Parent-child interactions and children with cerebral palsy: An exploratory study investigating emotional availability, functional ability, and parent distress.
Emotionally available parent-child relationships are supportive of child health and development. When a child has cerebral palsy, a range of child and parent factors can potentially impact the parent-child relationship; however, little research has specifically addressed this question. The aim of this study is to investigate links between parent-child emotional availability and both child functional abilities and parent distress in a sample of parents and children with cerebral palsy. Twenty-three mothers (mean age 37.3+/-5.7 years) and their children (mean age 4.9+/-3.3 years) with cerebral palsy completed a 20 min videoed parent-child interaction, scored using the Emotional Availability Scales. Parents also completed the Depression Anxiety Stress Scale, the Paediatric Evaluation of Disability Inventory, and the Strengths and Difficulties Questionnaire. Correlational analyses were conducted, and qualitative observations were made. Parent-child dyads in which the parent reported depressive symptoms scored poorer on all aspects of parent-child emotional availability. Where parents reported experiencing anxiety or stress, increased parent hostility and decreased child responsiveness was found. There was no relationship between child functional abilities and either parent distress or parent-child emotional availability. Parent sensitivity, structuring, and nonintrusiveness were negatively associated with child peer problems. Both child responsiveness and child involvement were negatively associated with hyperactivity/inattention. Observations of video footage suggested that parent implementation of therapy strategies impacted negatively on parent-child emotional availability for some dyads. Findings from this study are consistent with the wider literature showing a link between parental depression and the parent-child relationship and extend this link to the cerebral palsy population. The importance of routine screening for parental mental health problems in early childhood intervention is highlighted by these findings. In addition, this study emphasizes the need to better understand how therapists support parents to implement therapeutic strategies to minimize negative impact on the developing parent-child relationship.


Evaluation of HIV and AIDS knowledge in rural Cameroon men with the use of a questionnaire.
HIV/AIDS, the most important health problem in Africa, is the leading cause of death on the continent. Ignorance on HIV/AIDS status will hamper treatment and prevention. To investigate the level of HIV/AIDS knowledge among men in a rural area, we performed a questionnaire study on HIV/AIDS knowledge in men living in Banga Bakundu, a rural village in Cameroon. Forty-eight men, aged 17-66 years, were interviewed. They were divided in 2 groups: ≤ 29 years, being those young enough to be able to have knowledge about HIV/AIDS at the time of their first sexual contact, and those > 29 years who weren't. A semi-structured clinical interview was performed to obtain information about socio-demographic characteristics, sexual activity, knowledge about HIV/AIDS and its prevention. There is an overall good HIV/AIDS knowledge and what should be done about it. Men with a higher level of education and more HIV/AIDS knowledge seem to take less preventive measures. The differentiation per age group showed that age influenced the data on knowledge and behaviour. Our data are consistent with other studies. Remarkable is the difference in HIV/AIDS knowledge between the 2 age groups, and the relation between HIV/AIDS knowledge and sexual habits and prevention. Sufficient HIV/AIDS knowledge did not lead to significant changes in sexual behaviour. The questionnaire showed to provide sufficient information and was easy to use. Further research should be performed.


Evidence of microvascular dysfunction in patients with cystic fibrosis.
Cystic fibrosis (CF) is a genetic, multisystemic disorder with broad clinical manifestations apart from the well-characterized pulmonary dysfunction. Recent findings have described impairment in conduit vessel function in patients with CF; however, whether microvascular function is affected in this population has yet to be elucidated. Using laser-Doppler imaging, we evaluated microvascular function through postocclusive reactive hyperemia (PORH), local thermal hyperemia (LTH), and iontophoresis with acetylcholine (ACh). PORH [518 ± 174% (CF) and 801 ± 125% (control), P = 0.039], LTH [1,338 ± 436% (CF) and 1,574 ± 620% (control), P = 0.045], and iontophoresis with ACh [416 ± 140% (CF) and 617 ± 143% (control), P = 0.032] were significantly lower in patients with CF than control subjects. In addition, the ratio of PORH to LTH was significantly (P = 0.043) lower in patients with CF (55.3 ± 5.1%) than control subjects (68.8 ± 3.1%). Significant positive correlations between LTH and forced expiratory volume in 1 s (%predicted) (r = 0.441, P = 0.013) and between the PORH-to-LTH ratio and exercise capacity (r = 0.350, P = 0.049) were observed. These data provide evidence of microvascular dysfunction in patients with CF compared with control subjects. In addition, our data demonstrate a complex relationship between microvascular function and classical markers of disease severity (i.e., pulmonary function and exercise capacity) in CF.


Determinants of health-related quality of life in elderly in Tehran, Iran.
As Iran started to experience population ageing, it is important to consider and address the elderly people's needs and concerns, which might have direct impacts on their well-being and quality of life. There have been only a few researches into different aspects of life of the elderly population in Iran including their health-related quality of life. The purpose of this study was to measure health-related quality of life (HRQoL) of elderly Iranians and to identify its some determinant factors. This was a cross-sectional survey of a random sample of community residents of Tehran aged 65 years old and over. HRQoL was measured using the Short From Health Survey (SF-36). The study participants were interviewed at their homes. Uni-variate analysis was performed for group comparison and logistic regression analysis conducted to predict quality of life determinants. In all, 400 elderly Iranian were interviewed. The majority of the participants were men (56.5%) and almost half of the participants were illiterate (n = 199, 49.8%). Eighty-five percent of the elderly were living with their family or relatives and about 70% were married. Only 12% of participants evaluated their economic status as being good and most of people had moderate or poor economic status. The mean scores for the SF-36 subscales ranged from 70.0 (SD = 25.9) for physical functioning to 53.5 (SD = 29.1) for bodily pain and in general, the respondents significantly showed better condition on mental component of the SF-36 than its physical component (mean scores 63.8 versus 55.0). Performing uni-variate analysis we found that women reported significantly poorer HRQoL. Multiple logistic regression analysis showed that for the physical component summary score of the SF-36, age, gender, education and economic status were significant determinants of poorer physical health-related quality of life; while for the mental component summary score only gender and economic status were significant determinants of poorer mental health-related quality of life. The analysis suggested that the elderly people's economic status was the most significant predictor of their HRQoL. The study findings, although with a small number of participants, indicate that elderly people living in Tehran, Iran suffer from relatively poor HRQoL; particularly elderly women and those with lower education. Indeed to improve quality of life among elderly Iranians much more attention should be paid to all aspects of their life including their health, and economic status.


Phylogenetic evidence for underreporting of male-to-male sex among human immunodeficiency virus-infected donors in the Netherlands and Flanders.
Separate transmission networks for human immunodeficiency virus (HIV) coexist. Molecular typing of viral genomes can provide insight in HIV transmission routes in donors for whom risk behavior-based donor selection failed. This study includes all HIV-infected Dutch and Flemish donors in the period 2005 to 2014 (n = 55). Part of the HIV polymerase (pol) gene was amplified, sequenced, and compared with more than 10,000 HIV strains obtained from HIV-infected Dutch and Flemish patients. The most likely transmission route was determined based on HIV phylogeny and the donor's self-reported risk behavior during the exit interview. HIV-infected donors were predominantly male (69%), were repeat donors (73%), were born in the Netherlands or Belgium (95%), and harbored HIV Subtype B (68%). Seventy-five percent of HIV-infected male donors were part of robust phylogenetic clusters linked to male-to-male sex, while only 24% of HIV-infected male donors reported male-to-male sex during posttest counseling. Sex between men and women accounted for 13% of HIV infections in male donors and 93% of HIV infections in female donors based on phylogenetic analysis. Only 40% of HIV-infected female donors had HIV Subtype B; 65% of female donors reported a foreign partner and indeed HIV sequences interspersed with sequences from HIV-endemic areas abroad, in particular sub-Saharan Africa. HIV typing helps to understand HIV transmission routes in donor populations. We found substantial underreporting of male-to-male sex among HIV-infected male donors. Donor education on HIV risk factors and the danger of window-period donations and a donor environment that encourages frank disclosure of sexual behavior will contribute to a decrease of HIV-infected donors.


[Venous cerebral thrombosis. Mechanical and chemical thrombolysis].
Cerebral Venous Thrombosis is a disease not fully understood regarding its pathophysiology, natural course and prognosis. The therapeutics is not consensual. However it has been normally used anticoagulants plus thrombolysis or anticoagulation alone. The authors report the successful lysis of dural sinus thrombosis by mechanical and chemical (rt-PA) treatment.


Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain.
Fibroblasts can be directly reprogrammed to cardiomyocyte-like cells by introducing defined genes. However, the reprogramming efficiency remains low, delaying the clinical application of this strategy to regenerative cardiology. We previously showed that fusion of the MyoD transactivation domain to the pluripotency transcription factor Oct4 facilitated the transcriptional activity of Oct4, resulting in highly efficient production of induced pluripotent stem cells. We examined whether the same approach can be applied to cardiac transcription factors to facilitate cardiac reprogramming. We fused the MyoD domain to Mef2c, Gata4, Hand2, and Tbx5 and transduced these genes in various combinations into mouse non-cardiac fibroblasts. Transduction of the chimeric Mef2c with the wild-types of the other three genes produced much larger beating clusters of cardiomyocyte-like cells faster than the combination of the four wild-type genes, with an efficiency of 3.5%, >15-fold greater than the wild-type genes. Fusion of a powerful transactivation domain to heterologous factors can increase the efficiency of direct reprogramming of fibroblasts to cardiomyocytes.


