Desaturation of linoleic acid from exogenous lipids by isolated chloroplasts.
When [14C]diacylgalactosylglycerol was added to isolated pea or lettuce chloroplasts linolenate synthesis was seen. The desaturation of [14C]linoleate in diacylgalactosylglycerol to [14C]linolenate was stimulated by the addition of a soluble protein fraction containing lipid-exchange activity. Other [14C]acyl lipids were ineffective, except that [14C]phosphatidylcholine in the presence of UDP-galactose and sn-glycerol 3-phosphate could also supply [14C]linoleate for desaturation. These results are consistent with a role of diacylgalactosylglycerol in linolenate synthesis, as indirectly suggested by labelling experiments.


How can we assess the burden of muscle, bone and joint conditions in rural Botswana: context and methods for the MuBoJo focused ethnography.
Musculoskeletal diseases are the most common causes of long-term pain and disability worldwide and a growing international public health concern. However, the everyday burden and impact of musculoskeletal conditions are not well understood, especially among people living in low- and middle-income countries in Africa. Since 2011, World Spine Care, a nongovernmental organisation, has collaborated with the Botswana Ministry of Health to open spine care centres and to conduct research. The broad aim of the Muscle, Bone and Joint (MuBoJo) research project is to examine the sociocultural, organisational and clinical characteristics for the burden of living with and caring for people living with musculoskeletal conditions in rural Botswana. In this paper, we describe the community context, theoretical framework, and research methods to address the project aim with a qualitative study. This focused ethnography is based on eight months (November 2011, April 2013, October 2013-March 2014) of fieldwork in Botswana. The project was theoretically informed by the concepts of explanatory models of illness, social suffering, and biographical disruption. Data collection included fieldnotes, non-participant and participant observations, and informal and in-depth interviews with villagers and healthcare providers. Villager interviews were typically conducted in Setswana with an interpreter. Audio recordings were transcribed verbatim in the language spoken with Setswana contextually translated into English. Computer software supported qualitative data management. Analysis is ongoing using constant comparison and a template organising style to facilitate pattern-finding and reveal insights for the burden and care of musculoskeletal conditions. Findings from the MuBoJo Project will document the context of musculoskeletal burden, illness beliefs, self-care behaviours, and healthcare options in a Botswana rural village. These data will inform ongoing efforts to establish spine care clinics for underserved populations in low-middle income countries and sustain these healthcare services through local providers and volunteer health professionals. This study also will generate new knowledge about the burden and impact of muscle, bone and joint disorders for cross-cultural comparisons and patient-centred interventions. Our systematic and transparent methodology to conduct musculoskeletal research in more than one language and in a cross-cultural setting may be useful for investigators and NGO healthcare personnel.


Experiences of patients having tuberculosis (TB) regarding the use of Directly Observed Treatment Short-Course (DOTS) in the North West Province, South Africa.
Tuberculosis (TB) management remains a major challenge despite the implementation of Directly Observed Treatment Short-Course (DOTS). Some of the challenges include defaulting treatment, low TB cure rates and relapse after patients had been treated under DOTS. This study explored and described experiences of patients having TB regarding the use of DOTS in Doctor Ruth Segomotsi Mompati District of North West Province, South Africa. The study describes and recommends support required by patients having TB who are using DOTS. A qualitative, exploratory, descriptive and contextual design was used. The population consisted of all patients having TB under DOTS who had taken treatment for 2 months and more in one of the community health centres in Doctor Ruth Segomotsi Mompati District. Purposive sampling technique was applied to select participants receiving DOTS service. In-depth unstructured individual interviews were conducted, and data saturation occurred after having interviewed 15 participants. Ethical considerations were ensured throughout the study, and data were analysed using Tesch's method of coding and analysis. Two themes emerged from data and these are discussed as concerns related to ineffective use of DOTS and lack of resources as contributory factor to ineffective use of DOTS. Among other categories, poor nurse-patient relationships and difficulties in accessing the community health centre emerged as consistent themes related to default and inconsistent use of DOTS. Ineffective use of DOTS contributed to TB treatment default and low cure rate. Therefore, recommendations focused on strengthening effective use of DOTS for the management of TB.


Increase in Campylobacter jejuni invasion of intestinal epithelial cells under low-oxygen coculture conditions that reflect the in vivo environment.
Campylobacter jejuni infection often results in bloody, inflammatory diarrhea, indicating bacterial disruption and invasion of the intestinal epithelium. While C. jejuni infection can be reproduced in vitro using intestinal epithelial cell (IEC) lines, low numbers of bacteria invading IECs do not reflect these clinical symptoms. Performing in vitro assays under atmospheric oxygen conditions neither is optimal for microaerophilic C. jejuni nor reflects the low-oxygen environment of the intestinal lumen. A vertical diffusion chamber (VDC) model system creates microaerobic conditions at the apical surface and aerobic conditions at the basolateral surface of cultured IECs, producing an in vitro system that closely mimics in vivo conditions in the human intestine. Ninefold increases in interacting and 80-fold increases in intracellular C. jejuni 11168H wild-type strain bacteria were observed after 24-h coculture with Caco-2 IECs in VDCs under microaerobic conditions at the apical surface, compared to results under aerobic conditions. Increased bacterial interaction was matched by an enhanced and directional host innate immune response, particularly an increased basolateral secretion of the proinflammatory chemokine interleukin-8 (IL-8). Analysis of the invasive ability of a nonmotile C. jejuni 11168H rpoN mutant in the VDC model system indicates that motility is an important factor in the early stages of bacterial invasion. The first report of the use of a VDC model system for studying the interactions of an invasive bacterial pathogen with IECs demonstrates the importance of performing such experiments under conditions that represent the in vivo situation and will allow novel insights into C. jejuni pathogenic mechanisms.


Quantitative contribution of CD4 and CD8 to T cell antigen receptor serial triggering.
CD4 and CD8 are thought to function as coreceptors by binding to the cognate major histocompatibility complex (MHC) molecules recognized by the T cell antigen receptor (TCR) and initiating the signal transduction cascade. We report that during T cell-antigen-presenting cell interaction, triggered TCRs and coreceptors are downregulated and degraded with identical kinetics. This coordinated disappearance takes place whenever the TCR is triggered, even when the coreceptor does not engage the cognate MHC molecule and is the consequence of binding of the coreceptor-associated Lck to ZAP-70. The interaction of coreceptor and cognate MHC molecules is dispensable when T cells are stimulated by optimal ligands, but becomes crucial when suboptimal ligands are used. In the latter case the coreceptor increases the efficiency of TCR triggering without changing the activation threshold or the quality of the T cell response.


PHD2 regulates arteriogenic macrophages through TIE2 signalling.
Occlusion of the main arterial route redirects blood flow to the collateral circulation. We previously reported that macrophages genetically modified to express low levels of prolyl hydroxylase domain protein 2 (PHD2) display an arteriogenic phenotype, which promotes the formation of collateral vessels and protects the skeletal muscle from ischaemic necrosis. However, the molecular mechanisms underlying this process are unknown. Here, we demonstrate that femoral artery occlusion induces a switch in macrophage phenotype through angiopoietin-1 (ANG1)-mediated Phd2 repression. ANG blockade by a soluble trap prevented the downregulation of Phd2 expression in macrophages and their phenotypic switch, thus inhibiting collateral growth. ANG1-dependent Phd2 repression initiated a feed-forward loop mediated by the induction of the ANG receptor TIE2 in macrophages. Gene silencing and cell depletion strategies demonstrate that TIE2 induction in macrophages is required to promote their proarteriogenic functions, enabling collateral vessel formation following arterial obstruction. These results indicate an indispensable role for TIE2 in sustaining in situ programming of macrophages to a proarteriogenic, M2-like phenotype, suggesting possible new venues for the treatment of ischaemic disorders.


DNA testing for hypertrophic cardiomyopathy: a cost-effectiveness model.
Aims To explore the cost-effectiveness of alternative methods of screening family members for hypertrophic cardiomyopathy (HCM), the most common monogenic cardiac disorder and the most frequent cause of sudden cardiac death (SCD) in young people. Methods and results Economic decision model comparing cascade screening by genetic, as opposed to clinical methods. The incremental cost per life year saved was 14,397 euro for the cascade genetic compared with the cascade clinical approach. Genetic diagnostic strategies are more likely to be cost-effective than clinical tests alone. The costs for cascade molecular genetic testing were slightly higher than clinical testing in the short run, but this was largely because the genetic approach is more effective and identifies more individuals at risk. Conclusion The use of molecular genetic information in the diagnosis and management of HCM is a cost-effective approach to the primary prevention of SCD in these patients.


Genetic and environmental correlations between bone formation and bone mineral density: a twin study.
Bone mineral density (BMD) and bone turnover are both heritable. Although bone turnover affects bone mass, it is not clear whether these parameters are under common genetic or environmental control. The relative contribution of genetic and environmental factors to the determination of an index of bone turnover, bone specific alkaline phosphatase (BSAP), and the extent of common genetic regulation with BMD, were examined in 97 female twin pairs, aged 50 +/- 15 years (mean +/- SD), consisting of 48 monozygotic (MZ) and 49 dizygotic (DZ) pairs. BSAP was analyzed by radioimmunometric assay. Bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN) was measured by dual-energy X-ray absorptiometry. Twin resemblance for variable traits was assessed by intraclass correlation coefficients. Estimates of genetic and environmental components of variance were based on univariate and multivariate genetic models. As expected, BSAP in premenopausal women (9.8 +/- 4.3 microg/L) was significantly lower than in postmenopausal women (13.3 +/- 6.6 microg/L, p < 0.001), but similar to the subgroup of postmenopausal women on hormone replacement therapy (10.8 +/- 2.6 microg/L, p = 0.15). Although BSAP and BMD were correlated in a cross-sectional analysis (r = -0.35, p < 0.001 for LS-BMD; r = -0.16, p = 0.03 for FN-BMD), the intrapair difference in BSAP was not significantly correlated with the intrapair difference in BMD for MZ twin pairs. After adjustment for menopausal status, the intraclass correlation for BSAP was significantly higher in MZ than DZ twins (0.60 +/- 0.09 vs. 0.27 +/- 0.13, p = 0.03). Univariate model-fitting analyses indicated a heritability of 63% for BSAP, and 77% and 72% for lumbar spine and femoral neck BMD, respectively. By multivariate analyses, genes specifically influencing BSAP accounted for 16% of the total genetic variance in LS-BMD and 4% of the total genetic variance in FN-BMD. There was no evidence for shared environmental factors affecting BSAP and BMD. These findings indicate that BSAP and BMD are heritable and negatively correlated. However, the genetic loci influencing BSAP and BMD appear to be largely independent as are any environmental factors.


