Evidence of chronic Chlamydia pneumoniae infection in patients with Behçet's disease.
Behçet's disease is a chronic vasculitis of unknown aetiology. Particular viral and bacterial pathogens have long been suspected of playing a role in the pathogenesis of the disease. Chlamydia pneumoniae is an intracellular bacterium capable of causing chronic infections. Some reports have suggested that the microorganism might be involved in the pathogenesis of vasculitis. The purpose of the present study was to investigate a possible correlation between C. pneumoniae infection and Behçet's disease. For this purpose, 90 consecutive patients with Behçet's disease and 50 healthy controls were enrolled. Immunoglobulin A (IgA) and IgG antibodies to C. pneumoniae were determined by 2 different techniques, namely indirect fluorescent antibody assay (IFA) and enzyme linked immunosorbent assay (ELISA). IgA antibodies to C. pneumoniae were detected in 17 (18.9%) patients with Behçet's disease and in 1 (2%) healthy control by IFA. By ELISA 27 patients (30.0%) and 6 controls (12.0%) had C. pneumoniae IgA. A significant difference was observed for IgA seropositivity between the 2 groups. Although IgG seropositivity between the 2 groups did not differ significantly, the number of individuals with IgG titres of > or = 1:1000 was significantly higher in the patient group (43.1%) compared with the control group (13.9%). These finding provide serological evidence of chronic C. pneumoniae infection in association with Behçet's disease.


Enzyme-triggered approach to reduce water bodies' contamination using peroxidase-immobilized ZnO/SnO2/alginate nanocomposite.
Enzyme immobilization on solid support offers advantages over free enzymes by overcoming characteristic limitations. To synthesize new stable and hyperactive nano-biocatalysts (co-precipitation method), ginger peroxidase (GP) was surface immobilized (adsorption) on ZnO/SnO2 and ZnO/SnO2/SA nanocomposite with immobilization efficacy of 94 % and 99 %, respectively. Thereafter, catalytic and biochemical characteristics of free and immobilized GP were investigated by deploying various techniques, i.e., FTIR, PXRD, SEM, and PL. Diffraction peaks emerged at 2θ values of 26°, 33°, 37°, 51°, 31°, 34°, 36°, 56°, indicating the formation of SnO2 and ZnO. The OH stretching of the H2O molecules was attributed to broad peaks between 3200 and 3500 cm-1, whereas ZnO/SnO2 spikes occurred in the 1626-1637 cm-1 range. SnO stretching mode and ZnO terminal vibrational patterns have been verified at corresponding wavelengths of 625 cm-1 and 560 cm-1. Enzyme entrapment onto substrate was verified via interactions between GP and ZnO/SnO2/SA as corroborated by signals beneath 1100 cm-1. GP-immobilized fractions were optimally active at pH 5, 50 °C, and retained maximum activity after storage of 4 weeks at -4 °C. Kinetic parameters were determined by using a Lineweaver-Burk plot and Vmax for free GP, ZnO/SnO2/GP and ZnO/SnO2/SA/GP with guaiacol as a substrate, were found to be 322.58, 49.01 and 11.45 (μM/min) respectively. A decrease in values of Vmax and KM indicates strong adsorption of peroxidase on support and maximum affinity between nano support and enzyme, respectively. For environmental remediation, free ginger peroxidase (GP), ZnO/SnO2/GP and ZnO/SnO2/SA/GP fractions effectively eradicated highly intricate dye. Multiple scavengers had a significant impact on the depletion of the dye. In conclusion, ZnO/SnO2 and ZnO/SnO2/SA nanostructures comprise an ecologically acceptable and intriguing carrier for enzyme immobilization.


A low-cost and miniaturized potentiostat for sensing of biomolecular species such as TNF-α by electrochemical impedance spectroscopy.
Miniaturizing potentiostats, keeping their cost low and yet preserving full measurement characteristics (e.g. bandwidth, determination of capacitive/inductive contribution to sensor's impedance and parallel screening) is still an unresolved challenge in bioelectronics. In this work, the combination of simple analogue circuitry together with powerful microcontrollers and a digital filter implementation is presented as an alternative to complex and incomplete architectures reported in the literature. A low-cost acquisition electronic system fully integrated with a biosensors platform containing eight gold working microelectrodes and integrated reference and counter electrodes was developed and validated. The manufacturing cost of the prototype was kept below 300 USD. The performance of the proposed device was benchmarked against a commercial impedance analyzer through the electrochemical analysis of a highly sensitive biosensor for the detection of tumor necrosis factor α (TNF-α) within the randomly chosen range of 266pg/mL to 666ng/mL in physiological medium (PBS). A strong correlation between the outputs of both devices was found in a critical range of frequencies (1-10Hz), and several TNF-α cytokine concentrations were properly discriminated. These results are very promising for the development of low-cost, portable and miniaturized electrochemical systems for point-of-care and environmental diagnosis.


["Anything goes"?: the implicit dialogue between Paul Feyerabend and two Brazilian researchers, Maurício da Rocha e Silva and Newton Freire-Maia].
The philosopher Paul Feyerabend and Brazilian scientists Maurício da Rocha e Silva and Newton Freire-Maia were contemporaries and lived surrounded by the fundamental dilemnas of science. The anarchist proposal of Feyerabend, then embryonic, was formulated in parallel by Rocha e Silva in his criticism of the scientific method. Two decades later, Feyerabend's ideas seemed implicitly to stimulate Newton Freire-Maia in his reflections on science. The web of interrelationships in the ideas of these three men - who never interacted - touches on central issues for Brazilian science from 1960 to 1980, a period in which the latter is consolidated in a dialogue with the nascent reflection on science and the scientific method in Brazil.


The economics of food fortification.
This paper summarizes some of the literature on the cost effectiveness and cost benefit of food fortification with selected micronutrients most relevant for developing countries. Micronutrients covered include iron, iodine, vitamin A, and zinc. The main focus is on commercial fortification, although home fortification and biofortification are mentioned. Fortification with iron, vitamin A, and zinc averts significant numbers of infant and child deaths and is a very attractive preventive health-care intervention. Fortification with iron, iodine, and potentially zinc provides significant economic benefits and the low unit cost of food fortification ensures large benefit:cost ratios, with effects via cognition being very important for iron and iodine. Fortification will not reach all individuals and is most attractive as an investment where there is a convenient food vehicle, where processing is more centralized, and where either the deficiency is widespread or the adverse effects are very costly even though only a small group is affected.


Comparing psychosocial predictors of physical activity adoption and maintenance.
Most health behavior models do not distinguish between determinants of behavior adoption and maintenance. This study compared psychosocial predictors of physical activity (PA) adoption and predictors of PA maintenance among 205 initially sedentary adults enrolled in a home-based PA promotion trial. Psychosocial variables were measured at 6 months (at which point 107 participants remained inactive and 98 participants adopted regular PA) and used to predict 12-month PA status (an indicator of PA adoption among those inactive at 6 months and an indicator of PA maintenance among those active at 6 months). Six-month PA status moderated the relationships between 6-month measures of home access to PA equipment (p = .049), self-efficacy (p = .086), and perceived satisfaction (p = .062) and 12-month PA status. Simple effects analyses revealed that home access to PA equipment was predictive of PA adoption (OR = 1.73; 95% CI: 1.05, 2.85), but not PA maintenance (OR = 0.88; 95% CI: 0.58, 1.35), whereas self-efficacy and perceived satisfaction were predictive of PA maintenance (OR = 2.65; 95% CI: 1.55, 4.52; OR = 1.95; 95% CI: 0.93, 4.06), but not PA adoption (OR = 1.50; 95% CI: 0.87, 2.57; OR = 0.82, CI: 0.44, 1.52). Results suggest that these psychosocial variables may operate differently in predicting PA adoption versus maintenance.


A new approach to hierarchical data analysis: Targeted maximum likelihood estimation for the causal effect of a cluster-level exposure.
We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials are applied to learn about real-world implementation, sustainability, and population effects of interventions with proven individual-level efficacy. In these settings, individual-level outcomes are correlated due to shared cluster-level factors, including the exposure, as well as social or biological interactions between individuals. To flexibly and efficiently estimate the effect of a cluster-level exposure, we present two targeted maximum likelihood estimators (TMLEs). The first TMLE is developed under a non-parametric causal model, which allows for arbitrary interactions between individuals within a cluster. These interactions include direct transmission of the outcome (i.e. contagion) and influence of one individual's covariates on another's outcome (i.e. covariate interference). The second TMLE is developed under a causal sub-model assuming the cluster-level and individual-specific covariates are sufficient to control for confounding. Simulations compare the alternative estimators and illustrate the potential gains from pairing individual-level risk factors and outcomes during estimation, while avoiding unwarranted assumptions. Our results suggest that estimation under the sub-model can result in bias and misleading inference in an observational setting. Incorporating working assumptions during estimation is more robust than assuming they hold in the underlying causal model. We illustrate our approach with an application to HIV prevention and treatment.


More than a Pore: Nonlytic Antimicrobial Functions of Complement and Bacterial Strategies for Evasion.
The complement system is an evolutionarily ancient defense mechanism against foreign substances. Consisting of three proteolytic activation pathways, complement converges on a common effector cascade terminating in the formation of a lytic pore on the target surface. The classical and lectin pathways are initiated by pattern recognition molecules binding to specific ligands, while the alternative pathway is constitutively active at low levels in circulation. Complement-mediated killing is essential for defense against many Gram-negative bacterial pathogens, and genetic deficiencies in complement can render individuals highly susceptible to infection, for example, invasive meningococcal disease. In contrast, Gram-positive bacteria are inherently resistant to the direct bactericidal activity of complement due to their thick layer of cell wall peptidoglycan. However, complement also serves diverse roles in immune defense against all bacteria by flagging them for opsonization and killing by professional phagocytes, synergizing with neutrophils, modulating inflammatory responses, regulating T cell development, and cross talk with coagulation cascades. In this review, we discuss newly appreciated roles for complement beyond direct membrane lysis, incorporate nonlytic roles of complement into immunological paradigms of host-pathogen interactions, and identify bacterial strategies for complement evasion.


