Protein-protein association rates captured in a single geometric parameter.
Understanding factors that drive protein-protein association is of fundamental importance. We show that a single geometric parameter in crystal structures of protein-protein complexes, the angle between the electric dipole of one subunit and the partner-generated electric field at the same subunit, linearly correlates with experimentally determined protein-protein association rates. Imprint of a dynamic kinetic process in a single static geometric parameter, associated with mutual electrostatic orientation of subunits in protein-protein complexes, is elegant and demonstrates the universality of electrostatic steering in attenuating protein-protein association rates. That the essence of a complex phenomenon could be captured by properties of the final crystal structure of the complex implies that the electrostatic orientations of protein subunits in crystal structures and the associated transition states are nearly identical. Further, the cosine of the angle, alone, is shown to be sufficient in predicting association rate constants, with accuracies comparable to currently available predictors that use more intricate methodologies. Our results offer mechanistic insights and could be useful in development of coarse-grained models.


Transposon mutagenesis reveals differential pathogenesis of Ralstonia solanacearum on tomato and Arabidopsis.
Ralstonia solanacearum causes a deadly wilting disease on a wide range of crops. To elucidate pathogenesis of this bacterium in different host plants, we set out to identify R. solanacearum genes involved in pathogenesis by screening random transposon insertion mutants of a highly virulent strain, Pss190, on tomato and Arabidopsis thaliana. Mutants exhibiting various decreased virulence levels on these two hosts were identified. Sequence analysis showed that most, but not all, of the identified pathogenesis genes are conserved among distinct R. solanacearum strains. A few of the disrupted loci were not reported previously as being involved in R. solanacearum pathogenesis. Notably, a group of mutants exhibited differential pathogenesis on tomato and Arabidopsis. These results were confirmed by characterizing allelic mutants in one other R. solanacearum strain of the same phylotype. The significantly decreased mutants' colonization in Arabidopsis was found to be correlated with differential pathogenesis on these two plants. Differential requirement of virulence genes suggests adaptation of this bacterium in different host environments. Together, this study reveals commonalities and differences of R. solanacearum pathogenesis on single solanaceous and nonsolanaceous hosts, and provides important new insights into interactions between R. solanacearum and different host plants.


Association between monoamine oxidase A promoter polymorphism and the risk of sudden infant death syndrome: a meta-analysis.
The etiology of sudden infant death syndrome (SIDS) remains an unsolved problem. The aim of this meta-analysis is to investigate the potential association between monoamine oxidase A (MAOA) promoter variable number tandem repeat (VNTR) polymorphism and SIDS risk. A systematic review and meta-analysis were conducted on studies from accessible electronic databases. Each VNTR variant was examined in each gender independently by comparing with the pooled results of other alleles. A total of six independent case-control studies including 1022 SIDS cases and 1839 controls were enrolled in this meta-analysis. In both of the whole populations and Caucasian populations, male infants with the low-MAOA-expression alleles (2R+3R) were found to exhibit a statistically significant increased risk of SIDS, whereas those with a 4R allele exhibited a reduced risk of SIDS. Besides, an increased risk of SIDS was detected in male Caucasian infants with 2R or 3R alleles. However, none of the allele or genotype variants was associated with SIDS in female victims. In male Caucasian infants, the low expression of MAOA promoter VNTR alleles (2R and 3R) is associated with an increased risk of SIDS, and the existence of the 4R allele could be regarded as a protective factor.