Influence of a holey cladding structure on spectral characteristics of side-polished endlessly single-mode photonic crystal fibers.
We experimentally investigate the spectral characteristics of side-polished endlessly single-mode photonic crystal fibers of different polishing depths and radii of curvature that are important to mode field diameter, evanescent coupling, waveguide losses, higher-order mode excitation, and dispersion slopes of photonic crystal fiber components. A polished photonic crystal fiber with a greater polishing depth or a larger radius of curvature shows a more dispersive characteristic. In contrast to conventional single-mode fibers, in photonic crystal fibers the evanescent field is more strongly localized, and the propagating light can be more efficiently guided within the deformed core.


Interferon-gamma release assays for tuberculosis screening of healthcare workers: a systematic review.
Healthcare workers (HCWs) are at increased risk of exposure to tuberculosis (TB). Traditionally, screening for latent TB infection (LTBI) is done using the tuberculin skin test (TST). Interferon-gamma release assays (IGRAs) are now increasingly being used for diagnosis of LTBI, but their role in HCW screening is unclear. A systematic review was conducted of all IGRA studies in HCWs to summarise their performance in cross-sectional and serial testing settings. By searching four electronic databases and other sources, all available studies using any one of the commercial IGRA assays in HCWs were retrieved and screened. 50 unique studies were identified which met the inclusion criteria including five from high TB incidence settings. Among 24 cross-sectional studies in low TB incidence settings, the pooled prevalence of positive IGRA using either test was significantly lower than for a positive TST. However, in high-incidence settings (n=2) there were no consistent differences in the prevalence of positive tests. IGRAs showed good correlation with occupational risk factors for TB exposure in low-incidence settings. Only 10 studies assessed use of IGRA for serial testing and all showed large variation in the rates of conversions and reversions, with no data suggesting that IGRAs are better at identifying the incidence of new TB infection than the TST. The use of IGRAs instead of TST for one-time screening may result in a lower prevalence of positive tests and fewer HCWs who require LTBI treatment, particularly in low TB incidence settings. However, the use of IGRAs for serial testing is complicated by lack of data on optimum cut-offs for serial testing and unclear interpretation and prognosis of conversions and reversions. Further longitudinal research will be required to inform guidelines on serial testing using IGRAs.


Mechanism of bradykinin-induced venodilation in humans.
Bradykinin, a nonapeptide, dilates vascular smooth muscle at least in part via endothelial cell-dependent mechanisms. The aim of this study was to examine the action of bradykinin in human veins in vivo. Utilizing the dorsal hand vein technique, dose-response curves to bradykinin (maximum dose = 513 ng/min) were constructed in veins preconstricted with the alpha-adrenergic agonist phenylephrine in healthy young volunteers. Bradykinin almost fully dilated the veins back to their baseline diameter. To determine if desensitization of bradykinin-mediated vasodilation occurs, two bradykinin dose-response curves were constructed with a short (10 min) interval between studies. The second dose-response curve showed a diminished response. The EMAX of the first curve was 97.8 +/- 47.4% dilation and the EMAX of the second curve was 64.3 +/- 28.0% dilation (p < 0.05). However, when the two curves were separated by 40 min, there was no loss of responsiveness. To investigate the mechanism by which bradykinin caused vasodilation, we used methylene blue to antagonize endothelium-derived relaxing factor, and indomethacin to block prostaglandin-dependent effects. Methylene blue partially antagonized the vasodilatory response to bradykinin, decreasing the EMAX by 50%. Indomethacin also partially antagonized the vasodilatory response, but to a lesser extent than did methylene blue. The vasodilatory response to bradykinin was not fully antagonized with concurrent infusion of both methylene blue and indomethacin. The mechanism of bradykinin-induced vasodilation involves both EDRF and prostacyclin, and possibly another, as yet unidentified, mediator as well.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimizing the Management and Outcomes of Failed Back Surgery Syndrome: A Proposal of a Standardized Multidisciplinary Team Care Pathway.
Failed back surgery syndrome (FBSS) is a major, worldwide health problem that generates considerable expense for healthcare systems. A number of controversial issues concerning the management of FBSS are regularly debated, but no clear consensus has been reached. This pitfall is the result of lack of a standardized care pathway due to insufficient characterization of underlying pathophysiological mechanisms, which are essential to identify in order to offer appropriate treatment, and the paucity of evidence of treatment outcomes. In an attempt to address the challenges and barriers in the clinical management of FBSS, an international panel of physicians with a special interest in FBSS established the Chronic Back and Leg Pain (CBLP) Network with the primary intention to provide recommendations through consensus on how to optimize outcomes. In the first of a series of two papers, a definition of FBSS was delineated with specification of criteria for patient assessment and identification of appropriate evaluation tools in order to choose the right treatment options. In this second paper, we present a proposal of a standardized care pathway aiming to guide clinicians in their decision-making on how to optimize their management of FBSS patients. The utilization of a multidisciplinary approach is emphasized to ensure that care is provided in a uniform manner to reduce variation in practice and improve patient outcomes.


A Study of Critical Events That Lead to Spinal Cord Injury and the Importance of Rapid Reversal of Surgical Steps in Improving Neurological Outcomes: A Porcine Model.
Porcine model. To quantify critical vascular and mechanical events that occur before and during an evolving spinal cord injury. Spinal cord injuries are one of the most devastating complications in spine surgery. Intraoperative neuromonitoring changes can occur as a secondary event of spinal cord compression and decrease in spinal cord blood flow (SCBF). Laser Doppler flowmetry has been well validated for measuring blood flow. Seventeen pigs were studied, 14 of which completed the experiment. Multilevel, midthoracic laminectomies were performed. Laser Doppler flowmetry electrodes were placed on the dura to measure SCBF. Spinal cord injury was induced by incremental balloon inflation in the epidural space. The animals were separated into two groups. After motor-evoked potential (MEP) loss, group A underwent medical interventions and then balloon decompression approximately 20 minutes later. Group B underwent immediate balloon decompression followed by medical interventions. After interventions, wake-up test was performed and computed tomography scan measured thoracic spinal canal volume. Median SCBF changes were seen 15.8 (5.4-25.1) minutes before MEP loss. However, the 20% threshold interval was often reached before. At the 20% threshold, median pressure was 7 psi, balloon volume was 0.5 cm, and 50% of the spinal canal was compromised. In group A, no pigs moved and all had pathology indicating ischemia. In group B, 9 of 10 were found to be moving their hind legs with 7 indicating ischemia. Compression spinal cord injury is the end of a cascade involving increasing intracanal pressure, decreasing canal volume, and hypoperfusion. Rapid relief of compression leads to MEP return. SCBF monitoring can detect ischemia preinjury, giving surgeons an opportunity for early intervention. 4.


Implication of Posture Analysing Software to Evaluate the Postural Changes after Corrective Exercise Strategy on Subjects with Upper Body Dysfunction-A Randomized Controlled Trial.
The postural adaptation is very common now a days in school going children, office desk oriented job, computer users and frequent mobile users, and in all major industrial workers. Several studies have documented a high incidence of postural abnormalities in a given population; however, methods of postural measurement were poorly defined. The implication of postural pro software to analyse the postural imbalance of upper body dysfunction is very rare and literature studies says that the kinematic changes in particular segment will produce pain/discomfort and thereby lesser productivity of subjects. To evaluate the postural changes in subjects with upper body dysfunction after a corrective exercise strategy using postural analysis software and pectoralis minor muscle length testing. After explaining the procedure and benefits, informed consent was taken from the participating subjects (age 25-55 years). Subjects with upper body dysfunction were randomly allocated into two groups (each group 30 subjects). The Group-A received the corrective exercise strategy and Group-B received the conventional exercise for eight weeks of study duration (15 reps each exercise, total duration of 40 min; four days/week. Pre and Post posture analysis were analysed using posture pro software along with flexibility of pectoralis minor was assessed using ruler scale method. After interpretation of data, both the group showed the postural alteration and pectoralis minor muscle length changes, p-value (p<0.01) of both group showed highly significant changes. But comparing the both groups, the subjects who received the corrective exercise strategy shown more percentage of improvement in posture alteration (56.25%), pectoralis minor muscle length changes (68.69%) than the conventional exercise received subjects in posture alteration (24.86%) and pectoralis minor muscle length changes (21.9%). Altered postural changes and pectoralis minor muscle flexibility before and after the corrective exercise strategy evaluated by postural analysis software method shown to be a significant tool in clinical practice, which is easier and reproducible method.


