Clarifying differences in injury patterns between ground-level falls and falls from heights among the elderly in Japan.

OBJECTIVES: With the progress of aging, fall injuries have become a global public health issue. This research was conducted to describe in detail situations of injury occurrence among the elderly by distinguishing between falls from heights and ground-level falls. We assume that different fall mechanisms occur in different situations and result in a wide range of consequences. STUDY DESIGN: This is a registry-based descriptive study. METHODS: The analysis included 55,126 patients with fall injuries, aged 65 years and more, having an Injury Severity Score (ISS) ≧9, and registered in a trauma registry in Japan between 2004 and 2015. We described patients' distribution in terms of age, severity, outcome, season, time, and injured body parts by gender and fall mechanisms. RESULTS: Falls from heights (n = 15,748) were more common among men and those younger than 75 years. Ground-level falls (n = 39,378) were more common among women and those older than 75 years. The ISS was high in men and for those who fell from heights. Falls from heights were common in autumn, whereas ground-level falls were common in winter. Both mechanisms occurred frequently during the daytime. The head and lower extremities were the most commonly injured parts for those who fell from heights and ground-level falls, respectively. Injuries to the head, chest, spine, upper extremities, and pelvis were common among those who fell from heights. Injuries to the lower extremities were common in ground-level fallers. Among those who fell from heights, women had more frequent lower extremity injuries than did men. Among ground-level fallers, men had more frequent head injuries than did women. The highest case-fatality rate was recorded for abdominal injuries among those who fell from heights and head injuries among ground-level fallers. In both mechanisms of injury, the case-fatality rate of limbs was the lowest. CONCLUSIONS: Our study showed different patterns between falls from heights and ground-level falls, whereas previous studies rarely distinguished between these two fall mechanisms.

IκBNS induces Muc5ac expression in epithelial cells and causes airway hyper-responsiveness in murine asthma models.

BACKGROUND: In allergic asthma, environmental allergens including house dust mite (HDM) trigger pattern recognition receptors and activate downstream signaling pathways including NF-κB pathways not only in immune cells but also in airway epithelial cells. Recent studies have shown that NF-κB activation is regulated positively or negatively depending on the cellular context by IκBNS (encoded by the gene Nfkbid), one of atypical IκB proteins, in the nucleus. Therefore, we hypothesized that IκBNS expressed in immune cells or epithelial cells is involved in the regulation of asthmatic responses. AIM: To determine the roles of IκBNS in HDM-induced asthmatic responses. METHODS: Roles of IκBNS in HDM-induced airway inflammation and airway hyper-responsiveness (AHR) were examined by using IκBNS-deficient (Nfkbid-/- ) mice. Roles of IκBNS expressed in hematopoietic cells and nonhematopoietic cells were separately evaluated by bone marrow chimeric mice. Roles of IκBNS expressed in murine tracheal epithelial cells (mTECs) were examined by air-liquid interface culture. RESULTS: House dust mite-induced airway inflammation and AHR were exacerbated in mice lacking IκBNS in hematopoietic cells. In contrast, HDM-induced airway inflammation was exacerbated, but AHR was attenuated in mice lacking IκBNS in nonhematopoietic cells. The induction of Muc5ac, a representative mucin in asthmatic airways, was reduced in Nfkbid-/- mTEC, whereas the induction of Spdef, a master regulator of goblet cell metaplasia, was not impaired in Nfkbid-/- mTEC. Moreover, IκBNS bound to and activated the MUC5AC distal promoter in epithelial cells. CONCLUSION: IκBNS is involved in inducing Muc5ac expression in lung epithelial cells and causing AHR in HDM-induced asthma models.

Iron translocation in Pleurotus ostreatus basidiocarps: production, bioavailability, and antioxidant activity.

