Functional correlates and prevalence of mild parkinsonian signs in a community population of older people.
Mild parkinsonian signs (MPS) are associated with incident dementia and an increased risk of mortality. To our knowledge, the functional correlates of MPS have not been studied. To study the functional correlates of MPS, including self-reported and performance-based measures of function, and to determine the prevalence of MPS in a cohort of community-dwelling older people (aged >or=65 years). Participants (N = 1866) in the Washington Heights-Inwood Columbia Aging Project underwent a neurological assessment that included a modified motor portion of the Unified Parkinson's Disease Rating Scale, which yielded a parkinsonian sign score (range, 0-40) and parkinsonian sign subscores (axial function, rigidity, and tremor). A functional assessment included 3 self-reported measures of function and 2 performance-based tests. Participants with Parkinson disease were excluded. Mild parkinsonian signs were present in 469 (25.1%) of the 1866 participants. The parkinsonian sign score was correlated with functional and performance-based test scores (r = 0.24-0.32, P<.001). The axial function and rigidity subscores correlated to a greater extent with functional and performance-based test scores than did the tremor subscore. In analysis of covariance models, excluding participants with dementia and adjusting for age, sex, ethnicity, education, depressive symptoms, and medical illnesses (eg, arthritis), the parkinsonian sign score and age were strongly and independently associated with functional scores. Mild parkinsonian signs, and particularly axial dysfunction, were associated with functional disability, including self-reported and performance-based measures of functional difficulty. Given the high prevalence of these signs in elderly persons, MPS may be a significant indicator of disability in elderly persons.


Improving small molecule force fields by identifying and characterizing small molecules with inconsistent parameters.
Many molecular simulation methods use force fields to help model and simulate molecules and their behavior in various environments. Force fields are sets of functions and parameters used to calculate the potential energy of a chemical system as a function of the atomic coordinates. Despite the widespread use of force fields, their inadequacies are often thought to contribute to systematic errors in molecular simulations. Furthermore, different force fields tend to give varying results on the same systems with the same simulation settings. Here, we present a pipeline for comparing the geometries of small molecule conformers. We aimed to identify molecules or chemistries that are particularly informative for future force field development because they display inconsistencies between force fields. We applied our pipeline to a subset of the eMolecules database, and highlighted molecules that appear to be parameterized inconsistently across different force fields. We then identified over-represented functional groups in these molecule sets. The molecules and moieties identified by this pipeline may be particularly helpful for future force field parameterization.


Genetic Profile in Genes Associated with Cardiorespiratory Fitness in Elite Spanish Male Endurance Athletes.
most of the research concerning the influence of genetics on endurance performance has been carried out by investigating target genes separately. However, endurance performance is a complex trait that can stem from the interaction of several genes. The objective of this study was to compare the frequencies of polymorphisms in target genes involving cardiorespiratory functioning in elite endurance athletes vs. non-athlete controls. genotypic frequencies were determined in 123 elite endurance athletes and in 122 non-athletes. Genotyping of ACE (rs4340), NOS3 (rs2070744 and rs1799983), ADRA2a (rs1800544 and rs553668), ADRB2 (rs1042713 and rs1042714), and BDKRB2 (rs5810761) was performed by polymerase chain reaction. The total genotype score (TGS: from 0 to 100 arbitrary units; a.u.) was calculated from the genotype score in each polymorphism. the mean TGS in non-athletes (47.72 ± 11.29 a.u.) was similar to elite endurance athletes (46.54 ± 11.32 a.u., p = 0.415). The distribution of TGS frequencies were also similar in non-athletes and elite endurance athletes (p = 0.333). There was no TGS cut-off point to discriminate being elite endurance athletes. the genetic profile in the selected genes was similar in elite endurance athletes and in controls, suggesting that the combination of these genes does not determine endurance performance.


The Fanconi anemia proteins FANCD2 and FANCJ interact and regulate each other's chromatin localization.
Fanconi anemia is a genetic disease resulting in bone marrow failure, birth defects, and cancer that is thought to encompass a defect in maintenance of genomic stability. Mutations in 16 genes (FANCA, B, C, D1, D2, E, F, G, I, J, L, M, N, O, P, and Q) have been identified in patients, with the Fanconi anemia subtype J (FA-J) resulting from homozygous mutations in the FANCJ gene. Here, we describe the direct interaction of FANCD2 with FANCJ. We demonstrate the interaction of FANCD2 and FANCJ in vivo and in vitro by immunoprecipitation in crude cell lysates and from fractions after gel filtration and with baculovirally expressed proteins. Mutation of the monoubiquitination site of FANCD2 (K561R) preserves interaction with FANCJ constitutively in a manner that impedes proper chromatin localization of FANCJ. FANCJ is necessary for FANCD2 chromatin loading and focus formation in response to mitomycin C treatment. Our results suggest not only that FANCD2 regulates FANCJ chromatin localization but also that FANCJ is necessary for efficient loading of FANCD2 onto chromatin following DNA damage caused by mitomycin C treatment.


Graphene-supported tunable extraordinary transmission.
By depositing a graphene layer on the metallic film with subwavelength hole arrays, the tunable extraordinary transmission property based on the metal-dielectrics-graphene (MDG) structure has been investigated in the terahertz (THz) and near-infrared (NIR) regimes. The influences of operation frequency, composed materials, and the Fermi level of the graphene layer have been taken into account. The results show that by varying the Fermi level of the graphene layer, the transmission of the MDG structure can be tuned in a wide range and the modulation depth of the peak value of the transmission can reach more than 50%. But the tunable mechanisms in the THz and NIR regimes are quite different. In the infrared (THz) regime, the graphene behaves like the dielectric (metallic) layer; its dielectric constant decreases (increases) with the increase of Fermi level, resulting in the transmission increasing (decreasing). Compared with the metallic structure, the transmission of the semiconductor structure can also be modulated by using the doping or varying temperature; its peak position can also be changed in a much broader range. The results are very useful to understand the mechanism of the graphene plasmonic devices and to design novel filters, switchers, modulators, and sensors.


Vignette methodology and culture-relevance: lessons learned through a project on successful aging with Iranian immigrants to Sweden.
It is a well-known fact that cultural values play an important role in the construction of aging and old-age related understandings. This is why ethnogerontologists have tried to expand the gerontological imagination by arguing that research needs to become more culturally-relevant. Tapping into the values that people uphold and the understandings of aging that are shaped by them is a challenging endeavor. This is especially the case if one does not share the cultural background of the people whose values one is studying. The same holds true when one wants to shed light on understandings that mainstream social gerontology regards as deviations from the norm. It is after all relatively easy to "impose the Western template" under such circumstances. Vignette methodology has been found to be particularly useful when studying value-laden understandings. This is why it is an appropriate method to consider when designing research that aims to avoid the imposition of the Western template. This article focuses on the pros and cons of this methodology while discussing some of the lessons learned from a project that explored how the construct of successful aging is understood by a group of Iranian immigrants to Sweden. It will be argued that vignettes are particularly useful when trying to shed culturally-relevant light on aging and old age-related understandings.


Glycoprotein gB (gII) of pseudorabies virus can functionally substitute for glycoprotein gB in herpes simplex virus type 1.
Glycoproteins homologous to gB of herpes simplex virus (HSV) constitute the most highly conserved family of herpesvirus glycoproteins. All gB homologs analyzed so far have been shown to play essential roles in penetration and direct viral cell-to-cell spread. In studies aimed at assessing whether the high sequence homology is also indicative of functional homology, we analyzed the ability of the gB-homologous glycoprotein (former designation gII) of pseudorabies virus (PrV) to complement a gB- HSV type 1 (HSV-1) mutant and vice versa. The results show that a PrV gB-expressing cell line phenotypically complemented the lethal defect in gB- HSV-1 whereas reciprocal complementation of a gB- PrV mutant by HSV-1 gB was not observed.


Comparison of text messaging and paper-and-pencil for ecological momentary assessment of food craving and intake.
Electronic devices such as mobile phones are quickly becoming a popular way to gather participant reports of everyday thoughts, feelings, and behaviors, including food cravings and intake. Electronic devices offer a number of advantages over alternative methods such as paper-and-pencil (PNP) assessment including automated prompts, on-the-fly data transmission, and participant familiarity with and ownership of the devices. However, only a handful of studies have systematically compared compliance between electronic and PNP methods of ecological momentary assessment (EMA), and none have examined eating specifically. Existing comparisons generally find greater compliance for electronic devices than PNP, but there is variability in the results across studies that may be accounted for by differences across research domains. Here, we compared the two EMA methods in an unexamined domain - eating - in terms of response rate and response latency, and their sensitivity to individual difference variables such as body mass index (BMI). Forty-four participants were randomly assigned to report on their food craving, food intake, and hunger four times each day for 2 weeks using either a PNP diary (N = 19) or text messaging (TXT; N = 25). Response rates were higher for TXT than PNP (96% vs. 70%) and latencies were faster (29 min vs. 79 min), and response rate and latency were less influenced by BMI in the TXT condition than in the PNP condition. These results support the feasibility of using text messaging for EMA in the eating domain, and more broadly highlight the ways that research domain-specific considerations (e.g., the importance of response latency in measuring short-lived food craving) interact with assessment modality during EMA.


Fabrication of an efficient BaTaO2N photoanode harvesting a wide range of visible light for water splitting.
Photoanodes made from BaTaO2N that can harvest visible light up to 660 nm wavelength were fabricated on Ti substrates for achieving efficient water splitting. Both pre-treatment of BaTaO2N particles with an H2 stream and post-necking treatment with TaCl5 effectively increased the photocurrent due to the decreased electrical resistance in the porous BaTaO2N photoanode. A combination of pre-loading of CoO(x) on the BaTaO2N particles and post-loading of RhO(x) significantly improved both the photocurrent and stability under visible light irradiation, along with an obvious negative shift (ca. 300 mV) of the onset potential for water oxidation, while sole loading resulted in a lower photocurrent or insufficient stability. The IPCE value was estimated to be ca. 10% at 1.2 V vs RHE under 600 nm, which is the highest among photoanode materials that can harvest light beyond 600 nm for water oxidation. Photoelectrochemical water splitting into H2 and O2 under visible light was demonstrated using RhO(x)/CoO(x)/BaTaO2N/Ti photoanodes under an externally applied bias larger than 0.7 V to a Pt counter electrode.


