A novel mutation in a patient with a deficiency of the eighth component of complement associated with recurrent meningococcal meningitis.
Complement component C8 is one of the five terminal complement components required for the formation of the membrane attack complex. Complete absence of C8 results in increased susceptibility to gram-negative bacteria such as Neisseria species. Two functionally distinct C8 deficiency states have been described: C8 alpha-gamma deficiency has been predominantly reported amongst Afro-Caribbeans, Hispanics, and Japanese and C8beta mainly in Caucasians. We report a case of functional and immunochemical deficiency of the complement component C8, diagnosed in a Caucasian adult following three episodes of meningitis. Western blotting and hemolytic assay demonstrated absence of C8beta. In genetic studies, the common exon 9 C > T transition responsible for 85% of C8beta deficiencies was not found. Two mutations were identified: a novel duplication mutation, c.1047_1053 dupGGCTGTG in exon 7 that introduces a frame shift, resulting in the addition of seven novel amino acid residues and a premature stop codon, and a previously reported mutation, c.271C > T in exon 3. The parents each expressed one of these mutations, confirming compound heterozygosity. This is the first report of a duplication mutation in C8beta deficiency and extends the molecular heterogeneity of the disorder.


Lectin characterization of gonococci from an outbreak caused by penicillin-resistant Neisseria gonorrhoeae.
A total of 40 Neisseria gonorrhoeae isolates, representing 19 penicillin-resistant isolates (from 8 heterosexual patients and 11 homosexual patients) and 21 penicillin-susceptible isolates (from 15 heterosexual patients and 6 homosexual patients) and obtained from the same geographic area, were examined. Lectin agglutination patterns were based on the reactivity of the isolates with the following 14 lectins: concanavalin A, Lens culinaris, Trichosanthes kinlowii, Griffonia simplicifolia I, Arachis hypogeae (peanut agglutinin), Glycine max (soybean agglutinin), Dolichos bifloris, Griffonia simplicifolia II, Solanum tuberosum (potato starch agglutinin), Triticum vulgaris (wheat germ agglutinin), Limax flavus, Phaseolus vulgaris, Ulex europaeus I, and Lotus tetragonolobus. All isolates were serotyped with monoclonal antibodies specific for gonococcal outer membrane protein I and auxotyped, and the plasmid content was determined. Resistant patient isolates were selected for their decreased penicillin susceptibility, and control isolates were selected for their penicillin susceptibility. Even though the patient isolates demonstrated resistance to penicillin, no phenotypic differences in lectin-grouping patterns were demonstrated between the two study groups; i.e., two predominant lectin groups were observed. No resistance-associated plasmids were detected. All patient isolates were serogroup IB (serovars IB-1, IB-2, and IB-4), whereas 12 of 21 control isolates were serogroup IA (P less than 0.05). Isolates obtained from different anatomical sites in the same patient (cervical and rectal) agreed with regard to lectin patterns and serovars but not auxotypes.


Effect of nasal continuous positive airway pressure on the pharyngeal swallow in neonates.
Feeding neonates orally while on nasal continuous positive airway pressure (nCPAP) is a common practice. We hypothesize that pressurized airflow provided by nCPAP will alter the swallowing mechanism in neonates, increasing the risk of aspiration during oral feeding. Infants receiving nCPAP with a RAM cannula and tolerating at least 50% of their feeding orally were included in the study (one term; six preterm infants). Each participant underwent a videofluoroscopic swallow study while on nCPAP and off nCPAP. A non-parametric signed-rank test was used for paired data. The incidence of deep penetration (P=0.03) and aspiration (P=0.01) decreased significantly off-nCPAP compared with on-nCPAP. However, the incidence of mild penetration (P=0.65) and nasopharyngeal reflux (P=0.87) remained the same under both conditions. Oral feeding while on-nCPAP significantly increases the risk of laryngeal penetration and tracheal aspiration events. We recommend caution when initiating oral feedings on nCPAP.


Harlequin syndrome: the sudden onset of unilateral flushing and sweating.
Facial flushing and sweating were investigated in five patients who complained of the sudden onset of unilateral facial flushing in hot weather or when exercising vigorously. One patient probably suffered a brainstem infarct at the time that the unilateral flush was first noticed, and was left with a subtle Horner's syndrome on the side opposite to the flush. The other four had no other neurological symptoms and no ocular signs of Horner's syndrome. Thermal and emotional flushing and sweating were found to be impaired on the non-flushing side of the forehead in all five patients whereas gustatory sweating and flushing were increased on that side in four of the five patients, a combination of signs indicating a deficit of the second sympathetic neuron at the level of the third thoracic segment. CT and MRI of this area failed to disclose a structural lesion but latency from stimulation of the motor cortex and thoracic spinal cord to the third intercostal muscle was delayed on the non-flushing side in one patient. The complaint of unilateral flushing and sweating was abolished in one patient by ipsilateral stellate ganglionectomy. The unilateral facial flushing and sweating induced by heat in all five patients was thus a normal or excessive response by an intact sympathetic pathway, the other side failing to respond because of a sympathetic deficit. The onset in the four cases of peripheral origin followed strenuous exertion, which suggested that an anterior radicular artery may have become occluded at the third thoracic segment during torsion of the thoracic spine.


Mitochondrial-Targeted Catalase Protects Against High-Fat Diet-Induced Muscle Insulin Resistance by Decreasing Intramuscular Lipid Accumulation.
We explored the role of reactive oxygen species (ROS) in the pathogenesis of muscle insulin resistance. We assessed insulin action in vivo with a hyperinsulinemic-euglycemic clamp in mice expressing a mitochondrial-targeted catalase (MCAT) that were fed regular chow (RC) or a high-fat diet (HFD) or underwent an acute infusion of a lipid emulsion. RC-fed MCAT mice were similar to littermate wild-type (WT) mice. However, HFD-fed MCAT mice were protected from diet-induced insulin resistance. In contrast, an acute lipid infusion caused muscle insulin resistance in both MCAT and WT mice. ROS production was decreased in both HFD-fed and lipid-infused MCAT mice and cannot explain the divergent response in insulin action. MCAT mice had subtly increased energy expenditure and muscle fat oxidation with decreased intramuscular diacylglycerol (DAG) accumulation, protein kinase C-θ (PKCθ) activation, and impaired insulin signaling with HFD. In contrast, the insulin resistance with the acute lipid infusion was associated with increased muscle DAG content in both WT and MCAT mice. These studies suggest that altering muscle mitochondrial ROS production does not directly alter the development of lipid-induced insulin resistance. However, the altered energy balance in HFD-fed MCAT mice protected them from DAG accumulation, PKCθ activation, and impaired muscle insulin signaling.


Potential benefits of mindfulness during pregnancy on maternal autonomic nervous system function and infant development.
Mindfulness is known to decrease psychological distress. Possible benefits in pregnancy have rarely been explored. Our aim was to examine the prospective association of mindfulness with autonomic nervous system function during pregnancy and with later infant social-emotional development. Pregnant women (N = 156) completed self-report mindfulness and emotional distress questionnaires, and had their autonomic function assessed in their first and third trimesters, including heart rate (HR), indices of heart rate variability (HRV), preejection period (PEP), and systolic (SBP) and diastolic blood pressure (DBP). The social-emotional development of 109 infants was assessed at 4 months of age. More mindful pregnant women had less prenatal and postnatal emotional distress (p < .001) and higher cardiac parasympathetic activity: root mean square of successive differences (RMSSD: p = .03) and high-frequency (HF) HRV (p = .02). Between the first and third trimesters, women's overall HR increased (p < .001), and HRV (RMSSD, HF HRV, and low-frequency (LF) HRV: p < .001) and PEP decreased (p < .001). In more mindful mothers, parasympathetic activity decreased less (RMSSD: p = .01; HF HRV: p = .03) and sympathetic activity (inversely related to PEP) increased less (PEP: p = .02) between trimesters. Their offspring displayed less negative social-emotional behavior (p = .03) compared to offspring of less mindful mothers. Mindfulness in pregnancy was associated with ANS changes likely to be adaptive and with better social-emotional offspring development. Interventions to increase mindfulness during pregnancy might improve maternal and offspring health, but randomized trials are needed to demonstrate this.


Physicians' experiences with euthanasia: a cross-sectional survey amongst a random sample of Dutch physicians to explore their concerns, feelings and pressure.
Physicians who receive a request for euthanasia or assisted suicide may experience a conflict of duties: the duty to preserve life on the one hand and the duty to relieve suffering on the other hand. Little is known about experiences of physicians with receiving and granting a request for euthanasia or assisted suicide. This study, therefore, aimed to explore the concerns, feelings and pressure experienced by physicians who receive requests for euthanasia or assisted suicide. In 2016, a cross-sectional study was conducted. Questionnaires were sent to a random sample of 3000 Dutch physicians. Physicians who had been working in adult patient care in the Netherlands for the last year were included in the sample (n = 2657). Half of the physicians were asked about the most recent case in which they refused a request for euthanasia or assisted suicide, and half about the most recent case in which they granted a request for euthanasia or assisted suicide. Of the 2657 eligible physicians, 1374 (52%) responded. The most reported reason not to participate was lack of time. Of the respondents, 248 answered questions about a refused euthanasia or assisted suicide request and 245 about a granted EAS request. Concerns about specific aspects of the euthanasia and assisted suicide process, such as the emotional burden of preparing and performing euthanasia or assisted suicide were commonly reported by physicians who refused and who granted a request. Pressure to grant a request was mostly experienced by physicians who refused a request, especially if the patient was ≥80 years, had a life-expectancy of ≥6 months and did not have cancer. The large majority of physicians reported contradictory emotions after having performed euthanasia or assisted suicide. Society should be aware of the impact of euthanasia and assisted suicide requests on physicians. The tension physicians experience may decrease their willingness to perform euthanasia and assisted suicide. On the other hand, physicians should not be forced to cross their own moral boundaries or be tempted to perform euthanasia and assisted suicide in cases that may not meet the due care criteria.