Translocation of minerals from substrate to mushrooms can change the medicinal characteristics, commercial value, and biological efficiency of mushroom. In the present study, we demonstrated that addition of iron to the substrate reduces the yield of Pleurotus ostreatus mushroom. The biological efficiency of the mushroom varied from 36.53% on the unsupplemented substrate to 2.08% for the substrate with 500 mg/kg iron added. The maximum iron concentration obtained for mushroom was 478.66 mg/kg (dry basis) and the maximum solubility in vitro was 293.70 mg/kg (dry basis). Iron translocation increased the ash and protein content, reduced antioxidant activity, and enhanced the aroma and flavor characteristics of the mushroom. However mushroom has higher amounts of iron than vegetables like collard greens, it is not feasible to use mushrooms as the only dietary source of iron. The study also indicated that because of more bioaccumulation of iron in mycelium than in the mushroom, mycelium and not mushroom, could be a better alternative as a non-animal iron source.

Thermal-work strain in law enforcement personnel during chemical, biological, radiological, and nuclear (CBRN) training.

BACKGROUND: Thermal safety standards for the use of chemical, biological, radiological, and nuclear (CBRN) ensembles have been established for various US occupations, but not for law enforcement personnel. OBJECTIVES: We examined thermal strain levels of 30 male US law enforcement personnel who participated in CBRN field training in Arizona, Florida, and Massachusetts. METHODS: Physiological responses were examined using unobtrusive heart rate (HR) monitors and a simple thermoregulatory model to predict core temperature (Tc) using HR and environment. RESULTS: Thermal strain levels varied by environments, activity levels, and type of CBRN ensemble. Arizona and Florida volunteers working in hot-dry and hot-humid environment indicated high heat strain (predicted max Tc>38·5°C). The cool environment of Massachusetts reduced thermal strain although thermal strains were occasionally moderate. CONCLUSIONS: The non-invasive method of using physiological monitoring and thermoregulatory modeling could improve law enforcement mission to reduce the risk of heat illness or injury.

Different contributions of internal reviewers and external experts to labelling decisions on therapeutic indications in new drug reviews in Japan.

WHAT IS KNOWN AND OBJECTIVE: External experts play an important role in shaping regulatory decisions in the new drug review process in the United States, Europe and Japan. No rigorous study has been performed addressing how and to what extent external experts, in contrast to internal reviewers in the agency, influence the regulatory decisions during new drug reviews. We examined their contributions in Japanese regulatory reviews in contrast to the internal reviewers, focusing on the labelling decision on therapeutic indications. METHODS: With the data set of 219 new molecular entities (NMEs) approved in Japan from 2000 to 2009, we observed how proposed indications in labelling were modified in a stepwise manner during the review process and conducted multinomial logistic analysis to examine the possible mechanism behind. RESULTS AND DISCUSSION: We found that interim assessment of indications by the internal reviewers was modified substantially by the influence of the external experts in about 20% of the 219 NMEs. Our analysis suggested that internal reviewers provided their opinion mainly based on strict review discipline, whereas external experts added flexibility and reality to their reviews. Our analysis revealed different evaluations between internal reviewers and external experts during regulatory discussions in new drug reviews and how the external panel contributes to changing internal decisions. WHAT IS NEW AND CONCLUSION: This study provides a new and quantitative approach to better label setting by emphasizing the contributions of each stakeholder in new drug reviews, which would improve the efficiency, quality and transparency of new drug reviews to enhance public health.

S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial.

BACKGROUND: The ACTS-CC 02 trial demonstrated that S-1 plus oxaliplatin (SOX) was not superior to tegafur-uracil and leucovorin (UFT/LV) in terms of disease-free survival (DFS) as adjuvant chemotherapy for high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). We now report the final overall survival (OS) and subgroup analysis according to the pathological stage (TNM 7th edition) for treatment efficacy. PATIENTS AND METHODS: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, five cycles) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80 mg/m2/day of S-1 on days 1-14, every 21 days, eight cycles). The primary endpoint was DFS and the patients' data were updated in February 2020. RESULTS: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the final analysis. With a median follow-up time of 74.3 months, the 5-year DFS rate was 55.2% in the UFT/LV group and 58.1% in the SOX group [stratified hazard ratio (HR) 0.92; 95% confidence interval (CI) 0.76-1.11; P = 0.3973], and the 5-year OS rates were 78.3% and 79.1%, respectively (stratified HR 0.97; 95% CI 0.76-1.24; P = 0.8175). In the subgroup analysis, the 5-year OS rates in patients with T4N2b disease were 51.0% and 64.1% in the UFT/LV and SOX groups, respectively (HR 0.72; 95% CI 0.40-1.31). CONCLUSION: Our final analysis reconfirmed that SOX as adjuvant chemotherapy is not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer. The 5-year OS rate was similar in the UFT/LV and SOX groups.

