Iodo and diiodotyrosine epoxysuccinyl derivatives as selective inhibitors of cathepsin B

Eight new analogs of -trans-epoxysuccinyl- -leucylamido(3-methyl)butane (E-64-c) containing Phe, Tyr, Tyr(1) or Tyr(I₂) in place of Leu, were synthesized and tested as inhibitors of papain, bovine spleen cathepsin B, calpain I and II from porcine red cells and porcine kidney, respectively. By use of kinetic methods, the new E-64 analogs proved to irreversibly inactivate both papain and cathepsin B via reversible enzyme-inhibitor intermediates EI. Second-order rate constants for inactivation were in the range 3500-55 100 M⁻¹s⁻¹ for papain and 650–105 000 M⁻¹s⁻¹ for cathepsin B. For the inactivation of calpain I and II they ranged between 250 and 2000 M⁻¹s⁻¹ and were similar to those of the known E-64-c. The effectiveness of the amino acid contained in the inhibitors tested increased in the order Tyr(I) ≈ Tyr(I₂) < Tyr < Phe < Leu for papain and Phe < Tyr < Tyr(I) < Leu < Tyr(I₂) for cathepsin B inactivation. Replacement of the with the -trans-epoxysuccinyl unit caused a 10–100-fold decrease in inhibitor potencies.     

Respiratory response in simultaneous exposure to flax and hemp dust

Žuškin, E., and Valíc, F. (1973).British Journal of Industrial Medicine,30, 375-380. Respiratory response in simultaneous exposure to flax and hemp dust. The effect of exposure to high concentrations of mixtures of hemp and flax dust was studied in 124 workers in two textile mills (mill A: 65-70% hemp and the rest flax, mean dust concentration 13·9 mg/m³; and mill B: about 35% hemp and the rest flax, mean dust concentration 15·8 mg/m³). A high prevalence of byssinosis was found in both mills (80% in mill B; 46·8% in mill A) after a mean exposure of no more than 13 years. In both mills, byssinotics had a higher prevalence of all chronic respiratory symptoms than non-byssinotics. This difference was more pronounced in mill A. Forty-eight percent of byssinotic women and 43% of byssinotic men had byssinosis of grade 2 or 3. Significant mean acute reductions in FEV_1·0 and ˙V_max 50% VC on Monday were recorded in subjects with and without byssinosis with a significantly larger mean reduction in byssinotics (FEV_1·0, P < 0·01; ˙V_max 50% VC, P < 0·05). ˙V_max 50% VC proved to be a more sensitive test for detecting acute effects of vegetable dust than FEV_1·0. The acute respiratory response of the subjects exposed to similar concentrations of flax and mixtures of two different proportions of flax and hemp dust was found to be equal.     

Changes in peripheral immune cells after intraoperative radiation therapy in low-risk breast cancer

A detailed understanding of the interactions and the best dose-fractionation scheme of radiation to maximize antitumor immunity have not been fully established. In this study, the effect on the host immune system of a single dose of 20 Gy through intraoperative radiation therapy (IORT) on the surgical bed in low-risk breast cancer patients undergoing conserving breast cancer has been assessed. Peripheral blood samples from 13 patients were collected preoperatively and at 48 h and 3 and 10 weeks after the administration of radiation. We performed a flow cytometry analysis for lymphocyte subpopulations, natural killer cells (NK), regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSCs). We observed that the subpopulation of NK CD56^+high CD16⁺ increased significantly at 3 weeks after IORT (0.30–0.42%, P < 0.001), while no changes were found in immunosuppressive profile, CD4⁺CD25⁺Foxp3⁺Helios⁺ Treg cells, granulocytic MDSCs (G-MDSCs) and monocytic MDSCs (Mo-MDSCs). A single dose of IORT may be an effective approach to improve antitumor immunity based on the increase in NK cells and the non-stimulation of immunosuppressive cells involved in immune escape. These findings support future combinations of IORT with immunotherapy, if they are confirmed in a large cohort of breast cancer patients.     

Byssinosis, Chronic Bronchitis, and Ventilatory Capacities in Workers Exposed to Soft Hemp Dust

A study was made of 93 women and 13 men employed in the spinning department of a factory in Yugoslavia processing soft hemp (Cannabis sativa). There were seven occupational groups, with average concentrations of total airborne hemp dust ranging from 2·9 mg./m.³ to more than 19·5 mg./m.³. Thirtyeight women and 11 men, employed in other departments of the factory with average total dust concentrations below 1·0 mg./m.³, were studied as controls.

