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Japanese society has entered aging about 30 years earlier than China.Compared with the changes in the population aged 65-74 years and 75 years and above in Japan during 1980—2035 and the changes in the aging rate between Japan and China,the authors studied the evolution of the supply and demand balance of elderly care facilities in Japan,mainly studying the number of beds in elderly care facilities owned by the population aged 75 years and above per 1000 people in various regions of Japan in 2018;at the same time,according to the regional population structure of all age groups and the proportion of elderly care facilities used by all age groups,the number of elderly care facility beds from 2014 to 2018 was studied.The study found that the elderly population aged 80 years and older who need long-term care will rapidly increase after 2025,and if society continues to maintain the past trend of increasing demand for elderly facilities,Japanese society will need to continue to build elderl facilities.In China,the supply and demand prediction of such elderly facilities is essential for the development of elderly facilities.Given that older adults' health levels and values change over time,it is important to continue building models with higher accuracy while regularly revising predictive models.The situation 30 years ago and changes since then in Japan have important reference value when building a prediction model for long-term care needs in China.

Abstract Background Diffuse idiopathic skeletal hyperostosis (DISH) is a structural abnormality of the thoracic spine that is known to impair posture. However, the relationship between DISH and sagittal balance in the whole spine is unclear. The aims of this study were to investigate the prevalence of DISH in patients with cervical myelopathy caused by cervical ossification of the posterior longitudinal ligament (OPLL) or cervical spondylosis and to compare sagittal alignment of the spine between patients with and without DISH. Methods A total of 103 consecutive patients with a diagnosis of cervical myelopathy due to cervical OPLL or spondylosis were retrospectively enrolled in this single-center study. DISH was defined as an ossified lesion that was seen to be completely bridging at least four contiguous adjacent vertebral bodies in the thoracic spine on computed tomography scans. Cervical and spinopelvic sagittal parameters were measured in whole spine radiographs. Results The study population included 28 cases with DISH [DISH (+) group] and 75 without DISH [DISH (−) group]. OPLL was more prevalent in the DISH (+) group than in the DISH (−) group; however, there were no significant differences in other clinical findings. Propensity score matching produced 26 pairs. C7 slope, C2-7 sagittal vertical axis (C-SVA), whole thoracic kyphotic angles, upper thoracic kyphosis, and T5-T12 thoracic kyphosis values were significant higher in the DISH (+) group than in the DISH (−) group. There was no significant between-group difference in the other sagittal spinopelvic parameters. Conclusions This study is the first to compare sagittal alignment in patients with cervical myelopathy according to whether or not they have DISH. Patients with DISH are more likely to have excessive kyphosis in the thoracic spine, a high C7 slope, and a high C2-7 SVA.

Objective: Although soft tissue infections are common among injection drug users (IDUs), little is known about the health outcomes among those who seek care for these infections. Emergency department visits are an important point-of-health-care contact for IDUs. In this prospective cohort study, we aimed to determine the hospitalization and mortality rates and factors associated with hospitalization or death among IDUs seeking emergency care for soft tissue infection.Method: Participants were English-speaking IDUs, 18 years of age and older, who sought initial care for soft tissue infection in an urban emergency department. We conducted semistructured interviews, identified hospitalizations from hospital records, and identified deaths using the National Death Index. Cox proportional hazards regression was used to investigate associations between baseline characteristics and hospitalizations or death.Results: Of 211 eligible patients, 156 (74%) participated (mean age = 42 years). There were 255 subsequent hospitalizations over a mean of 3.9 years follow-up. The hospitalization rate was 42 hospitalizations per 100 person-years (95% confidence interval [CI]: 38-48). The mortality rate was 2.0 per 100 person-years (95% CI: 1.1-3.7). Factors associated with increased risk for hospitalization or death included living on the street or in a shelter (adjusted odds ratio [AOR] = 1.75, 95% CI: 1.10-2.79), being recently incarcerated (AOR = 1.90, 95% CI: 1.05-3.44), and having insurance (AOR: 1.98, 95% CI: 1.22-3.23).Conclusions: IDUs who sought care in the emergency department for soft tissue infections were at high risk for subsequent hospitalization and death. Visits for soft tissue infections represent missed opportunities for preventive care. [ABSTRACT FROM AUTHOR]

A letter to the editor in response to the article "First report of donor cell-derived acute leukemia as a complication of umbilical cord blood transplantation," by C.J. Fraser and B.A. Hirsch, and Dayton in a 2005 issue is presented.

Electrical conductivity in warm dense state has been evaluated by using isochoric pulsed-power discharge. The isochoric heating can be achieved by surrounding the foamed metal with a sapphire capillary as a rigid wall. The electrical conductivity and the temperature of copper foam/plasma have been evaluated by the applied voltage-current waveform and emission intensity. Observed electrical conductivity and foam/plasma temperature is about 104 S/m and 4000 K in 0.10ρs.