The measurement of multimorbidity.
The presence of multiple concurrent medical conditions (also known as multimorbidity) is now a common phenomenon, hence the importance of its measurement. The purpose of this paper is to review the multimorbidity measures that have been published in the literature to date and that are available for use in future research studies. Two main groups of measures of multimorbidity could be distinguished. The first group of measures is constituted by a simple count from various lists of chronic conditions. The second group of measures introduces a weighting for included chronic conditions thus creating a "weighted index" of multimorbidity. These groups are not mutually exclusive as the list of medical conditions in some weighted indices can be used as a list of conditions without weighting. This article includes a review of the multimorbidity literature to date that has reported these groups of measurements, showing the variety of existing measurements and highlighting their differences to provide an overview of the possibilities that are available to a researcher intending to measure multimorbidity. Finally, we outline some guidelines for the choice of a measurement of multimorbidity for research studies. We hope that this review of the existing literature will help inform the careful use of these tools by researchers moving forward. In addition to this review, it is advised that readers attempt to keep updated on the ever-increasing multimorbidity literature. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Rapid detection of green-pea adulteration in pistachio nuts using Raman spectroscopy and chemometrics.
Ground pistachio nut is prone to adulteration because of its high economic value and wide usage. Green pea is known as the main adulterant in frauds involving pistachio nuts. The present study developed a new, rapid, reliable and low-cost methodology by using a portable Raman spectrometer in combination with chemometrics for the detection of green pea in pistachio nuts. Three different methods of Raman spectroscopy-based chemometrics analysis were developed for the determination of green-pea adulteration in pistachio nuts. The first method involved the development of hierarchical cluster analysis (HCA) and principal component analysis (PCA), which differentiated authentic pistachio nuts from green pea and green pea-adulterated samples. The best classification pattern was observed in the adulteration range of 20-80% (w/w). In addition to classification methods, partial least squares regression (PLSR) and genetic algorithm-based inverse least squares (GILS) were also used to develop multivariate calibration models to determine quantitatively the degree of green-pea adulteration in grounded pistachio nuts. The spectral range of 1790-283 cm-1 was used in the case of multivariate data analysis. A green-pea adulteration level of 5-80% (w/w) was successfully identified by PLSR and GILS. The correlation coefficient of determination (R2 ) was determined as 0.91 and 0.94 for the PLSR and GILS analyses, respectively. A Raman spectrometer combined with chemometrics has a high capability with regard to the detection of adulteration in pistachio nuts, combined with low cost, strong reliability, a high level of accuracy, rapidity of analysis, and minimum sample preparation. © 2020 Society of Chemical Industry.


Association of calprotectin with leukocyte chemotactic and inflammatory mediators following acute aerobic exercise.
The objective of this study was to examine whether acute aerobic exercise-mediated calprotectin in plasma would be associated with monocyte chemotactic protein-1 (MCP-1), myeloperoxidase (MPO), and interleukin-6 (IL-6) in healthy individuals. Eleven healthy participants, aged 18 to 30 years, were recruited to perform a 30-min bout of aerobic exercise at 75% maximal oxygen uptake. Acute aerobic exercise elicited a significant elevation across time in plasma calprotectin, MCP-1, MPO, and IL-6. Body mass index (BMI) was positively correlated with calprotectin area-under-the-curve with "respect to increase" (AUCi) and IL-6 AUCi. Furthermore, calprotectin AUCi was positively correlated with IL-6 AUCi and MPO AUCi, even after controlling for BMI. Although MPO AUCi was positively correlated with IL-6 AUCi, this relationship no longer existed after controlling for BMI. These results suggest that acute aerobic exercise could mediate innate immune response associated with calprotectin and its related leukocyte chemotactic and inflammatory mediators, especially in individuals with elevated BMI.


The effects of sleep extension on the athletic performance of collegiate basketball players.
To investigate the effects of sleep extension over multiple weeks on specific measures of athletic performance as well as reaction time, mood, and daytime sleepiness. Stanford Sleep Disorders Clinic and Research Laboratory and Maples Pavilion, Stanford University, Stanford, CA. Eleven healthy students on the Stanford University men's varsity basketball team (mean age 19.4 ± 1.4 years). Subjects maintained their habitual sleep-wake schedule for a 2-4 week baseline followed by a 5-7 week sleep extension period. Subjects obtained as much nocturnal sleep as possible during sleep extension with a minimum goal of 10 h in bed each night. Measures of athletic performance specific to basketball were recorded after every practice including a timed sprint and shooting accuracy. Reaction time, levels of daytime sleepiness, and mood were monitored via the Psychomotor Vigilance Task (PVT), Epworth Sleepiness Scale (ESS), and Profile of Mood States (POMS), respectively. Total objective nightly sleep time increased during sleep extension compared to baseline by 110.9 ± 79.7 min (P < 0.001). Subjects demonstrated a faster timed sprint following sleep extension (16.2 ± 0.61 sec at baseline vs. 15.5 ± 0.54 sec at end of sleep extension, P < 0.001). Shooting accuracy improved, with free throw percentage increasing by 9% and 3-point field goal percentage increasing by 9.2% (P < 0.001). Mean PVT reaction time and Epworth Sleepiness Scale scores decreased following sleep extension (P < 0.01). POMS scores improved with increased vigor and decreased fatigue subscales (P < 0.001). Subjects also reported improved overall ratings of physical and mental well-being during practices and games. Improvements in specific measures of basketball performance after sleep extension indicate that optimal sleep is likely beneficial in reaching peak athletic performance.


Surgical treatment of axillary accessory breasts.
Accessory breast tissue is a remnant persisting after normal embryological development of the breast. Although accessory breasts may be asymptomatic, they can cause discomfort during menstruation, anxiety, cosmetic problems, pain, or restriction of arm movement. The data of all patients who presented with axillary accessory breasts between January 2000 and September 2008 were recruited from a computer database. Medical charts, outpatient records, operative notes, and pathology reports were reviewed. A total of 29 patients underwent surgical treatment of axillary accessory breasts in the Department of Breast Surgery and Department of Plastic, Reconstructive and Aesthetic Surgery. The ages of the patients at the time of surgery ranged from 19 to 54 years. The mean age was 28.8 years. All patients were female. Sixteen patients had unilateral accessory breast and 13 patients had bilateral accessory breasts. Fourteen patients had breast hypertrophy. Twenty-one patients had excision, five patients had liposuction, and three patients had both. Axillary accessory breasts can be satisfactorily treated with excision, liposuction, or both. In patients with concomitant macromastia, reduction mammaplasty and removal of accessory breasts can be performed at the same time with no additional morbidity.


Low-level shRNA cytotoxicity can contribute to MYC-induced hepatocellular carcinoma in adult mice.
Short hairpin RNAs (shRNAs) have emerged as a novel therapeutic modality, but there is increasing concern over nonspecific effects in vivo. Here, we used viral vectors to express shRNAs against endogenous p53 in livers of conditional MYC-transgenic mice. As expected, the shRNAs silenced hepatic p53 and accelerated liver tumorigenesis when MYC was concurrently expressed. Surprisingly, various irrelevant control shRNAs similarly induced a rapid onset of tumorigenesis, comparable to carbon tetrachloride (CCl4), a potent carcinogen. We found that even marginal shRNA doses can already trigger histologically detectable hepatoxicity and increased hepatocyte apoptosis. Moreover, we noted that shRNA expression globally dysregulated hepatic microRNA (miRNA) expression, and that shRNA levels and activity further increased in the presence of MYC. In MYC-expressing transgenic mice, the marginal shRNA-induced liver injury sufficed to further stimulate hepatocellular division that was in turn associated with markedly increased expression of the mitotic cyclin B1. Hence, even at low doses, shRNAs can cause low-level hepatoxicity that can facilitate the ability of the MYC oncogene to induce liver tumorigenesis. Our data warrant caution regarding the possible carcinogenic potential of shRNAs when used as clinical agent, particularly in circumstances where tissues are genetically predisposed to cellular transformation and proliferation.


Anxiety and depression among caregivers of young children with Congenital Zika Syndrome in Brazil.
To examine the psychological well-being of primary caregivers of infants and toddlers with Congenital Zika Syndrome (CZS), and the roles of family resources, parenting stress, and coping strategies in caregivers' adaptation. Family caregivers (N = 50) of children with CZS who were receiving treatment at a rehabilitation hospital in Recife, Brazil participated a cross-sectional survey study. Caregivers completed measures of anxiety and depression, coping strategies, family resources, and parenting stress. Mild to severe symptoms of depression were identified in 40% of caregivers and were a more prominent concern than symptoms of anxiety. Fewer family resources and high levels of parenting stress were significantly associated with both anxiety and depression. The association between parenting stress and depression was moderated by coping, such that parenting stress was associated with higher caregiver depression at low but not high levels of coping strategy use. Practitioners in Brazil should consider the role of family coping and resources as important resilience promoting factors in the development of new programs designed to promote psychological adaptation in caregivers to children with CZS. It is recommended that caregiver mental health support services be integrated into existing early intervention programs targeting children with CZS.Implications for RehabilitationParents and other primary caregivers are encouraged to take an active role in the care and developmental monitoring of children born with CZS, but their ability to provide care may be compromised by difficulties in psychological adaptation.Moderate and severe symptoms of depression were more prominent in caregivers than moderate and severe symptoms of anxiety (20% versus 6%, respectively).Practitioners should include assessment of coping strategies, parenting stress and family resources conjointly with evaluation of symptoms of depression and anxiety as part of routine CZS family evaluations.A useful approach for caregivers in Brazil may be to more fully integrate caregiver mental health support services into existing early intervention programs for children with CZS.


