Maleic acid is a biomarker for maleylacetoacetate isomerase deficiency; implications for newborn screening of tyrosinemia type 1.

Dried blood spot succinylacetone (SA) is often used as a biomarker for newborn screening (NBS) for tyrosinemia type 1 (TT1). However, false-positive SA results are often observed. Elevated SA may also be due to maleylacetoacetate isomerase deficiency (MAAI-D), which appears to be clinically insignificant. This study investigated whether urine organic acid (uOA) and quantitative urine maleic acid (Q-uMA) analyses can distinguish between TT1 and MAAI-D. We reevaluated/measured uOA (GC-MS) and/or Q-uMA (LC-MS/MS) in available urine samples of nine referred newborns (2 TT1, 7 false-positive), eight genetically confirmed MAAI-D children, and 66 controls. Maleic acid was elevated in uOA of 5/7 false-positive newborns and in the three available samples of confirmed MAAI-D children, but not in TT1 patients. Q-uMA ranged from not detectable to 1.16 mmol/mol creatinine in controls (n = 66) and from 0.95 to 192.06 mmol/mol creatinine in false-positive newborns and MAAI-D children (n = 10). MAAI-D was genetically confirmed in 4/7 false-positive newborns, all with elevated Q-uMA, and rejected in the two newborns with normal Q-uMA. No sample was available for genetic analysis of the last false-positive infant with elevated Q-uMA. Our study shows that MAAI-D is a recognizable cause of false-positive TT1 NBS results. Elevated urine maleic acid excretion seems highly effective in discriminating MAAI-D from TT1.

The Lived Experience of Human-Pet Relationships among Adult Survivors of Childhood Sexual Abuse: An Interpretative Phenomenological Analysis.

Given the high prevalence and severe consequences of childhood sexual abuse, it is essential to identify ways to support adult survivors. One potential and relatively unexplored resource available to survivors is the human-pet relationship. In the literature, the human-pet relationship is linked to many positive benefits to physiological regulation, mental health, physical health, and social support - areas of functioning where survivors of childhood sexual abuse may be particularly at risk. Despite existing evidence, there is little research on human-pet relationships among survivors of childhood sexual abuse. To help address this gap, this qualitative study explored the lived experience of human-pet relationships among adult survivors of childhood sexual abuse. Utilizing data collection and analysis methods from Interpretative Phenomenological Analysis, semi-structured interviews were conducted with 10 adult survivors of childhood sexual abuse. The following themes were developed from the data: (a) close bond with pet; (b) idiosyncrasies within the human-pet relationship; (c) moral responsibility; (d) fundamental differences between pets and humans; (e) safety in the human-pet relationship; (f) resource for coping with painful experience; (g) positive impact on well-being; (h) buttress for human-human social interaction; (i) medium for skill and knowledge development; and (j) shortcomings of the human-pet relationship. Findings are discussed in the context of the existing literature, along with considerations for practice and future research with childhood sexual abuse survivors.

Differences in attentional control and white matter microstructure in adolescents with attentional, affective, and behavioral disorders.

Adolescence is a critical time of physiological, cognitive, and social development. It is also a time of increased risk-taking and vulnerability for psychopathology. White matter (WM) changes during adolescence have been better elucidated in the last decade, but how WM is impacted by psychopathology during this time remains unclear. Here, we examined the link between WM microstructure and psychopathology during adolescence. Twenty youth diagnosed with affective, attentional, and behavioral disorders (clinical sample), and 20 age-matched controls were recruited to examine group differences in WM microstructure, attentional control, and the link between them. The main results showed that clinical sample had relatively lower attentional control and fractional anisotropy (FA) in WM throughout the brain: two association tracts were identified, and many differences were found in areas rich in callosal and projection fibers. Moreover, increased FA was positively associated with attention performance in the clinical sample in structures supporting ventral WM pathways, whereas a similar link was identified in controls in dorsal WM association fibers. Overall, these results support a model of general impairment in WM microstructure combined with reliance on altered, perhaps less efficient, pathways for attentional control in youth with affective, attentional, and behavioral disorders.

Mindfulness-based stress reduction for mental health in youth: a cluster randomized controlled trial.