House dust mites in Colorado.
Sixty-four samples of house dust from 16 long-established households in the Denver, Colorado area were analyzed for the presence of house dust mites (Dermatophagoides sp.). No mites were found in house dust from 12 of the sampled houses and small numbers (10 to 40 mites/g of house dust) were found from the other four. In an additional four houses which contained furniture recently imported from other areas, 100 to 360 mites/g of dust were found, and 2 years later up to 200 mites/g were still present. Twenty-eight percent of the mites in repeat collections from the latter homes were alive. The mite allergen content of house dust samples was analyzed by RAST inhibition against pooled sera from mite allergic patients. When dust from four long-established Denver households where no mites were found was employed, there was an average binding of 37.2%; with dust from the four Denver households with low levels of mites and no imported furniture, binding averaged 39.5%. In contrast, with house dust from four "positive control" homes in California and New York there was only 26.1% binding (P less than .005). The results of this study suggest that there are small numbers of nonintroduced house dust mites in some Denver houses, but that they contribute little mite antigen and are probably of minimal clinical significance in mite-sensitive patients. Large numbers of mites can be introduced with furnishings and may persist for at least 2 years. Similar small mite populations might be expected in other areas with comparable relative humidity.


The Household Food Security and Feeding Pattern of Preschool Children in North-Central Nigeria.
Children's feeding patterns and health outcomes are important determinants of any country's food and nutrition security status. This study assessed the household food security and feeding patterns of preschoolers in Niger State, Nigeria. A cross-sectional descriptive design and a multi-stage sampling technique were employed to analyze 450 preschool children from selected local government areas. Household food security was measured using the HFIAS nine-item questionnaire, and feeding patterns were evaluated using the qualitative food frequency questionnaire (FFQ). The mean age of the preschoolers was 3.71 ± 0.80 years. A majority (61.30%) of the children consumed cereal-based products, while fruits and vegetables were the least consumed (16.40%). More than half (59.80%) of the preschoolers met their minimum dietary diversity. Almost all (98.80%) of the children were from food-insecure households, with 40.3% being severely food insecure. Parity, religion, and having a breadwinner and source of potable water were significantly associated with the adequacy of minimum dietary diversity (MDD) among the preschoolers (F value = 5.528, p ≤ 0.05). The contribution of poor feeding patterns and household food insecurity to the overall health outcome of preschoolers cannot be overlooked. Hence, nations must prioritize improving the availability, accessibility, and utilization of food to better meet the nutritional needs of preschool children.


Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems.
Previous reports have shown that spleen cells from nonimmune adult mice of certain strains do regularly kill Moloney leukemia virus-induced lymphomas in short-term 51Cr release assays. This naturally occuring killer (NK) cell had low adherent properties and had the morphological appearance of a lymphocyte. Still it lacked surface characteristics of mature T or B lymphocytes. In the present report a functional study was carried out, comparing in parallel the NK system, the T-cell killing across an H-2 barrier (anti-P815), and the antibody-dependent cell-mediated chicken red blood cell (CRBC) system. In contrast to the effector cells in the CRBC system, the NK cells were insensitive to erythrocyte antibody complement (EAC) rosette depletion and would pass through nylon wool columns. NK activity was not inhibited by the presence of heat-aggregated human or mouse gamma globulin, in contrast to the strong inhibition noted in the CRBC system. Sensitivity to trypsin pretreatment was noted in the NK system as well as in the immune P815 system, whereas the CRBC system was relatively trypsin resistant. Antitheta plus complement eliminated the anti-P815 activity, but did not touch the NK activity. The present results thus further distinguish the NK cell from cytotoxic T lymphocytes or from antibody-dependent killer cells.


Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase beta to DNA.
Four isomalabaricane triterpenoids were isolated from an extract of the sponge Rhabdastrella globostellata that was active in an assay measuring stabilization of the binding of DNA with DNA polymerase beta. The known compounds stelliferin riboside (1) and 3-epi-29-acetoxystelliferin E (2) were shown to induce 29% and 23% binding, respectively, at 28 microg/mL, while the new compound stellettin J (3) induced 5% binding at 28 microg/mL. The new compound stellettin K (4) had no activity in the binding assay. The compounds were characterized by spectroscopic methods. These compounds displayed varying levels of activity toward the A2780 ovarian cancer cell line, revealing structure-based effects on both the level of cytotoxicity and DNA-polymerase beta binding. This is the first report of natural products with the ability to promote stabilization of the DNA-polymerase beta covalent binary complex.


Regulation of the phosphoenolpyruvate carboxykinase/human factor IX gene introduced into the livers of adult rats by receptor-mediated gene transfer.
Gene transfer systems targeting the asialoglycoprotein receptor have been developed to introduce functional genes into cells in culture and livers of intact animals. A synthetic neoglycoprotein carrier was constructed and complexed to a chimeric gene containing the cDNA for human factor IX ligated to the promoter-regulatory region of the gene for phosphoenolpyruvate carboxykinase from the rat. The complex was used to transfect human hepatoma cells that express the asialoglycoprotein receptor. Human factor IX DNA sequences were found in cells 10 days after treatment. A 1.4 kB mRNA transcript was detected by Northern blot hybridization, which was inducible by treatment with dexamethasone or cAMP with theophylline. Western blot hybridization of proteins secreted into the culture medium detected human factor IX. The chimeric gene was also transferred into livers of rats using the neoglycoprotein carrier system after partial hepatectomy. Although the results were variable, the exogenous gene was transcribed in livers of several animals, and maximal levels of expression of the fully processed human factor IX were detected 30 days after introduction. The concentration of factor IX in the blood returned to control levels 60 days after transfection. Factor IX production was induced as late as 96 days after treatment by feeding transfected animals a diet high in protein but devoid of carbohydrates. This DNA carrier system can be used to introduce functional genes into the livers of rats, and may be a useful technique for gene therapy targeting the liver.


The evolving pharmacy benefit market.
The growing number of pharmacy benefit management companies (PBMCs) signal the most significant trend in the pharmacy benefit marketplace in many years. The evolution of this industry has made pharmacy benefit management available to smaller health plans and self-insured employers alike. However, the growth of PBMCs has spurred more competition, and profits in the industry are becoming harder to attain. This setting should provide fertile ground for the continuing evolution of entities that offer pharmacy benefit management.


Microinstability of the Hip and the Splits Radiograph.
A normal hip has a natural tendency toward stability because of both osseous and soft tissue structures. Hip motion is primarily rotational around a center of rotation. When the femoral head and its center of rotation translate, with or without rotation, the inherent stability of the femoroacetabular articulation may be lost. The spectrum of hip instability ranges from subtle microinstability to traumatic dislocation. Microinstability may be the cause or the effect of several other hip pathologies. Soft tissue contributions to stability include the static capsule, dynamic musculotendinous units, and underlying generalized connective tissue (eg, Ehlers-Danlos). Osseous contributions include multiple femoral and acetabular radiographic coverage parameters. Iatrogenic contributions include an unrepaired capsulotomy, overresection of the acetabular rim (iatrogenic dysplasia), overresection of cam osteochondroplasty, iliopsoas tenotomy, labral debridement, and ligamentum teres debridement. Patients with hip microinstability often have deep groin pain, exhibited by a C sign. These patients frequently participate in flexibility sports and activities, such as ballet, gymnastics, figure skating, and martial arts. On physical examination, generalized hypermobility syndromes should be assessed, as should loss of log-roll external rotation recoil, excessive abduction, trochanteric-pelvic impingement, and abductor fatigue. Standard imaging, including plain radiographs, magnetic resonance imaging, and computed tomography, should be analyzed for all causes of hip pain. A new plain radiograph, the splits radiograph is introduced here, consistently showing lateral femoral head translation and creation of a vacuum sign, showing hip microinstability. The splits radiograph is illustrated in a 22-year-old female dancer who presented with bilateral deep anterolateral groin pain.


Microelectrode Sensor for Real-Time Measurements of Nitrite in the Living Brain, in the Presence of Ascorbate.
The impaired blood flow to the brain causes a decrease in the supply of oxygen that can result in cerebral ischemia; if the blood flow is not restored quickly, neuronal injury or death will occur. Under hypoxic conditions, the production of nitric oxide (●NO), via the classical L-arginine-●NO synthase pathway, is reduced, which can compromise ●NO-dependent vasodilation. However, the alternative nitrite (NO2-) reduction to ●NO, under neuronal hypoxia and ischemia conditions, has been viewed as an in vivo storage pool of ●NO, complementing its enzymatic synthesis. Brain research is thus demanding suitable tools to probe nitrite's temporal and spatial dynamics in vivo. In this work, we propose a new method for the real-time measurement of nitrite concentration in the brain extracellular space, using fast-scan cyclic voltammetry (FSCV) and carbon microfiber electrodes as sensing probes. In this way, nitrite was detected anodically and in vitro, in the 5-500 µM range, in the presence of increasing physiological concentrations of ascorbate (100-500 µM). These sensors were then tested for real-time and in vivo recordings in the anesthetized rat hippocampus; using fast electrochemical techniques, local and reproducible transients of nitrite oxidation signals were observed, upon pressure ejection of an exogenous nitrite solution into the brain tissue. Nitrite microsensors are thus a valuable tool for investigating the role of this inorganic anion in brain redox signaling.


Inhibition of rat liver regeneration after partial hepatectomy and induction of ERK phosphorylation by Cpd 5, a K vitamin-based anticancer compound.
Thioalkyl K vitamin derivatives, like 2-(2-mercaptoethanol)-3-methyl-1,4-naphthoquinone (Cpd 5), have been shown to inhibit both hepatoma cell growth and DNA synthesis in rat hepatocytes in vitro. We have here examined the tissue distribution, in vivo tolerance and growth inhibitory effects of a single injected dose of Cpd 5 in rats. Cpd 5 administered i.p. was sufficient to cause a 90% inhibition of the peak in DNA synthesis in rat liver 24 h after two-thirds partial hepatectomy (PH). However, DNA synthesis in post-PH, Cpd 5-treated rat livers did occur, but with a delay of 36 h. Dual phosphorylation of ERK2 was induced in rat liver dose-dependently as early as 0.5 h, but gradually returned to almost basal levels by 6 h after Cpd 5 treatment. The MEK1/2 inhibitor PD098059, administered in vivo 1 h prior to Cpd 5 treatment, antagonized both induction of ERK2 phosphorylation and inhibition of DNA synthesis in rat liver. Liver protein lysates post-PH exhibited protein phosphatase activity for phospho-ERK2, which was inhibited by Cpd 5. These results show that induction of ERK2 phosphorylation is likely involved in the mechanism by which Cpd 5 inhibits PH-induced DNA synthesis, probably as a result of its ability to inhibit the activity of ERK phosphatase(s).