Alternate use of thrombopoietin receptor agonists in adult primary immune thrombocytopenia patients: A retrospective collaborative survey from Italian hematology centers.
Sequential use of the TPO-RAs romiplostim and eltrombopag in ITP patients failing either agent was retrospectively evaluated to assess efficacy and impact of clinical characteristics on outcome. Patients were grouped into 5 categories: efficacy issues: 1st TPO-RA failure; loss of response; non-efficacy issues: platelet fluctuations; patient's preference; adverse event development. Either one TPO-RA sequence was analyzed at 3 month and at last follow-up. 106/546 patients on TPO-RA underwent switch and 65% achieved, regained or maintained a short- term response independent of switch sequence, gender or age; lower response rates were associated with lines of previous therapy; disease duration lowers probability to respond. Clinically, patients switched for efficacy issue did not differ from those switched for non-efficacy issues. Response was achieved/regained in 57.8% of patients switched for efficacy issues, the lowest response rates were observed in non-responders to 1st TPO-RA; 80% of patients switched for non-efficacy issues maintained a response. Platelet fluctuation resolved in 44.4%. Of the 49 patients evaluable for long-term outcome, 27 were in response on therapy; 16 discontinued the TPO-RA for reasons other than efficacy, while only 6 were non responders. We confirm the efficacy of TPO-RA switch; once achieved, response to the 2nd TPO-RA seems durable.


[The automatization of the control over the processes determining the risk of HIV-infection spreading among servicemen].
The possibilities of the control over the processes determining the HIV-infection spreading risk are considered. In the view of that the automated system which enables to evaluate risk factors predetermining the appearance of new infection cases was proposed. These factors are systematised in a multilevel database. On the basis of the statistical analysis of the risk factors situations of the spread of the HIV infection are revealed and analysed and measures for their liquidation are worked out promptly. The system is universal and can be used for the prevention of the beginning of other extreme situations caused by the spread of different infections. The examples of the comparative analysis of the risk of sexual behaviour in various groups of servicemen are given.


Engineering Phase Transition from 2H to 1T in MoSe2 by W Cluster Doping toward Lithium-Ion Battery.
Phase engineering synthesis strategy is extremely challenging to achieve stable metallic phase molybdenum diselenide for a better physicochemical property than the thermodynamically stable semiconducting phase. Herein, we introduce tungsten atom clusters into the MoSe2 layered structure, realizing the phase transition from the 2H semiconductor to 1T metallic phase at a high temperature. The combination of synchrotron radiation X-ray absorption spectroscopy, Cs-corrected transmission electron microscopy, and theoretical calculation demonstrates that the aggregation doping of W atoms is the factor of MoSe2 structure transformation. When utilizing this distinct structure as an anode component, it demonstrates outstanding rate capability and durability. After 500 cycles, this results in a specific capacity of 1007.4 mAh g-1 at 500 mA g-1. These discoveries could open the door for the future development of high-performance anodes for ion battery applications.


Benefits, harms, and costs for breast cancer screening after US implementation of digital mammography.
Compared with film, digital mammography has superior sensitivity but lower specificity for women aged 40 to 49 years and women with dense breasts. Digital has replaced film in virtually all US facilities, but overall population health and cost from use of this technology are unclear. Using five independent models, we compared digital screening strategies starting at age 40 or 50 years applied annually, biennially, or based on density with biennial film screening from ages 50 to 74 years and with no screening. Common data elements included cancer incidence and test performance, both modified by breast density. Lifetime outcomes included mortality, quality-adjusted life-years, and screening and treatment costs. For every 1000 women screened biennially from age 50 to 74 years, switching to digital from film yielded a median within-model improvement of 2 life-years, 0.27 additional deaths averted, 220 additional false-positive results, and $0.35 million more in costs. For an individual woman, this translates to a health gain of 0.73 days. Extending biennial digital screening to women ages 40 to 49 years was cost-effective, although results were sensitive to quality-of-life decrements related to screening and false positives. Targeting annual screening by density yielded similar outcomes to targeting by age. Annual screening approaches could increase costs to $5.26 million per 1000 women, in part because of higher numbers of screens and false positives, and were not efficient or cost-effective. The transition to digital breast cancer screening in the United States increased total costs for small added health benefits. The value of digital mammography screening among women aged 40 to 49 years depends on women's preferences regarding false positives.


Allodynia-like effects in rat after ischaemic spinal cord injury photochemically induced by laser irradiation.
We report behaviours suggesting the presence of allodynia elicited by non-noxious brushing and mechanical pressure following photochemically induced ischaemic spinal cord injury in the rat. Female rats were intravenously injected with Erythrosin B and the T10 vertebra was irradiated with a laser beam for 1, 5 or 10 min. These procedures initiated an intravascular photochemical reaction, resulting in ischaemic spinal cord injury. After irradiation a clear allodynia was observed in most rats. The animals vocalized intensely to light touch during gentle handling and were clearly agitated to light brushing of the flanks. The vocalization threshold in response to the mechanical pressure measured with von Frey hairs was markedly decreased during this period. In some animals the existence of spontaneous pain was suggested by spontaneous vocalization. The duration of the allodynia varied among animals from several hours to several days. The severity and duration of allodynia seemed not to be related to the duration of irradiation. In sham-operated rats a slight, transient allodynia was also noted around the wound within a few hours after surgery, which was effectively relieved by systemic morphine (2 mg/kg, i.p.). Morphine (2 mg/kg, i.p.) also partially relieved the allodynia in spinally injured rats 4 h after irradiation. However, morphine, even at a higher dose (5 mg/kg, i.p.), failed to alleviate the allodynia in spinally injured rats 24-48 h after the injury. Systemic injection of the GABAB agonist baclofen (0.01-0.1 mg/kg, i.p.), but not the GABAA agonist muscimol (1 mg/kg, i.p.), effectively relieved allodynia during this period. Pretreatment with guanethidine 24 h and just prior to the irradiation (20 mg/kg, s.c.) did not prevent the occurrence of allodynia in spinal cord injured rats. The present observation is the first to show that ischaemic spinal cord injury could result in cutaneous mechanical allodynia. This phenomenon is resistant to morphine and may not involve the sympathetic system. Histological examination of allodynic animals 3 days after spinal cord injury revealed considerable morphological damage in the dorsal spinal cord of a rat irradiated for 5 min. The related dorsal roots were also slightly affected in this animal, while the dorsal root ganglia were normal. However, in rats irradiated for 1 min, despite the existence of strong allodynia, no damage could be found at this time in the spinal cord, dorsal roots or dorsal root ganglia. It is suggested that functional deficits in the GABAB system in the spinal cord may be related to this allodynia-like phenomenon.(ABSTRACT TRUNCATED AT 400 WORDS)


Extracorporeal virus elimination for the treatment of severe Ebola virus disease--first experience with lectin affinity plasmapheresis.
Therapeutic options for Ebola virus disease (EVD) are currently limited to (1) best supportive care, and (2) evolving virus-specific therapies, resulting from decades of analyzing one of the world's deadliest diseases. Supportive care ranges from oral or intravenous rehydration therapy and anti-emetics in developing countries to much more extensive life-support interventions in resource-rich countries. Current EVD-specific therapies attempt to either interfere with the earliest steps of viral replication or to elicit a strong immune response against the virus. An entirely new approach is the extracorporeal elimination of viruses and viral glycoproteins by lectin affinity plasmapheresis. Herein, we report for the first time the successful and safe use of lectin affinity plasmapheresis in a patient with severe Ebola virus disease.


A small-angle X-ray scattering study of the structure of lysozyme-sodium dodecyl sulfate complexes.
The structure of lysozyme-sodium dodecyl sulfate (SDS) complexes in solution is studied using small-angle X-ray scattering (SAXS). The SAXS data cannot be explained by the necklace and bead model for unfolded polypeptide chain interspersed with surfactant micelles. For the protein and surfactant concentrations used in the study, there is only marginal growth of SDS micelles as they complex with the protein. Being a small and rather rigid protein, lysozyme can penetrate the micellar core which is occupied by flexible and disordered paraffin chains and also the shell occupied by the hydrated head groups. A partially embedded swollen micellar model seems appropriate and describes well the scattering data. The SAXS intensity profiles are analyzed by considering the change in the electron scattering length density of the micellar core and shell due to complexation with protein and treating the intermicellar interaction using rescaled mean spherical approximation (RMSA) for charged spheres.


An analysis of patient variables that influence intravenous patient-controlled analgesic use of morphine with quantile regression.
Previous studies using linear regression analysis have shown that age, weight, gender, and the site of operation affect intravenous patient-controlled analgesia (IVPCA) narcotic use. However, there are inconsistent observations in the literature. The authors postulate that patient variables could have different effects at various doses of narcotics. To test this hypothesis, the authors analyzed the effect of patient variables on increasing doses of IVPCA narcotic with quantile regression. The authors collected retrospective data from 1,782 patients who received IVPCA for a minimum of 3 days after surgery. The authors used stepwise linear regression model to identify variables that significantly affected the total IVPCA requirements. Quantile regression model was further applied to assess the effects of selected variables on the ascending percentile of IVPCA narcotic use. Gender, age, body weight, cancer, and surgical site were identified as significant predictors for IVPCA demand. Body weight had the most and cancer had the least significant effects on total IVPCA demands. The results of quantile regression model revealed that the determinants under consideration varied with different percentiles of IVPCA demand. The patient variables correlated with IVPCA narcotic use differently when the dose exceeded the seventieth to eightieth percentiles compared with other percentiles of narcotic use. The authors' findings highlight the heterogeneous postoperative pain requirements among patients and the consequent complex process of efficiently managing postoperative pain.


