Effects of Statins on Coronary Atherosclerotic Plaques: The PARADIGM Study.
This study sought to describe the impact of statins on individual coronary atherosclerotic plaques. Although statins reduce the risk of major adverse cardiovascular events, their long-term effects on coronary atherosclerosis remain unclear. We performed a prospective, multinational study consisting of a registry of consecutive patients without history of coronary artery disease who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. Atherosclerotic plaques were quantitatively analyzed for percent diameter stenosis (%DS), percent atheroma volume (PAV), plaque composition, and presence of high-risk plaque (HRP), defined by the presence of ≥2 features of low-attenuation plaque, positive arterial remodeling, or spotty calcifications. Among 1,255 patients (60 ± 9 years of age; 57% men), 1,079 coronary artery lesions were evaluated in statin-naive patients (n = 474), and 2,496 coronary artery lesions were evaluated in statin-taking patients (n = 781). Compared with lesions in statin-naive patients, those in statin-taking patients displayed a slower rate of overall PAV progression (1.76 ± 2.40% per year vs. 2.04 ± 2.37% per year, respectively; p = 0.002) but more rapid progression of calcified PAV (1.27 ± 1.54% per year vs. 0.98 ± 1.27% per year, respectively; p < 0.001). Progression of noncalcified PAV and annual incidence of new HRP features were lower in lesions in statin-taking patients (0.49 ± 2.39% per year vs. 1.06 ± 2.42% per year and 0.9% per year vs. 1.6% per year, respectively; all p < 0.001). The rates of progression to >50% DS were not different (1.0% vs. 1.4%, respectively; p > 0.05). Statins were associated with a 21% reduction in annualized total PAV progression above the median and 35% reduction in HRP development. Statins were associated with slower progression of overall coronary atherosclerosis volume, with increased plaque calcification and reduction of high-risk plaque features. Statins did not affect the progression of percentage of stenosis severity of coronary artery lesions but induced phenotypic plaque transformation. (Progression of AtheRosclerotic PlAque DetermIned by Computed TomoGraphic Angiography Imaging [PARADIGM]; NCT02803411).


Temperature mapping of magnetic resonance-guided laser interstitial thermal therapy (LITT) in lymphangiomas of the head and neck.
Lymphangiomas of the tongue and neck are uncommon benign congenital lymphatic tumors. These vascular lesions are difficult to treat, frequently recur, and can cause patients significant morbidity. Treatment may also be complicated by adjacent vital anatomic structures. Magnetic resonance (MR)-controlled laser-induced interstitial thermotherapy (LITT) has been proven to be a noninvasive safe treatment. Real-time monitoring of tissue temperature with thermosensitive sequences allows controlled coagulation necrosis. LITT was performed in a lymphangioma specimen ex vivo. In four patients (eight procedures) with lymphangiomas of the tongue and neck, MR-guided LITT was performed with a percutaneous approach in a multiapplicator technique. The laser system consisted of a titanium catheter and a protective catheter. The dome of the fiber end had a diameter of 1.4 mm with an active length of 20 mm. Temperature sensitive sequences were used in a 0.5 T open-configured MR scanner with the proton frequency shift technique to map the spatial and temporal distribution of Nd:YAG laser effects (7 Watts, 30 pulses per second, 10 minutes/location). Postoperative MR follow-up was performed at 1 week and at 3 months. In three patients, partial resection of the tumor was performed 6 months after LITT. In three patients, MR clearly showed a diminished tumor volume. All four patients reported subjective amelioration and in three patients former functional problems, such as speech and swallowing were improved. MR thermometry allowed accurate demarcation of changes by heat and distinction of affected tumor volume (3.0 cm +/- 0.3 cm). The histology of the patients 6 months after LITT showed laser-induced fibrosis of former lymphatic tissue. The results suggest that LITT can be performed safely with tissue preserving of vital structures and can be effective in the treatment of deep tumors, such as lymphangiomas. However, given the nature of the lesion, the potential for recurrence exists no matter what modality is chosen.


Anxiety and depression in Nepal: prevalence, comorbidity and associations.
Anxiety and depression are two important contributors to the global burden of disease. In many developing countries, including Nepal, their prevalences are yet to be assessed. A nationwide cross-sectional study was conducted among a representative sample of Nepalese adults aged 18-65 years (N = 2100), selected by multistage random cluster sampling and interviewed at home during unannounced visits. The validated questionnaires included the Hospital Anxiety and Depression Scale (HADS), to detect cases of anxiety (HADS-A), depression (HADS-D) and comorbid anxiety and depression (HADS-cAD), the Eysenck Personality Questionnaire Revised Short Form-Neuroticism (EPQRS-N), and the World Health Organization Quality of Life 8-question scale (WHOQOL-8). Logistic regression analyses were used to explore associations of caseness with four groups of variables: demographic, domicile, substance use, and behavioural and health. Age- and gender-adjusted point prevalences of HADS-A, HADS-D and HADS-cAD were 16.1, 4.2 and 5.9% respectively. In a multivariate model, HADS-A was positively associated with urban residence (AOR = 1.82; p < 0.001) and neuroticism (AOR = 1.32; p < 0.001), and negatively with alcohol consumption (AOR = 0.71; p = 0.041). HADS-D was positively associated with marijuana use (AOR = 3.61; p = 0.017) and negatively with quality of life (QoL) (AOR = 0.86; p < 0.001). HADS-cAD was positively associated with widowhood (AOR = 2.71; p = 0.002), urban residence (AOR = 2.37; p = 0.001), living at altitude ≥2000 m (AOR = 2.32; p = 0.002) and neuroticism (AOR = 1.26; p < 0.001), and negatively with alcohol use (AOR = 0.56; p = 0.026) and QoL (AOR = 0.79; p < 0.001). Depression and anxiety are important mental health conditions in Nepal, and major contributors to public ill health, being very highly prevalent, comorbid and associated with psychosocial burden. They are also linked to the unique topography, habitation and social structure of the country. High prevalence coupled with the disabling nature of these disorders establishes their health-care priority and their importance in national health policy.


Amyloidoma of the temporal bone and upper cervical spine; presentation of a rare clinical entity with a brief literature review.
The amyloidoses comprise a heterogeneous group of diseases characterized by the extracellular deposition of an insoluble protein complex in various tissues. Amyloidomas in bone are most common in patients with systemic amyloidosis and plasma cell dyscrasias. Decreased clearance of beta2 microglobulin frequently causes excessive amyloid deposition in the musculoskeletal system in patients with a history of chronic renal failure and long-term dialysis treatment. Calvarial and/or upper cervical amyloid depositions are rarely seen in clinical practice; therefore the diagnosis requires high index of suspicion and special staining of the tissue. In this article, we present a patient with amyloidoma at the right temporal bone and upper cervical spine. The etiology, radiological findings and differential diagnosis were briefly discussed in the highlights of relevant literature. Amyloidomas should be particularly kept in mind in patients with a history of long-term dialysis therapy, plasma cell dyscrasias or long-standing inflammatory diseases. Differential diagnosis mostly encounters benign or malign mesenchymal neoplasms of the dura and skull base, metastatic tumors, plasmacytoma and brown tumor in the calvarium, as well as primary osseous tumors or metastatic lesions in the spine.


Versican V2 and the central inhibitory domain of Nogo-A inhibit neurite growth via p75NTR/NgR-independent pathways that converge at RhoA.
Myelin is a major obstacle for regenerating nerve fibers of the adult mammalian central nervous system (CNS). Several proteins including Nogo-A, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp) and the chondroitin-sulfate proteoglycan (CSPG) Versican V2 have been identified as inhibitory components present in CNS myelin. MAG, OMgp as well as the Nogo specific domain Nogo-66 exert their inhibitory activity by binding to a neuronal receptor complex containing the Nogo-66 receptor NgR and the neurotrophin receptor p75(NTR). While this suggests a converging role of the p75(NTR)/NgR receptor complex for myelin-derived neurite growth inhibitors, we show here that NgR/p75(NTR) is not required for mediating the inhibitory activity of the two myelin components NiG, unlike Nogo-66 a distinct domain of Nogo-A, and Versican V2. Primary neurons derived from a complete null mutant of p75(NTR) are still sensitive to NiG and Versican V2. In line with this result, neurite growth of p75(NTR) deficient neurons is still significantly blocked on total bovine CNS myelin. Furthermore, modulation of RhoA and Rac1 in p75(NTR)-/- neurons persists with NiG and Versican V2. Finally, we demonstrate that neither NiG nor Versican V2 interact with the p75(NTR)/NgR receptor complex and provide evidence that the binding sites of NiG and Nogo-66 are physically distinct from each other on neural tissue. These results indicate not only the existence of neuronal receptors for myelin inhibitors independent from the p75(NTR)/NgR receptor complex but also establish Rho GTPases as a common point of signal convergence of diverse myelin-induced regeneration inhibitory pathways.


Sports-Related Sudden Cardiac Arrest in Germany.
Knowledge about causes of sports-related sudden cardiac arrest (SrSCA) may influence national strategies to prevent such events. Therefore, we established a prospective registry on SrSCA to estimate the incidence and in particular describe the etiologies of SrSCA in the general population in Germany. The registration of SrSCA based upon 4 pillars: a web-based platform to record SrSCA cases in competitive and recreational athletes, media-monitoring, cooperation with the German Resuscitation Registry, and 15 institutes of forensic medicine. After an observation period of 6 years, a total of 349 cases was recorded (mean age 48.0 ± 12.7 years); 109 subjects survived. Most of the cases occurred during nonelite competitive or recreational sports. Bystander cardiopulmonary resuscitation (CPR) was initiated in 262 cases (75%); however, rhythm analysis and defibrillation (if indicated) was mainly performed by medical services. In patients ≤ 35 years of age, premature coronary artery disease (CAD) and sudden arrhythmic death syndrome (SADS) prevailed, followed by myocarditis. In athletes ≥ 35 years of age, CAD predominated. Country-specific registries are necessary to define the national screening and prevention strategy optimally. In Germany, premature CAD, SADS, and myocarditis are the leading causes of SrSCA in young athletes, reinforcing the great disparity of the prevalence of cardiac diseases among different countries. Extension of on-site SCD-prevention campaigns, with training of CPR and explanation of the efficient use of automated external defibrillators (AEDs), may decrease the burden of SrSCD.