Potential avoidance of adverse analgesic effects using a biologically "smart" hydrogel capable of controlled bupivacaine release.
Acute pain remains a tremendous clinical and economic burden, as its prevalence and common narcotic-based treatments are associated with poorer outcomes and higher costs. Multimodal analgesia portends great therapeutic promise, but rarely allows opioid sparing, and new alternatives are necessary. Microparticles (MPs) composed of biodegradable polymers [e.g., poly(lactic-co-glycolic acid) or PLGA] have been applied for controlled drug release and acute pain treatment research. However, foreign particles' presence within inflamed tissue may affect the drug release or targeting, and/or cause a secondary inflammatory reaction. We examined how small alterations in the particulate nature of MPs affect both their uptake into and subsequent activation of macrophages. MPs composed of PLGA and chitosan (PLGA-Chi) loaded with bupivacaine (BP) were engineered at different sizes and their opsonization by J774 macrophages was assessed. Uptake of PLGA-Chi by macrophages was found to be size dependent, but they were not cytotoxic or proinflammatory in effect. Moreover, encapsulation of MPs in a thermoresponsive loading gel (pluronic F-127) effectively prevented opsonization. Finally, MPs displayed sustained, tunable release of BP up to 7 days. These results demonstrate our ability to develop a drug delivery system capable of controlled release of local anesthetics to treat acute/subacute pain while concurrently avoiding enhanced inflammation.


Dysfunctional gene splicing as a potential contributor to neuropsychiatric disorders.
Alternative pre-mRNA splicing is a major mechanism by which the proteomic diversity of eukaryotic genomes is amplified. Much akin to neuropsychiatric disorders themselves, alternative splicing events can be influenced by genetic, developmental, and environmental factors. Here, we review the evidence that abnormalities of splicing may contribute to the liability toward these disorders. First, we introduce the phenomenon of alternative splicing and describe the processes involved in its regulation. We then review the evidence for specific splicing abnormalities in a wide range of neuropsychiatric disorders, including psychotic disorders (schizophrenia), affective disorders (bipolar disorder and major depressive disorder), suicide, substance abuse disorders (cocaine abuse and alcoholism), and neurodevelopmental disorders (autism). Next, we provide a theoretical reworking of the concept of "gene-focused" epidemiologic and neurobiologic investigations. Lastly, we suggest potentially fruitful lines for future research that should illuminate the nature, extent, causes, and consequences of alternative splicing abnormalities in neuropsychiatric disorders.


Retinal Specialist versus Artificial Intelligence Detection of Retinal Fluid from OCT: Age-Related Eye Disease Study 2: 10-Year Follow-On Study.
To evaluate the performance of retinal specialists in detecting retinal fluid presence in spectral domain OCT (SD-OCT) scans from eyes with age-related macular degeneration (AMD) and compare performance with an artificial intelligence algorithm. Prospective comparison of retinal fluid grades from human retinal specialists and the Notal OCT Analyzer (NOA) on SD-OCT scans from 2 common devices. A total of 1127 eyes of 651 Age-Related Eye Disease Study 2 10-year Follow-On Study (AREDS2-10Y) participants with SD-OCT scans graded by reading center graders (as the ground truth). The AREDS2-10Y investigators graded each SD-OCT scan for the presence/absence of intraretinal and subretinal fluid. Separately, the same scans were graded by the NOA. Accuracy (primary), sensitivity, specificity, precision, and F1-score. Of the 1127 eyes, retinal fluid was present in 32.8%. For detecting retinal fluid, the investigators had an accuracy of 0.805 (95% confidence interval [CI], 0.780-0.828), a sensitivity of 0.468 (95% CI, 0.416-0.520), a specificity of 0.970 (95% CI, 0.955-0.981). The NOA metrics were 0.851 (95% CI, 0.829-0.871), 0.822 (95% CI, 0.779-0.859), 0.865 (95% CI, 0.839-0.889), respectively. For detecting intraretinal fluid, the investigator metrics were 0.815 (95% CI, 0.792-0.837), 0.403 (95% CI, 0.349-0.459), and 0.978 (95% CI, 0.966-0.987); the NOA metrics were 0.877 (95% CI, 0.857-0.896), 0.763 (95% CI, 0.713-0.808), and 0.922 (95% CI, 0.902-0.940), respectively. For detecting subretinal fluid, the investigator metrics were 0.946 (95% CI, 0.931-0.958), 0.583 (95% CI, 0.471-0.690), and 0.973 (95% CI, 0.962-0.982); the NOA metrics were 0.863 (95% CI, 0.842-0.882), 0.940 (95% CI, 0.867-0.980), and 0.857 (95% CI, 0.835-0.877), respectively. In this large and challenging sample of SD-OCT scans obtained with 2 common devices, retinal specialists had imperfect accuracy and low sensitivity in detecting retinal fluid. This was particularly true for intraretinal fluid and difficult cases (with lower fluid volumes appearing on fewer B-scans). Artificial intelligence-based detection achieved a higher level of accuracy. This software tool could assist physicians in detecting retinal fluid, which is important for diagnostic, re-treatment, and prognostic tasks.


Sex differences in succumbing to sexual temptations: a function of impulse or control?
Men succumb to sexual temptations (e.g., infidelity, mate poaching) more than women. Explanations for this effect vary; some researchers propose that men and women differ in sexual impulse strength, whereas others posit a difference in sexual self-control. These studies are the first to test such underlying mechanisms. In Study 1, participants reported on their impulses and intentional control exertion when they encountered a real-life tempting but forbidden potential partner. Study 2 required participants to perform a reaction-time task in which they accepted/rejected potential partners, and we used process dissociation to separate the effects of impulse and control. In both studies, men succumbed to the sexual temptations more than women, and this sex difference emerged because men experienced stronger impulses, not because they exerted less intentional control. Implications for the integration of evolutionary and self-regulatory perspectives on sex differences are discussed.


Effects of telephone health mentoring in community-recruited chronic obstructive pulmonary disease on self-management capacity, quality of life and psychological morbidity: a randomised controlled trial.
To assess benefits of telephone-delivered health mentoring in community-based chronic obstructive pulmonary disease (COPD). Cluster randomised controlled trial. Tasmanian general practices: capital city (11), large rural (3), medium rural (1) and small rural (16). Patients were invited (1207) from general practitioner (GP) databases with COPD diagnosis and/or tiotropium prescription, response rate 49% (586), refused (176) and excluded (criteria: smoking history or previous study, 68). Spirometry testing (342) confirmed moderate or severe COPD in 182 (53%) patients. By random numbers code, block stratified on location, allocation by sequentially numbered, opaque and sealed envelopes. Health mentor (HM) group received regular calls to manage illness issues and health behaviours from trained community health nurses using negotiated goal setting: problem solving, decision-making and action planning. usual care (UC) group received GP care plus non-interventional brief phone calls. Measured at 0, 6 and 12 months, the Short Form 36 (SF-36) and St George's Respiratory Questionnaire (SGRQ, primary); Partners In Health (PIH) Scale for self-management capacity, Hospital Anxiety and Depression Scale (HADS), Center for Epidemiologic Studies-Depression (CES-D) questionnaire, Post-Traumatic Stress Disorder Checklist, Satisfaction with life and hospital admissions (secondary). 182 participants with COPD (age 68±8 years, 62% moderate COPD and 53% men) were randomised (HM=90 and UC=92). Mixed model regression analysis accounting for clustering, adjusting for age, gender, smoking status and airflow limitation assessed efficacy (regression coefficient, β, reported per 6-month visit). There was no difference in quality of life between groups, but self-management capacity increased in the HM group (PIH overall 0.15, 95% CI 0.03 to 0.29; knowledge domain 0.25, 95% CI 0.00 to 0.50). Anxiety decreased in both groups (HADS A 0.35; 95% CI -0.65 to -0.04) and coping capacity improved (PIH coping 0.15; 95% CI 0.04 to 0.26). Health mentoring improved self-management capacity but not quality of life compared to regular phone contact, which itself had positive effects where decline is generally expected.


Assessing water resource system vulnerability to unprecedented hydrological drought using copulas to characterize drought duration and deficit.
Global climate models suggest an increase in evapotranspiration, changing storm tracks, and moisture delivery in many parts of the world, which are likely to cause more prolonged and severe drought, yet the weakness of climate models in modeling persistence of hydroclimatic variables and the uncertainties associated with regional climate projections mean that impact assessments based on climate model output may underestimate the risk of multiyear droughts. In this paper, we propose a vulnerability-based approach to test water resource system response to drought. We generate a large number of synthetic streamflow series with different drought durations and deficits and use them as input to a water resource system model. Marginal distributions of the streamflow for each month are generated by bootstrapping the historical data, while the joint probability distributions of consecutive months are constructed using a copula-based method. Droughts with longer durations and larger deficits than the observed record are generated by perturbing the copula parameter and by adopting an importance sampling strategy for low flows. In this way, potential climate-induced changes in monthly hydrological persistence are factored into the vulnerability analysis. The method is applied to the London water system (England) to investigate under which drought conditions severe water use restrictions would need to be imposed. Results indicate that the water system is vulnerable to drought conditions outside the range of historical events. The vulnerability assessment results were coupled with climate model information to compare alternative water management options with respect to their vulnerability to increasingly long and severe drought.


Neonatal detection of Aicardi Goutières Syndrome by increased C26:0 lysophosphatidylcholine and interferon signature on newborn screening blood spots.
Aicardi Goutières Syndrome (AGS) is a heritable interferonopathy associated with systemic autoinflammation causing interferon (IFN) elevation, central nervous system calcifications, leukodystrophy and severe neurologic sequelae. An infant with TREX1 mutations was recently found to have abnormal C26:0 lysophosphatidylcholine (C26:0 Lyso-PC) in a newborn screening platform for X-linked adrenoleukodystrophy, prompting analysis of this analyte in retrospectively collected samples from individuals affected by AGS. In this study, we explored C26:0 Lyso-PC levels and IFN signatures in newborn blood spots and post-natal blood samples in 19 children with a molecular and clinical diagnosis of AGS and in the blood spots of 22 healthy newborns. We used Nanostring nCounter™ for IFN-induced gene analysis and a high-performance liquid chromatography with tandem mass spectrometry (HPLC MS/MS) newborn screening platform for C26:0 Lyso-PC analysis. Newborn screening cards from patients across six AGS associated genes were collected, with a median disease presentation of 2months. Thirteen out of 19 (68%) children with AGS had elevations of first tier C26:0 Lyso-PC (>0.4μM), that would have resulted in a second screen being performed in a two tier screening system for X-linked adrenoleukodystrophy (X-ALD). The median (95%CI) of first tier C26:0 Lyso-PC values in AGS individuals (0.43μM [0.37-0.48]) was higher than that seen in controls (0.21μM [0.21-0.21]), but lower than X-ALD individuals (0.72μM [0.59-0.84])(p<0.001). Fourteen of 19 children had elevated expression of IFN signaling on blood cards relative to controls (Sensitivity 73.7%, 95%CI 51-88%, Specificity 95%, 95% CI 78-99%) including an individual with delayed disease presentation (36months of age). All five AGS patients with negative IFN signature at birth had RNASEH2B mutations. Consistency of agreement between IFN signature in neonatal and post-natal samples was high (0.85). This suggests that inflammatory markers in AGS can be identified in the newborn period, before symptom onset. Additionally, since C26:0 Lyso-PC screening is currently used in X-ALD newborn screening panels, clinicians should be alert to the fact that AGS infants may present as false positives during X-ALD screening.


