Hydroxyethyl starch - the importance of being earnest.
Despite ongoing controversial expert discussions the European Medicines Agency (EMA) recently recommended to suspend marketing authorisations for hydroxyethyl starch. This comment critically evaluates the line of arguments. Basically, the only indication for a colloid is intravascular hypovolemia. Crystalloid use appears reasonable to compensate ongoing extracellular losses beyond. In the hemodynamically instable patient this leads to the distinction between an initial resuscitation phase where colloids might be indicated and a crystalloidal maintenance phase thereafter. It is important to bear this in mind when reevaluating the studies the EMA referred to in the context of its recent decision: i) VISEP compared ringer's lactate to 10% HES 200/0.5 in septic patients and found an increased incidence of renal failure in HES receivers. Unfortunately, study treatment was started only after initial stabilization with HES, randomizing hemodynamically stable patients into a rational (crystalloids) and an irrational (high dose starch until ICU discharge) maintenance treatment. ii) 6S compared ringer's acetate to 6% HES 130/0.42 for fluid resuscitation in septic patients and found an increased need of renal replacement therapy and a higher mortality in the HES group. However, patients of both groups were again randomized only after initial stabilization with colloids, the actual comparison was, therefore, again rational vs. irrational. Beyond that, the documentation is partly fragmentary, leaving many important questions around the fate of the patients unanswered. iii) CHEST randomized ICU patients to receive saline or 6% HES 130/0.4 for fluid resuscitation. Actually, despite partly discussed in a different way, this trial showed no relevant differences in outcome. In all, two studies showed what happens to septic patients if starches are used in a way we do not observe in daily practice. The third one actually proves their safety. The benefit of perioperative goal-directed preload optimization using starches is unquestioned. Taking these informations into account, the recommendation of the EMA starches to be generally dangerous remains mysterious and incomprehensible. An authority being able to dictate behavior should stand clear from oppressively ending a worldwide expert discussion and step back into the role of the observer until science achieves an agreement.


Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy.
There is emerging evidence for an under-recognized hepatitis E virus (HEV) as a human pathogen. Among different reasons for this neglect are the unsatisfactory performance and under-utilization of commercial HEV diagnostic kits; for instance, the number of anti-HEV IgM kits marketed in China is about one-fifth of that of hepatitis A kits. Over the last two decades, substantial progress has been achieved in furthering our knowledge on the HEV-specific immune responses, antigenic features of HEV virions, and development of serological assays and more recently prophylactic vaccines. This review will focus on presenting the evidence of the importance of HEV infection for certain cohorts such as pregnant women, the key antigenic determinants of the virus, and immunogenicity and clinical efficacy conferred by a newly developed prophylactic vaccine. Robust immunogenicity, greater than 195-fold and approximately 50-fold increase of anti-HEV IgG level in seronegative and seropositive vaccinees, respectively, as well as impressive clinical efficacy of this vaccine was demonstrated. The protection rate against the hepatitis E disease and the virus infection was shown to be 100% (95% CI 75-100) and 78% (95% CI 66-86), respectively.


Current and Future Approaches for Monitoring Responses to Anti-complement Therapeutics.
Aberrations in complement system functions have been identified as either direct or indirect pathophysiological mechanisms in many diseases and pathological conditions, such as infections, autoimmune diseases, inflammation, malignancies, and allogeneic transplantation. Currently available techniques to study complement include quantification of (a) individual complement components, (b) complement activation products, and (c) molecular mechanisms/function. An emerging area of major interest in translational studies aims to study and monitor patients on complement regulatory drugs for efficacy as well as adverse events. This area is progressing rapidly with several anti-complement therapeutics under development, in clinical trials, or already in clinical use. In this review, we summarized the appropriate indications, techniques, and interpretations of basic complement analyses, exemplified by a number of clinical disorders.


Inclusion of climate change strategies in municipal Integrated Development Plans: A case from seven municipalities in Limpopo Province, South Africa.
The Intergovernmental Panel on Climate Change (IPCC) has made it clear that anthropogenic greenhouse gasses are the main cause of observed global warming that leads to climate change. Climate change is now a global reality. In the South African political set-up, local municipalities are the structures that are in direct contact with communities and they draw up Integrated Development Plans (IDPs), which are reviewed and upgraded annually. The article seeks to investigate the extent to which climate change adaptation and mitigation strategies are embedded IDPs in seven vulnerable municipalities in the Limpopo Province. The article conducted an in-depth content analysis of the IDPs of the seven municipalities and the results have revealed that these municipalities have not included adaptation and mitigation strategies adequately in their IDPs despite being the most vulnerable municipalities in the province. The article concludes that these municipalities have not as yet institutionalised climate change in their daily operations, planning and decision making. To this end, the paper recommends that local municipalities should include climate change adaptation and mitigation strategies in their IDPs.


Solitary fibrous tumor of the orbit--two cases and a review of the literature.
Solitary fibrous tumors of the orbit (SFT) are mesenchymal lesions that can develop either as malignant or benign neoplasias. We describe the histological features leading to the diagnosis in two females and review the current literature. Diagnosis of SFT only can be performed by histological examination, since clinical signs and radiological features are not specific enough. Even a malignant or benign course cannot be predicted, since clinical and radiological features do not correlate with histological signs of malignancy and vice versa. Radical resection is the treatment of choice, since no other treatment option has been proven to be efficient.


Errors, Omissions, and Offenses in the Health Record of Mental Health Care Patients: Results from a Nationwide Survey in Sweden.
Previous research reports that patients with mental health conditions experience benefits, for example, increased empowerment and validation, from reading their patient-accessible electronic health records (PAEHRs). In mental health care (MHC), PAEHRs remain controversial, as health care professionals are concerned that patients may feel worried or offended by the content of the notes. Moreover, existing research has focused on specific mental health diagnoses, excluding the larger PAEHR userbase with experience in MHC. The objective of this study is to establish if and how the experiences of patients with and those without MHC differ in using their PAEHRs by (1) comparing patient characteristics and differences in using the national patient portal between the 2 groups and (2) establishing group differences in the prevalence of negative experiences, for example, rates of errors, omissions, and offenses between the 2 groups. Our analysis was performed on data from an online patient survey distributed through the Swedish national patient portal as part of our international research project, NORDeHEALTH. The respondents were patient users of the national patient portal 1177, aged 15 years or older, and categorized either as those with MHC experience or with any other health care experience (nonmental health care [non-MHC]). Patient characteristics such as gender, age, education, employment, and health status were gathered. Portal use characteristics included frequency of access, encouragement to read the record, and instances of positive and negative experiences. Negative experiences were further explored through rates of error, omission, and offense. The data were summarized through descriptive statistics. Group differences were analyzed through Pearson chi-square. Of the total sample (N=12,334), MHC respondents (n=3131) experienced errors (1586/3131, 50.65%, and non-MHC 3311/9203, 35.98%), omissions (1089/3131, 34.78%, and non-MHC 2427/9203, 26.37%) and offenses (1183/3131, 37.78%, and non-MHC 1616/9203, 17.56%) in the electronic health record at a higher rate than non-MHC respondents (n=9203). Respondents reported that the identified error (MHC 795/3131, 50.13%, and non-MHC 1366/9203, 41.26%) and omission (MHC 622/3131, 57.12%, and non-MHC 1329/9203, 54.76%) were "very important," but most did nothing to correct them (MHC 792/3131, 41.29%, and non-MHC 1838/9203, 42.17%). Most of the respondents identified as women in both groups. About 1 in 2 MHC patients identified an error in the record, and about 1 in 3 identified an omission, both at a much higher rate than in the non-MHC group. Patients with MHC also felt offended by the content of the notes more commonly (1 in 3 vs 1 in 6). These findings validate some of the worries expressed by health care professionals about providing patients with MHC with PAEHRs and highlight challenges with the documentation quality in the records.


Causes, comorbidities and current status of chronic kidney disease: A community perspective from North Kerala.
Chronic kidney disease is an upcoming public health problem characterized by premature mortality and expensive treatment in low resource settings where diabetes is highly prevalent. To find out the causes and comorbidities and to explore the community support systems for treatments availed. Community based cross sectional design. Interview of known chronic kidney disease patients above 18 years registered under palliative clinics. Mean, SD, proportions, and 95% Confidence interval, chi square test at significance level P = 0.05. Majority of patients were males, below 60 years. Mean duration was 5.26 years and mean age at onset was 48.6 years and 62% were in advanced stages of disease. The commonest cause was diabetic nephropathy (44.6%) followed by hypertensive nephropathy (33.3%). The comorbidities included hypertension (61.4%), diabetes (47.3%), cardiovascular disease (30.6%), Chronic obstructive pulmonary disease (10%) malignancies (2.6%), and retinopathy (28%). Considering treatment status 60.6% were on dialysis 13.3% had undergone transplantation, mostly from private institutions with help of public donations and both at significant underutilization by women. Though 44.6% were protected by social security schemes, the median monthly cost of disease management amounted to Rs. 10,500 which was unaffordable for the majority who were below the poverty line. There is an impending need for strengthening management, high-risk screening among diabetic and hypertensive patients and provision for specialist care to delay the onset of end-stage renal disease. The social security support system should be improvised for our setting to facilitate dialysis and transplantation to minimize out of the pocket expenditure.


Afucosylated antibodies increase activation of FcγRIIIa-dependent signaling components to intensify processes promoting ADCC.
Antibody-dependent cellular cytotoxicity (ADCC) is a key mechanism by which therapeutic antibodies mediate their antitumor effects. The absence of fucose on the heavy chain of the antibody increases the affinity between the antibody and FcγRIIIa, which results in increased in vitro and in vivo ADCC compared with the fucosylated form. However, the cellular and molecular mechanisms responsible for increased ADCC are unknown. Through a series of biochemical and cellular studies, we find that human natural killer (NK) cells stimulated with afucosylated antibody exhibit enhanced activation of proximal FcγRIIIa signaling and downstream pathways, as well as enhanced cytoskeletal rearrangement and degranulation, relative to stimulation with fucosylated antibody. Furthermore, analysis of the interaction between human NK cells and targets using a high-throughput microscope-based antibody-dependent cytotoxicity assay shows that afucosylated antibodies increase the number of NK cells capable of killing multiple targets and the rate with which targets are killed. We conclude that the increase in affinity between afucosylated antibodies and FcγRIIIa enhances activation of signaling molecules, promoting cytoskeletal rearrangement and degranulation, which, in turn, potentiates the cytotoxic characteristics of NK cells to increase efficiency of ADCC.


Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection.
Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD. Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined. Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity. Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.


Strength Pareto particle swarm optimization and hybrid EA-PSO for multi-objective optimization.
This paper proposes an efficient particle swarm optimization (PSO) technique that can handle multi-objective optimization problems. It is based on the strength Pareto approach originally used in evolutionary algorithms (EA). The proposed modified particle swarm algorithm is used to build three hybrid EA-PSO algorithms to solve different multi-objective optimization problems. This algorithm and its hybrid forms are tested using seven benchmarks from the literature and the results are compared to the strength Pareto evolutionary algorithm (SPEA2) and a competitive multi-objective PSO using several metrics. The proposed algorithm shows a slower convergence, compared to the other algorithms, but requires less CPU time. Combining PSO and evolutionary algorithms leads to superior hybrid algorithms that outperform SPEA2, the competitive multi-objective PSO (MO-PSO), and the proposed strength Pareto PSO based on different metrics.


Antianginal and anti-ischemic efficacy of nisoldipine in stable angina pectoris: a randomized, double-blind, placebo-controlled trial.
Nisoldipine, a dihydropy ridine calcium antagonist, is a potent vasodilator with selectivity for the coronary tree. The purpose of the study was to evaluate the onset and duration of antianginal and anti-ischemic efficacy of a single oral dose of nisoldipine compared with placebo in patients with stable angina pectoris. In 33 patients with stable angina pectoris, nisoldipine was tested (10 mg daily) in a randomized, double-blind, placebo-controlled study. Drugs having antianginal and anti-ischemic effects (except sublingual nitroglycerin) were withdrawn Patients underwent a four-day "washout" phase, then were randomly assigned to nisoldipine (10 mg daily) or placebo for six days. On Day 4 and Day 10, three times of treadmill exercise testing were performed before daily medication was given, 2 hours and 6 hours after dosing, respectively. Twenty-eight patients (14 taking nisoldipine and 14 taking placebos completed the study and were included in the statistical evaluation. Compared with placebo, total exercise duration increased significantly during all three sequential exercise testing in patients receiving nisoldipine. The frequency of anginal attacks decreased significantly while patients were receiving nisoldipine (0.29 +/- 0.44/patient/ day versus 0.14 +/- 0.26/patient/day, p < 0.05). Similarly, there was a trend toward a decrease in the consumption of sublingual nitroglycerin while patients were receiving nisoldipine. Adverse effects were mild. The study confirms that nisoldipine is an active antianginal and anti-ischemic agent, with an acceptable side effect profile when used as monotherapy. The anti-ischemic effect lasted more than six hours and the drug could be administered once daily.


Urinary neutrophil gelatinase-associated lipocalin is associated with heavy metal exposure in welding workers.
Metals cause nephrotoxicity with acute and/or chronic exposure; however, few epidemiological studies have examined impacts of exposure to metal fumes on renal injury in welding workers. In total, 66 welding workers and 12 office workers were recruited from a shipyard located in southern Taiwan. Urine samples from each subject were collected at the beginning (baseline) and end of the work week (1-week exposure). Personal exposure to PM2.5 was measured. The 8-h mean PM2.5 was 50.3 μg/m(3) for welding workers and 27.4 μg/m(3) for office workers. iTRAQs coupled with LC-MS/MS were used to discover the pathways in response to welding PM2.5 in the urine, suggesting that extracellular matrix (ECM)-receptor interactions are a critical mechanism. ECM-receptor interaction-related biomarkers for renal injury, kidney injury molecule (KIM)-1 and neutrophil gelatinase-associated lipocalin (NGAL), were significantly elevated in welding workers post-exposure, as well as were urinary Al, Cr, Mn, Fe, Co, and Ni levels. NGAL was more significantly associated with Al (r = 0.737, p < 0.001), Cr (r = 0.705, p < 0.001), Fe (r = 0.709, p < 0.001), and Ni (r = 0.657, p < 0.001) than was KIM-1, suggesting that NGAL may be a urinary biomarker for welding PM2.5 exposure. Nephrotoxicity (e.g., renal tubular injury) may be an emerging concern in occupational health.


Measurement of vitamin C by capillary electrophoresis in biological fluids and fruit beverages using a stereoisomer as an internal standard.
Ascorbic acid (or vitamin C) is an important component of many biological systems and various physiological roles have been described for it. A rapid and simple capillary electrophoresis method for ascorbic acid measurements in biological fluids as well as in beverages was developed. A stereoisomer of ascorbic acid, isoascorbic acid, not normally found in nature, was used as the internal standard for this assay. The analysis was performed in a 30 cm x 75 microns I.D. fused-silica capillary with 100 mM tricine buffer, pH 8.8, and measured by UV absorbance at 254 nm. The method was sensitive to 1.6 micrograms/ml and linear to 480.1 micrograms/ml. Within-run R.S.D. was 3.2% (93.5 +/- 3.0 micrograms/ml, mean +/- S.D., n = 18) and run-to-run R.S.D. was 3.3% (35.6 +/- 1.2 micrograms/ml, mean +/- S.D., n = 10) and 1.9% (149.4 +/- 2.8 micrograms/ml, mean +/- S.D., n = 10). Average spiked recovery from human plasma samples was 98.0%. The technique has been demonstrated to be suitable for assay of vitamin C in biological samples and some fruit juices.


Onset of morning activity in bumblebee foragers under natural low light conditions.
Foraging on flowers in low light at dusk and dawn comes at an additional cost for insect pollinators with diurnal vision. Nevertheless, some species are known to be frequently active at these times. To explore how early and under which light levels colonies of bumblebees, Bombus terrestris, initiate their foraging activity, we tracked foragers of different body sizes using RFID over 5 consecutive days during warm periods of the flowering season. Bees that left the colony at lower light levels and earlier in the day were larger in size. This result extends the evidence for alloethism in bumblebees and shows that foragers differ in their task specialization depending on body size. By leaving the colony earlier to find and exploit flowers in low light, larger-sized foragers are aided by their more sensitive eyes and can effectively increase their contributions to the colony's food influx. The decision to leave the colony early seems to be further facilitated by knowledge about profitable food resources in specific locations. We observed that experience accrued over many foraging flights determined whether a bee started foraging under lower light levels and earlier in the morning. Larger-sized bees were not more experienced than smaller-sized bees, confirming earlier observations of wide size ranges among active foragers. Overall, we found that most foragers left at higher light levels when they could see well and fly faster. Nevertheless, a small proportion of foragers left the colony shortly after the onset of dawn when light levels were below 10 lux. Our observations suggest that bumblebee colonies have the potential to balance the benefits of deploying large-sized or experienced foragers during dawn against the risks and costs of foraging under low light by regulating the onset of their activity at different stages of the colony's life cycle and in changing environmental conditions.


Breast Cancer Screening: Women's Experiences of Waiting for Further Testing.
To describe anxiety experienced by participants in a breast cancer screening program who have received an abnormal screening mammography result and are waiting for further testing and diagnosis and to identify the social support needed during this period. Exploratory, descriptive. Quebec Breast Cancer Screening Program (QBCSP) participants in Montreal, Canada. Nonprobability sample of 631 asymptomatic women, aged 50-69, who had abnormal screening mammogram results in the two months prior to the survey and who spoke or read French or English. Mailed self-report questionnaire. Anxiety, social support, and breast cancer screening. Fifty-one percent of the participants were quite or very anxious at every stage of the prediagnostic phase. Seventy-five percent expressed their feelings to family and friends whose support was comforting but did not diminish participants' anxiety. Satisfaction from social support offered by healthcare professionals reduced their anxiety. To decrease anxiety in the prediagnostic phase, women need support from healthcare professionals during the early stage of the screening process to prevent exacerbation of their concerns. Support has to be integrated into a continuity-of-care process. Nurses can play a significant role in breast cancer screening programs. They can evaluate, at an early stage, participant anxiety and offer the appropriate social support. They also can ensure the follow-up and personalized support required while a patient awaits a diagnosis.


Nutritional care after critical illness: a qualitative study of patients' experiences.
The present qualitative study aimed to explore the factors influencing nutritional recovery in patients after critical illness and to develop a model of care to improve current management of nutrition for this patient group. Patients were recruited into the study on discharge from a general intensive care unit (ICU) of a large teaching hospital in central Scotland. Semi-structured interviews were carried out after discharge from the ICU, weekly for the duration of their ward stay, and at 3 months post ICU discharge. Observations of ward practice were undertaken thrice weekly for the duration of the ward stay. Seventeen patients were recruited into the study and, using a grounded theory approach, 'inter-related system breakdowns during the nutritional recovery process' emerged as the overarching core category that influenced patients' experiences of eating after critical illness. This encompassed the categories, 'experiencing a dysfunctional body', 'experiencing socio-cultural changes in relation to eating' and 'encountering nutritional care delivery failures'. The findings from the present study provide a unique contribution to knowledge by offering important insights into patients' experiences of eating after critical illness. The study has identified numerous nutritional problems and raises questions about the efficacy of current nutritional management in this patient group. Adopting a more individualised approach to nutritional care could ameliorate the nutritional issues experienced by post ICU patients. This will be evaluated in future work.