Two FtsH Proteases Contribute to Fitness and Adaptation of Pseudomonas aeruginosa Clone C Strains.
Pseudomonas aeruginosa is an environmental bacterium and a nosocomial pathogen with clone C one of the most prevalent clonal groups. The P. aeruginosa clone C specific genomic island PACGI-1 harbors a xenolog of ftsH encoding a functionally diverse membrane-spanning ATP-dependent metalloprotease on the core genome. In the aquatic isolate P. aeruginosa SG17M, the core genome copy ftsH1 significantly affects growth and dominantly mediates a broad range of phenotypes, such as secretion of secondary metabolites, swimming and twitching motility and resistance to aminoglycosides, while the PACGI-1 xenolog ftsH2 backs up the phenotypes in the ftsH1 mutant background. The two proteins, with conserved motifs for disaggregase and protease activity present in FtsH1 and FtsH2, have the ability to form homo- and hetero-oligomers with ftsH2 distinctively expressed in the late stationary phase of growth. However, mainly FtsH1 degrades a major substrate, the heat shock transcription factor RpoH. Pull-down experiments with substrate trap-variants inactive in proteolytic activity indicate both FtsH1 and FtsH2 to interact with the inhibitory protein HflC, while the phenazine biosynthesis protein PhzC was identified as a substrate of FtsH1. In summary, as an exception in P. aeruginosa, clone C harbors two copies of the ftsH metallo-protease, which cumulatively are required for the expression of a diversity of phenotypes.


Evaluation of Different Preosteotomy Determinants as Affecting the Success of Implant Therapy: A "CBCT"-based Clinical Study.
The success of implant therapy is of greatest concern for clinicians because a minor negligence can lead to ultimate failure of treatment. However, comprehensive and precise treatment planning can ensure high success rate of implant therapy. Cone-beam computed tomography (CBCT) is an innovation that allows clinicians to explore all related factors in details. This study was conducted to evaluate different preosteotomy determinants as affecting the success of implant therapy in the maxillary anterior region using CBCT. This study was conducted on 98 partially or complete denture patients willing for artificial replacement of their missing teeth by implant or implant over-denture. Demographic details of participating patients were collected. Furthermore, comprehensive local examination was also done to finalize the site of placement of implant. Cone-beam computed tomography was attempted in all patients for determining accurate implant location, status of bone, and other interrelated determinants of implant success. Cone-beam computed tomography was also prescribed for patients so as to have presurgical idea of implant dimensions as shown in virtual placement of implant. To rule out any interobserver bias, the interpretations of CBCT images were completed by two independent experienced observers. In the 98 studied patients, 61 were males and 37 were females. The study was restricted to the maxillary anterior region only. The studied preosteotomy determinants were available bone height and width in the edentulous region from ridge crest up to the maxillary sinus floor or the nasal fossa floor. A total of 107 implants were placed virtually (on CBCT) in the maxillary anterior region and compared quantitatively in postosteotomy phases. Implant placement sites were the maxillary central incisor region (39), the lateral incisor region (31), and canine (37). Authors also noticed that the relative length and width of virtual implant remained unaffected in 97% of the cases. Cone-beam computed tomography showed accurate status of various presurgical determinants like trabeculae, peri-ridiculer pathology, and amount of horizontal and vertical bone losses. Hence, it was further concluded that all these presurgical determinants greatly affect the final success rate of implant therapy. It is therefore deemed necessary to judiciously consider and clinically manage such factors before attempting implant in the maxillary anterior region. Presurgical evaluation of factors associated with implant dimensions significantly assists clinicians in deciding the finest treatment option. All additional information provided by CBCT genuinely led to a change in the treatment plan that provides enhanced clinical outcome with lesser postoperative complications. How to cite this article: Jain S, Kapoor K, Sethi K, et al. Evaluation of Different Preosteotomy Determinants as Affecting the Success of Implant Therapy: A "CBCT"-based Clinical Study. J Contemp Dent Pract 2019;20(10):1212-1216.


Quantitative relations between interaction parameter, miscibility and function in organic solar cells.
Although it is known that molecular interactions govern morphology formation and purity of mixed domains of conjugated polymer donors and small-molecule acceptors, and thus largely control the achievable performance of organic solar cells, quantifying interaction-function relations has remained elusive. Here, we first determine the temperature-dependent effective amorphous-amorphous interaction parameter, χaa(T), by mapping out the phase diagram of a model amorphous polymer:fullerene material system. We then establish a quantitative 'constant-kink-saturation' relation between χaa and the fill factor in organic solar cells that is verified in detail in a model system and delineated across numerous high- and low-performing materials systems, including fullerene and non-fullerene acceptors. Our experimental and computational data reveal that a high fill factor is obtained only when χaa is large enough to lead to strong phase separation. Our work outlines a basis for using various miscibility tests and future simulation methods that will significantly reduce or eliminate trial-and-error approaches to material synthesis and device fabrication of functional semiconducting blends and organic blends in general.


Perspectives of genetically engineered microbes for groundwater bioremediation.
Biodegradation is the main process for the removal of organic compounds from the environment, but proceeds slowly for many synthetic chemicals of environmental concern. Research on microbial biodegradation pathways revealed that recalcitrance is - among other factors - caused by biochemical blockages resulting in dysfunctional catabolic routes. This has raised interest in the possibility to construct microorganisms with improved catabolic activities by genetic engineering. Although this goal has been pursued for decades, no full-scale applications have emerged. This perspective explores the lagging implementation of genetically engineered microorganisms in practical bioremediation. The major technical and scientific issues are illustrated by comparing two examples, that of 1,2-dichloroethane where successful full-scale application of pump-and-treat biotreatment processes has been achieved, and 1,2,3-trichloropropane, for which protein and genetic engineering yielded effective bacterial cultures that still await application.


Total phenolic, total flavonoid content, and antioxidant capacity of the leaves of Meyna spinosa Roxb., an Indian medicinal plant.
The objective of the present study was to determine the total phenolic and total flavonoid contents, and to evaluate the antioxidant potential of different leaf extracts of Meyna spinosa Roxb. ex Link, a traditional medicinal plant of India. Free radical scavenging and antioxidant potential of the methanol, ethyl acetate, and petroleum ether extracts of Meyna spinosa leaves were investigated using several in vitro and ex vivo assays, including the 2, 2-diphenyl-picrylhydrazyl radical scavenging, superoxide anion scavenging, hydroxyl radical scavenging, nitric oxide radical scavenging, hydrogen peroxide scavenging activity, metal chelating assay, and reducing power ability method. Total antioxidant activity of the extracts was estimated by the ferric thiocyanate method. Inhibition assay of lipid peroxidation and oxidative hemolysis were also performed to confirm the protective effect of the extracts. Total phenolic and total flavonoid contents of the extracts were estimated using standard chemical assay procedures. Methanol extracts showed the highest polyphenolic content and possessed the better antioxidant activity than the other two extracts. Total phenolic and total flavonoid contents in the methanol extract were (90.08 ± 0.44) mg gallic acid equivalents/g and (58.50 ± 0.09) mg quercetin equivalents/g, respectively. The IC50 of the methanol extract in the DPPH(·), superoxide anion, hydroxyl radical, nitric oxide radical, hydrogen peroxide scavenging activity and metal chelating assays were (16.4 ± 0.41), (35.9 ± 0.19), (24.1 ± 0.33), (23.7 ± 0.09), (126.8 ± 2.92), and (117.2 ± 1.01) μg·mL(-1), respectively. The methanol extract showed potent reducing power ability, total antioxidant activity, and significantly inhibit lipid peroxidation and oxidative hemolysis which was similar to that of standards. The results indicated a direct correlation between the antioxidant activity and the polyphenolic content of the extracts, which may the foremost contributors to the antioxidant activity of the plant. The present study confirmed that the methanol extract of Meyna spinosa leaves is a potential source of natural antioxidants.


Risky sexual behavior among orphan and non-orphan adolescents in Nyanza Province, Western Kenya.
A household survey of male and female adolescents was conducted to establish whether orphanhood or other factors contribute to risky sexual behavior. Results show that orphanhood was not associated with risky sexual behavior. Sleeping in a different house from the household head and attending social activities at night were positively associated with sexual activity and transactional sex among boys and girls. Older adolescents were more likely to be sexually active while urban residents, and those who perceived their caregivers as able to provide for their basic needs, were less likely to have ever engaged in sex. Condom use at last sex was associated with older age and having talked with parents/caregivers about sexual risks. Interventions should address these predictors, promote risk reduction among all adolescents irrespective of orphan status, and strengthen parents'/guardians' capacity to discuss sexuality with adolescents and to provide for their basic needs.


[Sports cardiology - a general practice oriented update].
As a sub-speciality, Sports Cardiology focuses on sport and physical training interacting with cardiac issues. Particularly, Sports Cardiology deals with the so-called "Sports Paradox", which implicates the fact the on one side regular physical training leads to a multitude of relevant health benefits. But on the other hand, exercise can also be a trigger for sudden cardiac death, particularly in case of an underlying cardiac disease. However, health benefits by regular training outweigh potential risks by far, but only if an adequate cardiac screening and individual recommendations for sports participation have been provided. This review highlights various aspects of Sports Cardiology like strategies to prevent sudden cardiac death in sports and training recommendations in patients with an underlying cardiovascular disease.


The phylogenetic information profile of HIV-1 and the degradation effect of recombination.
HIV-1, while known to recombine frequently and evolve rapidly, is one of the most sequenced organisms. The availability of many and long sequences (almost full-length) renders HIV-1 as a good model for studying theoretical predictions linked to evolution and phylogenetic inferences. Here we study the effects of rapid and through-recombination evolution on phylogenetic information in order to confirm theoretical predictions of the characteristics of phylogenetic information on a real dataset. Firstly we study the fluctuation of the phylogenetic information along the HIV-1 genome showing that genomic regions such as the first part and the last part of the pol gene contain less phylogenetic information, while the vpr, vpu and the first exon of the tat gene contain more phylogenetic information compared to the rest of the genome. Moreover, we provide evidence that phylogenetic information is correlated to the sequence similarity of the dataset used and is degraded by the effect of recombination.


