Staphylococcus pettenkoferi bacteremia in a tertiary care hospital in Japan: Report of three cases.

Staphylococcus pettenkoferi is a coagulase-negative staphylococci (CoNS) species first isolated in 2002. Human infections caused by S. pettenkoferi are rare. We herein report three cases of S. pettenkoferi bacteremia in a tertiary care hospital in Japan. Staphylococcus pettenkoferi can be a causative pathogen of catheter related blood stream infection including complicated infection, and unknown source of bacteremia. All of the patients presented with fever and shaking chills, and good clinical outcome. Further research is needed to determine the role of this organism as a pathogen and frequency.

Neuromedin U suppresses glucose-stimulated insulin secretion in pancreatic ß cells.

Neuromedin U (NMU), a highly conserved peptide in mammals, is implicated in energy homeostasis and glycemic control, and may also be involved in the regulation of adipoinsular axis function. However, the role of NMU in regulating insulin secretion has not been clearly established. In this study, we investigated the role of NMU in the regulation of insulin secretion both in vitro and in vivo. We found that NMU and NMU receptor (NMUR) 1 were expressed in mouse islets and ß cell-derived MIN6-K8 cells. In mice, NMU suppressed glucose-stimulated insulin secretion (GSIS) both in vitro and in vivo. Additionally, an NMUR1 agonist inhibited GSIS in both MIN6-K8 cells and mice islets. Moreover, NMU attenuated intracellular Ca2+ influx in MIN6-K8 cells, potentially causing a decrease in insulin secretion. siNmu-transfected MIN6-K8 cells showed elevated GSIS. Treatment with anti-NMU IgG increased GSIS in isolated mouse pancreatic islets. These results suggested that NMU can act directly on ß cells through NMUR1 in an autocrine or paracrine fashion to suppress insulin secretion. Collectively, our results highlight the crucial role of NMU in suppressing pancreatic insulin secretion, and may improve our understanding of glucose homeostasis.

Ghrelin does not influence cancer progression in a lung adenocarcinoma cell line.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), is produced in the human stomach. Although ghrelin has therapeutic potential for cancer cachexia, ghrelin treatment may have a concern about accelerating cancer progression. Here, using the human lung adenocarcinoma cell line HLC-1, we investigated the effects of ghrelin on molecular mechanisms linked to cancer progression, including cell viability, proliferation, resistance to apoptosis, and mitochondrial activity. Both types of mouse alveolar epithelial cells (types I and II) expressed the GHSR, as did the human normal airway cell lines BEAS-2B and HLC-1. Treatment with ghrelin (10-2, 10-1, 1, 10 µM) did not affect cell viability or proliferation. Pretreatment of HLC-1 cells with ghrelin (10 µM) did not affect resistance to paclitaxel-induced apoptosis. The parameters of mitochondrial respiration, including basal respiration, proton leak, ATP production, maximal respiration, spare respiratory capacity, and non-mitochondrial respiration, of the HLC-1 cells pretreated with or without ghrelin were unchanged. Taken together, ghrelin does not influence cancer progression in lung adenocarcinoma cells.

The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections.

Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

Lipoprotein(a) levels predict adverse vascular events after acute myocardial infarction.