Plasma resistin concentration determined by common variants in the resistin gene and associated with metabolic traits in an aged Japanese population.

AIMS/HYPOTHESIS: Resistin is a cytokine derived from adipose tissue and is implicated in obesity-related insulin resistance and type 2 diabetes mellitus. Polymorphisms of the resistin gene (RETN) have been shown to affect the plasma resistin concentration. The aims of this study were to identify polymorphisms of RETN that influence plasma resistin concentration and to clarify the relation between plasma resistin level and metabolic disorders in an aged Japanese cohort. METHODS: The study participants comprised 3133 individuals recruited to a population-based prospective cohort study (KING study). Plasma resistin concentration, BMI, abdominal circumference, blood pressure, fasting plasma glucose and serum insulin concentrations, HbA(1c) content and serum lipid profile were measured in all participants. The HOMA index of insulin resistance (HOMA-IR) was also calculated. Eleven polymorphisms of RETN were genotyped. RESULTS: A combination of ANOVA and multiple linear regression analysis in screening and large-scale subsets of the study population revealed that plasma resistin concentration was significantly associated with rs34861192 and rs3745368 polymorphisms of RETN. Multiple linear regression analysis with adjustment for age and sex also showed that the plasma resistin level was significantly associated with serum concentrations of HDL-cholesterol, triacylglycerol and insulin, as well as with BMI. CONCLUSIONS/INTERPRETATION: Our results implicate the rs34861192 and rs3745368 polymorphisms of RETN as robust and independent determinants of plasma resistin concentration in the study population. In addition, plasma resistin level was associated with dyslipidaemia, serum insulin concentration and obesity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00262691.

Involvement of adhesion molecule in in vitro plaque-like formation of macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide.

BACKGROUND AND OBJECTIVE: Inflammatory agents, such as lipopolysaccharide (LPS), in periodontal pockets may promote atherogenesis by activating leukocytes. In our previous study, we developed a microchannel chip to observe the cell adhesion process in a fluid system. The objective of this investigation was to examine the mechanism by which periodontopathic bacterial LPS enhances plaque-like formation on a microchannel chip. MATERIAL AND METHODS: To evaluate the effect of Aggregatibacter actinomycetemcomitans LPS on the expression of adhesion molecules, e.g. intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen 1 (LFA-1) and L-selectin, on the surface of murine macrophage RAW264.7 cells, the expression of each adhesion molecule was examined by flow cytometry and western blot analysis. Moreover, a flow test on the microchannel chip involving anti-adhesion molecule antibodies was conducted to clarify which adhesion molecule is related to plaque-like formation of RAW264.7 cells. RESULTS: The expressions of ICAM-1 and LFA-1 on the surface of RAW 264.7 cells increased following 12 h culture with LPS; L-selectin expression was unaffected. An increase in ICAM-1 expression was also confirmed by western blot analysis. The flow test revealed that anti-ICAM-1 antibody inhibited plaque-like formation of LPS-stimulated macrophages on the micropillars of the microchannel chip. CONCLUSION: These findings indicate that ICAM-1 plays an important role in plaque-like formation of LPS-stimulated macrophages. Our microchannel chip is a suitable tool for the investigation of etiological factors of atherosclerosis, including periodontitis, in vitro.

The G1 cell cycle arrest of macrophages infected with Aggregatibacter actinomycetemcomitans.