Sexual and relationship satisfaction and vestibular pain sensitivity among women with provoked vestibulodynia.
Provoked vestibulodynia (PVD) is a common cause of painful intercourse. Despite the fact that PVD is associated with high levels of pain and negative impact on women's sexuality, research has not examined associations between affected women's pain sensitivity and their sexual and relationship satisfaction. This study aimed to examine sexual and relationship functioning/satisfaction and vestibular pain sensitivity among PVD-affected women, and potential associations between these variables. Participants were 17 women with PVD and 17 matched controls. Women were assessed via a gynecological examination, structured interview, and the Female Sexual Function Index (FSFI), Golombok Rust Inventory of Sexual Satisfaction (GRISS), and Dyadic Adjustment Scale (DAS). Additionally, women completed a quantitative sensory testing session to assess vestibular pain thresholds and associated pain ratings; specifically, vestibular pressure-pain and heat pain thresholds were measured. Gynecological and intercourse pain ratings; FSFI; GRISS; DAS; vestibular pressure-pain threshold; and vestibular heat pain thresholds. PVD-affected women reported significantly decreased sexual function in comparison with controls. While no differences in relationship satisfaction were found between groups, women with PVD did report less sexual satisfaction on the FSFI. PVD-affected women also reported significantly higher vestibular pain ratings associated with the gynecological examination and heat pain tolerance procedures, and lower pressure-pain threshold, heat pain threshold, and heat pain tolerance at the vestibule in comparison with controls. Among women with PVD, lower heat pain threshold was associated with less sexual satisfaction, and higher pain ratings related to intercourse and heat pain tolerance, respectively, were associated with lower sexual function and satisfaction. The results indicate that women with PVD experience negative sexual effects and increased pain sensitivity. This study also suggests that some aspects of pain may be related to lower levels of sexual function and satisfaction among affected women.


Improving Quality of Care in Federally Qualified Health Centers Through Ambulatory Care Accreditation.
HRSA supported health centers have a long history of participating in ambulatory care accreditation; however, there is a dearth of information on the relationship between accreditation and quality of care. We conducted a cross-sectional study of 1,202 health centers, using multivariate regression to estimate the association between accreditation and 14 clinical quality measures, controlling for patient and organizational characteristics. We also predicted national estimates of accreditation-related improvement in quality. Adjusted analyses show that accredited health centers achieved higher performance on adult weight screening and follow-up (coef = 0.037, p < .05), tobacco cessation intervention (coef = 0.042, p < .05), and use of lipid-lowering therapy (coef = 0.028, p < .05). Study results show that universal accreditation could result in additional 552,087 adult patients receiving weight screening and follow-up, 157,434 receiving tobacco cessation intervention and 25,289 receiving lipid-lowering therapy. This is the first national study to examine the impact of accreditation on health center quality of care. Findings suggest that HRSA support for accreditation has the potential to improve quality of care and as a result, reduce health disparities in underserved communities across the United States. Further research is necessary to identify specific elements of accreditation that have the greatest impact on quality of care.


Factors Influencing Vertical Transmission of Psittacine Bornavirus in Cockatiels (Nymphicus hollandicus).
The transmission of parrot bornavirus is still not fully understood. Although horizontal transmission through wounds can be one route, vertical transmission is still discussed. PaBV RNA and PaBV antigen were detected in psittacine embryos, but isolation of the virus failed, raising doubts about this route. In this study, cockatiels were infected either as adults (adult group) or during the first 6 days after hatching (juvenile group) and raised until sexual maturity to breed and lay eggs. A total of 92 eggs (adult group: 49, juvenile group: 43) were laid and incubated until day 17. The embryos and yolk samples were examined by RT-PCR for PaBV RNA and by infectivity assay for infectious virus. In the adult group, 14/31 embryos (45.2%) and 20/39 (51%) of the yolk samples demonstrated PaBV RNA in the PCR. Isolation of PaBV was not possible in any embryo of this group, but it was achieved in six yolk samples from one female. Anti-PaBV antibodies were detected in the yolk samples after seroconversion of all female parents. In the juvenile group, 22/29 embryos (74.9%) were positive for PaBV RNA. In 9/21 embryos (42.9%), PaBV isolation was possible. PaBV RNA was detected in 100% and infectious virus in 41% of the yolk samples. Anti-PaBV antibodies were detected in all yolk samples. For the first time, successful vertical transmission of PaBV was proven, but it seems to depend on the age when the parent birds are infected. Therefore, the age of the bird at time of infection may be an important factor in the occurrence of vertical transmission.


TLR4-Dependent Secretion by Hepatic Stellate Cells of the Neutrophil-Chemoattractant CXCL1 Mediates Liver Response to Gut Microbiota.
The gut microbiota significantly influences hepatic immunity. Little is known on the precise mechanism by which liver cells mediate recognition of gut microbes at steady state. Here we tested the hypothesis that a specific liver cell population was the sensor and we aimed at deciphering the mechanism by which the activation of TLR4 pathway would mediate liver response to gut microbiota. Using microarrays, we compared total liver gene expression in WT versus TLR4 deficient mice. We performed in situ localization of the major candidate protein, CXCL1. With an innovative technique based on cell sorting, we harvested enriched fractions of KCs, LSECs and HSCs from the same liver. The cytokine secretion profile was quantified in response to low levels of LPS (1ng/mL). Chemotactic activity of stellate cell-derived CXCL1 was assayed in vitro on neutrophils upon TLR4 activation. TLR4 deficient liver had reduced levels of one unique chemokine, CXCL1 and subsequent decreased of neutrophil counts. Depletion of gut microbiota mimicked TLR4 deficient phenotype, i.e., decreased neutrophils counts in the liver. All liver cells were responsive to low levels of LPS, but hepatic stellate cells were the major source of chemotactic levels of CXCL1. Neutrophil migration towards secretory hepatic stellate cells required the TLR4 dependent secretion of CXCL1. Showing the specific activation of TLR4 and the secretion of one major functional chemokine-CXCL1, the homolog of human IL-8-, we elucidate a new mechanism in which Hepatic Stellate Cells play a central role in the recognition of gut microbes by the liver at steady state.


EEG-based Identification of Evidence Accumulation Stages in Decision-Making.
Dating back to the 19th century, the discovery of processing stages has been of great interest to researchers in cognitive science. The goal of this paper is to demonstrate the validity of a recently developed method, hidden semi-Markov model multivariate pattern analysis (HsMM-MVPA), for discovering stages directly from EEG data, in contrast to classical reaction-time-based methods. To test the validity of stages discovered with the HsMM-MVPA method, we applied it to two relatively simple tasks where the interpretation of processing stages is straightforward. In these visual discrimination EEG data experiments, perceptual processing and decision difficulty were manipulated. The HsMM-MVPA revealed that participants progressed through five cognitive processing stages while performing these tasks. The brain activation of one of those stages was dependent on perceptual processing, whereas the brain activation and the duration of two other stages were dependent on decision difficulty. In addition, evidence accumulation models (EAMs) were used to assess to what extent the results of HsMM-MVPA are comparable to standard reaction-time-based methods. Consistent with the HsMM-MVPA results, EAMs showed that nondecision time varied with perceptual difficulty and drift rate varied with decision difficulty. Moreover, nondecision and decision time of the EAMs correlated highly with the first two and last three stages of the HsMM-MVPA, respectively, indicating that the HsMM-MVPA gives a more detailed description of stages discovered with this more classical method. The results demonstrate that cognitive stages can be robustly inferred with the HsMM-MVPA.


Lumboperitoneal shunting as a treatment for slit ventricle syndrome.
Slit ventricle syndrome (SVS) has been described in hydrocephalus patients who continue to have shunt malfunction-like symptoms in the presence of a functioning shunt system and small ventricles on imaging studies. These symptoms usually present years after shunt placement or revision and can consist of headache, nausea and vomiting, lethargy and decreased cognitive skills. Treatments offered range from observation, medical therapy (migraine treatment) and shunt revision to subtemporal decompression or cranial vault expansion. We describe a subset of patients with SVS who were symptomatic with high intracranial pressure (ICP) as measured by sedated lumbar puncture and whose symptoms completely resolved after lumboperitoneal shunt (LPS) placement. Seven patients with a diagnosis of SVS underwent lumboperitoneal shunting. The age at shunting ranged from 3 to 18 years. Most had undergone recent ventriculoperitoneal shunt (VPS) revisions for presentation of shunt malfunction-like symptoms. Despite this, all remained symptomatic and underwent a sedated lumbar puncture to measure opening pressure (OP). All had high OP in spite of a functional VPS and underwent LPS placement. All 7 patients had a prolonged period of overdrainage symptoms after lumboperitoneal shunting that resolved completely over several weeks. The initial etiology of hydrocephalus was reported to include trauma, aqueductal stenosis and intraventricular hemorrhage of prematurity. Two patients required revision of their LPS, after which their symptoms again resolved. In a certain subset of patients with SVS who are symptomatic from increased ICP, placement of an LPS is an effective treatment option. It appears that this subgroup of patients previously treated with ventriculoperitoneal shunting behave in a fashion similar to pseudotumor cerebri patients and respond well to lumboperitoneal shunting.


Training load quantification in elite swimmers using a modified version of the training impulse method.
Prior reports have described the limitations of quantifying internal training loads using hear rate (HR)-based objective methods such as the training impulse (TRIMP) method, especially when high-intensity interval exercises are performed. A weakness of the TRIMP method is that it does not discriminate between exercise and rest periods, expressing both states into a single mean intensity value that could lead to an underestimate of training loads. This study was designed to compare Banister's original TRIMP method (1991) and a modified calculation procedure (TRIMPc) based on the cumulative sum of partial TRIMP, and to determine how each model relates to the session rating of perceived exertion (s-RPE), a HR-independent training load indicator. Over four weeks, 17 elite swimmers completed 328 pool training sessions. Mean HR for the full duration of a session and partial values for each 50 m of swimming distance and rest period were recorded to calculate the classic TRIMP and the proposed variant (TRIMPc). The s-RPE questionnaire was self-administered 30 minutes after each training session. Both TRIMPc and TRIMP measures strongly correlated with s-RPE scores (r = 0.724 and 0.702, respectively; P < 0.001). However, TRIMPc was ∼ 9% higher on average than TRIMP (117 ± 53 vs. 107 ± 47; P < 0.001), with proportionally greater inter-method difference with increasing workload intensity. Therefore, TRIMPc appears to be a more accurate and appropriate procedure for quantifying training load, particularly when monitoring interval training sessions, since it allows weighting both exercise and recovery intervals separately for the corresponding HR-derived intensity.