Abstract Background Renal scintigraphy using 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) is widely used for the assessment of renal function in humans. However, the application of this method to animal models of renal disease is currently limited, especially in rodents. Here, we have applied 99mTc-MAG3 renal scintigraphy to a mouse model of unilateral ureteral obstruction (UUO) and evaluated its utility in studying obstructive renal disease. Methods UUO mice were generated by complete ligation of the left ureter. Sham-operated mice were used as a control. Renal function was investigated on days 0, 1, 3, and 6 post-surgery using dynamic planar imaging of 99mTc-MAG3 activity following retro-orbital injection. Time-activity curves (TACs) were produced for individual kidneys and renal function was assessed by 1) the slope of initial 99mTc-MAG3 uptake (SIU), which is related to renal perfusion; 2) peak activity; and 3) the time-to-peak (TTP). The parameters of tubular excretion were not evaluated in this study as 99mTc-MAG3 is not excreted from UUO kidneys. Results Compared to sham-operated mice, SIU was remarkably (>60%) reduced in UUO kidneys at day 1 post surgery and the TACs plateaued, indicating that 99mTc-MAG3 is not excreted in these kidneys. The plateau activity in UUO kidneys was relatively low (~40% of sham kidney’s peak activity) as early as day1 post surgery, demonstrating that uptake of 99mTc-MAG3 is rapidly reduced in UUO kidneys. The time to plateau in UUO kidneys exceeded 200 sec, suggesting that 99mTc-MAG3 is slowly up-taken in these kidneys. These changes advanced as the disease progressed. SIU, peak activity and TTPs were minimally changed in contra-lateral kidneys during the study period. Conclusions Our data demonstrate that renal uptake of 99mTc-MAG3 is remarkably and rapidly reduced in UUO kidneys, while the changes are minimal in contra-lateral kidneys. The parametric analysis of TACs suggested that renal perfusion as well as tubular uptake is reduced in UUO kidneys. This imaging technique should allow non-invasive assessments of UUO renal injury and enable a more rapid interrogation of novel therapeutic agents and protocols.

Abstract Background Reelin regulates neuronal positioning in cortical brain structures and neuronal migration via binding to the lipoprotein receptors Vldlr and Lrp8. Reeler mutant mice display severe brain morphological defects and behavioral abnormalities. Several reports have implicated reelin signaling in the etiology of neurodevelopmental and psychiatric disorders, including autism, schizophrenia, bipolar disorder, and depression. Moreover, it has been reported that VLDLR mRNA levels are increased in the post-mortem brain of autistic patients. Methods We generated transgenic (Tg) rats overexpressing Vldlr, and examined their histological and behavioral features. Results Spontaneous locomotor activity was significantly increased in Tg rats, without detectable changes in brain histology. Additionally, Tg rats tended to show performance deficits in the radial maze task, suggesting that their spatial working memory was slightly impaired. Thus, Vldlr levels may be involved in determining locomotor activity and memory function. Conclusions Unlike reeler mice, patients with neurodevelopmental or psychiatric disorders do not show striking neuroanatomical aberrations. Therefore, it is notable, from a clinical point of view, that we observed behavioral phenotypes in Vldlr-Tg rats in the absence of neuroanatomical abnormalities.

Abstract A patient with acute lymphoblastic leukemia repeatedly developed hypoglycemia during chemotherapy. Comparison of serum glucose trends between chemotherapy with and without L-asparaginase (L-Asp) demonstrated a strong association between L-Asp and hypoglycemia. Critical blood sampling during hypoglycemia indicated hyperinsulinism, suggesting that L-Asp induced hypoglycemia in the patient through inappropriate insulin secretion. Identification of hypoglycemia as an adverse effect will enable clinicians to understand and develop appropriate strategies for L-Asp use in chemotherapy regimens.

Abstract Background The progression of chronic obstructive pulmonary disease (COPD) considerably varies among patients. Those with emphysema identified by quantitative computed tomography (CT) are associated with the rapid progression assessed by forced expiratory volume in one second (FEV1). However, whether the rate of the decline in lung function is independently affected by the regional distribution or the severity of emphysema in the whole lung is unclear. Methods We followed up 131 male patients with COPD for a median of 3.7 years. We measured wall area percent (WA%) in right apical segmental bronchus, total lung volume, percent low attenuation volume (LAV%), and the standard deviation (SD) of LAV% values from CT images of 10 isovolumetric partitions (SD-LAV) as an index of cranial-caudal emphysema heterogeneity. Annual changes in FEV1 were then determined using a random coefficient model and relative contribution of baseline clinical parameters, pulmonary function, and CT indexes including LAV%, SD-LAV, and WA% to annual changes in FEV1 were examined. Results The mean (SD) annual change in FEV1 was −44.4 (10.8) mL. Multivariate random coefficient model showed that higher baseline FEV1, higher LAV%, current smoking, and lower SD-LAV independently contributed to an excessive decline in FEV1, whereas ratio of residual volume to total lung capacity, ratio of diffusing capacity to alveolar ventilation, and WA% did not, after adjusting for age, height, weight, and ratio of CT-measured total lung volume to physiologically-measured total lung capacity. Conclusions A more homogeneous distribution of emphysema contributed to an accelerated decline in FEV1 independently of baseline pulmonary function, whole-lung emphysema severity, and smoking status. In addition to whole-lung analysis of emphysema, CT assessment of the cranial-caudal distribution of emphysema might be useful for predicting rapid, progressive disease and for developing a targeted strategy with which to prevent disease progression.