Most Relevant Neuropathic Pain Treatment and Chronic Low Back Pain Management Guidelines: A Change Pain Latin America Advisory Panel Consensus.
Chronic pain conditions profoundly affect the daily living of a significant number of people and are a major economic and social burden, particularly in developing countries. The Change Pain Latin America (CPLA) advisory panel aimed to identify the most appropriate guidelines for the treatment of neuropathic pain (NP) and chronic low back pain (CLBP) for use across Latin America. Published systematic reviews or practice guidelines were identified by a systematic search of PubMed, the Guidelines Clearinghouse, and Google. Articles were screened by an independent reviewer, and potential candidate guidelines were selected for more in-depth review. A shortlist of suitable guidelines was selected and critically evaluated by the CPLA advisory panel. Searches identified 674 and 604 guideline articles for NP and CLBP, respectively. Of these, 14 guidelines were shortlisted for consensus consideration, with the following final selections made: "Recommendations for the pharmacological management of neuropathic pain from the Neuropathic Pain Special Interest Group in 2015-pharmacotherapy for neuropathic pain in adults: A systematic review and meta-analysis.""Diagnosis and treatment of low back pain: A joint clinical practice guideline from the American College of Physicians and the American Pain Society" (2007). The selected guidelines were endorsed by all members of the CPLA advisory board as the best fit for use across Latin America. In addition, regional considerations were discussed and recorded. We have included this expert local insight and advice to enhance the implementation of each guideline across all Latin American countries.


Signal production and detection specificity in Vibrio CqsA/CqsS quorum-sensing systems.
Quorum sensing is a process of bacterial cell-cell communication that enables populations of cells to carry out behaviours in unison. Quorum sensing involves detection of the density-dependent accumulation of extracellular signal molecules called autoinducers that elicit population-wide changes in gene expression. In Vibrio species, CqsS is a membrane-bound histidine kinase that acts as the receptor for the CAI-1 autoinducer which is produced by the CqsA synthase. In Vibrio cholerae, CAI-1 is (S)-3-hydroxytridecan-4-one. The C170 residue of V. cholerae CqsS specifies a preference for a ligand with a 10-carbon tail length. However, a phenylalanine is present at this position in Vibrio harveyi CqsS and other homologues, suggesting that a shorter CAI-1-like molecule functions as the signal. To investigate this, we purified the V. harveyi CqsS ligand, and determined that it is (Z)-3-aminoundec-2-en-4-one (Ea-C8-CAI-1) carrying an 8-carbon tail. The V. harveyi CqsA/CqsS system is exquisitely selective for production and detection of this ligand, while the V. cholerae CqsA/CqsS counterparts show relaxed specificity in both production and detection. We isolated CqsS mutants in each species that display reversed specificity for ligands. Our analysis provides insight into how fidelity is maintained in signal transduction systems.


Anaerobic growth of Escherichia coli on glycerol by importing genes of the dha regulon from Klebsiella pneumoniae.
The dha regulon of Klebsiella pneumoniae specifying fermentative dissimilation of glycerol was mobilized by the broad-host-range plasmid RP4:mini Mu and introduced conjugatively into Escherichia coli. The recipient E. coli was enabled to grow anaerobically on glycerol without added hydrogen acceptors, although its cell yield was less than that of K. pneumoniae. The reduced cell yield was probably due to the lack of the coenzyme-B12-dependent glycerol dehydratase of the dha system. This enzyme initiates the first step in an auxiliary pathway for disposal of the extra reducing equivalents from glycerol. The lack of this enzyme would also account for the absence of 1,3-propanediol (a hallmark fermentation product of glycerol) in the spent culture medium. In a control experiment, a large quantity of this compound was detected in a similar culture medium following the growth of K. pneumoniae. The other three known enzymes of the dha system, glycerol dehydrogenase, dihydroxyacetone kinase and 1,3-propanediol oxidoreductase, however, were synthesized at levels comparable to those found in K. pneumoniae. Regulation of the dha system in E. coli appeared to follow the same pattern as in K. pneumoniae: the three acquired enzymes were induced by glycerol, catabolite repressed by glucose, and glycerol dehydrogenase was post-translationally inactivated during the shift from anaerobic to aerobic growth. The means by which the E. coli recipient can achieve redox balance without formation of 1,3-propanediol during anaerobic growth on glycerol remains to be discovered.


Two-day dosing versus one-day dosing of azithromycin in children with severe trachoma in Tanzania.
To determine whether 2-day dosing of azithromycin may improve the efficacy of azithromycin dosing in children with severe trachoma. Fifty children with severe trachoma (defined as either trachoma intense or follicular trachoma with ten or more follicles) were enrolled from five villages in Kongwa, Tanzania. Enrollment occurred within 1 month and within the same district as the historical control population of 99 children with severe trachoma, all of whom received 1-day dosing. Baseline data on age, sex, and trachoma status were obtained, and swabs for determination of Chlamydia trachomatis were taken. All 50 children received 20 mg/kg azithromycin daily for 2 days, which was directly observed. Children were followed up at 6 weeks for trachoma and infection. The laboratory was masked to treatment assignment. Baseline characteristics were similar between the treatment group and the control group. A total of 1/46 (2.2%) of children in the treatment group were polymerase chain reaction (PCR)-positive at 6 weeks, a 96.3% reduction from baseline, compared to 13/96 (13.5%) in the historical control group, an 89.4% reduction. This difference was statistically significant. However when modeled using logistic regression and accounting for age, gender, weight, and baseline percent PCR positivity, the difference was not significant. Prevalence of clinical trachoma did not differ between the groups at 6 weeks. For children with severe trachoma, a randomized controlled trial of 2-day versus 1-day treatment may be warranted.


Natural selection and inheritance of breeding time and clutch size in the collared flycatcher.
Many characteristics of organisms in free-living populations appear to be under directional selection, possess additive genetic variance, and yet show no evolutionary response to selection. Avian breeding time and clutch size are often-cited examples of such characters. We report analyses of inheritance of, and selection on, these traits in a long-term study of a wild population of the collared flycatcher Ficedula albicollis. We used mixed model analysis with REML estimation ("animal models") to make full use of the information in complex multigenerational pedigrees. Heritability of laying date, but not clutch size, was lower than that estimated previously using parent-offspring regressions, although for both traits there was evidence of substantial additive genetic variance (h2 = 0.19 and 0.29, respectively). Laying date and clutch size were negatively genetically correlated (rA = -0.41 +/- 0.09), implying that selection on one of the traits would cause a correlated response in the other, but there was little evidence to suggest that evolution of either trait would be constrained by correlations with other phenotypic characters. Analysis of selection on these traits in females revealed consistent strong directional fecundity selection for earlier breeding at the level of the phenotype (beta = -0.28 +/- 0.03), but little evidence for stabilising selection on breeding time. We found no evidence that clutch size was independently under selection. Analysis of fecundity selection on breeding values for laying date, estimated from an animal model, indicated that selection acts directly on additive genetic variance underlying breeding time (beta = -0.20 +/- 0.04), but not on clutch size (beta = 0.03 +/- 0.05). In contrast, selection on laying date via adult female survival fluctuated in sign between years, and was opposite in sign for selection on phenotypes (negative) and breeding values (positive). Our data thus suggest that any evolutionary response to selection on laying date is partially constrained by underlying life-history trade-offs, and illustrate the difficulties in using purely phenotypic measures and incomplete fitness estimates to assess evolution of life-history trade-offs. We discuss some of the difficulties associated with understanding the evolution of laying date and clutch size in natural populations.


Featured Counter-Trafficking Program: ARPAN.
This invited article is one of several comprising part of a special issue of Child Abuse and Neglect focused on child trafficking and health. The purpose of each invited article is to describe a specific program serving trafficked children. Featuring these programs is intended to raise awareness of innovative counter-trafficking strategies emerging worldwide and facilitate collaboration on program development and outcomes research. This article describes a long-term psychotherapeutic intervention started by Arpan in 2010, in an institution named Advait Foundation. Advait runs a rehabilitation home, Project Baharati, in Vasai, Mumbai, India. Project Bharati serves adolescent females who have experienced commercial sexual exploitation and sexual abuse. The psychotherapeutic intervention uses group and individual therapy, employing trauma-focused cognitive behavioral and arts-based therapeutic techniques.