Lipoprotein(a) [Lp(a)], which is genetically determined, has been reported as an independent risk factor for atherosclerotic vascular disease. However, the prognostic value of Lp(a) for secondary vascular events in patients after coronary artery disease has not been fully elucidated. This 3-year observational study included a total of 176 patients with ST-elevated myocardial infarction (STEMI), whose Lp(a) levels were measured within 24 h after primary percutaneous coronary intervention. We divided enrolled patients into two groups according to Lp(a) level and investigated the association between Lp(a) and the incidence of major adverse cardiac and cerebrovascular events (MACCE). A Kaplan-Meier analysis demonstrated that patients with higher Lp(a) levels had a higher incidence of MACCE than those with lower Lp(a) levels (log-rank P = 0.034). A multivariate Cox regression analysis revealed that Lp(a) levels were independently correlated with the occurrence of MACCE after adjusting for other classical risk factors of atherosclerotic vascular diseases (hazard ratio 1.030, 95 % confidence interval: 1.011-1.048, P = 0.002). In receiver-operating curve analysis, the cutoff value to maximize the predictive power of Lp(a) was 19.0 mg/dl (area under the curve = 0.674, sensitivity 69.2 %, specificity 62.0 %). Evaluation of Lp(a) in addition to the established coronary risk factors improved their predictive value for the occurrence of MACCE. In conclusion, Lp(a) levels at admission independently predict secondary vascular events in patients with STEMI. Lp(a) might provide useful information for the development of secondary prevention strategies in patients with myocardial infarction.

Clinical benefit of tolvaptan in patients with acute decompensated heart failure and chronic kidney disease.

Tolvaptan, a vasopressin type 2 receptor antagonist, has an aquaretic effect without affecting renal function. The effects of long-term tolvaptan administration in heart failure patients with renal dysfunction have not been clarified. Here, we assessed the clinical benefit of tolvaptan during a 6-month follow-up in acute decompensated heart failure (ADHF) patients with severe chronic kidney disease (CKD; estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m(2)). We compared 33 patients with ADHF and severe CKD who were administered tolvaptan in addition to loop diuretics (TLV group), with 36 patients with ADHF and severe CKD who were administered high-dose loop diuretics (≥40 mg) alone (LD group). Alterations in serum creatinine and eGFR levels from the time of hospital discharge to 6-month follow-up were significantly different between the groups, with those in the TLV group being more favorable. Furthermore, Kaplan-Meier analysis revealed that rehospitalization for heart failure (HF) was significantly lower in the TLV group compared with the LD group. In ADHF patients with severe CKD, tolvaptan use for 6 months reduced worsening of renal function and rehospitalization rates for HF when compared with conventional diuretic therapy. In conclusion, tolvaptan could be a safe and effective agent for long-term management of HF and CKD.

Estimation of habitual iodine intake in Japanese adults using 16 d diet records over four seasons with a newly developed food composition database for iodine.

Although habitual seaweed consumption in Japan would suggest that iodine intake in Japanese is exceptionally high, intake data from diet records are limited. In the present study, we developed a composition database of iodine and estimated the habitual intake of iodine among Japanese adults. Missing values for iodine content in the existing composition table were imputed based on established criteria. 16 d diet records (4 d over four seasons) from adults (120 women aged 30-69 years and 120 men aged 30-76 years) living in Japan were collected, and iodine intake was estimated. Habitual intake was estimated with the Best-power method. Totally, 995 food items were imputed. The distribution of iodine intake in 24 h was highly skewed, and approximately 55 % of 24 h values were < 300 µg/d. The median iodine intake in 24 h was 229 µg/d for women and 273 µg/d for men. All subjects consumed iodine-rich foods (kelp or soup stock) on one or more days of the sixteen survey days. The mean (median) habitual iodine intake was 1414 (857) µg/d for women and 1572 (1031) µg/d for men. Older participants had higher intake than younger participants. The major contributors to iodine intake were kelp (60 %) and soup stock (30 %). Habitual iodine intake among Japanese was sufficient or higher than the tolerable upper intake level, particularly in older generations. The association between high iodine intake as that observed in the present study and thyroid disease requires further study.

Higher proportion of total and fat energy intake during the morning may reduce absolute intake of energy within the day. An observational study in free-living Japanese adults.

