Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model.
Neuropathic pain is a chronic and intractable pain, with very few effective analgesics. It involves an impaired cell autophagy process. Hydrogen-rich saline (HRS) reportedly reduces allodynia and hyperalgesia in a neuropathic pain model; however, it is unknown whether these effects involve autophagy induction. We investigated the relationship between HRS and cell autophagy in a neuropathic pain model generated by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats received an intraperitoneal injection of HRS (10 mL/kg daily, from 1 day before until 14 days after CCI), 3MA (autophagy inhibitor), 2ME2 (HIF-1α inhibitor), or EDHB (HIF-1α agonist). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested 1 day before and 1, 3, 7, 10, and 14 days after the operation. HIF-1α and cell autophagy markers in the spinal cord were evaluated by western blotting and real-time PCR assays at 14 days after CCI. Autophagosomes with double membranes were identified by transmission electron microscopy. CCI caused behavioral hypersensitivity to mechanical and thermal stimulation in the hind-paw of the injured side. HRS improved MWT and TWL, activated autophagy, and increased autophagosomes and autolysosomes in CCI rats. 3-MA aggravated hyperalgesia and allodynia and suppressed autophagy, while EDHB attenuated hyperalgesia and activated the autophagy procedure and the HIF-1α downstream target gene BNIP3. HIF-1α inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury. HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.


Technological State of the Art of Electronic Mental Health Interventions for Major Depressive Disorder: Systematic Literature Review.
Electronic mental (e-mental) health care for depression aims to overcome barriers to and limitations of face-to-face treatment. Owing to the high and growing demand for mental health care, a large number of such information and communication technology systems have been developed in recent years. Consequently, a diverse system landscape formed. This literature review aims to give an overview of this landscape of e-mental health systems for the prevention and treatment of major depressive disorder, focusing on three main research questions: (1) What types of systems exist? (2) How technologically advanced are these systems? (3) How has the system landscape evolved between 2000 and 2017? Publications eligible for inclusion described e-mental health software for the prevention or treatment of major depressive disorder. Additionally, the software had to have been evaluated with end users and developed since 2000. After screening, 270 records remained for inclusion. We constructed a taxonomy concerning software systems, their functions, how technologized these were in their realization, and how systems were evaluated, and then, we extracted this information from the included records. We define here as functions any component of the system that delivers either treatment or adherence support to the user. For this coding process, an elaborate classification hierarchy for functions was developed yielding a total of 133 systems with 2163 functions. The systems and their functions were analyzed quantitatively, with a focus on technological realization. There are various types of systems. However, most are delivered on the World Wide Web (76%), and most implement cognitive behavioral therapy techniques (85%). In terms of content, systems contain twice as many treatment functions as adherence support functions, on average. Furthermore, autonomous systems, those not including human guidance, are equally as technologized and have one-third less functions than guided ones. Therefore, lack of guidance is neither compensated with additional functions nor compensated by technologizing functions to a greater degree. Although several high-tech solutions could be found, the average system falls between a purely informational system and one that allows for data entry but without automatically processing these data. Moreover, no clear increase in the technological capabilities of systems showed in the field, between 2000 and 2017, despite a marked growth in system quantity. Finally, more sophisticated systems were evaluated less often in comparative trials than less sophisticated ones (OR 0.59). The findings indicate that when developers create systems, there is a greater focus on implementing therapeutic treatment than adherence support. Although the field is very active, as evidenced by the growing number of systems developed per year, the technological possibilities explored are limited. In addition to allowing developers to compare their system with others, we anticipate that this review will help researchers identify opportunities in the field.


Predictors and patterns of red blood cell transfusion use among newly diagnosed cancer patients with chemotherapy-associated anemia in Western Denmark (1998-2003).
Cancer patients receiving chemotherapy are at increased risk of anemia. We conducted a population-based historical cohort study in newly diagnosed cancer patients with chemotherapy-associated anemia in order to characterize red blood cell transfusion (RBCT) use. This study evaluated cancer patients diagnosed between January 1, 1998 and December 31, 2003 using Danish National Patient Registry data. Patients were receiving chemotherapy and had a hemoglobin level ≤10.9 g/dL during the 4 months following cancer diagnosis. We characterized patterns of RBCT use and inpatient and outpatient hospitalization for transfusion. Adjusted Poisson regression models were used to evaluate the likelihood of RBCT, estimated by relative risk (RR), based on demographic and clinical factors. Women constituted 58% of 1782 patients studied; the median age was 58 years. Two-thirds (67%) had solid tumors; 67% had stage III or IV disease at diagnosis. Overall, 713 (40%) patients received an RBCT within 120 days of cancer diagnosis, of which 94% were administered in the inpatient setting; 84% of these patients required subsequent transfusions. The median (Q1, Q3) pretransfusion hemoglobin level was 9.0 (8.4, 9.8) g/dL. Patients aged <20 years were more likely to receive an RBCT than older patients (RR 1.89; 95% confidence interval [CI] 1.44-2.49). Compared with stage IV disease, those with stage II or III disease had a lower likelihood of RBCT (stage II: RR 0.52, 95% CI: 0.37-0.72; stage III: RR 0.68, 95% CI: 0.55-0.83). Patients diagnosed with breast cancer were less likely to receive an RBCT than patients with hematologic cancers (RR 0.34, 95% CI: 0.21-0.55). In this study, 40% of cancer patients with chemotherapy-associated anemia in Western Denmark received an RBCT, usually in the inpatient setting; of these, most required subsequent transfusions. Younger age increased the likelihood of receiving an RBCT, and earlier stage or breast cancer decreased RBCT likelihood.


Boys and girls on the playground: sex differences in social development are not stable across early childhood.
Sex differences in human social behaviors and abilities have long been a question of public and scientific interest. Females are usually assumed to be more socially oriented and skillful than males. However, despite an extensive literature, the very existence of sex differences remains a matter of discussion while some studies found no sex differences whereas others reported differences that were either congruent or not with gender stereotypes. Moreover, the magnitude, consistency and stability across time of the differences remain an open question, especially during childhood. As play provides an excellent window into children's social development, we investigated whether and how sex differences change in social play across early childhood. Following a cross-sectional design, 164 children aged from 2 to 6 years old, divided into four age groups, were observed during outdoor free play at nursery school. We showed that sex differences are not stable over time evidencing a developmental gap between girls and boys. Social and structured forms of play emerge systematically earlier in girls than in boys leading to subsequent sex differences in favor of girls at some ages, successively in associative play at 3-4 years, cooperative play at 4-5 years, and social interactions with peers at 5-6 years. Preschool boys also display more solitary play than preschool girls, especially when young. Nevertheless, while boys catch up and girls move on towards more complex play, sex differences in social play patterns are reversed in favor of boys at the following ages, such as in associative play at 4-5 years and cooperative play at 5-6 years. This developmental perspective contributes to resolve apparent discrepancies between single-snapshot studies. A better understanding of the dynamics of sex differences in typical social development should also provide insights into atypical social developments which exhibit sex differences in prevalence, such as autism.


Photobleaching of organic laser dyes in solid matrices.
A technique is described for measuring the rate of photobleaching of anisotropic dye molecules in solid polymer matrices. Three dyes of different classes in two matrices (PMMA and epoxy resin) show bleaching rates that differ by a factor of 20. The bleaching rate is linearly proportional to the intensity of incident radiation, indicating a one-photon process; bleaching is probably due to a chemical reaction of the dye in its first excited singlet or lowest triplet state.


A systems-level gene regulatory network model for Plasmodium falciparum.
Many of the gene regulatory processes of Plasmodium falciparum, the deadliest malaria parasite, remain poorly understood. To develop a comprehensive guide for exploring this organism's gene regulatory network, we generated a systems-level model of P. falciparum gene regulation using a well-validated, machine-learning approach for predicting interactions between transcription regulators and their targets. The resulting network accurately predicts expression levels of transcriptionally coherent gene regulatory programs in independent transcriptomic data sets from parasites collected by different research groups in diverse laboratory and field settings. Thus, our results indicate that our gene regulatory model has predictive power and utility as a hypothesis-generating tool for illuminating clinically relevant gene regulatory mechanisms within P. falciparum. Using the set of regulatory programs we identified, we also investigated correlates of artemisinin resistance based on gene expression coherence. We report that resistance is associated with incoherent expression across many regulatory programs, including those controlling genes associated with erythrocyte-host engagement. These results suggest that parasite populations with reduced artemisinin sensitivity are more transcriptionally heterogenous. This pattern is consistent with a model where the parasite utilizes bet-hedging strategies to diversify the population, rendering a subpopulation more able to navigate drug treatment.


Convergent evolution of the genomes of marine mammals.
Marine mammals from different mammalian orders share several phenotypic traits adapted to the aquatic environment and therefore represent a classic example of convergent evolution. To investigate convergent evolution at the genomic level, we sequenced and performed de novo assembly of the genomes of three species of marine mammals (the killer whale, walrus and manatee) from three mammalian orders that share independently evolved phenotypic adaptations to a marine existence. Our comparative genomic analyses found that convergent amino acid substitutions were widespread throughout the genome and that a subset of these substitutions were in genes evolving under positive selection and putatively associated with a marine phenotype. However, we found higher levels of convergent amino acid substitutions in a control set of terrestrial sister taxa to the marine mammals. Our results suggest that, whereas convergent molecular evolution is relatively common, adaptive molecular convergence linked to phenotypic convergence is comparatively rare.