Utility of magnetic resonance imaging in the differential diagnosis of tubercular and pyogenic spondylodiscitis.
We evaluated the potential of magnetic resonance imaging (MRI) in the diagnosis of spinal infections and specifically its accuracy in differentiating tubercular and pyogenic spondylodiscitis. Totally, 50 patients referred for MRI scans with the clinical diagnosis of spinal infections were included in our study. The patients were classified as tubercular (TS), pyogenic (PS), and indeterminate spondylodiscitis on the basis of imaging findings and were correlated with the final diagnosis made by histopathology/cytology/culture/biochemistry or with successful therapeutic outcome. Imaging findings were subsequently analyzed for differentiating tubercular and pyogenic spondylodiscitis using the Chi-square test. The most common pattern of spinal infection was spondylodiscitis (78% incidence rate) with epidural extension (86%) and cord compression (64%) being most common complications observed. Imaging (postcontrast study) and final diagnosis correlated in 93.7% tubercular (sensitivity of 75% and specificity of 90%) and 75% pyogenic (sensitivity of 90% and specificity of 83.3%) spondylodiscitis. The patients with tubercular spondylitis had a significantly (P < 0.05) higher incidence of following MRI findings: A well-defined paraspinal abnormal signal (80% in TS vs. 40% in PS), a thin and smooth abscess wall (84.2% in TS vs. 10% in PS), presence of intraosseous abscess (35% in TS vs. 0% in PS), focal and heterogenous enhancement of the vertebral body (75% in TS vs. 20% in PS), vertebral destruction more than or equal to grade 3 (71.8% in TS vs. 0% in PS), loss of cortical definition (75% in TS vs. 20% in PS), and spinal deformity (50% in TS vs. 5% in PS). Contrast-enhanced images improve the sensitivity and specificity of detection and differentiation of tubercular and PS.


Myasthenic Crisis as the First Presentation of Myasthenia Gravis: A Case Report.
BACKGROUND Myasthenic crisis is a condition characterized by the sudden onset of myasthenic weakness involving the respiratory muscles and requires ventilatory support to prevent death. This is a case report of respiratory failure in a 43-year-old man as the first presentation of myasthenia gravis. CASE REPORT A 43-year-old man with underlying hypertension and a lacunar stroke with good muscle-power recovery presented with severe community-acquired pneumonia, complicated with respiratory failure requiring invasive ventilatory support. He responded well to the intravenous antibiotic therapy and after 1 week of treatment, he was hemodynamically stable and his septic parameters improved. However, he persistently failed to maintain adequate spontaneous respiratory effort after the removal of the ventilatory support and had to be reintubated multiple times. There was no other identifiable cause for the worsening respiratory failure. He had no clinical features or muscle weakness suggestive of myasthenia gravis. However, his blood test was positive for serum anti-acetylcholine receptor antibodies and repetitive nerve stimulation tests showed the characteristic decremental response of compound muscle action potential amplitude, in keeping with the diagnosis of myasthenia gravis. He responded well to intravenous immunoglobulin and was discharged with anticholinesterase inhibitors and long-term immunosuppression therapy. CONCLUSIONS This report demonstrates that when patients are admitted to the hospital with acute respiratory failure without any underlying pulmonary disease and with weakness of the respiratory muscles, the diagnosis of myasthenia gravis presenting with a myasthenic crisis should be considered.


Improving work for the body - a participatory ergonomic intervention aiming at reducing physical exertion and musculoskeletal pain among childcare workers (the TOY-project): study protocol for a wait-list cluster-randomized controlled trial.
The prevalence of musculoskeletal pain (MSP) is persistently high throughout the world. Work-related factors such as high physical workload (lifting, bending and twisting of the back) are considered to be among the main causes of MSP. Work in childcare includes the need to lift, carry, and support children in a range of activities, requiring several demanding postures and movements, such as bending forward and twisting of the back and sitting on the floor. Participatory ergonomics may represent a solution for decreasing the physical workload to reduce MSP. We present the protocol of a study aiming to evaluate the effect and process of a participatory ergonomics intervention designed to reduce physical exertion during work and MSP (including MSP interfering with work) among childcare workers. This study will use a two-arm cluster-randomized design employing a wait-list control, with childcare institutions forming the clusters. Three workshops will be conducted during the 4-month intervention period. Participants will identify risk factors for strenuous work and MSP, develop solutions for reducing the identified risk factors, and implement them in their team. An ergonomic consultant will guide the process. The data collection will consist of questionnaires and objective measures of heart rate and physical activity, observations of physical workload, and information on sickness absence based on company records. Primary outcomes are physical exertion during work and MSP (including pain-related work interference) measured at 4 months. Secondary outcomes measured at 4 months are sickness absence due to MSP; objectively measured occupational physical activity and heart rate; and self-reported self-efficacy, employee involvement, and need for recovery. Alongside the trial, a process evaluation and an economic evaluation will be conducted. The study will evaluate the effect and process of a participatory ergonomics intervention to reduce physical exertion at work and MSP among childcare workers. By performing a cluster-randomized controlled trial with an effect evaluation based on both objective and self-reported measures with the addition of a process evaluation and economic evaluation, this study will contribute to the evidence for prevention of MSP among a less studied occupational group. Results are expected in 2018-2019. ISRCTN, ISRCTN10928313 . Registered on 11 January 2017.


Exploring pharmacoepidemiologic groupings of drugs from a clinical perspective.
To investigate the extent to which pharmacoepidemiologic groupings are homogeneous in terms of clinical properties. In our analysis, we classified drug subgroups from the pharmacoepidemiologic Anatomical Therapeutic Chemical (ATC) classification system based on clinical drug properties. We established mappings from ATC fifth level drug entities to drug property annotations in the National Drug File Reference Terminology (NDF-RT), including therapeutic categories, mechanisms of action, and physiologic effects. Based on the annotations for the individual drugs we computed homogeneity scores for all ATC groups and analyzed their distribution. We found ATC groups to be generally homogeneous, more so for mechanisms of action, and physiologic effects than for therapeutic intent. However, only half of all ATC drugs can be analyzed with this approach, in part because of missing properties in NDF-RT.


Filamin A regulates focal adhesion disassembly and suppresses breast cancer cell migration and invasion.
The actin cross-linking protein filamin A (FLNa) functions as a scaffolding protein and couples cell cytoskeleton to extracellular matrix and integrin receptor signaling. In this study, we report that FLNa suppresses invasion of breast cancer cells and regulates focal adhesion (FA) turnover. Two large progression tissue microarrays from breast cancer patients revealed a significant decrease of FLNa levels in tissues from invasive breast cancer compared with benign disease and in lymph node-positive compared with lymph node-negative breast cancer. In breast cancer cells and orthotopic mouse breast cancer models, down-regulation of FLNa stimulated cancer cell migration, invasion, and metastasis formation. Time-lapse microscopy and biochemical assays after FLNa silencing and rescue with wild-type or mutant protein resistant to calpain cleavage revealed that FLNa regulates FA disassembly at the leading edge of motile cells. Moreover, FLNa down-regulation enhanced calpain activity through the mitogen-activated protein kinase-extracellular signal-regulated kinase cascade and stimulated the cleavage of FA proteins. These results document a regulation of FA dynamics by FLNa in breast cancer cells.


The Human Skeletal Muscle Transcriptome in Response to Oral Shilajit Supplementation.
The objective of the present study ( clinicaltrials.gov NCT02026414) was to observe the effects of oral supplementation of a purified and standardized Shilajit extract on skeletal muscle adaptation in adult overweight/class I obese human subjects from the U.S. Shilajit is a mineral pitch that oozes out of Himalayan rocks. The study design consisted of a baseline visit, followed by 8 weeks of 250 mg of oral Shilajit supplementation b.i.d., and additional 4 weeks of supplementation with exercise. At each visit, blood samples and muscle biopsies were collected for further analysis. Supplementation was well tolerated without any changes in blood glucose levels and lipid profile after 8 weeks of oral supplementation and the additional 4 weeks of oral supplementation with exercise. In addition, no changes were noted in creatine kinase and serum myoglobin levels after 8 weeks of oral supplementation and the additional 4 weeks of supplementation with exercise. Microarray analysis identified a cluster of 17 extracellular matrix (ECM)-related probe sets that were significantly upregulated in muscles following 8 weeks of oral supplementation compared with the expression at the baseline visit. This cluster included tenascin XB, decorin, myoferlin, collagen, elastin, fibrillin 1, and fibronectin 1. The differential expression of these genes was confirmed using quantitative real-time polymerase chain reaction (RT-PCR). The study provided maiden evidence that oral Shilajit supplementation in adult overweight/class I obese human subjects promoted skeletal muscle adaptation through upregulation of ECM-related genes that control muscle mechanotransduction properties, elasticity, repair, and regeneration.


Passing in Command Line Arguments and Parallel Cluster/Multicore Batching in R with batch.
It is often useful to rerun a command line R script with some slight change in the parameters used to run it - a new set of parameters for a simulation, a different dataset to process, etc. The R package batch provides a means to pass in multiple command line options, including vectors of values in the usual R format, easily into R. The same script can be setup to run things in parallel via different command line arguments. The R package batch also provides a means to simplify this parallel batching by allowing one to use R and an R-like syntax for arguments to spread a script across a cluster or local multicore/multiprocessor computer, with automated syntax for several popular cluster types. Finally it provides a means to aggregate the results together of multiple processes run on a cluster.