BACKGROUND: Although the distribution of energy intake throughout the day appears to impact overall daily energy intake, little is known about the ad libitum distribution of energy intake. OBJECTIVE: Our aim was to investigate associations between the distribution of energy intake during the day and subsequent or overall energy intake, and food choice in free-living adults. DESIGN: A total of 119 women and 116 men completed 16-day semi-weighed dietary records. The longitudinal dietary intake data for each participant were analyzed using a mixed model to examine the effect of energy intake at various times of day on subsequent or overall energy intake. RESULTS: Mean proportion of total energy intake in the morning (4:00 a.m.-10:29 a.m.), afternoon (10:30 a.m.-4:59 p.m.) and evening (5:00 p.m.-3:59 a.m.) meal was 22.6%, 33.8% and 43.6% in men, and 24.7%, 36.5%, 38.8% in women, respectively. Proportion of energy intake (%) in the morning meal was significantly and negatively associated with energy intake (kcal) in the subsequent afternoon and evening meals, and consequently in the whole day in both sexes. This significant and negative association was also observed for proportion of energy intake (%) of fat, but not of carbohydrate or protein, in both sexes. Proportion of energy intake (%) in the morning meal was negatively associated with overall energy intake (kcal) from the group of meats, fish, and eggs in both sexes, and from the group of confectioneries and soft drinks in women. CONCLUSIONS: More energy in the morning meal may reduce energy intake, especially that from fat, in the subsequent meals, and consequently in the whole day.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC1) gene is suppressed by transglutaminase 2 activation.

Pituitary adenylate cyclase-activating polypeptide (PACAP) functions as a neuroprotective factor through the PACAP type 1 receptor, PAC1. In a previous work, we demonstrated that nerve growth factor augmented PAC1 gene expression through the activation of Sp1 via the Ras/MAPK pathway. We also observed that PAC1 expression in Neuro2a cells was transiently suppressed during in vitro ischemic conditions, oxygen-glucose deprivation (OGD). Because endoplasmic reticulum (ER) stress is induced by ischemia, we attempted to clarify how ER stress affects the expression of PAC1. Tunicamycin, which induces ER stress, significantly suppressed PAC1 gene expression, and salubrinal, a selective inhibitor of the protein kinase RNA-like endoplasmic reticulum kinase signaling pathway of ER stress, blocked the suppression. In luciferase reporter assay, we found that two Sp1 sites were involved in suppression of PAC1 gene expression due to tunicamycin or OGD. Immunocytochemical staining demonstrated that OGD-induced transglutaminase 2 (TG2) expression was suppressed by salubrinal or cystamine, a TG activity inhibitor. Further, the OGD-induced accumulation of cross-linked Sp1 in nuclei was suppressed by cystamine or salubrinal. Together with cystamine, R283, TG2-specific inhibitor, and siRNA specific for TG2 also ameliorated OGD-induced attenuation of PAC1 gene expression. These results suggest that Sp1 cross-linking might be crucial in negative regulation of PAC1 gene expression due to TG2 in OGD-induced ER stress.

Rikkunshito ameliorates bleomycin-induced acute lung injury in a ghrelin-independent manner.

Acute lung injury (ALI) is a critical syndrome consisting of acute respiratory failure associated with extensive pulmonary infiltrates. The pathological characterization of ALI includes injuries of alveolar epithelial cells (AECs), alveolar neutrophilic infiltration, and increases in proinflammatory cytokines, which cause destruction of the alveolar capillary barrier and subsequent devastating lung fibrosis. Rikkunshito (RKT), a traditional Japanese herbal medicine, is widely used for the treatment of patients with gastrointestinal symptoms and is known to stimulate ghrelin secretion. The therapeutic effects of RKT on organ inflammation and fibrosis remain unknown. We investigated the pharmacological potential of RKT in the treatment of ALI by using a bleomycin-induced ALI model in mice. RKT or distilled water (DW) was given to mice daily starting 12 h after bleomycin administration. The RKT-treated mice showed a definitively higher survival rate than the DW-treated mice after injury. They also had smaller reductions in body weight and food intake. The amelioration of neutrophil alveolar infiltration, pulmonary vascular permeability, induction of proinflammatory cytokines, activation of the NF-κB pathway, apoptosis of AECs, and subsequent lung fibrosis were notable in the RKT-treated mice. RKT administration increased the plasma ghrelin levels in wild-type mice, and it also mitigated the ALI response in both ghrelin-deficient mice and growth hormone secretagogue receptor-deficient mice after lung injury. Our results indicate that RKT administration exerts protective effects against ALI by protecting the AECs and regulating lung inflammation independently of the ghrelin system, and they highlight RKT as a promising therapeutic agent for the management of this intractable disease.