Transcranial Direct Current Stimulation and Visual Illusion Effect According to Sensory Phenotypes in Patients With Spinal Cord Injury and Neuropathic Pain.
Treatment of neuropathic pain (NP) in patients with spinal cord injury (SCI) remains a major challenge. The aim of the present study is to investigate if the effect of transcranial direct current stimulation combined with visual illusion, following a previously published protocol, has differential effects on pain-related sensory symptoms according to sensory phenotypes profiles. One hundred and thirty SCI patients with NP participated in this open-label trial. Sixty-five patients were given a daily 20-minutes combined treatment of transcranial direct current stimulation and visual illusion for 2 weeks. Sixty-five patients served as a control group. Clinical assessment was performed before and 2 weeks later, by using Neuropathic Pain Symptom Inventory (NPSI), Brief Pain Inventory, and Patient Health Questionnaire-9. There was significant improvement in the combined treatment group according to NPSI, Brief Pain Inventory, and Patient Health Questionnaire-9, but no changes in the control group. Following a cluster analysis of NPSI items at baseline assessment, 5 subgroups of patients with different pain-related characteristics were identified among the treated group, although differences between clusters were not significant. There was also improvement in mood, sleep quality, and enjoyment of life in the treated group. Despite a reduction of NP with the combined treatment, the analysis of sensory phenotype pain profiles does not provide a predictive value regarding the analgesic results of this combined neuromodulatory treatment. PERSPECTIVE: In this article we confirm the analgesic effect of a combined neuromodulatory therapy, transcranial direct current stimulation associated with visual illusion in patients with NP after an SCI. We have identified 5 clusters of NP with distinct sensory phenotypes, but there was not any specific sensory phenotype cluster that significantly responded to the combined therapy better than the other.


Predictive Performance of a Recently Developed Population Pharmacokinetic Model for Morphine and its Metabolites in New Datasets of (Preterm) Neonates, Infants and Children.
Model validation procedures are crucial when models are to be used to develop new dosing algorithms. In this study, the predictive performance of a previously published paediatric population pharmacokinetic model for morphine and its metabolites in children younger than 3 years (original model) is studied in new datasets that were not used to develop the original model. Six external datasets including neonates and infants up to 1 year were obtained from four different research centres. These datasets contained postoperative patients, ventilated patients and patients on extracorporeal membrane oxygenation (ECMO) treatment. Basic observed versus predicted plots, normalized prediction distribution error analysis, model refitting, bootstrap analysis, subpopulation analysis and a literature comparison of clearance predictions were performed with the new datasets to evaluate the predictive performance of the original morphine pharmacokinetic model. The original model was found to be stable and the parameter estimates were found to be precise. The concentrations predicted by the original model were in good agreement with the observed concentrations in the four datasets from postoperative and ventilated patients, and the model-predicted clearances in these datasets were in agreement with literature values. In the datasets from patients on ECMO treatment with continuous venovenous haemofiltration (CVVH) the predictive performance of the model was good as well, whereas underprediction occurred, particularly for the metabolites, in patients on ECMO treatment without CVVH. The predictive value of the original morphine pharmacokinetic model is demonstrated in new datasets by the use of six different validation and evaluation tools. It is herewith justified to undertake a proof-of-principle approach in the development of rational dosing recommendations - namely, performing a prospective clinical trial in which the model-based dosing algorithm is clinically evaluated.


Evidence-based medicine for occupational health.
This study attempted to determine the feasibility and utility of methods used in evidence-based medicine for some common questions in the practice of occupational medicine. The following clinical questions were generated that were representative of the type of problems encountered by occupational health physicians: is work a cause of health problems and is impaired health a cause of diminished work capacity for a specific job? Answers were generated according to the method used in evidence-based medicine by formulating an answerable question, searching the literature, critically appraising the results, and applying the results to the clinical question. Answers were found to all the questions in a reasonable amount of time. The searches revealed a need for more systematic reviews and studies that use work-related health outcomes like return to work. However, there is more evidence available in Medline than is generally assumed by occupational health physicians. Using this evidence led to better clinical decisions. Pitfalls during the literature search were typing mistakes, problems in using medical subject headings, and unreliable search strategies. With the use of the abstracts only, most clinical questions could be answered satisfactorily, but concrete risk estimates were often lacking. The lack of availability of full text journals decreased the reliability of the critical appraisal and risk estimation. Evidence-based medicine is a feasible and useful method for occupational medicine. Instruction and training is needed for most occupational health physicians to increase their searching and critical appraisal skills. More research is needed to determine the information needs of occupational health physicians and to develop tools that facilitate literature searches.


The oncogenic transcription factor IRF4 is regulated by a novel CD30/NF-κB positive feedback loop in peripheral T-cell lymphoma.
Peripheral T-cell lymphomas (PTCLs) are generally aggressive non-Hodgkin lymphomas with poor overall survival rates following standard therapy. One-third of PTCLs express interferon regulatory factor-4 (IRF4), a tightly regulated transcription factor involved in lymphocyte growth and differentiation. IRF4 drives tumor growth in several lymphoid malignancies and has been proposed as a candidate therapeutic target. Because direct IRF4 inhibitors are not clinically available, we sought to characterize the mechanism by which IRF4 expression is regulated in PTCLs. We demonstrated that IRF4 is constitutively expressed in PTCL cells and drives Myc expression and proliferation. Using an inhibitor screen, we identified nuclear factor κB (NF-κB) as a candidate regulator of IRF4 expression and cell proliferation. We then demonstrated that the NF-κB subunits p52 and RelB were transcriptional activators of IRF4. Further analysis showed that activation of CD30 promotes p52 and RelB activity and subsequent IRF4 expression. Finally, we showed that IRF4 transcriptionally regulates CD30 expression. Taken together, these data demonstrate a novel positive feedback loop involving CD30, NF-κB, and IRF4; further evidence for this mechanism was demonstrated in human PTCL tissue samples. Accordingly, NF-κB inhibitors may represent a clinical means to disrupt this feedback loop in IRF4-positive PTCLs.


Hookworms Make Us Human: The Microbiome, Eco-immunology, and a Probiotic Turn in Western Health Care.
Historians of science have identified an ecological turn underway in immunology, driven by the mapping of the human microbiome and wider environmentalist anxieties. A figure is emerging of the human as a holobiont, composed of microbes and threatened by both microbial excess and microbial absence. Antimicrobial approaches to germ warfare are being supplemented by probiotic approaches to restoring microbial life. This article examines the political ecology of this probiotic turn in Western health care. It focuses on Necator americanus-a species of human hookworm-and its relations with immunologists. The analysis moves from a history of human disentanglement from hookworm, to contemporary anxieties about their absence. It examines the reintroduction of worms for helminthic therapy and explores emerging trajectories for probiotic health care involving the synthesis, modification, and/or restoration of worms and their salutary ecologies. The conclusion differentiates these trajectories and identifies an emerging model of "post-paleo" microbiopolitics.


Insulin granule dynamics in pancreatic beta cells.
Glucose-induced insulin secretion in response to a step increase in blood glucose concentrations follows a biphasic time course consisting of a rapid and transient first phase followed by a slowly developing and sustained second phase. Because Type 2 diabetes involves defects of insulin secretion, manifested as a loss of first phase and a reduction of second phase, it is important to understand the cellular mechanisms underlying biphasic insulin secretion. Insulin release involves the packaging of insulin in small (diameter approximately 0.3 micro m) secretory granules, the trafficking of these granules to the plasma membrane, the exocytotic fusion of the granules with the plasma membrane and eventually the retrieval of the secreted membranes by endocytosis. Until recently, studies on insulin secretion have been confined to the appearance of insulin in the extracellular space and the cellular events preceding exocytosis have been inaccessible to more detailed analysis. Evidence from a variety of secretory tissues, including pancreatic islet cells suggests, however, that the secretory granules can be functionally divided into distinct pools that are distinguished by their release competence and/or proximity to the plasma membrane. The introduction of fluorescent proteins that can be targeted to the secretory granules, in combination with the advent of new techniques that allow real-time imaging of granule trafficking in living cells (granule dynamics), has led to an explosion of our knowledge of the pre-exocytotic and post-exocytotic processes in the beta cell. Here we discuss these observations in relation to previous functional and ultra-structural data as well as the secretory defects of Type 2 diabetes.


Treatment of hospitalized adult patients with severe ulcerative colitis: Toronto consensus statements.
The objective of this study was to provide updated explicit and relevant consensus statements for clinicians to refer to when managing hospitalized adult patients with acute severe ulcerative colitis (UC). The Canadian Association of Gastroenterology consensus group of 23 voting participants developed a series of recommendation statements that addressed pertinent clinical questions. An iterative voting and feedback process was used to do this in conjunction with systematic literature reviews. These statements were brought to a formal consensus meeting held in Toronto, Ontario (March 2010), when each statement was discussed, reformulated, voted upon, and subsequently revised until group consensus (at least 80% agreement) was obtained. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. As a result of the iterative process, consensus was reached on 21 statements addressing four themes (General considerations and nutritional issues, Steroid use and predictors of steroid failure, Cyclosporine and infliximab, and Surgical issues). Key recommendations for the treatment of hospitalized patients with severe UC include early escalation to second-line medical therapy with either infliximab or cyclosporine in individuals in whom parenteral steroids have failed after 72 h. These agents should be used in experienced centers where appropriate support is available. Sequential therapy with cyclosporine and infliximab is not recommended. Surgery is an option when first-line steroid therapy fails, and is indicated when second-line medical therapy fails and/or when complications arise during the hospitalization.


Low salivary cortisol levels and externalizing behavior problems in youth.
Research linking basal cortisol levels with internalizing and externalizing behavior problems in youths has yielded inconsistent results. We hypothesize that the high moment to moment variation in adrenocortical activity requires an analytical strategy that separates variance in cortisol levels attributable to "stable traitlike" versus "state or situationally specific" sources. Early morning saliva samples were obtained from 724 youths (M age = 13.5 years; range = 6-16 years in Year 1) on 2 successive days 1 year apart. Latent state-trait modeling revealed that 70% of the variance in cortisol levels could be attributed to statelike sources, and 28% to traitlike sources. For boys only, higher levels of externalizing problem behaviors were consistently associated with lower cortisol attributable to traitlike sources across 3 years of behavioral assessment. The inverse association between individual differences in cortisol and externalizing problem behavior has previously only been reported in studies of at-risk or clinical groups. The present findings suggest the relationship is a stable phenomenon that spans both normative and atypical child development. Studies are needed to reveal the biosocial mechanisms involved in the establishment and maintenance of this phenomenon, and to decipher whether individual differences in this hormone-behavior link confers risk or resilience.