Effects of Regular Classes in Outdoor Education Settings: A Systematic Review on Students' Learning, Social and Health Dimensions.
Participants in Outdoor Education Programmes (OEPs) presumably benefit from these programmes in terms of their social and personal development, academic achievement and physical activity (PA). The aim of this systematic review was to identify studies about regular compulsory school- and curriculum-based OEPs, to categorise and evaluate reported outcomes, to assess the methodological quality, and to discuss possible benefits for students. We searched online databases to identify English- and German-language peer-reviewed journal articles that reported any outcomes on a student level. Two independent reviewers screened studies identified for eligibility and assessed the methodological quality. Thirteen studies were included for analysis. Most studies used a case-study design, the average number of participants was moderate (mean valued (M) = 62.17; standard deviation (SD) = 64.12), and the methodological quality was moderate on average for qualitative studies (M = 0.52; SD = 0.11), and low on average for quantitative studies (M = 0.18; SD = 0.42). Eight studies described outcomes in terms of social dimensions, seven studies in learning dimensions and four studies were subsumed under additional outcomes, i.e., PA and health. Eleven studies reported positive, one study positive as well as negative, and one study reported negative effects. PA and mental health as outcomes were underrepresented. Tendencies were detected that regular compulsory school- and curriculum-based OEPs can promote students in respect of social, academic, physical and psychological dimensions. Very little is known concerning students' PA or mental health. We recommend conducting more quasi-experimental design and longitudinal studies with a greater number of participants, and a high methodological quality to further investigate these tendencies.


Validity and Reliability of a Novel Ocular Pain Assessment Survey (OPAS) in Quantifying and Monitoring Corneal and Ocular Surface Pain.
To validate the Ocular Pain Assessment Survey (OPAS), specifically designed to measure ocular pain and quality of life for use by eye care practitioners and researchers. A single-center cohort study was conducted among patients with and without corneal and ocular surface pain at initial and follow-up visits over a 6-month period. The content of the OPAS was guided by literature review, a body of experts, and incorporating conceptual frameworks from existing pain questionnaires. The Wong-Baker FACES Pain Rating Scale served as the gold standard for measuring the intensity of ocular pain. A total of 102 patients aged 18 to 80 years completed the OPAS at the initial visit. A total of 21 patients were followed up after treatment. Indices of validity and internal consistency (Spearman's rank-order, rs, or Pearson's correlation coefficients, rp), and coefficient of reliability (Cronbach's α) were determined in addition to equivalence testing, exploratory factor analysis (EFA), and diagnostic analysis. Eye pain intensity was the primary outcome measure, and interference with quality of life (QoL), aggravating factors, associated factors, associated non-eye pain intensity, and self-reported symptomatic relief were the secondary outcome measures. The OPAS had criterion validity at both initial (rs = 0.71; n = 102; P < 0.01) and follow-up visits (rs = 0.97; n = 21; P < 0.01). Equivalence tests yielded OPAS and gold standard equivalence for both the initial and follow-up visits. The EFA supported 6 subscales (eye pain intensity at 24 hours and 2 weeks, non-eye pain intensity, QoL, aggravating factors, and associated factors) confirming multidimensionality. Cronbach's α >0.83 for all subscales established strong internal consistency, which correlated with the gold standard, including 24-hour eye pain intensity and QoL interference scores (rp = 0.81, 0.64, respectively P < 0.001). At follow-up, reduction in pain scores was accompanied by improvement in all dimensions of the OPAS. Percentage change in QoL correlated to percentage change in the gold standard (rp = 0.53; P < 0.05). The OPAS was sensitive (94%), specific (81%), and accurate (91%), with a diagnostic odds ratio >50. The OPAS is a valid, reliable, and responsive tool with strong psychometric and diagnostic properties in the multidimensional quantification of corneal and ocular surface pain intensity, and QoL.


Tunable Fano resonance in photonic crystal slabs.
A three dimensional analysis of a special class of anisotropic materials is presented. We introduce an extension of the Scattering Matrix Method (SMM) to investigate the behavior of anisotropic Photonic Crystal Slabs (PhCS) subject to external radiation. We show how the Fano effect can play a fundamental role in the realization of tunable optical devices. Moreover, we show how to utilize electron injection, electric field and temperature as parameters to control the Fano resonance shift in both isotropic and anisotropic materials as Si and Potassium Titanium Oxide Phosphate (KTP). We will see that because Fano modes are sensitive and controllable, a broad range of applications can be considered.


Does an online psychological intervention improve self-efficacy and disability in people also receiving Multimodal Manual Therapy for chronic low back pain compared to Multimodal Manual Therapy alone? Design of a randomized controlled trial.
Various interventions are available for the treatment of chronic low back pain (LBP), including Manual Therapy and Cognitive Behavioural Therapy (CBT). The purpose of this study is to evaluate whether the addition of an internet-based CBT program leads to better outcomes in patients who are treated with multimodal manual therapy for chronic LBP. A randomized controlled trial comparing a combined intervention, consisting of internet-based CBT utilising MoodGYM plus multimodal manual therapy, to multimodal manual therapy alone for patients with chronic LBP. Multimodal manual therapy will be delivered by experienced chiropractors and physiotherapists. Treatment sessions will consist of a combination of joint and soft tissue mobilisation; spinal manipulation as well as muscle and fascia massage; education and reassurance; and rehabilitative exercise prescription. In total, 108 adult participants will be recruited from multiple chiropractic and physiotherapy private practices in Australia. Participants older than 18 years of age and diagnosed with chronic non-specific LBP will be included in the trial, where chronic LBP is defined as continuous or fluctuating pain for a minimum of three months. The Keele STarT Back screening tool will be used to screen for potential participants who are in the medium risk category. The primary outcomes are self efficacy and disability measured by the Patient Self-Efficacy Questionnaire (PSEQ) and Roland Morris Disability Questionnaire (RMDQ) respectively. Secondary outcome measures will assess pain, catastrophising, depression, anxiety, stress and work ability. Participants will be randomly allocated into one of two groups. Both groups will receive an upper limit of 12 multimodal manual therapy sessions over a period of 8 weeks. The intervention group will also receive five weeks of MoodGYM covering five modules in total. Assessment will be conducted at pre-treatment, post-treatment 8- and follow-up at 26- and 52 weeks. In addition, a verbal pain measure will be completed by the treating practitioner at time of treatments on an 11-point VAS. The primary data analysis will be by intention to treat using a linear mixed model for each outcome. This paper outlines the design of a randomised controlled trial that investigates the potential benefits of adding a widely available and inexpensive internet-based psychological intervention to standard multimodal manual therapy for the management of chronic low back pain. ACTRN12615000269538.


Species-specific transcription in mice carrying human chromosome 21.
Homologous sets of transcription factors direct conserved tissue-specific gene expression, yet transcription factor-binding events diverge rapidly between closely related species. We used hepatocytes from an aneuploid mouse strain carrying human chromosome 21 to determine, on a chromosomal scale, whether interspecies differences in transcriptional regulation are primarily directed by human genetic sequence or mouse nuclear environment. Virtually all transcription factor-binding locations, landmarks of transcription initiation, and the resulting gene expression observed in human hepatocytes were recapitulated across the entire human chromosome 21 in the mouse hepatocyte nucleus. Thus, in homologous tissues, genetic sequence is largely responsible for directing transcriptional programs; interspecies differences in epigenetic machinery, cellular environment, and transcription factors themselves play secondary roles.


First Report of Watermelon chlorotic stunt virus in Watermelon in the Palestinian Authority.
In the summer of 2010, watermelon plants (Citrullus lanatus Thunb.) from eight fields surveyed in two districts (Jenin and Qalqilia) in the West Bank of the Palestinian Authority (PA) exhibited typical Watermelon chlorotic stunt virus (WmCSV) symptoms including yellow veining, chlorotic mottling, stunting of young leaves, and reduction of yield. Disease incidence ranged from 8 to 98% and was associated with whitefly (Bemisia tabaci) infestation. In symptomatic leaves of 79 of 215 watermelon plants examined, geminiviral DNA was detected by PCR (3) and rolling circle amplification (RCA) (2). Geminivirus DNA-A and DNA-B component fragments were amplified by PCR using degenerated and specific primers (3). The full-length DNA-A of WmCSV-[PAL] was amplified from field-collected watermelon plants using WAI-XbaI-(v)/WAI-XbaI-(c) primer pair, and the generated PCR product was sequenced (3). A DNA-A fragment (2,017 bp) (GenBank Accession No JN673223) comprising a conserved region of the coat protein (AV1), AC5, AC3, AC1, and AC2 genes, showed 99, 99, 99, 98, 98, and 97% nucleotide identity with sequences of WmCSV isolates from Jordan (GenBank Accession No. EU561237), Israel (LEF201809), Lebanon (HM368371), Sudan (AJ245650), Iran (AJ245652), and Yemen (AJ012081), respectively. The circular genomic DNA-A and DNA-B of WmCSV-[PAL] were amplified from a whitefly-inoculated watermelon plant by RCA (2) and used to inoculate 30 watermelon plants with a nonvacuum gene gun (4). Typical WmCSV symptoms developed in all these plants 4 weeks postinoculation and virus infection was confirmed by PCR. In 2011, WmCSV was detected from the southern and eastern parts of neighboring Jordan (1). The new emergent disease in the PA was detected in all of the surveyed watermelon fields in regions where cucurbits are intensively grown, only a few kilometers east of Israel. This suggests that the introduction of WmCSV to the PA might have occurred through transplant movement between Israel and the PA or through viruliferous whiteflies that moved from infected plants in Israel to neighboring fields in Jenin and Qalqilia districts. This is in accordance with the observation that disease incidence was always associated with high population of B. tabaci. The virus endangers the production of watermelon in the affected areas to the point of becoming the limiting factor of growing watermelon in open fields. To our knowledge, this is the first report of WmCSV infecting cucurbits in the PA. References: (1) A. Al-Musa et al. Virus Genes 43:79, 2011. (2) H. Jeske. Curr. Topics Microbiol. Immunol. 331:185, 2009. (3) A. Kheyr-Pour et al. Phytopathology 90:629, 2000. (4) S. Sikorskaite et al. J. Virol. Methods 165:320, 2010.


Rapid forgetting of social transmission of food preferences in aged rats: relationship to hippocampal CREB activation.
A major characteristic of age-related changes in memory in rodents is an increase in the rate of forgetting of new information, even when tests given soon after training reveal intact memory. Interference with CREB functions similarly results in rapid decay of memory. Using quantitative immunocytochemistry, the present experiment examined the number of CREB- and pCREB-immunoreactive neurons in three regions of the dorsal and ventral hippocampus (dentate gyrus, CA3, and CA1) as a function of age and training. Rats were trained in a social transmission of food preference task. Using different food pairings, memory was tested in each rat immediately and 1, 2, 3, and 7 d later. Both young and old rats had intact and comparable memory scores at the immediate and 24-h tests, but old rats exhibited more rapid forgetting thereafter relative to that of young rats. The main findings were that training resulted in large increases in the number of pCREB-immunoreactive cells throughout the hippocampus in both young and aged rats. However, particularly in the ventral hippocampus, the training-elicited increase in pCREB-positive neurons was significantly lower in old than in young rats. Based on Western blot analyses in a separate set of rats, CREB levels were not responsive to training but were lower in the ventral hippocampus of old rats than of young rats. The present findings suggest that lower activation of CREB after training may contribute to the rapid forgetting seen in aged rats.