Dissociation between neuronal activity in sensorimotor cortex and hand movement revealed as a function of movement rate.
It is often assumed that similar behavior is generated by the same brain activity. However, this does not take into account the brain state or recent behavioral history and movement initiation or continuation may not be similarly generated in the brain. To study whether similar movements are generated by the same brain activity, we measured neuronal population activity during repeated movements. Three human subjects performed a motor repetition task in which they moved their hand at four different rates (0.3, 0.5, 1, and 2 Hz). From high-resolution electrocorticography arrays implanted on motor and sensory cortex, high-frequency power (65-95 Hz) was extracted as a measure of neuronal population activity. During the two faster movement rates, high-frequency power was significantly suppressed, whereas movement parameters remained highly similar. This suppression was nonlinear: after the initial movement, neuronal population activity was reduced most strongly, and the data fit a model in which a fast decline rapidly converged to saturation. The amplitude of the beta-band suppression did not change with different rates. However, at the faster rates, beta power did not return to baseline between movements but remained suppressed. We take these findings to indicate that the extended beta suppression at the faster rates, which may suggest a release of inhibition in motor cortex, facilitates movement initiation. These results show that the relationship between behavior and neuronal activity is not consistent: recent movement influences the state of motor cortex and facilitates next movements by reducing the required level of neuronal activity.


Role of the Transforming-Growth-Factor-β1 Gene in Late-Onset Alzheimer's Disease: Implications for the Treatment.
Late-onset Alzheimer's disease (LOAD) is the most common form of dementia in the elderly. LOAD has a complex and largely unknown etiology with strong genetic determinants. Genetics of LOAD is known to involve several genetic risk factors among which the Apolipoprotein E (APOE) gene seems to be the major recognized genetic determinant. Recent efforts have been made to identify other genetic factors involved in the pathophysiology of LOAD such as genes associated with a deficit of neurotrophic factors in the AD brain. Genetic variations of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF), and transforming-growth-factor-β1 (TGF-β1) are known to increase the risk to develop LOAD and have also been related to depression susceptibility in LOAD. Transforming-Growth-Factor-β1 (TGF-β1) is a neurotrophic factor that exerts neuroprotective effects against ß-amyloid-induced neurodegeneration. Recent evidence suggests that a specific impairment in the signaling of TGF-β is an early event in the pathogenesis of AD. TGF-β1 protein levels are predominantly under genetic control, and the TGF-β1 gene, located on chromosome 19q13.1-3, con-tains several single nucleotide polymorphisms (SNPs) upstream and in the transcript region, such as the SNP at codon +10 (T/C) and +25 (G/C), which is known to influence the level of expression of TGF-β1. In the present review, we summarize the current literature on genetic risk factors for LOAD, focusing on the role of the TGF-β1 gene, finally discussing the possible implications of these genetic studies for the selection of patients eligible for neuroprotective strategies in AD.


Rural population estimates: an analysis of a large secondary data set.
Health services research often utilizes secondary data sources such as the Behavioral Risk Factor Surveillance System (BRFSS). Since 2006, the released BRFSS data do not include respondents who live in counties with 10,000 or fewer residents, and the CDC no longer offers the opportunity to access the unrestricted data set. As a result, rural residents can be underrepresented in BRFSS data after 2005. The purpose of this analysis is to examine the potential for bias introduced by rural underestimation. We utilized 6 BRFSS data sets; the 2005 full data and the 2005-2009 restricted data. We estimated population sizes for each survey year, and we compared these estimates to comparable data from the US Census intercensal estimates. We also compared estimates of preventive service utilization (mammography, Pap tests, colorectal cancer screening, and influenza vaccinations) between the two 2005 data versions. Rural populations were underrepresented, particularly with the smaller counties excluded. Remote rural residents were the most consistently underrepresented. Preventive service delivery estimates differed between the full and restricted 2005 data versions. Mammography and Pap test estimates tended to be higher in the restricted data, while colorectal cancer screening and influenza vaccinations were similar or inconsistent. These results indicate that restricting by county size introduced bias in these estimates. Having quality, nationally representative data is important to study disparities in service delivery. The potential bias introduced by the BRFSS county restriction may result in rural research being less effective for policy recommendations and interventions.


Seeking Consensus on the Terminology of Value-Based Transformation Through use of a Delphi Process.
Collaboration among diverse stakeholders involved in the value transformation of health care requires consistent use of terminology. The objective of this study was to reach consensus definitions for the terms value-based care, value-based payment, and population health. A modified Delphi process was conducted from February 2017 to July 2017. An in-person panel meeting was followed by 3 rounds of surveys. Panelists anonymously rated individual components of definitions and full definitions on a 9-point Likert scale. Definitions were modified in an iterative process based on results of each survey round. Participants were a panel of 18 national leaders representing population health, health care delivery, academic medicine, payers, patient advocacy, and health care foundations. Main measures were survey ratings of definition components and definitions. At the conclusion of round 3, consensus was reached on the following definition for value-based payment, with 13 of 18 panelists (72.2%) assigning a high rating (7- 9) and 1 of 18 (5.6%) assigning a low rating (1-3): "Value-based payment aligns reimbursement with achievement of value-based care (health outcomes/cost) in a defined population with providers held accountable for achieving financial goals and health outcomes. Value-based payment encourages optimal care delivery, including coordination across healthcare disciplines and between the health care system and community resources, to improve health outcomes, for both individuals and populations." The iterative process elucidated specific areas of agreement and disagreement for value-based care and population health but did not reach consensus. Policy makers cannot assume uniform interpretation of other concepts underlying health care reform efforts.


In the Belly of the Beast: Traumatic Countertransference.
The authors discuss their work together in a consultation process. One author led many groups that were created to facilitate recovery for persons directly impacted by the terrorist attacks on September 11, 2001; the other acted as consultant to the therapist/leader. The leader was a resident of New York City at the time of the attacks; the consultant lived in a distant Midwestern city and the two had never met prior to the work. They describe their experience of working together and the role of this collaboration in the lives of the leader and the groups. Well aware that little exists in the literature about groups led by leaders having experienced the same trauma as group members, the authors pay special attention to the countertransference that each underwent and raise questions about the effects of that on the group process.


TC2N Promotes Cell Proliferation and Metastasis in Hepatocellular Carcinoma by Targeting the Wnt/β-Catenin Signaling Pathway.
Hepatocellular carcinoma (HCC), one of the most prevalent types of cancer worldwide, has an exceedingly poor prognosis. Tandem C2 domain nuclear protein (TC2N) has been implicated in tumorigenesis and serves as an oncogene or tumor suppressor in different types of cancer. Here, we explore the possible regulatory activities and molecular mechanisms of TC2N in HCC progression. However, TC2N expression was significantly upregulated in HCC tissues and hepatoma cell lines, and this upregulation was positively correlated with tumor progression in HCC patients. The ectopic overexpression of TC2N accelerated the proliferation, migration, and invasion of HCC cells, whereas its knockdown showed the opposite effects. Bioinformatics analysis showed that TC2N participates in the regulation of the Wnt/β-catenin signaling pathway. Mechanistically, TC2N activated the Wnt/β-catenin signaling pathway by regulating the expression levels of β-catenin and its downstream targets CyclinD1, MMP7, c-Myc, c-Jun, AXIN2, and glutamine synthase. Furthermore, the deletion of β-catenin effectively neutralized the regulation of TC2N in HCC proliferation and metastasis. Overall, this study showed that TC2N promotes HCC proliferation and metastasis by activating the Wnt/β-catenin signaling pathway, indicating that TC2N might be a potential molecular target for the treatment of HCC.


Assessment of local recurrence after breast-conserving therapy with MRI.
The purpose of our study was to evaluate the relevance of MR mammography in the diagnosis of early and late tumor recurrence after breast-conserving therapy. Sixty-seven patients receiving breast-conserving therapy underwent 84 MR mammographies in a period between 1 month and 14 years after end of therapy. Dynamic measurements were made following application of contrast agent. The course of signal intensity changes was evaluated in focal lesions and irradiated and contralateral glandular tissue. All 10 malignant lesions (7 local recurrences, 1 chest wall recurrence, 2 contralateral carcinomas) showed a > 75% increase in signal intensity within th first minute after contrast agent application. In all patients examined during the first year after end of therapy (n = 29), increased enhancement in irradiated parenchyma was observed compared with the contralateral breast, but only in two patients the increase was > 75% within the first minute. Already in the first year after end of therapy, MRI can improve diagnostic accuracy in the assessment of breast cancer recurrence. More than 12 months following end of therapy, MR mammography can demonstrate tumor recurrence with a sensitivity of nearly 100% and a specificity rising to > 90% in differentiating tumor from therapy-induced changes.


Nd3+ sensitized dumbbell-like upconversion nanoparticles for photodynamic therapy application.
Better tissue penetration and lower overheating problems mean 808 nm near-infrared laser excited upconversion nanoparticles (UCNPs) have potential in bioapplications. Dumbbell-like structured NaYF4:Yb/Er@NaNdF4:Yb nanoparticles are fabricated in this work and applied in photodynamic therapy (PDT). The epitaxial growth along the c axis attributed to the large structure mismatch of NaNdF4versus NaYF4 has been demonstrated to play a key role in the growth of the dumbbell structure. Due to better space separation in this structure, energy back-transfer from Er3+ to Nd3+ is prohibited partially, and the optimized Nd3+ doping concentration is up to 90% for a high UC emission intensity. PDT effects of these dumbbell-like structured UCNPs upon 808 nm laser irradiation were examined and compared with isotropic NaYF4:Yb/Er@NaYF4:Nd0.2 core-shell and NaYF4:Yb/Er@NaYF4:Nd0.2@NaYF4 core-shell-shell UCNPs. The results show that the dumbbell-like UCNPs are most effective in generating singlet oxygen (1O2) and killing cancer cells in PDT though their UC emission intensity is lower than that of the core-shell-shell UCNPs. This research presents a simple yet valid strategy to balance the UCL efficiency and FRET efficiency, which may lead to better PDT therapeutic effect for cancer therapy.