Effect of temperature on transcapillary water movement in isolated cat hindlimb.
Capillary filtration coefficient (CFC) was measured in the isolated cat hindlimb preparation, perfused at 20 ml X min-1 X 100 g muscle-1 with a perfusate containing 6 g/dl albumin and normal electrolyte concentrations, to which were added 50 ml of the cat's blood and 6 micrograms of the vasodilator isoproterenol. CFC was determined three to six times in an initial control period during which the tissue temperature (measured by a 5-mm disk thermistor implanted in a thigh muscle) was controlled near 37 degrees C. Tissue temperature was decreased to 5-10 degrees C by lowering perfusate and ambient air temperatures. About 50 min were required for tissue temperature equilibration. CFC was measured at low temperature and then again at 37 degrees C. For nine experiments, the ratio of CFC at low temperature to that in the 37 degrees C control periods averaged 87% of the ratio of water viscosity at 37 degrees C to that at low temperature. The activation energy for water calculated from these data was 5.0 kcal/mol. These results may be explained by all transcapillary water flow moving by diffusion through narrow pores or by about 90% moving by convection, with the remainder going through a lipid pathway. However, the results may be entirely due to a direct effect of temperature on the geometry of the transcapillary pathway for water movement.


Differential regulation of ceramide synthase components LAC1 and LAG1 in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the essential ceramide synthase reaction requires the presence of one of a homologous pair of genes, LAG1 and LAC1. Mutants that lack both of these genes cannot produce ceramide and exhibit a striking synthetic growth defect. While the regulation of ceramide production is critical for the control of proliferation and for stress tolerance, little is known of the mechanisms that ensure proper control of this process. The data presented here demonstrate that the pleiotropic drug resistance (Pdr) regulatory pathway regulates the transcription of multiple genes encoding steps in sphingolipid biosynthesis, including LAC1. The zinc cluster transcriptional activators Pdr1p and Pdr3p bind to Pdr1p/Pdr3p-responsive elements (PDREs) in the promoters of Pdr pathway target genes. LAC1 contains a single PDRE in its promoter, but notably, LAG1 does not. Reporter gene, Northern blot, and Western blot assays indicated that the expression level of Lac1p is approximately three times that of Lag1p. Detailed analyses of the LAC1 promoter demonstrated that transcription of this gene is inhibited by the presence of the transcription factor Cbf1p and the anaerobic repressor Rox1p. LAG1 transcription was also elevated in cbf1Delta cells, indicating at least one common regulatory input. Although a hyperactive Pdr pathway altered the profile of sphingolipids produced, the loss of either LAC1 or LAG1 alone failed to produce further changes. Two other genes involved in sphingolipid biosynthesis (LCB2 and SUR2) were found to contain PDREs in their promoters and to be induced by the Pdr pathway. These data demonstrate extensive coordinate control of sphingolipid biosynthesis and multidrug resistance in yeast.


Parents' perceptions of child abuse and child discipline in Bangkok, Thailand.
Violation of a child's right to protection is an issue for children all over the world. In Thailand, the greatest barrier to intervening in child abuse issues is the lack of awareness and the positive attitudes and beliefs on using violence as a way to discipline children. The incongruent definition used amongst Thai society and relevant sectors, causes incidences to be under reported and an obstacle to child survival and development. The present study is a qualitative study and aims to explore the perceptions of child abuse and child discipline definitions amongst parents in the Bangkok Metropolitan Area in order to extend broader knowledge for interpretation, definitions and to differentiate the line between child abuse and child discipline. Focus group discussions were used as the primary data collection method and content analysis was applied as the data analysis. The results produced two categories of parents' perceptions regarding child abuse and discipline. First, was the perception of the causes of child punishment and child discipline, and second was the meaning and difference between child abuse and child discipline. The study results would be beneficial for policy makers, health and related sectors to understand the meaning of the terms used amongst family members in order to apply and promote child protection strategies in culturally appropriate


Intracranial metastasis from carcinoma of the paranasal sinus.
Carcinomas of the paranasal sinuses are locally invasive tumors that only occasionally metastasize. The tumor may spread intracranially by local invasion through the dura into the frontal lobes and extension along the vidian nerve. We describe two cases of cerebellar metastasis in patients with local recurrence and discuss the mechanism of spreading. It is possible that more aggressive treatment of these tumors, which results in longer survival, may be associated with an increased incidence of intracranial metastasis.


Muscle strength, muscle mass, and physical disability in women with systemic lupus erythematosus.
Data describing relationships between muscle strength, muscle mass, and physical disability among individuals with systemic lupus erythematosus (SLE) are limited. The present study examines the relationship of muscle strength and muscle mass with physical disability among adult women with SLE. A total of 146 women from a longitudinal SLE cohort participated in the study. All measures were collected during an in-person research visit. Lower extremity muscle strength was assessed by peak knee torque of extension and flexion and by chair-stand time. Total lean body mass, appendicular lean mass, and fat mass (kg/m(2) ) were measured by whole-body dual x-ray absorptiometry. Self-reported physical disability was assessed using the Short Form 36 health survey (SF-36) physical functioning subscale, and the Valued Life Activities (VLA) disability scale. Spearman's rank correlation coefficients tested the correlations between muscle strength, muscle mass, and disability scores. Regression analyses modeled the effect of lower extremity muscle strength and mass on SF-36 and VLA disability scores controlling for age, SLE duration, SLE disease activity measured with the Systemic Lupus Activity Questionnaire, physical activity level, prednisone use, body composition, and depression. On all measures, reduced lower extremity muscle strength was associated with poorer SF-36 and VLA disability scores. Trends persisted after adjustment for covariates. Muscle mass was moderately correlated with muscle strength, but did not contribute significantly to adjusted regression models. Lower extremity muscle strength, but not muscle mass, was strongly associated with physical disability scores. While further studies are needed, these findings suggest that improving muscle strength may reduce physical disability among women with SLE.


Considerations for planning COVID-19 treatment services in humanitarian responses.
The COVID-19 pandemic has the potential to cause high morbidity and mortality in crisis-affected populations. Delivering COVID-19 treatment services in crisis settings will likely entail complex trade-offs between offering services of clinical benefit and minimising risks of nosocomial infection, while allocating resources appropriately and safeguarding other essential services. This paper outlines considerations for humanitarian actors planning COVID-19 treatment services where vaccination is not yet widely available. We suggest key decision-making considerations: allocation of resources to COVID-19 treatment services and the design of clinical services should be based on community preferences, likely opportunity costs, and a clearly articulated package of care across different health system levels. Moreover, appropriate service planning requires information on the expected COVID-19 burden and the resilience of the health system. We explore COVID-19 treatment service options at the patient level (diagnosis, management, location and level of treatment) and measures to reduce nosocomial transmission (cohorting patients, protecting healthcare workers). Lastly, we propose key indicators for monitoring COVID-19 health services.


In Vitro Study To Evaluate the Bioactivity of Freezing a Heparin-Based Dalbavancin Lock Solution.
The use of dalbavancin as a catheter lock solution must be addressed in depth before implementation in clinical practice. We assessed whether a heparin-based dalbavancin lock solution could be frozen in single-dose vials for 6 months without affecting its bioactivity against biofilms of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE). Over 6 months, we tested the bioactivity of a frozen solution of dalbavancin (≈1 mg/ml) plus heparin (60 IU) in terms of CFU counts and metabolic activity against biofilms of Staphylococcus aureus ATCC 43300 (MRSA) and Staphylococcus epidermidis ATCC 35984 (MRSE). The Anti-Xa assay was also performed to assess whether the anticoagulant activity of heparin was reduced under freezing. Every month, we compared the mean value of each variable with that obtained at baseline (before freezing, month 0) using both clinical criteria (values were within 25% of the baseline value) and statistical criteria (linear mixed models). At the end of the experiment (month 6), neither a clinically nor a statistically significant reduction in the bioactivity of dalbavancin-heparin solution was observed in terms of CFU counts and metabolic activity against biofilm of MRSA. Regarding MRSE, considering the clinical criteria, neither CFU counts nor metabolic activity decreased significantly. However, the reduction was statistically significant for all variables. Anti-Xa values (mean [standard deviation] international units per milliliter) for heparin in combination with dalbavancin were within 25% of the heparin-water value. A heparin-based dalbavancin lock solution can be frozen for up to 6 months with no effect on its bioactivity against MRSA and MRSE biofilms.


Eating behaviours in preadolescence are associated with body dissatisfaction and mental disorders - Results of the CCC2000 study.
Preadolescence is a key period in the early stages of eating disorder development. The aim of the present study was, firstly, to investigate restrained, emotional and external eating in a general population-based sample of 11-12 year olds. Secondly, we sought to explore how these eating behaviours are associated with possible predictors of eating disorders, such as body dissatisfaction, weight status and mental disorders. A subsample of 1567 children (47.7% boys; 52.3% girls) from the Copenhagen Child Cohort (CCC2000) completed web-based questionnaires on eating behaviours and body dissatisfaction using The Eating Pattern Inventory for Children (EPI-C) and The Children's Figure Rating Scale. Mental disorders were assessed using the online version of the Development and Well-Being Assessment (DAWBA) based on parental replies with final DSM-IV diagnoses determined by experienced child- and adolescent psychiatrists. Height and weight were measured at a face-to-face assessment. The results showed that restrained eating was significantly associated with overweight, body dissatisfaction and emotional disorders in both genders. Emotional eating showed similar associations with overweight and body dissatisfaction in both genders, but was only associated with mental disorders in girls. External eating was significantly associated with body dissatisfaction and neurodevelopmental disorders in both genders, but was only associated with overweight in girls. Our findings show that problematic eating behaviours can be identified in preadolescence, and co-exist with weight problems and mental disorders. Thus restrained, emotional and external eating was, in different ways, associated with overweight, body dissatisfaction and mental disorders. Our findings point to significant eating behaviours in preadolescence, which could constitute potential predictors of later eating disorder risk.