The characteristics of the pressure waves generated in the soft target by impact and its contribution to indirect bone fractures.
When a high-velocity spherical fragment impacts a biological body, it will initiate strong pressure waves spreading throughout the body. A pressure wave, especially a shock wave with a steep front, generated by impact, may cause blood vessel injuries, viscera injuries, and indirect bone fractures. This paper reports research on pressure waves near the wound tracks, generated by spherical fragments, and calculates the zones of indirect bone fractures generated by pressure waves of impact.


Addressing the neglected tropical disease podoconiosis in Northern Ethiopia: lessons learned from a new community podoconiosis program.
Despite its great public health importance, few control initiatives addressing podoconiosis (non-filarial elephantiasis, a geochemical neglected tropical disease) exist. In June 2010, the first podoconiosis program in Northern Ethiopia, consisting of prevention, awareness, and care and support activities, began in Debre Markos, Northern Ethiopia. This study aims to document and disseminate the lessons learned from a new community podoconiosis program in Debre Markos. We used a content analysis approach to examine and evaluate data from a series of sources. These sources include conducted interview transcripts, a focus group discussion transcript and secondary sources including monitoring and evaluation field reports, observation notes, and research obtained from a literature review. Themes were identified and grouped into matrix tables. Overall, sixteen program steps were identified and grouped into 6 domains: Initial preparation, training and sensitization, foundation building, treatment activity implementation, awareness, and follow-up. Emphasis is placed on the need for baseline data, effective training, local leadership, experience-sharing, mass-awareness, cross-cutting sector issues (i.e., water and waste management), and integration with government health systems. Related successes and challenges are also described, as are stakeholder roles and misconceptions and socio-cultural challenges affecting the program start-up. Many of the identified successes and challenges are relevant to the aim of the podoconiosis program to be sustainable and community-led. Much of this information has already been used to improve the Debre Markos program. We also anticipate that the domains and steps identified will be useful in guiding new programs in other settings where podoconiosis is highly prevalent. We hope to encourage partnerships and collaboration among podoconiosis stakeholders in future growth and disease control expansion.


Software-based respiratory gating for small animal conebeam CT.
In volumetric CT imaging of small animals, the breathing motion of the lungs during the image acquisition process results in inconsistent projection data being acquired. When reconstructed, these inconsistent data may produce images with reduced spatial resolution and image contrast. In order to minimize these effects, various approaches have been utilized to capture the respiratory signal of the animals under study and to only obtain CT data at specific moments in the respiratory cycle. These approaches typically utilize hardware-based physiological monitoring equipment in order to record the respiratory signal and either prospectively or retrospectively correlate this signal with acquired CT projection data. In this work, a new method of CT respiratory gating is described that does not rely on external physiological monitoring. Rather, determination of the respiratory phase of the animal is performed by postprocessing the acquired projection data. With this approach, any CT projection data can be respiratory gated with minimal effort. Validation of the method has been performed using a dynamic phantom and accuracy in tidal volumes determined to be within 16%. Rats and mice have been scanned and processed using the proposed method and compared to physiological-based measurement. With the proposed method, image quality is significantly improved in addition to providing quantitative information regarding tidal lung volumes.


TLN-4601 suppresses growth and induces apoptosis of pancreatic carcinoma cells through inhibition of Ras-ERK MAPK signaling.
TLN-4601 is a structurally novel farnesylated dibenzodiazepinone discovered using Thallion's proprietary DECIPHER® technology, a genomics and bioinformatics platform that predicts the chemical structures of secondary metabolites based on gene sequences obtained by scanning bacterial genomes. Our recent studies suggest that TLN-4601 inhibits the Ras-ERK MAPK pathway post Ras prenylation and prior to MEK activation. The Ras-ERK MAPK signaling pathway is a well-validated oncogenic cascade based on its central role in regulating the growth and survival of cells from a broad spectrum of human tumors. Furthermore, RAS isoforms are the most frequently mutated oncogenes, occurring in approximately 30% of all human cancers, and KRAS is the most commonly mutated RAS gene, with a greater than 90% incidence of mutation in pancreatic cancer. To evaluate whether TLN-4601 interferes with K-Ras signaling, we utilized human pancreatic epithelial cells and demonstrate that TLN-4601 treatment resulted in a dose- and time-dependent inhibition of Ras-ERK MAPK signaling. The compound also reduced Ras-GTP levels and induced apoptosis. Finally, treatment of MIA PaCa-2 tumor-bearing mice with TLN-4601 resulted in antitumor activity and decreased tumor Raf-1 protein levels. These data, together with phase I/II clinical data showing tolerability of TLN-4601, support conducting a clinical trial in advanced pancreatic cancer patients.


Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats.
Dopaminergic signaling has long been known to be a critical factor in nicotine addiction, as well as other drugs of abuse. Dopaminergic projections from the VTA to the nucleus accumbens and prefrontal cortex have been well established to be critical to the reinforcing effects of these drugs. However, other projections of dopamine neurons are likely to have significant roles in this process. Also, the relative contributions of D1 and D2 dopamine receptors in drug addiction and its treatment remain to be fully understood. In this study, we examined the effects of blocking D1 and D2 receptors in the nucleus accumbens shell (AcS), anterior cingulate cortex (ACC), and parietal association cortex (PtA) on nicotine self-administration in rats. Female Sprague-Dawley rats were fitted with jugular catheters and allowed to self-administer nicotine (0.03 mg/kg/infusion) on an FR1 schedule. Rats were fitted with bilateral infusion cannulae to allow infusion of D1 or D2 antagonists (SCH-23390 or haloperidol) into each targeted brain area. Acute local infusions of SCH-23390 (1-4 μg/side) into the AcS and PtA significantly reduced nicotine self-administration by up to 75%. SCH-23390 infusion into the ACC was less effective with only suggestive non-significant reductions of nicotine self-administration. Acute, local infusions of haloperidol (0.5-2 μg/side) in any of the brain regions targeted did not have significant effects on nicotine self-administration. These results demonstrate a more significant role for D1 receptor mechanisms in the process of nicotine reinforcement and help provide a more detailed neuroanatomic map of nicotine dependence in the brain.


Variability in muscle dysmorphia symptoms: the influence of weight training.
The purpose of this study was to examine the influence of a weight training session on muscle dysmorphia symptoms in young men who regularly weight trained. Using a within-subjects crossover design, 30 men (mean ± SD; 20.93 ± 2.60 years, 86.87 ± 10.59 kg, and 1.76 ± 0.01 m) were randomly allocated to 1 of 2 groups, and completed the Muscle Dysmorphic Disorder Inventory twice, once each on 2 separate days. One day 1, group 1 completed the questionnaire after a weight training session and group 2 on a rest day. One day 2, group 1 completed the questionnaire on a rest day and group 2 after a weight training session. The mean score for drive for size was significantly higher on a rest day (18.00) than on a training day (15.87; p = 0.001, d = 1.03). The mean score for appearance intolerance was significantly higher on a rest day (10.10) compared with that on a training day (8.97; p = 0.001, d = 0.69). The mean score for functional impairment was significantly higher on a rest day (10.20) than on a training day (9.47; p = 0.037, d = 0.40). These results provide evidence that muscle dysmorphia symptoms have state-like properties and may be influenced by situational variables. The results may indicate that strength and conditioning specialists and mental health professionals need to observe clients over time and take into account environmental variables before making decisions about the presence or absence of the condition.


Integrated experimental and theoretical approach to probe the synergistic effect of ammonia in methanesulfonic acid reactions with small alkylamines.
While new particle formation events have been observed worldwide, our fundamental understanding of the precursors remains uncertain. It has been previously shown that small alkylamines and ammonia (NH3) are key actors in sub-3 nm particle formation through reactions with acids such as sulfuric acid (H2SO4) and methanesulfonic acid (CH3S(O)(O)OH, MSA), and that water also plays a role. Because NH3 and amines co-exist in air, we carried out combined experimental and theoretical studies examining the influence of the addition of NH3 on particle formation from the reactions of MSA with methylamine (MA) and trimethylamine (TMA). Experiments were performed in a 1 m flow reactor at 1 atm and 296 K. Measurements using an ultrafine condensation particle counter (CPC) and a scanning mobility particle sizer (SMPS) show that new particle formation was systematically enhanced upon simultaneous addition of NH3 to the MSA + amine binary system, with the magnitude depending on the amine investigated. For the MSA + TMA reaction system, the addition of NH3 at ppb concentrations produced a much greater effect (i.e. order of magnitude more particles) than the addition of ∼12 000 ppm water (corresponding to ∼45-50% relative humidity). The effect of NH3 on the MSA + MA system, which is already very efficient in forming particles on its own, was present but modest. Calculations of energies, partial charges and structures of small cluster models of the multi-component particles likewise suggest synergistic effects due to NH3 in the presence of MSA and amine. The local minimum structures and the interactions involved suggest mechanisms for this effect.


Design of a complex filter for depth of focus extension.
Different methods such as axilens and binary-phase filter have been investigated to improve the depth of focus. A method is proposed to calculate an amplitude-phase pupil filter and obtain the desired distribution of intensity along the optical axis. It produces a narrow spot with a uniform intensity level over a large depth of focus, comparable to the performance obtainable with binary-phase filters. This filter is of particular interest for applications where very low intensity fluctuations along the focus range are required.