Design of a high-precision, 0.5 m aperture Cassegrain collimator.
We present the realization of a high-precision, 0.5 m aperture size Cassegrain collimator system. The optical design, the optomechanical design, the mirror manufacturing, and the telescope alignment with a performance evaluation are extensively discussed. The optical design of the collimator is based on the Cassegrain telescope design with two aspheric mirrors. An athermalized, high stability optomechanical structure is conceived for the collimator to meet stringent performance requirements. The high-quality mirrors are made of low-expansion Zerodur glass-ceramic and the primary mirror is light-weighted to 63% of its initial weight. The design of a dedicated five-axis flexure mechanism driven by nanopositioner stages to compensate the secondary mirror misalignments is given. Primary and secondary mirrors with aspheric surfaces are manufactured, and their forms are measured by computer-generated holograms with a phase-shifting Fizeau interferometer. The alignment strategy is based on minimizing Fringe Zernike coefficients of wavefront decomposition measured by an autocollimation test setup. The alignment sensitivity and corresponding Fringe Zernike coefficient terms are determined by the ray-tracing software that introduces the intentional misalignments of the secondary mirror. The on-axis alignment of the collimator is performed with the guidance of sensitivity analysis results. The final root-mean-square wavefront error for the collimated beam is measured to be 0.021λ.


Effects of Smoking Versus Nonsmoking on Postprandial Glucose Metabolism in Heavy Smokers Compared With Nonsmokers.
Epidemiological studies suggest that smoking increases the risk of type 2 diabetes. We hypothesized that smoking-derived nicotine and ensuing activation of nicotinic cholinergic receptors in the gastrointestinal tract and the autonomic nervous system would have a detrimental effect on postprandial glucose metabolism and, thus, potentially constitute a link between smoking and the development of type 2 diabetes. We subjected 11 male heavy smokers to two identical 4-h liquid mixed-meal tests: one with concomitant cigarette smoking (immediately before and after meal intake) and one without smoking. Twelve age-, sex-, and BMI-matched nonsmokers underwent an identical meal test without smoking. The smokers were characterized by higher fasting plasma concentrations of glucagon compared with the nonsmokers. Among smokers, cigarette smoking before and after the meal significantly reduced postprandial plasma glucose excursions. There were no differences in gut or pancreatic hormone concentrations between the test days in the smoking group, and the responses were similar to those in the control group. Our results suggest that smoking in association with meal intake decreases the postprandial plasma glucose concentrations, possibly through decreased gastric emptying, and that elevated fasting glucagon concentrations rather than smoking-induced alterations in postprandial glucose and hormone responses may be associated with the elevated risk of type 2 diabetes in chronic smokers.


Health care über alles: how it works in Germany.
The German healthcare financing system combines regulated, employment-based "sickness funds" for most workers and private insurance available to those above an income threshold. Costs are paid on a fee-for-service basis to private physicians and at an all-inclusive per diem rate to hospitals. Workers and their employers contribute to sickness funds at a percentage of their earnings. The German government sets regulations by which services are provided but does not actively administer either services or payment.


Osteoimmunology: The Nexus between bone and immune system.
Osteoimmunology is an interdisciplinary research field which combines the existing fields of osteology (bone biology) and immunology under one umbrella. The observation that contributed enormously to the emergence of osteoimmunology as an independent field of investigation was the enhanced bone loss in various inflammatory bone diseases such as rheumatoid arthritis, osteoporosis and periodontitis. T helper cells (Th1, Th2, Treg and Th17) along with various other immune cells (B cells, DC, macrophages etc.) are actively involved in bone homeostasis. The present review thus provides an overview of the nexus between these two prominent systems (Bone and Immune system) of an organism, which reside in a common niche (bone marrow) and thus cross-communicate to modulate their respective development. Investigations in the field of osteoimmunology thus promise the advent of new era in the field with novel therapeutics for bone loss in various inflammatory conditions. A molecular insight into the field of osteoimmunology can lead to novel approaches for the prevention and treatment of diverse inflammatory conditions such as osteoporosis, rheumatoid arthritis and osteoarthritis.


Direct Base-Assisted C‒H Cyclonickelation of 6-Phenyl-2,2'-bipyridine.
The organonickel complexes [Ni(Phbpy)X] (X = Br, OAc, CN) were obtained for the first time in a direct base-assisted arene C(sp2)-H cyclometalation reaction from the rather unreactive precursor materials NiX2 and HPhbpy (6-phenyl-2,2'-bipyridine) or from the versatile precursor [Ni(HPhbpy)Br2]2. Different from previously necessary C‒Br oxidative addition at Ni(0), an extended scan of reaction conditions allowed quantitative access to the title compound from Ni(II) on synthetically useful timescales through base-assisted C‒H activation in nonpolar media at elevated temperature. Optimisation of the reaction conditions (various bases, solvents, methods) identified 1:2 mixtures of acetate and carbonate as unrivalled synergetic base pairs in the optimum protocol that holds promise as a readily usable and easily tuneable access to a wide range of direct nickelation products. While for the base-assisted C‒H metalation of the noble metals Ru, Ir, Rh, or Pd, this acetate/carbonate method has been established for a few years, our study represents the leap into the world of the base metals of the 3d series.


Survival and neurologic outcome after out-of-hospital cardiac arrest: results one year after regionalization of post-cardiac arrest care in a large metropolitan area.
Post-resuscitation care of cardiac arrest patients at specialized centers may improve outcome after out-of-hospital cardiac arrest (OOHCA). This study describes experience with regionalized care of resuscitated patients. Los Angeles (LA) County established regionalized cardiac care in 2006. Since 2010, protocols mandate transport of nontraumatic OOHCA patients with field return of spontaneous circulation (ROSC) to a STEMI Receiving Center (SRC) with a hypothermia protocol. All SRC report outcomes to a registry maintained by the LA County Emergency Medical Services (EMS) Agency. We report the first year's data. The primary outcome was survival with good neurologic outcome, defined by a Cerebral Performance Category (CPC) score of 1 or 2. The SRC treated 927 patients from April 2011 through March 2012 with median age 67; 38% were female. There were 342 patients (37%) who survived to hospital discharge. CPC scores were unknown in 47 patients. Of the 880 patients with known CPC scores, 197 (22%) survived to hospital discharge with a CPC score of 1 or 2. The initial rhythm was VF/VT in 311 (34%) patients, of whom 275 (88%) were witnessed. For patients with an initial shockable rhythm, 183 (59%) survived to hospital discharge and 120 (41%) had survival with good neurologic outcome. Excluding patients who were alert or died in the ED, 165 (71%) patients with shockable rhythms received therapeutic hypothermia (TH), of whom 67 (42%) had survival with good neurologic outcome. Overall, 387 patients (42%) received TH. In the TH group, the adjusted OR for CPC 1 or 2 was 2.0 (95%CI 1.2-3.5, p = 0.01), compared with no TH. In contrast, the proportion of survival with good neurologic outcome in the City of LA in 2001 for all witnessed arrests (irrespective of field ROSC) with a shockable rhythm was 6%. We found higher rates of neurologically intact survival from OOHCA in our system after regionalization of post-resuscitation care as compared to historical data.


Combined effect of using near-infrared spectroscopy for nutritional evaluation of feed ingredients and non-starch polysaccharide carbohydrase complex on performance of broiler chickens.
This study was carried out to evaluate the combined effect of using near-infrared spectroscopy (NIRS) for nutritional evaluation of feed ingredients and the addition of non-starch polysaccharide carbohydrase complex (NSP enzymes) on the growth performance of broilers fed diets produced with low-quality wheat and soybean meal. A 2 × 2 trial design was performed, with seven replicates of 40 male Ross 308 broilers per treatment, evaluating the effect of the addition of NSP enzymes and the ingredients' nutritional matrix based on table values or NIRS values. Diets without added enzymes were formulated to reach nutritional requirements, whereas diets with enzymes were reformulated, reducing the apparent metabolizable energy (AME) by 85 kcal/kg. In the overall period (days 0-35), broilers fed diets formulated using NIRS values had higher (P < 0.001) average daily gain (+11.3%) and daily feed intake (+7.2%), and a lower (P < 0.001) feed conversion ratio (-5.3%) compared to those fed diets formulated using table values. When formulating diets for broilers with low-quality feed ingredients, performance can be improved by considering NIRS values and by the addition of NSP enzymes, even with a reduction of AME. These nutritional approaches are efficient in improving broilers' performances by themselves and even more so when they are combined.


A case history of myopathic carnitine deficiency benefited by glucocorticoids and L-carnitine supplementation.
While the term "drug-nutrient interactions" tends to conjure up a concept of an adverse combination, such as anticonvulsants impairing folate metabolism or alcohol blocking active thiamine absorption, there are situations in which a drug and nutrient can act in a complementary manner, to correct a metabolic defect. This case history illustrates such a positive interaction of glucocorticoids and L-carnitine supplements improving muscle function in a patient with myopathic carnitine deficiency.


Slowing of bone loss in patients with rheumatoid arthritis by long-term high-intensity exercise: results of a randomized, controlled trial.
Patients with rheumatoid arthritis (RA) are more at risk for the development of osteoporosis and osteoporotic fractures than are their healthy peers. In this randomized, controlled, multicenter trial, the effectiveness of a 2-year high-intensity weight-bearing exercise program (the Rheumatoid-Arthritis-Patients-In-Training [RAPIT] program) on bone mineral density (BMD) was compared with usual care physical therapy, and the exercise modalities associated with changes in BMD were determined. Three hundred nine patients with RA were assigned to an intervention group, either the RAPIT program or usual care physical therapy. The primary end points were BMD of the hip and spine. The exercise modalities examined were aerobic fitness, muscle strength, and, as a surrogate for those effects not directly measured by the RAPIT program, attendance rate. The data on the 136 RAPIT participants and 145 usual care participants who completed the study were analyzed. The mean rate of decrease in hip BMD, but not in lumbar spine BMD, was smaller in patients participating in the RAPIT program when compared with that in the usual care group, with a mean decrease of 1.6% (95% confidence interval [95% CI] 0.8-2.5) over the first year and 0.5% (95% CI 1.1-2.0) over the second year. The change in hip BMD was significantly and independently associated with changes in both muscle strength (multivariate odds ratio [OR] 1.75, 95% CI 1.07-2.86) and aerobic fitness (OR 1.79, 95% CI 1.10-2.90), but not with the attendance rate (OR 1.00, 95% CI 0.99-1.00). A long-term high-intensity weight-bearing exercise program for RA patients is effective in slowing down the loss of BMD at the hip. The exercise modalities associated with this effect are muscle strength and aerobic fitness.