In the spinning department 40·6% of the workers had byssinosis and 15·1% had chronic bronchitis (defined as persistent cough and phlegm on most days for as much as three months each year during the last two years). None of the controls suffered from either disease.

After adjustment for age, sitting height, and sex, the F.E.V._0·75 and F.V.C. measured at the beginning of the shift were used to assess the long-term effects of hemp dust on the ventilatory function of the lung. The age-adjusted ratio F.E.V._0·75/F.V.C. was also used. A comparison between the control group and the seven exposed groups showed no meaningful association between ventilatory function and present levels of dust exposure, but byssinotics with chronic bronchitis had a mean age-adjusted F.E.V._0·75/F.V.C. ratio significantly lower than that of workers with neither disease (P<0·05).

Acute effects of hemp dust, measured by the change in F.E.V._0·75 and F.V.C. during the shift, were considerable. There were marked reductions in the mean F.E.V._0·75 and F.V.C. during the shift in all the occupational groups exposed to high concentrations of dust. Byssinotics with chronic bronchitis had a significantly greater mean decrease in F.E.V._0·75 during the shift than the byssinotics without chronic bronchitis, and the workers with neither disease (P<0·02).

There is no doubt that the dust of Cannabis sativa hemp can cause byssinosis and at least temporary impairment of ventilatory function, varying in severity according to the level of dust exposure and the presence of respiratory disease.

     

Upper airway inflammation in waste handlers exposed to bioaerosols

Aims: To examine work associated upper airway inflammation in 31 waste handlers, and to correlate these findings with personally monitored exposure to different bioaerosol components.

Methods: Cell differentials, interleukin 8 (IL-8), myeloperoxidase (MPO), and eosinophilic cationic protein (ECP) were examined in NAL (nasal lavage), and swelling of the nasal mucosa was determined by acoustic rhinometry before work start on Monday and the following Thursday. Bioaerosol exposure was determined by personal full shift exposure measurements on Monday, Tuesday, and Wednesday and analysed for total bacteria, fungal spores, endotoxin, and ß(1→3)-glucans.

Results: The increased percentage of neutrophils from Monday (28%) to Thursday (46%) correlated with increases in ECP (r_S = 0.71, p < 0.001) and MPO (r_S = 0.38, p < 0.05), and showed a close to significant correlation with nasal swelling (r_S = -0.55, p = 0.07). The Thursday levels of neutrophils, MPO, and IL-8 were associated with the exposure to fungal spores (range 0–2.0 x 10⁶/m³) and endotoxin (range 4–183 EU/m³) measured the day before, and the median exposure to ß(1→3)-glucans (range 3–217 ng/m³), respectively (r_S = 0.47–0.54, p < 0.01). Swelling of the nasal mucosa was associated with the fungal spore and ß(1→3)-glucan exposure (r_S = 0.58–0.59, p < 0.05).

Conclusion: These results are based on a relatively small population, and conclusions must be drawn with care. The results suggested that a moderate exposure to fungal spores, endotoxins, and ß(1→3)-glucans during waste handling induced upper airway inflammation dominated by neutrophil infiltration and swelling of the nasal mucosa.

     

Serum Levels of Vitamin D and Dental Caries in 7-Year-Old Children in Porto Metropolitan Area

Vitamin D deficiency has been associated with significant changes in dental structures. In children, it can induce enamel and dentin defects, which have been identified as risk factors for caries. This study aimed to assess the association between low serum 25-hydroxyvitamin D (25(OH) D) levels (<30 ng/mL) and the prevalence of caries in the permanent teeth and mixed dentition of 7-year-old children. A sample of 335 children from the population-based birth cohort Generation XXI (Porto, Portugal) was included. Data on children’s demographic and social conditions, health status, dental health behaviours, dental examination including erupted permanent first molars, and blood samples available for vitamin D analysis were collected. Dental outcomes included the presence of caries, including non-cavitated lesions (d_1–6mft/D_1–6MFT > 0), and advanced caries (d_3–6mft/D_3–6MF > 0). Serum 25(OH) D was measured using a competitive electrochemiluminescence immunoassay protein-binding assay. Bivariate analysis and multivariate logistic regression were used. Advanced caries in permanent teeth was significantly associated with children’s vitamin D levels <30 ng/mL, gastrointestinal disorders, higher daily intake of cariogenic food, and having had a dental appointment at ≤7 years old. Optimal childhood levels of vitamin D may be considered an additional preventive measure for dental caries in the permanent dentition.     