Analysis of the percentages of monocyte subsets and ILC2s, their relationships with metabolic variables and response to hypocaloric restriction in obesity.
Obesity results from excess energy intake over expenditure and is characterized by chronic low-grade inflammation involving circulating monocytes (Mo) and group 2 innate lymphoid cells (ILC2s) imbalance. We analyzed circulating Mo subsets and ILC2s percentages and β2-adrenergic receptor (β2AR) expression in lean and obese subjects, and the possible effect of hypocaloric restriction on these innate immune cells. In 139 individuals aged 45 to 57 years, classified in 74 lean individuals (>18.9kg/m2 BMI <24.9kg/m2) and 65 with obesity (n = 65), we collected fasting blood samples to detect Mo subsets, ILC2s number, and β2AR expression by flow cytometry. Lipids, insulin, leptin, and acylated-ghrelin concentrations were quantified. Resting energy expenditure (REE) was estimated by indirect calorimetry. These measurements were repeated in obese subjects after 7-weeks of hypocaloric restriction. Non-classical monocytes (NCM) and β2AR expression on intermediate Mo (IM) were increased in obese individuals (p<0.001, in both cases), whereas the percent of ILC2s was decreased (p<0.0001). Stepwise regression analysis showed significantly negative associations of ILC2s with caloric intake, β2AR expression on IM with REE, but a positive relationship between NCM and HOMA-IR. Caloric restriction allowed a significant diminution of NCM and the β2AR expression on IM, as well as, an increase in the percent of classical Mo (CM), and ILC2s. ΔREE was related to ΔCD16+/CD16- ratio. These findings show that in obesity occur changes in NCM, ILC2s and β2AR expression, which contribute to the low-grade inflammation linked to obesity and might revert with caloric restriction.


Acinetodin and Klebsidin, RNA Polymerase Targeting Lasso Peptides Produced by Human Isolates of Acinetobacter gyllenbergii and Klebsiella pneumoniae.
We report the bioinformatic prediction and structural validation of two lasso peptides, acinetodin and klebsidin, encoded by the genomes of several human-associated strains of Acinetobacter and Klebsiella. Computation of the three-dimensional structures of these peptides using NMR NOESY constraints verifies that they contain a lasso motif. Despite the lack of sequence similarity to each other or to microcin J25, a prototypical lasso peptide and transcription inhibitor from Escherichia coli, acinetodin and klebsidin also inhibit transcript elongation by the E. coli RNA polymerase by binding to a common site. Yet, unlike microcin J25, acinetodin and klebsidin are unable to permeate wild type E. coli cells and inhibit their growth. We show that the E. coli cells become sensitive to klebsidin when expressing the outer membrane receptor FhuA homologue from Klebsiella pneumoniae. It thus appears that specificity to a common target, the RNA polymerase secondary channel, can be attained by a surprisingly diverse set of primary sequences folded into a common threaded-lasso fold. In contrast, transport into cells containing sensitive targets appears to be much more specific and must be the major determinant of the narrow range of bioactivity of known lasso peptides.


The current status of animal use and alternatives in Korean veterinary medical schools.
Two new Korean laws regulating animal welfare and the humane use of animals in science came into effect in 2008 and 2009. Both these laws impose ethical committee review prior to the performance of animal experiments in research, testing and education. This study briefly summarises the new Korean laws, and investigates the current status regarding the numbers of animals used, the alternatives to animals which are used, the curricula relating to the humane use of animals, and ethical review practices in Korean veterinary education. Approximately 4,845 animals, representing 20 different species, were used in veterinary medical education in Korea in 2007. Korea has begun to introduce formal courses on animal welfare for the humane treatment of animals used in experiments, and an ethical protocol review system prior to animal use in education. Korea is moving toward better animal welfare, by incorporating practices consistent with international standards. The information presented represents the first such data gathered in Korea, which should prove useful for monitoring the implementation of replacement, reduction, and refinement measures in animal use for education purposes.


Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.
Despite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.


Isolation of serotype-specific antibodies against dengue virus non-structural protein 1 using phage display and application in a multiplexed serotyping assay.
The multidimensional nature of dengue virus (DENV) infections, which can be caused by four distinct serotypes of the virus, complicates the sensitivity of assays designed for the diagnosis of infection. Different viral markers can be optimally detected at different stages of infection. Of particular clinical importance is the early identification of infection, which is pivotal for disease management and the development of blood screening assays. Non-structural protein 1 (NS1) is an early surrogate marker of infection and its detection in serum coincides with detectable viraemia. The aim of this work was to isolate and characterise serotype-specific monoclonal antibodies that bind to NS1 for each of the four DENV serotypes. This was achieved using phage display and a subtractive biopanning strategy to direct the antibody selection towards serotype-specific epitopes. This antibody isolation strategy has advantages over immunisation techniques where it is difficult to avoid antibody responses to cross-reactive, immunodominant epitopes. Serotype specificity to recombinant antigen for each of the antibodies was confirmed by Enzyme Linked Immunosorbent Assay (ELISA) and Surface Plasmon Resonance. Confirmation of binding to native DENV NS1 was achieved using ELISA and immunofluorescence assay on DENV infected Vero cells. No cross-reactivity with Zika or Kunjin viruses was observed. A previously isolated pan-reactive antibody that binds to an immunodominant epitope was able to pair with each of the serotype-specific antibodies in a sandwich ELISA, indicating that the serotype specific antibodies bind to epitopes which are all spatially distinct from the immunodominant epitope. These antibodies were suitable for use in a multiplexed assay for simultaneous detection and serotyping of DENV NS1 in human serum. This work demonstrates that phage display coupled with novel biopanning strategies is a valuable in vitro methodology for isolation of binders that can discern amongst antigens with high homology for diagnostic applicability.


Evaluation of organ sparing surgery results in patients with kidney cancer in scheduled operations.
The aim of the study was retrospective analysis of nephron-sparing surgery results of 53 patients, performed due to unilateral small kidney tumors in the period of 1988-1998. The patients were followed-up according to EORTC directions for 20 to 143 months after the surgery. We have treated 25 women and 28 men of the average age of 53.7. In ten patients partial nephrectomy was performed and the remaining 43 had the tumor enucleated. The average observation time without any recurrences and metastases was 63.8 months, in 5.7% of patients local disease related recurrences and in 1.9% remote recurrences have been found. 1. Nephron-sparing surgery is a safe alternative to radical surgery in tumors of up to 4 cm in diameter. 2. Prospective 10-year survival time in our patients was 98%, including 92% of patients remaining without recurrence or metastases. 3. Positive prognostic factors are incidental diagnosis of a tumor and low staging and grading of a tumor.


Nasal-associated lymphoid tissue and olfactory epithelium as portals of entry for Burkholderia pseudomallei in murine melioidosis.
Burkholderia pseudomallei, the causative agent of melioidosis, is generally considered to be acquired via inhalation of dust or water droplets from the environment. In this study, we show that infection of the nasal mucosa is potentially an important portal of entry in melioidosis. After intranasal inoculation of mice, infection was monitored by bioluminescence imaging and by immunohistological analysis of coronal sections. The bacterial loads in organ and tissue specimens were also monitored. Bioluminescence imaging showed colonization and replication in the nasal cavity, including the nasal-associated lymphoid tissue (NALT). Analysis of coronal sections and immunofluorescence microscopy further demonstrated the presence of infection in the respiratory epithelium and the olfactory epithelium (including associated nerve bundles), as well as in the NALT. Of significance, the olfactory epithelium and the brain were rapidly infected before bacteria were detected in blood, and a capsule-deficient mutant infected the brain without significantly infecting blood. These data suggest that the olfactory nerve is the route of entry into the brain and that this route of entry may be paralleled in cases of human neurologic melioidosis. This study focuses attention on the upper respiratory tract as a portal of entry, specifically focusing on NALT as a route for the development of systemic infection via the bloodstream and on the olfactory epithelium as a direct route to the brain.


Caseload midwifery care versus standard maternity care for women of any risk: M@NGO, a randomised controlled trial.
Women at low risk of pregnancy complications benefit from continuity of midwifery care, but no trial evidence exists for women with identified risk factors. We aimed to assess the clinical and cost outcomes of caseload midwifery care for women irrespective of risk factors. In this unblinded, randomised, controlled, parallel-group trial, pregnant women at two metropolitan teaching hospitals in Australia were randomly assigned to either caseload midwifery care or standard maternity care by a telephone-based computer randomisation service. Women aged 18 years and older were eligible if they were less than 24 weeks pregnant at the first booking visit. Those who booked with another care provider, had a multiple pregnancy, or planned to have an elective caesarean section were excluded. Women allocated to caseload care received antenatal, intrapartum, and postnatal care from a named caseload midwife (or back-up caseload midwife). Controls received standard care with rostered midwives in discrete wards or clinics. The participant and the clinician were not masked to assignment. The main primary outcome was the proportion of women who had a caesarean section. The other primary maternal outcomes were the proportions who had an instrumental or unassisted vaginal birth, and the proportion who had epidural analgesia during labour. Primary neonatal outcomes were Apgar scores, preterm birth, and admission to neonatal intensive care. We analysed all outcomes by intention to treat. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12609000349246. Publicly insured women were screened at the participating hospitals between Dec 8, 2008, and May 31, 2011. 1748 pregnant women were randomly assigned, 871 to caseload and 877 to standard care. The proportion of caesarean sections did not differ between the groups (183 [21%] in the caseload group vs 204 [23%] in the standard care group; odds ratio [OR] 0·88, 95% CI 0·70-1·10; p=0·26). The proportion of women who had elective caesarean sections (before onset of labour) differed significantly between caseload and standard care (69 [8%] vs 94 [11%]; OR 0·72, 95% CI 0·52-0·99; p=0·05). Proportions of instrumental birth were similar (172 [20%] vs 171 [19%]; p=0·90), as were the proportions of unassisted vaginal births (487 [56%] vs 454 [52%]; p=0·08) and epidural use (314 [36%] vs 304 [35%]; p=0·54). Neonatal outcomes did not differ between the groups. Total cost of care per woman was AUS$566·74 (95% 106·17-1027·30; p=0·02) less for caseload midwifery than for standard maternity care. Our results show that for women of any risk, caseload midwifery is safe and cost effective. National Health and Medical Research Council (Australia).