Medical journals in Louisiana before the Civil War.
This study, an historical survey of medical journals in Louisiana before the outbreak of the Civil War in 1861, revealed that nine journals made an appearance during the period covered-all of them published in New Orleans. Of these, two were French language journals published by a French medical society. The others were all published by individuals rather than by professional societies. Medical practices, interests, and problems of the times were clearly reflected on the pages of the journals. It is evident that medical journalism reached a high plane in the era before the Civil War. Of the nine periodicals, only one emerged as a permanent publication after the War.


Bacterial organomercurial lyase: overproduction, isolation, and characterization.
Organomercurial lyase mediates the first of two steps in the microbial detoxification of organomercurial salts. This enzyme encoded on the plasmid R831 obtained from Escherichia coli J53-1 has been overproduced to the level of 3% of the soluble cell protein in E. coli by a construction using the T7 promoter. The enzyme has been purified to homogeneity in quantity in three steps. It is a monomer of Mr 22,400 with no detectable cofactors or metal ions. It catalyzes the protonolysis of the C-Hg bond in a wide range of organomercurial salts (primary, secondary, tertiary, alkyl, vinyl, allyl, and aryl) to the hydrocarbon and mercuric ion with turnover rates in the range of 1-240 min-1.


Changes in Medicaid physician fees and patterns of ambulatory care.
Controlling for state fixed effects and other factors, this paper estimates the effect of the generosity of Medicaid physician payment levels on the volume and site of ambulatory care received by Medicaid patients compared to privately insured patients. Results indicate that cuts in Medicaid physician fees lead to statistically significant reductions in the number of visits for Medicaid patients compared to privately insured patients. Cuts in fees also lead to a statistically significant shift away from physician offices and toward hospital emergency departments and especially outpatient departments. Primary diagnoses for which site of care shifts are most pronounced include hypertension, asthma, urinary tract infections, and diabetes.


Sexual and gender identity and note-leaving among adult suicide decedents in the USA.
Suicide is one of the leading causes of preventable death in the USA, representing a critical public health threat. Suicide risks differ for different populations. In particular, the sexual and gender minority (SGM) population remains at increased risk for suicide. One of the circumstances that may differ for SGM and non-SGM individuals is the propensity to leave a suicide note. Information regarding note-leaving may be helpful in informing suicide prevention and intervention. This study documents the differences in note-leaving in SGM individuals compared with non-SGM individuals, using recent data from the National Violent Death Reporting System (N = 98 515) and accounting for important covariates. We fit a logistic regression model with SGM status and covariates predicting note-leaving in suicide. SGM decedents were 1.508 times more likely to leave a note than their non-SGM counterparts, controlling for demographic, mental health and substance use covariates. These findings highlight the importance of tailoring suicide prevention and intervention efforts to meet the needs of SGM populations.


[Epidemiology and prevention in dialysis].
During the last years, prevention of hospital infections assumed the role of primary objective for active interventions and dedicated laws for safety in work areas and for facilities accreditation defined responsibilities and preventive measures to reduce the biological risk. Dialysis centers are areas where the infective risk is high but the strict application of the Universal Measures and of specific recommendations are sufficient to reduce the risk of diffusion and transmission of pathogens. The late referral of the ESRD patient, with or without infectious comorbidity, shows an intervention field, in which a local epidemiological survey gives useful data and stimulates the data management at hospital level (Epidemiologists and nefrologists) and family doctors, to improve the disease management of very complex and high cost patients.


[Aging of population in Russia and Ukraine: look into the future].
The paper aims at comparative analysis of future trends of population ageing in Russia and Ukraine. The UN Population Prospects (The 2004 Revision) and probabilistic projections for Russia and Ukraine up to the year 2050 are analyzed. A number of ageing characteristics (proportions of the population aged 65+ and 80+, old age dependency ratio, median age) are considered.


Alcoholic liver cirrhosis is associated with a decreased expression of the CD28 costimulatory molecule, a lower ability of T cells to bind exogenous IL-2, and increased soluble CD8 levels.
Despite the existence of high interleukin (IL)-12 serum levels in patients with chronic active alcoholism, previous studies from our group have shown that, during active ethanol intake, alcoholic patients with alcoholic liver cirrhosis (ALC) display an impaired T-helper-1 response together with abnormalities in the peripheral blood (PB) cytotoxic compartment. The aim of the present study was to gain further insights into the mechanisms underlying these abnormalities. For that purpose, we analyzed the expression on PB B- and T-cell subsets of both the CD28 and CD80 costimulatory molecules, the ability of T lymphocytes to bind to exogenous recombinant IL-2, and the serum levels of soluble CD8 (sCD8) that might interfere with CD8+ T-cell activation in a group of 10 ALC patients with active ethanol intake (ALCET group). As reference groups, we analyzed 10 healthy individuals, 10 chronic alcoholic patients without liver disease (AWLD group) but with active ethanol intake, and 10 ALC patients who had quit drinking for at least 1 year. Our results showed that ALCET patients display a significant decrease in the number of PB CD28+/CD8(hi) T cells (P < 0.05) and CD80+ B cells (P < 0.01) compared with both healthy controls and AWLD patients. In addition, in ALCET patients, PB T cells also showed a decreased ability to bind to exogenous IL-2 (P < 0.01). This was associated with the existence of increased serum levels of sCD8 in ALC patients, the highest levels being detected in the ALCET group (P < 0.01). Altogether, our results point to the existence of several abnormalities that would affect the cytotoxic response in ALCET patients.


Giving birth on the way to the clinic: undocumented migrant women's perceptions and experiences of maternal healthcare accessibility along the Thailand-Myanmar border.
Millions of women give birth annually without the support of a trained birth attendant. Generally and globally, countries provide maternal health services for their citizens but there is a coverage gap for undocumented migrant women who often can't access the same care due to their legal status. The objective of this investigation is to explore undocumented migrants' experiences and perceptions of maternal healthcare accessibility. We held focus groups discussions with 64 pregnant women at 3 migrant health clinics on the Thailand-Myanmar border and asked how they learned about the clinic, their health care options, travel and past experiences with birth services. In this context undocumented women could sign up for migrant health insurance at the clinic that would allow them to be referred for tertiary care at government hospitals if needed. Women learned about care options through a network approach often relying on information from community members and trusted care providers. For many, choice of alternate care was limited by lack of antenatal care services close to their homes, limited knowledge of other services and inability to pay fees associated with hospital care. Women travelled up to 4 h to get to the clinic by foot, bicycle, tractor, motorcycle or car, sometimes using multiple modes of transport. Journeys from the Myanmar side of the border were sometimes complicated by nighttime border crossing closures, limited transport and heavy rain. Undocumented migrant women in our study experienced a type of conditional or variable accessibility where time of day, transport and weather needed to align with the onset of labour to ensure that they could get to the migrant clinic on time to give birth. We anticipate that undocumented migrants in other countries may also experience conditional accessibility to birth care, especially where travel is necessary due to limited local services. Care providers may improve opportunities for undocumented pregnant women to access maternal care by disseminating information on available services through informal networks and addressing travel barriers through mobile services and other travel supports. Trial registration The research project was approved by Research Ethics Committee at the Faculty of Medicine, Chiang Mai University (FAM-2560-05204), and the Department of Community Medicine and Global Health at the University of Oslo-Norwegian Centre for Research Data (58542).


Website Analytics of a Google Ads Campaign for a Men's Mental Health Website: Comparative Analysis.
Men with mental health and addictions problems seek information and help from health service providers and community support less often than women with such problems. Online health resources offer men rapid access to self-care recommendations and resources and anonymity; however, only a few websites are specifically developed for men. Headstrong - Taking Things Head-On was a community pharmacy and online health promotion initiative for men living with mental health and addictions problems. The Headstrong website was developed to offer a curated collection of print and online recommended resources (primarily self-help oriented) for depression, anxiety, insomnia, tobacco and alcohol use problems, and suicide. To increase awareness of the initiative and use of the website's content and resource recommendations, a Google Ads campaign was developed. This study aimed to compare user acquisition and behavior on the Headstrong website during and after a Google Ads campaign. The Google Ads campaign was launched on December 21, 2017, and run until February 28, 2018. Website analytics (acquisition of new users, behavior in terms of at-website actions and duration, devices used, and conversions [link-outs to recommended resources]) in a 30-day period during the campaign (January 26, 2018 to February 24, 2018) were compared to a similar 30-day period after the campaign (March 23, 2018 to April 21, 2018). A cost analysis of the ad campaign was also performed. The ad campaign generated 3011 clicks and 4.5 million impressions in total. In addition, the campaign received 1311 website users during the 30-day period of the ad campaign as compared to 241 users during the 30-day period after the ad campaign (P<.001). Return visitor (17.7% vs 27.8%) and nonbounce (19.5% vs 39.8%) user rates as well as session duration (42 vs 102 seconds) and page views per session (1.4 vs 2.1) were lower during the ad campaign than after the campaign (P<.01 for all). The 30-day period of the ad campaign included 9 sessions with conversions initiated by an ad click. Paid and display ads accounted for 63% of the site traffic during the ad campaign, most of which came from mobile phone users. Desktops were the most-common device used after the ad campaign acquired the website via direct and organic searches primarily (92%). The estimated cost per session with one or more conversions was Can $54.69 and cost per conversion was Can $32.81. A Google Ads campaign designed to direct men to the Headstrong website increased the number of user visits by more than five-fold. However, engagement by users responding to the ad campaign was substantially lower than that by users who visited the website via other acquisition methods, possibly reflecting the nonspecific online targeting of men by the ad campaign. General targeting of men online to promote men's mental health appears to have limited value.