Association between atherosclerotic cardiovascular disease score and skin carotenoid levels estimated via refraction spectroscopy in the Japanese population: a cross-sectional study.

Carotenoids play a role in preventing and impeding the progression of atherosclerotic cardiovascular diseases (ASCVDs) through their anti-oxidative effects. This study evaluated associations between ASCVD risk and skin carotenoid (SC) levels, reflecting dietary carotenoid intake. Participants' ASCVD risk was assessed using the Hisayama ASCVD risk prediction model, and SC levels were measured through a reflection spectroscope (Veggie Meter). The associations between high ASCVD risk and SC levels were analyzed using logistic regression analysis and a restricted cubic spline (RCS) model. A total of 1130 men and women (mean age: 56 years) from participants who underwent a health examination in Seirei Center for Health Promotion and Prevention Medicine in 2019 and 2022 were analyzed. Of these, 4.6% had moderate or high ASCVD risk. Mean SC values were 236, 315, 376, 447, and 606 in quintile Q1 to Q5, respectively. The adjusted odds ratios (95% confidence intervals) of SC quintile for moderate- or high-risk ASCVD was 0.24 (0.12-0.51) in Q5 (495 ≤), 0.42 (0.23-0.77) in Q4, 0.50 (0.29-0.88) in Q3, and 0.68 (0.41-1.12) in Q2 compared to Q1 (< 281). High SC values continuously showed non-linear inverse association with moderate- or high-risk for ASCVD in Japanese adults. Non-invasive SC measurements may be a good indicator for recommending carotenoids to prevent cardiovascular disease.

Within- and between-individual variation in energy and nutrient intake in Japanese adults: effect of age and sex differences on group size and number of records required for adequate dietary assessment.

BACKGROUND: Information on within- and between-individual variation in energy and nutrient intake is critical for precisely estimating usual dietary intake; however, data from Japanese populations are limited. METHODS: We used dietary records to examine within- and between-individual variation by age and sex in the intake of energy and 31 selected nutrients among Japanese adults. We also calculated the group size required to estimate mean intake for a group and number of days required both to rank individuals within a group and to assess an individual's usual intake, all with appropriate arbitrary precision. A group of Japanese women (younger: 30-49 years, n = 58; older: 50-69 years, n = 63) and men (younger: 30-49 years, n = 54; older: 50-76 years, n = 67) completed dietary records for 4 nonconsecutive days in each season (16 days in total). RESULTS: Coefficients of within-individual variation and between-individual variation were generally larger in the younger group than in the older group and in men as compared with women. The group size required to estimate a group's mean intake, and number of days required to assess an individual's usual intake, were generally larger for the younger group and for men. In general, a longer period was required to rank women and older adults. CONCLUSIONS: In a group of Japanese adults, coefficients of within-individual variation and between-individual variation, which were used to estimate the group size and number of records required for adequate dietary assessment, differed by age, sex, and nutrient.

The importance of infectious disease specialists consulting on a weekly basis in a Japanese tertiary care hospital: A retrospective observational study.