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and persistent inflammation in the airways and lung parenchyma. Oxidative stress contributes to the pathogenesis of COPD. Interleukin (IL)-32 expression has been reported to increase in the lung tissue of patients with COPD. Here, we show that IFNγ upregulated IL-32 expression and that oxidative stress augmented IFNγ-induced-IL-32 expression in airway epithelial cells. We further investigated transcriptional regulation responsible for IFNγ induced IL-32 expression in human airway epithelial cells. Methods Human bronchial epithelial (HBE) cells were stimulated with H2O2 and IFNγ, and IL-32 expression was evaluated. The cell viability was confirmed by MTT assay. The intracellular signaling pathways regulating IL-32 expression were investigated by examining the regulatory effects of MAPK inhibitors and JAK inhibitor after treatment with H2O2 and IFNγ, and by using a ChIP assay to identify transcription factors (i.e. c-Jun, CREB) binding to the IL-32 promoter. Promoter activity assays were conducted after mutations were introduced into binding sites of c-Jun and CREB in the IL-32 promoter. IL-32 expression was also examined in HBE cells in which the expression of either c-Jun or CREB was knocked out by siRNA of indicated transcription factors. Results There were no significant differences of cell viability among groups. After stimulation with H2O2 or IFNγ for 48 hours, IL-32 expression in HBE cells was increased by IFNγ and synergistically upregulated by the addition of H2O2. The H2O2 augmented IFNγ induced IL-32 mRNA expression was suppressed by a JNK inhibitor, but not by MEK inhibitor, p38 inhibitor, and JAK inhibitor I. Significant binding of c-Jun and CREB to the IL-32 promoter was observed in the IFNγ + H2O2 stimulated HBE cells. Introducing mutations into the c-Jun/CREB binding sites in the IL-32 promoter prominently suppressed its transcriptional activity. Further, knocking down CREB expression by siRNA resulted in significant suppression of IL-32 induction by IFNγ and H2O2 in HBE cells. Conclusion IL-32 expression in airway epithelium may be augmented by inflammation and oxidative stress, which may occur in COPD acute exacerbation. c-Jun and CREB are key transcriptional factors in IFNγ and H2O2 induced IL-32 expression.

Abstract Background The endopeptidase encoded by Phex (phosphate-regulating gene with homologies to endopeptidases linked to the X chromosome) is critical for regulation of bone matrix mineralization and phosphate homeostasis. PHEX has been identified from analyses of human X-linked hypophosphatemic rickets and Hyp mutant mouse models. We here demonstrated a newly established dwarfism-like Kbus/Idr mouse line to be a novel Hyp model. Methods Histopathological and X-ray examination with cross experiments were performed to characterize Kbus/Idr. RT-PCR-based and exon-directed PCR screening performed to identify the presence of genetic alteration. Biochemical assays were also performed to evaluate activity of alkaline phosphatase. Results Kbus/Idr, characterized by bone mineralization defects, was found to be inherited in an X chromosome-linked dominant manner. RT-PCR experiments showed that a novel mutation spanning exon 16 and 18 causing hypophosphatemic rickets. Alkaline phosphatase activity, as an osteoblast marker, demonstrated raised levels in the bone marrow of Kbus/Idr independent of the age. Conclusions Kbus mice should serve as a useful research tool exploring molecular mechanisms underlying aberrant Phex-associated pathophysiological phenomena.

Abstract Background Inducible inactivation of a protein is a powerful approach for analysis of its function within cells. Fission yeast is a useful model for studying the fundamental mechanisms such as chromosome maintenance and cell cycle. However, previously published strategies for protein-depletion are successful only for some proteins in some specific conditions and still do not achieve efficient depletion to cause acute phenotypes such as immediate cell cycle arrest. The aim of this work was to construct a useful and powerful protein-depletion system in Shizosaccaromyces pombe. Results We constructed an auxin-inducible degron (AID) system, which utilizes auxin-dependent poly-ubiquitination of Aux/IAA proteins by SCFTIR1 in plants, in fission yeast. Although expression of a plant F-box protein, TIR1, decreased Mcm4-aid, a component of the MCM complex essential for DNA replication tagged with Aux/IAA peptide, depletion did not result in an evident growth defect. We successfully improved degradation efficiency of Mcm4-aid by fusion of TIR1 with fission yeast Skp1, a conserved F-box-interacting component of SCF (improved-AID system; i-AID), and the cells showed severe defect in growth. The i-AID system induced degradation of Mcm4-aid in the chromatin-bound MCM complex as well as those in soluble fractions. The i-AID system in conjunction with transcription repression (off-AID system), we achieved more efficient depletion of other proteins including Pol1 and Cdc45, causing early S phase arrest. Conclusion Improvement of the AID system allowed us to construct conditional null mutants of S. pombe. We propose that the off-AID system is the powerful method for in vivo protein-depletion in fission yeast.

Abstract We propose a TCP window-size delegation method for downlink TXOP (transmission opportunity) Exchange in wireless local area networks (WLANs). In our method, the 'compliant' stations (STAs) cooperatively use their available bandwidth in accordance with their throughput demand. We realize our method only with minimal modifications of the TCP functions of a proxy server, which lets one station (the TXOP provider) delegate TCP window size to another station (the TXOP client) so that the provider delegates its TXOPs in WLANs to the client. Our method enables an STA to flexibly delegate TXOPs to another STA without adversely affecting the legacy STAs, which is confirmed by computer simulations. We also confirmed that our method requires no modification to legacy access points and STAs.