Homocysteine, folate, methylation, and monoamine metabolism in depression.
Previous studies suggest that folate deficiency may occur in up to one third of patients with severe depression, and that treatment with the vitamin may enhance recovery of the mental state. There are, however, difficulties in interpreting serum and red cell folate assays in some patients, and it has been suggested that total plasma homocysteine is a more sensitive measure of functional folate (and vitamin B12) deficiency. Other studies suggest a link between folate deficiency and impaired metabolism of serotonin, dopamine, and noradrenaline (norepinephrine), which have been implicated in mood disorders. A study of homocysteine, folate, and monoamine metabolism has, therefore, been undertaken in patients with severe depression. In 46 inpatients with severe DSM III depression, blood counts, serum and red cell folate, serum vitamin B12, total plasma homocysteine, and, in 28 patients, CSF folate, S-adenosylmethionine, and the monoamine neurotransmitter metabolites 5HIAA, HVA, and MHPG were examined. Two control groups comprised 18 healthy volunteers and 20 patients with neurological disorders, the second group undergoing CSF examination for diagnostic purposes. Twenty four depressed patients (52%) had raised total plasma homocysteine. Depressed patients with raised total plasma homocysteine had significant lowering of serum, red cell, and CSF folate, CSF S-adenosylmethionine and all three CSF monoamine metabolites. Total plasma homocysteine was significantly negatively correlated with red cell folate in depressed patients, but not controls. Utilising total plasma homocysteine as a sensitive measure of functional folate deficiency, a biological subgroup of depression with folate deficiency, impaired methylation, and monoamine neurotransmitter metabolism has been identified. Detection of this subgroup, which will not be achieved by routine blood counts, is important in view of the potential benefit of vitamin replacement.


Valeriana officinalis ameliorates vacuous chewing movements induced by reserpine in rats.
Oral movements are associated with important neuropathologies as Parkinson's disease and tardive dyskinesia. However, until this time, there has been no known efficacious treatment, without side effects, for these disorders. Thus, the aim of the present study was to investigate the possible preventive effects of V. officinalis, a phytotherapic that has GABAergic and antioxidant properties, in vacuous chewing movements (VCMs) induced by reserpine in rats. Adult male rats were treated with reserpine (1 mg/kg, s.c.) and/or with V. officinalis (in the drinking water, starting 15 days before the administration of the reserpine). VCMs, locomotor activity and oxidative stress measurements were evaluated. Furthermore, we carried out the identification of valeric acid and gallic acid by HPLC in the V. officinalis tincture. Our findings demonstrated that reserpine caused a marked increase on VCMs and the co-treatment with V. officinalis was able to reduce the intensity of VCM. Reserpine did not induce oxidative stress in cerebral structures (cortex, hippocampus, striatum and substantia nigra). However, a significant positive correlation between DCF-oxidation (an estimation of oxidative stress) in the cortex and VCMs (p < 0.05) was observed. Moreover, a negative correlation between Na(+)K(+)-ATPase activity in substantia nigra and the number of VCMs was observed (p < 0.05). In conclusion, V. officinalis had behavioral protective effect against reserpine-induced VCMs in rats; however, the exact mechanisms that contributed to this effect have not been completely understood.


Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial.
Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone.


111In oxine labelled mesenchymal stem cell SPECT after intravenous administration in myocardial infarction.
Mesenchymal stem cells (MSCs) have shown therapeutic potential if successfully delivered to the intended site of myocardial infarction. The purpose of this pilot study was to test the feasibility of 111In oxine labelling of MSCs and single photon emission computed tomography (SPECT) imaging after intravenous administration in a porcine model of myocardial infarction. Adult farm pigs (n=2) were subjected to closed chest experimental myocardial infarction. 111In oxine labelled MSCs (1 x 10(7) to 2 x 10(7) cells) were infused intravenously, and SPECT imaging was performed initially and on days 1, 2, 7 and 14. High quality SPECT images were obtained through 2 weeks of imaging. High initial MSC localization occurred in the lungs and slow progressive accumulation occurred in the liver, spleen and bone marrow. Renal activity was mild and persistent throughout imaging. No appreciable accumulation occurred in the myocardium. It is concluded that 111In oxine radiolabelling of MSCs is feasible, and in vivo imaging with SPECT provides a non-invasive method for sequentially monitoring cell trafficking with good spatial resolution. Because intravenous administration of MSCs results in significant lung activity that obscures the assessment of myocardial cell trafficking, alternative routes of administration should be investigated for this application.


Metabolomic profiling reveals serum L-pyroglutamic acid as a potential diagnostic biomarker for systemic lupus erythematosus.
The spectrum of clinical manifestations and serological phenomena of SLE is heterogeneous among patients and even changes over time unpredictably in individual patients. For this reason, clinical diagnosis especially in complicated or atypical cases is often difficult or delayed leading to poor prognosis. Despite the medical progress nowadays in the understanding of SLE pathogenesis, disease-specific biomarkers for SLE remain an outstanding challenge. Therefore, we undertook this study to investigate potential biomarkers for SLE diagnosis. Serum samples from 32 patients with SLE and 25 gender-matched healthy controls (HCs) were analysed by metabolic profiling based on liquid chromatography-tandem mass spectrometry metabolomics platform. The further validation for the potential biomarker was performed in an independent set consisting of 36 SLE patients and 30 HCs. The metabolite profiles of serum samples allowed differentiation of SLE patients from HCs. The levels of arachidonic acid, sphingomyelin (SM) 24:1, monoacylglycerol (MG) 17:0, lysophosphatidyl ethanolamine (lysoPE) 18:0, lysoPE 16:0, lysophosphatidyl choline (lysoPC) 20:0, lysoPC 18:0 and adenosine were significantly decreased in SLE patients, and the MG 20:2 and L-pyroglutamic acid were significantly increased in SLE group. In addition, L-pyroglutamic acid achieved an area under the receiver-operating characteristic curve of 0.955 with high sensitivity (97.22%) and specificity (83.33%) at the cut-off of 61.54 μM in the further targeted metabolism, indicating diagnostic potential. Serum metabolic profiling is differential between SLE patients and HCs and depicts increased L-pyroglutamic acid as a promising bitformatomarker for SLE.


Congenital diaphragmatic hernias: Severe defect grade predicts the need for fundoplication.
Over one-third of infants with congenital diaphragmatic hernia (CDH) eventually require a Nissen fundoplication (NF). We examined pre- and intraoperative predictors for need of a NF in children undergoing CDH repair to elucidate, which patients will need a later NF.A retrospective analysis of all consecutive patients undergoing CDH repair at our institution from 2008 to 2018 was performed. Patients who underwent a NF were compared to those who did not (noNissen). Logistic regression analysis was performed to find independent predictors for NF in patients undergoing CDH repair. Severe Defect Grade was defined as defect >50% of the hemidiaphragm and intrathoracic liver.One hundred twenty-six patients were included, 42 (33%) underwent NF at a median of 61 days after CDH repair. Intrathoracic liver was more frequent in the NF (71%) versus noNissen (45%) group (P = .008). Absence of >50% of the hemidiaphragm was more frequent in the NF group (76% vs 31%, P < .001). Severe Defect Grade emerged as independent predictor for NF (odds ratio 7, 95% confidence interval 3-16, P < .001).Severe Defect Grade emerged as independent predictor for NF after CDH repair.


Nck in a complex containing the catalytic subunit of protein phosphatase 1 regulates eukaryotic initiation factor 2alpha signaling and cell survival to endoplasmic reticulum stress.
Stress imposed on the endoplasmic reticulum (ER) induces the phosphorylation of the alpha-subunit of the eukaryotic initiation factor 2 (eIF2) on Ser51. This results in transient inhibition of general translation initiation while concomitantly activating a signaling pathway that promotes the expression of genes whose products improve ER function. Conversely, dephosphorylation of eIF2alphaSer51 is accomplished by protein phosphatase 1 (PP1c) complexes containing either the protein CReP or GADD34, which target PP1c to eIF2. Here, we demonstrate that the Src homology (SH) domain-containing adaptor Nck is a key component of a molecular complex that controls eIF2alpha phosphorylation and signaling in response to ER stress. We show that overexpression of Nck decreases basal and ER stress-induced eIF2alpha phosphorylation and the attendant induction of ATF4 and CHOP. In contrast, we demonstrate that the mouse embryonic fibroblasts lacking both isoforms of Nck (Nck1-/-Nck2-/-) show higher levels of eIF2alpha phosphorylation and premature induction of ATF4, CHOP, and GADD34 in response to ER stress and finally, are more resistant to cell death induced by prolonged ER stress conditions. We establish that a significant amount of Nck protein localizes at the ER and is in a complex with eIF2 subunits. Further analysis of this complex revealed that it also contains the Ser/Thr phosphatase PP1c, its regulatory subunit CReP, and dephosphorylates eIF2alpha on Ser51 in vitro. Overall, we demonstrate that Nck as a component of the CReP/PP1c holophosphatase complex contributes to maintain eIF2alpha in a hypophosphorylated state. In this manner, Nck modulates translation and eIF2alpha signaling in response to ER stress.