Marine Oil from C. finmarchicus Enhances Glucose Homeostasis and Liver Insulin Resistance in Obese Prediabetic Individuals

The intermediate state between normal glucose tolerance and overt type 2 diabetes mellitus is associated with micro- and macrovascular diseases, requiring safe and cost-effective treatment measures interventions. A novel source of LC n-3 FAs is Calanus finmarchicus Oil, which showed promising effects on glucose homeostasis in preclinical studies due to anti-obesity effects and/or anti-inflammatory properties. In total, 43 obese patients (BMI: 31.7 ± 5.2 kg/m²) were allocated in the following two groups: (1) Calanus oil group (2 g CO/day) and (2) placebo group (2 g paraffin oil/day). Markers of glucose metabolism, body composition and energy intake were measured at the beginning (t0), after 12 weeks (t₁₂) and 16 weeks (t₁₆). Overall, parameters reflecting abnormal glucose homeostasis and insulin resistance in the liver, including fasting insulin (−2.9 mU/L ± 4.10, p < 0.05), HOMA-IR (−0.9 ± 1.28, p < 0.05) and hepatic insulin resistance index (−1.06 ± 1.72 × 10⁶, p < 0.05) significantly enhanced after a 12-week CO-intervention, while no differences were observed in HbA1c, AUC_0–2h Glucose, AUC_0–2h Insulin, 2 h plasma glucose and muscle insulin sensitivity index. Our results indicate that Calanus oil causes beneficial effects on glucose metabolism and insulin resistance in obese patients, with clinical relevance to be verified in further studies. In addition, the possible active compounds and their mechanisms of action should be elucidated.     

Synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes bearing the 4-[3-bromophenyl]quinazoline moiety as a biomarker for EGFR-TK imaging

Aiming at the development of technetium-99m (^99mTc) complexes for early detection and staging of EGFR positive tumors, the tyrosine kinase inhibitor 6-amino-4-[(3-bromophenyl)amino]quinazoline was derivatized with pyridine-2-carboxaldehyde to generate the imine 6-(pyridine-2-methylimine)-4-[(3-bromophenyl)amino]quinazoline suitable for reacting with the fac-[^99mTc(CO)₃]⁺ core as an N,N bidentate ligand.The labelling was performed in high yield (>90%) by ligand exchange reaction using fac-[^99mTc(OH₂)₃(CO)₃]⁺ as precursor. The ^99mTc complex was characterized by comparative HPLC analysis using the analogous rhenium (Re) complex as reference. The Re complex was prepared by ligand exchange reaction using the fac-[ReBr₃(CO)₃]²⁻ as precursor and was fully characterized by NMR and IR spectroscopies and elemental analysis. In vitro studies indicate that both the ligand and its Re complex inhibit the EGFR autophosphorylation (IC₅₀: 17 ± 3.7 and 114 ± 23 nM respectively) in intact A431 cells, bind the receptor in a reversible mode, and inhibit A431 cell growth (IC₅₀: 5.2 ± 1.1 and 2.0 ± 0.98 μM respectively). Biodistribution of the ^99mTc complex in healthy animals showed a rather fast blood and soft tissue clearance between 1 and 15 min p.i. with excretion occurring mainly via the hepatobiliary system.     

Secondhand Tobacco Smoke Exposure in Open and Semi-Open Settings: A Systematic Review