We focus on mobile P2P multicast, in which mobile end nodes not only act as receivers but also relay the received stream forward to others. In mobile P2P multicast, negative effects caused by the change of available bandwidth and the disconnection of mobile nodes are propagated to the downstream nodes. To solve this problem, we developed a novel node-allocation framework using the multidimensional context parameters of each mobile node, which include available bandwidth, disconnection rate, and the remaining battery capacity. Considering the significance of each parameter, our method integrates these parameters into a single parameter called relay ability. Taking the relay ability into account, each node is allocated to the multicast topology to minimize the negative effects mentioned above. To test our method, we applied our framework to conventional P2P multicast topology and show the results from comparative evaluations through computer simulation.

Abstract Background Influenza virus infection causes significant morbidity and mortality and has marked social and economic impacts throughout the world. The influenza surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), act cooperatively to support efficient influenza A virus replication and provide the most important targets for anti-influenza chemotherapy. In this study, povidone-iodine (PVP-I), which has a broad-spectrum microbicidal property, was examined for its inhibitory effects against influenza virus infection in MDCK cells and the mechanisms of PVP-I action on HA and NA were revealed. Results Results obtained using a novel fluorescence- and chromogenic-based plaque inhibition assay showed that 1.56 mg/ml PVP-I inhibited infections in MDCK cells of human (8 strains) and avian (5 strains) influenza A viruses, including H1N1, H3N2, H5N3 and H9N2, from 23.0–97.5%. A sialidase inhibition assay revealed that PVP-I inhibited N1, N2 and N3 neuraminidases with IC50 values of 9.5–212.1 μg/ml by a mixed-type inhibition mechanism. Receptor binding inhibition and hemagglutinin inhibition assays indicated that PVP-I affected viral hemagglutinin rather than host-specific sialic acid receptors. Conclusion Mechanisms of reduction of viral growth in MDCK cells by PVP-I involve blockade of viral attachment to cellular receptors and inhibition of viral release and spread from infected cells. Therefore, PVP-I is useful to prevent infection and limit spread of human and avian influenza viruses.

Abstract Background Hyperbolic discounting of delayed and probabilistic outcomes has drawn attention in psychopharmacology and neuroeconomics. Sozou's evolutionary theory proposed that hyperbolic delay discounting may be totally attributable to aversion to a decrease in subjective probability of obtaining delayed rewards (SP) which follows a hyperbolic decay function. However, to date, no empirical study examined the hypothesis, although this investigation is important for elucidating the roles of impatience, precaution, and uncertainty aversion in delay discounting processes. Methods In order to (i) determine the functional form of the relation between delay until receipt and SP, and (ii) examine whether delay discounting is attributable to a decrease in SP, we assessed the subjects' SP and their delay and probability discounting. We examined the fitness of hyperbolic and exponential functions to the assessed SP, and relations between the SP, and delay/probability discounting, and subjective-probability discounting for delayed rewards. Results The results demonstrated (a) SP decayed hyperbolically as delay increases, (b) a decay of SP was associated with delay discounting, and (c) subjective-probability discounting did not significantly correlate with delay discounting. Conclusion Our results demonstrated (i) hyperbolic decay of SP is related to delay discounting, and (ii) delay discounting is, however, not attributable to precautious foresight in intertemporal choice. Further, a novel parameter of pure time preference is proposed.

Abstract Background Probabilistic choice has been attracting attention in psychopharmacology and neuroeconomics. Several parametric models have been proposed for probabilistic choice; entropy model, Prelec's probability weight function, and hyperbola-like probability discounting functions. Methods In order to examine (i) fitness of the probabilistic models to behavioral data, (ii) relationships between the parameters and psychological processes, e.g., aversion to possible non-gain in each probabilistic choice and aversion to unpredictability, we estimated the parameters and AICc (Akaike Information Criterion with small sample correction) of the probabilistic choice models by assessing the points of subjective equality at seven probability values (95%–5%). We examined both fitness of the models parametrized by utilizing AICc, and the relationships between the model parameters and equation-free parameter of aversion to possible non-gain. Results Our results have shown that (i) the goodness of fitness for group data was [Entropy model>Prelec's function>General hyperbola>Simple hyperbola]; while Prelec's function best fitted individual data, (ii) aversion to possible non-gain and aversion to unpredictability are distinct psychological processes. Conclusion Entropy and Prelec models can be utilized in psychopharmacological and neuroeconomic studies of risky decision-making.

Abstract Background TGF-beta is one of the key cytokines implicated in various disease processes including cancer. TGF-beta inhibits growth and promotes apoptosis in normal epithelial cells and in contrast, acts as a pro-tumour cytokine by promoting tumour angiogenesis, immune-escape and metastasis. It is not clear if various actions of TGF-beta on normal and tumour cells are due to differential gene regulations. Hence we studied the regulation of gene expression by TGF-beta in normal and cancer cells. Results Using human 19 K cDNA microarrays, we show that 1757 genes are exclusively regulated by TGF-beta in A549 cells in contrast to 733 genes exclusively regulated in HPL1D cells. In addition, 267 genes are commonly regulated in both the cell-lines. Semi-quantitative and real-time qRT-PCR analysis of some genes agrees with the microarray data. In order to identify the signalling pathways that influence TGF-beta mediated gene regulation, we used specific inhibitors of p38 MAP kinase, ERK kinase, JNK kinase and integrin signalling pathways. The data suggest that regulation of majority of the selected genes is dependent on at least one of these pathways and this dependence is cell-type specific. Interestingly, an integrin pathway inhibitor, RGD peptide, significantly affected TGF-beta regulation of Thrombospondin 1 in A549 cells. Conclusion These data suggest major differences with respect to TGF-beta mediated gene regulation in normal and transformed cells and significant role of non-canonical TGF-beta pathways in the regulation of many genes by TGF-beta.