Familial aggregation of left ventricular geometry and association with parental heart failure: the Framingham Heart Study.
Data regarding the familial aggregation of left ventricular (LV) geometry and its relations to parental heart failure (HF) are limited. We evaluated concordance of LV geometry within 1093 nuclear families in 5758 participants of the original (parents) (n=2351) and offspring (n=3407) cohorts of the Framingham Heart Study undergoing routine echocardiography in mid- to late adulthood. LV geometry was categorized based on cohort- and sex-specific 80th percentile cutoffs of LV mass and relative wall thickness (RWT) into normal (both <80th percentile), concentric remodeling (LV mass <80th percentile; RWT >80th percentile), concentric hypertrophy (both >80th percentile), and eccentric hypertrophy (LV mass >80th percentile; RWT <80th percentile). Within nuclear families, LV geometry was concordant among related pairs (parent-child, sibling-sibling) (P=0.0015) but not among unrelated spousal pairs (P=0.60), a finding that remained unchanged after adjusting for clinical covariates known to influence LV remodeling (age, systolic blood pressure, body mass index), excluding individuals with prevalent HF and myocardial infarction, and varying the thresholds for defining LV geometry. The prevalence of abnormal LV geometry was higher in family members of affected individuals, with recurrence risks of 1.4 for concentric remodeling (95% CI, 1.2 to 1.7) and eccentric hypertrophy (95% CI, 1.1 to 1.8) and 3.9 (95% CI, 3.2 to 4.6) for concentric hypertrophy. In a subset of 1497 offspring, we observed an association between parental HF (n=458) and eccentric hypertrophy in offspring (P<0.0001). Our investigation of a 2-generational community-based sample demonstrates familial aggregation of LV geometry, with the greatest recurrence risk for concentric LV geometry, and establishes an association between eccentric LV geometry and parental HF.


Climate variables explain neutral and adaptive variation within salmonid metapopulations: the importance of replication in landscape genetics.
Understanding how environmental variation influences population genetic structure is important for conservation management because it can reveal how human stressors influence population connectivity, genetic diversity and persistence. We used riverscape genetics modelling to assess whether climatic and habitat variables were related to neutral and adaptive patterns of genetic differentiation (population-specific and pairwise FST ) within five metapopulations (79 populations, 4583 individuals) of steelhead trout (Oncorhynchus mykiss) in the Columbia River Basin, USA. Using 151 putatively neutral and 29 candidate adaptive SNP loci, we found that climate-related variables (winter precipitation, summer maximum temperature, winter highest 5% flow events and summer mean flow) best explained neutral and adaptive patterns of genetic differentiation within metapopulations, suggesting that climatic variation likely influences both demography (neutral variation) and local adaptation (adaptive variation). However, we did not observe consistent relationships between climate variables and FST across all metapopulations, underscoring the need for replication when extrapolating results from one scale to another (e.g. basin-wide to the metapopulation scale). Sensitivity analysis (leave-one-population-out) revealed consistent relationships between climate variables and FST within three metapopulations; however, these patterns were not consistent in two metapopulations likely due to small sample sizes (N = 10). These results provide correlative evidence that climatic variation has shaped the genetic structure of steelhead populations and highlight the need for replication and sensitivity analyses in land and riverscape genetics.


Arterial Elasticity in Ehlers-Danlos Syndromes.
Ehlers-Danlos Syndromes (EDS) are a group of heritable disorders of connective tissue (HDCT) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Orthostatic intolerance (OI) is highly prevalent in EDS however mechanisms linking OI to EDS remain poorly understood. We hypothesize that impaired blood pressure (BP) and heart rate control is associated with lower arterial stiffness in people with EDS. Orthostatic vital signs and arterial stiffness were assessed in a cohort of 60 people with EDS (49 female, 36 ± 16 years). Arterial elasticity was assessed by central and peripheral pulse wave velocity (PWV). Central PWV was lower in people with EDS compared to reference values in healthy subjects. In participants with EDS, central PWV was correlated to supine systolic BP (r = 0.387, p = 0.002), supine diastolic BP (r = 0.400, p = 0.002), and seated systolic BP (r = 0.399, p = 0.002). There were no significant correlations between PWV and changes in BP or heart rate with standing (p > 0.05). Between EDS types, there were no differences in supine hemodynamics or PWV measures (p > 0.05). These data demonstrate that increased arterial elasticity is associated with lower BP in people with EDS which may contribute to orthostatic symptoms and potentially provides a quantitative clinical measure for future genotype-phenotype investigations.


Maternal use of selective serotonin reuptake inhibitors and risk of miscarriage - assessing potential biases.
The use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy has been associated with miscarriage, but the association may be biased by maternal mental illness, lifestyle and exposure misclassification. A register study on all pregnancies in Denmark between 1996 and 2009 was conducted using individualised data from the Danish National Patient Register, the Medical Birth Register, the Danish Psychiatric Central Register, the Danish National Prescription database and the Danish National Birth Cohort (DNBC). A total of 1 191164 pregnancies were included in the study, of which 98275 also participated in the DNBC. Pregnancies exposed to SSRIs during or before pregnancy were more likely than unexposed pregnancies to result in first trimester miscarriage, hazard rate (HR)=1.08 [95% confidence interval (CI) 1.04, 1.13] and HR=1.26 [95% CI 1.16, 1.37], respectively. No difference was observed for second trimester miscarriage. SSRI-exposed pregnancies without a maternal depression/anxiety diagnosis from a psychiatric department were less likely to result in first trimester miscarriage than unexposed pregnancies with a diagnosis, HR=0.85 [95% CI 0.76, 0.95]. SSRI-exposed pregnancies were characterised by an unhealthier maternal lifestyle and mental health profile than unexposed pregnancies, whereas no convincing differences were observed between pregnancies exposed to SSRIs during versus before pregnancy. Substantial disagreement was found between prescriptions and self-reported use of SSRIs, but it did not affect the estimated hazard ratios. Confounding by indication and lifestyle in pregnancy may explain the association between SSRI use and miscarriage.


All for one and one for all! Disparity between overall crew's and individual rowers' pacing strategies during rowing.
This study examined individual contributions to overall pacing strategy during 2- and 5-km rowing trials in a coxless-4 boat. A crew of 4 male rowers performed maximal-effort on-water trials over 2 and 5 km, and power output during every individual stroke was measured for each crew member. Mean overall boat and individual rower stroke power were calculated for each 25% epoch (25% of total strokes taken), and power for each individual epoch was calculated as a percentage of mean power maintained over the entire distance. The coefficient of variation was used to determine stroke-to-stroke and epoch-to-epoch variability for individual rowers and the overall boat. In both trials, the overall pacing strategy consisted of a high power output in the initial 25% that decreased in the middle 50% and increased again in the final 25%. However, individual rower data indicate wide variation in individual power profiles that did not always mimic the overall boat profile. This study demonstrates that overall boat power profiles during 2- and 5-km rowing trials are similar to velocity profiles previously reported for individual ergometry and on-water racing events. However, this overall profile is achieved despite considerable variation in individual rower profiles. Further research is warranted to determine the mechanisms through which individual contributions to overall pacing strategy are regulated and the effectiveness or otherwise of seemingly disparate individual strategies on overall performance.


Post-Disaster Mental Health Among Parent-Child Dyads After a Major Earthquake in Indonesia.
The interdependent adjustment of children and their parents following disasters has been well documented. We used the Actor-Partner Interdependence Model (APIM) to provide an appropriate analytical framework for examining how family members may contribute to each other's post-disaster mental health. Independent self-reports were collected from parent-child dyads (n = 397) residing in a rural community in Indonesia that was devastated by a major earthquake. Elementary school children (M = 10 years; 51 % female) and one of their parents (M = 41 years; 73 % female) each reported on their disaster exposure, posttraumatic stress (PTS) symptoms, and general distress. The APIM was used to examine mental health within dyads and moderation by gender across dyads. Children reported lower disaster exposure and fewer PTS symptoms, but similar general distress levels, as their parents. Children's and parents' disaster-specific PTS symptoms were the strongest predictor of their own general distress. Parents' PTS symptoms were associated with children's general distress (b = 0.14, p < 0.001), but children's PTS symptoms were not associated with parents' general distress (b = -0.02, p > 0.05). Findings were not moderated by parents' or children's gender. Although children and parents may respond differently to natural disasters, they may be best understood as a dyad. APIM analyses provide new evidence suggesting a unidirectional path of influence from parents' disaster-related symptomatology to children's general mental health. Dyadic approaches to understanding mental health and treating symptoms of distress among disaster survivors and their families following trauma are encouraged.


A rapid and reliable technique for N-nitrosodimethylamine analysis in reclaimed water by HPLC-photochemical reaction-chemiluminescence.
A fast and reliable analytical technique was evaluated and validated for determination of N-nitrosodimethylamine (NDMA) formation and rejection by reverse osmosis (RO) membranes in potable water reuse applications. The analytical instrument used in this study is high-performance liquid chromatography (HPLC), photochemical reaction (PR) and chemiluminescence (CL) - namely HPLC-PR-CL. Results reported here show that HPLC-PR-CL can be used to measure NDMA with a similar level of accuracy compared to conventional and more time-consuming techniques using gas chromatography and tandem mass spectrometry detection in combination with solid phase extraction. Among key residual chemicals (i.e. monochloramine, hydrogen peroxide and hypochlorite) in reclaimed wastewater, hypochlorite was the only constituent that interfered with the determination of NDMA by HPLC-PR-CL. However, hypochlorite interference was eliminated by adding ascorbic acid as a reducing agent. Direct injection of ultrafiltration (UF)-treated wastewater samples into HPLC-PR-CL also resulted in an underestimation of the NDMA concentration possibly due to interference by organic substances in the UF-treated wastewater. Accurate determination of NDMA concentrations in UF-treated wastewater was achieved by reducing the sample injection volume from 200 to 20 μL, though this increased the method detection limit from 0.2 to 2 ng/L. In contrast, no interference was observed with RO permeate. These results suggest that RO membranes could remove part of substances that interfere with the NDMA analysis by HPLC-PR-CL. In addition, RO treatment experiments demonstrated that HPLC-PR-CL was capable of evaluating near real-time variation in NDMA rejection by RO.