[Parkinson disease: deep cerebral stimulation].
The effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) or the internal pallidum (GPi) on the parkinsonian triad and on levodopa-induced dyskinesias are very similar. The antiakinetic effect of STN DBS seems to be slightly better. On the contrary to pallidal DBS, stimulation of the STN allows to reduce dopaminergic treatment by more than 50 p. 100 on average. Moreover, the current drain is smaller in STN. Thus, the STN is a low budget target compared to the GPi. STN DBS seems to be as effective on PD tremor as stimulation of the classic thalamic target, the ventral intermediate nucleus (Vim), whereas Vim stimulation has no effect on akinesia and very little on levodopa-induced dyskinesias. Thus, the STN has become the main target nucleus for DBS in PD, which is most often performed bilaterally in one surgical procedure. There is a good correlation of the preoperative response to levodopa and postoperative effects of bilateral STN DBS and this defines the patient population. Given the large patient population, simple guidelines for patient selection are developed. The referring physician can preselect patients based mainly on age (less than 70), absence of dementia and presence of severe disability related to motor fluctuations or dyskinesias. It is the responsibility of the operating centre to determine the levodopa response, to confirm the diagnosis, to rule out contraindications and to make sure that the medical treatment cannot be further optimised. Severe surgical complications with permanent sequels are relatively rare, about 1 p. 100 per implanted side. The patient selection, the precision of the surgery and the quality of the postoperative follow-up are the three main determinants of success.


Reconfigurable optical channel waveguides in lithium niobate crystals produced by combination of low-dose O3+ ion implantation and selective white light illumination.
We report on a new method to form reconfigurable channel waveguides in lithium niobate crystals, based on a combination of low-dose O(3+) ion implantation and selective white light illumination. The fabricated structures show low loss as well as rather high resistivity against optical erasure with red or infrared light, while at the same time reconfiguration of the structures remains possible using homogeneous white light illumination. The transmission properties of the channel waveguide modes can be well simulated numerically by the beam propagation method, which allows for the fabrication of tailored optical interconnections.


Beyond demographic change in human resources planning: an extended framework and application to nursing.
To introduce health care production functions into human resources planning and to apply the approach to analysing the need for registered nurses in Ontario during a period of major reduction in inpatient capacity. Measurement of changes in services delivered by acute care hospitals in Ontario between 1994/95 and 1998/99, and comparison with changes in the mix of human resources, non-human resources and patient needs. Inpatient episodes per nurse fell by almost 2%. At the same time the number of beds was cut by over 20%. As a result, the number of patients per bed increased by 12%. Allowing for severity, there was a 20% reduction in beds per episode and a 3.7% reduction in nurses per episode. The demands on nurses in acute care hospitals have increased as an increasing number of severity-adjusted episodes are served using fewer beds by a reduced number of nurses. Human resources planning traditionally only considers the effects of demographic change on the need for and supply of health care. Failure to recognize the variable and endogenous nature of other health care inputs leads to false impressions about the adequacy of existing supplies of human resources. Consideration of human resources in the context of the production function for health services provides a meaningful way of improving the effectiveness and efficiency of human resources planning.


Overlapping cortical malformations and mutations in TUBB2B and TUBA1A.
Polymicrogyria and lissencephaly are causally heterogeneous disorders of cortical brain development, with distinct neuropathological and neuroimaging patterns. They can be associated with additional structural cerebral anomalies, and recurrent phenotypic patterns have led to identification of recognizable syndromes. The lissencephalies are usually single-gene disorders affecting neuronal migration during cerebral cortical development. Polymicrogyria has been associated with genetic and environmental causes and is considered a malformation secondary to abnormal post-migrational development. However, the aetiology in many individuals with these cortical malformations is still unknown. During the past few years, mutations in a number of neuron-specific α- and β-tubulin genes have been identified in both lissencephaly and polymicrogyria, usually associated with additional cerebral anomalies including callosal hypoplasia or agenesis, abnormal basal ganglia and cerebellar hypoplasia. The tubulin proteins form heterodimers that incorporate into microtubules, cytoskeletal structures essential for cell motility and function. In this study, we sequenced the TUBB2B and TUBA1A coding regions in 47 patients with a diagnosis of polymicrogyria and five with an atypical lissencephaly on neuroimaging. We identified four β-tubulin and two α-tubulin mutations in patients with a spectrum of cortical and extra-cortical anomalies. Dysmorphic basal ganglia with an abnormal internal capsule were the most consistent feature. One of the patients with a TUBB2B mutation had a lissencephalic phenotype, similar to that previously associated with a TUBA1A mutation. The remainder had a polymicrogyria-like cortical dysplasia, but the grey matter malformation was not typical of that seen in 'classical' polymicrogyria. We propose that the cortical malformations associated with these genes represent a recognizable tubulinopathy-associated spectrum that ranges from lissencephalic to polymicrogyric cortical dysplasias, suggesting shared pathogenic mechanisms in terms of microtubular function and interaction with microtubule-associated proteins.


Erg11 mutations associated with azole resistance in clinical isolates of Candida albicans.
The widespread use of azoles has led to increasing azole resistance among Candida albicans strains. One mechanism of azole resistance involves point mutations in the ERG11 gene, which encodes the target enzyme (cytochrome P450 lanosterol 14α-demethylase). In the present study, we amplified and sequenced the ERG11 gene of 23 C. albicans clinical isolates. Seventeen mutations encoding distinct amino acid substitutions were found, of which seven (K143Q, Y205E, A255V, E260V, N435V, G472R, and D502E) were novel. We further verified the contribution of the amino acid substitutions to azole resistance using site-directed mutagenesis of the ERG11 gene to recreate these mutations for heterologous expression in Saccharomyces cerevisiae. We observed that substitutions A114S, Y132H, Y132F, K143R, Y257H, and a new K143Q substitution contributed to significant increases (≧fourfold) in fluconazole and voriconazole resistance; changes in itraconazole resistance were not significant (≦twofold).


Increased proportion of CD56bright natural killer cells in active and inactive systemic lupus erythematosus.
Natural killer (NK) cells belong to the innate immune system but can also affect adaptive immune reactions. This immune regulatory function is often ascribed to the CD56(bright) subpopulation of NK cells that is prevalent in secondary lymphoid tissues and has potent cytokine-producing ability. The NK cells have been described as affecting autoimmune disease and stimulating B-cell production of antibodies, but their role in systemic lupus erythematosus (SLE) pathology has not been extensively studied. We have studied NK cells in SLE, a B-cell-driven systemic autoimmune disease, and phenotypically characterized peripheral blood NK cells in comparison to NK cells from patients with immunoglobulin A nephritis, rheumatoid arthritis and healthy individuals. We have found an increased proportion of CD56(bright) NK cells in SLE, regardless of disease activity. We detected a somewhat increased expression of the activating receptor NKp46/CD335 on NK cells from SLE patients, although neither the percentage of NK cells of all lymphocytes nor the expression of other NK receptors analysed (LIR-1/CD85j, CD94, NKG2C/CD159c, NKG2D/CD314, NKp30/CD337, NKp44/CD336, CD69) differed between patient groups. We show that type I interferon, a proinflammatory cytokine known to be abundant in SLE, can cause increases of CD56(bright) NK cells in vitro. We confirmed that serum levels of interferon-alpha were increased in active, but not in inactive, disease in the SLE patient group. In conclusion, we found an increased proportion of CD56(bright) NK cells in the blood of SLE patients, although it remains to be examined whether and how this relates to the disease process.


Arginine supplementation is well tolerated but does not enhance mitogen-induced lymphocyte proliferation in elderly nursing home residents with pressure ulcers.
Immune function declines with age, increasing risk for infection and delaying wound healing. Arginine enhances immune function and healing of standardized wounds in healthy elderly persons. The purpose of this study was to determine what level of arginine supplementation was orally and metabolically tolerated and effective in enhancing immune function in elderly persons with pressure ulcers. Residents with one or more pressure ulcers were recruited from two local nursing homes. Subjects were randomized to receive 0 g (n = 10; age, 82 +/- 3 years), 8.5 g (n = 11; 81 +/- 3 years), or 17 g (n = 11; 87 +/- 2 years) of supplemental arginine each day for 4 weeks. Oral tolerance, ie, absence of nausea, vomiting, abdominal distention, or diarrhea, was assessed daily. Metabolic tolerance was assessed weekly by evaluating serum electrolytes. Lymphocyte proliferation to phytohemagglutinin and interleukin 2 production were measured at baseline and after 4 weeks of supplementation as indicators of immune function. Supplemental arginine significantly increased plasma arginine levels and was orally and metabolically tolerated with no complaints of abdominal distress or no clinically relevant changes in electrolyte levels among groups. Lymphocyte proliferation and interleukin 2 production were significantly different between nursing homes. When data from nursing homes were considered individually, arginine supplementation did not enhance the proliferative response. In subjects from nursing home 2 only, there was a 38% and 75% decrease (p < .05) in lymphocyte proliferation with 8.5 and 17 g of supplemental arginine, respectively. Interleukin 2 production was no different among supplementation groups. Pharmacologic doses of arginine were well tolerated but did not enhance lymphocyte proliferation or interleukin 2 production in nursing home residents with pressure ulcers. CLINICAL RELEVANCY: Enteral formulas supplemented with pharmacologic levels of arginine are frequently administered to elderly persons. This study demonstrates that the very old can tolerate these nitrogen loads if baseline renal function is normal and fluid intake is encouraged. Further research needs to be completed investigating the effect of arginine supplementation on immune function in this population before recommending arginine use.


