Occupational Fall Risk Assessment Tool for older workers.

BACKGROUND: No easy-to-use fall risk assessment tools have been devised to assess occupational fall risk in older workers. AIMS: To develop an Occupational Fall Risk Assessment Tool (OFRAT) and report its predictive validity and reliability in older workers. METHODS: The baseline fall risk assessment was completed by 1113 participants aged ≥60 years who worked ≥4 days/month in Saitama, Japan. Participants were followed up for falls during occupational activities for 1 year, and 30 participants were assessed twice for test-retest reliability. The following assessment measures were summed to form the OFRAT risk score: older age, male sex, history of falls, physical work participation, diabetes, use of medications increasing fall risk, reduced vision, poor hearing, executive dysfunction and slow stepping. The scores were then classified into four grades (0-2 points: very low, 3 points: low, 4 points: moderate and ≥5 points: high). RESULTS: During follow-up, 112 participants fell 214 times during work. The negative binomial regression model showed that participants with higher grades had a higher incidence rate ratio [95% confidence interval] for falls than those with very low grades (low: 1.64 [1.08-2.47], moderate: 4.23 [2.82-6.34] and high: 6.12 [3.83-9.76]). The intraclass correlation coefficient for risk score was 0.86 [0.72-0.93], and the weighted kappa coefficient for grade assessment was 0.74 [0.52-0.95]. CONCLUSIONS: The OFRAT is a valid and reliable tool for estimating the occupational fall risk in older workers. It may assist occupational physicians implement strategies to prevent falls in this group.

Discrimination of Frailty Phenotype by KinectTM-Based Stepping Parameters.

Background: Frailty increases the risk of falling, hospitalization, and premature death, necessitating practical early-detection tools. Objectives: To examine the discriminative ability of KinectTM-based stepping parameters for identifying frailty phenotype. Design: Population-based cross-sectional study. Setting: Eighteen neighborhoods near Tokyo Metropolitan Institute for Geriatrics and Gerontology, Itabashi, Tokyo, Japan. Participants: In total, 563 community-dwelling older adults aged ≥75 years without mobility limitations, neurological disease, or dementia were included. Measurements: Step number (SN) and knee total movement distance (KMD) during a 20-s stepping test were evaluated using the KinectTM infrared depth sensor. Results: The number (%) of participants with frailty were 51 (9.1). The area under the receiver operating characteristic curves (95% confidence interval) of a parameter consisting of SN and KMD for frailty was 0.72 (0.64, 0.79). Conclusions: Stepping parameters evaluated using KinectTM provided acceptable ability in identifying frailty phenotype, making it a practical screening tool in primary care and home settings.

Cutaneous Histiocytic Sarcoma with Regional Lymph Node Metastasis in a Netherland Dwarf Rabbit (Oryctolagus cuniculus).

A 10-year-old male Netherland dwarf rabbit (Oryctolagus cuniculus) was presented with a red nodular mass (1 cm in diameter) with ulceration and hair loss in the skin of the left upper lip. Cytological examination revealed atypical round cells. The mass was excised surgically. Histologically, the mass was composed of large round to polyhedral neoplastic cells with marked cytological atypia. The neoplastic cells were often binucleated or multinucleated. Immunohistochemically, the neoplastic cells were intensely positive for Iba1 and vimentin, but fewer neoplastic cells expressed E-cadherin. Nuclear immunoreactivity for Ki67 was detected in approximately 41% of the neoplastic cells. Metastasis to the left cervical lymph nodes was detected 6 months after the surgical excision. Based on clinical, histopathological and immunohistochemical findings, the present case was diagnosed as cutaneous histiocytic sarcoma. To the authors' knowledge cutaneous histiocytic disease has not been reported previously in lagomorphs.

Multiple Histiocytic Foam Cell Nodules in the Tongue of Miniature Dachshund Dogs.

Miniature dachshund dogs are a common breed in Japan and are known to be predisposed to granulomatous diseases. Here we report the pathologic features of multiple lingual nodules in 7 miniature dachshunds. Seven dogs had multiple nodules of variable sizes mainly on the ventral and lateral surface of the tongue. In addition, 1 dog also had masses on the left oral mucosa. Three cases had recurrence after surgical resection. Histologically, the lingual nodules were composed of aggregates of foam cells with clear vacuolated cytoplasm that were negative for oil red O, PAS, and alcian blue. They stained positively for CD204 (macrophage scavenger receptor) and MHC class II and negatively for Iba-1, E-cadherin, adipophilin, cytokeratins, S-100, and nestin. These findings indicate that the multiple lingual nodules in miniature dachshunds are an unusual, unique lesion consisting of macrophage-derived foam cells, which does not correspond to canine lingual diseases reported to date.

A collision tumour consisting of malignant trichoblastoma and melanosarcoma in a rabbit.

