Potentiation of Methylmercury-Induced Death in Rat Cerebellar Granular Neurons Occurs by Further Decrease of Total Intracellular GSH with BDNF via TrkB in Vitro.

Brain-derived neurotrophic factor (BDNF) is a principal factor for neurogenesis, neurodevelopment and neural survival through a BDNF receptor, tropomyosin-related kinase (Trk) B, while BDNF can also cause a decrease in the intracellular glutathione (GSH) level. We investigated the exacerbation of methylmercury-induced death of rat cerebellar granular neurons (CGNs) by BDNF in vitro. Since methylmercury can decrease intracellular GSH levels, we hypothesized that a further decrease of the intracellular GSH level is involved in the process of the exacerbation of neuronal cell death. In the present study, we established that in CGN culture, a decrease of the intracellular GSH level was further potentiated with BDNF in the process of the methylmercury-induced neuronal death and also in GSH reducer-induced neuronal death. BDNF treatment promoted the decrease in GSH levels induced by methylmercury and also by L-buthionine sulfoximine (BSO) and diethyl maleate (DEM). The promoting effect of BDNF was observed in a TrkB-vector transformant of the rat neuroblastoma B35 cell line but not in the mock-vector transformant. These results indicate that the exacerbating effect of BDNF on methylmercury-induced neuronal death in cultures of CGNs includes a further decrease of intracellular GSH levels, for which TrkB is essential.

Exploring nurses' clinical judgment concerning the relative importance of fall risk factors: A mixed method approach using the Q Methodology.

BACKGROUND: Nurses are pivotal in averting patient falls through their assessment of cues presented by patients and their environments, rendering clinical judgments regarding the risk of falling, and implementing tailored interventions. Despite the intricate cognitive processes entailed in nurses' judgment, no prior studies have explored their approach to assessing the risk of falling. OBJECTIVE: This study aimed to examine how nurses judge the risk of falling among patients with different conditions, whether there are differences in the importance of risk factors as judged by nurses, how they justify their judgments, and what attributes of the nurses influence their judgments. DESIGN: A mixed method approach using the Q Methodology was employed. SETTING(S): Three public and private hospitals in Japan. PARTICIPANTS: Eighteen nurses participated in the study. METHODS: Participants were tasked with ranking 36 patient scenarios, each featuring a distinct set of fall risk factors. Subsequently, post-sorting interviews were conducted to gather insights into their typical approach to assessing fall risk and the rationale behind their ranking decisions. A by-person principal component factor extraction was employed to examine differences in the rankings of the scenarios. The interview data were analyzed descriptively to elucidate the reasons behind these discrepancies. RESULTS: Nurses engage in complex cognitive manipulations when evaluating the risk of patient falls, drawing extensively from their wealth of experience while utilizing assessment tools to support their judgments. In essence, nurses identify patients' tendency to act alone without calling a nurse, impaired gait and cognition, sedative use, drains, and limited information sharing among healthcare professionals as key fall risks. In addition, nurses vary in the importance they attribute to certain risk factors, leading to the discrimination of three distinct judgment profiles. One group of nurses judges patients with cognitive impairment and acting alone as high risk. Another group of nurses considers patients with unstable gait and acting alone as high risk. The last group of nurses sees patients wearing slippers as high risk. The post-sorting interviews revealed that their judgments are closely related to the healthcare context and patient population. CONCLUSIONS: Nurses operate within diverse contexts, wherein they interact with patients of varying characteristics, collaborate with professionals from diverse disciplines, and have access to varying levels of human and physical resources. This nuanced understanding empowers the formulation of judgments that are finely attuned to the specific context at hand. STUDY REGISTRATION: Not registered.

Spinal curvature and characteristics of postural change in pregnant women.