Clinical Application of Diagnostic Imaging of Chiari-Like Malformation and Syringomyelia.
Chiari-like malformation (CM) and syringomyelia (SM) is a frequent diagnosis in predisposed brachycephalic toy breeds since increased availability of MRI. However, the relevance of that MRI diagnosis has been questioned as CM, defined as identification of a cerebellar herniation, is ubiquitous in some breeds and SM can be asymptomatic. This article reviews the current knowledge of neuroanatomical changes in symptomatic CM and SM and diagnostic imaging modalities used for the clinical diagnosis of CM-pain or myelopathy related to SM. Although often compared to Chiari type I malformation in humans, canine CM-pain and SM is more comparable to complex craniosynostosis syndromes (i.e., premature fusion of multiple skull sutures) characterized by a short skull (cranial) base, rostrotentorial crowding with rostral forebrain flattening, small, and ventrally orientated olfactory bulbs, displacement of the neural tissue to give increased height of the cranium and further reduction of the functional caudotentorial space with hindbrain herniation. MRI may further reveal changes suggesting raised intracranial pressure such as loss of sulci definition in conjunction with ventriculomegaly. In addition to these brachycephalic changes, dogs with SM are more likely to have craniocervical junction abnormalities including rostral displacement of the axis and atlas with increased odontoid angulation causing craniospinal junction deformation and medulla oblongata elevation. Symptomatic SM is diagnosed on the basis of signs of myelopathy and presence of a large syrinx that is consistent with the neuro-localization. The imaging protocol should establish the longitudinal and transverse extent of the spinal cord involvement by the syrinx. Phantom scratching and cervicotorticollis are associated with large mid-cervical syringes that extend to the superficial dorsal horn. If the cause of CSF channel disruption and syringomyelia is not revealed by anatomical MRI then other imaging modalities may be appropriate with radiography or CT for any associated vertebral abnormalities.


Inflammatory blood laboratory levels as markers of prosthetic joint infection: a systematic review and meta-analysis.
The preoperative diagnosis of prosthetic joint infection in patients with a total hip or knee arthroplasty may rely in part on the use of systemic inflammation markers. These markers have unclear accuracy. The objective of this review was to summarize the evidence on the accuracy of the peripheral white blood-cell count, the erythrocyte sedimentation rate, serum C-reactive protein levels, and serum interleukin-6 levels for the diagnosis of prosthetic joint infection. We searched electronic databases (MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus) from 1950 through 2009. Eligible studies evaluated the accuracy of white blood-cell count, erythrocyte sedimentation rate, serum C-reactive protein level, and serum interleukin-6 level for the intraoperative diagnosis of prosthetic joint infection at the time of revision arthroplasty. Two reviewers working independently extracted study characteristics and data to estimate the diagnostic odds ratio and 95% confidence interval for each result. We included thirty eligible studies that included 3909 revision total hip or knee arthroplasties. The prevalence of prosthetic joint infection was 32.5% (1270 of 3909). The accuracy of assessed inflammation markers, represented with a diagnostic odds ratio, was 314.7 (95% confidence interval, 113.0 to 876.8) for interleukin-6 (three studies), 13.1 (95% confidence interval, 7.9 to 21.7) for C-reactive protein level (twenty-three studies), 7.2 (95% confidence interval, 4.7 to 10.9) for erythrocyte sedimentation rate (twenty-five studies), and 4.4 (95% confidence interval, 2.9 to 6.6) for white blood-cell count (fifteen studies). The diagnostic accuracy for prosthetic joint infection was best for interleukin-6, followed by C-reactive protein level, erythrocyte sedimentation rate, and white blood-cell count. Given the limited numbers of studies assessing interleukin-6 levels, further investigations assessing the accuracy of interleukin-6 for the diagnosis of prosthetic joint infection are warranted.


t-complex-associated embryonic surface antigen homologous to mLAMP-1. II. Expression and distribution analyses.
We have previously demonstrated that a mouse t-complex-associated antigen (ESGp) is present on the cell surface, specifically at areas of cell-cell contact, of cleavage stage embryos and embryonal carcinoma cell lines. In the accompanying paper, we document isolation, purification, and partial sequencing of this molecule. Amino-terminal and internal peptide fragments are highly homologous to the mouse lysosomal-associated membrane protein-1 (mLAMP-1). We also demonstrate considerable similarity, though not necessarily identity, between these two antigens through both biochemical and molecular analyses. In this report we use immunological techniques to compare the expression and distribution of these antigens in various cell lines as well as mouse tissues and preimplantation stage embryos. The data presented indicate that there are: (1) different antigenic forms of the ESGp/ mLAMP-1 homologues and (2) changes in the molecular composition and expression of these forms during embryogenesis and differentiation. It is obvious from these studies that mLAMP-1 is not strictly a static molecule whose sole function is to protect the lumenal side of the lysosomal membrane but rather is a dynamic molecule of potential import in many other cellular and organismal functions.


Examining the Promotion of Healthy Eating among Exercise Specialists: A Cross-sectional Study.
The aim of this cross-sectional study was to survey exercise specialists about nutrition counselling practices, their own dietary practices, and to identify potential relationships. An electronic survey was used to examine characteristics and strategies used for assessing and promoting healthy eating to clients. Exercise specialists (n = 94) were recruited through a public registry and through targeted advertising on 2 professional websites in Alberta, Canada. Eighty-five percent of respondents promoted healthy eating to clients. Confidence in assessing and promoting healthy eating was moderate to low. Those with more than 6 years of professional experience reported higher confidence compared with those with less than 1 year of experience in assessing healthy eating (P < 0.05) and promoting healthy eating (P < 0.01). Confidence was higher among those with more professional experience but who did not meet Canada's Food Guide recommendations (P < 0.05). Professional experience, personal dietary practices, and confidence are important characteristics when considering the assessment and promotion of healthy eating by exercise specialists. Promoting collaborative relationships between registered dietitians and exercise specialists would likely benefit exercise specialists when they are assessing and promoting healthy eating among their clients.


Cancer immunotherapy based on killing of Salmonella-infected tumor cells.
A major obstacle for the development of effective immunotherapy is the ability of tumors to escape the immune system. The possibility to kill tumor cells because they are recognized as infected rather than as malignant could help overcome immune escape mechanisms. Here we report a conceptually new approach of cancer immunotherapy based on in vivo infection of tumors and killing of infected tumor cells. Attenuated but still invasive, Salmonella typhimurium can be successfully exploited to invade melanoma cells that can present antigenic determinants of bacterial origin and become targets for anti-Salmonella-specific T cells. However, to fully appreciate the anticancer therapeutic properties of S. typhimurium, tumor-bearing mice need to be vaccinated against S. typhimurium before intratumoral Salmonella injection. Tumor infection when coupled to anti-Salmonella vaccination leads to 50% to 100% tumor-free mice with a better outcome on larger tumors. Invasive Salmonella also exert an indirect toxic effect on tumor cells through the recruitment of inflammatory cells and the cross-presentation of tumor antigens, which allow induction of tumor-specific immune response. This is effective in retarding the growth of untreated established distant tumors and in protecting the mice from subsequent tumor challenges.


Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.
The skin barrier is the body's first line of defence against environmental assaults, and is maintained by epithelial stem cells (EpSCs). Despite the vulnerability of EpSCs to inflammatory pressures, neither the primary response to inflammation nor its enduring consequences are well understood. Here we report a prolonged memory to acute inflammation that enables mouse EpSCs to hasten barrier restoration after subsequent tissue damage. This functional adaptation does not require skin-resident macrophages or T cells. Instead, EpSCs maintain chromosomal accessibility at key stress response genes that are activated by the primary stimulus. Upon a secondary challenge, genes governed by these domains are transcribed rapidly. Fuelling this memory is Aim2, which encodes an activator of the inflammasome. The absence of AIM2 or its downstream effectors, caspase-1 and interleukin-1β, erases the ability of EpSCs to recollect inflammation. Although EpSCs benefit from inflammatory tuning by heightening their responsiveness to subsequent stressors, this enhanced sensitivity probably increases their susceptibility to autoimmune and hyperproliferative disorders, including cancer.


A 3-D Gabor Phase-Based Coding and Matching Framework for Hyperspectral Imagery Classification.
As manual labeling is very difficult and time-consuming, the labeled samples used to train a supervised classifier are generally limited, which become one of the biggest challenge for hyperspectral imagery classification. In order to tackle this issue, a recent trend is to exploit the structure information of materials, as which reflects the region homogeneity in the spatial domain and offers an invaluable complement to the spectral information. In this respect, 3-D Gabor wavelets have been introduced to extract joint spectral-spatial features for hyperspectral images. One the one hand, the features extracted by 3-D Gabor wavelets lead to very good performance for classification. On the other hand, its drawbacks, i.e., big number of features and high computational cost, limit its applicability. In this paper, a 3-D Gabor-wavelet-based phase coding and Hamming distance-based matching (3DGPC-HDM) framework is developed for hyperspectral imagery classification. The proposed method, instead of taking into account the large volume of Gabor magnitude features, exploits the Gabor phase features with certain orientations (i.e., the direction parallel to the spectral axis), which are then encoded by a simple quadrant bit coding scheme. After that, a normalized Hamming distance matching (HDM) method is adopted to determine the similarity of two samples, and the nearest neighbor classifier is routinely utilized for pixelwise recognition. Finally, experiments on three real hyperspectral data sets show that the proposed 3DGPC-HDM leads to very good performance. Comparisons with the state-of-the-art methods in the literature, in terms of both classifier complexity and generalization ability from very small training sets, are also included.