Development and use of sulodexide in vascular diseases: implications for treatment.
Sulodexide (SDX), a sulfated polysaccharide complex extracted from porcine intestinal mucosa, is a blend of two glycosaminoglycan (GAG) entities, namely a fast-moving heparin (HP) fraction and a dermatan sulfate (DS; 20%) component. The compound is unique among HP-like substances in that it is biologically active by both the parenteral and oral routes. A main feature of the agent is to undergo extensive absorption by the vascular endothelium. For this reason, in preclinical studies, SDX administered parenterally displays an antithrombotic action similar to that of HPs but associated with fewer alterations of the blood clotting mechanisms and tests, thus being much less conducive to bleeding risk than HPs. When given orally, SDX is associated with minimal changes in classic coagulation tests, but maintains a number of important effects on the structure and function of endothelial cells (EC), and the intercellular matrix. These activities include prevention or restoration of the integrity and permeability of EC, counteraction versus chemical, toxic or metabolic EC injury, regulation of EC-blood cell interactions, inhibition of microvascular inflammatory and proliferative changes, and other similar effects, thus allowing oral SDX to be considered as an endothelial-protecting agent. The best available clinical evidence of the efficacy of SDX administered orally with or without an initial parenteral phase is the following: alleviation of symptoms in chronic venous disease and especially acceleration of healing of venous leg ulcers; prevention of cardiovascular events in survivors after acute myocardial infarction; marked improvement of intermittent claudication in patients with peripheral occlusive arterial disease; and abatement of proteinuria in patients with diabetic nephropathy that may contribute to the amelioration or stabilization of kidney function. Although further clinical trials are warranted, SDX is presently widely accepted in many countries as an effective and safe long-term, endothelial-protecting drug.


The evolution of the frontal lobes: a volumetric analysis based on three-dimensional reconstructions of magnetic resonance scans of human and ape brains.
Scenarios regarding the evolution of cognitive function in hominids depend largely on our understanding of the organization of the frontal lobes in extant humans and apes. The frontal lobe is involved in functions such as creative thinking, planning of future actions, decision making, artistic expression, aspects of emotional behavior, as well as working memory, language and motor control. It is often claimed that the frontal lobe is disproportionately larger in humans than in other species, but conflicting reports exist on this issue. The brain of the apes in particular remains largely unknown. In this report we measure the volume of the frontal lobe as a whole and of its main sectors (including cortex and immediately underlying white matter) in living humans, and in post-mortem brains of the chimpanzee, gorilla, orang-utan, gibbon and the macaque using three-dimensional reconstructions of magnetic resonance (MR) scans of the brain. On the basis of these data we suggest that although the absolute volume of the brain and the frontal lobe is largest in humans, the relative size of the frontal lobe is similar across hominoids, and that humans do not have a larger frontal lobe than expected from a primate brain of the human size. We also report that the relative size of the sectors of the frontal lobe (dorsal, mesial, orbital) is similar across the primate species studied. Our conclusions are preliminary, because the size of our sample, although larger than in previous studies, still remains small. With this caveat we conclude that the overall volume of the frontal lobe in hominids enlarged in absolute size along with the rest of the brain, but did not become relatively larger after the split of the human line from the ancestral African hominoid stock. Aspects other than relative volume of the frontal lobe have to be responsible for the cognitive specializations of the hominids.


Use of Cement Suspension as an Alternative Matrix Material for Textile-Reinforced Concrete.
Textile-reinforced concrete (TRC) is a material consisting of high-performance concrete (HPC) and tensile reinforcement comprised of carbon roving with epoxy resin matrix. However, the problem of low epoxy resin resistance at higher temperatures persists. In this work, an alternative to the epoxy resin matrix, a non-combustible cement suspension (cement milk) which has proven stability at elevated temperatures, was evaluated. In the first part of the work, microscopic research was carried out to determine the distribution of particle sizes in the cement suspension. Subsequently, five series of plate samples differing in the type of cement and the method of textile reinforcement saturation were designed and prepared. Mechanical experiments (four-point bending tests) were carried out to verify the properties of each sample type. It was found that the highest efficiency of carbon roving saturation was achieved by using finer ground cement (CEM 52.5) and the pressure saturation method. Moreover, this solution also exhibited the best results in the four-point bending test. Finally, the use of CEM 52.5 in the cement matrix appears to be a feasible variant for TRC constructions that could overcome problems with its low temperature resistance.


A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol.
Tiotropium, a once-daily anticholinergic, and salmeterol represent two inhaled, long-acting bronchodilators from different pharmacologic classes. A trial was designed to examine the efficacy and safety of both compounds with multiple outcome measures, including lung function, dyspnea, and health-related quality of life (HRQoL) in patients with COPD. A 6-month, randomized, placebo-controlled, double-blind, double-dummy, parallel-group study of tiotropium, 18 microg once daily via dry-powder inhaler, compared with salmeterol, 50 microg bid via metered-dose inhaler, was conducted in patients with COPD. Efficacy was assessed by 12-h monitoring of spirometry, transition dyspnea index (TDI), and the St. George's Respiratory Questionnaire (SGRQ). A total of 623 patients participated (tiotropium, n= 209; salmeterol, n = 213; and placebo, n = 201). The groups were similar in age (mean, 65 years), gender (75% men), and baseline FEV(1) (mean, 1.08 +/- 0.37 L; percent predicted, 40 +/- 12% [+/- SD]). Compared with placebo treatment, the mean predose morning FEV(1) following 6 months of therapy increased significantly more for the tiotropium group (0.14 L) than the salmeterol group (0.09 L; p < 0.01). The average FEV(1) (0 to 12 h) for tiotropium was statistically superior to salmeterol (difference, 0.08 L; p < 0.001). Tiotropium improved TDI focal score by 1.02 U compared with placebo (p = 0.01), whereas there was no significant change in TDI focal score with salmeterol (0.24 U). Tiotropium was superior to salmeterol in improving TDI focal score (p < 0.05). At 6 months, the mean improvement in SGRQ total score vs baseline was tiotropium, - 5.14 U (p < 0.05 vs placebo); salmeterol, - 3.54 U (p = 0.4 vs placebo); and placebo, - 2.43 U. A statistically higher proportion of patients receiving tiotropium achieved at least a 4-U change in SGRQ score compared to patients receiving placebo. Both active drugs reduced the need for rescue albuterol (p < 0.0001). Tiotropium once daily produces superior bronchodilation, improvements in dyspnea, and proportion of patients achieving meaningful changes in HRQoL compared to twice-daily salmeterol in patients with COPD.


Dynamics of aesthetic experience are reflected in the default-mode network.
Neuroaesthetics is a rapidly developing interdisciplinary field of research that aims to understand the neural substrates of aesthetic experience: While understanding aesthetic experience has been an objective of philosophers for centuries, it has only more recently been embraced by neuroscientists. Recent work in neuroaesthetics has revealed that aesthetic experience with static visual art engages visual, reward and default-mode networks. Very little is known about the temporal dynamics of these networks during aesthetic appreciation. Previous behavioral and brain imaging research suggests that critical aspects of aesthetic experience have slow dynamics, taking more than a few seconds, making them amenable to study with fMRI. Here, we identified key aspects of the dynamics of aesthetic experience while viewing art for various durations. In the first few seconds following image onset, activity in the DMN (and high-level visual and reward regions) was greater for very pleasing images; in the DMN this activity counteracted a suppressive effect that grew longer and deeper with increasing image duration. In addition, for very pleasing art, the DMN response returned to baseline in a manner time-locked to image offset. Conversely, for non-pleasing art, the timing of this return to baseline was inconsistent. This differential response in the DMN may therefore reflect the internal dynamics of the participant's state: The participant disengages from art-related processing and returns to stimulus-independent thought. These dynamics suggest that the DMN tracks the internal state of a participant during aesthetic experience.


Targeting the osteosarcoma cancer stem cell.
Osteosarcoma is the most common type of solid bone cancer and the second leading cause of cancer-related death in pediatric patients. Many patients are not cured by the current osteosarcoma therapy consisting of combination chemotherapy along with surgery and thus new treatments are urgently needed. In the last decade, cancer stem cells have been identified in many tumors such as leukemia, brain, breast, head and neck, colon, skin, pancreatic, and prostate cancers and these cells are proposed to play major roles in drug resistance, tumor recurrence, and metastasis. Recent studies have shown evidence that osteosarcoma also possesses cancer stem cells. This review summarizes the current knowledge about the osteosarcoma cancer stem cell including the methods used for its isolation, its properties, and its potential as a new target for osteosarcoma treatment.


Measurement of free triiodothyronine in intensive care patients--comparison of two routine methods.
One hundred sera from intensive care patients, and 93 sera from endocrinological outpatients were used for a comparison between two automated assays for free triiodothyronine (Enzymun Test, and Elecsys 2010, both Boehringer Mannheim, Mannheim, Germany). In outpatients a good correlation between both methods was found (r = 0.932). In contrast, comparability between the two assays was poor in intensive care patients (r = 0.75, after exclusion of two outliers); significantly more values in the hypothyroid range were found with the Elecsys 2010 assay (n = 83, compared with n = 33 with the Enzymun Test; chi 2 test p = 0.001). We conclude that routine measurement of free triiodothyronine which has the theoretical advantage of quantifying the biologically active fraction of thyroid hormones may have methodological limitations in severely ill patients.