BACKGROUND: Mental illness is among the most common causes of morbidity, mortality, and disability in childhood. Mindfulness-based stress reduction (MBSR) has shown significant benefit in mental health; however, evidence of its effectiveness in youth is limited. The objective of this study was to compare the efficacy of MBSR plus usual care versus usual care alone for reducing mental health symptoms in youth. METHODS: A two-arm, mixed methods, randomized cluster-controlled trial of 12-18 year olds who were residents of CASA House, a voluntary residential treatment program for adolescents, between January 2011 and March 2013 (clinicaltrials.gov, NCT01307943). INTERVENTIONS: Treatment terms were randomized to usual care, or MBSR plus usual care, which included eight MBSR sessions of 2 hr/week. OUTCOMES: The primary outcome was impact on emotions and behavior at the end of the program, using the Behavior Assessment System for Children, Second Edition (BASC-2). Secondary outcomes included perceived stress levels, mindfulness, and emotional regulation. RESULTS: A total of 85 participants were randomized to either the MBSR arm (n = 45) or control arm (n = 40). Significant differences in favor of MBSR were found on Teacher ratings of the Internalizing Problems (p = .038) and Adaptive Skills subscales (p = .022) on the BASC-2. No significant differences were found on other outcomes. A post hoc analysis found that the MBSR arm had a significantly shorter time to discharge (p = .02). CONCLUSION: The results of this study indicate that MBSR is effective for improved coping with internalizing problems and adaptive emotional skills in our sample. Future studies should focus on larger, longer-term studies in youth.

Comparison of Urdu Versions of the Resilience Scale and the Resilience Scale for Adults.

BACKGROUND AND PURPOSE: Several methodological challenges are associated with measuring resilience in women. This study compares the 14-item Resilience Scale (RS-14) and the Resilience Scale for Adults (RSA) in a community sample of women. METHODS: Data were collected from 120 women residing in low socioeconomic areas of Karachi, Pakistan. Construct validity, internal consistency, and responsiveness were calculated. RESULTS: Both scales demonstrated satisfactory psychometric characteristics. The total RS-14 score was significantly associated with all subscales of the RSA. However, two items of the RS-14 did not show any association with any of the subscales of the RSA. Medium effect size was noted on the "structured style"subscale of the RSA. CONCLUSION: Differences between the scales concluded that the Urdu version the of RSA yielded improved results in this sample.

Social support intervention to promote resilience and quality of life in women living in Karachi, Pakistan: a randomized controlled trial.

OBJECTIVES: This study tested the efficacy of a 6-week social support intervention for enhancing resilience and quality of life among women living in low socioeconomic areas of Karachi, Pakistan. METHODS: One hundred and twenty women were randomly allocated to the intervention (n = 60) or control group (n = 60). Women in the intervention group attended a 6-week social support program, while those in the control group attended a single mental health awareness session. Outcome variables were measured via the resilience scale-14 item (RS-14), the resilience scale for adults (RSA), and World Health Organization quality of life brief scale (WHOQOL-BREF). RESULTS: Compared to participants in the control group, women in the intervention group reported improvements in resilience measured by RS-14 (p = 0.022) and the structured style subscale of the RSA (p = 0.043). A medium effect size was also measured on the structured style subscale (d = 0.6, 95% CI = 0.62874, 2.57126). No significant findings were noted on QOL scores. CONCLUSIONS: Community-based social support interventions are a gender-sensitive-, culturally appropriate-, and resource-sparing approach to promote women's resilience and improve their mental health.

Impact of a mindfulness-based stress reduction program from the perspective of adolescents with serious mental health concerns.

BACKGROUND: While studies on mindfulness-based stress reduction (MBSR) for youth have recently emerged, there is a shortage of research on how adolescents from clinical populations experience MBSR. The purpose of this qualitative study was to explore the impact of MBSR from the subjective perspective of adolescents with serious mental health concerns. METHOD: Adolescents (n = 28) from a residential treatment center participated in an adapted 8-week MBSR program in which they learned a range of mindfulness skills and were encouraged to apply the skills to their everyday lives. At the end of the program and at a 3-month follow-up, the youth participated in semistructured interviews in which they were asked to describe the impact of the program from their perspectives. Basic interpretive qualitative analysis methods were used to code the data and to group the codes into higher level themes. RESULTS: Six main themes were found, including improved mood, enhanced relationship to self, increased self-control, improved problem-solving, awareness of the present, and enhanced interpersonal relationships. DISCUSSION: Results from this study suggest that the MBSR program was perceived as beneficial both in the short-term and follow-up in several aspects of emotional, cognitive, and interpersonal functioning.

Static mechanical strain induces capillary endothelial cell cycle re-entry and sprouting.