Staging chronic hepatitis B into seven categories, defining inactive carriers and assessing treatment impact using a fibrosis biomarker (FibroTest®) and elastography (FibroScan®).
The first aim was to extend the validation of FibroTest® (FT) and transient elastography (TE) as markers of occurrence of cirrhosis without complications (F4.1), oesophageal varices (F4.2), and severe complications (F4.3) in patients with chronic hepatitis B (CHB). The second aim was to validate a previous definition of an inactive carrier based on normal FT and ActiTest® (normal-FT-AT). The third aim was to assess the long-term dynamics of fibrosis in patients with sustained virological response. The 10-year updated individual data of 1434 patients were pooled from two prospective cohorts. Of the 1312 patients without a history of complications, varices had occurred after 10 years in 14 patients (F4.2, incidence of 1.7%, 95% CI [0.6-2.8]), and severe complications in 25 (F4.3 3.7% [1.8-5.7]), including hepatocellular carcinoma (HCC) in 21 (3.7% [1.5-5.8]). Using Cox-multivariate analysis adjusted for treatment, viral load, HBeAg status and ALT, FT, and TE were predictive of liver complications (n=37; AUROC=0.83 [0.71-0.90]; p<0.0001) and (n=8/844; AUROC=0.82 [0.72-0.89]; p<0.0001) respectively. Normal FT-AT better identified patients with lower fibrosis progression than the ALT-based standard: 3/163 (1.8%) vs. 16/181 (8.8%; p=0.004) in the Paris cohort, and 5/195 (2.6%) vs. 15/228 (6.6%; p=0.05) in the Bordeaux cohort. Of the 582 responders, 23 had complications (incidence 6.2% [3.2-9.1]) including 19 HCC (5.8% [2.6-9.0]) and 10 with varices (2.6% [0.8-4.4]). Of the 138 responders with advanced fibrosis, only 31% (15-47%) had fibrosis regression. FibroTest® and TE identified three categories of cirrhosis with increasing morbidity. Normal FibroTest® and ActiTest® were better able to identify inactive hepatitis B carriers than the standard definition. Despite virological response, the overall incidence of cirrhosis increased, with a remaining 5.8% risk of HCC.


[Prevention of liver fibrosis and liver cancer linked to hepatitis B virus in Africa: the Prolifica study].
Despite the existence of an effective vaccine, HBV infects 257 million people worldwide and is the cause of the majority of HCC. With an annual mortality rate of 887 000 patients in 2015, this cancer is the second deadliest. Low-income countries such as ones in sub-Saharan Africa are the most at risk due to the limited access to healthcare. To overcome this and born from an international research collaboration within an EU project, the Prolifica study aimed at evaluating a screen-and-treat program to prevent HBV complications, and more particularly HCC. Based on communities, facilities and hospitals HBsAg+ detection, the study lasted from 2011 to 2016. From the "cost effectiveness" feasibility of such a program to the development of simple scores for antiviral treatment, Prolifica uncovered data of crucial importance in a region with low HBV infection awareness, transmissions modes and prevention means which could have impacts on public health policies.


Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates.
The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information regarding cancer occurrence and trends in the United States. This year's report includes trends in colorectal cancer (CRC) incidence and death rates and highlights the use of microsimulation modeling as a tool for interpreting past trends and projecting future trends to assist in cancer control planning and policy decisions. Information regarding invasive cancers was obtained from the NCI, CDC, and NAACCR; and information on deaths was obtained from the CDC's National Center for Health Statistics. Annual percentage changes in the age-standardized incidence and death rates (based on the year 2000 US population standard) for all cancers combined and for the top 15 cancers were estimated by joinpoint analysis of long-term trends (1975-2006) and for short-term fixed-interval trends (1997-2006). All statistical tests were 2-sided. Both incidence and death rates from all cancers combined significantly declined (P < .05) in the most recent time period for men and women overall and for most racial and ethnic populations. These decreases were driven largely by declines in both incidence and death rates for the 3 most common cancers in men (ie, lung and prostate cancers and CRC) and for 2 of the 3 leading cancers in women (ie, breast cancer and CRC). The long-term trends for lung cancer mortality in women had smaller and smaller increases until 2003, when there was a change to a nonsignificant decline. Microsimulation modeling demonstrates that declines in CRC death rates are consistent with a relatively large contribution from screening and with a smaller but demonstrable impact of risk factor reductions and improved treatments. These declines are projected to continue if risk factor modification, screening, and treatment remain at current rates, but they could be accelerated further with favorable trends in risk factors and higher utilization of screening and optimal treatment. Although the decrease in overall cancer incidence and death rates is encouraging, rising incidence and mortality for some cancers are of concern.


Growth hormone therapy in Turner's syndrome: an update on final height. Genentech National Cooperative Study Group.
The Genentech National Cooperative Study of growth hormone (GH) therapy in Turner's syndrome was initiated in 1983; 70 girls with Turner's syndrome were randomly assigned to observation or to treatment with GH alone, oxandrolone alone, or a combination of GH plus oxandrolone for a period of 12-24 months. After completion of this phase, patients receiving GH alone were continued on GH, while all other patients received the combination of GH plus oxandrolone. Data are currently available on the 62 girls who were treated for a minimum of 3-6 years. When compared with the height velocities anticipated for girls of comparable ages with untreated Turner's syndrome, both GH alone and a combination of GH plus oxandrolone resulted in an increase in height velocity, which was most prominent during the first 2 years of treatment and was sustained for at least 6 years. Although GH therapy is continuing at present in half of the patients, 14 of 17 girls (82%) receiving GH alone and 42 of 45 girls (93%) receiving combination therapy have exceeded their projected adult heights. For the 30 girls who have stopped therapy, the current mean height is 151.9 cm, compared with their original mean projected adult height of 143.8 cm. These results demonstrate that GH therapy can result in short-term (3-6 years) acceleration of growth, as well as in improved adult height.


Dystroglycan function is a novel determinant of tumor growth and behavior in prostate cancer.
Dystroglycan is a ubiquitously expressed cell adhesion molecule frequently found to be altered or reduced in adenocarcinomas, however the mechanisms or consequences of dystroglycan loss have not been studied extensively. We examined the consequence of overexpression or RNAi depletion of dystroglycan on properties of in vitro growth migration and invasion of LNCaP, PC3, and DU145 prostate cancer cell lines. Using LNCaP cells we observed cell density-dependent changes in β-dystroglycan with the appearance of several lower molecular weight species ranging in size from 43 to 26 kDa. The bands of 31 and 26 kDa were attributed to proteolysis, whereas bands between 43 and 38 kDa were a consequence of mis-glycosylation. The localization of β-dystroglycan in LNCaP colonies in culture also varied, cells with a mesenchymal appearance at the periphery of the colony had more pronounced membrane localization of dystroglycan. Whereas some cells demonstrated nuclear dystroglycan. Increased dystroglycan levels were inhibitory to growth in soft agar but promoted Matrigel invasion, whereas reduced dystroglycan levels promoted growth in soft agar but inhibited invasion. Similar results were also obtained for PC3 and DU145 cells. This study suggests that changes in β-dystroglycan distribution within the cell and/or the loss of dystroglycan during tumorigenesis, through a combination of proteolysis and altered glycosylation, leads to an increased ability to grow in an anchorage independent manner, however dystroglycan may need to be re-expressed for cell invasion and metastasis to occur.


Who pays for home care? A study of nationally representative data on disabled older Americans.
We examine who pays for services that support disabled older Americans at home. We consider both personal sources (e.g., out-of-pocket payment, family members) and publicly funded programs (e.g., Medicaid) as sources of payment for services. We examine how the funding mix for home care services is related to older people's economic resources, needs for care, and other socio-demographic characteristics. Our sample consists of 11,725 person-years from the 1989, 1994, 1999, and 2004 waves of the National Long-Term Care Survey. Two-part regression analyses were performed to model hours of care received from each payer. "Random effects" and "fixed effects" estimation yielded similar results. About six in ten caregivers (63%) providing home care services are paid by personal sources alone. By contrast, 28% receive payment from publicly funded programs alone, and 9% from a combination of personal and public program sources. Older people with family incomes over 75,000 dollars per year receive 8.5 more hours of home care overall than those in the lowest income category (less than 15,000 dollars). While the funding mix for home care services is strongly related to older people's economic resources, in all income groups at least 65% of services are provided by caregivers paid in whole or in part from personal sources. In fact, almost all (97%) home care received by those with family incomes over 75,000 dollars per year are financed by personal sources alone. We outline the implications that heavy reliance on personally financed services and economic disparities in overall services use has for disabled older Americans and their families.


Variation in state spending for long-term care: factors associated with more balanced systems.
Pressures to turn over responsibility for long-term care to the states will exacerbate the already sizable difference in such efforts. This article describes the nature of the interstate variation in the types and amounts of long-term care provided under Medicaid. The average Medicaid long-term care expenditure on persons sixty-five years and older varies from $2,720 in New York to $380 in Arizona. Likewise, payments for home and community-based services (HCBS) vary from $1,180 in New York to $29 in Mississippi. Only a modest portion (28 percent) of the variance in total long-term care expenditures appears to be related to differences in population characteristics, and even less (7 percent) appears to be related to differences in HCBS expenditures. When supply factors (e.g., nursing home beds) are added, the explained variance increases to 52 percent and 17 percent, respectively. Medicare replaces some--but not most--of the difference in Medicaid home and community-based services payments.


Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria.
The PfEMP1 family of surface proteins is central for Plasmodium falciparum virulence and must retain the ability to bind to host receptors while also diversifying to aid immune evasion. The interaction between CIDRα1 domains of PfEMP1 and endothelial protein C receptor (EPCR) is associated with severe childhood malaria. We combine crystal structures of CIDRα1:EPCR complexes with analysis of 885 CIDRα1 sequences, showing that the EPCR-binding surfaces of CIDRα1 domains are conserved in shape and bonding potential, despite dramatic sequence diversity. Additionally, these domains mimic features of the natural EPCR ligand and can block this ligand interaction. Using peptides corresponding to the EPCR-binding region, antibodies can be purified from individuals in malaria-endemic regions that block EPCR binding of diverse CIDRα1 variants. This highlights the extent to which such a surface protein family can diversify while maintaining ligand-binding capacity and identifies features that should be mimicked in immunogens to prevent EPCR binding.


Water penetration of damaged self-assembled monolayers.
The interaction of water with self-assembled monolayers (SAMs) on amorphous silica is investigated using classical molecular dynamics simulation. Damage is induced through shear simulations with model atomic force microscopy (AFM) tips and separately with controlled extraction. We find that SAM coatings that have been slightly damaged (by normal loads close to 10 nN from a 10-nm-diameter AFM tip) are susceptible to water penetration and migration to the underlying hydrophilic substrate. The controlled damage studies indicate that the presence of water tends to heal damage below a threshold radius and exploits and magnifies damage above this threshold. For the systems studied here, Si(OH)3(CH2)10CH3 alkylsilane chains on amorphous silica, this threshold radius is between 0.5 and 1.0 nm.


Noninvasive Prenatal Testing and Incidental Detection of Occult Maternal Malignancies.
Understanding the relationship between aneuploidy detection on noninvasive prenatal testing (NIPT) and occult maternal malignancies may explain results that are discordant with the fetal karyotype and improve maternal clinical care. To evaluate massively parallel sequencing data for patterns of copy-number variations that might prospectively identify occult maternal malignancies. Case series identified from 125,426 samples submitted between February 15, 2012, and September 30, 2014, from asymptomatic pregnant women who underwent plasma cell-free DNA sequencing for clinical prenatal aneuploidy screening. Analyses were conducted in a clinical laboratory that performs DNA sequencing. Among the clinical samples, abnormal results were detected in 3757 (3%); these were reported to the ordering physician with recommendations for further evaluation. NIPT for fetal aneuploidy screening (chromosomes 13, 18, 21, X, and Y). Detailed genome-wide bioinformatics analysis was performed on available sequencing data from 8 of 10 women with known cancers. Genome-wide copy-number changes in the original NIPT samples and in subsequent serial samples from individual patients when available are reported. Copy-number changes detected in NIPT sequencing data in the known cancer cases were compared with the types of aneuploidies detected in the overall cohort. From a cohort of 125,426 NIPT results, 3757 (3%) were positive for 1 or more aneuploidies involving chromosomes 13, 18, 21, X, or Y. From this set of 3757 samples, 10 cases of maternal cancer were identified. Detailed clinical and sequencing data were obtained in 8. Maternal cancers most frequently occurred with the rare NIPT finding of more than 1 aneuploidy detected (7 known cancers among 39 cases of multiple aneuploidies by NIPT, 18% [95% CI, 7.5%-33.5%]). All 8 cases that underwent further bioinformatics analysis showed unique patterns of nonspecific copy-number gains and losses across multiple chromosomes. In 1 case, blood was sampled after completion of treatment for colorectal cancer and the abnormal pattern was no longer evident. In this preliminary study, a small number of cases of occult malignancy were subsequently diagnosed among pregnant women whose noninvasive prenatal testing results showed discordance with the fetal karyotype. The clinical importance of these findings will require further research.


Model-Based and Model-Free Social Cognition: Investigating the Role of Habit in Social Attitude Formation and Choice.
Do habits play a role in our social impressions? To investigate the contribution of habits to the formation of social attitudes, we examined the roles of model-free and model-based reinforcement learning in social interactions - computations linked in past work to habit and planning, respectively. Participants in this study learned about novel individuals in a sequential reinforcement learning paradigm, choosing financial advisors who led them to high- or low-paying stocks. Results indicated that participants relied on both model-based and model-free learning, such that each type of learning was expressed in both advisor choices and post-task self-reported liking of advisors. Specifically, participants preferred advisors who could provide large future rewards as well as advisors who had provided them with large rewards in the past. Although participants relied more heavily on model-based learning overall, they varied in their use of model-based and model-free learning strategies, and this individual difference influenced the way in which learning related to self-reported attitudes: among participants who relied more on model-free learning, model-free social learning related more to post-task attitudes. We discuss implications for attitudes, trait impressions, and social behavior, as well as the role of habits in a memory systems model of social cognition.


Comparison of in-hospital outcomes and readmissions for valve-in-valve transcatheter aortic valve replacement vs. reoperative surgical aortic valve replacement: a contemporary assessment of real-world outcomes.
We sought to perform a head-to-head comparison of contemporary 30-day outcomes and readmissions between valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) patients and a matched cohort of high-risk reoperative surgical aortic valve replacement (re-SAVR) patients using a large, multicentre, national database. We utilized the nationally weighted 2012-16 National Readmission Database claims to identify all US adult patients with degenerated bioprosthetic aortic valves who underwent either VIV-TAVR (n = 3443) or isolated re-SAVR (n = 3372). Thirty-day outcomes were compared using multivariate analysis and propensity score matching (1:1). Unadjusted, VIV-TAVR patients had significantly lower 30-day mortality (2.7% vs. 5.0%), 30-day morbidity (66.4% vs. 79%), and rates of major bleeding (35.8% vs. 50%). On multivariable analysis, re-SAVR was a significant risk factor for both 30-day mortality [adjusted odds ratio (aOR) of VIV-SAVR (vs. re-SAVR) 0.48, 95% confidence interval (CI) 0.28-0.81] and 30-day morbidity [aOR for VIV-TAVR (vs. re-SAVR) 0.54, 95% CI 0.43-0.68]. After matching (n = 2181 matched pairs), VIV-TAVR was associated with lower odds of 30-day mortality (OR 0.41, 95% CI 0.23-0.74), 30-day morbidity (OR 0.53, 95% CI 0.43-0.72), and major bleeding (OR 0.66, 95% CI 0.51-0.85). Valve-in-valve TAVR was also associated with shorter length of stay (median savings of 2 days, 95% CI 1.3-2.7) and higher odds of routine home discharges (OR 2.11, 95% CI 1.61-2.78) compared to re-SAVR. In this large, nationwide study of matched high-risk patients with degenerated bioprosthetic aortic valves, VIV-TAVR appears to confer an advantage over re-SAVR in terms of 30-day mortality, morbidity, and bleeding complications. Further studies are warranted to benchmark in low- and intermediate-risk patients and to adequately assess longer-term efficacy.


Use of a Video Scoring Anchor for Rapid Serial Assessment of Social Communication in Toddlers.
Reciprocal social behavior (RSB), an early-emerging capacity to engage in social contingency-which is foundational for both social learning and social competency-is hypothesized to be disrupted in autism spectrum disorder (ASD). The ability to quantify the full range of RSB during the toddler period, when core symptoms of ASD often arise, is pivotal for evaluating early risk for ASD, characterizing social development, and tracking response to early interventions. However, important parameters of variation in RSB-especially prior to the development of verbal language-can be nuanced and difficult to characterize using questionnaire-based methods. To address this challenge, we developed a system for measuring quantitative variation in RSB in toddlers (ages 18 - 30 months) that incorporated not only standard questionnaire data from caregivers but also a novel set of video-referenced items, through which a respondent compares the behavior of a subject to that observed in a short video of a young child manifesting a highly competent level of social communication. Testing of this measure in a general population sample of twins confirmed that both the video-referenced items and the RSB Total Score (video-referenced items plus non-video-referenced items) displayed unimodal, continuous distributions, strong internal consistency, marked preservation of individual differences, and extremely high heritability. In addition, video-referenced items were particularly sensitive to quantifying incremental changes in social communication, a major element of RSB, over the course of early childhood development. Scores on the vrRSB clearly differentiated children with and without ASD and these data comprise an initial validation of this promising method for quantifying early RSB-cross-sectionally, over time, and as a function of early intervention.


Ischemic Toe Ulceration Due to Foreign Body Embolus From Hydrophilic Polymer-Coated Intravascular Device.
Hydrophilic polymer coatings are now widely applied to catheters and other intravascular devices used in neurovascular, cardiovascular, and peripheral vascular procedures. Emboli consisting of these materials have been previously identified in biopsies and autopsies following pulmonary infarction, stroke, gangrene, or death. We report a case involving a nonhealing foot ulcer that appeared following cardiac catheterization, stenting, and automatic implanted cardiac defibrillator (AICD) implantation in a patient without other evidence of significant peripheral artery disease. An 85-year-old woman with chronic atrial fibrillation, aortic valve stenosis, and coronary artery disease underwent coronary stenting and AICD implantation for ventricular tachycardia and syncope. She developed a toe ulcer shortly thereafter, which did not respond to standard treatment. A histological examination following amputation of the toe found amorphous basophilic material in capillaries adjacent to the edge of the ulcer, which was similar to material associated with hydrophilic polymer coatings. Ischemia and infarcts following endovascular procedures should not be presumed to result from thrombus or vascular disease, even if intravascular devices appear intact or properly placed after the procedure. To help establish the incidence of ischemia caused by hydrophilic polymer device coatings, if excision of ischemic or infarcted tissue after endovascular procedures using coated devices becomes necessary, the tissue should be evaluated microscopically. Surgeons should also consider the tolerance of distal organs to infarct or ischemia when selecting coated intravascular devices.


Transcript normalization and segmentation of tiling array data.
For the analysis of transcriptional tiling arrays we have developed two methods based on state-of-the-art machine learning algorithms. First, we present a novel transcript normalization technique to alleviate the effect of oligonucleotide probe sequences on hybridization intensity. It is specifically designed to decrease the variability observed for individual probes complementary to the same transcript. Applying this normalization technique to Arabidopsis tiling arrays, we are able to reduce sequence biases and also significantly improve separation in signal intensity between exonic and intronic/intergenic probes. Our second contribution is a method for transcript mapping. It extends an algorithm proposed for yeast tiling arrays to the more challenging task of spliced transcript identification. When evaluated on raw versus normalized intensities our method achieves highest prediction accuracy when segmentation is performed on transcript-normalized tiling array data.