FIRST EURADOS INTERCOMPARISON EXERCISE OF EYE LENS DOSEMETERS FOR MEDICAL APPLICATIONS.
In the context of the decrease in the eye lens dose limit for occupational exposure to 20 mSv per year stated by the recent revision of the European Basic Safety Standards Directive 2013/59/EURATOM, the European Radiation Dosimetry Group (EURADOS) has organised in 2014, for the first time, an intercomparison exercise for eye lens dosemeters. The main objective was to assess the capabilities of the passive eye lens dosemeters currently in use in Europe for occupational monitoring in medical fields. A total of 20 European individual monitoring services from 15 different countries have participated. The dosemeters provided by the participants were all composed of thermoluminescent detectors, of various types and designs. The irradiations were carried out with several photon fields chosen to cover the energy and angle ranges encountered in medical workplace. Participants were asked to report the doses in terms of Hp(3) using their routine protocol. The results provided by each participant were compared with the reference delivered doses. All the results were anonymously analysed. Results are globally satisfactory since, among the 20 participants, 17 were able to provide 90 % of their response in accordance with the ISO 14146 standard requirements.


Social evolution of spatial patterns in bacterial biofilms: when conflict drives disorder.
A key feature of biological systems is the emergence of higher-order structures from interacting units, such as the development of tissues from individual cells and the elaborate divisions of labor in insect societies. Little is known, however, of how evolutionary competition among individuals affects biological organization. Here we explore this link in bacterial biofilms, concrete systems that are well known for higher-order structures. We present a mechanistic model of cell growth at a surface, and we show that tension between growth and competition for nutrients can explain how empirically observed patterns emerge in biofilms. We then apply our model to evolutionary simulations and observe that the maintenance of patterns requires cooperation between cells. Specifically, when different genotypes meet and compete, natural selection favors energetically costly spreading strategies, like polymer secretion, that simultaneously reduce productivity and disrupt the spatial patterns. Our theory provides a formal link between higher-level patterning and the potential for evolutionary conflict by showing that both can arise from a single set of scale-dependent processes. Moreover, and contrary to previous theory, our analysis predicts an antagonistic relationship between evolutionary conflict and pattern formation: conflict drives disorder.


Chronic wound repair and healing in older adults: current status and future research.
The incidence of chronic wounds is increased among older adults, and the impact of chronic wounds on quality of life is particularly profound in this population. It is well established that wound healing slows with age. However, the basic biology underlying chronic wounds and the influence of age-associated changes on wound healing are poorly understood. Most studies have used in vitro approaches and various animal models, but observed changes translate poorly to human healing conditions. The impact of age and accompanying multi-morbidity on the effectiveness of existing and emerging treatment approaches for chronic wounds is also unknown, and older adults tend to be excluded from randomized clinical trials. Poorly defined outcomes and variables, lack of standardization in data collection, and variations in the definition, measurement, and treatment of wounds also hamper clinical studies. The Association of Specialty Professors, in conjunction with the National Institute on Aging and the Wound Healing Society, held a workshop, summarized in this paper, to explore the current state of knowledge and research challenges, engage investigators across disciplines, and identify key research questions to guide future study of age-associated changes in chronic wound healing.


A blessing and a curse: is high NK cell activity good for health and bad for reproduction?
Few topics in recent reproductive medicine have been the subject of as much controversy, media attention and passionate debate as natural killer (NK) cells and their role in reproductive failure. The question of whether elevated NK cell levels are a cause of infertility and pregnancy loss, and whether they provide a potential target for therapy to improve reproductive outcomes, lacks a definitive answer. It is clear, however, that a significant number of women with reproductive failure have abnormal NK cell parameters reflecting high immunological activity. Amongst all the debate, the wider implications of NK cell overactivity - and attempts to suppress it - have not yet been considered. The literature suggests that although elevated NK cell activity may not be conducive to reproduction, it could in fact be beneficial in other areas of health and disease such as cancer and infection. Further research is needed to determine whether this hypothesis holds true in women with NK cell-related reproductive failure.


Progressive impairment of CSF beta-EP levels in migraine sufferers.
Common migraine (CM) is an evolutive disease characterized by a progressive increase in the number of attacks and a consequent reduction in the free periods, eventually reaching a state of continuous migraine with interparoxysmal headache (MIH). To evaluate the role of central pro-opiocortin-related peptides in the pathogenesis of the disease, cerebrospinal fluid (CSF) levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP) and ACTH were measured in two groups of migraine sufferers with increasing severity of the disease (CM and MIH), and in healthy controls. ACTH values were similar in the 3 groups, while beta-LPH levels were significantly lower (P less than 0.005) in patients affected by MIH (10.4 +/- 8.6 fmol/ml) than in patients with CM (35.7 +/- 8.3) and in controls (32.9 +/- 15.33). beta-EP levels were closely correlated with the severity of the disease: they decreased significantly from those found in healthy controls (86.1 +/- 37 fmol/ml) to those of CM sufferers (38.5 +/- 3.5; P less than 0.005) and showed a further significant fall (P less than 0.01) to the lowest levels which were found in MIH patients (14.8 +/- 9.8). These data showing that the progressive evolution of migraine is concomitant with a progressive impairment in the CSF levels of beta-EP, sustain the concept that non-organic central pain is related to a reduced activity of the neurons responsible for the CSF content of beta-EP.


Host-derived interleukin-5 promotes adenocarcinoma-induced malignant pleural effusion.
IL-5 is a T helper 2 cytokine important in the trafficking and survival of eosinophils. Because eosinophils can be found in malignant pleural effusions (MPE) from mice and humans, we asked whether IL-5 is involved in the pathogenesis of MPE. To determine the role of IL-5 in MPE formation. The effects of IL-5 on experimental MPE induced in C57BL/6 mice by intrapleural injection of syngeneic lung (Lewis lung cancer [LLC]) or colon (MC38) adenocarcinoma cells were determined using wild-type (il5(+/+)) and IL-5-deficient (il5⁻(/)⁻) mice, exogenous administration of recombinant mouse (rm) IL-5, and in vivo antibody-mediated neutralization of endogenous IL-5. The direct effects of rmIL-5 on LLC cell proliferation and gene expression in vitro were determined by substrate reduction and microarray. Eosinophils and IL-5 were present in human and mouse MPE, but the cytokine was not detected in mouse (LLC) or human (A549) lung and mouse colon (MC38) adenocarcinoma-conditioned medium, suggesting production by host cells in MPE. Compared with il5(+/+) mice, il5⁻(/)⁻ mice showed markedly diminished MPE formation in response to both LLC and MC38 cells. Exogenous IL-5 promoted MPE formation in il5(+/+) and il5⁻(/)⁻ mice, whereas anti-IL-5 antibody treatment limited experimental MPE in il5(+/+) mice. Exogenous IL-5 had no effects on LLC cell proliferation and gene expression; however, IL-5 was found to be responsible for recruitment of eosinophils and tumor-promoting myeloid suppressor cells to MPE in vivo. Host-derived IL-5 promotes experimental MPE and may be involved in the pathogenesis of human MPE.


Chronic stress induces anxiety via an amygdalar intracellular cascade that impairs endocannabinoid signaling.
Collapse of endocannabinoid (eCB) signaling in the amygdala contributes to stress-induced anxiety, but the mechanisms of this effect remain unclear. eCB production is tied to the function of the glutamate receptor mGluR5, itself dependent on tyrosine phosphorylation. Herein, we identify a novel pathway linking eCB regulation of anxiety through phosphorylation of mGluR5. Mice lacking LMO4, an endogenous inhibitor of the tyrosine phosphatase PTP1B, display reduced mGluR5 phosphorylation, eCB signaling, and profound anxiety that is reversed by genetic or pharmacological suppression of amygdalar PTP1B. Chronically stressed mice exhibited elevated plasma corticosterone, decreased LMO4 palmitoylation, elevated PTP1B activity, reduced amygdalar eCB levels, and anxiety behaviors that were restored by PTP1B inhibition or by glucocorticoid receptor antagonism. Consistently, corticosterone decreased palmitoylation of LMO4 and its inhibition of PTP1B in neuronal cells. Collectively, these data reveal a stress-responsive corticosterone-LMO4-PTP1B-mGluR5 cascade that impairs amygdalar eCB signaling and contributes to the development of anxiety.


Removal of metal ions and humic acids through polyetherimide membrane with grafted bentonite clay.
Functional surfaces and polymers with branched structures have a major impact on physicochemical properties and performance of membrane materials. With the aim of greener approach for enhancement of permeation, fouling resistance and detrimental heavy metal ion rejection capacity of polyetherimide membrane, novel grafting of poly (4-styrenesulfonate) brushes on low cost, natural bentonite was carried out via distillation-precipitation polymerisation method and employed as a performance modifier. It has been demonstrated that, modified bentonite clay exhibited significant improvement in the hydrophilicity, porosity, and water uptake capacity with 3 wt. % of additive dosage. SEM and AFM analysis showed the increase in macrovoides and surface roughness with increased additive concentration. Moreover, the inclusion of modified bentonite displayed an increase in permeation rate and high anti-irreversible fouling properties with reversible fouling ratio of 75.6%. The humic acid rejection study revealed that, PEM-3 membrane having rejection efficiency up to 87.6% and foulants can be easily removed by simple hydraulic cleaning. Further, nanocomposite membranes can be significantly employed for the removal of hazardous heavy metal ions with a rejection rate of 80% and its tentative mechanism was discussed. Conspicuously, bentonite clay-bearing poly (4-styrenesulfonate) brushes are having a synergistic effect on physicochemical properties of nanocomposite membrane to enhance the performance in real field applications.


Influence of transmucosal designs of three one-piece implant systems on early tissue responses: a histometric study in beagle dogs.
The purpose of this study was to investigate the early tissue response around three one-piece implant systems with different transmucosal designs. Three one-piece dental implant systems with different profiles and surface roughnesses on the transmucosal portion were examined in the current study. The transmucosal portions were flared and machined (FM), concave and machined with microgrooves (CMG), or straight and anodic oxidized (SA). A total of 30 implants (10 of each type) were placed in computer-generated randomized order in the mandibular residual ridges of five beagle dogs. Six months later, all animals were sacrificed and histologic sections were prepared to measure epithelial tissue height, connective tissue contact, and the amount of bone resorption. One-way analysis of variance and the Bonferroni post hoc test were used for statistical evaluation (alpha = 95%). After a 6-month nonfunctional loading period, all 30 implants were clinically immobile. Slight swelling and redness of the peri-implant soft tissue were noticed around most of the implant abutments. Histometric analysis showed that the FM implants had a longer epithelial tissue height than the CMG implants. The CMG implants showed the greatest amount of connective tissue attachment among the three groups and the least amount of marginal bone resorption. The CMG and SA implants showed bone growth above the initial reference point at 10 and 7 measurement sites, respectively, whereas no bone overgrowth was noted around the FM implants. Based on this study conducted in five beagle dogs, a concave transmucosal profile with a microgrooved surface was associated with longer connective tissue attachments and less bone resorption versus implants that were flared with a machined surface or straight with an anodic oxidized surface in the early healing phase. Int J Oral Maxillofac Implants 2010;25:309-314.


COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.
Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging.


Changing patterns and re-distribution of antigen in poorly differentiated carcinomas: its implications in tumour diagnosis.
The variability of expression of tumour-associated antigens via either antigenic heterogeneity or antigenic modulation presents a basic problem in immunohistochemical diagnosis of poorly/undifferentiated tumours. This work was designed to study antigenic expression on human resected epithelial tumours by a panel of most widely used antibodies (EMA, CEA, AUAI & Cytokeratin) in relation to tumour differentiation and polarization. It was observed that poorly differentiated carcinoma with loss of polarity show homogeneous membrane staining (with antibodies against EMA, CEA & AUAI) in contrast to either apical (luminal) or basolateral membrane staining in well differentiated counterparts. Biochemical studies have shown that apical and basolateral epithelial cell membrane domains have a characteristic set of glycoproteins. Tight junctions are essential for maintaining this functional polarization. It was concluded that structural and functional abnormalities of tight junctions in poorly differentiated carcinomas results in loss of polarity with progressive invasion of the cell surface by antigenic glycoprotein and resultant homogeneous individual cell antigenic expression in poorly differentiated carcinomas. This study demonstrates that antigenic expression on tumour cells is not static, but dynamic and heterogeneity of antigenic expression may well be due to biological factors such as spatial configuration of the lesion.


Transfusion-transmitted Babesia spp.: bull's-eye on Babesia microti.
Babesia spp. are intraerythrocytic protozoan parasites of animals and humans that cause babesiosis, a zoonotic disease transmitted primarily by tick vectors. Although a variety of species or types of Babesia have been described in the literature as causing infection in humans, the rodent parasite Babesia microti has emerged as the focal point of human disease, especially in the United States. Not only has B. microti become established as a public health concern, this agent is increasingly being transmitted by blood transfusion: estimates suggest that between 70 and 100 cases of transfusion-transmitted Babesia (TTB) have occurred over the last 30 years. A recent upsurge in TTB cases attributable to B. microti, coupled with at least 12 fatalities in transfusion recipients diagnosed with babesiosis, has elevated TTB to a key policy issue in transfusion medicine. Despite clarity on a need to mitigate transmission risk, few options are currently available to prevent the transmission of B. microti by blood transfusion. Future mitigation efforts may stress serological screening of blood donors in regionalized areas of endemicity, with adjunct nucleic acid testing during the summer months, when acute infections are prevalent. However, several hurdles remain, including the absence of a licensed blood screening assay and a thorough cost-benefit analysis of proposed interventions. Despite current obstacles, continued discussion of TTB without proactive intervention is no longer a viable alternative.


"I cannot say no when a pregnant woman needs my support to get to the health centre": involvement of community health workers in Rwanda's maternal health.
In Rwanda, maternal community health workers (M-CHWs) are involved in the country's overall health system. In maternal health, their role includes the provision of preventive and promotional health services at the community level. They provide services such as health education on maternal health wellbeing, advice and information on access and timely utilization of health facilities for prenatal, delivery and postpartum care. The contribution of M-CHWs in the health sector combined with other government initiatives led the country to achieving the fifth Millennium Development Goal (MDG) - target 5A- that aimed to improve maternal health through the reduction of maternal mortality ratio by 75% between 1990 and 2015). The objective of this study was to explore M-CHWs' perceptions and experiences on access and provision of maternal health services. We used a case study methodology, a qualitative research approach to explore M-CHWs' experiences and perceptions on access and provision of maternal health services at the community level in Rwanda. For the period of June-August 2014, in-depth interviews were conducted with sixteen M-CHWs who had been providing maternal health services in the Eastern Province of Rwanda. Participants shared their experiences and perceptions on access and provision of maternal health service in their communities. The results of this research highlight the role of M-CHWs in promoting the use of health facilities for prenatal care and delivery and the ways they use to reach out to women. Several challenges prohibit M-CHWs to deliver adequate maternal health services and these are related to the poor resources settings in which they operate. The results of this study highlight the experiences and perceptions of M-CHWs on the provision and access to maternal health services in their communities. The fact that M-CHWs are volunteers operating in limited resources settings with no formal training in maternal health and with considerable workloads translates into challenges regarding the quality and quantity of services they provide in their communities. Such challenges create an impact on M-CHWs service provision, satisfaction and retention. The voices of M-CHWs and the communities they serve are needed to explore areas that are specific to each community context that would contribute to making the M-CHW program sustainable to achieve equitable access to maternal health services.


A method for cytometric image parameterization.
New advances in wide-angle cytometry have allowed researchers to obtain micro- and nano-structural information from biological cells. While the complex two-dimensional scattering patterns generated by these devices contain vital information about the structure of a cell, no computational analysis methods have been developed to rapidly extract this information. In this work we demonstrate a multi-agent computational pipeline that is able to extract features from a two-dimensional laser scattering image, cluster these features into spatially distinct regions, and extract a set of parameters relating to the structure of intensity regions within the image. This parameterization can then be used to infer medically relevant properties of the scattering object.


Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy.
IgE-mediated peanut allergy is a complex trait with strong heritability, but its genetic basis is currently unknown. Loss-of-function mutations within the filaggrin gene are associated with atopic dermatitis and other atopic diseases; therefore, filaggrin is a candidate gene in the etiology of peanut allergy. To investigate the association between filaggrin loss-of-function mutations and peanut allergy. Case-control study of 71 English, Dutch, and Irish oral food challenge-positive patients with peanut allergy and 1000 non peanut-sensitized English population controls. Replication was tested in 390 white Canadian patients with peanut allergy (defined by food challenge, or clinical history and skin prick test wheal to peanut ≥ 8 mm and/or peanut-specific IgE ≥ 15 kUL(-1)) and 891 white Canadian population controls. The most prevalent filaggrin loss-of-function mutations were assayed in each population: R501X and 2282del4 in the Europeans, and R501X, 2282del4, R2447X, and S3247X in the Canadians. The Fisher exact test and logistic regression were used to test for association; covariate analysis controlled for coexistent atopic dermatitis. Filaggrin loss-of-function mutations showed a strong and significant association with peanut allergy in the food challenge-positive patients (P = 3.0 × 10(-6); odds ratio, 5.3; 95% CI, 2.8-10.2), and this association was replicated in the Canadian study (P = 5.4 × 10(-5); odds ratio, 1.9; 95% CI, 1.4-2.6). The association of filaggrin mutations with peanut allergy remains significant (P = .0008) after controlling for coexistent atopic dermatitis. Filaggrin mutations represent a significant risk factor for IgE-mediated peanut allergy, indicating a role for epithelial barrier dysfunction in the pathogenesis of this disease.


Extracting work from a single heat bath via vanishing quantum coherence.
We present here a quantum Carnot engine in which the atoms in the heat bath are given a small bit of quantum coherence. The induced quantum coherence becomes vanishingly small in the high-temperature limit at which we operate and the heat bath is essentially thermal. However, the phase phi, associated with the atomic coherence, provides a new control parameter that can be varied to increase the temperature of the radiation field and to extract work from a single heat bath. The deep physics behind the second law of thermodynamics is not violated; nevertheless, the quantum Carnot engine has certain features that are not possible in a classical engine.


Exchange of conduction pathways between two related K+ channels.
The structure of the ion conduction pathway or pore of voltage-gated ion channels is unknown, although the linker between the membrane spanning segments S5 and S6 has been suggested to form part of the pore in potassium channels. To test whether this region controls potassium channel conduction, a 21-amino acid segment of the S5-S6 linker was transplanted from the voltage-activated potassium channel NGK2 to another potassium channel DRK1, which has very different pore properties. In the resulting chimeric channel, the single channel conductance and blockade by external and internal tetraethylammonium (TEA) ion were characteristic of the donor NGK2 channel. Thus, this 21-amino acid segment controls the essential biophysical properties of the pore and may form the conduction pathway of these potassium channels.


Chronic fatigue syndrome and quality of life.
Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), is a challenging long-term condition (LTC) with complex and fluctuating symptoms. It is heterogeneous in presentation without diagnostic indicators; therefore, in health care encounters, insight must be gained from the patient's perspective. One indicator of impact can be gained by measuring quality of life (QoL). By applying a patient-reported outcome measure (PROM), professionals can gather insights with direct relevance to the patient questioned. Such a tool can act therapeutically tool to promote holistic and individualized professional interventions and interval measurement can inform commissioning of specialist services. Standard practice appears not fully to capture the experience of CFS, while a search of the literature turned up QoL patient-reported outcome tools, but failed to reveal a CFS/ME-specific measure. The author explores a valid and reliable PROM that can monitor change and evaluate the UK National Institute of Clinical Excellence rehabilitation program, as delivered by specialist National Health Service units. An alternative, the World Health Organization's quality-of life instrument (WHOQoL)-Bref26, is reviewed for relevance to the condition, measuring treatment outcomes and the wider debate of measuring QoL in LTCs.