OBJECTIVE: Pregnant women often report complaints due to physiological and postural changes. Postural changes during pregnancy may cause low back pain and pelvic girdle pain. This study aimed to compare the characteristics of postural changes in pregnant compared with non-pregnant women. DESIGN: Prospective case-control study. SETTING: Pregnancy care center. POPULATION: Fifteen women at 17-34 weeks pregnancy comprised the study group, while 10 non-pregnant female volunteers comprised the control group. METHODS: Standing posture was evaluated in the sagittal plane with static digital pictures. Two angles were measured by image analysis software: (1) between the trunk and pelvis; and (2) between the trunk and lower extremity. Spinal curvature was measured with Spinal Mouse® to calculate the means of sacral inclination, thoracic and lumbar curvature and inclination. MAIN OUTCOME MEASURES: The principal components were calculated until eigenvalues surpassed 1. RESULTS: Three distinct factors with eigenvalues of 1.00-2.49 were identified, consistent with lumbosacral spinal curvature and inclination, thoracic spine curvature, and inclination of the body. These factors accounted for 77.2% of the total variance in posture variables. Eleven pregnant women showed postural characteristics of lumbar kyphosis and sacral posterior inclination. Body inclination showed a variety of patterns compared with those in healthy women. CONCLUSIONS: Spinal curvature demonstrated a tendency for lumbar kyphosis in pregnant women. Pregnancy may cause changes in spinal curvature and posture, which may in turn lead to relevant symptoms. Our data provide a basis for investigating the effects of spinal curvature and postural changes on symptoms during pregnancy.

Vitamin K has the potential to protect neurons from methylmercury-induced cell death in vitro.

Vitamin K (VK) has a protective effect on neural cells. Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro. Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury. To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1); menaquinone-4, vitamin K(2) ) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups. As expected, VKs inhibited the death of the primary cultured neurons. It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH). Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study. Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells. Treatment with VKs affected BSO- and DEM-induced cell death in both cultures. On the other hand, the intracellular GSH assay showed that VK(2), menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments. These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels. The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion.

Relationship between the degree of endolymphatic hydrops and electrocochleography.

The purpose of this study was to evaluate the relationship between the endolymphatic space image obtained using magnetic resonance imaging (MRI) and the results of electrocochleography. Electrocochleography recordings were obtained from 25 ears of 24 patients, who underwent MRI 1 day after the intratympanic injection of gadolinium diethylenetriamine pentaacetic acid bismethylamide. The average summating potential to action potential (SP/AP) ratio in patients with significant endolymphatic hydrops in the cochlea was 54 +/- 17%. However, in some patients who had significant endolymphatic hydrops in the cochlea, the SP/AP ratio was not enlarged. This may imply that elevation of the SP/AP ratio is related to not only the degree of endolymphatic hydrops but also to the persistence of hydrops.

Corticosterone synthesis inhibitor-induced decrease in the age-dependant expression of nitric oxide synthase 3 in the preterm ductus arteriosus of rats.

Previous studies have shown that the dilating effect of nitric oxide (NO) on the fetal ductus arteriosus (DA) is age dependent and more marked in the premature stages in rats, but the factors that mediate this effect are poorly understood. The purpose of this study is to determine the changes in the expression of NO synthase (NOS) mRNA in the fetal DA and to examine the effect of an 11-beta-hydroxylase inhibitor of corticosterone synthesis, namely, metyrapone, on NOS expression. NOS 3 mRNA expression was observed in 17.5-day-old rat fetuses; thereafter, its level significantly increased and reached its peak on day 19.5 and then decreased until the end of the gestation period (day 21.5). To inhibit corticosterone synthesis, a constant infusion of metyrapone was administered to rats; this significantly decreased the fetal plasma corticosterone concentration as well as NOS 3 mRNA expression in the DA in a time-dependent manner. These results indicate that NO is generated by NOS 3 in the DA and that the age-dependant expression of NOS 3 in the premature DA is attributable to corticosterone-associated activity.

Gestational changes in production of NO and expression of NOS mRNA isoforms in the rat placenta.