Limited data are available regarding part-time infectious disease consultations (IDCs) and their importance in tertiary care teaching hospitals in Japan. This is a retrospective review of IDCs from June 2016 to March 2021 and describes IDC services provided by part-time infectious disease specialists once a week for 4 hours, and their impact on the quality of medical care, including antimicrobial stewardship. Data, such as the requesting department, requesting reasons, and final diagnoses, were analyzed. In April 2018, part-time infectious disease specialists launched consultation services and attended an antimicrobial stewardship team conference. Meropenem, tazobactam/piperacillin, and cefepime monthly days of therapy (DOT) were calculated to assess the effect of each intervention; a pre-post analysis was conducted using the Kruskal-Wallis test. Additional quality improvement (QI) projects related to infectious diseases were implemented. There were 237 IDCs during the study period. Consultations were mostly requested by the General Internal Medicine, Emergency Medicine, and Cardiology departments. The most common diagnoses were bone/joint, respiratory, and genitourinary infections. Infectious disease services, even on a part-time basis, achieve good outcomes in patient management, antimicrobial stewardship, and QI projects. DOT/1000 patient-days were reduced for meropenem and cefepime, while it increased for tazobactam/piperacillin. The DOT/1000 patient-days for the 3-antipseudomonal agents significantly decreased during this period. After implementing the QI tetanus vaccination project in the Emergency Room, the number of tetanus toxoid vaccinations per month increased.

The Changes in Broad-spectrum Antimicrobial Consumption during the COVID-19 Pandemic in a Japanese Acute Tertiary-care Hospital: An Interrupted Time-series Analysis.

Objective The novel coronavirus disease 2019 (COVID-19) pandemic has spread worldwide, and hospitals in Japan have been forced to respond to the situation. This study evaluated the broad-spectrum antimicrobial use before and during the COVID-19 pandemic in an acute tertiary-care hospital. Methods This single-center, retrospective study was conducted between January 2019 and June 2021. Patients We reviewed patients treated with three broad-spectrum antipseudomonal agents: carbapenems, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1,000 patient-days, and the monthly incidences of Clostridioides difficile infection (CDI), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenemase-producing Enterobacteriaceae (CPE) were recorded. Results The median monthly carbapenem-DOTs during the pre-pandemic and pandemic era were 8.4 and 8.2 per 1,000 patient-days, respectively. A time-series analysis showed non-significant changes in the level between periods (coefficients: 2.08; 95% confidence interval [CI]: -2.9 to 7.0; p=0.44). No change in the trend of monthly carbapenem-DOTs was observed after intervention. No post-intervention changes in the incidence of MRPA or CPE were observed; however, the trend in the incidence of CDI per 1,000 patient-days significantly differed between the two periods (coefficient: -0.04; 95% CI: -0.07, 0.00; p=0.01), and a downward trend was observed in the monthly CDI incidence during the COVID-19 period. Conclusion The consumption of broad intravenous antimicrobial agents has not changed significantly during the pandemic. We need to maintain the quality of medical care, including antimicrobial stewardship, even in specialized resource-limited facilities during a pandemic.

The NERP-4-SNAT2 axis regulates pancreatic ß-cell maintenance and function.

Insulin secretion from pancreatic ß cells is regulated by multiple stimuli, including nutrients, hormones, neuronal inputs, and local signalling. Amino acids modulate insulin secretion via amino acid transporters expressed on ß cells. The granin protein VGF has dual roles in ß cells: regulating secretory granule formation and functioning as a multiple peptide precursor. A VGF-derived peptide, neuroendocrine regulatory peptide-4 (NERP-4), increases Ca2+ influx in the pancreata of transgenic mice expressing apoaequorin, a Ca2+-induced bioluminescent protein complex. NERP-4 enhances glucose-stimulated insulin secretion from isolated human and mouse islets and ß-cell-derived MIN6-K8 cells. NERP-4 administration reverses the impairment of ß-cell maintenance and function in db/db mice by enhancing mitochondrial function and reducing metabolic stress. NERP-4 acts on sodium-coupled neutral amino acid transporter 2 (SNAT2), thereby increasing glutamine, alanine, and proline uptake into ß cells and stimulating insulin secretion. SNAT2 deletion and inhibition abolish the protective effects of NERP-4 on ß-cell maintenance. These findings demonstrate a novel autocrine mechanism of ß-cell maintenance and function that is mediated by the peptide-amino acid transporter axis.