Metabolic stress evokes decreases in epithelial barrier function.
The epithelial lining of the gastrointestinal tract is the major interface between the external world (e.g., the gut lumen) and the body, and as such the proper maintenance and regulation of epithelial barrier function is a key determinant of digestive health and host well-being. Many enteropathies are associated with increased gut permeability, including inflammatory bowel disease (IBD). Maintaining the barrier function of the epithelium, independent of whether paracellular or transcellular permeation pathways are considered, is an energy-dependent process. Here we present an overview of the impact that metabolic stress (e.g., reductions in epithelial ATP synthesis) can have on permeability characteristics of epithelial monolayers and show that metabolic stress in the presence of a commensal flora results in a significant loss of epithelial integrity, and that this increase in epithelial permeability can be enhanced by the presence of tumor necrosis factor-alpha (TNFalpha). We speculate that the combination of these factors in vivo would result in significant perturbations in epithelial barrier function that could be of pathophysiological significance and contribute to the initiation of IBD or the induction of disease relapses.


Prescription medicine use by pedestrians and the risk of injurious road traffic crashes: A case-crossover study.
While some medicinal drugs have been found to affect driving ability, no study has investigated whether a relationship exists between these medicines and crashes involving pedestrians. The aim of this study was to explore the association between the use of medicinal drugs and the risk of being involved in a road traffic crash as a pedestrian. Data from 3 French nationwide databases were matched. We used the case-crossover design to control for time-invariant factors by using each case as its own control. To perform multivariable analysis and limit false-positive results, we implemented a bootstrap version of Lasso. To avoid the effect of unmeasured time-varying factors, we varied the length of the washout period from 30 to 119 days before the crash. The matching procedure led to the inclusion of 16,458 pedestrians involved in an injurious road traffic crash from 1 July 2005 to 31 December 2011. We found 48 medicine classes with a positive association with the risk of crash, with median odds ratios ranging from 1.12 to 2.98. Among these, benzodiazepines and benzodiazepine-related drugs, antihistamines, and anti-inflammatory and antirheumatic drugs were among the 10 medicines most consumed by the 16,458 pedestrians. Study limitations included slight overrepresentation of pedestrians injured in more severe crashes, lack of information about self-medication and the use of over-the-counter drugs, and lack of data on amount of walking. Therapeutic classes already identified as impacting the ability to drive, such as benzodiazepines and antihistamines, are also associated with an increased risk of pedestrians being involved in a road traffic crash. This study on pedestrians highlights the necessity of improving awareness of the effect of these medicines on this category of road user.


Melatonin and aromatase stimulating activity of human seminal plasma.
Melatonin concentrations and aromatase stimulating activity were determined in human seminal plasma and correlated with sperm density and motility. Aromatase stimulating activity was determined with an in vitro rat granulosa cell system and melatonin by radioimmunoassay. Compared to normal semen, aromatase stimulating activity was lower in azoospermic individuals, while melatonin was higher in oligospermic and azoospermic samples. Aromatase stimulating activity correlated positively with sperm concentrations and a negative correlation was found between melatonin and sperm progression. These findings suggest that low sperm production is associated with low aromatase stimulating bioactivity in seminal plasma; and melatonin may have an effect upon both sperm production and motility.


Knockdown of lncRNA XIST Suppresses Cell Tumorigenicity in Human Non-Small Cell Lung Cancer by Regulating miR-142-5p/PAX6 Axis.
Long noncoding RNA X inactivate-specific transcript (lncRNA XIST) has been identified to contribute to the development and progression of non-small cell lung cancer (NSCLC). Thus, it is important to explore more specific functions and molecular mechanisms of XIST in NSCLC tumorigenesis. The expression of XIST, microRNA (miR)-142-5p and paired box 6 (PAX6) was measured using quantitative real-time polymerase chain reaction or Western blot, respectively. Cell proliferation was analyzed using cell counting kit-8 (CCK-8) assay. Flow cytometry was utilized to measure apoptotic cells. Cell migration and invasion were determined by Transwell assay. The interaction between miR-142-5p and XIST or PAX6 was confirmed by the dual-luciferase reporter assay and RNA immunoprecipitation assay. In vivo experiments were performed through the murine xenograft model. XIST was elevated in NSCLC, and XIST knockdown suppressed cell proliferation, migration, invasion and induced apoptosis in vitro as well as repressed tumor growth in vivo. MiR-142-5p was a target of XIST, and silencing miR-142-5p reversed the anti-tumor functions mediated by XIST knockdown in NSCLC cells. PAX6 was confirmed to be a target of miR-142-5p, and the inhibitory effects caused by miR-142-5p restoration in NSCLC cell malignant phenotypes were attenuated by PAX6 overexpression. Besides that, XIST could indirectly regulate PAX6 expression by sponging miR-142-5p in vivo and in vitro. XIST suppresses cell tumorigenicity in human NSCLC by regulating miR-142-5p/PAX6 axis, which indicates a novel insight into the pathogenesis of NSCLC and lays a foundation for the molecular therapy of NSCLC.


ACR Appropriateness Criteria® Acute Pelvic Pain in the Reproductive Age Group.
Premenopausal women who present with acute pelvic pain frequently pose a diagnostic dilemma, exhibiting nonspecific signs and symptoms, the most common being nausea, vomiting, and leukocytosis. Diagnostic considerations encompass multiple organ systems, including obstetric, gynecologic, urologic, gastrointestinal, and vascular etiologies. The selection of imaging modality is determined by the clinically suspected differential diagnosis. Thus, a careful evaluation of such a patient should be performed and diagnostic considerations narrowed before a modality is chosen. Transvaginal and transabdominal pelvic sonography is the modality of choice when an obstetric or gynecologic abnormality is suspected, and computed tomography is more useful when gastrointestinal or genitourinary pathology is more likely. Magnetic resonance imaging, when available in the acute setting, is favored over computed tomography for assessing pregnant patients for nongynecologic etiologies because of the lack of ionizing radiation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.


RNA interference: antiviral weapon and beyond.
RNA interference (RNAi) is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. RNA interference is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and it may become a powerful tool to manipulate gene expression experimentally. RNAi technology is currently being evaluated not only as an extremely powerful instrument for functional genomic analyses, but also as a potentially useful method to develop specific dsRNA based gene-silencing therapeutics. Several laboratories have been interested in using RNAi to control viral infection and many reports in Nature and in Cell show that short interfering (si) RNAs can inhibit infection by HIV-1, polio and hepatitis C viruses in a sequence-specific manner. RNA-based strategies for gene inhibition in mammalian cells have recently been described, which offer the promise of antiviral therapy.


Functional mapping of N deficiency-induced response in wheat yield-component traits by implementing high-throughput phenotyping.
As overfertilization leads to environmental concerns and the cost of N fertilizer increases, the issue of how to select crop cultivars that can produce high yields on N-deficient soils has become crucially important. However, little information is known about the genetic mechanisms by which crops respond to environmental changes induced by N signaling. Here, we dissected the genetic architecture of N-induced phenotypic plasticity in bread wheat (Triticum aestivum L.) by integrating functional mapping and semiautomatic high-throughput phenotyping data of yield-related canopy architecture. We identified a set of quantitative trait loci (QTLs) that determined the pattern and magnitude of how wheat cultivars responded to low N stress from normal N supply throughout the wheat life cycle. This analysis highlighted the phenological landscape of genetic effects exerted by individual QTLs, as well as their interactions with N-induced signals and with canopy measurement angles. This information may shed light on our mechanistic understanding of plant adaptation and provide valuable information for the breeding of N-deficiency tolerant wheat varieties.


Romantic partner influences on prenatal and postnatal substance use in young couples.
Alcohol, tobacco and other drug use (ATOD) among adolescent and young adult couples during prenatal and postnatal periods is a significant public health problem, and couples may mutually influence each others' ATOD behaviors. The current study investigated romantic partner influences on ATOD among adolescent and young adult couples during pregnancy and postnatal periods. Participants were 296 young couples in the second or third trimester of pregnancy recruited from OBGYN clinics between July 2007 and February 2011. Participants completed questionnaires at prenatal, 6 months postnatal, and 12 months postnatal periods. Dyadic data analysis was conducted to assess the stability and interdependence of male and female ATOD over time. Male partner cigarette and marijuana use in the prenatal period significantly predicted female cigarette and marijuana use at 6 months postnatal (b = 0.14, P < 0.01; b = 0.11, P < 0.05, respectively). Male partner marijuana use at 6 months postnatal also significantly predicted female marijuana use at 12 months postnatal (b = 0.11, P < 0.05). Additionally, significant positive correlations were found for partner alcohol and marijuana at pre-pregnancy and 6 months postnatal, and partner cigarette use at pre-pregnancy, 6 months and 12 months postnatal. Partner ATOD among young fathers, particularly during the prenatal period, may play an important role in subsequent ATOD among young mothers during postnatal periods.


Passage of cytokines across the blood-brain barrier.
One mechanism by which blood-borne cytokines might affect the function of the central nervous system (CNS) is by crossing the blood-brain barrier (BBB) for direct interaction with CNS tissue. Saturable transport systems from blood to the CNS have been described for interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-6, and tumor necrosis factor-alpha (TNF-alpha). Blood-borne cytokines have been shown to cross the BBB to enter cerebrospinal fluid and interstitial fluid spaces of the brain and spinal cord. IL-2 does not cross the BBB by a saturable transport system. The blood-to-brain uptakes of IL-1 alpha, IL-beta, and IL-1ra are interrelated for most brain sites, but the posterior division of the septum shows selective uptake of blood-borne IL-1 alpha. The saturable transport systems for IL-6 and TNF-alpha are distinguishable from each other and from the IL-1 systems. The amount of blood-borne cytokines entering the brain is modest but comparable to that of other water-soluble compounds, such as morphine, known to cross the BBB in sufficient amounts to affect brain function. CNS to blood efflux of cytokines has also been shown to occur, but the mechanism of passage is unclear. Taken together, the evidence shows that passage of cytokines across the BBB occurs, providing a route by which blood-borne cytokines could potentially affect brain function.