Concurrent visuomotor behaviour improves form discrimination in a patient with visual form agnosia.
It is now well established that the visual brain is divided into two visual streams, the ventral and the dorsal stream. Milner and Goodale have suggested that the ventral stream is dedicated for processing vision for perception and the dorsal stream vision for action [A.D. Milner & M.A. Goodale (1995) The Visual Brain in Action, Oxford University Press, Oxford]. However, it is possible that ongoing processes in the visuomotor stream will nevertheless have an effect on perceptual processes. This possibility was examined in the present study. We have examined the visual form-discrimination performance of the form-agnosic patient D.F. with and without a concurrent visuomotor task, and found that her performance was significantly improved in the former condition. This suggests that the visuomotor behaviour provides cues that enhance her ability to recognize the form of the target object. In control experiments we have ruled out proprioceptive and efferent cues, and therefore propose that D.F. can, to a significant degree, access the object's visuomotor representation in the dorsal stream. Moreover, we show that the grasping-induced perceptual improvement disappears if the target objects only differ with respect to their shape but not their width. This suggests that shape information per se is not used for this grasping task.


Progression of coronary disease in a Behcet's patient in remission.
Behcet's disease is characterised histologically by vasculitis. In the heart this can lead to aneurysm formation and thrombosis. There is also accelerated atherosclerosis, the mechanism of which is unclear. Patients with external disease from Behcet's disease are treated with immunosuppression. The authors present a case of aneurysmal disease in a Behcet's patient. This case demonstrates that coronary disease may progress in Behcet's patients despite external disease remission. Therefore, internal disease may progress in the absence of external symptoms when immunosuppressive therapy is usually stopped. This case raises the issue of whether immunosuppression should be continued in Behcet's patients with coronary disease to suppress disease progression or included in a treatment protocol for patients with Behcet's related coronary disease. Clinical trials on the use of immunosuppressive therapy for coronary disease in Behcet's patients are needed.


Catecholamine interference in enzymatic creatinine assays.
Enzymatic creatinine assays are routinely used in clinical laboratories to provide more accurate estimated glomerular filtration rates and to avoid a perceived lack of analytical specificity associated with picrate (Jaffe) methods. Negative interferences with the enzymatic creatinine assay, which we noted in several patients on dopamine or dobutamine, prompted our further investigation into interference of catecholamines with enzymatic methods. Spiked solutions of dopamine, dobutamine, epinephrine, and norepinephrine were added to pooled sera at catecholamine concentrations consistent with clinically relevant dosing. Creatinine was measured enzymatically on the Roche P-Modular, Ortho Clinical Diagnostics Vitros 350, and Abbott i-STAT. Jaffe methods were performed on the Roche P-Modular and Siemens Dimension RxL. In 10 patients receiving dopamine and/or dobutamine via a venous or arterial line we evaluated and compared the extent of in vivo creatinine interference in paired serum samples obtained by venipuncture and from indwelling catheters. All catecholamines caused significant negative interference with the Roche enzymatic creatinine assay, most pronounced for dopamine and dobutamine. The Vitros enzymatic assay demonstrated slight negative interferences, and i-STAT enzymatic and Jaffe methods were unaffected by the presence of catecholamines. Significant (P < 0.001) differences in creatinine concentrations by Roche enzymatic vs Jaffe methods were observed in venipuncture specimens compared with arterial or venous catheter specimens, suggesting dopamine and dobutamine reversibly adhere to the catheter lumen. Negative interferences were pronounced for Roche enzymatic results in blood samples obtained from indwelling catheters, a phenomenon not observed in peripheral draws. Physicians and laboratorians should be alert to the possibility of a falsely low creatinine result and reevaluate questionable samples using a method unaffected by catecholamines.


Relationship between self-reported racial composition of high school and health literacy among community health center patients.
Intervention and policy approaches targeting the societal factors that affect health literacy (e.g., educational systems) could have promise to improve health outcomes, but little research has investigated these factors. This study examined the associations between self-reported racial composition of prior educational and neighborhood contexts and health literacy among 1,061 English- and Spanish-speaking adult community health center patients. The authors found that self-reported racial composition of high school was a significant predictor of health literacy among those who received schooling in the United States, controlling for race/ethnicity, education, age, country of birth, and survey language. Black and Hispanic patients had significantly lower health literacy than White patients within educational strata among those schooled in the United States. The findings revealed substantial disparities in health literacy. Self-reported racial composition of school context was a significant predictor of health literacy. Transdisciplinary, multilevel intervention approaches are likely to be needed to address the health literacy needs of this population.


Antibacterial and antifungal activities of punica granatum peel extracts against oral pathogens.
Punica granatum has been used for many years in folk medicine due to several purposes. The aim of the present study was to evaluate the effect of methanolic extract of Punica granatum peel (MEPGP) against Streptococcus mutans, Staphylococcus aureus, Streptococcus salivarius, Streptococcus sanguinis, Staphylococcus epidermidis, Actynomyces viscosus, Lactobacillus acidophilus and Candida albicans. In this in vitro study, the mentioned oral organisms were cultured in blood agar and mueller-hinton media and then paper disks containing MEPGP at concentrations of 4 mg/ml, 8 mg/ml and 12 mg/ml were inserted on medias. The antimicrobial activity was evaluated by agar disk diffusion method. The effects of three different concentrations of MEPGP against microorganisms were compared using one-way ANOVA and Tukey tests. All concentrations of MEPGP had antibacterial activity against S. aureus and S. epidermidis. Only at concentration of 8 mg/ml and 12 mg/ml MEPGP was effective against L. acidophilus, S. mutans and S. salivarius. Furthermore; no concentrations of MEPGP inhibited A. viscosus and C. albicans. This study suggests that MEPGP might be used as an antibacterial agent in controlling oral infections.


UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses.
Genomics data from The Cancer Genome Atlas (TCGA) project has led to the comprehensive molecular characterization of multiple cancer types. The large sample numbers in TCGA offer an excellent opportunity to address questions associated with tumo heterogeneity. Exploration of the data by cancer researchers and clinicians is imperative to unearth novel therapeutic/diagnostic biomarkers. Various computational tools have been developed to aid researchers in carrying out specific TCGA data analyses; however there is need for resources to facilitate the study of gene expression variations and survival associations across tumors. Here, we report UALCAN, an easy to use, interactive web-portal to perform to in-depth analyses of TCGA gene expression data. UALCAN uses TCGA level 3 RNA-seq and clinical data from 31 cancer types. The portal's user-friendly features allow to perform: 1) analyze relative expression of a query gene(s) across tumor and normal samples, as well as in various tumor sub-groups based on individual cancer stages, tumor grade, race, body weight or other clinicopathologic features, 2) estimate the effect of gene expression level and clinicopathologic features on patient survival; and 3) identify the top over- and under-expressed (up and down-regulated) genes in individual cancer types. This resource serves as a platform for in silico validation of target genes and for identifying tumor sub-group specific candidate biomarkers. Thus, UALCAN web-portal could be extremely helpful in accelerating cancer research. UALCAN is publicly available at http://ualcan.path.uab.edu.


Heat shock proteins and heat adaptation of the whole organism.
Adaptation to heat may occur through acclimatization or thermotolerance; however, the linkage of these phenomena is poorly understood. The importance of heat shock proteins (HSPs) in thermotolerance and differences in their accumulation in organisms adapted to the heat suggest a role for HSPs in acclimatization as well. The role of HSPs in heat adaptation of the whole organism and the interrelationships among heat adaptation, endotoxin tolerance, and cytokine resistance through HSPs are reviewed.


Mechanisms of Communicating Health Information Through Facebook: Implications for Consumer Health Information Technology Design.
Consumer health information technology (IT) solutions are designed to support patient health management and have the ability to facilitate patients' health information communication with their social networks. However, there is a need for consumer health IT solutions to align with patients' health management preferences for increased adoption of the technology. It may be possible to gain an understanding of patients' needs for consumer health IT supporting their health information communication with social networks by explicating how they have adopted and adapted social networking sites, such as Facebook, for this purpose. Our aim was to characterize patients' use of all communication mechanisms within Facebook for health information communication to provide insight into how consumer health IT solutions may be better designed to meet patients' communication needs and preferences. This study analyzed data about Facebook communication mechanisms use from a larger, three-phase, sequential, mixed-methods study. We report here on the results of the study's first phase: qualitative interviews (N=25). Participants were over 18, used Facebook, were residents or citizens of the United States, spoke English, and had a diagnosis consistent with type 2 diabetes. Participants were recruited through Facebook groups and pages. Participant interviews were conducted via Skype or telephone between July and September 2014. Data analysis was grounded in qualitative content analysis and the initial coding framework was informed by the findings of a previous study. Participants' rationales for the use or disuse of a particular Facebook mechanism to communicate health information reflected six broad themes: (1) characteristics and circumstances of the person, (2) characteristics and circumstances of the relationship, (3) structure and composition of the social network, (4) content of the information, (5) communication purpose, and (6) attributes of the technology. The results of this study showed that participants consider multiple factors when choosing a Facebook mechanism for health information communication. Factors included what information they intended to share, what they were trying to accomplish, attributes of technology, and attributes and communication practices of their social networks. There is a need for consumer health IT that allows for a range of choices to suit the intersectionality of participants' rationales. Technology that better meets patients' needs may lead to better self-management of health conditions, and therefore, improve overall health outcomes.


One hundred mosaic embryos transferred prospectively in a single clinic: exploring when and why they result in healthy pregnancies.
To investigate the parameters of mosaicism and the biological mechanisms leading to healthy pregnancies from mosaic embryo transfers. Prospective study. IVF center and associated research laboratory. Fifty-nine patients. Embryos underwent blastocyst-stage preimplantation genetic testing for aneuploidy by next-generation sequencing. Trophectoderm biopsies containing 20%-80% abnormal cells were deemed mosaic, and corresponding blastocysts were transferred. Mosaic embryos donated to research were examined for karyotype concordance in multiple biopsies and assessed for cell proliferation and death by immunofluorescence and computational quantitation. Chemical start of pregnancy, implantation, fetal heartbeat, and birth. Globally, mosaic embryos showed inferior clinical outcomes compared with euploid embryos. Aneuploid cell percentage in trophectoderm biopsies did not correlate with outcomes, but type of mosaicism did, as embryos with single mosaic segmental aneuploidies fared better than all other types. Mosaic blastocysts generated from oocytes retrieved at young maternal ages (≤34 years) showed better outcomes than those retrieved at older maternal ages. Mosaic embryos displayed low rates of karyotype concordance between multiple biopsies and showed significant elevation of cell proliferation and death compared with euploid embryos. After euploid embryos, mosaic embryos can be considered for transfer, prioritizing those of the single segmental mosaic type. If a patient has mosaic embryos available that were generated at different ages, preference should be given to those made at younger ages. Intrablastocyst karyotype discordance and differential cell proliferation and death might be reasons that embryos classified as mosaic can result in healthy pregnancies and babies.