Inflammatory potential of the diet and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.
Proinflammatory diets are associated with risk of developing colorectal cancer (CRC), however, inconsistencies exist in subsite- and sex-specific associations. The relationship between CRC and combined lifestyle-related factors that contribute toward a low-grade inflammatory profile has not yet been explored. We examined the association between the dietary inflammatory potential and an inflammatory profile and CRC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. This cohort included 476,160 participants followed-up of 14 years and 5,991 incident CRC cases (3,897 colon and 2,094 rectal tumors). Dietary inflammatory potential was estimated using an Inflammatory Score of the Diet (ISD). An Inflammatory Profile Score (IPS) was constructed, incorporating the ISD, physical activity level and abdominal obesity. The associations between the ISD and CRC and IPS and CRC were assessed using multivariable regression models. More proinflammatory diets were related to a higher CRC risk, particularly for colon cancer; hazard ratio (HR) for highest versus lowest ISD quartile was 1.15 (95% confidence interval [CI] 1.04-1.27) for CRC, 1.24 (95% CI 1.09-1.41) for colon cancer and 0.99 (95% CI 0.83-1.17) for rectal cancer. Associations were more pronounced in men and not significant in women. The IPS was associated with CRC risk, particularly colon cancer among men; HRs for the highest versus lowest IPS was 1.62 (95% CI 1.31-2.01) for colon cancer overall and 2.11 (95% CI 1.50-2.97) for colon cancer in men. Our study shows that more proinflammatory diets and a more inflammatory profile are associated with higher risk of CRC, principally colon cancer and in men.


A polymeric micro-optical interface for flow monitoring in biomicrofluidics.
We describe design and miniaturization of a polymeric optical interface for flow monitoring in biomicrofluidics applications based on polydimethylsiloxane technology, providing optical transparency and compatibility with biological tissues. Design and ray tracing simulation are presented as well as device realization and optical analysis of flow dynamics in microscopic blood vessels. Optics characterization of this polymeric microinterface in dynamic experimental conditions provides a proof of concept for the application of the device to two-phase flow monitoring in both in vitro experiments and in vivo microcirculation investigations. This technology supports the study of in vitro and in vivo microfluidic systems. It yields simultaneous optical measurements, allowing for continuous monitoring of flow. This development, integrating a well-known and widely used optical flow monitoring systems, provides a disposable interface between live mammalian tissues and microfluidic devices making them accessible to detectionprocessing technology, in support or replacing standard intravital microscopy.


Cardiac vagal tone and sustained attention in school-age children.
Three hypotheses tested relationships between cardiac responses mediated via the vagus and sustained attention in a population of normal school-age children. These hypotheses addressed the theoretical relationships among resting cardiac vagal tone (using the Porges estimate of respiratory sinus arrhythmia, V), performance measures of sustained attention, and cardiac reactivity during sustained attention. Thirty-two fourth and fifth grade children performed a continuous performance task while their electrocardiograms were monitored. Children with higher resting levels of V performed better on the first 3-min block of the continuous performance task. Additionally, levels of V were significantly reduced across the blocks of the 9-min task for all children. No relationships were found between resting levels of V and change in either V or heart period during task performance. These findings support two of the three hypotheses proposed by Porges regarding individual differences in cardiac vagal tone and sustained attention.


Developmental factors of urethral human papillomavirus lesions: correlation with circumcision.
To assess the relationship between circumcision and urethral human papillomavirus (HPV) lesions, and the influence of urethritis on the development of urethral HPV infections on inducing squamous metaplasia of the urethral epithelium. The study included 210 heterosexual, HIV-negative men (median age 29 years) who all had female partners with genital HPV infection. The patients were divided into three groups according to clinical findings, i.e. 97 patients with no clinical HPV lesions on peniscopy and urethroscopy, 70 patients with balanopreputial lesions but no urethral lesions, and 43 patients with urethral HPV lesions, including 17 who had associated penile lesions. They all underwent meatopeniscopy for HPV screening, urethral biopsy for histological analysis, and bacterial cultures were taken. The results in each subgroup were compared between circumcised and uncircumcised men. There was no significant difference in the incidence of HPV infection (58% vs 42%, odds ratio, OR, 1.8; 95% confidence interval, CI, 0.98-3.62) between uncircumcised and circumcised men, but this relationship differed with the developmental site of HPV lesions (shaft-foreskin, P<0.02; urethra, not significant). There was also a significant difference in the prevalence of urethritis between uncircumcised and circumcised men (34.5% vs 19%, OR 2.35, 95% CI 1. 08-5.11), and between HPV-infected and uninfected men (41.5% vs 18%, OR 3.17, 95% CI 1.71-5.83). This positive relationship of the prevalence of urethritis for both factors (circumcision and HPV) depended on the type of organism (sexually transmitted disease, not significant; common organism, P<0.02). The frequency of urethritis was related to the site of HPV lesions; urethritis was present in 36% of the patients with preputial HPV lesions, compared with 51% of those with urethral HPV lesions. Chlamydia trachomatis was detected in 1% of the patients without and in 7% of those with HPV lesions. In 68% of the patients, histological analysis of the urethral mucosa showed a squamous metaplasia of the urethral epithelium associated with urethritis. Being uncircumcised did not seem to increase the risk of HPV urethral infection in young men. Genital bacterial infections and urethral HPV lesions appear to be linked. Urethritis can induce squamous metaplasia of the urethral epithelium, which appears to favour the colonization of the anterior urethra by HPVs.


One-step transfer of diffractive structure from a designed pattern to a replica by use of a hybrid solgel film.
A one-step method for microfabrication of a diffractive lens mold with continuous relief, including a solgel process for replication, is presented. The mold is fabricated by focused ion beam milling (FIBM) on a substrate of bulk silicon and is then used directly for replication of the diffractive structure by means of a hybrid solgel glass stamping process. The surface roughness of the replica, Ra, is 4 nm over a 5 m x 5 m area. The measured diffraction efficiency is 86% and is influenced by accumulated mold geometry and solgel process errors. The demonstrated process of direct stamping by use of the master fabricated by FIBM offers the potential for mass production at very low cost.


MicroRNA expression during chick embryo development.
MicroRNAs (miRNAs) are small, abundant, noncoding RNAs that modulate protein abundance by interfering with target mRNA translation or stability. miRNAs are detected in organisms from all domains and may regulate 30% of transcripts in vertebrates. Understanding miRNA function requires a detailed determination of expression, yet this has not been reported in an amniote species. High-throughput whole mount in situ hybridization was performed on chicken embryos to map expression of 135 miRNA genes including five miRNAs that had not been previously reported in chicken. Eighty-four miRNAs were detected before day 5 of embryogenesis, and 75 miRNAs showed differential expression. Whereas few miRNAs were expressed during formation of the primary germ layers, the number of miRNAs detected increased rapidly during organogenesis. Patterns highlighted cell-type, organ or structure-specific expression, localization within germ layers and their derivatives, and expression in multiple cell and tissue types and within sub-regions of structures and tissues. A novel group of miRNAs was highly expressed in most tissues but much reduced in one or a few organs, including the heart. This study presents the first comprehensive overview of miRNA expression in an amniote organism and provides an important foundation for investigations of miRNA gene regulation and function.


Treatment of chronic hepatitis B infection-2017.
Since the registration of the first effective nucleoside analogue against the hepatitis B virus almost two decades ago, major progress has been made in the management of chronic hepatitis B infection. However, hepatitis B-related morbidity and mortality remain a major global health threat. This is partly due to the escalating costs and the decrease in compliance related to the need for prolonged therapy for most patients who cannot be "cured". New biomarkers such as quantitative hepatitis B surface antigen might help to determine if hepatitis B e antigen negative patients can be taken off nucleos(t)ide analogues. On the other hand, novel compounds that target the viral life cycle or modulate host immune response are in the pipeline. In the next few years, one should expect breakthrough advancement to be made leading to a "cure" for patients with chronic hepatitis B infection by inducing hepatitis surface antigen loss with or without the development of the hepatitis B surface antibody. In addition, attention and necessary actions should also be taken in patients with hepatitis B infection who are being treated with immunosuppressive therapy and direct anti-viral (DAAs) agents for hepatitis C infection to prevent hepatitis from hepatitis B reactivation.


Effective Targeting of Estrogen Receptor-Negative Breast Cancers with the Protein Kinase D Inhibitor CRT0066101.
Invasive ductal carcinomas (IDC) of the breast are associated with altered expression of hormone receptors (HR), amplification or overexpression of HER2, or a triple-negative phenotype. The most aggressive cases of IDC are characterized by a high proliferation rate, a great propensity to metastasize, and their ability to resist to standard chemotherapy, hormone therapy, or HER2-targeted therapy. Using progression tissue microarrays, we here demonstrate that the serine/threonine kinase protein kinase D3 (PKD3) is highly upregulated in estrogen receptor (ER)-negative (ER(-)) tumors. We identify direct binding of the ER to the PRKD3 gene promoter as a mechanism of inhibition of PKD3 expression. Loss of ER results in upregulation of PKD3, leading to all hallmarks of aggressive IDC, including increased cell proliferation, migration, and invasion. This identifies ER(-) breast cancers as ideal for treatment with the PKD inhibitor CRT0066101. We show that similar to a knockdown of PKD3, treatment with this inhibitor targets all tumorigenic processes in vitro and decreases growth of primary tumors and metastasis in vivo. Our data strongly support the development of PKD inhibitors for clinical use for ER(-) breast cancers, including the triple-negative phenotype.


Permeating protons contribute to tachyphylaxis of the acid-sensing ion channel (ASIC) 1a.
The homomeric acid-sensing ion channel 1a (ASIC1a) is a H+-activated ion channel with important physiological functions and pathophysiological impact in the central nervous system. Here we show that homomeric ASIC1a is distinguished from other ASICs by a reduced response to successive acid stimulations. Such a reduced response is called tachyphylaxis. We show that tachyphylaxis depends on H+ permeating through ASIC1a, that tachyphylaxis is attenuated by extracellular Ca2+, and that tachyphylaxis is probably linked to Ca2+ permeability of ASIC1a. Moreover, we provide evidence that tachyphylaxis is probably due to a long-lived inactive state of ASIC1a. A deeper understanding of ASIC1a tachyphylaxis may lead to pharmacological control of ASIC1a activity that could be of potential benefit for the treatment of stroke.