Abstract Background The International Classification of Functioning, Disability and Health (ICF) was published by the World Health Organization (WHO) to standardize descriptions of health and disability. Little is known about the reliability and clinical relevance of measurements using the ICF and its qualifiers. This study examines the test-retest reliability of ICF codes, and the rate of immeasurability in long-term care settings of the elderly to evaluate the clinical applicability of the ICF and its qualifiers, and the ICF checklist. Methods Reliability of 85 body function (BF) items and 152 activity and participation (AP) items of the ICF was studied using a test-retest procedure with a sample of 742 elderly persons from 59 institutional and at home care service centers. Test-retest reliability was estimated using the weighted kappa statistic. The clinical relevance of the ICF was estimated by calculating immeasurability rate. The effect of the measurement settings and evaluators' experience was analyzed by stratification of these variables. The properties of each item were evaluated using both the kappa statistic and immeasurability rate to assess the clinical applicability of WHO's ICF checklist in the elderly care setting. Results The median of the weighted kappa statistics of 85 BF and 152 AP items were 0.46 and 0.55 respectively. The reproducibility statistics improved when the measurements were performed by experienced evaluators. Some chapters such as genitourinary and reproductive functions in the BF domain and major life area in the AP domain contained more items with lower test-retest reliability measures and rated as immeasurable than in the other chapters. Some items in the ICF checklist were rated as unreliable and immeasurable. Conclusion The reliability of the ICF codes when measured with the current ICF qualifiers is relatively low. The result in increase in reliability according to evaluators' experience suggests proper education will have positive effects to raise the reliability. The ICF checklist contains some items that are difficult to be applied in the geriatric care settings. The improvements should be achieved by selecting the most relevant items for each measurement and by developing appropriate qualifiers for each code according to the interest of the users.

A new species of Aleiodes Wesmael in the gastritor Thunberg species-group is described and illustrated. The new species, Aleiodes ceres Shimbori sp.n., occurs in Southern Brazil and Argentina. It is a potential biological control agent of caterpillars in the genus Spodoptera Guenée, namely S. cosmioides (Walker), S. eridania (Stoll), and S. frugiperda (J.E. Smith), which are serious pests on major crops including maize and soybean. The position of the new species within Aleiodes is discussed in relation to existing proposals of subdivisions of the genus into species-groups. In agreement with recent publications, the gastritor species-group is treated as separate from the circumscriptus Nees/bicolor Spinola group, as evidence suggests the latter is absent in the New World. We also propose the provisional shakirae Shimbori & Shaw species-group, to accommodate a clade of Neotropical species with geometrid hosts and morphological features similar to the gastritor and circumscriptus groups. A key to Neotropical species in the gastritor group and similar species is provided, except for species recently named without a morphological description., (© 2023. The Author(s).)

The egg parasitoid Telenomus remus (Hymenoptera: Scelionidae) has been investigated for classical and applied biological control of noctuid pests, especially Spodoptera (Lepidoptera: Noctuidae) species. Although T. remus was introduced into Brazil over three decades ago for classical biological control of S. frugiperda, this wasp has not been recorded as established in corn or soybean crops. We used an integrative approach to identify T. remus, combining a taxonomic key based on the male genitalia with DNA barcoding, using a cytochrome c oxidase subunit I mitochondrial gene fragment. This is the first report of natural parasitism of T. remus on S. frugiperda and S. cosmioides eggs at two locations in Brazil. We also confirmed that the T. remus lineage in Brazil derives from a strain in Venezuela (originally from Papua New Guinea and introduced into the Americas, Africa, and Asia). The occurrence of T. remus parasitizing S. frugiperda and S. cosmioides eggs in field conditions, not associated with inundative releases, suggests that the species has managed to establish itself in the field in Brazil. This opens possibilities for future biological control programs, since T. remus shows good potential for mass rearing and egg parasitism of important agricultural pests such as Spodoptera species.

A new species of Trichogramma Westwood (Hymenoptera: Trichogrammatidae) is described: Trichogramma foersteri sp. nov. Takahashi from eggs of Anticarsia gemmatalis Hübner, (Lepidoptera: Erebidae) a major soybean defoliating pest. The parasitoid was collected in São José dos Pinhais, Paraná State, Brazil, and molecular and morphological characters were used to confirm the identity of the new species. Preliminary biological data are provided to demonstrate its high capacity of parasitism. The new species is a potential candidate as a biological control agent against some lepidopteran-pests.

Background: The number of graduating primary care physicians will not meet the demands of the growing and aging US population. In 2011, the Veterans Affairs (VA) Office of Academic Affiliations established 5 Centers of Excellence in Primary Care Education (CoEPCE) to transform primary care training., Objective: We created an innovative training model with immersive primary care experiences to foster careers in primary care for residents., Methods: As a CoEPCE, the Seattle VA partnered with the University of Washington internal medicine residency program to form a Center of Excellence (CoE) pathway with increased outpatient training time. The CoEPCE created a longitudinal curriculum of continuity clinic immersion and new thematically based rotations (eg, Homeless Health) for CoE residents. These rotations expanded primary care experiences and allowed for in-depth opportunities to care for the unique needs of veterans. Resident feedback was solicited through program evaluations, and career choices were tracked., Results: Eighty-five of 102 (83%) possible rotation evaluations from 2014 to 2017 were reviewed. Residents reported that CoEPCE rotations had a positive effect on their care of patients and career choice, and provided opportunities to interface with faculty role models. Seventy-five percent of Seattle VA CoE residents selected primary care careers compared to 36% of historical controls., Conclusions: The CoEPCE rotation curriculum offers in-depth primary care training and may contribute to trainees maintaining interest in primary care careers., Competing Interests: Conflict of interest: The authors declare they have no competing interests. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs or the University of Washington., (Accreditation Council for Graduate Medical Education 2019.)