Physical health and mental illness: listening to the voice of carers.
Shortened life expectancy of people with mental illness is now widely known and the focus of research and policy activity. To date, research has primarily reflected perspectives of health professionals with limited attention to the views and opinions of those most closely affected. The voice of carers is particularly minimal, despite policy stipulating carer participation is required for mental health services. To present views and opinions of carers regarding physical health of the people they care for. Qualitative exploratory. Two focus groups and one individual interview were conducted with 13 people identifying as carers of a person with mental illness. Research was conducted in the Australian Capital Territory. Data analysis was based on the thematic framework of Braun and Clarke. Two main themes were interaction between physical and mental health; and, carers' own physical and mental health. Participants described the impact of mental illness and its treatments on physical health, including their own. Carers are acknowledged as crucial for the delivery of high quality mental health services. Therefore they have an important role to play in addressing the poor physical health of people with mental illness. Hearing their views and opinions is essential.


Patient-reported dietetic care post hospital for free-living patients: a Canadian Malnutrition Task Force Study.
Transitions out of hospital can influence recovery. Ideally, malnourished patients should be followed by someone with nutrition expertise, specifically a dietitian, post discharge from hospital. Predictors of dietetic care post discharge are currently unknown. The present study aimed to determine the patient factors independently associated with 30-days post hospital discharge dietetic care for free-living patients who transitioned to the community. Nine hundred and twenty-two medical or surgical adult patients were recruited in 16 acute care hospitals in eight Canadian provinces on admission. Eligible patients could speak English or French, provide their written consent, were anticipated to have a hospital stay of ≥2 days and were not considered palliative. Telephone interviews were completed with 747 (81%) participants using a standardised questionnaire to determine whether dietetic care occurred post discharge; 544 patients discharged to the community were included in the multivariate analyses, excluding those who were admitted to nursing homes or rehabilitation facilities. Covariates during and post hospitalisation were collected prospectively and used in logistic regression analyses to determine independent patient-level predictors. Dietetic care post discharge was reported by 61/544 (11%) of participants and was associated with severe malnutrition [Subjective Global Assessment category C: odd's ratio (OR) 2.43 (1.23-4.83)], weight loss post discharge [(OR 2.86 (1.45-5.62)], comorbidity [(OR 1.09 (1.02-1.17)] and a dietitian consultation on admission [(OR 3.41 (1.95-5.97)]. Dietetic care post discharge occurs in few patients, despite the known high prevalence of malnutrition on admission and discharge. Dietetic care in hospital was the most influential predictor of post-hospital care.


Skin-safe photothermal therapy enabled by responsive release of acid-activated membrane-disruptive polymer from polydopamine nanoparticle upon very low laser irradiation.
How to ablate tumor without damaging skin is a challenge for photothermal therapy. We, herein, report skin-safe photothermal cancer therapy provided by the responsive release of acid-activated hemolytic polymer (aHLP) from the photothermal polydopamine (PDA) nanoparticle upon irradiation at very low dosage. Upon skin-permissible irradiation (via an 850 nm laser irradiation at the power density of 0.4 W cm-2), the nanoparticle aHLP-PDA generates sufficient localized-heat to bring about mild hyperthermia treatment and consequently, responsively sheds off the aHLP polymer from its PDA nanocore; this leads to selective cytotoxicity to cancer cells under the acidic conditions of the extracellular microenvironment of tumor. As a result, our aHLP-PDA nanoparticle upon irradiation at a low dosage effectively inhibits tumor growth without damaging skin, as demonstrated using animal models. Effective in mitigating the otherwise inevitable skin damage in tumor photothermal therapy, the nanosystem reported herein offers an efficient pathway towards skin-safe photothermal therapy.


[Role of tissue plasminogen activator in the rewarding effect of nicotine].
Nicotine, a primary component of tobacco, is one of the most abused drugs worldwide. Approximately four million people die a year because of diseases associated with tobacco smoking. Nicotine rapidly reaches the brain through smoking and this leads to nicotine dependence. Drugs of abuse including nicotine acutely modulate the activity of mesolimbic dopaminergic neurons, projecting from the ventral tegmental area of the midbrain to the nucleus accumbens (NAc). Recently, it has been proposed that activity-dependent synaptic plasticity and remodeling of the mesolimbic dopaminergic system play a crucial role in the development of drug dependence. Tissue plasminogen activator (tPA) is a serine protease that catalyzes the conversion of plasminogen to plasmin. In our previous study, we have demonstrated that the tPA-plasmin system participates in the rewarding effect of morphine and methamphetamine. Here we show that the tPA-plasmin system regulates nicotine-induced reward and dopamine release. In vivo microdialysis revealed that microinjection of either tPA or plasmin into the NAc significantly potentiated whereas plasminogen activator inhibitor-1 reduced the nicotine-induced dopamine release in the NAc in a dose-dependent manner. Nicotine-induced dopamine release was markedly diminished in tPA-deficient (tPA-/-) mice, and the defect of dopamine release in tPA-/- mice was restored by microinjection of either exogenous tPA or plasmin into the NAc. Nicotine increased tPA protein levels and promoted the release of tPA into the extracellular space in the NAc. Immunohistochemistry revealed that protease activated receptor-1 (PAR1)-immunoreactivity was localized to the nerve terminals positive for tyrosine hydroxylase in the NAc. Furthermore, we demonstrated that plasmin activated PAR1 and that nicotine-induced place preference and dopamine release were diminished in PAR1-deficient (PAR1-/-) mice. Our findings suggest that targeting the tPA-plasmin-PAR1 system would provide new therapeutic approaches to the treatment of nicotine dependence.


Anti-inflammatory effect of capsaicin in Helicobacter pylori-infected gastric epithelial cells.
Capsaicin, the main pungent ingredient of hot red and chilli pepper, has been considered as not only a cytoprotective but also a detrimental agent to the gastric mucosa. However, the effect and mechanism of capsaicin that modulate the induction of pro-inflammatory cytokine in Helicobacter pylori-infected epithelial cells have not been investigated previously. Herein, we demonstrated that capsaicin inhibited the release of pro-inflammatory cytokine, interleukin-8 (IL-8) by H. pylori-infected gastric epithelial cells through nuclear factor-kappaB (NF-kappaB) signal pathway. AGS or MKN45 cells as gastric epithelial cells and Vac A+, CagA+ wild-type H. pylori strain ATCC 49503 were used. Gastric epithelial cells were pre-treated with various concentrations of capsaicin and infected with H. pylori for different periods of time to determine IL-8 concentrations in culture supernatant by an ELISA assay. We measured IL-8 mRNA transcripts in H. pylori-infected gastric epithelial cells co-treated with capsaicin by reverse transcriptase-polymerase chain reaction analysis. We performed electrophoretic mobility shift assay to examine the NF-kappaB DNA binding activity with capsaicin and immunofluorescence microscopy to examine nuclear staining of p65. We also performed immunoblotting for IkappaB, IKK activity with capsaicin. Capsaicin inhibits H. pylori-induced IL-8 production by gastric epithelial cells in dose- and time-dependent manner. Capsaicin as low as 100 micromol/L significantly inhibited IL-8 production in H. pylori-infected MKN45 cells (43.2% of control) at 24 hours incubation, whereas inhibited IL-8 production in H. pylori-infected AGS cells (70% of control). We confirmed that capsaicin inhibited IL-8 mRNA expression after infection of gastric epithelial cells with H. pylori for 6 hours. The addition of capsaicin (100 micromol/L) suppressed H. pylori-induced NF-kappaB activation in gastric epithelial cells at 1 hour post-infection. We also found that the degradation of IkappaB and IKK activation were inhibited by capsaicin. Nontoxic dose of capsaicin inhibited H. pylori-induced IL-8 production by gastric epithelial cells through the modulation of IkappaB-, NF-kappaB-, and IL-8 pathways. We conclude that capsaicin can be proposed as a potential anti-inflammatory drug by inhibition of the production of IL-8 in H. pylori-infected gastric epithelium.


Women's perceptions of antenatal, delivery, and postpartum services in rural Tanzania.
Maternal health care provision remains a major challenge in developing countries. There is agreement that the provision of quality clinical services is essential if high rates of maternal death are to be reduced. However, despite efforts to improve access to these services, a high number of women in Tanzania do not access them. The aim of this study is to explore women's views about the maternal health services (pregnancy, delivery, and postpartum period) that they received at health facilities in order to identify gaps in service provision that may lead to low-quality maternal care and increased risks associated with maternal morbidity and mortality in rural Tanzania. We gathered qualitative data from 15 focus group discussions with women attending a health facility after child birth and transcribed it verbatim. Qualitative content analysis was used for analysis. 'Three categories emerged that reflected women's perceptions of maternal health care services: "mothers perceive that maternal health services are beneficial," "barriers to accessing maternal health services" such as availability and use of traditional birth attendants (TBAs) and the long distances between some villages, and "ambivalence regarding the quality of maternal health services" reflecting that women had both positive and negative perceptions in relation to quality of health care services offered'. Mothers perceived that maternal health care services are beneficial during pregnancy and delivery, but their awareness of postpartum complications and the role of medical services during that stage were poor. The study revealed an ambivalence regarding the perceived quality of health care services offered, partly due to shortages of material resources. Barriers to accessing maternal health care services, such as the cost of transport and the use of TBAs, were also shown. These findings call for improvement on the services provided. Improvements should address, accessibility of services, professionals' attitudes and stronger promotion of the importance of postpartum check-ups, both among health care professionals and women.


Purification and characterization of three forms of glutathione transferase from Proteus mirabilis.
Three forms of glutathione transferase (GST) with pI values of 6.0, 6.4 and 7.3 were isolated from Proteus mirabilis AF 2924 by glutathione-affinity chromatography followed by isoelectric focusing, and their structural, kinetic and immunological properties were investigated. Upon SDS/polyacrylamide-slab-gel electrophoresis, all forms proved to be composed of two subunits of identical (22,500) Mr. GST-6.0 and GST-6.4 together account for about 95% of the total activity, whereas GST-7.3 is present only in trace amounts. Extensive similarities have been found between GST-6.0 and GST-6.4. These include subunit molecular mass, amino acid composition, substrate specificities and immunological characteristics. GST-7.3 also cross-reacted (non-identity) with antisera raised against bacterial GST-6.0. None of the antisera raised against a number of human, rat and mouse GSTs cross-reacted with the bacterial enzymes, indicating major structural differences between them and the mammalian GSTs. This conclusion is further supported by c.d. spectra.