Background: Some countries have recently extended smoke-free policies to particular outdoor settings; however, there is controversy regarding whether this is scientifically and ethically justifiable.Objectives: The objective of the present study was to review research on secondhand smoke (SHS) exposure in outdoor settings.Data sources: We conducted different searches in PubMed for the period prior to September 2012. We checked the references of the identified papers, and conducted a similar search in Google Scholar.Study selection: Our search terms included combinations of “secondhand smoke,” “environmental tobacco smoke,” “passive smoking” OR “tobacco smoke pollution” AND “outdoors” AND “PM” (particulate matter), “PM_2.5” (PM with diameter ≤ 2.5 µm), “respirable suspended particles,” “particulate matter,” “nicotine,” “CO” (carbon monoxide), “cotinine,” “marker,” “biomarker” OR “airborne marker.” In total, 18 articles and reports met the inclusion criteria.Results: Almost all studies used PM_2.5 concentration as an SHS marker. Mean PM_2.5 concentrations reported for outdoor smoking areas when smokers were present ranged from 8.32 to 124 µg/m³ at hospitality venues, and 4.60 to 17.80 µg/m³ at other locations. Mean PM_2.5 concentrations in smoke-free indoor settings near outdoor smoking areas ranged from 4 to 120.51 µg/m³. SHS levels increased when smokers were present, and outdoor and indoor SHS levels were related. Most studies reported a positive association between SHS measures and smoker density, enclosure of outdoor locations, wind conditions, and proximity to smokers.Conclusions: The available evidence indicates high SHS levels at some outdoor smoking areas and at adjacent smoke-free indoor areas. Further research and standardization of methodology is needed to determine whether smoke-free legislation should be extended to outdoor settings.     

Plasma Vitamin B12 and Folate Alter the Association of Blood Lead and Cadmium and Total Urinary Arsenic Levels with Chronic Kidney Disease in a Taiwanese Population

Heavy metals causing chronic nephrotoxicity may play a key role in the pathogenesis of chronic kidney disease (CKD). This study hypothesized that plasma folate and vitamin B₁₂ would modify the association of CKD with total urinary arsenic and blood lead and cadmium levels. We recruited 220 patients with CKD who had an estimated glomerular filtration rate of <60 mL/min/1.73 m² for ≥3 consecutive months and 438 sex- and age-matched controls. We performed inductively coupled plasma mass spectrometry to measure blood cadmium and lead levels. The urinary arsenic level was determined using a high-performance liquid chromatography–hydride generator–atomic absorption spectrometry. Plasma vitamin B₁₂ and folate levels were measured through the SimulTRAC-SNB radioassay. Compared with patients with plasma vitamin B₁₂ ≤ 6.27 pg/mL, the odds ratio (OR) and 95% confidence interval of CKD for patients with plasma vitamin B₁₂ > 9.54 pg/mL was 2.02 (1.15–3.55). However, no association was observed between plasma folate concentration and CKD. A high level of plasma vitamin B₁₂ combined with high levels of blood lead and cadmium level and total urinary arsenic tended to increase the OR of CKD in a dose-response manner, but the interactions were nonsignificant. This is the first study to demonstrate that patients with high plasma vitamin B₁₂ level exhibit increased OR of CKD related to high levels of blood cadmium and lead and total urinary arsenic.     

Preprocessing cotton to prevent byssinosis

Merchant, J. A., Lumsden, J. C., Kilburn, K. H., Germino, V. H., Hamilton, J. D., Lynn, W. S., Byrd, H., and Baucom, D. (1973).British Journal of Industrial Medicine,30, 237-247. Preprocessing cotton to prevent byssinosis. A fundamental approach of cleaning or deactivating cotton prior to manufacturing has long been advocated to prevent byssinosis, but no trial had been conducted to test the feasibility of such an approach. In the study described, it was possible to be directed by both biological observations and the results of manufacturing trials.

An exposure chamber was built in a cotton textile mill which had been previously studied as part of a large cross-sectional survey. The chamber was provided with an independent air conditioning system and a carding machine which served as a dust generator. Sixteen subjects, who had shown reductions in expiratory flow rate with exposure to cotton dust, were chosen to form a panel for exposure to raw cottons and cottons which had been preprocessed by heating, washing, and steaming. Indicators of effects were symptoms of chest tightness and/or dyspnoea, change in FEV_1·0, and fine dust levels over 6 hours of exposure.