Contrast-enhanced computed tomographic imaging of the auditory tube in mesaticephalic dogs.
Computed tomography after contrast medium injection was performed in three mesaticephalic canine cadavers to image the auditory tube. Cadavers were positioned in lateral recumbency for imaging. A myringotomy incision was made in the left tympanic membrane of each dog, and contrast medium was infused into the ear canal and middle ear through a balloon-tip catheter. With this method, contrast medium filled the left bulla and auditory tube in all three cadavers. Computed tomography following contrast medium injection was effective for evaluation of the canine auditory tube. Future studies are required to determine the usefulness, as well as the safety, of this procedure in the evaluation of the auditory tube in other breeds of dogs as well as dogs with otitis


Decoding the chromatin proteome of a single genomic locus by DNA sequencing.
Transcription, replication, and repair involve interactions of specific genomic loci with many different proteins. How these interactions are orchestrated at any given location and under changing cellular conditions is largely unknown because systematically measuring protein-DNA interactions at a specific locus in the genome is challenging. To address this problem, we developed Epi-Decoder, a Tag-chromatin immunoprecipitation-Barcode-Sequencing (TAG-ChIP-Barcode-Seq) technology in budding yeast. Epi-Decoder is orthogonal to proteomics approaches because it does not rely on mass spectrometry (MS) but instead takes advantage of DNA sequencing. Analysis of the proteome of a transcribed locus proximal to an origin of replication revealed more than 400 interacting proteins. Moreover, replication stress induced changes in local chromatin proteome composition prior to local origin firing, affecting replication proteins as well as transcription proteins. Finally, we show that native genomic loci can be decoded by efficient construction of barcode libraries assisted by clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Thus, Epi-Decoder is an effective strategy to identify and quantify in an unbiased and systematic manner the proteome of an individual genomic locus by DNA sequencing.


Association of Social Distancing, Population Density, and Temperature With the Instantaneous Reproduction Number of SARS-CoV-2 in Counties Across the United States.
Local variation in the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the United States has not been well studied. To examine the association of county-level factors with variation in the SARS-CoV-2 reproduction number over time. This cohort study included 211 counties, representing state capitals and cities with at least 100 000 residents and including 178 892 208 US residents, in 46 states and the District of Columbia between February 25, 2020, and April 23, 2020. Social distancing, measured by percentage change in visits to nonessential businesses; population density; and daily wet-bulb temperatures. Instantaneous reproduction number (Rt), or cases generated by each incident case at a given time, estimated from daily case incidence data. The 211 counties contained 178 892 208 of 326 289 971 US residents (54.8%). Median (interquartile range) population density was 1022.7 (471.2-1846.0) people per square mile. The mean (SD) peak reduction in visits to nonessential business between April 6 and April 19, as the country was sheltering in place, was 68.7% (7.9%). Median (interquartile range) daily wet-bulb temperatures were 7.5 (3.8-12.8) °C. Median (interquartile range) case incidence and fatality rates per 100 000 people were approximately 10 times higher for the top decile of densely populated counties (1185.2 [313.2-1891.2] cases; 43.7 [10.4-106.7] deaths) than for counties in the lowest density quartile (121.4 [87.8-175.4] cases; 4.2 [1.9-8.0] deaths). Mean (SD) Rt in the first 2 weeks was 5.7 (2.5) in the top decile compared with 3.1 (1.2) in the lowest quartile. In multivariable analysis, a 50% decrease in visits to nonessential businesses was associated with a 45% decrease in Rt (95% CI, 43%-49%). From a relative Rt at 0 °C of 2.13 (95% CI, 1.89-2.40), relative Rt decreased to a minimum as temperatures warmed to 11 °C, increased between 11 and 20 °C (1.61; 95% CI, 1.42-1.84) and then declined again at temperatures greater than 20 °C. With a 70% reduction in visits to nonessential business, 202 counties (95.7%) were estimated to fall below a threshold Rt of 1.0, including 17 of 21 counties (81.0%) in the top density decile and 52 of 53 counties (98.1%) in the lowest density quartile.2. In this cohort study, social distancing, lower population density, and temperate weather were associated with a decreased Rt for SARS-CoV-2 in counties across the United States. These associations could inform selective public policy planning in communities during the coronavirus disease 2019 pandemic.


History of sexual abuse among HIV-infected women.
The objective of this study is to describe the characteristics associated with a history of sexual abuse among HIV-infected women enrolled in a public inner-city HIV outpatient clinic. A retrospective chart review of 238 women of childbearing age enrolled in the HIV outpatient clinic between 1987 and 1995 was performed. Characteristics of the study population were 83% African American, 69% single, and 53% finished high school or were still in school. The mean age was 25.7 years. Of the 238 women, 32% had a history of sexual abuse. Factors associated with sexual abuse history after controlling for age included living in a non-permanent situation (OR=4.8), history of non-intravenous drug use (OR=4.65), and having dropped out of school (OR=2.2). HIV-infected women should be screened for a history of sexual abuse and carefully counselled regarding their reproductive choices and drug treatment.


What motion distributions yield global transparency and spatial segmentation?
We have examined the ability of observers to parse bimodal local-motion distributions into two global motion surfaces, either overlapping (yielding transparent motion) or spatially segregated (yielding a motion boundary). The stimuli were random dot kinematograms in which the direction of motion of each dot was drawn from one of two rectangular probability distributions. A wide range of direction distribution widths and separations was tested. The ability to discriminate the direction of motion of one of the two motion surfaces from the direction of a comparison stimulus was used as an objective test of the perception of two discrete surfaces. Performance for both transparent and spatially segregated motion was remarkably good, being only slightly inferior to that achieved with a single global motion surface. Performance was consistently better for segregated motion than for transparency. Whereas transparent motion was only perceived with direction distributions which were separated by a significant gap, segregated motion could be seen with abutting or even partially overlapping direction distributions. For transparency, the critical gap increased with the range of directions in the distribution. This result does not support models in which transparency depends on detection of a minimum size of gap defining a bimodal direction distribution. We suggest, instead, that the operations which detect bimodality are scaled (in the direction domain) with the overall range of distribution. This yields a flexible, adaptive system that determines whether a gap in the direction distribution serves as a segmentation cue or is smoothed as part of a unitary computation of global motion.


Does gender matter? A one year follow-up of autistic, attention and anxiety symptoms in high-functioning children with autism spectrum disorder.
Gender differences in autism spectrum disorder (ASD) symptoms and associated problem behaviours over development may provide clues regarding why more males than females are diagnosed with ASD. Fifty-six high-functioning children with ASD, and 44 typically developing controls, half of the participants female, were assessed at baseline (aged 7-12 years) and one-year later, collecting measures of autism, attention and anxiety symptoms, school placement and support information. Findings indicated no gender differences in autistic symptoms. Males were more hyperactive and received more integration-aide support in mainstream schools, and females were more socially anxious. Overall, similar gender profiles were present across two time points. Lower hyperactivity levels in females might contribute to their under-identification. Implications are discussed using a biopsychosocial model of gender difference.


Drosophila Vps13 Is Required for Protein Homeostasis in the Brain.
Chorea-Acanthocytosis is a rare, neurodegenerative disorder characterized by progressive loss of locomotor and cognitive function. It is caused by loss of function mutations in the Vacuolar Protein Sorting 13A (VPS13A) gene, which is conserved from yeast to human. The consequences of VPS13A dysfunction in the nervous system are still largely unspecified. In order to study the consequences of VPS13A protein dysfunction in the ageing central nervous system we characterized a Drosophila melanogaster Vps13 mutant line. The Drosophila Vps13 gene encoded a protein of similar size as human VPS13A. Our data suggest that Vps13 is a peripheral membrane protein located to endosomal membranes and enriched in the fly head. Vps13 mutant flies showed a shortened life span and age associated neurodegeneration. Vps13 mutant flies were sensitive to proteotoxic stress and accumulated ubiquitylated proteins. Levels of Ref(2)P, the Drosophila orthologue of p62, were increased and protein aggregates accumulated in the central nervous system. Overexpression of the human Vps13A protein in the mutant flies partly rescued apparent phenotypes. This suggests a functional conservation of human VPS13A and Drosophila Vps13. Our results demonstrate that Vps13 is essential to maintain protein homeostasis in the larval and adult Drosophila brain. Drosophila Vps13 mutants are suitable to investigate the function of Vps13 in the brain, to identify genetic enhancers and suppressors and to screen for potential therapeutic targets for Chorea-Acanthocytosis.


Dental needs and socioeconomic status associated with utilization of dental services in the presence of dental pain: a case-control study in children.
To identify the effect of unmet dental treatment needs and socioeconomic and sociodemographic variables on the patterns of dental visits in the presence of dental pain in 6- to 12-year-old Mexican schoolchildren. A case-control study included 379 patients that had a dental visit because of dental pain in the 12 months preceding this study and 1,137 controls. Mothers and/or guardians supplied sociodemographic, socioeconomic, and oral health-related information through a questionnaire. The profiles of unmet dental needs and of oral hygiene were ascertained by means of a standardized dental examination administered to participating children. Odds ratios (OR) and 95% confidence intervals (CIs) were calculated with logistic regression. Higher unmet dental needs and lack of health insurance were associated with the experience of dental visits because of dental pain in the preceding 12 months. Boys who attended public schools had a 70% (95% CI = 1.29 to 2.23) higher probability of having had a dental visit in which dental pain was one of the main reasons for attendance, compared to boys attending private schools. The effect for girls was only 28% (95% CI = 1.10 to 1.50) higher for girls attending a public school, compared to girls attending private schools. Older children had a higher occurrence of dental visits because of dental pain than younger children. While higher unmet dental needs and lack of health insurance were strong predictors of having had dental visits because of dental pain in the preceding 12 months, some socioeconomic variables and sociodemographic variables modified these relationships.


Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer's disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin.
cerebrolysin is a neuropeptide preparation mimicking the effects of neurotrophic factors. This subgroup analysis assessed safety and efficacy of Cerebrolysin in patients with moderate to moderately severe Alzheimer's disease (AD) (ITT data set: N = 133; MMSE: 14-20) included in a dose-finding study (ITT data set: N = 51; MMSE: 14-25). Results of the mild AD subgroup (ITT data set: N = 118; MMSE: 21-25) are also presented. patients with AD received 100 ml IV infusions of Cerebrolysin (10, 30 or 60 ml diluted in saline; N = 32, 34 and 35, respectively) or placebo (saline; N = 32) over twelve weeks (5 days per week for 4 weeks and 2 days per week for another 8 weeks). Primary efficacy criteria ADAS-cog+ (Alzheimer's Disease Assessment Scale Cognitive Subpart Modified) and CIBIC+ (Clinical Interview-based Impression of Change with Caregiver Input) were assessed 24 weeks after baseline. at week 24, Cerebrolysin improved the global clinical function significantly with all three dosages and induced significant improvements in cognition, initiation of activities of daily living (ADL) and neuropsychiatric symptoms at 10-, 30- and 60-ml doses, respectively. Treatment effects on total ADL and other secondary parameters (MMSE, Trail-making test) were not significant. Cerebrolysin was safe and well tolerated. these results demonstrate the efficacy of Cerebrolysin in moderate to moderately severe AD, showing dose-specific effects similar to those reported for patients with mild to moderate AD. The benefits of Cerebrolysin in advanced AD need to be confirmed in larger trials.