Association of Comorbidities With Pneumonia and Death Among COVID-19 Patients in Mexico: A Nationwide Cross-sectional Study.
The goal of this study was to identify chronic conditions and multimorbidity patterns in patients with coronavirus disease 2019 (COVID-19) and to examine their associations with pneumonia and death. This cross-sectional study analyzed the official data of COVID-19 patients in Mexico through May 18, 2020 (released by the Secretaría de Salud de México). Adjusted logistic regression models were applied to assess the associations of comorbidities with pneumonia and death. The marginal effects were estimated, and the probability of pneumonia or death according to the number of comorbidities was graphed for each year of age. Of the 51 053 COVID-19 patients enrolled in the final analysis, 27 667 (54.2%) had no chronic conditions, while 13 652 (26.7%), 6518 (12.8%) and 3216 (6.3%) were reported to have 1, 2, and 3 or more simultaneous conditions, respectively. Overall, a significant incremental gradient was observed for the association between multimorbidity and pneumonia (p<0.001); for 2 chronic conditions, the adjusted odds ratio (aOR) was 2.07 (95% confidence interval [CI], 1.95 to 2.20), and for ≥3 conditions, the aOR was 2.40 (95% CI, 2.22 to 2.60). A significant incremental gradient was also found for the relationship between multimorbidity and death (p<0.001); an aOR of 2.51 (95% CI, 2.30 to 2.73) was found for 2 chronic conditions and an aOR of 3.49 (95% CI, 3.15 to 3.86) for ≥3 conditions. Underlying chronic conditions and multimorbidity are associated with pneumonia and death in Mexican COVID-19 patients. Future investigation is necessary to clarify the pathophysiological processes behind this association, given the high burden of chronic diseases in various countries, including Mexico.


Pulmonary and leg VO2 during submaximal exercise: implications for muscular efficiency.
Insights into muscle energetics during exercise (e.g., muscular efficiency) are often inferred from measurements of pulmonary gas exchange. This procedure presupposes that changes of pulmonary O2 (VO2) associated with increases of external work reflect accurately the increased muscle VO2. The present investigation addressed this issue directly by making simultaneous determinations of pulmonary and leg VO2 over a range of work rates calculated to elicit 20-90% of maximum VO2 on the basis of prior incremental (25 or 30 W/min) cycle ergometry. VO2 for both legs was calculated as the product of twice one-leg blood flow (constant-infusion thermodilution) and arteriovenous O2 content difference across the leg. Measurements were made 3-5 min after each work rate imposition to avoid incorporation of the VO2 slow component above the lactate threshold. For all 17 subjects, the slope of pulmonary VO2 (9.9 +/- 0.2 ml O2.W-1.min-1) was not different (P greater than 0.05) from that for leg VO2 (9.2 +/- 0.6 ml O2.W-1.min-1). Estimation of "delta" efficiency (i.e., delta work accomplished divided by delta energy expended, calculated from slope of VO2 vs. work rate and a caloric equivalent for O2 of 4.985 cal/ml) using pulmonary VO2 measurements (29.1 +/- 0.6%) was likewise not significantly different (P greater than 0.05) from that made using leg VO2 measurements (33.7 +/- 2.4%). These data suggest that the net VO2 cost of metabolic "support" processes outside the exercising legs changes little over a relatively broad range of exercise intensities. Thus, under the conditions of this investigation, changes of VO2 measured from expired gas reflected closely those occurring within the exercising legs.


Clinical characteristics and outcome of Penicillium marneffei infection among HIV-infected patients in northern Vietnam.
This study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam. We conducted a retrospective chart review of all patients with laboratory confirmed Penicilliummarneffei infection admitted to the National Hospital for Tropical Diseases in Hanoi, Vietnam, between July 2006 and September 2009. 127 patients with P. marneffei infection were identified. All were HIV-infected; median CD4+ T-cell count was 24 cells/μl (IQR:12-48); 76% were men. Common clinical features were fever (92.9%), skin lesions (82.6%), hepatomegaly (61.4%), lymphadenopathy (40.2%), weight loss (59.1%) and cough (49.6%). Concurrent opportunistic infections were present in 22.0%; half of those had tuberculosis. Initial treatment regimens were: itraconazole or ketoconazole capsule (77.2%), amphotericin B (20.5%), and fluconazole (1.6%). In-hospital mortality was 12.6% and showed no significant difference in patients treated with itraconazole (or ketoconazole) and amphotericin B (p = 0.43). Dyspnea, ascites, and increased LDH level were independent predictors of mortality. No seasonality was observed. The clinical features, treatments and outcomes of HIV-associated P. marneffei infection in northern Vietnam are similar to those reported in other endemic regions. Dyspnea was an important predictor of mortality. More patients were treated with itraconazole than amphotericin B and no significant difference in treatment outcome was observed. It would be of clinical value to compare the efficacy of oral itraconazole and amphotericin B in a clinical trial.


Predicting soil respiration from peatlands.
This study considers the relative performance of six different models to predict soil respiration from upland peat. Predicting soil respiration is important for global carbon budgets and gap filling measured data from eddy covariance and closed chamber measurements. Further to models previously published new models are presented using two sub-soil zones and season. Models are tested using data from the Bleaklow plateau, southern Pennines, UK. Presented literature models include ANOVA using logged environmental data, the Arrhenius equation, modified versions of the Arrhenius equation to include soil respiration activation energy and water table depth. New models are proposed including the introduction of two soil zones in the peat profile, and season. The first new model proposes a zone of high CO(2) productivity related to increased soil microbial CO(2) production due to the supply of labile carbon from plant root exudates and root respiration. The second zone is a deeper zone where CO(2) production is lower with less labile carbon. A final model allows the zone of high CO(2) production to become dormant during winter months when plants will senesce and will vary depending upon vegetation type within a fixed location. The final model accounted for, on average, 31.9% of variance in net ecosystem respiration within 11 different restoration sites whilst, using the same data set, the best fitting literature equation only accounted for 18.7% of the total variance. Our results demonstrate that soil respiration models can be improved by explicitly accounting for seasonality and the vertically stratified nature of soil processes. These improved models provide an enhanced basis for calculating the peatland carbon budgets which are essential in understanding the role of peatlands in the global C cycle.


Systematic analysis of the role of target site accessibility in the activity of DNA enzymes.
We employed an approach using oligonucleotide scanning arrays and computational analysis to conduct a systematic analysis of the interaction between catalytic nucleic acids (DNA enzymes or DNAzymes) and long RNA targets. A radio-labelled transcript representing mRNA of Xenopus cyclin B5 was hybridised to an array of oligonucleotides scanning the first 120 nucleotides of the coding region to assess the ability of the immobilised oligonucleotides to form heteroduplexes with the target. The hybridisation revealed oligonucleotides showing varying levels of signal intensities along the length of the array, reflecting on the variable accessibility of the corresponding complementary regions in the target RNA. Deoxyribozymes targeting a number of these regions were selected and tested for their ability to cleave the target RNA. The mRNA cleavage observed indicates that indeed target accessibility was an important component in the activity of deoxyribozymes and that it was important that at least one of the two binding arms was complementary to an accessible site. Computational analysis suggested that intra-molecular folding of deoxyribozymes into stable structures may also negatively contribute to their activity. 10-23 type deoxyribozymes generally appeared more active than 8-17 type and it was possible to predict deoxyribozymes with high cleavage efficiency using scanning array hybridization and computational analysis as guides. The data presented here therefore have implications on designing effective DNA enzymes.


Extending "color constancy" outside the visible region.
In this paper, the results of an investigation of the possibility of extending "color constancy" to obtain illuminant-invariant reflectance features from data in the near-ultraviolet (UV) and near-infrared (IR) wavelength regions are reported. These features are obtained by extending a blackbody-model-based color constancy algorithm proposed by Ratnasingam and Collins [J. Opt. Soc. Am. A27, 286 (2010)] to these additional wavelengths. Ratnasingam and Collins applied the model-based algorithm in the visible region to extract two illuminant-invariant features related to the wavelength-dependent reflectance of a surface from the responses of four sensors. In this paper, this model-based algorithm is extended to extract two illuminant-invariant reflectance features from the responses of sensors that cover the visible and either the near-UV or near-IR wavelength. In this investigation, test reflectance data sets are generated using the goodness-fitness coefficient (GFC). The appropriateness of the GFC for generating the test data sets is demonstrated by comparing the results obtained with these data with those obtained from data sets generated using the CIELab distance. Results based upon the GFC are then presented that suggest that the model-based algorithm can extract useful features from data from the visible and near-IR wavelengths. Finally, results are presented that show that, although the spectrum of daylight in the near UV is very different from a blackbody spectrum, the algorithm can be modified to extract useful features from visible and near-UV wavelengths.


Individual and Social Network Sexual Behavior Norms of Homeless Youth at High Risk for HIV Infection.
Although previous research shows that homeless youth engage in numerous risky sexual behaviors, little is known about whether or not specific rules govern this conduct within their social networks and how group norms influence subsequent sexual actions. The current study utilizes 19 in-depth interviews with homeless youth to investigate different elements of their sexual behavior. Findings reveal that their decision to have sex generally depends on chemistry and physical appearance whereas a potential partner's risky sexual history and heavy substance use discourages youth from engaging in sex. Both males and females discuss condom usage as it relates to unknown sexual history, availability, pregnancy, and the prevention of sexually transmitted infections (STIs). Sixteen homeless youth indicate that they do not discuss safe sex practices with their partners or social network members.