Nanodepots Encapsulating a Latency Reversing Agent and Broadly Neutralizing Antibody Enhance Natural Killer Cell Cytotoxicity Against an in vitro Model of Latent HIV.
Current antiretroviral therapies (ART) for human immunodeficiency virus (HIV) are not curative, as the virus persists in latent reservoirs, requiring lifelong adherence to ART and increasing the risk of co-morbidities. "Shock and kill" approaches to reactivate HIV from latent reservoirs followed by administration of anti-HIV drugs represent a promising strategy for eradicating latent HIV. To achieve effective shock and kill, we describe a strategy to eradicate the HIV reservoir that combines latency reversing agents (LRAs), broadly neutralizing antibodies (bnAbs), and natural killer (NK) cells. This strategy utilizes a polymer nanodepot (ND) that co-encapsulates the LRA and bnAb to reactivate latent infection and elicit enhanced cytotoxicity from co-administered NK cells. Poly(lactic-co-glycolic acid) (PLGA) NDs were synthesized using the nanoprecipitation method to co-encapsulate an LRA (TNF-α) and a bnAb (3BNC117) (TNF-α-3BNC117-NDs). ACH-2 cells were used as a cellular model of latent HIV infection. An NK92 subline, genetically modified to constitutively express the Fc receptor CD16, was administered to ACH-2 cells in combination with TNF-α-3BNC117-NDs. ACH-2 cell death and extracellular p24 were measured via flow cytometry and ELISA, respectively. Stable PLGA NDs co-encapsulated TNF-α and 3BNC117 with high efficiencies and released these agents in physiological conditions. NK92 phenotype remained similar in the presence of TNF-α-3BNC117-NDs. TNF-α released from NDs efficiently reactivated HIV in ACH-2 cells, as measured by a 3.0-fold increase in the frequency of intracellular p24 positive cells. Released 3BNC117 neutralized and bound reactivated virus, targeting 57.5% of total ACH-2 cells. Critically, TNF-α-3BNC117-NDs significantly enhanced NK92 cell-mediated killing of ACH-2 cells (1.9-fold) and reduced extracellular levels of p24 to baseline. These findings suggest the therapeutic potential of our novel ND-based tripartite strategy to reactivate HIV from latently infected cells, generate an HIV-specific site for bnAb binding, and enhance the killing of reactivated HIV-infected target cells by NK92 cells.


Genetic diversity and genomic signatures of selection among cattle breeds from Siberia, eastern and northern Europe.
Domestication in the near eastern region had a major impact on the gene pool of humpless taurine cattle (Bos taurus). As a result of subsequent natural and artificial selection, hundreds of different breeds have evolved, displaying a broad range of phenotypic traits. Here, 10 Eurasian B. taurus breeds from different biogeographic and production conditions, which exhibit different demographic histories and have been under artificial selection at various intensities, were investigated using the Illumina BovineSNP50 panel to understand their genetic diversity and population structure. In addition, we scanned genomes from eight breeds for signatures of diversifying selection. Our population structure analysis indicated six distinct breed groups, the most divergent being the Yakutian cattle from Siberia. Selection signals were shared (experimental P-value < 0.01) with more than four breeds on chromosomes 6, 7, 13, 16 and 22. The strongest selection signals in the Yakutian cattle were found on chromosomes 7 and 21, where a miRNA gene and genes related to immune system processes are respectively located. In general, genomic regions indicating selection overlapped with known QTL associated with milk production (e.g. on chromosome 19), reproduction (e.g. on chromosome 24) and meat quality (e.g. on chromosome 7). The selection map created in this study shows that native cattle breeds and their genetic resources represent unique material for future breeding.


IL-21 is required for CD4 memory formation in response to viral infection.
IL-21 has been shown to play an important role in the CD8 T cell response during acute and chronic viral infections. However, the role of IL-21 signaling in the CD4 T cell response to viral infection remains incompletely defined. In a model of infection with vaccinia virus, we show that intrinsic IL-21 signaling on CD4 T cells was critical for the formation of memory CD4 T cells in vivo. We further reveal that IL-21 promoted CD4 T cell survival in a mechanism dependent on activation of the STAT1 and STAT3 signaling pathways. In addition, the activation of Akt is also required for IL-21-dependent survival of CD4 T cells in vivo. These results identify a critical role for intrinsic IL-21 signaling in CD4 T cell survival and memory formation in response to viral infection in vivo and may provide insights into the design of effective vaccine strategies.


Microenvironment proteinases, proteinase-activated receptor regulation, cancer and inflammation.
We propose that in the microenvironment of inflammatory tissues, including tumours, extracellular proteinases can modulate cell signalling in part by regulating proteinase-activated receptors (PARs). We have been exploring this mechanism in a variety of inflammation and tumour-related settings that include tumour-derived cultured cells from prostate and bladder cancer, as well as immune inflammatory cells that are involved in the pathology of inflammatory diseases including multiple sclerosis. Our work showed that proteinase signalling via the PARs affects prostate and bladder cancer-derived tumour cell behaviour and can regulate calcium signalling in human T-cell and macrophage-related inflammatory cells as well as in murine splenocytes. Further, we found that the tumour-derived prostate cancer cells and immune-related cells (Jurkat, THP1, mouse splenocytes) can produce PAR-regulating proteinases (including kallikreins: kallikrein-related peptidases), that can control tissue function by both a paracrine and autocrine mechanism. We suggest that this PAR-driven signalling process involving secreted microenvironment proteinases can play a key role in cancer and inflammatory diseases including multiple sclerosis.


Electroanalytical Overview: Electrochemical Sensing Platforms for Food and Drink Safety.
Robust, reliable, and affordable analytical techniques are essential for screening and monitoring food and water safety from contaminants, pathogens, and allergens that might be harmful upon consumption. Recent advances in decentralised, miniaturised, and rapid tests for health and environmental monitoring can provide an alternative solution to the classic laboratory-based analytical techniques currently utilised. Electrochemical biosensors offer a promising option as portable sensing platforms to expedite the transition from laboratory benchtop to on-site analysis. A plethora of electroanalytical sensor platforms have been produced for the detection of small molecules, proteins, and microorganisms vital to ensuring food and drink safety. These utilise various recognition systems, from direct electrochemical redox processes to biological recognition elements such as antibodies, enzymes, and aptamers; however, further exploration needs to be carried out, with many systems requiring validation against standard benchtop laboratory-based techniques to offer increased confidence in the sensing platforms. This short review demonstrates that electroanalytical biosensors already offer a sensitive, fast, and low-cost sensor platform for food and drink safety monitoring. With continued research into the development of these sensors, increased confidence in the safety of food and drink products for manufacturers, policy makers, and end users will result.


Screening for intimate-partner violence in the pediatric emergency department.
The aims of this study were to determine the annual prevalence of intimate-partner violence (IPV) in an urban pediatric emergency department (ED) among mothers seeking care for their children, to examine the associations between IPV and family socioeconomic characteristics, triage time, and child's diagnosis, and to describe perceptions and preferences for IPV screening. A confidential 15-item survey was completed by 451 women caretakers who were unaccompanied by a male partner in an urban pediatric ED associated with a children's hospital. Women were enrolled during 4-hour time blocks selected to represent ED use patterns during June and July 2002. Survey questions addressed experiences of IPV (physical or sexual violence and perception of safety) in the preceding year and preferences for IPV screening. We also collected information about the women's socioeconomic characteristics and the child's triage time and diagnosis. Fifty women reported IPV, an annual prevalence of 11%. Compared with white women, the relative risk of IPV among black women was 1.1 (95% confidence interval [CI], 1.0-1.2) and among Hispanic women was 1.1 (95% CI, 1.0-1.2). Compared with women who completed college, the relative risk of women who had not completed high school was 5.8 (95% CI, 2.0-26.4). We observed no association with poverty. Women who reported IPV more often sought care for their child in the evening (4-12 pm, chi2, P < 0.01); there was no association with the child's diagnosis. Most (75%) stated that IPV screening in the pediatric ED was appropriate. The annual prevalence of IPV in a pediatric ED is 11%. As socioeconomic and visit characteristics are imprecise in identifying women at risk, screening should include all women. Screening for IPV in the pediatric ED is acceptable to women.


Effects of compassion training on brain responses to suffering others.
Compassion meditation (CM) is a promising intervention for enhancing compassion, although its active ingredients and neurobiological mechanisms are not well-understood. To investigate these, we conducted a three-armed placebo-controlled randomized trial (N = 57) with longitudinal functional magnetic resonance imaging (fMRI). We compared a 4-week CM program delivered by smartphone application with (i) a placebo condition, presented to participants as the compassion-enhancing hormone oxytocin, and (ii) a condition designed to control for increased familiarity with suffering others, an element of CM which may promote compassion. At pre- and post-intervention, participants listened to compassion-eliciting narratives describing suffering others during fMRI. CM increased brain responses to suffering others in the medial orbitofrontal cortex (mOFC) relative to the familiarity condition, p < 0.05 family-wise error rate corrected. Among CM participants, individual differences in increased mOFC responses positively correlated with increased compassion-related feelings and attributions, r = 0.50, p = 0.04. Relative to placebo, the CM group exhibited a similar increase in mOFC activity at an uncorrected threshold of P < 0.001 and 10 contiguous voxels. We conclude that the mOFC, a region closely related to affiliative affect and motivation, is an important brain mechanism of CM. Effects of CM on mOFC function are not explained by familiarity effects and are partly explained by placebo effects.