Impact of activated sludge configuration and operating conditions on in vitro and in vivo responses and trace organic compound removal.
This study tested municipal sewage effluents generated at the pilot scale using conventional activated sludge (CAS), nitrifying activated sludge (CAS-N) and biological nutrient removal (BNR) in terms of the removal of trace organic compounds (TrOCs) and final effluent quality as indicated by yeast estrogenicity screening (YES), short term zebrafish reproduction and fathead minnow life-cycle tests. Under cold weather conditions (extended SRTs), the BNR configuration reduced the concentrations of the largest number of TrOCs while under warm weather conditions (reduced SRTs) the CAS-N was most effective. By comparison, YES test results indicated statistically lower responses in the BNR effluent in the warm weather tests and no difference between the effluents of CAS-N and BNR in the cold weather tests. Short term tests with adult zebrafish revealed no impact of the BNR and CAS-N effluents on egg production. By contrast egg production and gene expression in the CAS-exposed zebrafish were substantially less than that of control exposures and were similar to that of exposures to ammonia at similar concentrations as the CAS exposures. In fathead minnow life-cycle tests, exposures to CAS effluent (70-50% v/v) resulted in considerable mortality, reduced growth and reduced egg production that was likely due to the elevated ammonia concentrations. The CAS-N effluent (100% v/v) also resulted in some mortality and reduced growth and egg production in the fathead minnows. By contrast, the BNR effluent (100% v/v) had no effect on mortality, growth or egg production. The results suggest that enhancements to wastewater treatment plants that are associated with improved nitrogen removal can result in enhanced removal of TrOCs and can reduce the harmful effects of the effluents on aquatic biota.


Semiparametric estimation and testing for panel count data with informative interval-censored failure event.
Panel count data and interval-censored data are two types of incomplete data that often occur in event history studies. Almost all existing statistical methods are developed for their separate analysis. In this paper, we investigate a more general situation where a recurrent event process and an interval-censored failure event occur together. To intuitively and clearly explain the relationship between the recurrent current process and failure event, we propose a failure time-dependent mean model through a completely unspecified link function. To overcome the challenges arising from the blending of nonparametric components and parametric regression coefficients, we develop a two-stage conditional expected likelihood-based estimation procedure. We establish the consistency, the convergence rate and the asymptotic normality of the proposed two-stage estimator. Furthermore, we construct a class of two-sample tests for comparison of mean functions from different groups. The proposed methods are evaluated by extensive simulation studies and are illustrated with the skin cancer data that motivated this study.


Thymotaxin: a thymic epithelial peptide chemotactic for T-cell precursors.
The embryonic thymus is seeded by invading hemopoietic precursor cells that differentiate intrathymically into T lymphocytes. We have recently reported that avian thymic epithelial cells secrete chemotactic peptides, which provoke oriented migration of hemopoietic precursor cells in vitro. The established rat thymic epithelial cell line IT-45 R1 produced a polypeptide that resolves as a single band in the region of 11 kDa on NaDodSO4/polyacrylamide gels. This molecule, which we have named thymotaxin, induced a chemotactic response in a subpopulation of hemopoietic cells from juvenile rat bone marrow. Responding cells were generated by short-term coculture of rat bone marrow hemopoietic cells with mouse bone marrow stroma in a steroid-free medium. Cells selected in a chemotactic chamber have a lymphoid or blast cell morphology. The phenotype of the responding cells is Thy-1+, CD4- [corrected] and CD8-. In contrast, CD8 T-lymphocyte differentiation antigen was expressed after coculture with embryonic thymic monolayers, suggesting that the responding cells correspond to the precursors colonizing the thymus.


Model-Based Design of Long-Distance Tracer Transport Experiments in Plants.
Studies of long-distance transport of tracer isotopes in plants offer a high potential for functional phenotyping, but so far measurement time is a bottleneck because continuous time series of at least 1 h are required to obtain reliable estimates of transport properties. Hence, usual throughput values are between 0.5 and 1 samples h-1. Here, we propose to increase sample throughput by introducing temporal gaps in the data acquisition of each plant sample and measuring multiple plants one after each other in a rotating scheme. In contrast to common time series analysis methods, mechanistic tracer transport models allow the analysis of interrupted time series. The uncertainties of the model parameter estimates are used as a measure of how much information was lost compared to complete time series. A case study was set up to systematically investigate different experimental schedules for different throughput scenarios ranging from 1 to 12 samples h-1. Selected designs with only a small amount of data points were found to be sufficient for an adequate parameter estimation, implying that the presented approach enables a substantial increase of sample throughput. The presented general framework for automated generation and evaluation of experimental schedules allows the determination of a maximal sample throughput and the respective optimal measurement schedule depending on the required statistical reliability of data acquired by future experiments.


Treatment of benign prostatic hypertrophy by a long-acting gonadotropin-releasing hormone analogue: 1-year experience.
Benign prostatic hypertrophy, a common ailment among elderly men, usually is treated by surgery. Since androgens enhance prostatic hypertrophy, their withdrawal seems a logical way to treat this condition. Recently gonadotropin-releasing hormone analogues, known to produce "chemical castration," have been tried in cases of benign prostatic hypertrophy. We report our experience with 20 men treated by a monthly injection of gonadotropin-releasing hormone for prolonged periods. In 17 men treated for 6 months the prostatic volume decreased to an average of 63% of the initial volume; however, this did not correlate with clinical objective improvement. Only 6 men attained normal flow rates. Residual urine volume remained unaltered. Ten patients experienced subjective amelioration, while only 7 (40%) reported objective and subjective improvement. Maximal decrease in prostatic volumes was reached at 9 months of treatment and further treatment did not cause additional shrinkage. At 3 months after discontinuation of treatment prostatic volumes returned to 95 +/- 10.5% of pre-treatment values. A similar decrease in flow rates also was noted. Symptoms remained improved for longer periods. We conclude that this mode of treatment offers little to the majority of men with benign prostatic hypertrophy. Proper patient selection, based perhaps on serum prostate specific antigen, might augment positive results. This therapy should be restricted to patients considered high risk for any surgical and anesthetic intervention, and then it will have to be continued indefinitely.


Exploring the short-term impact of community water fluoridation cessation on children's dental caries: a natural experiment in Alberta, Canada.
Dental caries (tooth decay) is common and can be serious. Dental caries is preventable, and community water fluoridation is one means of prevention. There is limited current research on the implications of fluoridation cessation for children's dental caries. Our objective was to explore the short-term impact of community water fluoridation cessation on children's dental caries, by examining change in caries experience in population-based samples of schoolchildren in two Canadian cities, one that discontinued community water fluoridation and one that retained it. We used a pre-post cross-sectional design. We examined dental caries indices (deft [number of decayed, extracted, or filled primary teeth] and DMFT [number of decayed, missing, or filled permanent teeth]) among grade 2 schoolchildren in 2004/05 and 2013/14 in two similar cities in the province of Alberta, Canada: Calgary (cessation of community water fluoridation in 2011) and Edmonton (still fluoridated). We compared change over time in the two cities. For Calgary only, we had a third data point from 2009/10, and we considered trends across the three points. We observed a worsening in primary tooth caries (deft) in Calgary and Edmonton, but changes in Edmonton were less consistent and smaller. This effect was robust to adjustment for covariates available in 2013/14 and was consistent with estimates of total fluoride intake from biomarkers from a subsample. This finding occurred despite indication that treatment activities appeared better in Calgary. The worsening was not observed for permanent teeth. For prevalence estimates only (% with >0 deft or DMFT), the three data points in Calgary suggest a trend that, though small, appears consistent with an adverse effect of fluoridation cessation. Our results suggest an increase in dental caries in primary teeth during a time period when community fluoridation was ceased. That we did not observe a worsening for permanent teeth in the comparative analysis could reflect the limited time since cessation. It is imperative that efforts to monitor these trends continue.


Regulatory factors controlling muscle mass: Competition between innate immune function and anabolic signals in regulation of atrogin-1 in Atlantic salmon.
Atrogin-1 is a conserved ubiquitin E3 ligase that is central to the early stages of skeletal and cardiac muscle wasting and degradation following starvation and inflammatory diseases. The control of protein turnover is different between endothermic and ectothermic animals reflecting the body energy requirements. Here we have characterised the promoter of the atrogin-1 gene in a phylogenetically diverse group of vertebrates and show conserved FOXO elements are present in all species examined. We have examined the gene expression responses in primary muscle cell culture to key immune modulators (IL-1β, interferon type 1 and interferon γ) and to the anabolic hormone insulin like growth factor (IGF-1). We show that the IL-1β and interferon type 1 increased atrogin-1 mRNA expression whereas IGF-1 suppressed atrogin-1 expression. The proximal promoter of salmon atrogin-1 was used to transfect primary muscle cell cultures and we found all three cytokines increased promoter activity whereas there was a decrease caused by IGF-1 exposure. We hypothesise that the main drivers for atrogin-1 expression are via the conserved FOXO site, but other transcription binding sites such as NFκB, STAT and IRFs may also be involved in a synergistic manner following immune stimulation when free amino acids need to be released for muscle protein reserves.


Optical imaging predicts mechanical properties during decellularization of cardiac tissue.
Decellularization of xenogeneic hearts offers an acellular, naturally occurring, 3D scaffold that may aid in the development of an engineered human heart tissue. However, decellularization impacts the structural and mechanical properties of the extracellular matrix (ECM), which can strongly influence a cell response during recellularization. We hypothesized that multiphoton microscopy (MPM), combined with image correlation spectroscopy (ICS), could be used to characterize the structural and mechanical properties of the decellularized cardiac matrix in a noninvasive and nondestructive fashion. Whole porcine hearts were decellularized for 7 days by four different solutions of Trypsin and/or Triton. The compressive modulus of the cardiac ECM decreased to < 20% of that of the native tissue in three of the four conditions (range 2-8 kPa); the modulus increased by -150% (range 125-150 kPa) in tissues treated with Triton only. The collagen and elastin content decreased steadily over time for all four decellularization conditions. The ICS amplitude of second harmonic generation (SHG, ASHG) collagen images increased in three of the four decellularization conditions characterized by a decrease in fiber density; the ICS amplitude was approximately constant in tissues treated with Triton only. The ICS ratio (R(SHG), skew) of collagen images increased significantly in the two conditions characterized by a loss of collagen crimping or undulations. The ICS ratio of two-photon fluorescence (TPF, R(TPF)) elastin images decreased in three of the four conditions, but increased significantly in Triton-only treated tissue characterized by retention of densely packed elastin fibers. There were strong linear relationships between both the log of A(SHG) (R(2) = 0.86) and R(TPF) (R(2) = 0.92) with the compressive modulus. Using these variables, a linear model predicts the compressive modulus: E=73.9 × Log(A(SHG))+70.1 × R(TPF) - 131 (R(2) = 0.94). This suggests that the collagen content and elastin alignment determine the mechanical properties of the ECM. We conclude that MPM and ICS analysis is a noninvasive, nondestructive method to predict the mechanical properties of the decellularized cardiac ECM.