The heat shock response in neurons and astroglia and its role in neurodegenerative diseases.
Protein inclusions are a predominant molecular pathology found in numerous neurodegenerative diseases, including amyotrophic lateral sclerosis and Huntington's disease. Protein inclusions form in discrete areas of the brain characteristic to the type of neurodegenerative disease, and coincide with the death of neurons in that region (e.g. spinal cord motor neurons in amyotrophic lateral sclerosis). This suggests that the process of protein misfolding leading to inclusion formation is neurotoxic, and that cell-autonomous and non-cell autonomous mechanisms that maintain protein homeostasis (proteostasis) can, at times, be insufficient to prevent protein inclusion formation in the central nervous system. The heat shock response is a pro-survival pathway induced under conditions of cellular stress that acts to maintain proteostasis through the up-regulation of heat shock proteins, a superfamily of molecular chaperones, other co-chaperones and mitotic regulators. The kinetics and magnitude of the heat shock response varies in a stress- and cell-type dependent manner. It remains to be determined if and/or how the heat shock response is activated in the different cell-types that comprise the central nervous system (e.g. neurons and astroglia) in response to protein misfolding events that precede cellular dysfunctions in neurodegenerative diseases. This is particularly relevant considering emerging evidence demonstrating the non-cell autonomous nature of amyotrophic lateral sclerosis and Huntington's disease (and other neurodegenerative diseases) and the destructive role of astroglia in disease progression. This review highlights the complexity of heat shock response activation and addresses whether neurons and glia sense and respond to protein misfolding and aggregation associated with neurodegenerative diseases, in particular Huntington's disease and amyotrophic lateral sclerosis, by inducing a pro-survival heat shock response.


A dual-targeted soybean protein is involved in Bradyrhizobium japonicum infection of soybean root hair and cortical cells.
The symbiotic interaction between legumes and soil bacteria (e.g., soybean [Glycine max L.] and Bradyrhizobium japonicum]) leads to the development of a new root organ, the nodule, where bacteria differentiate into bacteroids that fix atmospheric nitrogen for assimilation by the plant host. In exchange, the host plant provides a steady carbon supply to the bacteroids. This carbon can be stored within the bacteroids in the form of poly-3-hydroxybutyrate granules. The formation of this symbiosis requires communication between both partners to regulate the balance between nitrogen fixation and carbon utilization. In the present study, we describe the soybean gene GmNMNa that is specifically expressed during the infection of soybean cells by B. japonicum. GmNMNa encodes a protein of unknown function. The GmNMNa protein was localized to the nucleolus and also to the mitochondria. Silencing of GmNMNa expression resulted in reduced nodulation, a reduction in the number of bacteroids per infected cell in the nodule, and a clear reduction in the accumulation of poly-3-hydroxybutyrate in the bacteroids. Our results highlight the role of the soybean GmNMNa gene in regulating symbiotic bacterial infection, potentially through the regulation of the accumulation of carbon reserves.


Racial variation in the cancer caregiving experience: a multisite study of colorectal and lung cancer caregivers.
As cancer care shifts from hospital to outpatient settings, the number of cancer caregivers continues to grow. However, little is known about the cancer caregiving experience. This gap in knowledge is especially evident for racially diverse caregivers. This study, part of a multisite study of care recipients with either lung or colorectal cancer and their caregivers, examined the caregiving experiences of African American (AA) and white caregivers. Caregivers were identified by cancer patients in the Cancer Care Outcomes Research and Surveillance consortium. Caregivers completed a self-administered, mailed questionnaire that assessed their characteristics and experiences. Analysis of covariance was used to compare racial groups by objective burden and caregiving resources while controlling for covariates. Despite greater preparedness for the caregiving role (P = .006), AA caregivers reported more weekly hours caregiving than whites did (26.5 ± 3.1 vs 18.0 ± 1.7; P = .01). In later phases of caregiving, AAs reported having more social support (P = .02), spending more hours caregiving (31.9 ± 3.5 vs 16.9 ± 1.9; P < .001), and performing more instrumental activities of daily living on behalf of their care recipient (P = .021). Racial differences in the caregiving experience exist. Nurses play a key role in educating cancer patients and their caregivers on how to effectively cope with and manage cancer. Because AA caregivers seem to spend more time in the caregiving role and perform more caregiving tasks, AA caregivers may benefit from interventions tailored to their specific caregiving experience.


Oxidative Phosphorylation as a Target Space for Tuberculosis: Success, Caution, and Future Directions.
The emergence and spread of drug-resistant pathogens, and our inability to develop new antimicrobials to combat resistance, have inspired scientists to seek out new targets for drug development. The Mycobacterium tuberculosis complex is a group of obligately aerobic bacteria that have specialized for inhabiting a wide range of intracellular and extracellular environments. Two fundamental features in this adaptation are the flexible utilization of energy sources and continued metabolism in the absence of growth. M. tuberculosis is an obligately aerobic heterotroph that depends on oxidative phosphorylation for growth and survival. However, several studies are redefining the metabolic breadth of the genus. Alternative electron donors and acceptors may provide the maintenance energy for the pathogen to maintain viability in hypoxic, nonreplicating states relevant to latent infection. This hidden metabolic flexibility may ultimately decrease the efficacy of drugs targeted against primary dehydrogenases and terminal oxidases. However, it may also open up opportunities to develop novel antimycobacterials targeting persister cells. In this review, we discuss the progress in understanding the role of energetic targets in mycobacterial physiology and pathogenesis and the opportunities for drug discovery.


Monitoring of Protein Biomarkers of Inflammation in Human Traumatic Brain Injury Using Microdialysis and Proximity Extension Assay Technology in Neurointensive Care.
Traumatic brain injury (TBI) is followed by secondary injury mechanisms strongly involving neuroinflammation. To monitor the complex inflammatory cascade in human TBI, we used cerebral microdialysis (MD) and multiplex proximity extension assay (PEA) technology and simultaneously measured levels of 92 protein biomarkers of inflammation in MD samples every three hours for five days in 10 patients with severe TBI under neurointensive care. One μL MD samples were incubated with paired oligonucleotide-conjugated antibodies binding to each protein, allowing quantification by real-time quantitative polymerase chain reaction. Sixty-nine proteins were suitable for statistical analysis. We found five different patterns with either early (<48 h; e.g., CCL20, IL6, LIF, CCL3), mid (48-96 h; e.g., CCL19, CXCL5, CXCL10, MMP1), late (>96 h; e.g., CD40, MCP2, MCP3), biphasic peaks (e.g., CXCL1, CXCL5, IL8) or stable (e.g., CCL4, DNER, VEGFA)/low trends. High protein levels were observed for e.g., CXCL1, CXCL10, MCP1, MCP2, IL8, while e.g., CCL28 and MCP4 were detected at low levels. Several proteins (CCL8, -19, -20, -23, CXCL1, -5, -6, -9, -11, CST5, DNER, Flt3L, and SIRT2) have not been studied previously in human TBI. Cross-correlation analysis revealed that LIF and CXCL5 may play a central role in the inflammatory cascade. This study provides a unique data set with individual temporal trends for potential inflammatory biomarkers in patients with TBI. We conclude that the combination of MD and PEA is a powerful tool to map the complex inflammatory cascade in the injured human brain. The technique offers new possibilities of protein profiling of complex secondary injury pathways.


Longitudinal outcome study of sessile serrated adenomas of the colorectum: an increased risk for subsequent right-sided colorectal carcinoma.
Sessile serrated adenomas (SSAs) are associated with colorectal carcinomas (CRCs) that demonstrate high microsatellite instability (MSI-H). Currently, SSAs are managed clinically in a similar fashion to adenomatous polyps (APs). We studied the natural history of SSA by analyzing the outcome of previously undiagnosed SSAs and comparing it with that of hyperplastic polyps (HPs) and APs. All colorectal polyps diagnosed between 1980 and 2001 as HP were selected for study. Polyps identified as possible SSAs were reviewed by 3 pathologists, and the diagnosis was confirmed. Clinical follow-up was obtained for each SSA patient and matched with control HP and AP patients. In total, 1402 colorectal polyps diagnosed as HP were examined and 81 polyps in 55 patients (5.8%) were rediagnosed as SSA. Of these, 40 SSA patients had no previous history of either CRC or AP with high-grade dysplasia (HGD). Of these 40 patients, 5 developed subsequent CRCs and 1 developed AP with HGD. The incidence of subsequent CRCs was significantly higher in SSA patients than in control patients with HP (12.5% vs. 1.8%) and AP (12.5% vs. 1.8%). All of the subsequent CRCs or APs with HGD developed in the proximal colon. Four of the 5 CRCs demonstrated a high microsatellite instability phenotype. We conclude that SSAs are high-risk lesions, with 15% of the SSA patients developing subsequent CRCs or APs with HGD. This incidence is higher than that of the control HP and AP patients, and would support close endoscopic follow-up in patients harboring SSAs.


Fatal attack by a juvenile tiger shark, Galeocerdo cuvier, on a kitesurfer in New Caledonia (South Pacific).
We present a case of a non-provoked fatal shark attack on a 15-year old male kitesurfer in New Caledonia. The victim lost his board and was pulled by the sail along the water surface in a reef passage when a shark attacked. The shark inflicted at least two bites on the left leg, including a severe one around the knee, resulting in a quick hypovolemic shock that was fatal. The analysis of one of these bites indicated that a 2.8 m TL (est. length) tiger shark was responsible for this attack. The features of the attack are consistent with those of a predator response to a surface feeding stimulus.