A 7-year-old mixed breed neutered female rabbit (Orytolagus cuniculus) developed a solitary black nodular mass (1 cm in diameter) in the skin of the right flank. Microscopically, the mass consisted of an admixture of neoplastic trichoblasts and melanocytes. The former were arranged as solid, trabecular, island-like and gland-like structures and the cells had oval nuclei with prominent nucleoli and lightly eosinophilic scant cytoplasm. The latter population exhibited prominent nuclear atypia and high mitotic index in the clusters of a few cells or single cells. Immunohistochemically, the neoplastic trichoblasts expressed cytokeratins and E-cadherin, while the neoplastic melanocytes expressed vimentin, S100 protein, melan-A and melanoma antigen. A diagnosis of collision tumour involving malignant trichoblastoma and melanosarcoma was made.

Multiple-slice magnetic resonance imaging can detect visceral adipose tissue reduction more accurately than single-slice imaging.

BACKGROUND/OBJECTIVE: Imaging methods by magnetic resonance imaging are being increasingly used to quantify visceral adipose tissue (VAT), but there is no clear consensus as to a standardized protocol. We compared the ability of two commonly used imaging protocols (multiple slice versus single slice) to detect changes in VAT with diet or exercise. SUBJECTS/METHODS: We utilized data from the participants who completed our diet (n=22) or exercise (n=35) based weight-loss interventions. The intervention mainly comprised of weekly dietary modification sessions or aerobic exercise sessions over 12 weeks. Multiple-slice images obtained from T9 to S1 and a single-slice image at L4-L5 were compared using the effect size of the VAT change. In addition, we calculated the sample size needed to compare the two imaging protocols' ability to detect significant changes in VAT. RESULTS: VAT and subcutaneous adipose tissue volumes and areas, and other anthropometry decreased significantly after both the diet and exercise interventions. For VAT, a single-slice image had a lower effect size (diet: 1.23; exercise: 0.49) than the multiple-slice images (diet: 1.81; exercise: 0.90). The sample size required for multiple slice was substantially lower than for the single-slice with both weight-loss interventions. CONCLUSIONS: The different image protocols may lead to different results in relative VAT changes. Furthermore, single-slice imaging required a substantially larger sample size than multiple-slice imaging, and for researchers to detect smaller changes in VAT with single-slice imaging, a larger sample size would be needed. Thus, multiple-slice imaging has advantages for assessing VAT change in future clinical research.

Cardiac hamartoma in a young squirrel monkey who died suddenly.

A case of cardiac hamartoma in a 2-month-old squirrel monkey is reported. The monkey showed a loss of appetite and died suddenly. Microscopically, an encapsulated nodular lesion was found at the right atrial wall. The lesion consisted of irregularly shaped, slender myocytes intermingled with a few fibroblasts and collagen fibers. Neither nuclear atypia nor inflammatory cell infiltrate was seen. The constituting cells had stratified striations in the cytoplasm and reacted immunohistochemically for desmin, indicating the nature of myocytes. Based on the above findings, a diagnosis of cardiac hamartoma was made. This is the first case of cardiac hamartoma in this species.

Asymptomatic hypoesthesia of the maxillary alveolar ridge in complete denture wearers.

This study was carried out to investigate the effect of compression induced by complete dentures on the function of the nerves underlying the dentures. The influence of compression induced by complete dentures on nerve function was analysed using current perception threshold (CPT) in 33 complete denture wearers aged 50-80 at Nihon University School of Dentistry (Matsudo, Japan). Based on the age range of the complete denture group, dentate subjects were selected as a control. Because the group characteristics (such as subject age, gender, body mass index) and oral mucosal thickness were not matched, a multiple regression analysis was used to adjust for the influence of heterogeneous characteristics on the CPT. Statistically significant differences were found between subject groups for the nasopalatine and the greater palatine nerve. The results of the study were that complete denture wearers experience asymptomatic hypoesthesia mainly affecting the nasopalatine and greater palatine nerves, but not the infraorbital nerve.

Effect of CETP on the plasma lipoprotein profile in four strains of transgenic mouse.

The plasma cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism and reverse cholesterol transport. There are conflicting views regarding whether or not excessive CETP activity is one of the risk factors of atherosclerosis. To study how much effect CETP can have on the profiles of plasma lipoproteins in vivo, we produced four strains of transgenic mouse that expressed different levels of human CETP gene. We analyzed seven groups of mice that had different levels of CETP expression. The cholesterol level of HDL, chylomicron (CM) and VLDL, intermediate density lipoprotein (IDL) and LDL were proportionally changed in association with plasma CETP concentrations (2.9 +/- 0.6 to 37.4 +/- 1.7 microg/ml) in an allelic dose-dependent manner. We further characterized one of the transgenic strains, CETP-4, by optimizing the experimental condition for the mouse model of atherosclerosis, and found that it would be useful for the development of therapeutics against atherosclerosis.