Cruciform structures are a common DNA feature important for regulating biological processes.
DNA cruciforms play an important role in the regulation of natural processes involving DNA. These structures are formed by inverted repeats, and their stability is enhanced by DNA supercoiling. Cruciform structures are fundamentally important for a wide range of biological processes, including replication, regulation of gene expression, nucleosome structure and recombination. They also have been implicated in the evolution and development of diseases including cancer, Werner's syndrome and others.Cruciform structures are targets for many architectural and regulatory proteins, such as histones H1 and H5, topoisomerase IIβ, HMG proteins, HU, p53, the proto-oncogene protein DEK and others. A number of DNA-binding proteins, such as the HMGB-box family members, Rad54, BRCA1 protein, as well as PARP-1 polymerase, possess weak sequence specific DNA binding yet bind preferentially to cruciform structures. Some of these proteins are, in fact, capable of inducing the formation of cruciform structures upon DNA binding. In this article, we review the protein families that are involved in interacting with and regulating cruciform structures, including (a) the junction-resolving enzymes, (b) DNA repair proteins and transcription factors, (c) proteins involved in replication and (d) chromatin-associated proteins. The prevalence of cruciform structures and their roles in protein interactions, epigenetic regulation and the maintenance of cell homeostasis are also discussed.


Biomotor status and kinesiological education of girls aged 10 to 12 years--example: volleyball.
The aim of this study was to define processes of orientation and/or selection towards sports game of volleyball in schoolgirls of Kastela, aged 10-12, by examining the relations between regular classes of physical education (PE) and extracurricular sport activities. For this purpose, two morphological measures were used (body height and body mass) and a set of 11 motor tests (6 basic motor abilities tests and 5 motor achievement tests) on a sample of 242 girls aged 10-12 was used, divided into a subsample of 42 girls participating in volleyball training (Volleyball players) and a subsample of 200 girls who do not participate in volleyball training (volleyball non-players). Based on the comparison of test results of schoolgirls from Kastela and Croatian norms, factor analysis of applied variables and discriminant analysis of these variables between volleyball players and non-players, processes and/or phases of selection in forming quality volleyball players were defined. Selection processes are preceded by orientation processes in physical education classes, i.e. choosing those sport activities which are in accordance with the biomotor status of students. Results have shown that orientation and initial selection in female volleyball needs to be executed based on the motor set of psychomotor speed, repetitive strength of the trunk and flexibility (muscle tone regulation), and body height. Volleyball training has affected the muscle mass development and the development of strength factors, so that explosive strength of jumping and/or takeoff along with body height, has predominantly differentiated female volleyball players from non-players, aged 10 to 12, and serve and spike quality will have dominant influence on the match outcome.


How Culture Influences the "Social" in Social Media: Socializing and Advertising on Smartphones in India and the United States.
The importance of the mobile phone is evidenced by predictions that there will be 1.76 billion smartphone users worldwide at the start of 2015. A country that is spearheading this movement toward the digital era is India. To illustrate this, India is expected to surpass the United States in 2015 and record the second highest smartphone sales globally. Despite the rising penetration and adoption of smartphones, there is limited advertising research that sheds light on the Indian smartphone user. The current study aims to fill that void by cross-culturally comparing a national online panel of smartphone users from India (n=158) with users from the United States (n=114). Findings reveal that entertainment impacts Indians' attitudes toward smartphone advertising while informativeness is stronger for the American sample. Collectivism was found to be the driving force behind socializing activities on social networking sites for Indian consumers. Implications are discussed.


Report of stroke-like symptoms predicts incident cognitive impairment in a stroke-free cohort.
The present study characterizes the relationship between report of stroke symptoms (SS) or TIA and incident cognitive impairment in the large biracial cohort of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. The REGARDS Study is a population-based, biracial, longitudinal cohort study that has enrolled 30,239 participants from the United States. Exclusion of those with baseline cognitive impairment, stroke before enrollment, or incomplete data resulted in a sample size of 23,830. Participants reported SS/TIA on the Questionnaire for Verifying Stroke-free Status at baseline and every 6 months during follow-up. Incident cognitive impairment was detected using the Six-item Screener, which was administered annually. Logistic regression found significant association between report of SS/TIA and subsequent incident cognitive impairment. Among white participants, the odds ratio for incident cognitive impairment was 2.08 (95% confidence interval: 1.81, 2.39) for those reporting at least one SS/TIA compared with those reporting no SS/TIA. Among black participants, the odds ratio was 1.66 (95% confidence interval: 1.45, 1.89) using the same modeling. The magnitude of impact was largest among those with fewer traditional stroke risk factors, particularly among white participants. Report of SS/TIA showed a strong association with incident cognitive impairment and supports the use of the Questionnaire for Verifying Stroke-free Status as a quick, low-cost instrument to screen for people at increased risk of cognitive decline.


Is sympathetic sprouting in the dorsal root ganglia responsible for the production of neuropathic pain in a rat model?
Partial peripheral nerve injury often results in neuropathic pain that is aggravated by sympathetic excitation and induces sympathetic nerve sprouting in both the injured nerve and corresponding dorsal root ganglia (DRGs). Presently, the functional mechanisms of the interactions between the sprouting and injured somatic afferents remain uncertain. This study was performed to see whether the sprouting in the DRGs plays a key role in the development of neuropathic pain. To this aim, we compared two groups of rats, both of which were subjected to unilateral transection of the superior and inferior caudal trunks at the level between the S1 and S2 spinal nerves, with respect to sympathetic fiber sprouting; one group showed well-developed neuropathic pain behaviors (i.e. mechanical, cold and warm allodynia signs) and the other group showed poorly-developed ones. Immuno-histochemical staining with tyrosine hydroxylase (TH) antibody of the injured S1 DRG taken from both groups of rats after behavioral tests revealed that the magnitude of penetration of TH-positive fibers into the S1 DRG was not significantly different between the two groups. These results suggest that sympathetic nerve sprouting in the injured DRG is not a key factor in the development of neuropathic pain.


Meanings of being received and met by others as experienced by women with fibromyalgia.
Fibromyalgia (FM) is a common chronic pain syndrome that mostly affects middle-aged women. Our aim with this study was to elucidate meanings of being received and met by others as experienced by women with FM. Interviews with a narrative approach were conducted with 9 women. We analyzed the transcribed interviews with a phenomenological hermeneutical interpretation. The findings revealed two themes: being seen as a malingerer and being acknowledged. Meanings of being received and met by others, as experienced by women with FM, can be understood as a movement between the two perspectives. When they were acknowledged, their feelings of security and trust increased, but the women could not rely on this because others received and met them in such an unpredictable manner.


Is money a cure? Follow-up of litigants in England.
American and British authors collaborated on a follow-up study in England of accident victims who brought litigation which had been resolved. Eighteen subjects who had complained of psychiatric symptoms during the course of the litigation were recruited from the British psychiatrist's files. Based on review of court documents and extensive interviews of the subjects, the authors describe case examples that demonstrate a complicated relationship between monetary compensation and outcome. Some of the litigants improved after they received compensation, but this seemed to be related to issues besides the money, e.g., feelings about their impairment, family support, the loss or gain of a relationship, personality characteristics, and ability to return to work. The authors discuss the results of this study in light of differences between the British and American legal systems.


Human papillomavirus vaccine uptake among young gay and bisexual men who have sex with men with a time-limited targeted vaccination programme through sexual health clinics in Melbourne in 2017.
In mid-2017, the Victorian Government funded a free time-limited human papillomavirus (HPV) vaccination catch-up programme for gay and bisexual men who have sex with men (MSM) aged up to 26 years through sexual health clinics or other immunisation centres. We aimed to examine the uptake of the HPV vaccine among young MSM attending the Melbourne Sexual Health Centre (MSHC). MSM aged ≤26 attending MSHC between 27 April 2017 and 31 December 2017 were included in the analysis. HPV vaccine uptake was calculated based on the first consultation of each patient during the period. Multivariable logistic regression was performed to examine the association between vaccine uptake and patient factors. There were 2108 MSM aged ≤26 who attended MSHC over the study period, with 7.6% (n=161) reporting previous HPV vaccination. Of the 1947 eligible men, 1134 (58.2%, 95% CI 56.0% to 60.4%) were offered the vaccine by the clinicians, and 830 men received it on the day. The vaccine coverage among all eligible MSM was 42.6% (95% CI 40.4% to 44.9%; 830 of 1947) and among MSM who were offered the vaccine by the clinicians was 73.2% (95% CI 70.5% to 75.8%; 830 of 1134). Men with a history of genital warts (adjusted OR (aOR)=3.11, 95%CI 1.39 to 6.99) and those who had >4male partners in the last 12 months (aOR=1.38, 95% CI 1.04 to 1.85) were more likely to receive the HPV vaccine on the day. 304 men declined the vaccine; most men did not specify the reason (31.3%, n=95), while 27.3% (n=83) needed time to think. Although vaccine uptake was 73.2% among those offered, the actual coverage of those eligible remained unsatisfactory (42.6%) in a sexual health clinic. This highlights a clinic-based targeted MSM programme may not reach sufficiently high vaccine coverage to provide MSM with the same vaccine benefits as heterosexuals.


Characterizing responses to gamma radiation by a highly clonogenic fish brain endothelial cell line.
The clonogenic property and radiobiological responses of a fish brain endothelial cell line, eelB, derived from the American eel were studied. Clonogenic assays were performed to determine the plating efficiency of the eelB cells and to evaluate the clonogenic survival fractions after direct irradiation to low-dose low-LET gamma radiation or receiving irradiated cell conditioned medium in the bystander effect experiments. eelB had the second highest plating efficiency ever reported to date for fish cell lines. Large eelB macroscopic colonies could be formed in a short period of time and were easy to identify and count. Unlike with other fish clonogenic cell lines, which had a relatively slow proliferation profile, clonogenic assays with the eelB cells could be completed as early as 12 days in culture. After direct irradiation with gamma rays at low doses ranging from 0.1Gy to 5Gy, the dose-clonogenic survival curve of the eelB cell line showed a linear trend and did not develop a shoulder region. A classical radio-adaptive response was not induced with the clonogenic survival endpoint when the priming dose (0.1 or 0.5Gy) was delivered 6h before the challenge dose (3 or 5Gy). However, a radio-adaptive response was observed in progeny cells that survived 5Gy and developed lethal mutations. eelB appeared to lack the ability to produce damaging radiation-induced bystander signals on both eelB and HaCaT recipient cells. eelB cell line could be a very useful cell model in the study of radiation impacts on the aquatic health.