Morphology Under Control: Engineering Biodegradable Stomatocytes.
Biodegradable nanoarchitectures, with well-defined morphological features, are of great importance for nanomedical research; however, understanding (and thereby engineering) their formation is a substantial challenge. Herein, we uncover the supramolecular potential of PEG-PDLLA copolymers by exploring the physicochemical determinants that result in the transformation of spherical polymersomes into stomatocytes. To this end, we have engineered blended polymersomes (comprising copolymers with varying lengths of PEG), which undergo solvent-dependent reorganization inducing negative spontaneous membrane curvature. Under conditions of anisotropic solvent composition across the PDLLA membrane, facilitated by the dialysis methodology, we demonstrate osmotically induced stomatocyte formation as a consequence of changes in PEG solvation, inducing negative spontaneous membrane curvature. Controlled formation of unprecedented, biodegradable stomatocytes represents the unification of supramolecular engineering with the theoretical understanding of shape transformation phenomena.


Propionibacterium acnes Strains Differentially Regulate the Fate of Th17 Responses in the Skin.
Agak et al. demonstrate that different strains of Propionibacterium acnes, a bacterium colonizing pilosebaceous units in healthy skin and acne, have the ability to induce T helper type 17 cells secreting either IFN-γ or IL-10 and exhibiting either pathogenic or protective properties, respectively. This work contributes to growing evidence indicating that the phenotype of T helper type 17 cells is largely dependent on their microbiological environment.


Neuroectodermal autonomy of Hox-2.9 expression revealed by rhombomere transpositions.
Involvement of the Hox genes in regional specifications of the vertebrate body axis is suggested by sequence similarity with the homeotic selector genes of Drosophila, the conservation of a collinear relationship between genomic organization and site of expression, and mutational analysis. Subdivision of vertebrate embryo hindbrain neuroepithelium into lineage compartments (rhombomeres) underlies segmental patterning of neuronal differentiation. The rhombomere boundaries delimit domains of expression of Hox genes, presumed to be determinants of rhombomere phenotype, suggesting that Hox genes confer positional value; the formation of rhombomere 4 (r4) is followed by strong expression of Hox-2.9 within its confines. If the Hox genes are determinants, their expression should be autonomous from the developmental stage at which regional commitment becomes fixed and irreversible. We have transplanted the future r4 region (from state-9-chick embryos) into the more anterior position of r2 and probed for Hox-2.9 transcripts. We report here that Hox-2.9 was expressed in the ectopic r4 as strongly as in the normal r4, whereas reciprocal grafts of future r2 to r4 position did not express Hox-2.9. The phenotype of ectopic rhombomeres developed according to their original position, as demonstrated by retrograde tracing of efferent cranial nerve nuclei. As early as stage-9-(six somites), both Hox-2.9 expression and segment identity are autonomous in the chick embryo hindbrain, independent both of position in the neuroepithelium and of signals from the underlying mesoderm.


Prenatal Particulate Matter Exposure Is Associated with Saliva DNA Methylation at Age 15: Applying Cumulative DNA Methylation Scores as an Exposure Biomarker.
Exposure in utero to particulate matter (PM2.5 and PM10) is associated with maladaptive health outcomes. Although exposure to prenatal PM2.5 and PM10 has cord blood DNA methylation signatures at birth, signature persistence into childhood and saliva cross-tissue applicability has not been tested. In the Fragile Families and Child Wellbeing Study, a United States 20-city birth cohort, average residential PM2.5 and PM10 during the three months prior to birth was estimated using air quality monitors with inverse distance weighting. Saliva DNA methylation at ages 9 (n = 749) and 15 (n = 793) was measured using the Illumina HumanMethylation 450 k BeadArray. Cumulative DNA methylation scores for particulate matter were estimated by weighting participant DNA methylation at each site by independent meta-analysis effect estimates and standardizing the sums. Using a mixed-effects regression analysis, we tested the associations between cumulative DNA methylation scores at ages 9 and 15 and PM exposure during pregnancy, adjusted for child sex, age, race/ethnicity, maternal income-to-needs ratio, nonmartial birth status, and saliva cell-type proportions. Our study sample was 50.5% male, 56.3% non-Hispanic Black, and 19.8% Hispanic, with a median income-to-needs ratio of 1.4. Mean exposure levels for PM2.5 were 27.9 μg/m3/day (standard deviation: 7.0; 23.7% of observations exceeded safety standards) and for PM10 were 15.0 μg/m3/day (standard deviation: 3.1). An interquartile range increase in PM2.5 exposure (10.73 μg/m3/day) was associated with a -0.0287 standard deviation lower cumulative DNA methylation score for PM2.5 (95% CI: -0.0732, 0.0158, p = 0.20) across all participants. An interquartile range increase in PM10 exposure (3.20 μg/m3/day) was associated with a -0.1472 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: -0.3038, 0.0095, p = 0.06) across all participants. The PM10 findings were driven by the age 15 subset where an interquartile range increase in PM10 exposure was associated with a -0.024 standard deviation lower cumulative DNA methylation score for PM10 (95% CI: -0.043, -0.005, p = 0.012). Findings were robust to adjustment for PM exposure at ages 1 and 3. In utero PM10-associated DNA methylation differences were identified at age 15 in saliva. Benchmarking the timing and cell-type generalizability is critical for epigenetic exposure biomarker assessment.


Brain morphometry and cognitive performance in detoxified alcohol-dependents with preserved psychosocial functioning.
The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals.


The association between workplace smoking bans and self-perceived, work-related stress among smoking workers.
There is substantial empirical evidence on the benefits of smoking bans; however, the unintended consequences of this anti-smoking measure have received little attention. This paper examines whether workplace smoking bans (WSB's) are associated with higher self-perceived, work-related stress among smoking workers. A longitudinal representative sample of 3,237 individuals from the Canadian National Population Health Survey from 2000 to 2008 is used. Work-related stress is derived from a 12-item job questionnaire. Two categories of WSB's, full and partial, are included in the analysis, with no ban being the reference category. Analysis also controls for individual socio-demographic characteristics, health status, provincial and occupational fixed-effects. We use fixed-effects linear regression to control for individual time-invariant confounders, both measured and unmeasured, which can affect the relationship between WSB's and work-related stress. To examine the heterogeneous effects of WSB's, the analysis is stratified by gender and age. We check the robustness of our results by re-estimating the baseline specification with the addition of different control variables and a separate analysis for non-smokers. Multivariate analysis reveals a positive and statistically significant association between full (β = 0.75, CI = 0.19-1.32) or partial (β = 0.69, CI = 0.12-1.26) WSB's, and the level of self-perceived, work-related stress among smoking workers compared to those with no WSB. We also find that this association varies by gender and age. In particular, WSB's are significantly associated with higher work stress only for males and young adults (aged 18-40). No statistically significant association is found between WSB's and the level of self-perceived work-related stress among non-smoking workers. The results of this study do not imply that WSB's are the main determinant of self-perceived, work-related stress among smokers but provides suggestive evidence that these may be positively related.


Emerging infectious disease (EID) communication during the 2009 H1N1 influenza outbreak: literature review (2009-2013) of the methodology used for EID communication analysis.
This year alone has seen outbreaks of epidemics such as Ebola, Chikungunya, and many other emerging infectious diseases (EIDs). We must look to the responses of recent outbreaks to help guide our strategies in current and future outbreaks or we risk repeating the same mistakes. The objective of this paper was to conduct a systematic literature review of the methodology used by studies that examined EID communication during the 2009 H1N1 pandemic outbreak through different communication channels or by analyzing contents and strategies. This was a systematic review of the literature (n=61) studying risk communication strategies of H1N1 influenza, published between 2009 and 2013, and retrieved from searches of computerized databases, hand searches, and authoritative texts by use of specific search criteria. Searches were followed by review, categorization, and mixed qualitative and quantitative content analysis. Of 41 articles that used quantitative methods, most used surveys (n=35); some employed content analyses (n=4) and controlled trials (n=2). The 16 articles that employed qualitative methods relied on content analyses (n=10), semi-structured interviews (n=2) and focus groups (n=4). Four more articles used mixed-methods or nonstandard methods. Seven different topic categories were found: risk perception and effects on behaviors, framing the risk in the media, public concerns, trust, optimistic bias, uncertainty, and evaluating risk communication. Up until 2013, studies tended to be descriptive and quantitative rather than discursive and qualitative and to focus on the role of the media as representing information and not as a medium for actual communication with the public. Several studies from 2012, and increasingly more in 2013, addressed issues of discourse and framing and the complexity of risk communication with the public. Formative evaluations that use recommendations from past research when designing communication campaigns from the first stages of crises are recommended. Research should employ diverse triangulation processes based on representatives from different stakeholders. Further studies should address the potential offered by social media to create dialogue with individuals and the public at large.


Radiation induced gastroparesis-case report and literature review.
Radiation induced gastroparesis as well as the other autonomic nervous system radiation induced neuropathies are poorly described in the literature. A case of gastroparesis associated with phrenic and recurrent laryngeal nerves paralysis was observed in a 69-year old patient. She was already treated two times by rachis radiotherapy in a context of breast cancer with bone metastases. Anatomical and chronological correlation of lesions, concomitant nerve damage in the radiation fields and elimination of the main differential diagnoses allowed us to link this case of gastroparesis with the background of radiotherapy. It confirms the role of vagus nerve lesion in radiation induced gastroparesis. This specific diagnosis led to a successful treatment and a quality of life improvement.