2,2,2-trifluoroethanol-induced molten globule state of concanavalin a and energetics of 8-anilinonaphthalene sulfonate binding: calorimetric and spectroscopic investigation.
The interaction of 2,2,2-trifluoroethanol (TFE) with concanavalin A has been investigated by using a combination of differential scanning calorimetry, isothermal titration calorimetry (ITC), circular dichroism (CD), and fluorescence spectroscopy at pH 2.5 and 5.2. All of the calorimetric transitions at both the pH values were found to be irreversible. In the presence of 4 mol kg(-1) TFE at pH 2.5, concanavalin A is observed to be in a partially folded state with significant loss of native tertiary structure. The loss of specific side chain interactions in the transition from native to the TFE-induced partially folded state is demonstrated by the loss of cooperative thermal transition and reduction of the CD bands in the aromatic region. Acrylamide quenching, 8-anilinonaphthalene sulfonate (ANS) binding, and energy transfer also suggest that in the presence of 4 mol kg(-1) TFE at pH 2.5 concanavalin A is in a molten globule state. ITC has been used for the first time to characterize the energetics of ANS binding to the molten globule state. ITC results indicate that the binding of ANS to the molten globule state and acid-induced state at pH 2.5 displays heterogeneity with two classes of non-interacting binding sites. The results provide insights into the role of hydrophobic and electrostatic interactions in the binding of ANS to concanavalin A. The results also demonstrate that ITC can be used to characterize the partially folded states of the protein both qualitatively and quantitatively.


Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes.
Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%-20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.


Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion.
Aortic surgery requiring hypothermic circulatory arrest is associated with a high incidence of brain injury. However, knowledge of neuropsychometric outcome is limited. Retrograde cerebral perfusion has become a popular adjunctive technique to hypothermic circulatory arrest. The aim of this study was to assess neuropsychometric outcome and compare the 2 techniques. In a prospective randomized trial, 38 patients requiring elective aortic arch surgery were allocated to either hypothermic circulatory arrest plus retrograde cerebral perfusion or hypothermic circulatory arrest alone. Neuropsychometric testing was performed preoperatively, and at 6 weeks and 12 to 24 weeks postoperatively. Deficit was defined as a 20% decline in 2 tests or more. Standardized Z scores were calculated for each patient and test. Eighteen patients underwent hypothermic circulatory arrest and 20 patients underwent hypothermic circulatory arrest plus retrograde cerebral perfusion. The mean cardiopulmonary bypass, hypothermic circulatory arrest, and retrograde cerebral perfusion durations were 169, 30, and 25 minutes, respectively. There were 2 deaths and 2 neurological deficits. At 6 weeks postoperatively, 77% of the hypothermic circulatory arrest group and 93% of the hypothermic circulatory arrest plus retrograde cerebral perfusion group had a deficit (P =.22). At 12 weeks this was reduced to 55% and 56%, respectively (P =.93). There was a worse total Z test score in the hypothermic circulatory arrest plus retrograde cerebral perfusion group at 12 weeks (P =.05). Neuropsychometric change did not correlate with hypothermic circulatory arrest duration, presence of aortic atheroma, cannulation technique, or procedure. Hypothermic circulatory arrest plus/minus retrograde cerebral perfusion is associated with a high incidence of neuropsychometric change despite ostensibly normal clinical outcomes and apparently safe arrest duration. Retrograde cerebral perfusion did not improve outcome in this small study.


Strain fidelity of chronic wasting disease upon murine adaptation.
Chronic wasting disease (CWD), a prion disease of deer and elk, is highly prevalent in some regions of North America. The establishment of mouse-adapted CWD prions has proven difficult due to the strong species barrier between mice and deer. Here we report the efficient transmission of CWD to transgenic mice overexpressing murine PrP. All mice developed disease 500 +/- 62 days after intracerebral CWD challenge. The incubation period decreased to 228 +/- 103 days on secondary passage and to 162 +/- 6 days on tertiary passage. Mice developed very large, radially structured cerebral amyloid plaques similar to those of CWD-infected deer and elk. PrP(Sc) was detected in spleen, indicating that murine CWD was lymphotropic. PrP(Sc) glycoform profiles maintained a predominantly diglycosylated PrP pattern, as seen with CWD in deer and elk, across all passages. Therefore, all pathological, biochemical, and histological strain characteristics of CWD appear to persist upon repetitive serial passage through mice. These findings indicate that the salient strain-specific properties of CWD are encoded by agent-intrinsic components rather than by host factors.


Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia.
Sensorimotor processing is abnormal in Idiopathic/Genetic dystonias, but poorly studied in Acquired dystonias. Beta-Corticomuscular coherence (CMC) quantifies coupling between oscillatory electroencephalogram (EEG) and electromyogram (EMG) activity and is modulated by sensory stimuli. We test the hypothesis that sensory modulation of CMC and intermuscular coherence (IMC) is abnormal in Idiopathic/Genetic and Acquired dystonias. Participants: 11 children with Acquired dystonia, 5 with Idiopathic/Genetic dystonia, 13 controls (12-18 years). CMC and IMC were recorded during a grasp task, with mechanical perturbations provided by an electromechanical tapper. Coherence patterns pre- and post-stimulus were compared across groups. Beta-CMC increased post-stimulus in Controls and Acquired dystonia (p = 0.001 and p = 0.010, respectively), but not in Idiopathic/Genetic dystonia (p = 0.799). The modulation differed between groups, being larger in both Controls and Acquired dystonia compared with Idiopathic/Genetic dystonia (p = 0.003 and p = 0.022). Beta-IMC increased significantly post-stimulus in Controls (p = 0.004), but not in dystonia. Prominent 4-12 Hz IMC was seen in all dystonia patients and correlated with severity (rho = 0.618). Idiopathic/Genetic and Acquired dystonia share an abnormal low-frequency IMC. In contrast, sensory modulation of beta-CMC differed between the two groups. The findings suggest that sensorimotor processing is abnormal in Acquired as well as Idiopathic/Genetic dystonia, but that the nature of the abnormality differs.


Increase of B-lymphocyte number and activity during experimental murine schistosomiasis mansoni.
1. In schistosomal infection, the hyperergic acute phase of the disease evolves progressively into the chronic one, with establishment of a relative equilibrium between the parasites and the corresponding host responses. This down-regulation of host reactivity is considered to be under the control of T-lymphocyte circuits. 2. In the present study, we investigated lymphocyte populations in spleens of normal mice and the kinetics of the B-cell number increase in mice in the acute, chronic and late chronic phases of schistosomal infection, and we monitored their proliferation and activity in antibody isotype secretion. 3. We observed polyclonal B-cell activation and modulation of Ig isotype production, compatible with the alternate predominance of TH2 and TH1 lymphocyte subsets, in the acute and the chronic phases of the disease, respectively.


Seasonal and gestation stage associated differences in aflatoxin exposure in pregnant Gambian women.
Aflatoxin is known to cross the placental barrier and exposures in utero could influence genomic programming, foetal growth and development, resulting in long-term health effects. We aimed to determine aflatoxin exposure in Gambian women at two stages of pregnancy and during the rainy and dry seasons. We examined aflatoxin exposure in pregnant Gambian women at early (<16 weeks) and later (16 weeks onward) stages of pregnancy and at different times of the year, during the rainy (June to October 2009) or dry (November to May 2010) season, using aflatoxin-albumin adducts (AF-alb). Mean AF-alb was higher during the dry season than in the rainy season, in both early and later pregnancy although the difference was strongest in later pregnancy. There was a modest increase in AF-alb in later than early pregnancy (geometric mean 41.8 vs. 34.5 pg/mg, P < 0.05), but this was restricted to the dry season when exposures were generally higher. The study confirmed that Gambian pregnant women were exposed to aflatoxin throughout the pregnancy, with higher levels in the dry season. There was some evidence in the dry season that women in later pregnancy had higher AF-alb levels than those in earlier pregnancy. Further research on the effects of exposure to this potent mutagen and carcinogen throughout pregnancy, including the epigenetic modification of foetal gene expression and impact on pre- and post-natal growth and development, are merited.


Reliability of Breast Ultrasound BI-RADS Final Assessment in Mammographically Negative Patients with Nipple Discharge and Radiologic Predictors of Malignancy.
The purpose of this study was to retrospectively investigate the reliability of breast ultrasound (US) Breast Imaging Reporting and Data System (BI-RADS) final assessment in mammographically negative patients with pathologic nipple discharge, and to determine the clinical and ultrasonographic variables associated with malignancy in this group of patients. A total of 65 patients with 67 mammographically negative breast lesions that were pathologically confirmed through US-guided biopsy were included. Of the 53 BI-RADS category 4 and 5 lesions, eight (15.1%) were malignant (six ductal carcinomas in situ, one invasive ductal carcinoma, and one solid papillary carcinoma). There was no malignancy among the remaining 14 category 3 lesions. Malignant lesions more frequently displayed a round or irregular shape (75.0%, 6/8; p=0.030) and nonparallel orientation (33.3%, 4/12; p=0.029) compared to the benign lesions. The increase in the BI-RADS category corresponded with a rise in the malignancy rate (p=0.004). The BI-RADS lexicon and final assessment of breast US reliably detect and characterize malignancy in mammographically negative patients with pathologic nipple discharge.


Preoperative factors predictive of continence recovery after radical retropubic prostatectomy.
We assessed the factors predictive of continence recovery after radical retropubic prostatectomy performed by use a single operative technique by a single surgeon. Preoperative factors, including age, body mass index (BMI), prostate volume, prostate-specific antigen level, and anatomical information from preoperative magnetic resonance imaging (MRI), such as membranous urethral length, thickness of the levator ani muscle, and urogenital diaphragm, were evaluated in 94 consecutive patients who underwent radical retropubic prostatectomy between April 2005 and October 2010. Patients were also categorized into four different groups according to the overlying pattern of the prostatic apex and the membranous urethra. Continence status was evaluated by direct patient questioning at 12 months after the operation. The overall continence rate at 12 months after the operation was 79.8%. In the age- and BMI-adjusted logistic regression analysis, the membranous urethral length and the overlying pattern of the prostatic apex were significant predictive factors of the continence rate at 12 months after the operation (p=0.006 and p=0.007, respectively). Other predictive factors were not contributory. Patients with no overlapping observed between the prostatic apex and membranous urethra had longer membranous urethral lengths (14.24±2.73 mm) and higher rates of recovery of continence compared with other groups. Membranous urethral length and shape of the prostatic apex as assessed by preoperative MRI are significantly associated with recovery of urinary continence after radical retropubic prostatectomy.