To monitor changes in NO production over time in the fetal placenta of rats, we used electron paramagnetic resonance spectroscopy with the Fe-N-(dithiocarboxy) sarcosine (Fe-DTCS) complex as an NO-trapping reagent. The expression of nitric oxide synthase (NOS) isoforms was examined in parallel using quantitative RT-PCR. NO production was first detected on day 13.5 of gestation. NO levels reached a peak on day 15.5, then decreased significantly during the last few days of gestation. The pattern of expression of NOS II mRNA was in good agreement with changes in NO levels, whereas NOS III mRNA expression did not change markedly during gestation. Thus, it appears that NO levels in the placenta are NOS II-dependent and differ at different gestational stages.

Effects of maternal exposure to diethylstilbestrol on epididymal development in rat offspring.

In our previous study, prenatal diethylstilbestrol (DES) exposure (days 7-21 of gestation) suppressed plasma testosterone levels and histological development in the epididymis of rat offspring. In this study, we measured cell proliferation in epididymal ductules and the expression of steroid hormone receptors and 5alpha-reductase 1 in the epididymis to assess the effect of DES on epididymal development in the offspring. Prenatal DES exposure did not alter the cell division index, but suppressed the expression of androgen receptor mRNA at 15 weeks after birth, and stimulated estrogen receptor alpha mRNA at 6 weeks. These results suggest that prenatal DES exposure results in the retardation of epididymal tissue maturation by disruption of the postnatal expression of steroid hormone receptors.

Involvement of independent mechanism upon poly(ADP-ribose) polymerase (PARP) activation in methylmercury cytotoxicity in rat cerebellar granule cell culture.

Poly(ADP-ribose) polymerase (PARP) activation plays a role in repairing injured DNA, while its overactivation is involved in various diseases, including neuronal degradation. In the present study, we investigated the use of a PARP inhibitor, 3,4-dihydro-5-[4-(1-piperidinyl)butoxy]-1(2H)-isoquinolinone (DPQ), whether methylmercury-induced cell death in the primary culture of cerebellar granule cells involved PARP activation. DPQ decreased the methylmercury-induced cell death in a dose-dependent manner. Unexpectedly, this protective effect was DPQ specific; none of the other PARP inhibitors--1,5-dihydroxyisoquinoline, 3-aminobenzamide, or PJ34--affected neuronal cell death. Methylmercury-induced cell death involves the decrease of glutathione (GSH) and production of reactive oxygen species. Therefore, to understand the mechanism by which DPQ inhibits cytotoxicity, we first studied the effect of DPQ on buthionine sulfoximine- or diethyl maleate-induced death of primary cultured cells and human neuroblastoma IMR-32 cells, both of which are mediated by GSH depletion. DPQ inhibited the cell death of both cultured cells, but it did not restore the decrease of cellular GSH by buthionine sulfoximine to the control level. Second, we evaluated the antioxidant activity of PARP inhibitors by methods with ABTS (2-2'-azinobis(3-ethylbenzothiazoline 6-sulfonate) or DPPH (1,1-diphenyl-2-picrylhydrazyl) used as a radical because antioxidants also efficiently suppress methylmercury-induced cell death. The antioxidant activity of DPQ was the lowest among the tested PARP inhibitors. Taken together, our results indicate that DPQ effectively protects cells against methylmercury- and GSH depletion-induced death. Furthermore, they suggest that DPQ exerts its protective effect through a mechanism other than PARP inhibition and direct antioxidation, and that PARP activation is not involved in methylmercury-induced neuronal cell death.

Developmental toxicity of indium: embryotoxicity and teratogenicity in experimental animals.