Vascular endothelial cells are known to respond to a range of biochemical and time-varying mechanical cues that can promote blood vessel sprouting termed angiogenesis. It is less understood how these cells respond to sustained (i.e., static) mechanical cues such as the deformation generated by other contractile vascular cells, cues which can change with age and disease state. Here we demonstrate that static tensile strain of 10%, consistent with that exerted by contractile microvascular pericytes, can directly and rapidly induce cell cycle re-entry in growth-arrested microvascular endothelial cell monolayers. S-phase entry in response to this strain correlates with absence of nuclear p27, a cyclin-dependent kinase inhibitor. Furthermore, this modest strain promotes sprouting of endothelial cells, suggesting a novel mechanical 'angiogenic switch'. These findings suggest that static tensile strain can directly stimulate pathological angiogenesis, implying that pericyte absence or death is not necessarily required of endothelial cell re-activation.

Combinatorial molecular optimization of cement hydrates.

Despite its ubiquitous presence in the built environment, concrete's molecular-level properties are only recently being explored using experimental and simulation studies. Increasing societal concerns about concrete's environmental footprint have provided strong motivation to develop new concrete with greater specific stiffness or strength (for structures with less material). Herein, a combinatorial approach is described to optimize properties of cement hydrates. The method entails screening a computationally generated database of atomic structures of calcium-silicate-hydrate, the binding phase of concrete, against a set of three defect attributes: calcium-to-silicon ratio as compositional index and two correlation distances describing medium-range silicon-oxygen and calcium-oxygen environments. Although structural and mechanical properties correlate well with calcium-to-silicon ratio, the cross-correlation between all three defect attributes reveals an indentation modulus-to-hardness ratio extremum, analogous to identifying optimum network connectivity in glass rheology. We also comment on implications of the present findings for a novel route to optimize the nanoscale mechanical properties of cement hydrate.

Thermodynamics of water confined in porous calcium-silicate-hydrates.

Water within pores of cementitious materials plays a crucial role in the damage processes of cement pastes, particularly in the binding material comprising calcium-silicate-hydrates (C-S-H). Here, we employed Grand Canonical Monte Carlo simulations to investigate the properties of water confined at ambient temperature within and between C-S-H nanoparticles or "grains" as a function of the relative humidity (%RH). We address the effect of water on the cohesion of cement pastes by computing fluid internal pressures within and between grains as a function of %RH and intergranular separation distance, from 1 to 10 Å. We found that, within a C-S-H grain and between C-S-H grains, pores are completely filled with water for %RH larger than 20%. While the cohesion of the cement paste is mainly driven by the calcium ions in the C-S-H, water facilitates a disjoining behavior inside a C-S-H grain. Between C-S-H grains, confined water diminishes or enhances the cohesion of the material depending on the intergranular distance. At very low %RH, the loss of water increases the cohesion within a C-S-H grain and reduces the cohesion between C-S-H grains. These findings provide insights into the behavior of C-S-H in dry or high-temperature environments, with a loss of cohesion between C-S-H grains due to the loss of water content. Such quantification provides the necessary baseline to understand cement paste damaging upon extreme thermal, mechanical, and salt-rich environments.

Poor endoscopic findings in children with non variceal upper gastrointestinal bleeding: is biopsy necessary?

BACKGROUND: Gastrointestinal bleeding in infants and children is a potentially serious condition in the practice of general pediatrics that requires investigation. The objective of this study is to describe the endoscopic and histopathological findings in children with upper gastrointestinal (UGI) bleeding of non variceal origin. PATIENTS AND METHODS: We performed a retrospective study of the medical records of 181 children, aged 1 month to 15.2 years, with non variceal UGI bleeding, who were admitted in our department over the period 1988-2008 and underwent upper GI endoscopy accompanied by histology. Patients were divided in 4 groups according to their age (=0-1 years, = 1-6 years, C=6-12 years, D= 12-16 years). RESULTS: An endoscopically evident bleeding source was detected in only 5% of all patients. Histological examination revealed increased incidence of eosinophilic infiltration in infants, in contrast to all other age groups, where non-specific or H. pylori related inflammation predominated. Peptic ulcer was found in 4.4% of all patients. CONCLUSION: Although an evident bleeding source was detected in only a small percentage of patients, the accompanying histological examination provided additional information regarding possible underlying diseases and contributed to the subsequent therapeutic management.

The role of attributions in the process of overcoming shame: A qualitative analysis.