Concept of improved rigidity: how to make enantioselective hydrophosphonylation of cyclic imines catalyzed by chiral heterobimetallic lanthanoid complexes almost perfect

The catalytic and enantioselective hydrophosphonylation of cyclic imines using cyclic phosphites is described for the first time. In contrast to the application of acyclic phosphites, significant improvements are presented arising from the concept of improved rigidity by utilization of cyclic phosphites in the lanthanoid BINOL complex catalyzed hydrophosphonylation of 3-thiazolines. Cyclic phosphites are shown to provide certain improvements within the catalytic cycle. Influence of parameters such as concentration of the catalyst and the phosphite on the catalysis is examined as well as the effects of the substituents on the starting material. The pharmacologically interesting thiazolidinyl phosphonates are synthesized in excellent optical purities of up to 99% ee and high chemical yields of up to 99%. The required amount of catalyst is reduced to 2.5 mol %. The highest efficiency of the reaction involving cyclic phosphites is achieved using the catalytic system "2.5 mol % (S)-YbPB/2.5 equiv phosphite/50 degrees C/48 h/THF-toluene (1:7)". On the basis of the results a refinement of the proposed catalytic cycle has been provided. For comparison cyclic phosphites were used in hydrophosphonylation with a chiral titanium catalyst.

A novel method for constructing gene-targeting vectors.

We developed a simple and rapid method for constructing knockout vectors using inverse-PCR (IPCR). The method consists of three steps: (i) digestion of a target bacterial artificial chromosome with several restriction enzymes (six-base cutters) followed by self-ligation; (ii) IPCR using circular DNAs as templates and two primers which are oriented in opposite directions; and (iii) cloning into a vector containing a positive selection marker, which results in a typical replacement knockout vector. We successfully targeted three mouse genes including the HPRT gene using this method. Compared with the conventional method, this method requires much less time (no more than 3 weeks). Notably, this method requires only small amounts of sequence information (several hundred base pairs such as is available from expressed sequence tags) and can be extended to a systematic mass production of targeting vectors applicable to many organisms, including yeast.

Proteomic analysis of the small intestine and colon epithelia of adenomatous polyposis coli gene-mutant mice by two-dimensional gel electrophoresis.

Mutations of the adenomatous polyposis coli gene (APC) have been implicated in the occurrence of sporadic colon cancer. Various APC mutant strains of mice have been created to better understand the function of this gene. Previously, we had mice express a mutant form of mRNA of the APC protein that encoded 474 amino acids instead of the 2845 amino acids due to exon duplication. These APC mutant mice (APC delta 474) developed intestinal and mammary tumors, as have other APC mutant mice previously reported (Sasai, H., et al. Carcinogenesis, in press). To elucidate the mechanism of the tumor development, we prepared protein samples from both normal and tumor tissues from APC delta 474 mutant mice, as well as tissues from normal mice, and used them for proteomic analysis. After two-dimensional electrophoresis, the gels were silver stained and the protein spots were analyzed. We analyzed about 1000 protein spots per sample and found several protein spots that are specific for normal or tumor samples from APC delta 474 mutant mice, as well as proteins with altered expression levels. Among the identified protein spots, truncated beta-tubulins were specific to APC delta 474 mutant mice polyp samples. The apparent molecular mass of these proteins suggested that these beta-tubulins may be truncated very close to the binding site of the anti-tumor drug taxol.

Disruption of the epilepsy KCNQ2 gene results in neural hyperexcitability.

Benign familial neonatal convulsion (BFNC) is a common idiopathic epilepsy with autosomal dominant inheritance. Recently, two novel voltage-dependent potassium channel genes, KCNQ2 and KCNQ3, were identified by positional cloning as being responsible for BFNC. Heterotetramers of the products of these genes form M-channels and regulate the threshold of electrical excitability of neurons. We disrupted the mouse KCNQ2 gene via gene targeting to study the relationship between KCNQ2 and epilepsy. Homozygous pups (KCNQ2 -/-) died within a few hours after birth owing to pulmonary atelectasis that was not due to the status of epileptic seizures, although their development was morphologically normal. Heterozygous mice had decreased expression of KCNQ2 and showed hypersensitivity to pentylenetetrazole, an inducer of seizure. These data indicate that the decreased expression of KCNQ2 might cause a hyperexcitability of the CNS, which accounts for the mechanism of BFNC.

Echocardiographic diagnosis of dirofilariasis in a ferret.

Heartworm disease is described in a 14-month-old neutered female ferret (Mustela putorius furo) which had a three-week history of sneezing, anorexia and dyspnoea. Echocardiography revealed the presence of heartworms as hyperechoic densities within the right atrial and ventricular cavities. At necropsy, four Dirofilaria immitis parasites (three females, one male) were found in the right heart, the cranial vena cava and the caudal vena cava. Histopathological findings were similar to those reported in canine heartworm disease. Echocardiography may be a useful method of diagnosis of heartworm disease in the ferret.