OBJECTIVES: Infection of murine macrophage cell line J774.1 with the periodontopathic bacterium Aggregatibacter actinomycetemcomitans induces apoptotic cell death. The infection induces cell cycle arrest in the G1 phase prior to the appearance of apoptotic cells. This study determined the involvement of various cell cycle-related signal molecules in A. actinomycetemcomitans-induced G1 cell cycle arrest. MATERIALS AND METHODS: Cell cycle in J774.1 cells infected with A. actinomycetemcomitans was analyzed with a flow cytometer. Immunoblot analysis was also employed to determine the expression levels of intracellular signal molecules. RESULTS: Flow cytometric analysis revealed that the percentage of cells in the G1 phase increased to 77.2% at 12 h after A. actinomycetemcomitans infection. Additionally, according to immunoblot analysis, expression levels of hyperphosphorylated forms of retinoblastoma protein (ppRb) declined in J774.1 cells following A. actinomycetemcomitans infection, whereas hypophosphorylated Rb (pRb) expression levels were elevated slightly. Expression levels of cyclin D1 and D2 in the cells decreased gradually postinfection; CDK2, CDK4, CDK6 and cyclin E levels were not changed. Furthermore, postinfection, p21(CIP1/WAF1) expression increased at 6 h, followed by a subsequent decrease. CONCLUSION: These findings suggest that cyclin D1 and D2 and p21(CIP1/WAF1) participate in G1 cell cycle arrest in A. actinomycetemcomitans-infected J774.1 cells.

Establishment of a strain inheriting a sex-linked SNP marker in Patagonian pejerrey (Odontesthes hatcheri), a species with both genotypic and temperature-dependent sex determination.

The Patagonian pejerrey Odontesthes hatcheri is an atherinopsid species presenting genotypic sex determination (GSD) at intermediate temperatures and temperature-dependent sex determination at the low and high ranges of thermal tolerance. A recent study revealed the presence of a sex-linked SNP marker in some males of this species, but a strain which inherits the marker faithfully has not been established. This research was conducted to develop such a strain, for use as a tool to study the molecular mechanisms of gonadal sex differentiation and sexual dimorphism, and to obtain basic information on the GSD mode in this species. For these purposes, we performed backcrosses and full-sibling crosses using males and females whose presumptive genotypic sex was inferred from the presence of the sex-linked SNP marker. Four backcrosses between SNP(-) daughters and their SNP(+) father generated balanced sex ratios with the phenotypic sex matching the genotypic sex in most cases (98.21%) at an intermediate, sexually neutral temperature (21 degrees C). Full-sibling crosses between these four SNP(-) females and their SNP(+) brothers produced three progenies with balanced sex ratios and one with 94.4% males. The results of this study confirm that a strain inheriting the sex-linked SNP marker was successfully developed. Moreover, the inheritance pattern of the marker and the sex ratios of the progenies provide strong evidence that the GSD mode in O. hatcheri is the XX-XY system.

Transnasal inferior meatal antrostomy with a mucosal flap for post-Caldwell-Luc mucoceles in the maxillary sinus.

OBJECTIVE: Transnasal inferior meatal antrostomy is increasingly used for the treatment of post-Caldwell-Luc mucoceles in maxillary sinus. This study aimed to report the outcomes after inferior meatal antrostomy with a mucosal flap for recurrent mucoceles. METHOD: The records of patients who had undergone transnasal inferior meatal antrostomy with or without a mucosal flap were reviewed. RESULTS: Transnasal endoscopic inferior meatal antrostomy with or without a mucosal flap was performed in 21 and 49 patients, respectively. No complications were observed. A closing of the antrostomy was found in 9 (18.4 per cent) of the 49 patients who underwent antrostomy without a mucosal flap. No closings were observed in the 21 patients who underwent antrostomy with a mucosal flap. There was a significant difference in the rate of closing for surgery with and without the mucosal flap. CONCLUSION: Transnasal endoscopic inferior meatal antrostomy with a mucosal flap is a safe method for the treatment of post-Caldwell-Luc maxillary mucoceles that effectively prevents recurrence.

The effects of resection of the peripheral branches of the posterior nasal nerves in the inferior turbinate, with special focus on olfactory dysfunction.