Indium, a precious metal classified in group 13 (IIIB) in the periodic table, has been used increasingly in the semiconductor industry. Because indium is a rare metal, technology for indium recycling from transparent conducting films for liquid crystal displays is desired, and its safety evaluation is becoming increasingly necessary. The developmental toxicity of indium in experimental animals was summarized. The intravenous or oral administration of indium to pregnant animals causes growth inhibition and the death of embryos in hamsters, rats, and mice. The intravenous administration of indium to pregnant animals causes embryonic or fetal malformation, mainly involving digit and tail deformities, in hamsters and rats. The oral administration of indium also induces fetal malformation in rats and rabbits, but requires higher doses. No teratogenicity has been observed in mice. Caudal hypoplasia, probably due to excessive cell loss by increased apoptosis in the tailbud, in the early postimplantation stage was considered to account for indium-induced tail malformation as a possible pathogenetic mechanism. Findings from in vitro experiments indicated that the embryotoxicity of indium could have direct effects on the conceptuses. Toxicokinetic studies showed that the embryonic exposure concentration was more critical than the exposure time regarding the embryotoxicity of indium. It is considered from these findings that the risk of the developmental toxicity of indium in humans is low, unless an accidentally high level of exposure or unknown toxic interaction occurs because of possible human exposure routes and levels (i.e. oral, very low-level exposure).

The factors related to self-other agreement/disagreement in nursing competence assessment: Comparative and correlational study.

BACKGROUND: While assessment made by nurses of themselves (self-assessment) and assessment made of them by others (other-assessment) provide unique and valuable information as to individual nurses' competence, the subjective nature of both assessments often causes a disagreement between them. This is problematic when educational interventions to foster nurses' competence are designed. However, the question of what factors contribute to the self-other disagreement in competence assessment has rarely been investigated in nursing. OBJECTIVES: The aims of this study were to compare competence assessments made by nurses with that by others, and to investigate what types of demographic variables of nurses and others, and which personality traits of nurses were associated with the self-other agreement/disagreement in the competence assessment. DESIGN: A cross-sectional survey design. SETTINGS: Three hospitals in Japan. PARTICIPANTS: A total of 1167 registered nurses, who were practising in these three hospitals, were invited to participate in the study. The inclusion criteria of the participants were as follows: 1) currently working in an inpatient department, and 2) directly involved in patient care. METHODS: The survey package included two sets of questionnaires: one for self-assessment and the other for other-assessment, each of which was accompanied by an ID number for matching. Collected data were analysed using a Wilcoxon signed-rank test to compare the scores on competence assessed by nurses and others, and using multiple regression to examine the relationships between the demographics, personality traits, and the degree of self-other disagreement. RESULTS: A total of 207 matched questionnaires were obtained. The results showed that the scores on the assessment made by others were statistically significantly higher than those made by nurses of themselves. Moreover, regression analysis suggested that the age of nurses (i.e., younger nurses) and that of others (i.e., older evaluators), and nurses' personality traits of conscientiousness and extraversion were statistically significantly related to the agreement in self-other competence assessment. CONCLUSIONS: Nurse managers need to understand which factors contribute to self-other disagreement in competence assessment, and to identify a way to precipitate mutual agreement between them. By doing so, both nurses and managers can comprehend nurses' own strengths and weaknesses, and can determine educational needs and goals regarding nurses' competence development.

Effects of nurses' personality traits and their environmental characteristics on their workplace learning and nursing competence.

AIM: A good fit between an individual's personality traits and job characteristics motivates employees, and thus enhances their work behavior. However, how nurses' personality traits and their environmental characteristics relate to nurses' engagement in workplace learning, which improves their competence, has not been investigated. The aim of this study was to investigate how nurses' personality traits, environmental characteristics, and workplace learning were related to nursing competence. METHODS: A cross-sectional survey design was used. Questionnaires were distributed to 1167 Japanese registered nurses. Multiple regression analysis was used to examine the relationships between nurses' personality traits, the environmental characteristics, the nurses' engagement in workplace learning, and their competence. RESULTS: A total of 315 nurses returned questionnaires (i.e., a return rate of 27.0%). The results showed that both the personality traits (extraversion, conscientiousness, openness to experience) and environmental characteristics (autonomy at work and feedback given) were related to workplace learning and self-rated nursing competence. The results also showed that the relationship between extraversion (active, adventurous and ambitious dispositions of an individual) and self-rated nursing competence was moderated by environmental characteristics, and partially mediated by workplace learning. CONCLUSION: Positive personality traits, such as extraversion, conscientiousness, and openness to experience could enhance workplace learning and nursing competence. Moreover, environmental characteristics that allow nurses to express their personality traits have the potential to improve their learning and competence further.