Suppression of polypogenesis in a new mouse strain with a truncated Apc(Delta474) by a novel COX-2 inhibitor, JTE-522.

Mutations of the adenomatous polyposis coli gene (Apc) have been implicated in the occurrence of sporadic colon cancer. Various Apc knockout strains of mice have been created to better understand the function of this gene. In the present study, using gene targeting, we disrupted the mouse Apc gene at the end of exon 10 to compare its effect with the effects of other types of Apc gene disruption, all of which are on exon 15. The mice expressed a mutant form of mRNA that encoded 474 amino acids instead of 2845 amino acids due to exon duplication. In addition, these Apc(Delta474) knockout mice developed intestinal and mammary tumors. Since the most severe cases of familial adenomatous polyposis are associated with mutations on exon 15, our mutation at exon 10 was expected to result in a mild phenotype. However, the number of polyps that our mice developed was similar to that of other Apc knockout mice such as Apc(Min) and Apc(1309) mice. Cyclooxygenase-2 (COX-2) has been implicated in colorectal carcinoma. Apc(Delta474) mice treated with JTE-522, a novel COX-2-selective inhibitor, showed a significantly reduced number of polyps. These results suggest that COX-2 plays an important role in polypogenesis and COX-2-selective inhibitors can be used as new preventive therapeutics against colorectal tumors.

Future molecular approaches to the diagnosis and treatment of glomerular disease.

Current diagnoses and treatment decisions for renal disease are made based upon a combination of clinical and pathological determinations. With the advances in both biochemical and molecular biological techniques, identifying the underlying biochemical and genetic changes that may have initiated and/or contributed to the disease is possible. We describe here technologies that may lead to significant changes in renal disease diagnosis, characterization, treatment, and potentially prevention. For example, differential display techniques and DNA gene chip arrays show the changes in mRNA expression patterns and can potentially identify previously unknown genes and reveal new roles for previously known genes in renal disease. The generation of the single nucleotide polymorphisms (SNP) genomic map will facilitate genetic screening that may identify a gene or combination of genes that produce enhanced disease susceptibility. Combining genomic analysis with epidemiological studies may identify environmental factors that contribute to renal disease onset in genetically susceptible individuals. A number of novel therapies are already on the horizon. These include reagents that abrogate the function of specific cytokines, chemokines, and effector cells. With the list of renal disease genes in hand, their role in renal physiology and pathophysiology can be determined, which should lead to the discovery of pharmacological intervention directed at those genes and their products that play a role in the pathogenesis of renal disease.

Immobilization of heterobimetallic multifunctional asymmetric catalyst

Immobilization of an asymmetric AlLibis(binaphthoxide) catalyst (ALB) is described. The immobilized ALBs (poly-ALBs) are readily prepared from polymeric BINOL derivatives and LiAlH(4). The combined use of 9 mol % of BuLi with ca. 10 mol % (as a monomeric catalyst) of 6,6'-aryl-tethered poly-ALB gave the Michael adducts with up to 93% ee. After completion of the reaction, the insoluble catalyst was recovered in air and is reusable.

Obesity and mild hyperinsulinemia found in neuropeptide Y-Y1 receptor-deficient mice.

To elucidate the role of neuropeptide Y (NPY)-Y1 receptor (Y1-R) in food intake, energy expenditure, and other possible functions, we have generated Y1-R-deficient mice (Y1-R-/-) by gene targeting. Contrary to our hypothesis that the lack of NPY signaling via Y1-R would result in impaired feeding and weight loss, Y1-R-/- mice showed a moderate obesity and mild hyperinsulinemia without hyperphagia. Although there was some variation between males and females, typical characteristics of Y1-R-/- mice include: greater body weight (females more than males), an increase in the weight of white adipose tissue (WAT) (approximately 4-fold in females), an elevated basal level of plasma insulin (approximately 2-fold), impaired insulin secretion in response to glucose administration, and a significant changes in mitochondrial uncoupling protein (UCP) gene expression (up-regulation of UCP1 in brown adipose tissue and down-regulation of UCP2 in WAT). These results suggest either that the Y1-R in the hypothalamus is not a key molecule in the leptin/NPY pathway, which controls feeding behavior, or that its deficiency is compensated by other receptors, such as NPY-Y5 receptor. We believe that the mild obesity found in Y1-R-/- mice (especially females) was caused by the impaired control of insulin secretion and/or low energy expenditure, including the lowered expression of UCP2 in WAT. This model will be useful for studying the mechanism of mild obesity and abnormal insulin metabolism in noninsulin-dependent diabetes mellitus.