Uncaria rhynchophylla Ameliorates Parkinson's Disease by Inhibiting HSP90 Expression: Insights from Quantitative Proteomics.
Uncaria rhynchophylla, known as "Gou-teng", is a traditional Chinese medicine (TCM) used to extinguish wind, clear heat, arrest convulsions, and pacify the liver. Although U. rhynchophylla has a long history of being often used to treat central nervous system (CNS) diseases, its efficacy and potential mechanism are still uncertain. This study investigated neuroprotective effect and the underlying mechanism of U. rhynchophylla extract (URE) in MPP+-induced SH-SY5Y cells and MPTP-induced mice. MPP+-induced SH-SY5Y cells and MPTP-induced mice were used to established Parkinson's disease (PD) models. Quantitative proteomics and bioinformatics were used to uncover proteomics changes of URE. Western blotting was used to validate main differentially expressed proteins and test HSP90 client proteins (apoptosis-related, autophagy-related, MAPKs, PI3K, and AKT proteins). Flow cytometry and JC-1 staining assay were further used to confirm the effect of URE on MPP+-induced apoptosis in SH-SY5Y cells. Gait analysis was used to detect the behavioral changes in MPTP-induced mice. The levels of dopamine (DA) and their metabolites were examined in striatum (STR) by HPLC-EC. The positive expression of tyrosine hydroxylase (TH) was detected by immunohischemical staining and Western blotting. URE dose-dependently increased the cell viability in MPP+-induced SH-SY5Y cells. Quantitative proteomics and bioinformatics results confirmed that HSP90 was an important differentially expressed protein of URE. URE inhibited the expression of HSP90, which further reversed MPP+-induced cell apoptosis and autophagy by increasing the expressions of Bcl-2, Cyclin D1, p-ERK, p-PI3K p85, PI3K p110α, p-AKT, and LC3-I and decreasing cleaved caspase 3, Bax, p-JNK, p-p38, and LC3-II. URE also markedly decreased the apoptotic ratio and elevated mitochondrial transmembrane potential (DΨm). Furthermore, URE treatment ameliorated behavioral impairments, increased the contents of DA and its metabolites and elevated the positive expressions of TH in SN and STR as well as the TH protein. URE possessed the neuroprotective effect in vivo and in vitro, regulated MAPK and PI3K-AKT signal pathways, and inhibited the expression of HSP90. U. rhynchophylla has potentials as therapeutic agent in PD treatment.


LD status and achievement: confounding variables in the study of children's social status, self-esteem, and behavioral functioning.
The purpose of the present study was to examine the role of achievement in explaining the poor social and behavioral functioning associated with LD status, and to evaluate potential gender differences in patterns of interpersonal functioning among youth with learning disabilities (LD) and nondisabled (NLD) youth. Thirty-two students with learning disabilities (21 boys, 11 girls) were matched with same-sex, same-race classmates whose reading achievement was low (LA) or average (AA), and these groups were compared on peer ratings of liking and disliking, perceptions of self-worth and social acceptance, and teacher ratings of conduct problems, anxiety-withdrawal, and attention problems. Students with learning disabilities were less accepted and less well-liked than children in the LA or AA groups and also perceived their self-worth and social acceptance to be lower than LA or AA students. Group by Sex interactions were apparent for several of the peer rating and behavioral variables, indicating that different patterns of social and behavioral functioning distinguished LD boys and LD girls from their NLD peers. The findings highlight the potential role of low achievement in peers' dislike of LD girls and suggest the importance of investigating well-defined subgroups of youth with LD in future research.


A clinicopathological study of women with adnexal masses presenting with acute symptoms.
Abdominal pain is one of the most common presentations of adnexal pathology in gynecology. Early diagnosis and intervention is essential especially in adolescent girls and reproductive age group women to conserve reproductive function. The purpose of the following study is to assess the clinicopathologic outcome of women with adnexal masses presenting with acute pain. A retrospective study of women with adnexal masses who had surgical intervention for acute symptoms from June 2007 to May 2012 was undertaken. During the study period, a total of 57 women were operated for adnexal masses as emergency. Of the 57 women operated for adnexal masses as emergency, the most common pathology was teratoma 26% (15/57) followed by corpus luteal hemorrhage (16%) and endometriosis (14%). Laparoscopy was the initial surgical approach in just over 50% of patients, but surgery was completed laparoscopically only in about one-third of patients. Conservative surgery in the form of ovarian cystectomy was possible in 70% of patients. Complications of adnexal masses such as torsion and hemorrhage are common causes of acute abdominal pain. Timely diagnosis of the adnexal pathology and surgical intervention will help to preserve the reproductive outcome. Conservative surgery was possible in 70% of our study group.


Antidepressant-like effects of Z-ligustilide on chronic unpredictable mild stress-induced depression in rats.
Depression is a significant public health issue and its neuropathogenesis is associated with the dysfunction of progesterone and allopregnanolone biosynthesis. Z-ligustilide (LIG), one of the main components of the herb Angelica sinensis (Oliv.) Diels (AS), is reported to have antidepressant activities. The present study aimed to evaluate the antidepressant-like effects of LIG via behavioral tests and to measure the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus. The results demonstrated that LIG (20 and 40 mg/kg) exerted antidepressant-like effects, confirmed by increased mobility, locomotion, rearing frequency and preference to sucrose. Furthermore, the levels of progesterone and allopregnanolone in the prefrontal cortex and hippocampus were markedly increased following treatment with LIG (20 and 40 mg/kg), indicating that both neurosteroids could serve a significant role in the antidepressant-like effects of LIG.


Escalation-related decision making in acute deterioration: a retrospective case note review.
To describe how decision making inter-relates with the sequence of events in individuals who die during admission and identify situations where formal treatment escalation plans (TEPs) may have utility. A retrospective case note review using stratified sampling. Two data analysis methods were applied concurrently: directed content analysis and care management process mapping via annotated timelines for each case. Analysis was followed by expert clinician review (n=7), contributing to data interpretation. 45 cases, age range 38-96 years, 23 females and 22 males. Length of admission ranged from <24 hours to 97 days. Process mapping led to a typology of care management, encompassing four trajectories: early de-escalation due to catastrophic event; treatment with curative intent throughout; treatment with curative intent until significant point; and early treatment limits set. Directed content analysis revealed a number of contextual issues influencing decision making. Three categories were identified: multiple clinician involvement, family involvement and lack of planning clarity; all framed by clinical complexity and uncertainty. The review highlighted the complex care management and related decision-making processes for individuals who face acute deterioration. These processes involved multiple clinicians, from numerous specialities, often within hierarchical teams. The review identified the need for visible and clear management plans, in spite of the frame of clinical uncertainty. Formal TEPs can be used to convey such a set of plans. Opportunities need to be created for patients and their families to request TEPs, in consultation with the clinicians who know them best, outside of the traumatic circumstances of acute deterioration.


Seasonal variation of intra-ocular pressure in glaucoma with and without dry eye.
The management of intra-ocular pressure (IOP) is important for glaucoma treatment. IOP is recognized for showing seasonal fluctuation. Glaucoma patients can be at high risk of dry eye disease (DED). We thus evaluated seasonal variation of IOP with and without DED in glaucoma patients. This study enrolled 4,708 patients, with mean age of 55.2 years, who visited our clinics in Japan from Mar 2015 to Feb 2017. We compared the seasonal variation in IOP (mean ± SD) across spring (March-May), summer (June-August), fall (September-November), and winter (December-February). IOP was highest in winter and lowest in summer, at 14.2/13.7 for non-glaucoma without DED group (n = 2,853, P = 0.001), 14.5/13.6 for non-glaucoma with DED group (n = 1,500, P = 0.000), 14.0/13.0 for glaucoma without DED group (n = 240, P = 0.051), and 15.4/12.4 for glaucoma with DED group (n = 115, P = 0.015). Seasonal variation was largest across the seasons in the glaucoma with DED group. IOP was also inversely correlated with corneal staining score (P = 0.000). In conclusion, the seasonal variation was significant in most of study groups and IOP could tend to be low in summer.


Biodegradable Materials and Green Processing for Green Electronics.
There is little question that the "electronic revolution" of the 20th century has impacted almost every aspect of human life. However, the emergence of solid-state electronics as a ubiquitous feature of an advanced modern society is posing new challenges such as the management of electronic waste (e-waste) that will remain through the 21st century. In addition to developing strategies to manage such e-waste, further challenges can be identified concerning the conservation and recycling of scarce elements, reducing the use of toxic materials and solvents in electronics processing, and lowering energy usage during fabrication methods. In response to these issues, the construction of electronic devices from renewable or biodegradable materials that decompose to harmless by-products is becoming a topic of great interest. Such "green" electronic devices need to be fabricated on industrial scale through low-energy and low-cost methods that involve low/non-toxic functional materials or solvents. This review highlights recent advances in the development of biodegradable materials and processing strategies for electronics with an emphasis on areas where green electronic devices show the greatest promise, including solar cells, organic field-effect transistors, light-emitting diodes, and other electronic devices.


Elucidating mechanisms of immunotoxicity by benzotriazole ultraviolet stabilizers in zebrafish (Danio rerio): Implication of the AHR-IL17/IL22 immune pathway.
Benzotriazole ultraviolet stabilizers (BUVSs) are widely used additives in industrial materials and personal care products that protect products from ultraviolet damage. Due to their high production volume and potential to bioaccumulate, BUVSs are an environmental pollutant of concern. In this study, juvenile zebrafish (Danio rerio) were exposed to 4 BUVSs (UV-234, UV-326, UV-329, and UV-P) at 10 and 100 μg/L for 28 d. BUVSs induced hepatic vacuolization and nuclei pyknosis in the liver following 100 μg/L UV-234 and UV-329 exposure. Transcriptomic analysis in the liver uncovered pathways related to inflammation that were affected by BUVSs. Based upon these data, we measured the expression levels of 9 genes involved in AHR-IL17/IL22 pathway in zebrafish larvae exposed to each BUVSs at one dose of either 10 or 100 μg/L for 6 days in a second set experiment. Transcript levels of interleukins il17a and il22 were decreased, while il6 mRNA was increased with exposure to UV-234, UV-329, and UV-P. No change to targeted transcripts was observed with UV-326 treatments. Moreover, cyp1a1 and ahr2 levels were increased in larvae treated with 100 μg/L UV-329 or UV-P. Consistent with expression data, protein abundance of IL22 was decreased by 29% with exposure to 100 μg/L UV-P. Taken together, these results demonstrate that exposure to different benzotriazole congeners may be associated with immunotoxicity in zebrafish through the AHR-IL17/IL22 pathway, and this may be associated with hepatic damage with prolonged exposures. This study provides new insight into unique pathways perturbed by specific BUVSs congeners.