OBJECTIVES: While attributions have been found to play an important role in the experience of shame, little is currently known about attributions that occur as part of shame reparation. This exploratory study investigated the attributions associated with recovery from shame, based on the perspectives of participants. DESIGN: Grounded theory was used in data collection and analysis. This approach has been used extensively for developing understandings of how people construct meaning, interpret events, and act on the basis of their beliefs and interpretations. METHODS: The participants were nine women and four men between the ages of 24 and 70. Data came from interviews in which the participants recalled a distressing shame experience and described how they recovered. Emphasis was on the participants' subjective perspectives, meanings, and interpretations. RESULTS: Shame involved global and stable dispositional attributions where the entire self was regarded as flawed and unattractive, and participants perceived themselves as powerless to change an unwanted identity. Internal causal attributions and self-blame were present in most but not all shame experiences. Recovery involved a movement towards specific and unstable attributions that enhanced self-concept and maximized a sense of power and control over the future. Shared and external factors that contributed to the event were also identified. CONCLUSIONS: When applied to psychotherapy for shame-related distress, these findings point to the importance of exploring clients' attributions related to specific shame events and using interventions that promote attributional change. Directions for further research are discussed.

Blood glucose awareness training in Dutch type 1 diabetes patients: one-year follow-up.

BACKGROUND: American studies have shown positive effects of Blood Glucose Awareness Training (BGAT) on the recognition of hypoglycaemia. We evaluated the effects of BGAT among Dutch patients, and compared individual training with training in the original group format. METHODS: Fifty-nine type 1 diabetes patients participated in BGAT in either a group (n = 37) or an individual (n = 22) setting. Before and one year after training they performed up to 70 measurements, two to four a day, at home on a handheld computer. During each measurement they estimated their blood glucose (BG), indicated whether they would be participating in traffic and raised their BG on the basis of their estimation, and then measured their BG. The incidence of severe hypoglycaemia and traffic accidents was also assessed. RESULTS: BGAT had positive effects on hypoglycaemic awareness, decisions not to drive and to raise the blood glucose during hypoglycaemia, severe hypoglycaemic episodes and traffic accidents. The accuracy of BG estimations only improved after group training, while after individual training patients tended to measure more or more extremely high BG values. CONCLUSION: The training improved awareness of hypoglycaemia, and seems worthy of implementation in The Netherlands.

Endothelial cells as mechanical transducers: enzymatic activity and network formation under cyclic strain.

Although it is established that endothelial cells can respond to external mechanical cues (e.g., alignment in the direction of fluid shear stress), the extent to which mechanical stress and strain applied via the endothelial cell substrate impact biomolecular and cellular processes is not well-understood. This issue is particularly important in the context of inflammation, vascular remodeling, and cancer progression, as each of these processes occurs concurrently with localized increases in strain and marked changes in molecules secreted by adjacent cells. Here, we systematically vary the level and duration of cyclic tensile strain applied to human dermal microvascular and bovine capillary endothelial cells via substrate deflection, and then correlate these cues with the secretion of extracellular matrix-degrading enzymes and a morphological transition from confluent monolayers to well-defined multicellular networks that resemble capillary tube-like structures. For a constant chemical environment, we find that super-physiological mechanical strain stimulates both endothelial cell secretion of latent matrix metalloprotease-2 and multicellular networks in a time- and strain-dependent manner. These results demonstrate coupling between the mechanical and biochemical states of microvascular endothelial cells, and indicate that elevated local stress may directly impact new capillary growth (angiogenesis) toward growing tumors and at capillary wall defect sites.

Blood Glucose Awareness Training in Dutch Type 1 diabetes patients. Short-term evaluation of individual and group training.

AIMS: The aims of the present study were: (i) to evaluate the effects of a Dutch translation and adaptation of Blood Glucose Awareness Training (BGAT-III) on blood glucose (bg) perception, glycaemic control, and decisions not to drive or to raise the bg during hypoglycaemia; (ii) to compare the effects of individual and group BGAT. METHODS: Fifty-nine patients with Type 1 diabetes participated in BGAT in either a group or an individual setting. Before and after BGAT, 39 (66%) of them completed 30-70 measurements on a hand-held computer (hhc). During every measurement, they estimated their bg, indicated whether they would drive or raise their bg on the basis of their estimation, and then measured their bg. RESULTS: Individual and group BGAT did not have significantly different effects (P = 0.35-0.98). Overall, BGAT did not significantly affect bg perception (P = 0.11-0.65). Before BGAT patients recognized a mean of 32% of their hypoglycaemic episodes, after BGAT a mean of 39% (P = 0.12). After BGAT, patients more often decided not to drive when their bg was low (P = 0.03). They tended to decide more often to raise their bg during hypoglycaemia (P = 0.09). CONCLUSIONS: The effects of BGAT were smaller than expected. Possible reasons for this negative outcome may be the adapted version of BGAT (shorter in duration), a lack of statistical power, or a difference between American and European samples in their reaction to BGAT.