Classification of correlated patterns with a configurable analog VLSI neural network of spiking neurons and self-regulating plastic synapses.
We describe the implementation and illustrate the learning performance of an analog VLSI network of 32 integrate-and-fire neurons with spike-frequency adaptation and 2016 Hebbian bistable spike-driven stochastic synapses, endowed with a self-regulating plasticity mechanism, which avoids unnecessary synaptic changes. The synaptic matrix can be flexibly configured and provides both recurrent and external connectivity with address-event representation compliant devices. We demonstrate a marked improvement in the efficiency of the network in classifying correlated patterns, owing to the self-regulating mechanism.


Characterization of the flavoenzyme XiaK as an N-hydroxylase and implications in indolosesquiterpene diversification.
Flavoenzymes are ubiquitous in biological systems and catalyze a diverse range of chemical transformations. The flavoenzyme XiaK from the biosynthetic pathway of the indolosesquiterpene xiamycin A is demonstrated to mediate the in vivo biotransformation of xiamycin A into multiple products, including a chlorinated adduct as well as dimers characterized by C-N and N-N linkages that are hypothesized to form via radical-based mechanisms. Isolation and characterization of XiaK in vitro shows that it acts as a flavin-dependent N-hydroxylase that catalyzes the hydroxylation of xiamycin A at the carbazole nitrogen to form N-hydroxyxiamycin, a product which was overlooked in earlier in vivo experiments because its chemical and chromatographic properties are similar to those of oxiamycin. N-Hydroxyxiamycin is shown to be unstable under aerobic conditions, and characterization by electron paramagnetic resonance spectroscopy demonstrates formation of an N-hydroxycarbazole radical adduct. This radical species is proposed to serve as a key intermediate leading to the formation of the multiple xiamycin A adducts. This study suggests that non-enzyme catalyzed reactions may play a greater role in the biosynthesis of natural products than has been previously recognized.


Referral to an Acute Child and Adolescent Inpatient Unit: The Experiences and Views of Community Mental Health Referrers.
Admission to an acute mental health inpatient unit is a significant event for a young person. The interface between inpatient and community teams negotiating the admission and later discharge can be fraught. To understand how to improve the transition between inpatient and community care, we interviewed 48 community clinicians about their experiences of engaging with an acute child and adolescent mental health inpatient unit. Through thematic analysis, we identified management of risk was a central issue. Participants wanted more time in hospital, and more communication and collaboration. They expressed appreciation, but some gave intense descriptions of dissatisfaction. The analysis suggests avenues to improve communication and experience, recognizing the (felt) power differential between inpatient and referring community clinicians. Managing the power dynamics requires inpatient clinicians to use active inquiry to bring forward community clinicians' views and be mindful of the risk of community clinicians experiencing communication as criticism.


Characterizing the Structure and Oligomerization of Major Royal Jelly Protein 1 (MRJP1) by Mass Spectrometry and Complementary Biophysical Tools.
Royal jelly (RJ) triggers the development of female honeybee larvae into queens. This effect has been attributed to the presence of major royal jelly protein 1 (MRJP1) in RJ. MRJP1 isolated from royal jelly is tightly associated with apisimin, a 54-residue α-helical peptide that promotes the noncovalent assembly of MRJP1 into multimers. No high-resolution structural data are available for these complexes, and their binding stoichiometry remains uncertain. We examined MRJP1/apisimin using a range of biophysical techniques. We also investigated the behavior of deglycosylated samples, as well as samples with reduced apisimin content. Our mass spectrometry (MS) data demonstrate that the native complexes predominantly exist in a (MRJP14 apisimin4) stoichiometry. Hydrogen/deuterium exchange MS reveals that MRJP1 within these complexes is extensively disordered in the range of residues 20-265. Marginally stable secondary structure (likely antiparallel β-sheet) exists around residues 266-432. These weakly structured regions interchange with conformers that are extensively unfolded, giving rise to bimodal (EX1) isotope distributions. We propose that the native complexes have a "dimer of dimers" quaternary structure in which MRJP1 chains are bridged by apisimin. Specifically, our data suggest that apisimin acts as a linker that forms hydrophobic contacts involving the MRJP1 segment 316VLFFGLV322. Deglycosylation produces large soluble aggregates, highlighting the role of glycans as aggregation inhibitors. Samples with reduced apisimin content form dimeric complexes with a (MRJP12 apisimin1) stoichiometry. The information uncovered in this work will help pave the way toward a better understanding of the unique physiological role played by MRJP1 during queen differentiation.


Immediate hypersensitivity in the Flinders rat: further evidence for a possible link between susceptibility to allergies and depression.
Rats of the Flinders sensitive line (FSL, selectively bred for their increased cholinergic activity and used as a genetic animal model of depression) were compared with their control counterparts, the Flinders resistant line, for their susceptibility to anaphylaxis and the response of small intestinal tissues to the muscarinic agonist, bethanechol. Following sensitization to ovalbumin (OA), rats of both lines were challenged in vivo either with 3 mg OA i.p. or with saline. In spite of the absence of line-related differences in IgE titers, FSL rats were more susceptible to the induction of anaphylactic shock as evidenced by (1) more pronounced mast cell degranulation; (2) a greater drop in rectal temperature; (3) higher hematocrit values; and (4) changes in gut function characterized by an elevation of basal short-circuit current and increased conductance (indicating increases in transport tone and permeability) of the tissues mounted in Ussing chambers. Thus, this study provides further evidence for a common cholinergic mechanisms in susceptibility to both allergies and depression.


Effectiveness of general practitioner online training and an information booklet for parents on antibiotic prescribing for children with respiratory tract infection in primary care: a cluster randomized controlled trial.
Antibiotics are too often prescribed in childhood respiratory tract infection (RTI), despite limited effectiveness, potential side effects and bacterial resistance. We aimed to reduce antibiotic prescribing for children with RTI by online training for general practitioners (GPs) and information for parents. A pragmatic cluster randomized controlled trial in primary care. The intervention consisted of online training for GPs and an information booklet for parents. The primary outcome was the antibiotic prescription rate for children presenting with RTI symptoms, as registered by GPs. Secondary outcomes were number of reconsultations within the same disease episode, consultations for new episodes, hospital referrals and pharmacy-dispensed antibiotic courses for children. This trial was registered at the Dutch Trial Register (NTR), registration number: NTR4240. After randomization, GPs from a total of 32 general practices registered 1009 consultations. An antibiotic was prescribed in 21% of consultations in the intervention group, compared with 33% in the usual care group, controlled for baseline prescribing (rate ratio 0.65, 95% CI 0.46-0.91). The probability of reconsulting during the same RTI episode did not differ significantly between the intervention and control groups, and nor did the numbers of consultations for new episodes and hospital referrals. In the intervention group antibiotic dispensing was 32 courses per 1000 children/year lower than the control group, adjusted for baseline prescribing (rate ratio 0.78, 95% CI 0.66-0.92). The numbers and proportion of second-choice antibiotics did not differ significantly. Concise, feasible, online GP training, with an information booklet for parents, showed a relevant reduction in antibiotic prescribing for children with RTI.


Is passive smoking in the workplace hazardous to health?
Apart from evidence on the acute effects of passive smoking, there is relatively little information available on whether breathing other people's smoke at work causes disease. However, exposure does commonly occur at work, and it does not differ qualitatively from passive smoking occurring in other settings. Therefore it appears sensible to extrapolate from what is known about health risks in settings such as the home. There is too little known to quantify precisely workplace risks due to passive smoking. However, the weight and consistency of the epidemiologic evidence, backed up by the data from active smoking, favor a causal link between passive smoking and serious disease, especially lung cancer. In the light of this evidence, enough is known to justify action to reduce smoking at work.


Changes in DNA methylation are associated with the development of drug resistance in cervical cancer cells.
Changes in DNA methylation are associated with changes in somatic cell fate without the alteration of coding sequences. In addition to its use as a traceable biomarker, reversible DNA methylation could also serve as a therapeutic target. In particular, if the development of drug resistance is associated with changes in DNA methylation, then demethylation might reverse the resistance phenotype. The reversion of the drug-resistance might then be feasible if the association between abnormal DNA methylation and the development of drug-resistance could be identified. Methylation differences between the drug-resistance cervical cancer cell, SiHa, and its derived oxaliplatin-resistant S3 cells were detected by methylation specific microarray. The drug-resistance cells were treated with demethylation agent to see if the resistance phenotype were reversed. Targeted methylation of one of the identified locus in normal cell is expected to recapitulate the development of resistance and a two-component reporter system is adopted to monitor the increase of DNA methylation in live cells. In this report, we identified methylation changes, both genome-wide and within individual loci, in the oxaliplatin-resistant cervical cancer cell S3 compared with its parental cell line SiHa. Treatment of S3 with a demethylation agent reversed increases in methylation and allowed the expression of methylation-silenced genes. Treatment with the demethylation agent also restored the sensitivity of S3 to cisplatin, taxol, and oxaliplatin to the same level as that of SiHa. Finally, we found that methylation of the target gene Casp8AP2 is sufficient to increase drug resistance in different cells. These results suggest that global methylation is associated with the development of drug resistance and could serve as a biomarker and therapeutic target for drug resistance in cervical cancer.


Chemokine binding and activities mediated by the mouse IL-8 receptor.
In humans and rabbits two similar IL-8R mediate the chemotaxis and activation of neutrophils induced by alpha chemokines. We present data to suggest that there is only one such IL-8R gene in mice. We then use mice with a targeted deletion of this gene to characterize alpha chemokine ligands that signal via the mouse IL-8R. These experiments show that mouse macrophage inflammatory protein 2 binds the receptor with high affinity (Kd = approximately 1.5 nM) and potently activates both an intracellular Ca2+ flux and a chemotactic response, events absent in neutrophils from receptor-deleted mice. Mouse KC is approximately 10-fold less potent. These results show that macrophage inflammatory protein 2 and KC potently activate mouse neutrophils via a unique IL-8R, and these proteins may function as the major proinflammatory alpha chemokines in mice.