Digital breast tomosynthesis (DBT) is a relatively new imaging technology that is being adopted widely for breast cancer screening. Initial evidence suggests that it may reduce recall rates and increase cancer detection rates when added to digital mammography screening. However, more rigorous, prospective studies are needed to determine whether it improves long-term clinical outcomes of breast cancer screening., (Copyright © 2017 Cleveland Clinic.)

Women generally spend the last third of their lifetime in menopause, after their reproductive years have ended. During menopause, women experience a variety of predictable symptoms and conditions related to changes in sex hormone levels and aging. The menopausal transition precedes menopause by several years and is usually characterized by irregularity of the menstrual cycle and by hot flashes and night sweats. After menopause, genitourinary symptoms predominate, including vulvovaginal atrophy and dryness and lower urinary tract symptoms, including urinary frequency, urgency, and nocturia. Hormonal treatment is effective for vasomotor and genitourinary symptoms, but the understanding of its impact on cardiovascular disease, cognitive dysfunction, and depression continues to evolve., (Published by Elsevier Inc.)

By using the toxin receptor-mediated cell knockout (TRECK) method, we have generated two transgenic (Tg) murine lines that model type 1 (insulin-dependent) diabetes. The first strain, C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg, carries the diphtheria toxin receptor (hDTR) driven by the human insulin gene promoter, while the other strain, C57BL/6-ins2(BAC)-TRECK-Tg, expresses hDTR cDNA under the control of the mouse insulin II gene promoter. With regard to the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg strain, only one of three Tg strains exhibited proper expression of hDTR in pancreatic β cells. By contrast, hDTR was expressed in the pancreatic β cells of all four of the generated C57BL/6-ins2(BAC)-TRECK-Tg strains. Hyperglycemia, severe ablation of pancreatic β cells and depletion of serum insulin were observed within 3days after the administration of diphtheria toxin (DT) in these Tg mice. Subcutaneous injection of a suitable dosage of insulin was sufficient for recovery from hyperglycemia in all of the examined strains. Using the C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg model, we tried to perform regenerative therapeutic approaches: allogeneic transplantation of pancreatic islet cells from C57BL/6 and xenogeneic transplantation of CD34(+) human umbilical cord blood cells. Both approaches successfully rescued C.B-17/Icr-Prkdc(scid)/Prkdc(scid)-INS-TRECK-Tg mice from hyperglycemia caused by DT administration. The high specificity with which DT causes depletion in pancreatic β cells of these Tg mice is highly useful for diabetogenic research., (Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Umbilical cord blood (CB) has been widely used for unrelated allogeneic stem cell transplantation. It is important to determine the quality of CB units to avoid frequent problem of limited cell yields. However, no practical and/or optimum obstetric factors to predict them are yet available. This study analyzed the relationship between maternal/neonatal obstetric factors and the laboratory parameters of CB units to identify the optimum factors associated with a high yield of total nucleated cells (TNC). Primiparae in their early 30s may be one of the first selection criteria for CB donors to obtain higher yield of TNC., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

As the first step of UCB banking, UCB collection has an important role in banking procedures. The aim of this study was to reveal the current status of UCB collection and discuss the management of the UCB bank. We conducted a questionnaire survey at medical centers collecting UCB, followed by semi-structured interviews with some respondents. Out of 38 institutes, 11 respondents (28.9%) thought that collection of UCB in addition to their routine medical services puts a burden on physicians. The obstetricians involved in the UCB collection are generally willing to participate in the procedure under current circumstances at medical institutes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Human umbilical cord blood (CB) is a potential source for mesenchymal stem cells (MSC) capable of forming specific tissues, for example, bone, cartilage, or muscle. However, difficulty isolating MSC from CB (CB-MSC) has impeded their clinical application. Using more than 450 CB units donated to two public CB banks, we found that successful cell recovery fits a hyper-exponential function of time since birth with very high fidelity. Additionally, significant improvement in the isolation of CB-MSC was achieved by selecting cord blood units having a volume ≥90  ml and time ≤2  h after donor's birth. This resulted in 90% success in isolation of CB-MSC by density gradient purification and without a requirement for immunoaffinity methods as previously reported. Using MSC isolated from bone marrow (BM-MSC) and adipose tissue (AT-MSC) as reference controls, we observed that CB-MSC exhibited a higher proliferation rate and expanded to the order of the 1 × 10(9)  cells required for cell therapies. CB-MSC showed karyotype stability after prolonged expansion. Functionally, CB-MSC could be more readily induced to differentiate into chondrocytes than could BM-MSC and AT-MSC. CB-MSC showed immunosuppressive activity equal to that of BM-MSC and AT-MSC. Collectively, our data indicate that viable CB-MSC could be obtained consistently and that CB should be reconsidered as a practical source of MSC for cell therapy and regenerative medicine using the well established CB banking system., (Copyright © 2011 Wiley-Liss, Inc.)