Imagined viewer and object rotations dissociated with event-related FMRI.
Human spatial reasoning may depend in part on two dissociable types of mental image transformations: object-based transformations, in which an object is imagined to move in space relative to the viewer and the environment, and perspective transformations, in which the viewer imagines the scene from a different vantage point. This study measured local brain activity with event-related fMRI while participants were instructed to either imagine an array of objects rotating (an object-based transformation) or imagine themselves rotating around the array (a perspective transformation). Object-based transformations led to selective increases in right parietal cortex and decreases in left parietal cortex, whereas perspective transformations led to selective increases in left temporal cortex. These results argue against the view that mental image transformations are performed by a unitary neural processing system, and they suggest that different overlapping systems are engaged for different image transformations.


Role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh.
In Bangladesh, cholera is endemic and maintains a regular seasonal pattern. The role of phytoplankton in maintaining endemicity and seasonality of cholera was monitored in Matlab, Bangladesh. Phytoplankton and water samples were collected from two ponds bi-weekly for 1 year. The association of Vibrio cholerae O1 with phytoplankton was studied by culture and direct fluorescent antibody techniques. The bio-physicochemical parameters of water were measured and data for cases of cholera were collected from the records of Matlab hospital. The correlation of cholera cases with levels of phytoplankton, V. cholerae and bio-physicochemical parameters of water was carried out using Pearson's correlation coefficients. V. cholerae O1 survived for 48 days in association with Anabaena variabilis in a culturable state, but survived for a year in a viable but non-culturable (VBNC) state. V. cholerae survived for 12 and 32 days in a culturable state in control water (without algae) and water with algae, respectively. There was a significant correlation between changing levels of cholera cases in the community and the blue green algae and total phytoplankton in the aquatic environment. A significant correlation was also found between the cholera cases and chlorophyll-a and VBNC V. cholerae O1 in the aquatic environment. This study demonstrated the role of phytoplankton in maintaining endemicity and seasonality of cholera in Bangladesh.


Dietary patterns and cognitive decline in an Australian study of ageing.
The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet.


The Meaning and Predictive Value of Self-rated Mental Health among Persons with a Mental Health Problem.
Self-rated health is a valid measure of health that predicts quality of life, morbidity, and mortality. Its predictive value reflects a conceptualization of health that goes beyond a traditional medical model. However, less is known about self-rated mental health (SRMH). Using data from the Medical Expenditure Panel Survey ( N = 2,547), we examine how rating your mental health as good-despite meeting criteria for a mental health problem-predicts outcomes. We found that 62% of people with a mental health problem rated their mental health positively. Persons who rated their mental health as good (compared to poor) had 30% lower odds of having a mental health problem at follow-up. Even without treatment, persons with a mental health problem did better if they perceived their mental health positively. SRMH might comprise information beyond the experience of symptoms. Understanding the unobserved information individuals incorporate into SRMH will help us improve screening and treatment interventions.


Experimental Entanglements: Surveillance Science, Sex Worker Activism, and Evidentiary Politics in Kenya.
In Kenya, globally circulating HIV surveillance techniques are implicated in an emergent experimental terrain that merges scientific interest with health administration agendas. Sex worker activists reroute and repurpose this technocratic knowledge to more precisely pinpoint and defy the undemocratic imperatives of an encroaching experimental order that aims to govern the health of key populations. Reconstructing the conditions of emergence of these evidentiary politics reveals growing interdependencies between sex workers and scientific and technical experts as they are brought into increasing interaction with each other.


Tissue specificity of decellularized rhesus monkey kidney and lung scaffolds.
Initial steps in establishing an optimal strategy for functional bioengineered tissues is generation of three-dimensional constructs containing cells with the appropriate organization and phenotype. To effectively utilize rhesus monkey decellularized kidney scaffolds, these studies evaluated two key parameters: (1) residual scaffold components after decellularization including proteomics analysis, and (2) the use of undifferentiated human embryonic stem cells (hESCs) for recellularization in order to explore cellular differentiation in a tissue-specific manner. Sections of kidney and lung were selected for a comparative evaluation because of their similar pattern of organogenesis. Proteomics analysis revealed the presence of growth factors and antimicrobial proteins as well as stress proteins and complement components. Immunohistochemistry of recellularized kidney scaffolds showed the generation of Cytokeratin+ epithelial tubule phenotypes throughout the scaffold that demonstrated a statistically significant increase in expression of kidney-associated genes compared to baseline hESC gene expression. Recellularization of lung scaffolds showed that cells lined the alveolar spaces and demonstrated statistically significant upregulation of key lung-associated genes. However, overall expression of kidney and lung-associated markers was not statistically different when the kidney and lung recellularized scaffolds were compared. These results suggest that decellularized scaffolds have an intrinsic spatial ability to influence hESC differentiation by physically shaping cells into tissue-appropriate structures and phenotypes, and that additional approaches may be needed to ensure consistent recellularization throughout the matrix.


Association Between Tracheal Intubation During Pediatric In-Hospital Cardiac Arrest and Survival.
Tracheal intubation is common during pediatric in-hospital cardiac arrest, although the relationship between intubation during cardiac arrest and outcomes is unknown. To determine if intubation during pediatric in-hospital cardiac arrest is associated with improved outcomes. Observational study of data from United States hospitals in the Get With The Guidelines-Resuscitation registry. Pediatric patients (<18 years) with index in-hospital cardiac arrest between January 2000 and December 2014 were included. Patients who were receiving assisted ventilation, had an invasive airway in place, or both at the time chest compressions were initiated were excluded. Tracheal intubation during cardiac arrest . The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation and neurologic outcome. A favorable neurologic outcome was defined as a score of 1 to 2 on the pediatric cerebral performance category score. Patients being intubated at any given minute were matched with patients at risk of being intubated within the same minute (ie, still receiving resuscitation) based on a time-dependent propensity score calculated from multiple patient, event, and hospital characteristics. The study included 2294 patients; 1308 (57%) were male, and all age groups were represented (median age, 7 months [25th-75th percentiles, 21 days, 4 years]). Of the 2294 included patients, 1555 (68%) were intubated during the cardiac arrest. In the propensity score-matched cohort (n = 2270), survival was lower in those intubated compared with those not intubated (411/1135 [36%] vs 460/1135 [41%]; risk ratio [RR], 0.89 [95% CI, 0.81-0.99]; P = .03). There was no significant difference in return of spontaneous circulation (770/1135 [68%] vs 771/1135 [68%]; RR, 1.00 [95% CI, 0.95-1.06]; P = .96) or favorable neurologic outcome (185/987 [19%] vs 211/983 [21%]; RR, 0.87 [95% CI, 0.75-1.02]; P = .08) between those intubated and not intubated. The association between intubation and decreased survival was observed in the majority of the sensitivity and subgroup analyses, including when accounting for missing data and in a subgroup of patients with a pulse at the beginning of the event. Among pediatric patients with in-hospital cardiac arrest, tracheal intubation during cardiac arrest compared with no intubation was associated with decreased survival to hospital discharge. Although the study design does not eliminate the potential for confounding, these findings do not support the current emphasis on early tracheal intubation for pediatric in-hospital cardiac arrest.


Pattern of seizure cases in tertiary care hospitals in Karnataka state of India.
The prevalence and incidence of epilepsy is higher in developing countries than in developed countries. Understanding pattern and risk factors of seizure cases will help in suggesting appropriate preventive measures. This study was carried out to assess the pattern of seizure, its management and compliance with treatment. Data from medical records of seizure cases in three tertiary care hospitals of Mangalore city in south India admitted from January 2006 to December 2011 were collected and analyzed. Nearly half (44.4%) of the 196 cases belonged to productive age group (15-45 years) and 2/3(rd) (60.7%) were males. Majority (>80% cases) were unskilled workers and of low socio-economic status groups. Family history of seizures was present in 8.4% cases. Mean age of onset of seizure was found to be 19.9 years. Proportion of generalized tonic clonic seizure cases was 78.1%. Secondary seizures were seen in 66 (33.7%) cases with the most common cause being trauma to the head (24.2%). Refractory seizures were present in 2.7% cases. Monotherapy was the most commonly followed treatment regimen and phenytoin was the most popular anti-epileptic drug (AED) used. Non-compliance with AEDs was seen in 18.1% cases and was more among patients on polytherapy (P = 0.032). Seizure manifestations and treatment compliance vary widely in the studied population. In depth analysis of each seizure type will give more information about the factors associated with it.


Effect of American ginseng (Panax quinquefolium) on male copulatory behavior in the rat.
The effects of American ginseng (Panax quinquefolium) on male rat copulatory behavior were investigated. Adult Sprague-Dawley rats were administered either 10, 50 or 100 mg/kg of Panax quinquefolium or a sesame oil vehicle per os (p.o.) for 28 days and copulatory behavior parameters were measured. Ginseng-treated male rats demonstrated a significant decrease in mount, intromission and ejaculation latencies compared to vehicle controls. Hormone analyses revealed no difference in plasma luteinizing hormone or testosterone levels between ginseng- and vehicle-treated animals; however, plasma prolactin levels were significantly reduced by all doses of ginseng tested. When male rats were treated with the 100 mg/kg dose of ginseng for 1, 14 or 28 days, mount and intromission latencies were significantly reduced at 14 and 28 days of daily ginseng treatment, whereas ejaculation latency was significantly reduced after 1 day of ginseng treatment when compared to vehicle controls. Plasma prolactin levels were also significantly decreased after 14 and 28 days of daily ginseng administration. There were no differences in body weight or in testes, seminal vesicle, anterior pituitary or spleen weights between ginseng- and vehicle-treated rats. These results demonstrate that P. quinquefolium significantly facilitates male copulatory behavior. The reduction in plasma prolactin levels suggests that ginseng-induced alterations in dopaminergic neurotransmission may play a role in the ability of P. quinquefolium to stimulate copulatory behavior in the male rat.