Electrochemistry of single droplets of inverse (water-in-oil) emulsions.
We demonstrate the feasibility of electrochemically detecting individual water droplets dispersed in an oil phase (inverse emulsions) via the use of a redox probe confined in the droplet phase. The water droplets were tagged with potassium ferrocyanide, and were injected into an electrolyte cyclohexene/dichloromethane oil solution. Via simple cyclic voltammetry scans it is shown that single water droplets from a water-in-oil emulsion can be detected provided that rapid anion transfer from the oil to the water phase maintains electro-neutrality in the droplet.


Intestinal Neuronal Dysplasia-Like Submucosal Ganglion Cell Hyperplasia at the Proximal Margins of Hirschsprung Disease Resections.
Intestinal neuronal dysplasia type B (IND) denotes an increased proportion of hyperplastic submucosal ganglia, as resolved histochemically in 15-μm-thick frozen sections. IND has been reported proximal to the aganglionic segment in patients with Hirschsprung disease (HSCR) and is putatively associated with a higher rate of postsurgical dysmotility. We developed and validated histological criteria to diagnose IND-like submucosal ganglion cell hyperplasia (IND-SH) in paraffin sections and used the approach to study the incidence and clinical and/or genetic associations of IND-SH at the proximal margins of HSCR pull-through resection specimens. Full-circumference paraffin sections from the proximal margins of 64 HSCR colonic pull-through specimens and 24 autopsy controls were immunostained for neuron-specific Hu antigen, and nucleated ganglion cells in each submucosal ganglion were counted. In controls, an age-related decline in the relative abundance of "giant" ganglia (≥7 nucleated Hu-positive [Hu+] ganglion cells) was observed. A conservative diagnostic threshold for IND-SH (control mean ± 3× standard deviation) was derived from 15 controls less than 25 weeks of age. No control exceeded this threshold, whereas in the same age range, IND-SH was observed at the proximal margins in 15% (7 of 46) of HSCR resections, up to 15 cm proximal to the aganglionic segment. No significant correlation was observed between IND-SH and length of or distance from the aganglionic segment, sex, trisomy 21, RET or SEMA3C/D polymorphisms, or clinical outcome, but analysis of more patients, with better long-term follow-up will be required to clarify the significance of this histological phenotype.


Identification and quantification of seven volatile n-nitrosamines in cosmetics using gas chromatography/chemical ionization-mass spectrometry coupled with head space-solid phase microextraction.
An analytical method was developed for the identification and quantification of seven volatile n-nitrosamines (n-nitrosodimethylamine [NDMA], n-nitrosoethylmethylamine [NMEA], n-nitrosodiethylamine [NDEA], n-nitrosodipropylamine [NDPA], n-nitrosodibutylamine [NDBA], n-nitrosopiperidine [NPIP], and n-nitrosopyrrolidine [NPYR]) in water insoluble cream type cosmetics. It was found that the head space-solid phase microextraction (HS-SPME) was suitable for extraction, clean up, and pre-concentration of n-nitrosamines in the cream type samples so its optimal conditions were investigated. Identification and quantification of n-nitrosamines using single quadrupole gas chromatography/mass spectrometry (GC/MS) in chemical ionization (CI) mode were carried out with accurate mass measurements. Their accurate masses of protonated molecular ions were obtained within 10 mDa of the theoretical masses when sufficiently high signal was acquired from the unique calibration method using mass and isotope accuracy. For the method validation of quantification, spiking experiments were carried out to determine the linearity, recovery, and method detection limit (MDL) using three deuterated internal standards. The average recovery was 79% within 20% relative standard deviation (RSD) at the concentration of 50 ng/g. MDLs ranged from 0.46 ng/g to 36.54 ng/g, which was satisfactory for the directive limit of 50 ng/g proposed by the European Commission (EC). As a result, it was concluded that the method could be provided for the accurate mass screening, confirmation, and quantification of n-nitrosamines when applied to cosmetic inspection.


Lidocaine block of human heart sodium channels expressed in Xenopus oocytes.
The tertiary amine lidocaine is used clinically for preventing cardiac arrhythmias, and has been widely studied on mammalian tissue. Xenopus oocytes were used as an expression system to study the effect of lidocaine on a sodium (Na) channel, derived from a full-length human heart (hH1) cDNA clone. The concentration dependence of the lidocaine block of hH1 Na current was consistent with a binding stoichiometry of 1:1. At low frequency stimulation, and at holding potentials < or = 100 mV, the IC50 was 226 microM, comparable to values found in mammalian cardiac cells. Lidocaine also shifted the steady-state inactivation of hH1 Na current to hyperpolarized potentials in a dose-dependent manner. Our experiments suggest that lidocaine block is state dependent, with high affinity for an inactivated state (KI = 11 microM) and low affinity for the resting state (KR = 3.9 mM). The quaternary amine derivative of lidocaine, QX-314, had no effect on Na current at an extracellular concentration of 1 mM.


Children Exposed to Violence: Child Custody and its Effects on Children in Intimate Partner Violence Related Cases in Hungary.
Violence might increase post-separation, and visitation can offer an opportunity to the perpetrator for maintaining power and control over the mother and child. In relationships where intimate partner violence (IPV) exists, it is hypothesized that fathers may continue their violent behaviors throughout visitation with children. The study uses mixed methods: After completing of a screening questionnaire (n = 593) we recruited 168 individuals from our sample with problematic child custody cases who completed an online survey. Semi-structured interviews were conducted with 30 mothers with experience of problematic child custody cases. This paper reports only the qualitative results of the research. The findings highlight how custody and visitation rights may be used as a form of custodial violence and a continuation of IPV. Problematic child custody and visitation cases were reported following separation from an abusive partner because using legal proceedings as a weapon to maintain power and control over the former partner and child. Institutions involved in custody and contact-related legal procedures do not take into consideration the violence of the abusive ex-partner as a factor when determining custody and contact arrangements, even though it may work in opposition to the child's wellbeing. The analysis of the data shows that child custody and visitation arrangements did not reflect clear understanding of domestic violence, coercive control and the effects of these on children's wellbeing. Fathers were reported to be able to control the everyday lives of their ex-partners and their children through lack of institutional recognition of domestic violence.


Maternal Gestational Immune Response and Autism Spectrum Disorder Phenotypes at 7 Years of Age in the Seychelles Child Development Study.
Findings from observational and experimental studies suggest that maternal inflammation during pregnancy is associated with autism spectrum disorder (ASD). We report the first study in humans to examine this association in a large prospective birth cohort. We studied 788 mother-child pairs from the Seychelles Child Development Study Nutrition Cohort 2. Thirteen inflammatory markers were measured in mothers' serum at 28 weeks' gestation, along with the sum of T-helper 1 (Th1) and 2 (Th2) cytokines. The Social Communication Questionnaire (SCQ) and Social Responsiveness Scale (SRS) were administered at age 7 years to obtain information on ASD phenotype. We evaluated associations between maternal inflammatory markers and ASD phenotype using multivariable linear regression. For the SCQ, increased MCP-1 (a chemokine that is upregulated in response to pro-inflammatory cytokines) was associated with fewer ASD symptoms (B = - 0.40; 95% CI = - 0.72, - 0.09). Increased IL-4 (a cytokine that is typically associated with an enhanced anti-inflammatory response) was associated with more ASD symptoms (B = 2.10; 95% CI = 0.78, 3.43). For the SRS, higher concentrations of the anti-inflammatory cytokine IL-10 were associated with fewer ASD symptoms (B = - 0.18; 95% CI = - 0.35, - 0.01), but only after removal of outliers. No associations were observed for other markers. These findings suggest that a shift in the maternal immune balance during pregnancy may be associated with ASD symptomatology. While the use of well-established measures that capture ASD phenotypic variability is a strength of the study, measurement of peripheral immune markers only once during gestation is a limitation. Our results should be confirmed using maternal immune markers measured throughout gestation.


Revealing the Empty-State Electronic Structure of Single-Unit-Cell FeSe/SrTiO3.
We use scanning tunneling spectroscopy to investigate the filled and empty electronic states of superconducting single-unit-cell FeSe deposited on SrTiO3(001). We map the momentum-space band structure by combining quasiparticle interference imaging with decay length spectroscopy. In addition to quantifying the filled-state bands, we discover a Γ-centered electron pocket 75 meV above the Fermi energy. Our density functional theory calculations show the orbital nature of empty states at Γ and explain how the Se height is a key tuning parameter of their energies, with broad implications for electronic properties.


Cardiac innervation imaging as a risk stratification tool for potential device therapy candidates.
As a scintigraphic approach evaluating cardiac nerve integrity, 123I-metaiodobenzylguanidine (123I-mIBG) has been recently Food and Drug Administration approved. A great deal of progress has been made by the prospective ADMIRE-HF trial, which primarily demonstrated the association of denervated myocardium assessed by 123I-mIBG and cardiac events. However, apart from risk stratification, myocardial nerve function evaluated by molecular imaging should also be expanded to other clinical contexts, in particular to guide the referring cardiologist in selecting appropriate candidates for specific therapeutic interventions. In the present issue of the Journal of Nuclear Cardiology®, the use of 123I-mIBG for identifying cardiomyopathy patients, which would most likely not benefit from ICD due to low risk of arrhythmias, is described. If we aim to deliver on the promise of cardiac innervation imaging as a powerful tool for risk stratification in a manner similar to nuclear oncology, studies such as the one reviewed here may imply an important step to lay the proper groundwork for a more widespread adoption in clinical practice.