Skin and soft tissue infections (SSTIs) are common complications of illicit drug use. Studies at single, urban hospitals demonstrate high rates of emergency department visits and hospitalizations for these infections. This study sought to estimate nationwide and regional incidence and costs of hospitalizations for illicit drug users with SSTIs in the US. AHRQ's Nationwide Inpatient Sample was used to conduct a retrospective cross-sectional, time-series study. Hospitalizations of illicit drug users with SSTIs were identified using International Classification of Diseases, 9th Revision Clinical Modification codes. An estimated 106,126 hospitalizations for illicit drug users with SSTIs represented 0.07% of all US non-Federal hospitalizations from 1998 to 2001 and cost over 193 million dollars in 2001. Higher rates of hospitalization were found in the West, Northeast, and urban teaching hospitals. Hospitalization rates for illicit drug users with SSTIs vary significantly according to US region. Resources to reduce the incidence and severity of these infections should be targeted accordingly.

Placental/umbilical cord blood (CB) contains nucleated cells and hematopoietic stem/progenitor cells (CD34(+) cells). However it is difficult to predict the number of nucleated/CD34(+) cells in each CB before cell processing. Despite many previous studies from institutes affiliated with CB banks in metropolitan areas, little information is available regarding the characteristics of CB units from other medical facilities. The purpose of the present study was to analyze the maternal/neonatal factors on the yield of cells in CB units. A total of 176 CB units were obtained from single-birth and normal vaginal deliveries. Mononuclear low-density (LD) cells were separated using Ficoll-Paque within 24 hrs after CB collection and then processed for the purification of CD34(+) cells. A multiple linear regression analysis was performed to assess the correlations between the yield of cells and maternal/neonatal factors including maternal age, gravid status, duration of labor, gestational age, neonatal height and weight, cord length, and meconium in the amniotic fluid. The total LD cells per CB unit had a weak positive correlation with the maternal age of primigravidae. The total LD cells per CB unit from the primigravidae aged > or = 25 were significantly higher than those from the primigravidae aged < or = 24. The total CD34(+) cells per CB unit from the 1-gravidae were significantly higher than those from the 2-gravidae and 3-gravidae, respectively among all donors. These results indicate that the CB units from the primigravidae aged > or = 25 are more likely to contain higher yield of LD/CD34(+) cells.

Background: Clinical transplant outcome with umbilical cord blood (UCB) as source of hematopoietic progenitor cells (HPCs) is, among other factors, determined by the total number of viable nucleated cells and/or CD34+ cells in the unit. Quantitative and qualitative losses by processing and cryopreservation and by thawing and washing before transfusion may occur, however. Another reason for a discrepancy between the number of cells in the unit released by the cord blood bank and found in the transplant center may be technical differences in cell counting methods between the two sites., Study Design and Methods: With the collaborative group for Biomedical Excellence for Safer Transfusion (BEST), an interlaboratory exercise was conducted among nine sites for thawed UCB variables: total nucleated cells, CD34+ cells, viability, and HPC cultures. Three frozen UCB samples were shipped, with instructions for thawing, counting, and HPC plating., Results: Unexpectedly samples arrived at all nine receiving centers without detectable hematopoietic progenitor colony-forming cells. Nevertheless, wide interlaboratory ranges for viability were obtained. The proportion of viable cells was found higher with manual methods, but all viability assays used in the study overestimated functional progenitor cells., Conclusions: The results underscore the complexity of evaluation of frozen-thawed cord blood cells and the need for standardization of assessment.

Placental tissue draws great interest as a source of cells for regenerative medicine because of the phenotypic plasticity of many of the cell types isolated from this tissue. Furthermore, placenta, which is involved in maintaining fetal tolerance, contains cells that display immunomodulatory properties. These two features could prove useful for future cell therapy-based clinical applications. Placental tissue is readily available and easily procured without invasive procedures, and its use does not elicit ethical debate. Numerous reports describing stem cells from different parts of the placenta, using nearly as numerous isolation and characterization procedures, have been published. Considering the complexity of the placenta, an urgent need exists to define, as clearly as possible, the region of origin and methods of isolation of cells derived from this tissue. On March 23-24, 2007, the first international Workshop on Placenta Derived Stem Cells was held in Brescia, Italy. Most of the research published in this area focuses on mesenchymal stromal cells isolated from various parts of the placenta or epithelial cells isolated from amniotic membrane. The aim of this review is to summarize and provide the state of the art of research in this field, addressing aspects such as cell isolation protocols and characteristics of these cells, as well as providing preliminary indications of the possibilities for use of these cells in future clinical applications.