Hand surgery using local anesthesia.
Most hand traumas and elective surgical disorders of the hand can be treated quickly, easily, inexpensively, and effectively in an outpatient clinic. Although many surgeons prefer general anesthesia, the senior author routinely uses local anesthesia without sedation almost exclusively for carpal and cubital tunnel release, fasciectomy, arthrodesis, arthroplasty, synovectomy, and trauma, including the repair of tendons, nerves, ligaments, fractures, and soft tissue defects. After completing more than 10,000 procedures, the authors have found great benefits through the use of local anesthesia, which are detailed in the article.


The influence of a high-bran diet on trace element retention in primates.
Proton-induced x-ray emission (PIXE) has become an established analytical method for the determination of trace elements in biomedical samples. The standard PIXE technique has been modified, resulting in a considerable improvement in detection limits. Refinements include the use of an external proton beam, the incorporation of a triggered beam-pulsing system, and the backward angle location (135 degrees to the incident ions) of the Si(Li) x-ray detector. The technique is now clearly capable of rapid, multielemental investigations, and requires a minimum of target preparation. Samples of liver and oesophagus tissue were obtained from 26 baboons at autopsy. Of these, 13 had been maintained on a semi-synthetic (high-bran) diet, with the remaining 13 forming the control group. Some 15 elements were analysed quantitatively; optimum detection limits were in the range 10-20 PPB (1 billion = 10(9). Clear differences were obtained: the high-bran diet is shown to produce imbalances in biologically active elements such as S, K, Ca, Ni Cu and Zn. These results are discussed on the basis of the phytate hypothesis, in terms of which trace elements in the diet are rendered physiologically unavailable to the subject.


Proteomic profiling of beta-cells using a classical approach - two-dimensional gel electrophoresis.
Proteomics has rapidly become a major field of research in biology and medicine. Its main aim is to obtain a global overview of the expression pattern of proteins and their relationship in any given condition of a biological system. This knowledge is of particular interest to elucidate the pathogenesis of complex disorders, such as diabetes. Separation of proteins by two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS) for their identification is perhaps the most widely used proteomic approach. In this review we have focused our attention on studies that have taken advantage of these methodologies to investigate the proteome of pancreatic islets, beta-cells and insulinoma cells in different conditions. As beta-cells of the pancreatic islets produce and secrete insulin, the main hormone for control of glucose homeostasis, these analyses may help to elucidate the mechanisms regulating insulin secretion and the development of various forms of diabetes, as well as to identify drug targets for therapeutic approaches.


A population-level and longitudinal study of adolescent mothers and intergenerational maltreatment.
For teenage mothers in California, we generated population-level estimates of the relationship between maternal history of maltreatment and next-generation abuse and neglect. California birth records for all infants born to primiparous teen mothers in 2006 or 2007 were linked to statewide child protective services (CPS) records. For each birth, we used CPS records to document 1) whether the teen mother had a history of reported or substantiated maternal maltreatment at or after age 10 years and before the estimated date of conception and 2) whether the teen's child was reported or substantiated for maltreatment before age 5 years. We fitted multivariable survival models to examine the association between a teenage mother's CPS involvement and child maltreatment, after adjusting for a range of sociodemographic variables. Our final data set included 85,084 births to first-time mothers aged 15-19 years. Significantly heightened rates of abuse and neglect were observed for children of mothers who had been reported to CPS as possible victims of maltreatment (P < 0.001). After adjustment for other risk factors, a maternal history of either unsubstantiated (hazard ratio = 2.19, 95% confidence interval: 2.06, 2.33) or substantiated (hazard ratio = 3.19, 95% confidence interval: 3.00, 3.39) maltreatment emerged as a strong predictor of maltreatment and CPS involvement in the next generation.


Facial Diplegia as a Rare Late Neurologic Manifestation of SARS-CoV-2 Infection.
Multiple recent publications have reported numerous neurologic complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Among these is Guillain-Barre syndrome and its variants, including facial diplegia. In this case we present a patient with facial diplegia following a confirmed SARS-CoV-2 infection. The patient initially presented with respiratory symptoms and subsequently developed bilateral facial weakness approximately 3 weeks later prompting an emergency department (ED) visit. Extensive laboratory and imaging workup was negative for other etiologies. Cerebrospinal fluid (CSF) analysis was notable only for mild elevation in white blood cells and protein. Patients with acute neurologic symptoms should be evaluated carefully regarding recent infections or possible exposures to help identify and minimize late complications of this novel virus.


Islet isolation from human pancreas with extended cold ischemia time.
The general consensus among transplant centers is that a cold ischemia time (CIT) beyond 8 hours results in reduced yields and quality of human islets. We sought to optimize the isolation process and enzymes for pancreata with extended CIT. We processed 16 extended CIT pancreata (13.2 +/- 0.7 hours). Donors averaged 50.8 +/- 2.6 (standard error of the mean) years old with a body mass index of 28.6 +/- 1.5. Glands were shipped in cold organ preservation solution without oxygenated perfluorocarbon. Isolations were performed under a protocol optimized for digestion with the new cGMP collagenase from Roche. Purification used continuous Euroficoll/University of Wisconsin gradients. Islets were cultured in two types of Prodo cGMP islet culture media and/or in Miami 1A media. Glucose-stimulated insulin secretion assays were performed after 8 to 16 days of culture. Prepurification yield averaged 415 +/- 41 KIEQ postpurification, 359 +/- 29 KIEQ (purification loss 13.5%); and postculture 317 +/- 27 KIEQ (culture loss 11.7%). Our process liberated an average of 4278 IEQ/g of pancreas (97 +/- 5 g). Most islets were recovered in the purest fraction (purity 79.7% +/- 1.9%). Culture loss in our enhanced culture media was 11.7%. After 2 to 3 days in culture, viability was 92% +/- 1%. Islets exhibited compactness and dithizone staining. Glucose-stimulated insulin secretion assays performed after 3 to 23 days in our PIM(R) media resulted in a stimulation index of 6.8 +/- 1.7 (G50 to G350). We concluded that our human islet isolation process permitted the recovery of large numbers of high-quality human islets from extended CIT pancreata and that our cGMP islet culture media was superior to the current standard CMRL-based media.


Epigenome-Wide Association Study of Prostate Cancer in African Americans Identifies DNA Methylation Biomarkers for Aggressive Disease.
DNA methylation plays important roles in prostate cancer (PCa) development and progression. African American men have higher incidence and mortality rates of PCa than other racial groups in U.S. The goal of this study was to identify differentially methylated CpG sites and genes between clinically defined aggressive and nonaggressive PCa in African Americans. We performed genome-wide DNA methylation profiling in leukocyte DNA from 280 African American PCa patients using Illumina MethylationEPIC array that contains about 860K CpG sties. There was a slight increase of overall methylation level (mean β value) with the increasing Gleason scores (GS = 6, GS = 7, GS ≥ 8, P for trend = 0.002). There were 78 differentially methylated CpG sites with P < 10-4 and 9 sites with P < 10-5 in the trend test. We also found 77 differentially methylated regions/genes (DMRs), including 10 homeobox genes and six zinc finger protein genes. A gene ontology (GO) molecular pathway enrichment analysis of these 77 DMRs found that the main enriched pathway was DNA-binding transcriptional factor activity. A few representative DMRs include HOXD8, SOX11, ZNF-471, and ZNF-577. Our study suggests that leukocyte DNA methylation may be valuable biomarkers for aggressive PCa and the identified differentially methylated genes provide biological insights into the modulation of immune response by aggressive PCa.


Phosphorylation of p190 on Tyr1105 by c-Src is necessary but not sufficient for EGF-induced actin disassembly in C3H10T1/2 fibroblasts.
p190 RhoGAP is a tyrosine phosphorylated protein that contains an N-terminal GTP binding domain, a middle domain (MD) that mediates interaction with p120 RasGAP and a C-terminal GTPase-activating protein (GAP) domain that is specific for the &Rgr; family of small GTPases. Evidence is accumulating to suggest that p190 participates in actin cytoskeleton rearrangements that occur following transformation by v-Src or stimulation by growth factors, and that tyrosine phosphorylation of p190 by Src influences these processes. The current study was performed to establish whether p190RhoGAP directly participates in epidermal growth factor-induced actin stress fiber disassembly and how c-Src is involved in this process. Our results support a model in which the p190 MD negatively regulates the activity of the GAP domain and that c-Src phosphorylation of Y1105 is necessary, but insufficient on its own, for actin stress fiber disassembly.


Zidovudine (AZT) overdose in a healthy newborn receiving postnatal prophylaxis.
Pediatric medication dosing and administration, faced with inherent challenges of dose to body weight adjustment and variable delivery vehicles, may lead to inadvertent errors effectively resulting in overdose. Zidovudine (AZT), a nucleoside analog reverse transcriptase inhibitor (NRTI), is a commonly prescribed medication to treat HIV-exposed newborns, with limited overdose data in this patient population. Metabolic acidosis with elevated lactate is the most serious consequence of AZT toxicity in the adult population, associated with mortality. Other significant effects may include neutropenia and hepatic dysfunction. A 4-day-old male infant who received two inadvertent 10-fold overdoses of AZT while being treated for HIV postnatal prophylaxis. The newborn developed a transient metabolic acidosis with elevated lactate that resolved within 24 h, a small increase in AST, and persistent neutropenia for 5 weeks. The patient's mother cited several key factors leading to the dosing error. The paucity of AZT overdose data in newborns and infants compels this case report, which reviews the published literature and provides insight into prevention and improvement of pediatric patient safety.