Exposure of the panel to no cotton dust resulted in no change in FEV_1·0 and served as the control for subsequent trials. Exposure to strict middling cotton resulted in a byssinosis symptom prevalence of 22%, a significant decrement in FEV_1·0 of 2·9%, and a fine dust level of 0·26 mg/m³. Exposure to strict low middling cotton resulted in a byssinosis symptom prevalence of 79%, a decrement in FEV_1·0 of 8·5%, and a fine dust level of 0·89 mg/m³. Oven heating strict low middling cotton resulted in a byssinosis symptom prevalence of 56% and a relatively greater drop in FEV_1·0 of 8·3% for 0·48 mg/m³ of fine dust. Washing the strict low grade cotton eliminated detectable biological effects with a symptom prevalence of 8%, an increase of 1·4% in FEV_1·, and a dust level of 0·16 mg/m³, but the cotton proved to be difficult to process. As an alternative method, strict low middling cotton was steamed initially in large dyeing vats, on a conveyor, in an autoclave, and in a modified yarn dyeing apparatus or `pipe' steamer. Of these methods, autoclaving cotton was the most successful, reducing symptom prevalence to 8%, the drop in FEV<sub>1·0</sub> to 0·4%, and the dust level to 0·23 mg/m<sup>3</sup>. Development of a high capacity cotton steamer based on the small `pipe' steaming model resulted in a symptom prevalence of 8%, a decrement in FEV_1·0 of 0·8%, and a mean dust level of 0·27 mg/m³. Regressions calculated from raw and high capacity steaming trials indicate that at low dust levels steamed cotton dust was roughly one half as biologically active as raw cotton dust.

     

Phytoestrogen Coumestrol Selectively Inhibits Monoamine Oxidase-A and Amyloid β Self-Aggregation

Pueraria lobata leaves contain a variety of phytoestrogens, including flavonoids, isoflavonoids, and coumestan derivatives. In this study, we aimed to identify the active ingredients of P. lobata leaves and to elucidate their function in monoamine oxidase (MAO) activation and Aβ self-aggregation using in vitro and in silico approaches. To the best of our knowledge, this is the first study to elucidate coumestrol as a selective and competitive MAO-A inhibitor. We identified that coumestrol, a coumestan-derivative, exhibited a selective inhibitory effect against MAO-A (IC₅₀ = 1.99 ± 0.68 µM), a key target protein for depression. In a kinetics analysis with 0.5 µg MAO-A, 40–160 µM substrate, and 25 °C reaction conditions, coumestrol acts as a competitive MAO-A inhibitor with an inhibition constant of 1.32 µM. During an in silico molecular docking analysis, coumestrol formed hydrogen bonds with FAD and pi–pi bonds with hydrophobic residues at the active site of the enzyme. Moreover, based on thioflavin-T-based fluorometric assays, we elucidated that coumestrol effectively prevented self-aggregation of amyloid beta (Aβ), which induces an inflammatory response in the central nervous system (CNS) and is a major cause of Alzheimer’s disease (AD). Therefore, coumestrol could be used as a CNS drug to prevent diseases such as depression and AD by the inhibition of MAO-A and Aβ self-aggregation.     

Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer

The present study analyzed the transepithelial transport of the dietary anti-inflammatory peptide, γ-glutamyl valine (γ-EV). γ-EV is naturally found in dry edible beans. Our previous study demonstrated the anti-inflammatory potency of γ-EV against vascular inflammation at a concentration of 1mM, and that it can transport with the apparent permeability coefficient (P_app) of 1.56 × 10⁻⁶ ± 0.7 × 10⁻⁶ cm/s across the intestinal Caco-2 cells. The purpose of the current study was to explore whether the permeability of the peptide could be enhanced and to elucidate the mechanism of transport of γ-EV across Caco-2 cells. The initial results indicated that γ-EV was nontoxic to the Caco-2 cells up to 5 mM concentration and could be transported across the intestinal cells intact. During apical-to-basolateral transport, a higher peptide dose (5 mM) significantly (p < 0.01) enhanced the transport rate to 2.5 × 10⁻⁶ ± 0.6 × 10⁻⁶ cm/s. Cytochalasin-D disintegrated the tight-junction proteins of the Caco-2 monolayer and increased the P_app of γ-EV to 4.36 × 10⁻⁶ ± 0.16 × 10⁻⁶ cm/s (p < 0.001), while theaflavin 3′-gallate and Gly-Sar significantly decreased the P_app (p < 0.05), with wortmannin having no effects on the peptide transport, indicating that the transport route of γ-EV could be via both PepT1-mediated and paracellular.     