Background: There is growing interest in the use of in vitro-expanded dendritic cells (DC) in cancer immunotherapy as cellular-based vaccines. However, the methods used for in vitro preparation vary widely between institutions. Therefore, a strong need exists for standardization, characterization and quality control (QC) of such vaccines. A first prospective multicenter pilot study was performed to investigate basic QC parameters of frozen/thawed DC. The study design was focused on comparison of test results for cell counts, immunophenotyping and cell viability., Methods: CD14+ monocytes were isolated from three healthy volunteers. The cells were expanded in vitro, matured and cryopreserved using a standardized protocol in one laboratory. The aliquots of cryopreserved DC and a panel of reagents were shipped to eight laboratories worldwide. The objective was to compare the results of non-functional QC assays between sites by testing identical DC vaccines and using a pre-defined test protocol., Results: Measurements of nucleated cell (NC) content of thawed DC vaccines with different types of hematology analyzers (HA) gave similar results for the majority of sites. Immunophenotyping using identical clones of monoclonal antibodies for the detection of surface antigens (i.e. CD1a, CD14, CD16, CD83, CD86 and HLA-DR) provided mostly comparable results between laboratories with an acceptable level of variation. In contrast, highly different results between study sites were generated for measuring the viability of thawed DC by flow cytometry using 7-amino-actinomycin D (7-AAD) dye exclusion., Discussion: In characterizing frozen/thawed DC vaccines, NC counts generated by HA yielded similar results between different laboratories. Furthermore, immunophenotyping of DC vaccines can be standardized between centers, i.e. by using identical reagents. Because of highly variable results between laboratories, 7-AAD viability testing of thawed DC needs to be studied further to identify potential causes for the observed variability.

Background: Soft tissue infections (STIs) from injection drug use are a common cause of Emergency Department visits, hospitalizations, and operating room procedures, yet little is known about factors that may predict the need for these costly medical services., Objective: To describe a cohort of injection drug users seeking Emergency Department care for STIs and to identify risk factors associated with hospitalization. We hypothesized that participants who delayed seeking care would be hospitalized more often than those who did not., Design: Cohort study using in-person structured interviews and medical record review. Logistic regression assessed the association between hospital admission and delay in seeking care as well as other demographic, clinical, and psychosocial factors., Participants: Injection drug users who sought Emergency Department care for STIs from May 2001 to March 2002., Results: Of the 136 participants, 55 (40%) were admitted to the hospital. Delay in seeking care was not associated with hospital admission. Participants admitted for their infection were significantly more likely to be living in a shelter (P = .01) and to report being hospitalized 2 or more times in the past year (P < .01)., Conclusions: We identified a subpopulation of injection drug users, mostly living in shelters, who were hospitalized frequently in the past year and who were more likely to be hospitalized for their current infections compared to others. As members of this subpopulation can be easily identified and located, they may benefit from interventions to reduce the health care utilization resulting from these infections.

Objective: We assessed the feasibility and efficacy of dendritic cell (DC) therapy for advanced thyroid papillary and follicular cancer., Design: Six Japanese patients (2 men and 4 women; aged 46-72 years, mean 60 years), who were diagnosed as advanced thyroid cancer with refractory distant metastases (papillary, n=5; follicular, n=1), were enrolled. Patients were first vaccinated weekly for 4 weeks with 10(7) autologous tumor lysate-pulsed monocyte-derived mature DCs followed by fortnightly vaccinations for 8 weeks (total=8 vaccinations). Lowdose (350 KIU) interleukin-2 was also administered for 3 days at each vaccination. Clinical response, adverse effects, delayed-type hypersensitivity skin testing (DTH), and IFN-( ) production by peripheral CD3(+) lymphocytes were evaluated., Main Outcome: Of the 6 patients, disease was assessed as stable in 2 and as progressive in 4. No adverse events were observed. Results of DTH and IFN-( ) production in peripheral lymphocytes did not correlate to the clinical response., Conclusions: DC immunotherapy could be administered to patients with thyroid papillary or follicular cancer without substantial side effects.

We reported previously that mesenchymal progenitor cells derived from chorionic villi of the human placenta could differentiate into osteoblasts, adipocytes, and chondrocytes under proper induction conditions and that these cells should be useful for allogeneic regenerative medicine, including cartilage tissue engineering. However, similar to human mesenchymal stem cells (hMSCs), though these placental cells can be isolated easily, they are difficult to study in detail because of their limited life span in vitro. To overcome this problem, we attempted to prolong the life span of human placenta-derived mesenchymal cells (hPDMCs) by modifying hTERT and Bmi-1, and investigated whether these modified hPDMCs retained their differentiation capability and multipotency. Our results indicated that the combination of hTERT and Bmi-1 was highly efficient in prolonging the life span of hPDMCs with differentiation capability to osteogenic, adipogenic, and chondrogenic cells in vitro. Clonal cell lines with directional differentiation ability were established from the immortalized parental hPDMC/hTERT+Bmi-1. Interestingly, hPDMC/Bmi-1 showed extended proliferation after long-term growth arrest and telomerase was activated in the immortal hPDMC/Bmi-1 cells. However, the differentiation potential was lost in these cells. This study reports a method to extend the life span of hPDMCs with hTERT and Bmi-1 that should become a useful tool for the study of mesenchymal stem cells.

Bacteriuria and urinary tract infection occur relatively frequently in older men, but data regarding the causative microorganisms are limited. We retrospectively identified all positive cultures of urine specimens (n = 4943) obtained over a 5-year period at our institution. We determined the frequency of causative microorganisms and grouped these by Gram type, setting of patient care, and method of urine specimen collection. We also assessed the performance characteristics of the Gram-stained smear of uncentrifuged urine. Among our patients, Gram-positive cocci (GPC) were isolated as often as Gram-negative rods (GNR). Escherichia coli was the single or predominant isolate in only 14% of cases, and Enterococcus was the single most commonly identified genus (22.5%). The Gram stain was accurate in predicting the culture results (positive likelihood ratio, 7.0 for GPC and 8.1 for GNR). We conclude that the microorganisms causing bacteriuria in older male veterans are substantially different from those found in women, and the Gram-stained smear provides useful information on the causative organisms.