Comparison of N-acetylcysteine and methylene blue, alone or in combination, for treatment of acetaminophen toxicosis in cats.
Acetaminophen is widely used in human beings for analgesic purposes, but is one of the most frequent causes of poisoning in cats. Acetaminophen-poisoned cats develop methemoglobinemia and sometimes hepatic failure. To determine the benefit of using methylene blue, a treatment for methemoglobinemia, along with N-acetylcysteine (NAC), the recommended treatment for acetaminophen-poisoned cats, groups of 3 male and 3 female cats each were given methylene blue NAC, or both after administration of acetaminophen (120 mg/kg of body weight, PO). Male cats seemed more susceptible than female cats to acetaminophen toxicosis, because 3 males died of hepatic failure (2 cats given acetaminophen/methylene blue and 1 given acetaminophen/NAC/methylene blue). Although NAC alone seemed to elicit the best overall response, methylene blue, alone or in combination with NAC, may be useful in female cats.


Integrated Machine Learning and Chemoinformatics-Based Screening of Mycotic Compounds against Kinesin Spindle ProteinEg5 for Lung Cancer Therapy.
Among the various types of cancer, lung cancer is the second most-diagnosed cancer worldwide. The kinesin spindle protein, Eg5, is a vital protein behind bipolar mitotic spindle establishment and maintenance during mitosis. Eg5 has been reported to contribute to cancer cell migration and angiogenesis impairment and has no role in resting, non-dividing cells. Thus, it could be considered as a vital target against several cancers, such as renal cancer, lung cancer, urothelial carcinoma, prostate cancer, squamous cell carcinoma, etc. In recent years, fungal secondary metabolites from the Indian Himalayan Region (IHR) have been identified as an important lead source in the drug development pipeline. Therefore, the present study aims to identify potential mycotic secondary metabolites against the Eg5 protein by applying integrated machine learning, chemoinformatics based in silico-screening methods and molecular dynamic simulation targeting lung cancer. Initially, a library of 1830 mycotic secondary metabolites was screened by a predictive machine-learning model developed based on the random forest algorithm with high sensitivity (1) and an ROC area of 0.99. Further, 319 out of 1830 compounds screened with active potential by the model were evaluated for their drug-likeness properties by applying four filters simultaneously, viz., Lipinski's rule, CMC-50 like rule, Veber rule, and Ghose filter. A total of 13 compounds passed from all the above filters were considered for molecular docking, functional group analysis, and cell line cytotoxicity prediction. Finally, four hit mycotic secondary metabolites found in fungi from the IHR were screened viz., (-)-Cochlactone-A, Phelligridin C, Sterenin E, and Cyathusal A. All compounds have efficient binding potential with Eg5, containing functional groups like aromatic rings, rings, carboxylic acid esters, and carbonyl and with cell line cytotoxicity against lung cancer cell lines, namely, MCF-7, NCI-H226, NCI-H522, A549, and NCI H187. Further, the molecular dynamics simulation study confirms the docked complex rigidity and stability by exploring root mean square deviations, root mean square fluctuations, and radius of gyration analysis from 100 ns simulation trajectories. The screened compounds could be used further to develop effective drugs against lung and other types of cancer.


Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.
Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml-1, 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.


Randomized Trial of an Integrated Behavioral Health Home: The Health Outcomes Management and Evaluation (HOME) Study.
Behavioral health homes provide primary care health services to patients with serious mental illness treated in community mental health settings. The objective of this study was to compare quality and outcomes of care between an integrated behavioral health home and usual care. The study was a randomized trial of a behavioral health home developed as a partnership between a community mental health center and a Federally Qualified Health Center. A total of 447 patients with a serious mental illness and one or more cardiometabolic risk factors were randomly assigned to either the behavioral health home or usual care for 12 months. Participants in the behavioral health home received integrated medical care on-site from a nurse practitioner and a full-time nurse care manager subcontracted through the health center. Compared with usual care, the behavioral health home was associated with significant improvements in quality of cardiometabolic care, concordance of treatment with the chronic care model, and use of preventive services. For most cardiometabolic and general medical outcomes, both groups demonstrated improvement, although there were no statistically significant differences between the two groups over time. The results suggest that it is possible, even under challenging real-world conditions, to improve quality of care for patients with serious mental illness and cardiovascular risk factors. Improving quality of medical care may be necessary, but not sufficient, to improve the full range of medical outcomes in this vulnerable population.


How the COVID-19 pandemic highlights the necessity of animal research.
Recently, a petition was offered to the European Commission calling for an immediate ban on animal testing. Although a Europe-wide moratorium on the use of animals in science is not yet possible, there has been a push by the non-scientific community and politicians for a rapid transition to animal-free innovations. Although there are benefits for both animal welfare and researchers, advances on alternative methods have not progressed enough to be able to replace animal research in the foreseeable future. This trend has led first and foremost to a substantial increase in the administrative burden and hurdles required to make timely advances in research and treatments for human and animal diseases. The current COVID-19 pandemic clearly highlights how much we actually rely on animal research. COVID-19 affects several organs and systems, and the various animal-free alternatives currently available do not come close to this complexity. In this Essay, we therefore argue that the use of animals is essential for the advancement of human and veterinary health.


The Epidemiology of Burns in Children in Guatemala: A Single Center Report.
Children in low- to middle-income countries are at high risk for sustaining severe burns. This study aimed to analyze the characteristics of pediatric burns in Guatemala that could help identify risk factors and guide prevention efforts. A retrospective review of the characteristics of patients < 18 years of age that were burned in Guatemala between 2015 and 2018 and treated at the Hospital Roosevelt Burn Unit in Guatemala City was performed. The medical records of 949 patients were reviewed (year 2015: 224, year 2016: 238, year 2017: 251, year 2018: 236). Mean age of the patients was 4.0 ± 3.6 years. Majority of the patients were male (54.2%) and suffered from scald burns (68.5%) due to spilling or falling into hot water. Children under the age of 9 years predominantly suffered from scald burns, whereas older children more frequently sustained flame burns. The mortality rate over the 4-year period was 5.2%. As in other low-income countries, pediatric burns in Guatemala are frequent and usually due to scald. Demographic characteristics have to be taken into account when developing strategies for improvements of prevention and treatment or transferring these from high-income countries. Especially education of parents and safety of daily tasks are crucial. Special attention and focusing of efforts in areas of higher incidence should be sought.


Clinical status and implications of antimalarial drug resistance.
Africa carries the greatest burden of disease caused by Plasmodium falciparum, and we can expect this burden to rise in the near future, mainly because of drug resistance. Although effective drugs are available (such as artemether-lumefantrine, mefloquine, atovaquone-proguanil and halofantrine) they are uniformly too expensive for routine use. Affordable options include chloroquine plus sulfadoxine-pyrimethamine (SP), amodiaquine (alone or in combination with SP) and chlorproguanil-dapsone. Artemisinin combination therapy may offer considerable advantages over alternative therapies, but its introduction faces considerable logistic difficulty.


Evaluation of new speed limits in Sweden: a sample survey.
The study sought to estimate changes in actual driving speed occurring after new speed limits were introduced in Sweden's rural road network. The effects of speed limit changes were estimated for 7 groups of roads of different types and initial speed limits. To study the effects on the entire road network and not only at specific road sites, a sampling survey was conducted in which speed was measured at randomly selected sites before and after the speed limit changes. Systematic sampling was used to select sites that were widely distributed geographically, though the analysis treats the data as if the sites were selected by simple random sampling. The speed of passing vehicles was generally measured using pneumatic tubes stretched across the road. The survey results indicate that the mean car speed increased by 3.5 km/h when the speed limit increased by 10 km/h on motorways and 2 + 1 roads. Reducing the speed limit by 10 km/h on 2 + 1 roads and rural roads with a speed limit of 110 km/h resulted in a 2 km/h decrease in mean speed. On rural roads where the speed limit was lowered from 90 to 80 km/h, the mean speed decreased by 3.3 km/h. These changes are statistically significant. The present results are in line with previous results indicating an average change in mean speed of approximately 2.5 km/h when the speed limit changes by 10 km/h. The confidence intervals were in most instances fairly small, indicating a sufficiently large number of measurement sites.


Health Is Power: Active Transportation, Physical Activity, and Cardiometabolic Health Among Ethnic Minority Women.
Active transportation (AT) increases physical activity, reducing cardiometabolic risk among non-Hispanic white adults; however, research on these linkages in racial/ethnic minority women is sparse. This study explored these associations in 327 African American and Hispanic/Latina women. This analysis used sociodemographics, self-reported AT via the International Physical Activity Questionnaire, accelerometer-measured moderate to vigorous physical activity (MVPA), body mass index, systolic and diastolic blood pressures, resting heart rate, and body fat percentage (BF). Unadjusted bivariate associations and associations adjusted for sociodemographic factors were examined. AT users had higher levels of objective MVPA, but this was not statistically significant. AT was not associated with cardiometabolic risk factors in adjusted models (Ps > .05); however, systolic blood pressure was lower for AT users. MVPA was negatively associated with diastolic blood pressure and BF overall, body mass index and BF in African American women, and BF in Hispanic/Latina women (Ps <.05). MVPA was associated with improvements in body mass index, diastolic blood pressure, and BF among minority women, and these relationships may vary by race/ethnicity. Practitioners should recommend increased participation in MVPA. Future research, using longitudinal designs should investigate AT's potential for increasing MVPA and improving cardiometabolic health along with the role of race/ethnicity in these associations.