Effects of subthalamic nucleus stimulation on striatal dopaminergic transmission in patients with Parkinson's disease within one-year follow-up.
The mechanisms by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) leads to clinical benefit in Parkinson's disease (PD), especially with regard to dopaminergic transmission, remain unclear. Therefore, the objective of our study was to evaluate alterations of synaptic dopaminergic signaling following bilateral STN-DBS in advanced PD within a one-year follow-up. We used [(123)I]FP-CIT single-photon emission computed tomography (SPECT) to measure dopamine transporter (DAT) availability and [(123)I]IBZM SPECT to assess dopamine D(2) receptor (D2R) availability (stimulator ON condition).Patients (n=18) showed a tendency towards a better suppression of symptoms after STN-DBS (Unified Parkinson's Disease Rating Scale motor score with medication decreased from 24.1+/-16.1 to 15.4+/-7.45; p=0. 002) while medication was strongly reduced (61% reduction of levodopa equivalent units; p<0. 0001). No changes of striatal [(123)I]FP-CIT binding and an increase of [(123)I]IBZM binding up to 16% (p<0. 05) between pre-surgery and follow-up investigations were noticed. These data show that clinical improvement and reduction of dopaminergic drugs in patients with advanced PD undergoing bilateral STN-DBS are paralleled by stable DAT and recovery of striatal D2R availability 12 months after surgery.


Effect of antiretroviral therapy on malaria incidence in HIV-infected Ugandan adults.
Using the data of a trial on cotrimoxazole (CTX) cessation, we investigated the effect of different antiretroviral therapy (ART) regimens on the incidence of clinical malaria. During the cotrimoxazole cessation trial (ISRCTN44723643), HIV-infected Ugandan adults with CD4 at least 250 cells/μl were randomized to receive either CTX prophylaxis or placebo and were followed for a median of 2.5 years. Blood slides for malaria microscopy were examined at scheduled visits and at unscheduled visits when the participant felt unwell. CD4 cell counts were done 6-monthly. Malaria was defined as fever with a positive blood slide. ART regimens were categorized as nucleoside reverse transcriptase inhibitor (NRTI) only, non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing or protease inhibitor containing. Malaria incidence was calculated using random effects Poisson regression to account for clustering of events. Malaria incidence in the three ART regimen groups was 9.9 (3.6-27.4), 9.3 (8.3-10.4), and 3.5 (1.6-7.6) per 100 person-years, respectively. Incidence on protease inhibitors was lower than that on the other regimens with the results just reaching significance (adjusted rate ratio 0.4, 95% confidence interval = 0.2-1.0, comparing with NNRTI regimens). Stratification by CTX/placebo use gave similar results, without evidence of an interaction between the effects of CTX/placebo use and ART regimen. There was no evidence of an interaction between ART regimen and CD4 cell count. There was some evidence that protease inhibitor-containing ART regimens may be associated with a lower clinical malaria incidence compared with other regimens. This effect was not modified by CTX use or CD4 cell count. The antimalarial properties of protease inhibitors may have clinical and public health importance.


Effects of body condition on buoyancy in endangered North Atlantic right whales.
Buoyancy is an important consideration for diving marine animals, resulting in specific ecologically relevant adaptations. Marine mammals use blubber as an energy reserve, but because this tissue is also positively buoyant, nutritional demands have the potential to cause considerable variation in buoyancy. North Atlantic right whales Eubalaena glacialis are known to be positively buoyant as a result of their blubber, and the thickness of this layer varies considerably, but the effect of this variation on buoyancy has not been explored. This study compared the duration and rate of ascending and descending glides, recorded with an archival tag, with blubber thickness, measured with an ultrasound device, in free-swimming right whales. Ascending whales with thicker blubber had shorter portions of active propulsion and longer passive glides than whales with thinner blubber, suggesting that blubber thickness influences buoyancy because the buoyant force is acting in the same direction as the animal's movement during this phase. Whales with thinner layers also used similar body angles and velocities when traveling to and from depth, while those with thicker layers used shallower ascent angles but achieved higher ascent velocities. Such alterations in body angle may help to reduce the cost of transport when swimming against the force of buoyancy in a state of augmented positive buoyancy, which represents a dynamic response to reduce the energetic consequences of physiological changes. These results have considerable implications for any diving marine animal during periods of nutritional stress, such as during seasonal migrations and annual variations in prey availability.


Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression.
We profiled the expression of genes in benign and untreated human prostate cancer tissues using oligonucleotide microarrays. We report here 50 genes with distinct expression patterns in metastatic and confined tumors (Gleason score 6 and 9; lymph node invasive and noninvasive). Validation of expression profiles of 6 genes by quantitative PCR revealed a strong inverse correlation in the expression of zinc finger protein 185 (ZNF185), bullous pemphigoid antigen gene (BPAG1), and prostate secretory protein (PSP94) with progression of prostate cancer. Treatment of prostate cancer cell lines with 5-aza-2'-deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, restored ZNF185 expression levels. Moreover, methylation-specific PCR confirmed methylation of the 5'CpG islands of the ZNF185 gene in all of the metastatic tissues and 44% of the localized tumor tissues, as well as in the prostate cancer cell lines tested. Thus, transcriptional silencing of ZNF185 by methylation in prostate tumor tissues implicates the ZNF185 gene in prostate tumorigenesis.


Dynamical theory of spin relaxation.
The dynamics of a spin system is usually calculated using the density matrix. However, the usual formulation in terms of the density matrix predicts that the signal will decay to zero, and does not address the issue of individual spin dynamics. Using stochastic calculus, we develop a dynamical theory of spin relaxation, the origins of which lie in the component spin fluctuations. This entails consideration of random pure states for individual protons, and how these pure states are correctly combined when the density matrix is formulated. Both the lattice and the spins are treated quantum mechanically. Such treatment incorporates both the processes of spin-spin and (finite temperature) spin-lattice relaxation. Our results reveal the intimate connections between spin noise and conventional spin relaxation.


Two evolutionarily conserved essential beta-barrel proteins in the chloroplast outer envelope membrane.
Chloroplasts are organelles specific to photosynthetic eukaryotes that support the lives of most organisms on earth. Chloroplasts were derived from an ancient cyanobacterium by endosymbiosis, and one characteristic shared between them and extant cyanobacteria is the presence of beta-barrel proteins in the outer membrane. These integral membrane proteins are also found in the outer membranes of proteobacteria and mitochondria. In particular, a group of homologous beta-barrel proteins called BamA homologs are present in all Gram-negative bacteria and the endosymbiotic organelles, i.e., chloroplasts and mitochondria. It was recently revealed that, in both proteobacteria and mitochondria, there is a single essential BamA homolog that mediates beta-barrel protein assembly. In a chloroplast, there are two distinct BamA homologs, Toc75 and OEP80, which diverged early in the evolution of chloroplasts from their common ancestor with extant cyanobacteria. Recent genetic studies demonstrated that each of these proteins is indispensable for viability of plants although neither has been shown to be involved in beta-barrel protein assembly. Toc75 catalyzes import of nuclear-encoded precursor proteins, a process that is not required for bacteria, whereas the molecular function of OEP80 remains elusive. Establishment of a protein import apparatus was required to facilitate the transfer of genes from the endosymbiont to the host cell nucleus. Hence, we propose that the gene duplication giving rise to the two essential BamA homologs was a prerequisite for the successful conversion of the cyanobacterial endosymbiont into the chloroplast. Consequently, continued study of these two chloroplast proteins should advance our understanding of endosymbiosis and evolutionarily conserved proteins in general.


Body image perceptions in Western and post-communist countries: a cross-cultural pilot study of children and parents.
The development of an unrealistic ideal body image and body size dissatisfaction among children is common in Western countries, including the USA and many European nations. However, little is known about children's body image perceptions in post-communist countries. This pilot study evaluated body image perceptions in a sample of Czech school-aged children and their parents and compared them with the perceptions of American children and parents. Ninety-seven Czech and 45 American 4th-6th graders and their parents from eight urban schools participated in this study. A previously developed silhouette body image instrument was utilized in a parent questionnaire and during child interviews to measure perceived and ideal body image perceptions of children and parents. Descriptive statistics, independent t-tests and paired t-tests were used to compare differences between children's and parents' perceived and ideal body image perceptions. Associations between body image perceptions and other variables were explored using bivariate correlations. American children had a thinner ideal body image compared with Czech children (P < 0.05). However, a larger proportion of Czech boys desired to be thinner compared with American boys (34.2% vs. 20%). Parent's ideal body image for their children did not differ by nationality (P = 0.858). While the pressure on children to look thinner was apparent among both American and Czech children, Czech children considered a larger body size as more ideal. A future study should evaluate body image perceptions and factors influencing these perceptions in a representative sample of Czech children and parents.


Love as harm reduction: fighting AIDS and stigma in Vietnam.
In the summer of 2009, I visited a humble orphanage for children with HIV/AIDS in Vietnam. Here, like many parts in the world, the very existence of marginalized people with stigmatized illness is hidden away. Relegated to the shadows of society, these children lacked something more fundamental than housing, shelter, nutrition and medications. They lacked families to love and care for them unconditionally. One might think it self-evident that a visit to an orphanage for children with HIV would be profound, but the profundity wasn't where I expected to find it. It was in how the children had created their own family, loving each other like brothers and sisters, and the way the priest who operated the shelters was more than a Father, he was a dad to dozens of children. This is an account of love as harm reduction in the Mai Tam orphanage in Ho Chi Minh City.


Recombinant protein secretion by Bacillus subtilis and Lactococcus lactis: pathways, applications, and innovation potential.
Secreted recombinant proteins are of great significance for industry, healthcare and a sustainable bio-based economy. Consequently, there is an ever-increasing need for efficient production platforms to deliver such proteins in high amounts and high quality. Gram-positive bacteria, particularly bacilli such as Bacillus subtilis, are favored for the production of secreted industrial enzymes. Nevertheless, recombinant protein production in the B. subtilis cell factory can be very challenging due to bottlenecks in the general (Sec) secretion pathway as well as this bacterium's intrinsic capability to secrete a cocktail of highly potent proteases. This has placed another Gram-positive bacterium, Lactococcus lactis, in the focus of attention as an alternative, non-proteolytic, cell factory for secreted proteins. Here we review our current understanding of the secretion pathways exploited in B. subtilis and L. lactis to deliver proteins from their site of synthesis, the cytoplasm, into the fermentation broth. An advantage of this cell factory comparison is that it identifies opportunities for protein secretion pathway engineering to remove or bypass current production bottlenecks. Noteworthy new developments in cell factory engineering are the mini-Bacillus concept, highlighting potential advantages of massive genome minimization, and the application of thus far untapped 'non-classical' protein secretion routes. Altogether, it is foreseen that engineered lactococci will find future applications in the production of high-quality proteins at the relatively small pilot scale, while engineered bacilli will remain a favored choice for protein production in bulk.