Improving Skin Carotenoid Levels in Young Students through Brief Dietary Education Using the Veggie Meter.

The antioxidant and anti-inflammatory effects of carotenoid have been determined to aid in the prevention of a wide range of oxidative disorders, arteriosclerosis, obesity, and various types of cancers. In order to keep high carotenoid levels in the body, much of the vegetable and fruit (V/F) intake is mandatory. However, the actual intake of V/F is not enough in many countries. The aim of this study was to assess whether brief dietary education using the Veggie Meter (VM) that could measure skin carotenoid (SC) levels could induce the increase in carotenoid levels via V/F intake. Two hundred and sixty-one elementary and junior high school students (ages 7−14 years old) received brief educational session and SC evaluation by VM, and the changes in SC levels were examined after 6 months. The baseline VM scores ranged from 131 to 825, and the average significantly increased from 400.0 ± 124.7 (standard deviation) to 447.4 ± 140.4 at Month 6 (p < 0.0001). The percentage of increase at month 6 was negatively correlated with the baseline values (r = −0.36, p < 0.0001). This finding implies that subjects who became aware of their inferiority tended to make a significant effort to change their behavior. The multivariate logistic regression analysis demonstrated that subjects taking much of green and yellow vegetables, drinking vegetable/tomato juice, and eating any fruit had higher VM scores than the average value. In conclusion, the educational approach using VM was supposed to be an effective method of raising awareness of the V/F shortage and increasing V/F intake that could indue the increase in SC levels.

Impact of the antimicrobial stewardship program on hospital-acquired candidemia.

Antibiotic stewardship programs reduce antibiotic use without negative clinical outcomes. However, epidemiological data describing the relationship between implementing antimicrobial stewardship and candidemia incidence are scarce. This study aimed to evaluate the effect of antibiotic stewardship on the incidence of hospital acquired candidemia. We conducted a retrospective study from April 2017 to September 2020. We reviewed patients that were treated with three broad-spectrum antipseudomonal agents: carbapenem, tazobactam/piperacillin, and cefepime. Monthly aggregated hospital antimicrobial consumption was measured as days of therapy (DOTs) per 1000 patient-days, and the monthly incidence of hospital acquired candidemia was recorded. The median monthly carbapenem-DOTs during pre-intervention and intervention were 28.4 and 10.0, respectively. Time-series analysis showed significant level changes after intervention: - 10.0 DOTs (p = 0.02). There was a downward trend in the monthly carbapenem-DOTs after intervention. The median hospital-acquired candidemia incidence was 0.17 and 0.08 per 1000 patient-days during pre-intervention and intervention periods, respectively. Time-series analysis showed a significant level change after intervention (- 0.16 per 1000 patient-days; p = 0.048). The trend in the incidence of hospital-acquired candidemia did not significantly change between pre-intervention and intervention. Decreased broad-spectrum antibiotic use (particularly carbapenem) by our antimicrobial stewardship term may reduce hospital-acquired candidemia incidences.

Significance of nuclear LOXL2 inhibition in fibroblasts and myofibroblasts in the fibrotic process of acute respiratory distress syndrome.