Progressive recruitment of Runx2 to genomic targets despite decreasing expression during osteoblast differentiation.
The mRNAs encoding Runx2, a master osteoblast transcription factor, and its target gene Osteocalcin (OC), are commonly used as markers of osteoblast differentiation. We found that while OC mRNA levels do indeed increase during development of the osteoblast phenotype in MC3T3-E1 cultures, Runx2 mRNA levels surprisingly decrease. Neither translational control of Runx2 (based on Western analysis) nor regulation of its DNA-binding ability (assessed by electrophoretic mobility shift assay) could explain the unexpected opposite patterns of Runx2 and OC expression. Instead, a series of chromatin immunoprecipitation (ChIP) assays during osteoblast differentiation revealed that early on, when Runx2 protein amount and DNA-binding activity are maximal, it is practically absent from the OC promoter. At later stages, Runx2 is recruited to the OC promoter while Runx2 mRNA, protein, and in vitro DNA binding progressively decrease. We also followed Runx2 occupancy at a novel genomic target discovered by ChIP-Chip analysis of cells in which the OC promoter is maximally occupied. The results revealed that Runx2 is recruited to this locus and to the OC promoter with a remarkably similar temporal pattern. These observations highlight a mechanism that restrains Runx2-mediated transcriptional control by confining its access to genomic targets to a narrow window of time. The need for such stringent control is consistent with the severe consequences of Runx2 over-expression in vivo.


Multidimensional LC x LC analysis of phenolic and flavone natural antioxidants with UV-electrochemical coulometric and MS detection.
A comprehensive 2-D LC x LC system was developed for the separation of phenolic and flavone antioxidants, using a PEG-silica column in the first dimension and a C(18) column with porous-shell particles or a monolithic column in the second dimension. Combination of PEG and C18 or C8 stationary phase chemistries provide low selectivity correlations between the first dimension and the second dimension separation systems. This was evidenced by large differences in structural contributions to the retention by -COOH, -OH and other substituents on the basic phenol or flavone structure. Superficially porous columns with fused core particles or monolithic columns improve the resolution and speed of second dimension separation in comparison to a fully porous particle C(18) column. Increased peak capacity and high orthogonality in different 2-D setups was achieved by using gradients with matching profiles running in parallel in the two dimensions over the whole 2-D separation time range. Multi-dimensional set-up combining the LC x LC separation on-line with UV and multi-channel coulometric detection and off-line with MS/MS technique allowed positive peak identification. The Coularray software compensates for the effects of the baseline drift during the gradient elution and is compatible with parallel gradient comprehensive LC x LC technique. Furthermore, it provides significant improvement in the sensitivity and selectivity of detection in comparison to both UV and MS detection. The utility of these systems has been demonstrated in the analysis of beer samples.


Natural and Induced Antibody Polyreactivity.
Healthy immune repertoire contains a fraction of immunoglobulins that do not possess exquisite antigen specificity but are able to recognize numerous unrelated antigens with similar values of the binding affinity. These antibodies are referred to as polyreactive. Besides natural polyreactive antibodies immune repertoires contain antibodies that acquire polyreactivity post-translationally, upon structural changes in their variable regions. In this article we made an overview of the recent findings about antibody polyreactivity. After introduction of the concept, and description of the origin, functions, and molecular mechanisms of polyreactive antibodies, we discussed their role in autoimmunity, malignancy and infectious diseases. We made a parallel with similar data about antibodies with induced polyreactivity. This review highlights the importance of natural and acquired antibody polyreactivity in immune defense and surveillance and reveals their potential as a new type of therapeutics.


A controlled 6-month clinical trial to study the effects of a stannous fluoride dentifrice on gingivitis.
This study was conducted to assess anti-plaque and anti-gingivitis benefits of a stabilized stannous fluoride (SnF(2))/sodium hexametaphosphate (SHMP) dentifrice versus a negative control. This was a randomized, 6-month, stratified, single-centre, double-blind, parallel group, clinical study conducted in harmony with the guidelines for evaluating chemotherapeutic products for the control of gingivitis outlined by the American Dental Association. A stabilized 0.454% SnF(2)/SHMP dentifrice was tested against a commercially available negative control dentifrice. Following baseline measurements, subjects received a dental prophylaxis. Subjects were instructed to brush twice daily for 60 s using their assigned product. Efficacy measurements were obtained at baseline, 3 and 6 months post treatment using the Modified Gingival Index, Gingival Bleeding Index and the Turesky Modified Quigley-Hein Plaque Index. Oral tissue examinations were performed at all visits. A total of 140 subjects were enroled and 128 completed the study. RESULTS after 6 months showed the SnF(2) dentifrice delivered a 16.9% reduction in gingivitis (p<0.001), a 40.8% reduction (p<0.001) in gingival bleeding, and an 8.5% reduction in plaque (p=0.001) versus the negative control. Both treatments were well tolerated. Twice daily use of the SnF(2)/SHMP dentifrice over 6 months provided statistically significant anti-plaque and anti-gingivitis benefits relative to a negative control.


Chromosomal-level assembly of Juglans sigillata genome using Nanopore, BioNano, and Hi-C analysis.
Juglans sigillata, or iron walnut, belonging to the order Juglandales, is an economically important tree species in Asia, especially in the Yunnan province of China. However, little research has been conducted on J. sigillata at the molecular level, which hinders understanding of its evolution, speciation, and synthesis of secondary metabolites, as well as its wide adaptability to its plateau environment. To address these issues, a high-quality reference genome of J. sigillata would be useful. To construct a high-quality reference genome for J. sigillata, we first generated 38.0 Gb short reads and 66.31 Gb long reads using Illumina and Nanopore sequencing platforms, respectively. The sequencing data were assembled into a 536.50-Mb genome assembly with a contig N50 length of 4.31 Mb. Additionally, we applied BioNano technology to identify contacts among contigs, which were then used to assemble contigs into scaffolds, resulting in a genome assembly with scaffold N50 length of 16.43 Mb and contig N50 length of 4.34 Mb. To obtain a chromosome-level genome assembly, we constructed 1 Hi-C library and sequenced 79.97 Gb raw reads using the Illumina HiSeq platform. We anchored ∼93% of the scaffold sequences into 16 chromosomes and evaluated the quality of our assembly using the high contact frequency heat map. Repetitive elements account for 50.06% of the genome, and 30,387 protein-coding genes were predicted from the genome, of which 99.8% have been functionally annotated. The genome-wide phylogenetic tree indicated an estimated divergence time between J. sigillata and Juglans regia of 49 million years ago on the basis of single-copy orthologous genes. We provide the first chromosome-level genome for J. sigillata. It will lay a valuable foundation for future research on the genetic improvement of J. sigillata.


Calorie restriction and bone health in young, overweight individuals.
Calorie restriction (CR) is promoted to increase longevity, yet this regimen could lead to bone loss and fracture and therefore affect quality of life. Forty-six individuals were randomized to 4 groups for 6 months: (1) healthy diet (control group); (2) 25% CR from baseline energy requirements (CR group); (3) 25% energy deficit by a combination of CR and increased aerobic exercise (CR + EX group); and (4) low-calorie diet (890 kcal/d; goal, 15% weight loss) followed by weight maintenance (LCD group). Bone mineral density (total body and hip by dual-energy x-ray absorptiometry) and serum bone markers (bone-specific alkaline phosphatase, osteocalcin, cross-linked C-telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured at baseline and after 6 months. Mean +/- SE body weight was reduced by -1.0% +/- 1.1% (control), -10.4% +/- 0.9% (CR), -10.0% +/- 0.8% (CR + EX), and -13.9% +/- 0.7% (LCD). Compared with the control group, none of the groups showed any change in bone mineral density for total body or hip. Bone resorption by serum cross-linked C-telopeptide of type I collagen was increased in all 3 intervention groups, with the largest change observed in the LCD group (CR, 23% +/- 10%; CR + EX, 22% +/- 9%; and LCD, 74% +/- 16% vs control, 4% +/- 10%). Serum levels of cross-linked N-telopeptide of type I collagen were also increased in the LCD group. With regard to bone formation, bone alkaline phosphatase levels were decreased in the CR group (-23% +/- 10%) but were unchanged in the CR + EX, LCD, and control groups. Moderate CR, with or without exercise, that preserves calcium intake for 6 months leads to large changes in body composition without significant bone loss in young adults. Longer studies with assessments of bone architecture are needed to confirm that CR nutrient-dense diets have no deleterious effect on bone health. clinicaltrials.gov Identifier: NCT00099151.


Management of fluid and electrolyte balance in thermal injuries: implications for perioperative nursing practice.
Thermal injury results in damage to the skin and underlying subcutaneous tissues. Extensive cutaneous injuries result in loss of water and electrolytes, and a disturbance in the homeostatic balance. The purpose of this article is to describe the pathophysiological changes that occur following extensive thermal injury and the common fluid-management challenges they provide. Implications for perioperative nursing practice are discussed.


Betacellulin, a member of the epidermal growth-factor family, is overexpressed in human pancreatic-cancer.
Human pancreatic ductal adenocarcinomas overexpress the epidermal growth factor (EGF) receptor. Betacellulin is a mitogenic polypeptide that binds and activates this receptor. To determine whether betacellulin has a role in human pancreatic cancer, we studied its expression in cultured human pancreatic cancer cell lines and in normal and cancerous pancreatic tissues. Five of 6 pancreatic cancer cell lines expressed the 3 kb betacellulin mRNA moiety, T3M4, MiaPaCa-2 and COLO-357 cells exhibiting the highest expression levels. EGF, heparin-binding EGF-like growth factor (HB-EGF), and basic fibroblast growth factor (bFGF) increased betacelullin mRNA levels. Only 2 of 15 normal samples and 1 of 10 cancer samples failed to exhibit the betacellulin transcript. Densitometric analysis of the autoradiographs revealed a 7.5-fold increase in betacellulin mRNA levels in the cancer tissues by comparison with the normal tissues. By in situ hybridization, the duct-like cancer cells exhibited many betacellulin mRNA in situ hybridization grains. These findings indicate that human pancreatic cancer cells express betacellulin in culture and in vivo, and suggest that this EGF-like ligand may participate in aberrant autocrine and paracrine activation of the EGF receptor in human pancreatic cancer.


Antigen disappearance in hibernating ground squirrels.
The rate of antigen disappearance was studied in hibernating ground squirrels (Citellus tridecemlineatus) injected with I(131)-labeled bovine serum albumin. There was no detectable disappearance of antigen during 14 days of hibernation. The induction period, however, ended 5 days after arousal as compared to a 7-day induction period in nonhibernating ground squirrels.