Determinants of patient activation and its association with cardiovascular disease risk in chronic kidney disease: A cross‐sectional study

BackgroundPatient activation describes the knowledge, skills and confidence in managing one''s own health. Promoting patient activation is being prioritized to reduce costs and adverse outcomes such as cardiovascular disease (CVD). The increasing prevalence of chronic kidney disease (CKD) presents a need to understand the characteristics that influence patient activation and the effect on health outcomes.DesignCross‐sectional study.Setting and participantsPatients with non‐dialysis CKD recruited from 14 sites (general nephrology and primary care) in England, UK.Outcome measuresPatient activation was measured using the PAM‐13. Demographic and health‐related variables, self‐reported symptom burden, health‐related quality of life (HRQOL), socioeconomic status (SES), were assessed as determinants of patient activation. Major CVD risk factors included hypertension, dyslipidaemia, obesity and hyperkalaemia.Results743 patients were included (eGFR: 32.3 (_SD17.1) mL/min/1.73 m², age 67.8 (_SD13.9) years, 68% male). The mean PAM score was 55.1 (_SD14.4)/100. Most patients (60%) had low activation. Those with low activation were older (P<.001), had lower eGFR (P = .004), greater number of comorbidities (P = .026) and lower haemoglobin (P = .025). Patients with low activation had a 17% greater number of CVD risk factors (P < .001). Risk factors in those with low activation were being older (P < .001) and having diabetes (P < .001).ConclusionThis study showed that only a minority of CKD patients are activated for self‐management. Our findings help better understand the level of activation in these patients, particularly older individuals with multimorbidity, and further the knowledge regarding the characteristics that influence activation.Patient or Public ContributionPatients were involved in the design of main study.     

Pharmacokinetics of Nitrate and Nitrite Following Beetroot Juice Drink Consumption

Background: Nitrate (NO₃⁻)-rich beetroot (BR) juice supplementation has been shown to improve cardiovascular function via reduction to nitrite (NO₂⁻) and then to the bioactive molecule nitric oxide (NO). However, limited research exists for the role of inorganic NO₂⁻ that is contained naturally within BR. Objective: As BR juice can naturally contain both NO₃⁻ and NO₂⁻ the objective of this study was to evaluate the individual effects of NO₃⁻ and NO₂⁻ consumed from BR on plasma [NO₃⁻]/[NO₂⁻] and their subsequent effects on various cardiovascular measures. Design: In four separate treatments, 11 healthy adults consumed 250 mL of BR containing one of the following: (i) high NO₃⁻, low NO₂⁻ (HL; 572 mg NO₃⁻, 32 mg NO₂⁻); (ii) medium NO₃⁻, medium NO₂⁻ (MM; 280 mg NO₃⁻, 237 mg NO₂⁻); (iii) low NO₃⁻, medium NO₂⁻ (LM; 43 mg NO₃⁻, 262 mg NO₂⁻); (iv) placebo (PL; low NO₃⁻, low NO₂⁻: 8 mg NO₃⁻, 5.8 mg NO₂⁻). Plasma [NO₃⁻]/[NO₂⁻], blood pressure, heart rate, mean arterial pressure (MAP), cardiac output and stroke volume were measured at baseline and every hour or second hour for 6 h post-BR consumption. Outcomes: Ingestion of the HL and MM BR increased plasma [NO₂⁻] and [NO₃⁻] after 2 h, with both remaining elevated after 6 h (p < 0.05). LM increased plasma [NO₃⁻] (p < 0.05) but did not increase plasma [NO₂⁻] compared to PL (p = 0.177). MAP was lower following the consumption of HL at 4 h and LM at 6 h (p < 0.05). Conclusion: Inorganic NO₃⁻ consumption is the critical factor in elevating plasma [NO₃⁻] and [NO₂⁻]; however, both NO₂⁻ and NO₃⁻ show potential to reduce MAP. The known reduction of systolic blood pressure (SBP)/diastolic blood pressure (DBP) following NO₃⁻ supplementation was not observed, making it unclear if NO₂⁻ contributes to a reduction in SBP/DBP alongside NO₃⁻.     

Coarse particulate matter and emergency ambulance dispatches in Fukuoka,Japan: a time-stratified case-crossover study

Objectives

There is no conclusive evidence of adverse health effects caused by short-term exposure to coarse particulate matter, so in this case-crossover study we looked for an association between exposure and emergency ambulance dispatches (as a proxy of acute health outcomes).