Early development of pleuroperitoneal fold of the diaphragm in the rat fetus.

The embryonic diaphragm comprises four major structural components derived from the transverse septum, the dorsal foregut mesentery, the pleuroperitoneal folds (PPFs), and the body wall. In this study, the appearance of PPFs and related factors were investigated using light microscopy of horizontal sections of rat fetuses from embryonic day 12 to 13. In rat fetuses, the sign of PPF projection was noted in the sidewall of the pericardioperitoneal canal at embryonic day 12, and was confirmed as folds at embryonic day 12.25. Expressions of GATA4, COUP-TF2, and FOG2 were detected in PPF at the early stage of formation. Localizations of these factors suggested that COUP-TF2 and FOG2 are the main factors in PPF appearance and that GATA4 is unlikely to be a main factor, although it is necessary for PPF formation.

Effects of growth factors on development of fetal islet B-cells in vitro.

To investigate the role of growth factors (epidermal growth factor [EGF], betacellulin, and activin A) in the development of islet B cells of rat fetal pancreatic explants in vitro, pancreases from rat fetuses at day 18 of gestation were cultured for 96 hr, with or without these growth factors. Culture medium was changed every 24 hr, and the level of insulin released in the culture medium was measured. After 72 hr of culture, pancreases were examined histologically. As a result, EGF promoted cell proliferation, but reduced B cell volume. Whereas, betacellulin and activin A inhibited cell division, but promoted increased B cell volume and insulin secretion, especially activin A, which stimulated insulin release in a time dependent manner. These results suggest that EGF, betacellulin, and activin A promote pancreatic cell proliferation, islet B-cell differentiation, and islet B-cell differentiation and functional maturation, respectively, and that EGF, betacellulin, and activin A, in this order, regulate islet B-cell neogenesis.

Effects of Nurses' Perceptions of Actual and Demanded Competence on Turnover Intentions.

With the growing focus on continuous professional development, demands placed on nurses to uphold nursing competence have been increasing. This study examined how nurses with different lengths of clinical experience perceived the relationship between their actual competence and the competence they felt was demanded of them, and how this relationship was related to their turnover intentions. Survey questionnaires were distributed to 1,377 nurses, of whom 765 returned usable completed forms. The results showed that across all the groups of clinical experience, nurses perceived the demanded competence levels to be higher than their actual competence levels. However, turnover intentions were not related to nurses' perceptions of demanded competence and were negatively related to perceptions of actual competence. The levels of competence demanded should not be considered as threats for nurses. Improving nurses' competence may reduce their turnover intentions.

Effects of maternal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB126) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB169) on testicular steroidogenesis and spermatogenesis in male offspring rats.