A lipoprotein lipase gene polymorphism interacts with consumption of alcohol and unsaturated fat to modulate serum HDL-cholesterol concentrations.
There are limited data from prospective studies regarding interactions between lipoprotein lipase gene (LPL) and lifestyle factors in association with HDL-cholesterol (HDL-C) concentrations, a biomarker of coronary heart disease risk. Our prospective cohort study investigated the interactive effects of a common LPL polymorphism and lifestyle factors, including obesity, smoking, alcohol consumption, physical activity, and dietary intake, on follow-up measurements of HDL-C and triglyceride (TG) concentrations. A total of 5314 Korean men and women aged 40-69 y participated in the study. Serum HDL-C and TG concentrations were measured in all participants at baseline and 6-y follow-up examinations. On the basis of genome-wide association data for HDL-C and TG concentrations, we selected the most significant polymorphism (rs10503669), which was in high linkage disequilibrium with the serine 447 stop (S447×) mutation (D' = 0.99) of LPL. We found that carrying the T allele reflecting the LPL ×447 allele was positively associated with follow-up measurement of HDL-C concentrations (P < 0.001). In the linear regression model adjusted for baseline HDL-C concentration and potential risk factors, we observed interactive effects of the polymorphism and consumption of alcohol (P-interaction < 0.01) and unsaturated fat (P-interaction < 0.05) on follow-up measurement of HDL-C concentrations. We also observed interactive effects of the polymorphism and body mass index (P-interaction < 0.01) on follow-up measurement of TG concentrations after adjusting for the baseline level and potential risk factors. Our findings suggest that carriers of the LPL ×447 allele benefit from moderate alcohol consumption and a diet high in unsaturated fat to minimize reduction of blood HDL-C concentrations and that obese persons who do not carry the LPL ×447 allele need to control body weight to prevent hypertriglyceridemia.


Sexual partner characteristics and incident rectal Neisseria gonorrhoeae and Chlamydia trachomatis infections among gay men and other men who have sex with men (MSM): a prospective cohort in Abuja and Lagos, Nigeria.
STIs including Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) potentiate HIV acquisition and transmission especially among gay men and other men who have sex with men (MSM). We investigated the influence of sexual network composition on incident rectal NG and/or CT infections among Nigerian MSM. TRUST/RV368 is a cohort of MSM recruited using respondent-driven sampling at trusted community centres in Abuja and Lagos, Nigeria. MSM respondents (egos) provided STI risk factors and demographic information for up to five of their most recent sexual partners (alters) within their sexual networks. Egos were tested for HIV, NG and CT every 3 months. Log-binomial regression was used to assess associations between alter characteristics and incident NG and/or CT. Between March 2013 and October 2015, 492 MSM were longitudinally screened for STIs, of which 28.0% (n=138) were positive for incident rectal STI (61 NG only, 42 CT only and 35 NG and CT). Among egos, condom use was associated with STIs (half of the time vs never (adjusted risk ratio (aRR) 0.5; 95% CI 0.3 to 0.8), always/almost always vs never (aRR 0.7; 95% CI 0.5 to 1.0)). Incident STIs were associated with having a younger alter ≤19 versus 30 years (aRR 0.6; 95% CI 0.4 to 1.0), HIV infection (aRR 1.5; 95% CI 1.1 to 2.0) and engaging in sex under the influence of alcohol (aRR 1.4 95% CI 1.1 to 1.7) among regular alters and age ≤19 versus 30 years (aRR 0.3; 95% CI 0.2 to 0.6), HIV infection (aRR 1.4; 95% CI 1.1 to 1.8) and engaging in sex under the influence of alcohol (aRR 1.2 95% CI 1.0 to 1.4) among casual alters. Given the centrality of sexual partner characteristics as risks for incident STIs among Nigerian MSM, there is a need to move beyond individual interventions and syndromic surveillance and get 'out there' in the STI management.


The Association between Suicide Attempts and Toxoplasma gondii Infection.
Chronic 'latent' infection by Toxoplasma gondii is common and most of the hosts have minimal symptoms or they are even asymptomatic. However, there are possible mechanisms by which T. gondii may affect human behavior and it may also cause humans to attempt suicide. This article aimed to investigate the potential pathophysiological relationship between suicide attempts and T. gondii infection in Korea. One hundred fifty-five psychiatric patients with a history of suicide attempt and 135 healthy control individuals were examined with enzyme-linked immunoassays and fluorescent antibody technique for T. gondii seropositivity and antibody titers. The group of suicide attempters was interviewed regarding the history of suicide attempt during lifetime and evaluated using 17-item Korean version of Hamilton Depression Scale (HAMD), Columbia Suicide Severity Rating Scale (C-SSRS), State-Trait Anxiety Inventory (STAI) and Korean-Barratt Impulsiveness Scale (BIS). Immunoglobulin G antibodies were found in 21 of the 155 suicide attempters and in 8 of the 135 controls (p=0.011). The Toxoplasma-seropositive suicide attempters had a higher HAMD score on the depressed mood and feeling of guilt subscales and a higher total score than the seronegative suicide attempters. T. gondii seropositive status was associated with higher C-SSRS in the severity and lethality subscales. T. gondii IgG seropositivity was significantly associated with higher STAI-X1 scores in the suicide attempters group. Suicide attempters showed higher seroprevalence of T. gondii than healthy controls. Among the suicide attempters, the T. gondii seropositive and seronegative groups showed several differences in the aspects of suicide. These results suggested a significant association between T. gondii infection and psychiatric problems in suicidality.


Variation in population levels of physical activity in European children and adolescents according to cross-European studies: a systematic literature review within DEDIPAC.
Regular physical activity is associated with physical, social and mental health benefits, whilst insufficient physical activity is associated with several negative health outcomes (e.g. metabolic problems). Population monitoring of physical activity is important to gain insight into prevalence of compliance to physical activity recommendations, groups at risk and changes in physical activity patterns. This review aims to provide an overview of all existing studies that measure physical activity in youth, in cross-European studies, to describe the variation in population levels of physical activity and to describe and define challenges regarding assessment methods that are used. A systematic search was performed on six databases (PubMed, EMBASE, CINAHL, PsycINFO, SportDiscus and OpenGrey), supplemental forward- and backward tracking was done and authors' and experts' literature databases were searched to identify relevant articles. Journal articles or reports that reported levels of physical activity in the general population of youth from cross-European studies were included. Data were reviewed, extracted and assessed by two researchers, with disagreements being resolved by a third researcher. The review protocol of this review is published under registration number CRD42014010684 in the PROSPERO database. The search resulted in 9756 identified records of which 30 articles were included in the current review. This review revealed large differences between countries in prevalence of compliance to physical activity recommendations (i.e. 60 min of daily moderate- to vigorous-intensity physical activity (MVPA)) measured subjectively (5-47%) and accelerometer measured minutes of MVPA (23-200 min). Overall boys and children were more active than girls and adolescents. Different measurement methods (subjective n = 12, objective n = 18) and reported outcome variables (n = 17) were used in the included articles. Different accelerometer intensity thresholds used to define MVPA resulted in substantial differences in MVPA between studies conducted in the same countries when assessed objectively. Reported levels of physical activity and prevalence of compliance to physical activity recommendations in youth showed large variation across European countries. This may reflect true variation in physical activity as well as variation in assessment methods and reported outcome variables. Standardization across Europe, of methods to assess physical activity in youth and reported outcome variables is warranted, preferably moving towards a pan-European surveillance system combining objective and self-report methods.


Return to Play in Amateur Soccer Players Undergoing Hip Arthroscopy: Short- to Mid-Term Follow-Up.
To describe patient-reported outcomes (PROs) and return to play at any level in amateur soccer players undergoing hip arthroscopy for femoroacetabular impingement syndrome at short- to mid-term follow-up. Data were prospectively collected and retrospectively reviewed for patients who underwent hip arthroscopy between March 2009 and June 2014. Patients who participated in amateur soccer within 1 year prior to surgery and intended to return to their sport after hip arthroscopy for femoroacetabular impingement syndrome were considered for inclusion in our study. Patients were excluded if they had a preoperative Tönnis osteoarthritis grade of 2 or greater, previous ipsilateral hip conditions or hip surgical procedures, or Workers' Compensation status. The patients from the initial group who had preoperative and minimum 2-year postoperative measures for the modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Sports Specific Subscale, and visual analog scale for pain were included in our final group. In addition to PROs, data regarding the patients' return to soccer, surgical complications, and secondary surgical procedures were collected. A total of 41 patients were eligible for inclusion in our study, of whom 34 (82.9%) had a mean follow-up period of 47.4 months. Five patients were not eligible because they did not intend to return to soccer. There were 15 male hips (44.1%) and 19 female hips (55.9%). The mean age at surgery was 20.8 ± 7.4 years. All PROs and the visual analog scale score improved significantly from preoperatively to latest follow-up. Of the 34 patients, 27 (79.4%) returned to soccer. Of the patients who returned to soccer, 19 (70.4%) were competing at the same level or a higher level compared with their highest level within 1 year of surgery. Regardless of competitive level, 21 patients (77.8%) reported that their athletic ability was the same as or higher than it was within 1 year of surgery. Hip arthroscopy was associated with significant improvements in PROs for amateur soccer players. There was a high level of return to soccer and a high proportion of patients whose competitive level was similar or improved. As such, hip arthroscopy is a good option for soccer players, in the absence of underlying osteoarthritis, presenting with hip pathology. Level IV, case series.