular disease (Jikei Heart Study): a randomised, open-label, blinded endpoint morbidity-mortality study.

BACKGROUND: Drugs that inhibit the renin-angiotensin-aldosterone system benefit patients at risk for or with existing cardiovascular disease. However, evidence for this effect in Asian populations is scarce. We aimed to investigate whether addition of an angiotensin receptor blocker, valsartan, to conventional cardiovascular treatment was effective in Japanese patients with cardiovascular disease. METHODS: We initiated a multicentre, prospective, randomised controlled trial of 3081 Japanese patients, aged 20-79 years, (mean 65 [SD 10] years) who were undergoing conventional treatment for hypertension, coronary heart disease, heart failure, or a combination of these disorders. In addition to conventional treatment, patients were assigned either to valsartan (40-160 mg per day) or to other treatment without angiotensin receptor blockers. Our primary endpoint was a composite of cardiovascular morbidity and mortality. Analysis was by intention to treat. The study was registered at clintrials.gov with the identifier NCT00133328. FINDINGS: After a median follow-up of 3.1 years (range 1-3.9) the primary endpoint was recorded in fewer individuals given valsartan than in controls (92 vs 149; absolute risk 21.3 vs 34.5 per 1000 patient years; hazard ratio 0.61, 95% CI 0.47-0.79, p=0.0002). This difference was mainly attributable to fewer incidences of stroke and transient ischaemic attack (29 vs 48; 0.60, 0.38-0.95, p=0.028), angina pectoris (19 vs 53; 0.35, 0.20-0.58, p<0.0001), and heart failure (19 vs 36; 0.53, 0.31-0.94, p=0.029) in those given valsartan than in the control group. Mortality or tolerability did not differ between groups. INTERPRETATION: The addition of valsartan to conventional treatment prevented more cardiovascular events than supplementary conventional treatment. These benefits cannot be entirely explained by a difference in blood pressure control.

Synthesis and catalytic performance of Ti-MCM-68 for effective oxidation reactions.

Microporous titanosilicate Ti-MCM-68 (Ti-MSE) was successfully synthesized by post-synthetic isomorphous substitution of Ti for Al and proved to be a high-performance catalyst, in particular showing superior performance to TS-1, Ti-BEA, and Ti-MWW for phenol oxidation using H(2)O(2) as an oxidant.

Exposure to air pollution and meteorological factors associated with children's primary care visits at night due to asthma attack: case-crossover design for 3-year pooled patients.

OBJECTIVE: We examined the association of outdoor air pollution and meteorological parameters with primary care visits (PCVs) at night due to asthma attack. SETTING: A case-crossover study was conducted in a primary care clinic in Himeji City, Japan. PARTICIPANTS: Participants were 1447 children aged 0-14 years who visited the clinic with an asthma attack from April 2010 until March 2013. EXPOSURE: Daily concentrations of air pollutants and meteorological parameters were measured. PRIMARY OUTCOME: PCVs at night due to asthma attack. A conditional logistic regression model was used to estimate ORs of PCVs per unit increment of air pollutants or meteorological parameters (the per-unit increments of particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) and ozone were 10 µg/m(3) and 10 ppb, respectively). Analyses took into consideration the effects of seasonality. RESULTS: We noted an association between PCVs and daily ozone levels on the day before a PCV (OR=1.17; 95% CI 1.01 to 1.35; p=0.04), as well as between PCVs and 3-day mean ozone levels before a PCV (OR=1.29; 95% CI 1.00 to 1.46; p=0.04), from April until June. We also observed an association between PCVs and daily PM2.5 levels on the day before a PCV from December until March (OR=1.16; 95% CI 1.01 to 1.33; p=0.05). Meteorological parameters, such as hours of sunshine from September until November, atmospheric pressure from April until June, and temperature from April until August, were also found to be associated with PCVs. CONCLUSIONS: The findings in the present study supported an association between ozone and PCVs and suggest that certain meteorological items may be associated with PCVs.

Characterization of polar-flagellar-length mutants in Vibrio alginolyticus.

Vibrio alginolyticus has two types of flagella, polar (Pof) and lateral (Laf). From a Laf-defective mutant (Pof+Laf-), polar-flagellar-length mutants which have short Pof and long Pof were isolated. The mean lengths of the helical axis in wild-type, short and long Pof were 5.5.0.9 µm, 2.5.0.6 µm and 11.2.3.6 µm, respectively. The swimming speeds of the short- and long-Pof mutants were slower than that of the wild-type strain. The relationship between swimming speed and flagellar length in a population of mutant cells was examined. In the short-Pof mutant, the decrease of swimming speed seemed to be derived from the decrease in flagellar length. In the long-Pof mutant, there was almost no correlation between swimming speed and flagellar length, and the slow swimming was explained by the helical shape of the flagella, whose pitch and radius were 1.4 µm and 0.062 µm, respectively, whereas those of the wild-type flagella were 1.5 µm and 0.16 µm. The relative amounts of the various molecular components of the long Pof were different from those of the wild-type or the short Pof. This seems to be the reason for the difference in flagellar shape and length, though the mutation may be pleiotropic and affect flagellar function or regulation.

Effects of efonidipine, an L- and T-Type dual calcium channel blocker, on heart rate and blood pressure in patients with mild to severe hypertension: an uncontrolled, open-label pilot study.

BACKGROUND: Dihydropyridines (DHPs), a type of calcium channel blocker (CCB), are commonly prescribed for the treatment of hypertension and angina pectoris. DHPs act mainly on L-type calcium channels, essentially causing reflex tachycardia (elevated heart rate [HR]), which negatively affects cardiac function. Because T-type calcium channels in the sinoatrial node attenuate reflex tachycardia, a dual L- and T-type CCB (eg, efonidipine hydrochloride) may favorably affect cardiac pacing, thereby reducing reflex tachycardia. The effect of efonidipine as a DHP on HR deserves special consideration with regard to reflex tachycardia. OBJECTIVE: The aim of this study was to determine whether the L- and T-type CCB efonidipine can decrease the elevated HR induced by prior treatment using traditional DHPs. METHODS: This uncontrolled, open-label pilot study was conducted at the Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine (Tokyo, Japan). Patients aged 48 to 80 years with mild to severe hypertension and angina pectoris and who were receiving therapy with a DHP other than efonidipine were eligible. During an 8-week observation period, patients continued therapy with their DHP. After those 8 weeks, therapy was switched to oral efonidipine (40-mg tablet once daily) in patients whose blood pressure (BP) was stable and well controlled and whose HR was >80 bpm. BP and HR were monitored every 4 weeks of treatment with efonidipine. RESULTS: Eighteen patients (12 men, 6 women; mean [SD] age, 62.6 [12] years) were enrolled. After the switch to efonidipine, mean (SD) HR decreased significantly, from 94 (7) bpm to 86 (11) bpm at 12 weeks (P<0.05). The antihypertensive effect of efonidipine was similar to that of the DHPs used before the switch to efonidipine therapy, and reflex tachycardia was attenuated. CONCLUSION: In this study of a small sample of patients with mild to severe essential hypertension and angina pectoris, efonidipine was as effective as other DHPs. Moreover, the drug attenuated the reflex tachycardia that occurred with traditional DHPs.