Photo-stability of peptide-bond aggregates: N-methylformamide dimers.
The formation of weakly-bound dimers of N-methylformamide (NMF) and the photochemistry of these dimers after irradiation at 248 nm were explored using matrix-isolation spectroscopy. Calculations were used to characterize the diverse isomers and assign their IR spectra; non-adiabatic dynamics was simulated to understand their photo-deactivation mechanism. The most stable dimers, and , were obtained by trans-trans aggregation (N-HO[double bond, length as m-dash]C interactions) and could be identified in the matrix. The main products formed after irradiation are the trans-cis dimers ( and ), also stabilized by N-HO[double bond, length as m-dash]C interactions. In contrast to the photochemistry of the monomers, no dissociative products were observed after 248 nm irradiation of the dimers. The absence of dissociative products can be explained by a proton-transfer mechanism in the excited state that is faster than the photo-dissociative mechanism. The fact that hydrogen bonding has such a significant effect on the photochemical stability of NMF has important implications to understand the stability of peptide-bonded systems to UV irradiation.


The effect of environment on endosperm cell-wall development in Triticum aestivum during grain filling: an infrared spectroscopic imaging study.
One of the major factors contributing to the failure of new wheat varieties is seasonal variability in end-use quality. Consequently, it is important to produce varieties which are robust and stable over a range of environmental conditions. Recently developed sample preparation methods have allowed the application of FT-IR spectroscopic imaging methods to the analysis of wheat endosperm cell wall composition, allowing the spatial distribution of structural components to be determined without the limitations of conventional chemical analysis. The advantages of the methods, described in this paper, are that they determine the composition of endosperm cell walls in situ and with minimal modification during preparation. Two bread-making wheat cultivars, Spark and Rialto, were selected to determine the impact of environmental conditions on the cell-wall composition of the starchy endosperm of the developing and mature grain, focusing on the period of grain filling (starting at about 14 days after anthesis). Studies carried out over two successive seasons show that the structure of the arabinoxylans in the endosperm cell walls changes from a highly branched form to a less branched form. Furthermore, during development the rate of restructuring was faster when the plants were grown at higher temperature with restricted water availability from 14 days after anthesis with differences in the rate of restructuring occurring between the two cultivars.


Multistability and Instability of Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.
In this paper, we discuss the coexistence and dynamical behaviors of multiple equilibrium points for recurrent neural networks with a class of discontinuous nonmonotonic piecewise linear activation functions. It is proved that under some conditions, such n -neuron neural networks can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable, based on the contraction mapping theorem and the theory of strict diagonal dominance matrix. The investigation shows that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibrium points and more locally stable equilibrium points than the ones with continuous Mexican-hat-type activation function or discontinuous two-level activation functions. An illustrative example with computer simulations is presented to verify the theoretical analysis.


Mental imagery in emotion and emotional disorders.
Mental imagery has been considered relevant to psychopathology due to its supposed special relationship with emotion, although evidence for this assumption has been conspicuously lacking. The present review is divided into four main sections: (1) First, we review evidence that imagery can evoke emotion in at least three ways: a direct influence on emotional systems in the brain that are responsive to sensory signals; overlap between processes involved in mental imagery and perception which can lead to responding "as if" to real emotion-arousing events; and the capacity of images to make contact with memories for emotional episodes in the past. (2) Second, we describe new evidence confirming that imagery does indeed evoke greater emotional responses than verbal representation, although the extent of emotional response depends on the image perspective adopted. (3) Third, a heuristic model is presented that contrasts the generation of language-based representations with imagery and offers an account of their differing effects on emotion, beliefs and behavior. (4) Finally, based on the foregoing review, we discuss the role of imagery in maintaining emotional disorders, and its uses in psychological treatment.


The Alice Springs Hospital Readmission Prevention Project (ASHRAPP): a randomised control trial.
Hospitals are frequently faced with high levels of emergency department presentations and demand for inpatient care. An important contributing factor is the subset of patients with complex chronic diseases who have frequent and preventable exacerbations of their chronic diseases. Evidence suggests that some of these hospital readmissions can be prevented with appropriate transitional care. Whilst there is a growing body of evidence for transitional care processes in urban, non-indigenous settings, there is a paucity of information regarding rural and remote settings and, specifically, the indigenous context. This randomised control trial compares a tailored, multidimensional transitional care package to usual care. The objective is to evaluate the efficacy of the transitional care package for Indigenous and non-Indigenous Australian patients with chronic diseases at risk of recurrent readmission with the aim of reducing readmission rates and improving transition to primary care in a remote setting. Patients will be recruited from medical and surgical admissions to Alice Springs Hospital and will be followed for 12 months. The primary outcome measure will be number of admissions to hospital with secondary outcomes including number of emergency department presentations, number of ICU admissions, days alive and out of hospital, time to primary care review post discharge and cost-effectiveness. Successful transition from hospital to home is important for patients with complex chronic diseases. Evidence suggests that a coordinated transitional care plan can result in a reduction in length of hospital stay and readmission rates for adults with complex medical needs. This will be the first study to evaluate a tailored multidimensional transitional care intervention to prevent readmission in Indigenous and non-Indigenous Australian residents of remote Australia who are frequently admitted to hospital. If demonstrated to be effective it will have implications for the care and management of Indigenous Australians throughout regional and remote Australia and in other remote, culturally and linguistically diverse populations and settings. Australian New Zealand Clinical Trials Registry, ACTRN12615000808549 - Retrospectively registered on 4/8/15.


High-resolution EM of colloidal nanocrystal growth using graphene liquid cells.
We introduce a new type of liquid cell for in situ transmission electron microscopy (TEM) based on entrapment of a liquid film between layers of graphene. The graphene liquid cell facilitates atomic-level resolution imaging while sustaining the most realistic liquid conditions achievable under electron-beam radiation. We employ this cell to explore the mechanism of colloidal platinum nanocrystal growth. Direct atomic-resolution imaging allows us to visualize critical steps in the process, including site-selective coalescence, structural reshaping after coalescence, and surface faceting.


Dystroglycan controls signaling of multiple hormones through modulation of STAT5 activity.
Receptors for basement membrane (BM) proteins, including dystroglycan (DG), coordinate tissue development and function by mechanisms that are only partially defined. To further elucidate these mechanisms, we generated a conditional knockout of DG in the epithelial compartment of the mouse mammary gland. Deletion of DG caused an inhibition of mammary epithelial outgrowth and a failure of lactation. Surprisingly, loss of DG in vivo did not disrupt normal tissue architecture or BM formation, even though cultured Dag1-null epithelial cells failed to assemble laminin-111 at the cell surface. The absence of DG was, however, associated with a marked loss in activity of signal transducer and activator of transcription 5 (STAT5). Loss of DG perturbed STAT5 signaling induced by either prolactin or growth hormone. We found that DG regulates signaling by both hormones in a manner that is dependent on laminin-111 binding, but independent of the DG cytoplasmic domain, suggesting that it acts via a co-receptor mechanism reliant on DG-mediated laminin assembly. These results demonstrate a requirement for DG in the growth and function of a mammalian epithelial tissue in vivo. Moreover, we reveal a selective role for DG in the control of multiple STAT5-dependent hormone signaling pathways, with implications for numerous diseases in which DG function is compromised.


The origin and development of nonlymphoid tissue CD103+ DCs.
CD103(+) dendritic cells (DCs) in nonlymphoid tissues are specialized in the cross-presentation of cell-associated antigens. However, little is known about the mechanisms that regulate the development of these cells. We show that two populations of CD11c(+)MHCII(+) cells separated on the basis of CD103 and CD11b expression coexist in most nonlymphoid tissues with the exception of the lamina propria. CD103(+) DCs are related to lymphoid organ CD8(+) DCs in that they are derived exclusively from pre-DCs under the control of fms-like tyrosine kinase 3 (Flt3) ligand, inhibitor of DNA protein 2 (Id2), and IFN regulatory protein 8 (IRF8). In contrast, lamina propria CD103(+) DCs express CD11b and develop independently of Id2 and IRF8. The other population of CD11c(+)MHCII(+) cells in tissues, which is CD103(-)CD11b(+), is heterogenous and depends on both Flt3 and MCSF-R. Our results reveal that nonlymphoid tissue CD103(+) DCs and lymphoid organ CD8(+) DCs derive from the same precursor and follow a related differentiation program.


Bond breaking, electron pushing, and proton pulling: active and passive roles in the interaction between aqueous ions and water as manifested in the O 1s Auger decay.
A core-ionized H(2)O molecule in liquid water primarily relaxes through normal Auger decay, leading to a two-hole final state in which both valence holes are localized on the same water molecule. Electronic coupling to the environment, however, allows for alternative decays resembling Intermolecular Coulombic Decay (ICD), producing final states with one of the holes delocalized on a neighboring water molecule. Here we present an experimental study of such minority processes, which adds to our understanding of dynamic interactions of electronically excited H(2)O molecules with their local surrounding in liquid water and aqueous solution. We show that the solvation of metal-halide salts considerably influences these minority decay channels from the water O 1s(-1) state. By breaking water-water bonds, both the metal cations and halide anions are found to reduce the decay into water-water delocalized states, thus having a ″passive″ effect on the Auger spectrum. The halide anions also play an ″active″ role by opening a new ICD-like decay pathway into water-halide delocalized states. The importance of this contribution increases from F(-) to I(-), which we suggest to be caused by a directional polarization of the halide anion toward the core-ionized H(2)O(+) cation in the intermediate state of the Auger process. This increases the electronic overlap between the two centers and makes delocalized decays more probable. We furthermore show that F(-), the smallest and most strongly hydrated of the halides, plays an additional role as proton puller during the core-hole lifetime, resulting in proton dynamics on the low femtosecond time scale. Our results represent a step forward toward a better understanding of how aqueous solutions, when exposed to soft X-rays, channel excess energy. This has implications for several aspects of physical and radiation chemistry, as well as biology.