On days 7-21 of gestation, Sprague-Dawley rats were orally administered 3 or 30 mug/kg/d of 3,3',4,4',5-pentachlorobiphenyl (PCB126) or 3,3',4,4',5,5'-hexachlorobiphenyl (PCB169) daily. Their male offspring were autopsied at 3, 6, and 15 weeks after birth to investigate the effects of the 2 polychlorinated biphenyls (PCBs) on spermatogenesis and steroidogenesis in their testes. PCB treatment caused a decrease in the area ratio of 3beta-hydroxysteroid dehydrogenase (HSD)-expressing cells (Leydig cells)/testis at 3 weeks after birth. When PCB126 was administered to pregnant rats, the plasma testosterone levels in their offspring were decreased at 3 weeks. The expression levels of P450scc, 3beta-HSD, and P450(17alpha) mitochondrial RNAs (mRNAs) were unchanged, although the StAR (steroidogenic acute regulatory protein) mRNA expression level was increased at 6 weeks. On the other hand, when PCB169 was administered, plasma testosterone levels were decreased at 3 and 6 weeks and were increased at 15 weeks. Plasma luteinizing hormone (LH) levels were decreased at 6 weeks, and plasma follicle-stimulating hormone (FSH) levels were increased at 15 weeks. The expression levels of 3beta-HSD and P450(17alpha) were increased, and the mRNA level of 5alpha-reductase 1 was decreased at 15 weeks. PCB169 treatment suppressed the conversion of round spermatids between stages VII and VIII. These results indicate that in utero and lactational exposure to PCB126 or PCB169 decreases plasma testosterone levels in 3-week-old rats, with no change in the expression levels of the mRNAs of enzymes, and that PCB169 inhibits testicular steroid synthesis more strongly than PCB126. PCB169 greatly altered the concentration of testosterone, indicating a stronger inhibitory effect on spermatogenesis. Low testosterone and LH levels in prenatally PCB169-exposed rats until 6 weeks after birth presumably retard the functional differentiation of testicular Leydig cells; however, the increased testosterone levels at 15 weeks suggest that Leydig cells in PCB-exposed rats are virtually mature by the 15th week.

Effects of maternal exposure to a low dose of diethylstilbestrol on sexual dimorphic nucleus volume and male reproductive system in rat offspring.

Diethylstilbestrol (DES) was administered subcutaneously at 0.5, 1.5 or 4.5 microg/kg/day (DES 0.5, 1.5 and 4.5 groups, respectively) to pregnant SD rats daily on days 7-21 of gestation, to investigate its effects on the development and functions of the reproductive system in their male offspring. Of the 10 pregnant rats in the DES 4.5 group, only 1 delivered, and this rat could not suckle the pups. Rat pups in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. The testosterone concentrations in the DES 1.5 and 0.5 groups at 6 weeks were significantly decreased and the plasma LH concentrations were not altered. In the DES 1.5 group, DES treatment did not change the volume of the sexually dimorphic nucleus in the preoptic area (SDN-POA) in the male offspring, although this dose of DES increased the volume of SDN-POA in female offspring. The DES treatment altered frequencies in the cycles of the seminiferous tubules, and suppressed histological maturation in the epididymis and the prostate weight. These observations indicate that prenatally administered DES impairs testicular endocrine function continuously as well as pituitary function, but the induced low level of testosterone disrupts spermatogenesis and permanently inhibits the morphological development of epididymis and prostate.

Adaptation of the hindlimbs for climbing in bears.

The hindlimbs of the Malayan sun bear (Helarctos malayanus), the polar bear (Ursus maritimus), the brown bear (Ursus arctos) and the giant panda (Ailuropoda melanoleuca) have been anatomically and osteometrically studied. The Musculus tibialis cranialis of the Malayan sun bear and the giant panda possessed a well-developed rich fleshy portion until the distal end of the tibia. In the polar bear and the brown bear, however, the fleshy portion of the M. tibialis cranialis was not developed until the distal end of the tibia. The tendon of the M. tibialis cranialis inserting on the proximal end of the Ossa metatarsalia was shorter in the Malayan sun bear and the giant panda than in the polar bear and the brown bear. In the Malayan sun bear and the giant panda, moreover, the M. popliteus was attached more distally to the tibia than in the polar bear and the brown bear. The stable dorsiflexion and supination of the foot and the efficient pronation of the crus are important for skillful tree climbing. The present study suggests that the Malayan sun bear and the giant panda have hindlimbs especially adapted to tree climbing by the well-developed fleshy portion of the M. tibialis cranialis reaching the distal end of the tibia, its short tendon, and the M. popliteus inserting near the distal end of the tibia.