Multicenter proficiency testing of nucleic acid amplification methods for the detection of enteroviruses.

A multicenter study of molecular detection of enteroviruses was conducted using a proficiency panel. Of 70 data sets, 46 (66%) reported correct results for samples containing at least 1 50% infective dose per ml and for negative samples. Variation in performance between laboratories demonstrates the need for ongoing quality control.

Nanoindentation. Simulation of defect nucleation in a crystal.

Nanoindentation is the penetration of a surface to nanometre depths using an indenting device. It can be simulated using the Bragg bubble-raft model, in which a close-packed array of soap bubbles corresponds to the equilibrium positions of atoms in a crystalline solid. Here we show that homogeneous defect nucleation occurs within a crystal when its surface roughness is comparable to the radius of the indenter tip, and that the depth of the nucleation site below the surface is proportional to the half-width of the contact. Our results may explain the unusually high local stress required for defect nucleation in nano-indented face-centred cubic crystals.

Borna disease virus and schizophrenia in Surinamese immigrants to the Netherlands.

Borna disease virus (BDV) has been suggested to play a role in the etiology of schizophrenia. We tested the hypothesis that markers of BDV infection are more frequent in Surinamese immigrants to the Netherlands, diagnosed with schizophrenia, than in Dutch-born healthy subjects. For reasons that are poorly understood there is an increased incidence of schizophrenia in this immigrant group. Blood was obtained from 29 male schizophrenic patients (DSM-IV criteria) and from 26 healthy males. For detection of anti-BDV antibodies an indirect immunofluorescence assay (IFA) was performed. A nested, reverse-transcriptase-PCR, using primers specific for the p24 and p40 BDV genes, was used to determine BDV-RNA in peripheral blood mononuclear cells. Contrary to our expectations, the frequencies of BDV markers in the group of healthy subjects, as determined by IFA and both PCRs, exceeded that in the group of patients. The results do not support an association between markers of BDV infection in blood and schizophrenia. It is unlikely that the high incidence of schizophrenia in Surinamese immigrants is caused by BDV, but the small number of subjects examined do not warrant definitive conclusions.

Sex differences in illness beliefs and illness behavior in patients with suspected coronary artery disease.

The aim of this study was to explore sex differences in illness beliefs and behavior in patients with suspected coronary artery disease (CAD). Twenty-eight patients, 16 women and 12 men, were interviewed. The results show that both men and women think of CAD as a 'men's disease' and have equal knowledge of CAD risk factors. However, especially the men considered their own risk of developing CAD lower than their estimated probability of their own sex and as low as their estimated risk for women. Both men and women did not attribute their symptoms indicative of CAD to their heart. Women, especially those who did not attribute their symptoms to their heart, had a longer patient delay than men, although their symptoms were indicative of CAD. To conclude, men as well as women should be made more aware of their own risk of developing CAD and of the manifestation of CAD symptoms. Physicians could be encouraged to ask patients more explicitly and thoroughly about their illness beliefs, to check their knowledge and inform them about CAD.

Multicenter evaluation of the Amplicor Enterovirus PCR test with cerebrospinal fluid from patients with aseptic meningitis. The European Union Concerted Action on Viral Meningitis and Encephalitis.

The Amplicor Enterovirus PCR test was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid (CSF) specimens. In a multicenter study in which nine laboratories participated, a total of 476 CSF specimens were collected from patients with suspected aseptic meningitis. Sixty-eight samples were positive by PCR (14.4%), whereas 49 samples were positive by culture (10.4%), demonstrating that the Amplicor Enterovirus PCR test was significantly more sensitive than culture (P < 0.001). After discrepancy analysis the sensitivity and specificity of the Amplicor Enterovirus PCR test obtained by using viral culture as the "gold standard" were 85.7 and 93.9%, respectively. Our results with the CSF specimens collected in different countries demonstrate that the Amplicor test is capable of detecting a large variety of enterovirus serotypes and epidemiologically unrelated isolates in CSF specimens from patients with aseptic meningitis. The Amplicor Enterovirus PCR test is a rapid assay which can be routinely performed with CSF samples and is an important improvement for the rapid diagnosis of enteroviral meningitis.