OBJECTIVE: There are few detailed studies about peripheral branch resection of the posterior nasal nerves in the inferior turbinate; thus, this study aimed to investigate this. METHODS: Patients who underwent submucosal turbinoplasty with or without resection of the peripheral branches of posterior nasal nerves in the inferior turbinate were included. RESULTS: The resection of the posterior nasal nerves with turbinoplasty significantly reduced detection and recognition thresholds on olfactory testing. The rhinorrhoea severity, detection threshold and recognition threshold were significantly lower after resection of the posterior nasal nerves with turbinoplasty than after turbinoplasty alone, although there were no significant differences between the two groups before surgery. CONCLUSION: This is the first study to show that the resection of the peripheral branches of the posterior nasal nerves in the inferior turbinate with turbinoplasty more effectively inhibits allergic symptoms compared with turbinoplasty alone. It also showed that the resection of the peripheral branches of the posterior nasal nerves can inhibit olfactory dysfunction.

Sinonasal organised haematoma: clinical features and successful application of modified transnasal endoscopic medial maxillectomy.

OBJECTIVE: Although organised haematoma often induces bone thinning and destruction similar to malignant diseases, the aetiology of organised haematoma and the optimal treatment remain unclear. This paper presents the clinical features of individuals with organised haematoma, and describes cases in which a novel modified approach was successfully applied for resection of organised haematoma in the maxillary sinus. METHOD: Pre-operative examination data were evaluated retrospectively. Modified transnasal endoscopic medial maxillectomy was employed. RESULTS: Fourteen patients with organised haematoma were treated. Contrast-enhanced computed tomography showed heterogeneous enhancement in all patients. Eight patients underwent modified transnasal endoscopic medial maxillectomy, without complications such as facial numbness, tooth numbness, facial tingling, lacrimation and eye discharge. Dissection of the apertura piriformis and anterior maxillary wall was not necessary for any of these eight patients. No recurrence was observed. CONCLUSION: Pre-operative examinations can be helpful in determining the likelihood of organised haematoma. Modified transnasal endoscopic medial maxillectomy appears to be a safe and effective method for organised haematoma resection.

Pilocarpine-induced salivation and thirst in conscious rats.

The muscarinic receptor agonist pilocarpine is widely used as a sialogogue. It has been well-established that it also induces water intake in animals. However, the mechanisms underlying the relationships between these events are unknown. To address this problem, we examined water intake and parotid salivary secretion in conscious rats. Intraperitoneally injected pilocarpine increased both water intake and salivary secretion. Intracerebroventricularly injected pilocarpine also induced water intake, but not salivary secretion. Intracerebroventricularly applied atropine, a muscarinic receptor antagonist, suppressed the water intake produced by pilocarpine applied intraperitoneally and intracerebroventricularly. However, it did not affect the salivary secretion induced by pilocarpine applied peripherally. We conclude that peripherally applied pilocarpine affects the parotid glands and the thirst center in the central nervous system, while it may induce salivary secretion mainly via peripheral responses, but water intake mainly via the central nervous system.

Gender difference in unstimulated whole saliva flow rate and salivary gland sizes.

OBJECTIVE: A gender difference in the unstimulated whole saliva flow rate (UWSFR) may be due to a difference in the sizes of the salivary glands. In this study, we investigated the relationships among the UWSFR, gland sizes and body sizes of healthy young adult males and females. DESIGN: Unstimulated whole saliva was collected for 5 min by the spitting method in 50 healthy young adults, and the flow rate of the saliva was measured. Heights and weights were measured, and body mass indices (BMI) were calculated. The sizes of the salivary glands were measured by use of a magnetic resonance imaging technique. RESULTS: Parotid and submandibular gland sizes and flow rates in females were significantly smaller than those in males, as were also the weights, heights and BMI. In both males and females, there were significant positive correlations between gland sizes and the flow rates, weights and BMI. The variations of the flow rates were reduced by standardizing them with gland sizes, weights and BMI. CONCLUSIONS: These results suggest that the lower UWSFR in females as compared with males is due to the smaller gland sizes due to the smaller body sizes.