Investigation of relationship of visceral body fat and inflammatory markers with metabolic syndrome and its components among apparently healthy individuals.
Metabolic syndrome is a cluster of disorders and great risk for cardiovascular diseases. We aimed to investigate association between severity of metabolic syndrome (MetS) and anthropometric measurements, and to evaluate correlation of MetS and its components with metabolic deterioration and inflammatory indexes. The cross-sectional study enrolled 1474 patients with obesity and overweight. The patients were grouped as MetS and Non-MetS, and were sub-grouped as group 1 (three criteria), 2 (four criteria) and 3 (≥ five criteria) according to NCEP ATP III. Mean age was 38.7 ± 11.9 years and BMI was 35.1 ± 6.3 kg/m(2). Lipid profile, anthropometric and blood pressure measurements, liver function tests, bioelectric impedance body fat compositions, insulin resistance and HbA1c, and spot urinary albumin-creatinine ratio were significantly different between groups of MetS and Non-MetS. Age, lipid profile, bioelectric impedance fat analyses, BMI, blood pressure values, glucose, insulin resistance, uric acid and hs-CRP levels were significantly different between groups of MetS component groups. ROC analysis revealed that hs-CRP was found to be more predictive for severity of metabolic syndrome components 3 and 4 (P=0.030); uric acid and visceral fat were more actual to predict severity of metabolic syndrome between 3 and 5 MetS components, (P=0.006) and uric acid was detected as more actual to predict severity of MetS between 4 and 5 components (P=0.023). In conclusion, uric acid, hs-CRP and visceral body fat composition were useful to predict to severity of MetS in primary care.


Differing Effects of Younger and Older Human Plasma on C2C12 Myocytes in Vitro.
Ageing is associated with a general reduction of physiological function and a reduction of muscle mass and strength. Endocrine factors such as myostatin, activin A, growth and differentiation factor 11 (GDF-11) and their inhibitory peptides influence muscle mass in health and disease. We hypothesised that myocytes cultured in plasma from older and younger individuals would show an ageing effect, with reduced proliferation and differentiation in older environments. C2C12 myoblasts were grown as standard and stimulated with media conditioned with 5% plasma from healthy male participants that were either younger (n = 6, 18-35 years of age) or older (n = 6, >57 years of age). Concentration of plasma myostatin (total and free), follistatin-like binding protein (FLRG), GDF-11 and activin A were quantified by ELISA. Both FLRG and activin A were elevated in older individuals (109.6 and 35.1% increase, respectively), whilst myostatin (free and total) and GDF-11 were not. Results indicated that plasma activin A and FLRG were increased in older vs. younger participants, GDF11 and myostatin did not differ. Myoblasts in vitro showed no difference in proliferation rate between ages, however scratch closure was greater in younger vs. older plasma stimulated myoblasts (78.2 vs. 87.2% of baseline scratch diameter, respectively). Myotube diameters were larger in cells stimulated with younger plasma than with older at 24 and 48 h, but not at 2 h. A significant negative correlation was noted between in vivo plasma FLRG concentration and in vitro myotube diameter 48 h following plasma stimulation (r2 = 0.392, p = 0.030). Here we show that myoblasts and myotubes cultured in media conditioned with plasma from younger or older individuals show an ageing effect, and further this effect moderately correlates with circulating FLRG concentration in vivo. The effect of ageing on muscle function may not be innate to the tissue, but involve a general cellular environment change. Further work is needed to examine the effect of increased FLRG concentration on muscle function in ageing populations.


A Systematic Review of Metastatic Hepatocellular Carcinoma to the Spine.
Hepatocellular carcinoma (HCC) frequently metastasizes to the spine. The impact of medical and/or surgical intervention on overall survival has been examined in a limited number of clinical studies, and herein we systematically review these data. We performed a literature review using PubMed, Embase, CINAHL, and Web of Science to identify articles that reported survival, clinical outcomes, and/or prognostic factors associated with patients diagnosed with spinal metastases. The methodologic quality of each review was assessed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses tool. There were 26 articles (152 patients) that met the inclusion criteria and were treated with either surgery, radiotherapy, chemotherapy, and/or observation. There were 3 retrospective cohort studies, 17 case reports, 5 case series, and 1 longitudinal observational study. Of the patients with known overall survival after diagnosis of spinal metastasis, survival at 3 months, 6 months, 1 year, 2 years, and 5 years was 95.2%, 83.0%, 28.6%, 2.0%, and 1.4%, respectively. The median survival after diagnosis of the metastasis was 0.7 months in the patients who received no treatment, 7 months in the patients treated with surgical intervention alone, 6 months for patients who received chemotherapy and/or radiation, and 13.5 months in the patients treated with a combination of surgery and medical management. All other clinical or prognostic parameters were of low or insufficient strength. Patients diagnosed with HCC spinal metastasis have a 10.6-month overall survival. Further analysis of patients in prospective controlled trials will be essential to the development of treatment algorithms for these patients in the future.


Cytokine and eosinophil responses in the lung, peripheral blood, and bone marrow compartments in a murine model of allergen-induced airways inflammation.
Selective accumulation of eosinophils and activated CD4+ cells is now considered a central event in the pathogenesis of asthma, and this process is thought to be mediated by a number of cytokines including tumor necrosis factor-alpha (TNF-alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), and the Type 2 cytokines interleukin-4 (IL-4) and IL-5. To carry out a detailed time-course analysis of cellular changes in the bronchoalveolar lavage fluid (BAL), peripheral blood (PB), and bone marrow (BM), and of changes in the aforementioned cytokines in BAL and serum, Balb/c mice were sensitized by intraperitoneal injection with ovalbumin (OVA) adsorbed to aluminum hydroxide on two occasions 5 days apart, and were subjected to an OVA aerosol challenge 12 days after the second sensitization. This resulted in an airways inflammatory response characterized by early transient neutrophilia, marked eosinophilia, and, to a lesser extent, lymphocytosis in the BAL. Inflammatory events were first observed 3 h and 24 h after antigen challenge in the lung tissue and BAL, respectively, and lasted for 21 days. In the BM, we detected a 1.5- and 5-fold increase in the total number of cells and eosinophils, respectively, 4 days after the second sensitization. This was followed by a decrease, although BM eosinophilia remained clearly present at the time of antigen challenge. A second eosinopoietic event was observed in the BM shortly after challenge and reached a peak at day 3. BM cellularity returned to normal at day 21 after challenge. Serum OVA-specific IgE was first detected 3 days following the second sensitization (150 ng/ml). IgE levels then decreased but remained at the 75 ng/ml range at the time of the aerosol challenge. During the sensitization period, TNF-alpha (approximately 25 pg/ml), IL-4 (approximately 40 pg/ml), and IL-5 (approximately 250 pg/ml) were detected in serum, but not in the BAL fluid (BALF) and returned to background levels at the time of the antigen challenge. After antigen challenge, TNF-alpha, IL-4, IL-5, and GM-CSF were detected in serum. Peak levels were observed at 3 h (approximately 40 pg/ml), 3 h (approximately 120 pg/ml), 12 h (approximately 350 pg/ml), and 3 h (approximately 10 pg/ml), respectively, and returned to background levels 24 h after challenge. In the BALF, we detected peak levels of TNF-alpha, IL-4, IL-5, and GM-CSF at 6 h (approximately 250 pg/ml), 24 h (approximately 140 pg/ml), 24 h (350 pg/ml), and 3 h (approximately 10 pg/ml), respectively, with a return to background levels 5 days after challenge. No IL-10 could be detected at any time point during sensitization or after challenge in either serum or BAL. We also detected approximately 40 pg/ml of interferon-gamma (IFN-gamma) in the serum of normal untreated mice. Serum IFN-gamma levels fluctuated during sensitization and after challenge, but never exceeded those observed in untreated mice. Thus, the cytokine profile observed in this experimental model of allergic inflammation is characterized by IL-4 and IL-5 dominance, with an apparently minor TNF-alpha and GM-CSF contribution and relatively low or undetectable levels of IFN-gamma and IL-10.


Hepatitis C virus infection and renal transplantation.
With the success of organ transplantation, liver disease has emerged as an important cause of morbidity and mortality of renal transplant (RT) recipients. Numerous studies performed during the 1990s have shown that hepatitis C virus (HCV) infection is the leading cause of chronic liver disease among RT recipients. The transmission of HCV by renal transplantation of a kidney from an HCV-infected organ donor has been shown unequivocally. Liver biopsy is essential in the evaluation of liver disease of RT recipients, and histological studies have shown that HCV-related liver disease after renal transplantation is progressive. The outcome of HCV-related liver disease is probably more aggressive in RT recipients than immunocompetent individuals. Various factors can affect the progression of HCV in the RT population: coinfection with hepatitis B virus, time of HCV acquisition, type of immunosuppressive treatment, and concomitant alcohol abuse. The role of virological features of HCV remains unclear. The natural history of HCV infection after renal transplantation is under evaluation; however, recent surveys with long follow-ups have documented adverse effects of HCV infection on patient and graft survival in RT recipients. Use of renal grafts from HCV-infected donors in recipients with HCV infection does not appear to result in a greater burden of liver disease, at least for a short period. The association between HCV and de novo or recurrent glomerulonephritis after RT has been hypothesized and is an area of avid research. Reported studies do not support interferon (IFN) treatment for RT recipients with chronic hepatitis C because of the frequent occurrence of graft failure, and information on the use of other types of IFN or combined therapy (IFN plus ribavirin or amantadine) is not yet available in the RT population.