High-performance inertial impaction filters for particulate matter removal.
Airborne particulate matter (PM) is causing more and more serious air pollution and threatening the public health. However, existing air filter technologies with the easy-to-block manner can rarely meet the requirements of high-performance PM filters. Here we propose a conceptually new type of inertial impaction filters for rapidly high-efficiency PM removal. Under the airflow velocity of 8.0 m/s, the real inertial impaction filters show high PM removal efficiencies of up to 97.77 ± 1.53% and 99.47 ± 0.45% for PM2.5 and PM10, respectively. Compared with the traditional air filters reported previously, the inertia impaction filters exhibit extremely low pressure drop of 5-10 Pa and high quality factor (QF) values of 0.380 Pa-1 and 0.524 Pa-1 for PM2.5 and PM10, respectively. These greatly improved QF values are achieved through a series of inertial separation processes. The feature dimension of filtration channel is dozens of times larger than PM average size, which greatly decreases airflow resistance. Particularly, this inertial structure can be made of various types of materials, which shows great potential for low-cost fabrication of large-area devices. As a stand-alone device or incorporated with the existing PM air filter, this inertial impaction filter will bring great benefits to the public health.


Towards understanding the messengers of extracellular space: Computational models of outside-in integrin reaction networks.
The interactions between cells and their extracellular matrix (ECM) are critically important for homeostatic control of cell growth, proliferation, differentiation and apoptosis. Transmembrane integrin molecules facilitate the communication between ECM and the cell. Since the characterization of integrins in the late 1980s, there has been great advancement in understanding the function of integrins at different subcellular levels. However, the versatility in molecular pathways integrins are involved in, the high diversity in their interaction partners both outside and inside the cell as well as on the cell membrane and the short lifetime of events happening at the cell-ECM interface make it difficult to elucidate all the details regarding integrin function experimentally. To overcome the experimental challenges and advance the understanding of integrin biology, computational modeling tools have been used extensively. In this review, we summarize the computational models of integrin signaling while we explain the function of integrins at three main subcellular levels (outside the cell, cell membrane, cytosol). We also discuss how these computational modeling efforts can be helpful in other disciplines such as biomaterial design. As such, this review is a didactic modeling summary for biomaterial researchers interested in complementing their experimental work with computational tools or for seasoned computational scientists that would like to advance current in silico integrin models.


Prevalence, progress, and subgroup disparities in pharmacological antidepressant treatment of those who screen positive for depressive symptoms: A repetitive cross-sectional study in 19 European countries.
The European Mental Health Action Plan (EMHAP) 2013-2020 promoted community-based mental health services. One potential success indicator is the provision of antidepressant medication to those needing it. Public data from two surveys (Health Survey for England, UK; Survey of Health, Ageing and Retirement in Europe) covered 19 European countries across EMHAP phases one (2011-2015) and two (2015-2018). People screening positive for depressive symptoms by self-report were included. The primary outcome was antidepressant use: using country-specific weighted regression models, we estimated temporal trends and subgroup disparities in antidepressant receipt, with secondary analysis by country-level measures including healthcare expenditure. Across 37,250 participants, after controlling for age, sex, wealth, and physical disability, antidepressant use (amongst those screening positive) increased significantly in 14/19 countries, with the smallest increase being in Slovenia (adjusted OR[AOR] for trend=1.68[1.20-2.36]) and the highest increase being in Germany (AOR for trend=10.07[7.54-13.46]) and Austria (AOR for trend=10.07[7.32-13.74]). The overall proportion using antidepressants was positively associated with national health expenditure (coefficient=5.43[1.62-9.25]), but not with gross national income per capita or the number of psychiatrists, general practitioners, or psychiatric hospital beds. In 15/19 countries, antidepressants were used less by ≥65-year-olds than 50-64-year-olds, with the smallest differential reported in Luxembourg (AOR=0.70[0.49, 0.98]) and the highest in Germany (AOR=0.28[0.21, 0.37]); this disparity widened in 12/15 countries. Men used antidepressants less than women in 8/19 countries, across phases. In 13/19 countries, people with physical disability were more likely to receive antidepressants, with the smallest gap in Italy (AOR=1.42[1.12-1.80]) and the largest in Israel (AOR=2.34[1.46-3.74]); this disparity narrowed in 5/13 countries. Disparity by wealth was found in 8/19 countries, but its temporal trend varied. Usage of antidepressants by those with depressive symptoms has increased, with wide variation between countries and subgroups. Disparities across age, sex, and disability should prompt further research. Medical Research Council (grants MC_PC_17213 and MR/W014386/1), UK National Institute for Health Research (NIHR) Applied Research Collaboration (ARC) East of England, NIHR Cambridge Biomedical Research Centre (BRC-1215-20014).


Telmisartan ameliorates lipopolysaccharide-induced innate immune response through peroxisome proliferator-activated receptor-γ activation in human monocytes.
Angiotensin II type 1 receptor (AT1) blockers (ARBs) reduce the bacterial endotoxin lipopolysaccharide (LPS)-induced innate immune response in human circulating monocytes expressing few AT1. To clarify the mechanisms of anti-inflammatory effects of ARBs with different peroxisome proliferator-activated receptor-γ (PPARγ)-activating potencies, we focused our study on telmisartan, an ARB with the highest PPARγ-stimulating activity. Human circulating monocytes and monocytic THP-1 (human acute monocytic leukemia cell line) cells were exposed to 50 ng/ml LPS with or without pre-incubation with telmisartan. AT1 mRNA and protein expressions were determined by real-time PCR and membrane receptor binding assay, respectively. The expression of pro-inflammatory factors was determined by real-time PCR, western blot analysis and ELISA. PPARγ activation was measured by electrophoretic mobility shift assay and its role was determined by pharmacological inhibition and PPARγ gene silencing. In human monocytes, telmisartan significantly attenuated the LPS-induced expression of pro-inflammatory factors, the release of pro-inflammatory cytokines and prostaglandin E2, nuclear factor-κB activation and reactive oxygen species formation. In THP-1 cells, telmisartan significantly reduced LPS-induced tumor necrosis factor-α, inhibitor of κB-α, monocyte chemotactic protein-1 (MCP-1) and lectin-like oxidized low-density lipoprotein receptor-1 gene expression and MCP-1-directed migration. Telmisartan also stimulated the expression of the PPARγ target genes cluster of differentiation 36 and ATP-binding cassette subfamily G member 1 in monocytes. The anti-inflammatory effects of telmisartan were prevented by both PPARγ antagonism and PPARγ gene silencing. Anti-inflammatory effects of ARBs correlated with their PPARγ agonist potency. Our observations demonstrate that in human monocytes, ARBs inhibit the LPS-induced pro-inflammatory response to a major extent through the PPARγ activation pathway and may be beneficial for the treatment of cardiovascular and metabolic disorders in which inflammation plays a major role.


Method for measuring the diffusion coefficient of homogeneous and layered media.
A method for measuring the diffusion coefficient of homogeneous and layered media, based on multidistance measurements of time-resolved reflectance, is proposed. The diffusion coefficient is retrieved from the logarithm between two measurements of reflectance at two different distances. The proposed procedure is simpler than others usually employed and also provides a reliable criterion for retrieval of information on the layered structure of a diffusive medium.


Ontogeny of human locomotor control. I. Infant stepping, supported locomotion and transition to independent locomotion.
Locomotor patterns of human infants were studied during stepping in the newborn period (first two months of life), during supported locomotion (6-12 months of age) and during independent locomotion in children who just were able to walk by themselves without external support (10-18 months of age). Leg movements, pattern of muscular activity and reaction forces were studied by a computerized system. The locomotor pattern during the newborn period lacked the specific functions that are unique for human plantigrade locomotion. There was no heel strike in front of the body; the foot was placed instead on its forepart straight under the body. Hip and knee joints were hyperflexed during the whole step cycle and flexed synchronously during swing. The specific knee-ankle coordination of human adults was missing. The ankle extensors were activated prior to touch down together with other extensor muscles. There was no propulsive force. A similar immature non-plantigrade pattern recurred after an inactive period. During the subsequent period of supported locomotion there was a gradual transformation of the infantile pattern towards the plantigrade pattern continuing after establishment of independent locomotion. It is suggested that innate pattern generators in the spinal cord produce the infant stepping and also generate the basic locomotor rhythm in adults, but that neural circuits specific for humans develop late in ontogeny and transform the original, non-plantigrade motor activity to a plantigrade locomotor pattern.


Distinct bone marrow findings in T-cell granular lymphocytic leukemia revealed by paraffin section immunoperoxidase stains for CD8, TIA-1, and granzyme B.
Unlike other leukemia types in which the bone marrow findings are diagnostic, the bone marrow pathology of T-cell granular lymphocytic leukemia (GLL) is subtle and ill-defined. In this study, bone marrow biopsy specimens from 36 patients with T-cell GLL and from 25 control patients with cytopenias and relative or absolute increases in blood large granular lymphocytes were studied by immunohistochemistry using antibodies to the cytolytic lymphocyte antigens CD8, CD56, CD57, TIA-1, and granzyme B. The goals were to clarify the bone marrow pathology of T-cell GLL and to refine the diagnostic criteria for T-cell GLL. Most bone marrow specimens from the T-cell GLL patients contained interstitially distributed clusters of at least 8 CD8(+) (83%) or TIA-1(+) (75%) lymphocytes or clusters of at least 6 granzyme B(+) (50%) lymphocytes. Interstitial clusters of CD8(+), TIA-1(+), or granzyme B(+) cells were present in 36%, 12%, and 0%, respectively, of the control bone marrows (all values significantly different, P <.001). An additional T-cell GLL disease-specific finding was the presence of linear arrays of intravascular CD8(+), TIA-1(+), or granzyme B(+) lymphocytes, found in 67% of cases of T-cell GLL and in none of the 25 control samples (P <.001). Staining for CD56 and CD57 was noncontributory. These findings clarify the bone marrow histopathology of T-cell GLL and provide an additional tool by which the discrete, abnormal lymphocyte population required for a diagnosis of T-cell GLL can be identified.