Surface glycopeptide change triggered by contact between normal cells from rat liver and their simian virus 40-transformed cells from the same virus.

Surface glycopeptide changes triggered by mixed culture of normal cells from rat liver cell line WIRL-3 and simian virus 40-transformed cells from the same line were studied. In addition, biologic responses of the normal cells and the transformed cells to three kinds of surface glycopeptides derived from the normal cells, the transformed cells, and these cells in mixed culture were investigated. Surface glycopeptide derived from the mixed culture showed a quantitative increase and a qualitative change in the glycopeptide structure, not detected in the surface glycopeptide of normal cells and transformed cells cultured separately. The surface glycopeptide changes observed in the mixed culture were mainly ascribable to normal cells responding to transformed cells, and a surface glycopeptide change in normal cells induced a qualitative surface glycopeptide change in transformed cells. Differences in biologic response of normal cells and transformed cells to the above three surface glycopeptides were investigated with the use of inhibition of [3H]thymidine uptake of the cells by the three different surface glycopeptide preparations. The inhibition rates of uptake in normal cells were 30% by all three surface glycopeptides (200 microgram/ml culture medium); inhibition rates in transformed cells were 65% by mixed-culture surface glycopeptide, 50% by normal cell-surface glycopeptide, and 35% by transformed cell-surface glycopeptide.

Structural and immunological relationships of isoferritins in normal and malignant cells.

Ferritins from normal adult human liver and heart were compared with ferritins from a lung carcinoma metastatic to liver and from HeLa cells on the basis of their isoferritin profiles, subunit composition, and immunological relationships. Each ferritin preparation gave different isoferritin profiles, but several contained common isoferritins. All of the tumor isoferritins had counterparts in the normal tissues. All ferritins contained similar subunits but in different proportions. Qualitative differences were demonstrable in some ferritins with antibodies to different tissue ferritins. These differences correlated with the subunit composition of the ferritins. By appropriate absorption, an antibody population was obtained that was apparently specific for one subunit type. Heart ferritin gave lines of apparent identity with the tumor ferritins with these antibodies. It is concluded that tumor ferritins are not tumor-specific antigens but correspond to isoferritins in normal adult heart.

Multiple hormone receptors in the adenylate cyclase of human adrenocortical tumors.

Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals. The adenylate cyclase of two normal adrenals was activated only by ACTH and PGE1 among the hormones tested, while that of two hyperplastic adrenal tissues due to excessive pituitary ACTH secretion was stimulated only by ACTH. Of five ACTH-responsive adrenocortical adenomas, in contrast, three were stimulated by norepinephrine, two by epinephrine, one by thyroid-stimulating hormone, and one by luteinizing hormone in addition to ACTH, indicating the presence of multiple receptors for hormones other than ACTH and PGE1 in these four tumors. The cyclase of an ACTH-unresponsive adrenocortical carcinoma ws activated only by PGE1 and not by other hormones including ACTH, whereas that of an ACTH-responsive adrenocortical nodular hyperplasia was stimulated by ACTH and glucagon but not by other hormones including PGE1. These results indicate the presence of multiple receptors for hormones other than ACTH and PGE1, the normal adrenocortical stimulants, in human adrenocortical tumors, particularly in adrenal adenomas, but not in normal and hyperplastic (of whichever an etiology) adrenocortical tissues, suggesting a functional alteration of the cellular membrane receptors in human adrenocortical tumors.

Development of a new tracer-encapsulated solid pellet injection system for more precise control of tracer-impurity-deposit location in LHD.

A new tracer-encapsulated solid pellet (TESPEL) injection system has been developed additionally for the LHD heliotron. This system has three-dimensionally bended guide tubes, which allows us to inject the TESPEL obliquely on a poloidal cross-section of the LHD plasma. Consequently, this system enables us to control a tracer-impurity-deposited location more precisely. Moreover, this system can make it possible for the tracer impurity to be deposited even only inside the ergodic region (outside a last closed flux surface of the LHD plasma). A stereoscopic fast camera system has been also developed for capturing a three-dimensional TESPEL trajectory.