Application of zebrafish oculomotor behavior to model human disorders.
To ensure high acuity vision, eye movements have to be controlled with astonishing precision by the oculomotor system. Many human diseases can lead to abnormal eye movements, typically of the involuntary oscillatory eye movements type called nystagmus. Such nystagmus can be congenital (infantile) or acquired later in life. Although the resulting eye movements are well characterized, there is only little information about the underlying etiology. This is in part owing to the lack of appropriate animal models. In this review article, we describe how the zebrafish with its quick maturing visual system can be used to model oculomotor pathologies. We compare the characteristics and assessment of human and zebrafish eye movements. We describe the oculomotor properties of the zebrafish mutant belladonna, which has non-crossing optical fibers, and is a particularly informative model for human oculomotor deficits. This mutant displays a reverse optokinetic response, spontaneous oscillations that closely mimic human congenital nystagmus and abnormal motor behavior linked to circular vection.


Differential diagnosis and management of ankylosing spondylitis masked as adhesive capsulitis: a resident's case problem.
Resident's case problem. Ankylosing spondylitis is a potentially debilitating seronegative spondyloarthropathy, with inflammatory low back pain as the most commonly reported symptom. In the absence of low back pain, identification of other diagnostic criteria or associated impairments and joint involvement, such as involvement of the hip or shoulder, may be beneficial. A 32-year-old man with right shoulder pain and decreased range of motion was referred with a diagnosis of adhesive capsulitis. He had been managed by multiple healthcare providers for 3 years before being referred to a physical therapist. Glenoid labral pathology was evident on prior magnetic resonance imaging, which had led to a persistent focus on the shoulder. The evaluation by the physical therapist revealed significant mobility deficits in the cervical, thoracic, and lumbar spine. Radiographs and laboratory tests were ordered and a referral was made to rheumatology after the initial physical therapy assessment. The diagnostic work-up confirmed the diagnosis of ankylosing spondylitis and led to multidisciplinary management of the disease. Low back pain is often the primary symptom of ankylosing spondylitis later in the disease process. Earlier indicators of ankylosing spondylitis, such as severely impaired mobility and spine stiffness, may help guide detection in the absence of spinal pain. In this case, an appropriate diagnosis led to improvement in the management strategy of what might have appeared to be unrelated shoulder pain. Early differential diagnosis is important, as emerging interventions show promise when used earlier in the disease process.


Improvements in Diet and Physical Activity-Related Psychosocial Factors Among African Americans Using a Mobile Health Lifestyle Intervention to Promote Cardiovascular Health: The FAITH! (Fostering African American Improvement in Total Health) App Pilot Study.
African Americans continue to have suboptimal cardiovascular health (CVH) related to diet and physical activity (PA) behaviors compared with White people. Mobile health (mHealth) interventions are innovative platforms to improve diet and PA and have the potential to mitigate these disparities. However, these are understudied among African Americans. This study aims to examine whether an mHealth lifestyle intervention is associated with improved diet and PA-related psychosocial factors in African Americans and whether these changes correlate with diet and PA behavioral change. This study is a retrospective analysis evaluating changes in diet and PA-related self-regulation, social support, perceived barriers, and CVH behaviors (daily fruit and vegetable intake and moderate-intensity PA [MPA] per week) in 45 African American adults (mean age 48.7 years, SD 12.9 years; 33/45, 73% women) enrolled in the FAITH! (Fostering African American Improvement in Total Health) app pilot study. The intervention is a 10-week, behavioral theory-informed, community-based mHealth lifestyle intervention delivered through a mobile app platform. Participants engaged with 3 core FAITH! app features: multimedia education modules focused on CVH with self-assessments of CVH knowledge, self-monitoring of daily fruit and vegetable intake and PA, and a sharing board for social networking. Changes in self-reported diet and PA-related self-regulation, social support, perceived barriers, and CVH behaviors were assessed by electronic surveys collected at baseline and 28 weeks postintervention. Changes in diet and PA-related psychosocial factors from pre- to postintervention were assessed using paired 2-tailed t tests. The association of changes in diet and PA-related psychosocial variables with daily fruit and vegetable intake and MPA per week was assessed using Spearman correlation. Associations between baseline and 28-week postintervention changes in diet and PA-related psychosocial measures and CVH behaviors with covariates were assessed by multivariable linear regression. Participants reported improvements in 2 subscales of diet self-regulation (decrease fat and calorie intake, P=.01 and nutrition tracking, P<.001), one subscale of social support for healthy diet (friend discouragement, P=.001), perceived barriers to healthy diet (P<.001), and daily fruit and vegetable intake (P<.001). Improvements in diet self-regulation (increase fruit, vegetable, and grain intake, and nutrition tracking) and social support for healthy diet (friend encouragement) had moderate positive correlations with daily fruit and vegetable intake (r=0.46, r=0.34, and r=0.43, respectively). A moderate negative correlation was observed between perceived barriers to healthy diet and daily fruit and vegetable intake (r=-0.25). Participants reported increases in PA self-regulation (P<.001). Increase in social support subscales for PA (family and friend participation) had a moderate positive correlation with MPA per week (r=0.51 and r=0.61, respectively). Our findings highlight key diet and PA-related psychosocial factors to target in future mHealth lifestyle interventions aimed at promoting CVH in African Americans.


[Therapeutic results in children with acute non-lymphoblastic leukemia treated with modified BFM-87 protocol].
The effectiveness of modification of the BFM-87 schedule of treatment received by 32 children with different forms of acute non-lymphoblastic leukemia since April, 1991, has been studied. Complete remission was recorded in 90% and 5-year recurrence-free survival--in 47%. Although the complication rate was higher as compared with the "7 + 3" schedule, mortality rates were relatively lower due to application of adjuvant therapy.


[Modern approaches to the diagnosis of head injury].
The diagnosis of head injury should be based on certain principles. Each of them is important and has its own history. The authors summarize the experience of treatment of head injury using clinical and neuroimaging methods at the NN Burdenko Neurosurgery Institute (now the NN Burdenko National Research Center for Neurosurgery) for more than 30 years. The following principles of diagnosis of head injury were suggested and tested in clinical practice: severity of patient's state; clinical syndromes; topical diagnosis; neuroimaging; phasicity; age-related approach; data synthesis; sufficiency; individual approach. Taken together, these principles provide complete personalized diagnosis and prognosis which allow choosing an optimal management of the patient. The strategy for better diagnosis, prognosis and treatment of head injury is the combined use of clinical, neuroimaging and ethical approaches.


Quantification of Adhesion Force of Bacteria on the Surface of Biomaterials: Techniques and Assays.
Biomaterials associated infection (BAI) has been identified as one of the leading causes of failure of bioimplants. A failed implant requires revision surgery, which is about 20 times costlier and more painful than primary surgery. Infection starts from initial attachment of bacteria onto the surface of biomaterials followed by colonization and biofilm formation. Once a biofilm is developed the bacteria become resistant toward antibiotics. On account of microbial cell development, their metabolic activity and viability are strongly affected by the adhesion. Hence a thorough investigation warrants an in-depth understanding of the interfacial adhesion. Several methods such as plate-and-wash assay, spinning-disc assay, centrifugation assay, step-pressure technique, optical tweezers, atomic force microscopy (AFM) and nanoindentation are used for the measurement of the bacterial adhesion. Most of the aforementioned techniques are nonquantitative and provide only approximate values of adhesion forces. Techniques such as AFM and nanoindentation can quantify a wide range of force 10 pN to 1 μN and 1 nN to 10 μN respectively, and hence they are particularly useful for exact quantification of the adhesion force as well as adhesion strength of bacterial cells on various surfaces of biomaterials. In this review, we present a comparative study of the techniques available to measure the bacterial adhesion force and strength, discuss the use of AFM in adhesion force quantification in detail and conclude by hypothesizing that the AFM technique has an edge over other techniques for quantification of bacterial adhesion force.


Biological monitoring of pesticide exposures in residents living near agricultural land.
There is currently a lack of reliable information on the exposures of residents and bystanders to pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure for regulatory purposes are appropriate for farm workers 1. However, there were indications that the exposures of bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this study aims to collect measurements to determine if the current methods and tools are appropriate for assessing pesticide exposure for residents living near agricultural fields. The study will recruit owners of farms and orchards (hereafter both will be referred to as farms) that spray their agricultural crops with certain specified pesticides, and which have residential areas in close proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the spray season. Informed consenting residents (adults (18 years and over) and children (aged 4-12 years)) will be asked to provide urine samples and accompanying activity diaries during the spraying season and in addition for a limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and mathematical modelling will use the laboratory results, along with the additional data collected from the farmers and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected areas of the United Kingdom over two years (2011 and 2012), covering two spraying seasons and the time between the spraying seasons. The described study protocol was implemented for the sample and data collection procedures carried out in 2011. Based on experience to date, no major changes to the protocol are anticipated for the 2012 spray season although the pesticides and regional areas for inclusion in 2012 are still to be confirmed.


Expression Quantitative Trait Loci (eQTL) Mapping in Korean Patients With Crohn's Disease and Identification of Potential Causal Genes Through Integration With Disease Associations.
Expression quantitative trait loci (eQTL) datasets have extensively been used to help interpret genome-wide association study signals. Most eQTL analyses have been conducted with populations of European ancestry. To determine the most functionally relevant genes at the Crohn's disease (CD) loci identified in genome-wide association studies (GWAS) involving Asian populations and to find novel disease-associated genes, we conducted an eQTL analysis. eQTL analysis was performed using whole-blood RNA-sequencing of 101 Korean patients with CD. FastQTL was used for a pair-wise genome analysis of ∼ 6.5 M SNPs and ∼ 22 K transcripts. We identified 135,164 cis-eQTL and 3,816 eGenes with a false discovery rate less than 0.05. A significant proportion of the genes identified in our study overlapped with those identified in previous studies. The significantly enriched pathways of these 3,816 eGenes included neutrophil degranulation and small molecule biosynthetic process. Integrated analysis of CD GWAS with Korean eQTL revealed two putative target genes, TNFSF15 and GPR35, at two previously reported loci, whereas TNFSF15 only with the whole blood data from the Genotype-Tissue Expression (GTEx) project, highlighting the utility of building a population-specific data set, even of modest size. The risk alleles of these genes were found to be associated with lower expression levels of TNFSF15 and GPR35, respectively. Our eQTL browser can be accessed at "http://asan.crohneqtl.com/". This resource would be useful for studies that need to employ genome-wide association analyses involving Asian populations.