Formation of thin films of organic-inorganic perovskites for high-efficiency solar cells.
Organic-inorganic perovskites are currently one of the hottest topics in photovoltaic (PV) research, with power conversion efficiencies (PCEs) of cells on a laboratory scale already competing with those of established thin-film PV technologies. Most enhancements have been achieved by improving the quality of the perovskite films, suggesting that the optimization of film formation and crystallization is of paramount importance for further advances. Here, we review the various techniques for film formation and the role of the solvents and precursors in the processes. We address the role chloride ions play in film formation of mixed-halide perovskites, which is an outstanding question in the field. We highlight the material properties that are essential for high-efficiency operation of solar cells, and identify how further improved morphologies might be achieved.


Ultrastructural aging of the RPE-Bruch's membrane-choriocapillaris complex in the D-galactose-treated mouse.
Low-dose D-galactose treatment in mice induces accelerated aging due to advanced glycation endproduct (AGEs) formation. The purpose of this study was to identify ultrastructural aging in the retinal pigment epithelium (RPE)-Bruch's membrane-choriocapillaris. Five-month-old C57Bl6 mice were injected daily with D-galactose or control buffer for 8 weeks. Eighteen-month-old mice were also treated with control buffer for 8 weeks. Eyes were prepared for electron microscopy and AGE-specific fluorescence at ex = 370 nm/em = 440 nm and ex = 330 nm/ex = 390 nm. D-Galactose treatment induced AGE-specific fluorescence in lens and RPE/choroid compared to buffer-treated controls. In D-galactose-treated animals, the RPE had dilated and fewer basolateral infoldings. Bruch's membrane had alterations that included significant thickening, sub-RPE and prominent outer collagenous layer deposits, and choriocapillaris basement membrane duplication/splitting and thickening. The choriocapillaris endothelium displayed fenestration loss. Ultrastructural aging to the RPE-Bruch's membrane-choriocapillaris developed in mice treated with low-dose D-galactose. These changes could contribute to age-related changes that promote early age-related disease.


Blood flow restricted resistance training in older adults at risk of mobility limitations.
High-load resistance training (HL) may be contraindicated in older adults due to pre-existing health conditions (e.g. osteoarthritis). Low-load blood flow restricted (BFR) resistance training offers an alternative to HL with potentially similar strength improvement. To compare muscle strength, cross-sectional area (CSA), physical function, and quality of life (QOL) following 12-weeks of HL or BFR training in older adults at risk of mobility limitations. Thirty-six males and females (mean: 75.6years 95% confidence interval: [73.4-78.5], 1.67m [1.64-1.70], 74.3kg [69.8-78.8]) were randomly assigned to HL (70% of one repetition maximum [1-RM]) or low-load BFR (30% 1-RM coupled with a vascular restriction) exercise for the knee extensors and flexors twice per week for 12weeks. A control (CON) group performed light upper body resistance and flexibility training. Muscle strength, CSA of the quadriceps, 400-m walking speed, Short Physical Performance Battery (SPPB), and QOL were assessed before, midway and after training. Within 6-weeks of HL training, increases in all strength measures and CSA were evident and the gains were significantly greater than the CON group (P<0.05). The BFR group had strength increases in leg extension and leg press 1-RM tests, but were significantly lower in leg extension isometric maximum voluntary contraction (MVC) and leg extension 1-RM than the HL group (P<0.01). At 12-weeks HL and BFR training did not differ in MVC (P=0.14). Walking speed increased 4% among all training groups (P<0.01) and no changes were observed for overall SPPB score and QOL (P>0.05). Both training programs resulted in muscle CSA improvements and HL training had more pronounced strength gains than BFR training after 6-weeks and were more similar to BFR after 12-weeks of training. These changes in both groups did not transfer to improvements in QOL, SPPB, and walking speed. Since both programs result in strength and CSA gains, albeit at different rates, future research should consider using a combination of HL and BFR training in older adults with profound muscle weakness and mobility limitations.


An integrated theory of language production and comprehension.
Currently, production and comprehension are regarded as quite distinct in accounts of language processing. In rejecting this dichotomy, we instead assert that producing and understanding are interwoven, and that this interweaving is what enables people to predict themselves and each other. We start by noting that production and comprehension are forms of action and action perception. We then consider the evidence for interweaving in action, action perception, and joint action, and explain such evidence in terms of prediction. Specifically, we assume that actors construct forward models of their actions before they execute those actions, and that perceivers of others' actions covertly imitate those actions, then construct forward models of those actions. We use these accounts of action, action perception, and joint action to develop accounts of production, comprehension, and interactive language. Importantly, they incorporate well-defined levels of linguistic representation (such as semantics, syntax, and phonology). We show (a) how speakers and comprehenders use covert imitation and forward modeling to make predictions at these levels of representation, (b) how they interweave production and comprehension processes, and (c) how they use these predictions to monitor the upcoming utterances. We show how these accounts explain a range of behavioral and neuroscientific data on language processing and discuss some of the implications of our proposal.


CHA2DS2-VASc Score and Stroke Prediction in Atrial Fibrillation in Whites, Blacks, and Hispanics.
Background and Purpose- Despite modest predictive ability for ischemic stroke (IS), the CHA2DS2-VASc score is widely used for stroke prediction in atrial fibrillation. Among patients with atrial fibrillation, we aimed to (1) compare the IS or transient ischemic attack (TIA) incidence by CHA2DS2-VASc in blacks and Hispanics versus whites; (2) compare predictive ability of CHA2DS2-VASc score for IS or TIA in blacks and Hispanics versus whites; and (3) determine improvement in predictive ability of CHA2DS2-VASc score from addition of race/ethnicity. Methods- Using data from Optum Clinformatics, a large administrative claims database, we analyzed patients with atrial fibrillation enrolled in commercial and Medicare Advantage health plans from 2009 to 2015. We computed IS or TIA incidence rates, improvement in C statistic, continuous and categorical net reclassification improvement, and relative integrated discrimination improvement from addition of race/ethnicity to CHA2DS2-VASc. Results- A total of 267 419 patients (mean age, 73.1 [SD, 12.3] years; 46.6% women; 84.2% white, 8.5% black, 7.3% Hispanic) were studied. After a mean follow-up of 22 months, there were 6202 IS or TIA events. IS or TIA incidence rates were higher in blacks than Hispanics or whites (1.65, 1.40, and 1.22 cases per 100 person-years, respectively) and increased with higher CHA2DS2-VASc, with no race/ethnicity-based differences (P for interaction=0.17). The CHA2DS2-VASc and CHA2DS2-VASc+race/ethnicity C statistic (95% CI) were 0.679 (0.670-0.686) and 0.679 (0.671-0.688). The CHA2DS2-VASc C statistic in the 3 groups were comparable. With addition of race/ethnicity, the categorical net reclassification improvement, continuous net reclassification improvement, and relative integrated discrimination improvement were -0.045 (95% CI, -0.067 to -0.025), 0.045 (95% CI, 0.025-0.068), and 0.016 (95% CI, 0.014-0.018). Conclusions- The predictive ability of CHA2DS2-VASc for IS or TIA in atrial fibrillation is comparable among whites, blacks, and Hispanics; hence, it can be used in the latter 2 groups. Addition of race/ethnicity to the CHA2DS2-VASc does not improve its predictive ability.


Inhibition of granulocyte erythrophagocytosis by HLA antisera.
The ability of HLA antisera to inhibit granulocyte erythrophagocytosis (EP) of opsonized red blood cells (RBC) was evaluated. Human granulocytes (PMN) were separated from heparinized whole blood by the Ficoll-Isopaque technique and suspended in McCoy's medium. EP occurred when the PMN were incubated with opsonized RBC. For six HLA antibody specificities evaluated, prior incubation of PMN with HLA antisera resulted in significant inhibition of EP without cytolysis when the PMN donor was positive for the specific HLA antigen, but not when the donor was negative for the antigen. The inhibition was time- and dose-dependent. Prior absorption of HLA antisera with HLA-specific platelets reduced or abolished the inhibition. An example of anti-NB1 also inhibited EP in 4 individuals. These data suggest that HLA antibody may adversely affect granulocyte phagocytic function. Inhibition of EP might be useful in evaluating compatibility prior to granulocyte transfusion.


Discussing and Teaching about Race and Health Inequities.
Health inequities are prevalent in our medical institutions and result in unfair access to and delivery of healthcare. Some of the most profound health disparities are related to race, which has erroneously been used to make biologic inferences to explain disease states in medicine. Our profession continues to shift away from such race-based medical narratives which do not examine how social determinants of health, social injustice, systemic racism, and existing power structures shape health outcomes towards a health equity mindset and race-conscious medicine. Clinician educators are responsible for teaching and engaging with learners around issues of inequity in medicine, though many may feel they lack the knowledge or skills to do so. Opportunities for conversations on health equity abound, either as a response to statements made by clinical peers or patients, or through direct clinical care of affected populations. In this paper, we focus our discussion of health equity around the topic of race-corrections in spirometry, which is one of several salient areas of conversation in the field of pulmonary medicine undergoing reconciliation. We review basic definitions and concepts in health equity and apply three strategies to engage in conversations around equity with colleagues and learners: actively learning and reflecting on health inequities, recognizing and naming inequities, and consciously role-modeling equity-conscious language and care. We also will summarize strategies for implementing health equity concepts into the continuum of medical education and our clinical learning environments.


The Baby-Friendly Hospital Initiative shows positive effects on breastfeeding indicators in Brazil.
The Baby-Friendly Hospital Initiative (BFHI) has been implemented by WHO and Unicef with a view to protect, promote and support breast feeding. This paper aims to assess the influence of the BFHI on breastfeeding indicators in Brazil, using data from the 2nd Survey of Breastfeeding Prevalence, conducted in 2008. Data on 64 municipalities were analysed: a total of 65,936 infants under the age of 1 year who were covered by the 2008 immunisation campaign. The outcomes of interest were breast feeding in the first hour of life in infants under 1 year of age; exclusive breast feeding on the first day after hospital discharge in infants under 4 months of age; exclusive breast feeding in infants under 2, 3 and 6 months of age; and pacifier use in infants under 6 months of age. The influence of birth in baby-friendly hospitals (BFHs) on these end points was analysed by means of Poisson regression with robust variance for complex samples. Infants born in BFHs were 9% more likely to be breast fed in the first hour of life and 6% more likely to be breast fed on the first day at home. Exclusive breast feeding was 13%, 8% and 6% more likely in infants under the ages of 2, 3 and 6 months, respectively, born in BFHs. Birth in a BFH also correlated with significant less pacifier use. The BFHI has had an impact on several indicators of breast feeding. The authors hope the results of this study will make policy makers and health professionals aware of the importance and potential of this strategy.