Nerve Transfers for the Restoration of Wrist, Finger, and Thumb Extension After High Radial Nerve Injury.
High radial nerve injury is a common pattern of peripheral nerve injury most often associated with orthopedic trauma. Nerve transfers to the wrist and finger extensors, often from the median nerve, offer several advantages when compared to nerve repair or grafting and tendon transfer. In this article, we discuss the forearm anatomy pertinent to performing these nerve transfers and review the literature surrounding nerve transfers for wrist, finger, and thumb extension. A suggested algorithm for management of acute traumatic high radial nerve palsy is offered, and our preferred surgical technique for treatment of high radial nerve palsy is provided.


Age differences in speed of processing are partially mediated by differences in axonal integrity.
Advanced age is associated with declines in brain structure and in cognitive performance, but it is unclear which aspects of brain aging mediate cognitive declines. We inquired if individual differences in white matter integrity contribute to age differences in two cognitive domains with established vulnerability to aging: executive functioning and speed of processing. The participants were healthy volunteers aged 50-81, some of whom had elevated blood pressure, a known vascular risk factor. Using latent variable analyses, we examined whether age differences in regional white matter integrity mediated age-related differences in executive functions and speed of processing. Although diffusion-related latent variables showed stronger age differences than white matter volumes and white matter hyperintensity volumes, only one of them was significantly associated with cognitive performance. Smaller linear anisotropy partially mediated age-related reduction in speed of processing. The effect was significant in posterior (temporal-parietal-occipital) but not anterior (frontal) region, and appeared stronger for cognitive rather than reaction time measures of processing speed. The presence of hypertensive participants did not affect the results. We conclude that in healthy adults, deterioration of axonal integrity and ensuing breech of connectivity may underpin age-related slowing of information processing.


The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.
In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.


Contribution of metabolic disease to bone fragility in MAGP1-deficient mice.
Microfibril-associated glycoprotein-1 (MAGP1) is an extracellular matrix protein that interacts with fibrillin and is involved in regulating the bioavailability of signaling molecules such as TGFβ. Mice with germline MAGP1 deficiency (Mfap2-/-) develop increased adiposity, hyperglycemia, insulin resistance, bone marrow adipose tissue expansion, reduced cancellous bone mass, cortical bone thinning and bone fragility. The goal of this study was to assess whether the Mfap2-/- bone phenotypes were due to loss of MAGP1 locally or secondary to a change in whole body physiology (metabolic dysfunction). To do this, mice with conditional deletion of MAGP1 in the limb skeleton were generated by crossing MAGP1-flox mice (Mfap2lox/lox) with Prx1-Cre mice. Mfap2Prx-/- mice did not show any changes in peripheral adiposity, hyperglycemia or insulin sensitivity, but did have increased bone length and cancellous bone loss that was comparable to the germline Mfap2-/- knockout. Unlike the germline knockout, marrow adiposity, cortical bone thickness and bone strength in Mfap2Prx-/- mice were normal. These findings implicate systemic metabolic dysfunction in the development of bone fragility in germline Mfap2-/- mice. An unexpected finding of this study was the detection of MAGP1 protein in the Mfap2Prx-/- hematopoietic bone marrow, despite the absence of MAGP1 protein in osseous bone matrix and absent Mfap2 transcript expression at both sites. This suggests MAGP1 from a secondary site may accumulate in the bone marrow, but not be incorporated into the bone matrix, during times of regional MAGP1 depletion.


Friendship and the religiosity of Indonesian Muslim adolescents.
Adolescents' religious involvement occurs within a social context, an understudied aspect of which is relationships with peers. This longitudinal study assessed changes in religiosity over 1 year and explored the extent to which these were associated with their friends' religiosity and problem behavior. The first year sample included 1,010 (52.5% female) Muslim 13 and 15 year old Indonesian adolescents; 890 of these were assessed 1 year later. Adolescents were similar to their friends in religiosity. Changes in religiosity from year one to two were associated with friends' religiosity such that adolescents with religious friends were more religious at year two than those with less religious friends. Reductions in religiosity were also associated with the presence of problem behavior, consistent with the inverse relationship between these. Peers may play an important role in the development of adolescent religiousness and exploring these influences deserves further study.


An eHealth Intervention for Patients in Rural Areas: Preliminary Findings From a Pilot Feasibility Study.
eHealth facilitation of chronic disease management has potential to increase engagement and effectiveness and extend access to care in rural areas. The objective of this study was to demonstrate the feasibility and acceptability of an eHealth system for the management of chronic conditions in a rural setting. We developed an online management program which incorporated content from the Flinders Chronic Condition Management Program (Flinders Program) and used an existing software platform (goACT), which is accessible by patients and health care workers using either Web-enabled mobile phone or Internet, enabling communication between patients and clinicians. We analyzed the impact of this eHealth system using qualitative and simple quantitative methods. The eHealth system was piloted with 8 recently hospitalized patients from rural areas, average age 63 (SD 9) years, each with an average of 5 chronic conditions and high level of psychological distress with an average K10 score of 32.20 (SD 5.81). Study participants interacted with the eHealth system. The average number of logins to the eHealth system by the study participants was 26.4 (SD 23.5) over 29 weeks. The login activity was higher early in the week. The pilot demonstrated the feasibility of implementing and delivering a chronic disease management program using a Web-based patient-clinician application. A qualitative analysis revealed burden of illness and low levels of information technology literacy as barriers to patient engagement.


Cognitive estimation abilities in healthy and clinical populations: the use of the Cognitive Estimation Test.
Estimation abilities are a group of processes that involve functions such as planning, attention, abstract reasoning, and also mnemonic processes, like semantic and working memory. They are allocated in order to solve problems for which the answers are not readily available. Estimation abilities can be measured using the Cognitive Estimation Test (CET). The aim of this article was to review the use of the CET and other tests of cognitive estimation in healthy and pathological populations. We discussed studies examining correlations between the CET and other measures of executive functions and the importance of the standardization of measures that assess estimation abilities.


Assessment of Diastolic Function in Single-Ventricle Patients After the Fontan Procedure.
Patients with functional single ventricles after the Fontan procedure have abnormal cardiac mechanics. The aims of this study were to determine factors that influence diastolic function and to describe associations of diastolic function with current clinical status. Echocardiograms were obtained as part of the Pediatric Heart Network Fontan Cross-Sectional Study. Diastolic function grade (DFG) was assessed as normal (grade 0), impaired relaxation (grade 1), pseudonymization (grade 2), or restrictive (grade 3). Studies were also classified dichotomously (restrictive pattern present or absent). Relationships between DFG and pre-Fontan variables (e.g., ventricular morphology, age at Fontan, history of volume-unloading surgery) and current status (e.g., systolic function, valvar regurgitation, exercise performance) were explored. DFG was calculable in 326 of 546 subjects (60%) (mean age, 11.7 ± 3.3 years). Overall, 32% of patients had grade 0, 9% grade 1, 37% grade 2, and 22% grade 3 diastolic function. Although there was no association between ventricular morphology and DFG, there was an association between ventricular morphology and E', which was lowest in those with right ventricular morphology (P < .001); this association remained significant when using Z scores adjusted for age (P < .001). DFG was associated with achieving maximal effort on exercise testing (P = .004); the majority (64%) of those not achieving maximal effort had DFG 2 or 3. No additional significant associations of DFG with laboratory or clinical measures were identified. Assessment of diastolic function by current algorithms results in a high percentage of patients with abnormal DFG, but few clinically or statistically significant associations were found. This may imply a lack of impact of abnormal diastolic function on clinical outcomes in this cohort, or it may indicate that the methodology may not be applicable to pediatric patients with functional single ventricles.


Harnessing Population Pedigree Data and Machine Learning Methods to Identify Patterns of Familial Bladder Cancer Risk.
Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer. This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using standardized incidence risk (SIR) ratios that account for sex, age, birth cohort, and person-years of the pedigree members. We identify 1,023 families with a significantly higher bladder cancer rate than population controls (familial bladder cancer). Familial SIRs are then calculated across 25 cancer types, and a weighted Gower distance with K-medoids clustering is used to identify familial multicancer configurations (FMC). We found five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial bladder cancer clusters. Laryngeal, lung, stomach, acute lymphocytic leukemia, Hodgkin disease, soft-tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial bladder cancer families. This study identified five familial bladder cancer FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial bladder cancer. FMC configurations could permit better definitions of cancer phenotypes (subtypes or multicancer) for gene discovery and environmental risk factor studies.


Novel TIGR/MYOC mutations in families with juvenile onset primary open angle glaucoma.
Mutations in the trabecular meshwork induced glucocorticoid response protein (TIGR) or myocilin (MYOC) has recently been shown to cause juvenile onset primary open angle glaucoma (JOAG). In this study, we identified two new mutations (Asp380Ala and Ser502Pro) in two British families and another (Pro370Leu) in a French-Canadian family. These mutations were not present in a total of 106 normal chromosomes. In another Turkish family with JOAG, we also detected a sequence variant that was proven to be an amino acid polymorphism (Arg76Lys). No other sequence changes were found in the entire coding region and splice junctions of the TIGR/MYOC gene in this family. However, it is still possible that mutations either in the TIGR promoter or in another neighbouring gene could cause glaucoma in this JOAG family. Our results confirm the role of the TIGR/MYOC gene in the aetiology of the JOAG phenotype.