Fibrotic scarring is an important prognostic factor of acute respiratory distress syndrome (ARDS). There are currently no antifibrotic drugs or other therapeutic agents for ARDS. Lysyl oxidase-like 2 (LOXL2), an amine oxidase, contributes to fibrotic scarring by facilitating collagen cross-linking. Recent clinical trials revealed that a monoclonal inhibitory antibody against LOXL2 failed to show benefit over placebo in patients with fibrotic disorders involving the lungs. These clinical results raise the possibility that targeting the extracellular enzymic activity of LOXL2 is not in itself sufficient to prevent fibrotic scarring. We investigated the role of LOXL2 in the pathogenesis of ARDS in vivo, in vitro, and in samples from patients with ARDS. After lung injury, LOXL2 was unevenly expressed in the nuclei of lung fibroblasts and myofibroblasts in the fibrotic phase. Nuclear LOXL2 expression was upregulated in lung fibroblasts after transforming growth factor-beta1 (TGF-ß1)-treatment. LOXL2 silencing abrogated the TGF-ß1-induced expression of a myofibrogenic-progenitor marker, the appearance of proto-myofibroblasts, and the evolution of differentiated myofibroblasts in lung fibroblasts. Nuclear upregulation of Snail was evident in myofibroblasts during the fibrotic phase after lung injury. We detected high levels of LOXL2 protein in the lungs of ARDS patients, specifically during the proliferative and fibrotic phases. Our results highlight nuclear LOXL2 in fibroblasts as a primary causative driver of cell-fate decision toward myofibroblasts and of the progression of fibrotic scarring. A nuclear-LOXL2-targeted agent could be a promising therapeutic strategy against fibrotic disorders including ARDS.

Recombinant Mycobacterium bovis BCG prime-recombinant adenovirus boost vaccination in rhesus monkeys elicits robust polyfunctional simian immunodeficiency virus-specific T-cell responses.

While mycobacteria have been proposed as vaccine vectors because of their persistence and safety, little has been done systematically to optimize their immunogenicity in nonhuman primates. We successfully generated recombinant Mycobacterium bovis BCG (rBCG) expressing simian immunodeficiency virus (SIV) Gag and Pol as multigenic, nonintegrating vectors, but rBCG-expressing SIV Env was unstable. A dose and route determination study in rhesus monkeys revealed that intramuscular administration of rBCG was associated with local reactogenicity, whereas intravenous and intradermal administration of 10(6) to 10(8) CFU of rBCG was well tolerated. After single or repeat rBCG inoculations, monkeys developed high-frequency gamma interferon enzyme-linked immunospot responses against BCG purified protein derivative. However, the same animals developed only modest SIV-specific CD8(+) T-cell responses. Nevertheless, high-frequency SIV-specific cellular responses were observed in the rBCG-primed monkeys after boosting with recombinant adenovirus 5 (rAd5) expressing the SIV antigens. These cellular responses were of greater magnitude and more persistent than those generated after vaccination with rAd5 alone. The vaccine-elicited cellular responses were predominantly polyfunctional CD8(+) T cells. These findings support the further exploration of mycobacteria as priming vaccine vectors.

Estimation of trans fatty acid intake in Japanese adults using 16-day diet records based on a food composition database developed for the Japanese population.

BACKGROUND: The Standard Tables of Food Composition in Japan do not include information on trans fatty acids. Previous studies estimating trans fatty acid intake among Japanese have limitations regarding the databases utilized and diet assessment methodologies. We developed a comprehensive database of trans fatty acid food composition, and used this database to estimate intake among a Japanese population. METHODS: The database was developed using analytic values from the literature and nutrient analysis software encompassing foods in the US, as well as values estimated from recipes or nutrient compositions. We collected 16-day diet records from 225 adults aged 30 to 69 years living in 4 areas of Japan. Trans fatty acid intake was estimated based on the database and the 16-day diet records. RESULTS: Mean total fat and trans fatty acid intake was 56.9 g/day (27.7% total energy) and 1.7 g/day (0.8% total energy), respectively, for women and 66.8 g/day (25.5% total energy) and 1.7 g/day (0.7% total energy) for men. Trans fatty acid intake accounted for greater than 1% of total energy intake, which is the maximum recommended according to the World Health Organization, in 24.4% of women and 5.7% of men, and was particularly high among women living in urban areas and those aged 30-49 years. The largest contributors to trans fatty acid intake were confectionaries in women and fats and oils in men. CONCLUSIONS: Although mean trans fatty acid intake was below the maximum recommended intake of the World Health Organization, intake among subgroups was of concern. Further public health efforts to reduce trans fatty acid intake should be encouraged.