Hypoglycemia in small-for-dates newborn infants.
In 24% (18 out of 76) small-for-dates a "significant" though asymptomatic hypoglycemia was demonstrated during the first six hours of life. The cord blood glucose concentration was lower in the hypoglycemic compared to that of the small-for-date normoglycemic group. In the hypoglycemic infants, the disappearance rate of glucose was significantly elevated and the lipid mobilization disturbed. It is suggested that a lack of lipids for energy metabolism increases the glucose expenditure and hence increases the risk for hypoglycemia.


Molecular correlates of genes exhibiting RNAi phenotypes in Caenorhabditis elegans.
Understanding genome-wide links between genotype and phenotype has generally been difficult due to both the complexity of phenotypes, and until recently, inaccessibility to large numbers of genes that might underlie a trait. To address this issue, we establish the association between particular RNAi phenotypes in Caenorhabditis elegans and sequence characteristics of the corresponding proteins and DNA. We find that genes showing RNAi phenotypes are long and highly expressed with little noncoding DNA and high rates of synonymous site substitution (KS). In addition, genes conferring RNAi phenotypes have significantly lower rates of nonsynonymous site substitution (KA). Collectively, these sequence features explain nearly 20% of the difference between the sets of loci that display or lack a RNAi-mediated effect, and reflect aspects both of the RNAi mechanism and the biological function of the genes. For example, the particularly low rate of evolution of genes in the sterility RNAi phenotype class suggests a role of C. elegans life history in shaping these patterns of sequence and expression characteristics on phenotypes. This approach also allows prediction of a set of heretofore-uncharacterized loci for which we expect future RNAi studies to reveal phenotypic effects (i.e., false negatives in present screens).


[Socioeconomic inequity in self-rated health status and contribution of health behavioral factors in Korea].
The study is investigated socioeconomic variations in self-rated health status and contribution of health behavioral factors in Korea. A nationally representative sample (2,800 men and 3,230 women aged 20-64 years) from the 2005 Korea National Health and Nutrition Surveys was analyzed using logistic regression. Self-rated health was lower among lower socioeconomic groups compared with higher socioeconomic groups, with gender being irrelevant. This association was attenuated when health behavioral and socio-demographic factors were adjusted. When each health behavioral factor was considered separately, mediators such as smoking in men, and stress or exercise in women explained a large part of the decreased socioeconomic health inequalities. In Korea, subjective health inequalities arise from different socioeconomic status, but this difference is decreased by health behavioral factors. Therefore, socioeconomic inequity in self-rated health status can be corrected more effectively by promotional health behaviors.


New analogue of cyclolinopeptide B modified by amphiphilic residue of alpha-hydroxymethylmethionine.
In order to evaluate the role and influence of the methionine residue on the biological activity of cyclolinopeptide B, an analogue with methionine residue in position 7 replaced by the amphiphilic (S)-alpha-hydroxymethylmethionine residue was synthesized. This peptide exhibits high immunosuppressive activity in the cellular, and to a lesser degree in the humoral immune response, comparable to that of CsA. In addition, the peptide was devoid of toxicity, even at high doses.


Javanese species of the mite genus Macrocheles (Arachnida: Acari: Gamasina: Macrochelidae).
Twelve mite species of the genus Macrocheles (Acari: Macrochelidae) were collected from the body surface of dung beetles in Java, Indonesia. Of these, three species, i.e., Macrocheles jabarensis, M. jonggolensis, and M. sukabumiensis, were described as new to science. Female of M. dispar was redescribed. Two species, i.e., M. baliensis and M. sukaramiensis, were recorded from Java for the first time. The occurrence of five species previously recorded from Java, i.e., M. hallidayi, M. kraepelini, M. limue, M. oigru, and M. merdarius, were reconfirmed. Taxonomic status of M. sp. aff. glaber was not settled in the present study, because we could not obtain the male and immatures which are indispensable for exact identification. In total 15 species of the genus Macrocheles, including 3 species already recorded but not collected in this research (M. crispa, M. krantzi, and M. subbadius), are known from Java up to date.


In vivo evaluation of nylon suture material by the scanning electron microscope.
Sixty common carotid arteries in rats were divided and anastomosed with four needles that differed in suture to needle diameter ratios. Scanning electron microscopic observations of the suture revealed endothelial bridges with associated fibrin, platelets and leukocytes arising from needle holes to adhere to the sutures within two hours of anastomosis. These earliest reported observations of suture endothelialization merit further investigation regarding the possibility of an arterial thrombosis occurring after suture.


Analysis of under- and overprescribing of antibiotics in acute otitis media in general practice.
To assess clinical determinants of under- and overprescribing of antibiotics according to the Dutch national guideline for patients with acute otitis media (AOM) in general practice. A total of 146 general practitioners (GPs) from the Netherlands included all patients with AOM during a 4 week period in winter, and recorded patient characteristics, clinical presentation and management. Under- and overprescribing of antibiotics in AOM was assessed using the Dutch national guideline. A total of 458 AOM consultations were recorded. In seven out of 10 consultations (310/439; excluding 19 consultations in which patients were referred to secondary care), antibiotic prescribing decisions were according to the national guideline. In 11% of all consultations (50/439), there was underprescribing and in 18% (79/439) there was overprescribing. Patients with an antibiotic indication but without an antibiotic prescription (underprescribing; n=50) had more short-term symptoms (OR: 0.93), relatively few inflammation signs (OR: 0.47) and were less severely ill (OR: 0.30), compared with patients with an antibiotic indication and an antibiotic prescription (n=167). Patients without an antibiotic indication but with an antibiotic prescription (overprescribing; n=79) were more often younger than 24 months (OR: 0.34), more severely ill (OR: 3.30) and expected more often an antibiotic as perceived by their GP (OR: 2.11), compared with patients without an antibiotic indication and without an antibiotic prescription (n=143). Clinical determinants which are stated as criteria for antibiotic treatment of AOM in the Dutch national guideline were recognized by GPs as important items, but were frequently given too much weight.


Cytotoxic Effect Induced by Sicilian Oregano Essential Oil in Human Breast Cancer Cells.
Origanum vulgare L. is an aromatic plant that exerts antibacterial, antioxidant, anti-inflammatory, and antitumor activities, mainly due to its essential oil (EO) content. In this study, we investigated the possible mechanism underlying the in vitro antitumor activity of EO extracted by hydrodistillation of dried flowers and leaves of Origanum vulgare L. grown in Sicily (Italy) in MDA-MB-231 and MCF-7 breast cancer cell lines. Gas chromatography-mass spectrometry analysis of Oregano essential oil (OEO) composition highlighted the presence of twenty-six major phytocompounds, such as p-cymene, γ-terpinene, and thymoquinone p-acetanisole. OEO possesses strong antioxidant capacity, as demonstrated by the DPPH test. Our studies provided evidence that OEO reduces the viability of both MCF-7 and MDA-MB-231 cells. The cytotoxic effect of OEO on breast cancer cells was partially counteracted by the addition of z-VAD-fmk, a general caspase inhibitor. Caspases and mitochondrial dysfunction appeared to be involved in the OEO-induced death mechanism. Western blotting analysis showed that OEO-induced activation of pro-caspases-9 and -3 and fragmentation of PARP decreased the levels of Bcl-2 and Bcl-xL while increasing those of Bax and VDAC. In addition, fluorescence microscopy and cytofluorimetric analysis showed that OEO induces a loss of mitochondrial membrane potential in both cell lines. Furthermore, we tested the effects of p-cymene, γ-terpinene, thymoquinone, and p-acetanisole, which are the main components of OEO. Our findings highlighted that the effect of OEO on MDA-MB-231 and MCF-7 cells appears to be mainly due to the combination of different constituents of OEO, providing evidence of the potential use of OEO for breast cancer treatment.


Hypersaline nasal irrigation in children with symptomatic seasonal allergic rhinitis: a randomized study.
Recent evidence suggests that nasal irrigation with hypertonic saline may be useful as an adjunctive treatment modality in the management of many sinonasal diseases. However, no previous studies have investigated the efficacy of this regimen in the prevention of seasonal allergic rhinitis-related symptoms in the pediatric patient. Twenty children with seasonal allergic rhinitis to Parietaria were enrolled in the study. Ten children were randomized to receive three-times daily nasal irrigation with hypertonic saline for the entire pollen season, which had lasted 6 weeks. Ten patients were allocated to receive no nasal irrigation and were used as controls. A mean daily rhinitis score based on the presence of nasal itching, rhinorrea, nasal obstruction and sneezing was calculated for each week of the pollen season. Moreover, patients were allowed to use oral antihistamines when required and the mean number of drug assumption per week was also calculated. In patients allocated to nasal irrigation, the mean daily rhinitis score was reduced during 5 weeks of the study period. This reduction was statistically significantly different in the 3th, 4th and 5th week of therapy. Moreover, a decreased consumption of oral antihistamines was observed in these patients. This effect became evident after the second week of treatment and resulted in statistically significant differences during the 3th, 4th and 6th week. This study supports the use of nasal irrigation with hypertonic saline in the pediatric patient with seasonal allergic rhinitis during the pollen season. This treatment was tolerable, inexpensive and effective.


Nanoceria as a DNase I mimicking nanozyme.
We herein communicate the DNase I like activity of nanoceria (CeO2 nanoparticles). Both CeO2 and DNase I cleave polyadenine (poly-A) DNA down to ∼5-mer fragments as the major products, although further cleavage to even shorter fragments was observed with CeO2. Mass spectrometry indicates a hydrolytic cleavage mechanism instead of oxidative cleavage.