Factors contributing to the effectiveness of four school-based sexual violence interventions.
This study extends past research by examining factors associated with changes in attitudes, knowledge, and intended behaviors related to sexual assault. This study included 1,182 participants from four unique multiple-session school-based sexual violence interventions. Implementation and participant factors examined include single- versus mixed-gender groups, group setting versus classroom lecture setting, and participant gender. Participants completed self-administered, paper-and-pencil pre- and postsurveys. A significant desired overall effect was found on participants' reports of positive attitudes, beliefs, and behavior regarding sexual harassment and personal boundaries and positive dating relationship norms (from pretest to posttest). There were steeper increases over time in both measures, with larger mixed-gender/single-gender differences among boys than among girls. Differences in the impact of participating in mixed- versus single-gender groups depended on classroom versus small group settings. The implications of these findings are discussed for sexual assault prevention programs.


Redefining public health leadership in the sustainable development goal era.
Adoption of the Sustainable Development Goals (SDGs) by member states of the United Nations (UN) has set a new agenda for public health action at national and global levels. The changed context calls for a reframing of what constitutes effective leadership in public health, through a construct that reflects the interdependence of leadership at multiple levels across the health system and its partners in other sectors. This is especially important in the context of Low and Middle Income Countries (LMICs) that are facing complex demographic and epidemiological transitions. The health system needs to exercise leadership that effectively mobilises all its resources for maximising health impact, and channels trans-disciplinary learning into well-coordinated multi-sectoral action on the wider determinants of health. Leadership is essential not only at the level of inspirational individuals who can create collective vision and commitment but also at the level of supportive institutions situated in or aligned to the health system. In turn, the health system as a whole has to exercise leadership that advances public health in the framework of sustainable development. This commentary examines the desirable attributes of effective leadership at each of these levels and explores the nature of their inter-dependence.


Delay of diagnosis of growth hormone deficiency in Taiwan.
In view of the importance of early detection of growth hormone deficiency, the height and age at the first pediatric endocrinologic clinic visit of 45 patients with growth hormone (GH) deficiency between January 1988 to December 1989 were retrospectively analyzed. Twenty-three patients with idiopathic GH deficiency had a median age of 13 years (range, from 3.8 to 29.9 years) at their first visit and a median height standard deviation score (SDS) of -3.87 (-2.14 to -7.93). Nineteen children with hypothalamopituitary tumors at their first visit, at a median of 2.17 years (0.42 to 7.83 years) after diagnosis of the tumor, had a median height SDS of -3.15 (-0.58 to -4.70). Three children with GH deficiency secondary to cranial irradiation at their first visit, at 8.17 years (1.33 to 10 years) after treatment for their malignancy, had a height SDS of -3.15 (-2.13 to -3.72). It is well known that the earlier the replacement therapy is begun in such patients, the better the prognosis is for final adult height. Regular height measurement and routine screening for shortness at school entry may overcome this delay in diagnosis. In addition, patients who have received cranial irradiation or had hypothalamopituitary tumors should be regularly measured and studied if their height velocities become subnormal. Physicians dealing with children should keep the possibility of growth hormone deficiency in mind when examining a short child.


Transverse plane tendon and median nerve motion in the carpal tunnel: ultrasound comparison of carpal tunnel syndrome patients and healthy volunteers.
The median nerve and flexor tendons are known to translate transversely in the carpal tunnel. The purpose of this study was to investigate these motions in differential finger motion using ultrasound, and to compare them in healthy people and carpal tunnel syndrome patients. Transverse ultrasounds clips were taken during fist, index finger, middle finger and thumb flexion in 29 healthy normal subjects and 29 CTS patients. Displacement in palmar-dorsal and radial-ulnar direction was calculated using Analyze software. Additionally, the distance between the median nerve and the tendons was calculated. We found a changed motion pattern of the median nerve in middle finger, index finger and thumb motion between normal subjects and CTS patients (p<0.05). Also, we found a changed motion direction in CTS patients of the FDS III tendon in fist and middle finger motion, and of the FDS II and flexor pollicis longus tendon in index finger and thumb motion, respectively (p<0.05). The distance between the median nerve and the FDS II or FPL tendon is significantly greater in patients than in healthy volunteers for index finger and thumb motion, respectively (p<0.05). Our results suggest a changed motion pattern of the median nerve and several tendons in carpal tunnel syndrome patients compared to normal subjects. Such motion patterns may be useful in distinguishing affected from unaffected individuals, and in studies of the pathomechanics of carpal tunnel syndrome.


Migration-Related Stressors and Their Effect on the Severity Level and Symptom Pattern of Depression among Vietnamese in Germany.
Vietnamese in Germany represent a scarcely researched and vulnerable group for mental health problems, especially under exposure to migration-related stressors (MRS). This study analyzes the effect of those MRS on the severity level and symptom pattern of depression. We analyzed the data of 137 depressed Vietnamese patients utilizing Germany's first Vietnamese psychiatric outpatient clinic. Hierarchical linear regression models were applied to investigate how the quantity of MRS influenced (1) the overall severity of self-reported depression symptoms; (2) the cognitive, affective, and somatic BDI-II subscale; and (3) the single BDI-II items of these subscales. A greater number of MRS were related to a higher severity level of depression in general, as well as to a higher level on the cognitive depression subscale in particular. The BDI-II single items pessimism, past failure, guilt feelings, punishment feelings, and suicidal thoughts were particularly associated with a higher quantity of perceived MRS. Among depressed Vietnamese migrants in Germany, a higher number of reported MRS were associated with higher overall depression severity. Within the domains of depression, particularly the cognitive domain was linked to perceived MRS. The association between MRS and suicidal thoughts is clinically highly relevant.


Sub-100 nm Si nanowire and nano-sheet array formation by MacEtch using a non-lithographic InAs nanowire mask.
We report a non-lithographical method for the fabrication of ultra-thin silicon (Si) nanowire (NW) and nano-sheet arrays through metal-assisted-chemical-etching (MacEtch) with gold (Au). The mask used for metal patterning is a vertical InAs NW array grown on a Si substrate via catalyst-free, strain-induced, one-dimensional heteroepitaxy. Depending on the Au evaporation angle, the shape and size of the InAs NWs are transferred to Si by Au-MacEtch as is (NWs) or in its projection (nano-sheets). The Si NWs formed have diameters in the range of ∼25-95 nm, and aspect ratios as high as 250 in only 5 min etch time. The formation process is entirely free of organic chemicals, ensuring pristine Au-Si interfaces, which is one of the most critical requirements for high yield and reproducible MacEtch.


Feature engineering combined with machine learning and rule-based methods for structured information extraction from narrative clinical discharge summaries.
A system that translates narrative text in the medical domain into structured representation is in great demand. The system performs three sub-tasks: concept extraction, assertion classification, and relation identification. The overall system consists of five steps: (1) pre-processing sentences, (2) marking noun phrases (NPs) and adjective phrases (APs), (3) extracting concepts that use a dosage-unit dictionary to dynamically switch two models based on Conditional Random Fields (CRF), (4) classifying assertions based on voting of five classifiers, and (5) identifying relations using normalized sentences with a set of effective discriminating features. Macro-averaged and micro-averaged precision, recall and F-measure were used to evaluate results. The performance is competitive with the state-of-the-art systems with micro-averaged F-measure of 0.8489 for concept extraction, 0.9392 for assertion classification and 0.7326 for relation identification. The system exploits an array of common features and achieves state-of-the-art performance. Prudent feature engineering sets the foundation of our systems. In concept extraction, we demonstrated that switching models, one of which is especially designed for telegraphic sentences, improved extraction of the treatment concept significantly. In assertion classification, a set of features derived from a rule-based classifier were proven to be effective for the classes such as conditional and possible. These classes would suffer from data scarcity in conventional machine-learning methods. In relation identification, we use two-staged architecture, the second of which applies pairwise classifiers to possible candidate classes. This architecture significantly improves performance.


Influence of Diurethane Linkers on the Langmuir Layer Behavior of Oligo[(rac-lactide)-co-glycolide]-based Polyesterurethanes.
Three oligo[(rac-lactide)-co-glycolide] based polyesterurethanes (OLGA-PUs) containing different diurethane linkers are investigated by the Langmuir monolayer technique and compared to poly[(rac-lactide)-co-glycolide] (PLGA) to elucidate the influence of the diurethane junction units on hydrophilicity and packing motifs of these polymers at the air-water interface. The presence of diurethane linkers does not manifest itself in the Langmuir layer behavior both in compression and expansion experiments when monomolecular films of OLGA-PUs are spread on the water surface. However, the linker retard the evolution of morphological structures at intermediate compression level under isobaric conditions (with a surface pressure greater than 11 mN m-1 ) compared to the PLGA, independent on the chemical structure of the diurethane moiety. The layer thicknesses of both OLGA-PU and PLGA films decrease in the high compression state with decreasing surface pressure, as deduced from ellipsometric data. All films must be described with the effective medium approximation as water swollen layers.


Sex-dependent effects of delta 9-tetrahydrocannabinol on locomotor activity in mice.
Sex differences in the effects of several drugs of abuse have previously been demonstrated. The present study evaluated sex differences in the effects of acute and repeated dosing with Delta(9)-tetrahydrocannabinol on locomotor activity in male and female Swiss Webster (CFW) mice. Results showed that acute Delta(9)-tetrahydrocannibol (1-30 mg/kg) increased locomotor activity in female, but not in male, mice. Following 3 days of daily injections of 10 mg/kg Delta(9)-tetrahydrocannabinol, re-tests of the same doses of Delta(9)-tetrahydrocannabinol tested acutely showed that female mice continued to exhibit greater sensitivity to the stimulatory effects of Delta(9)-tetrahydrocannabinol than did male mice; however, higher doses were required to produce these increases, suggesting a modest degree of tolerance development. These results are consistent with those of previous studies in which cannabinoids were more potent at producing locomotor suppression and antinociception in female than in male rats.