Methods

We used data on emergency ambulance dispatches in Fukuoka City, Japan between 2005 and 2010. After excluding ambulance dispatches related to external injuries and pregnancy/childbirth, we analyzed data on 176,123 dispatches. Citywide daily mean concentrations of suspended particulate matter (SPM) and fine particulate matter (PM_2.5) were calculated from ambient monitoring data, and the differences between concentrations of SPM and PM_2.5 were used as an exposure surrogate of coarse particulate matter. Using a conditional logistic regression model, we estimated the ambient temperature and relative humidity adjusted odds ratios (ORs) per 10 μg/m³ increase in coarse particulate matter.

Results

The average daily concentration of coarse particulate matter over the study period was 9.9 μg/m³, representing 33 % of the total concentration of SPM. Elevated concentrations of coarse particulate matter were associated with an increase in respiratory disease-related emergency ambulance dispatches for adults aged 65 years or older (9,716 dispatches, OR for lag0–1 = 1.065, 95 % confidence interval = 1.023–1.109). After additional adjustment for exposure to PM_2.5, we observed a statistically non-significant increased risk (OR = 1.035, 0.986–1.086).

Conclusions

We found weak evidence of adverse effects of short-term exposure to coarse particulate matter on human health.     

The Relationship of Energy Malnutrition,Skeletal Muscle and Physical Functional Performance in Patients with Stable Chronic Obstructive Pulmonary Disease

Weight loss is a factor that affects prognosis in patients with chronic obstructive pulmonary disease (COPD) independent of lung function. One of the major factors for weight loss is energy malnutrition. There have been no reports on the factors related to energy malnutrition in COPD patients. This retrospective observational study aimed to investigate these factors. We included 163 male subjects with COPD. Respiratory quotient (RQ), an index of energy malnutrition, was calculated by expiratory gas analysis using an indirect calorimeter. RQ < 0.85 was defined as the energy-malnutrition group and RQ ≥ 0.85 as the no energy-malnutrition group. Factors related to energy malnutrition were examined by multivariate and decision-tree analysis. We finally analyzed data from 56 selected subjects (median age: 74 years, BMI: 22.5 kg/m²). Energy malnutrition was observed in 43%. The independent factors associated with energy malnutrition were tidal volume (VT) (OR 0.99; 95% CI 0.985–0.998; p = 0.015) and Th12 erector spinae muscle cross-sectional area SMI (Th12ESM_SMI) (OR 0.71; 95% CI 0.535–0.946; p = 0.019). In decision-tree profiling of energy malnutrition, VT was extracted as the first distinguishable factor, and Th12ESM_SMI as the second. In ROC analysis, VT < 647 mL (AUC, 0.72) or Th12ESM_SMI < 10.1 (AUC, 0.70) was the cutoff value for energy malnutrition. Energy malnutrition may be an early warning sign of nutritional disorders.     

Body mass index and waist circumference are independent risk factors for low vital capacity among Japanese participants of a health checkup: a single-institution cross-sectional study

Objective

This study aimed to examine the associations between obesity and percentage vital capacity (%VC), as well as lifestyle-related disorders, among Japanese participants of a voluntary health checkup.

Methods

Subjects were 7,892 individuals who participated in a medical health checkup from January to December 2007. Multivariate logistic regression analysis was performed to assess associations between low %VC (<80) and body mass index (BMI) and waist circumference (WC), as well as lifestyle-related disorders.

Results

Medical histories of hypertension and dyslipidemia were more frequent in the low %VC group than in the normal %VC group in both sexes. In men, BMI was significantly associated with low %VC (25.0 ≤ C2 < 27.5, odds ratio (OR) = 2.10; 27.5 ≤ C3 < 30.0, OR = 2.23; C4 ≥ 30.0, OR = 3.46) relative to the first category (C1 < 25.0). A significant association was also observed between WC and low %VC (85 ≤ C2 < 90, OR = 1.40; 90 ≤ C3 < 95, OR = 1.55; 95 ≤ C4, OR = 2.51; relative to C1 < 85.0 cm). In women, BMI was significantly associated with low %VC in C3 and C4 (C3, OR = 2.05; C4, OR = 2.84), and WC was significantly associated with low %VC in C4 (C4, OR = 2.32).

Conclusion

Our results suggest that obesity may be associated with restrictive pulmonary function and underscore the importance of maintaining ideal body weight for the prevention of restrictive pulmonary dysfunction.