Transcriptome Profiling Reveals the Effects of Nitric Oxide on the Growth and Physiological Characteristics of Watermelon under Aluminum Stress.
Excessive aluminum ions (Al3+) in acidic soil can have a toxic effect on watermelons, restricting plant growth and reducing yield and quality. In this study, we found that exogenous application of nitric oxide (NO) could increase the photochemical efficiency of watermelon leaves under aluminum stress by promoting closure of leaf stomata, reducing malondialdehyde and superoxide anion in leaves, and increasing POD and CAT activity. These findings showed that the exogenous application of NO improved the ability of watermelon to withstand aluminum stress. To further reveal the mitigation mechanism of NO on watermelons under aluminum stress, the differences following different types of treatments-normal growth, Al, and Al + NO-were shown using de novo sequencing of transcriptomes. In total, 511 differentially expressed genes (DEGs) were identified between the Al + NO and Al treatment groups. Significantly enriched biological processes included nitrogen metabolism, phenylpropane metabolism, and photosynthesis. We selected 23 genes related to antioxidant enzymes and phenylpropane metabolism for qRT-PCR validation. The results showed that after exogenous application of NO, the expression of genes encoding POD and CAT increased, consistent with the results of the physiological indicators. The expression patterns of genes involved in phenylpropanoid metabolism were consistent with the transcriptome expression abundance. These results indicate that aluminum stress was involved in the inhibition of the photosynthetic pathway, and NO could activate the antioxidant enzyme defense system and phenylpropane metabolism to protect cells and scavenge reactive oxygen species. This study improves our current understanding by comprehensively analyzing the molecular mechanisms underlying NO-induced aluminum stress alleviation in watermelons.


Monitoring the Aggregation of GPCRs by Fluorescence Microscopy.
G protein-coupled receptors (GPCRs) contain highly hydrophobic domains that are subject to aggregation when exposed to the crowded environment of the cytoplasm. Many events can lead to protein aggregation such as mutations, endoplasmic reticulum (ER) stress, and misfolding. These processes have been widely known to impact GPCR folding, maturation, and localization. Protein aggregates are transported toward the microtubule-organizing center via dynein to form a large juxta-nuclear structure called the aggresome, and in due course, are then targeted for degradation. Here, we describe a method to study aggregation of GPCRs by fluorescence microscopy.


School-age children born to diabetic mothers and to mothers with gestational diabetes exhibit a high rate of inattention and fine and gross motor impairment.
To study the neurobehavioral effects that pregestational and gestational diabetes might have on offspring at school age. We studied neurobehavioral function at school age of 57 children born to 48, well controlled, diabetic mothers and of 32 children born to 32 women with gestational diabetes. Their development was compared with 57 control children matched by age, birth order and parental socio-economic status, using a number of cognitive, behavioral, sensory and motor neurological tests. The IQ scores on the WISC-R and Bender tests of the children born to diabetic mothers were similar to those of control children, but the Bender scores of the children born to mothers with gestational diabetes were slightly lower. No differences were found between the study groups in various sensory-motor functions in comparison to controls. However, both study group children performed less well than controls in fine and gross motor functions as observed on the Bruininks-Oseretzki test of motor proficiency. The scores of children born to the mothers with pregestational diabetes were higher than controls on the Touwen & Prechtl neurological examination (worse function). The children from both research groups also performed worse on the Pollack taper test that is designed to detect inattention and hyperactivity. The children of the two study groups also had slightly higher scores on the Conners abbreviated parents-teachers questionnaire measuring hyperactivity and inattention, but the differences from controls were not statistically significant. We found a negative correlation between the performance of the children born to mothers with pregestational diabetes on various neurodevelopmental and behavioral tests and the severity of maternal hyperglycemia as assessed by blood glycosylated hemoglobin levels and acetonuria. Pregestational or gestational diabetes was found to adversely affect attention span and motor functions of offspring at school age, but not their cognitive ability. These effects were negatively correlated with the degree of maternal glycemic control, and were more pronounced in younger children.


Photoprocesses of chlorin e6 glucose derivatives.
The ground and excited state processes of chlorin e6, the monomethyl ester C1, the glucose derivative C2 and the 3-heptylchlorin-glucose C3, were studied in solvents of lower and higher polarity. The excited singlet and lowest triplet states of C1-C3 were characterized by spectroscopic methods for several conditions. The quantum yields of formation of singlet molecular oxygen and the other triplet properties of the three chlorins and chlorin e6 are similar, whereas the fluorescence quantum yield decreases on going from C1 to C3. Time-resolved optoacoustic experiments revealed a ca. 30 kJ mol(-1) higher triplet level for C3 with respect to C1/2.


Prediction of employment status following traumatic brain injury using a behavioural measure of frontal lobe functioning.
To examine whether a behavioural measure of frontal lobe functioning, the Brock Adaptive Functioning Questionnaire (BAFQ), could predict employment status following traumatic brain injury (TBI). A discriminant function analysis was conducted to determine the ability of the BAFQ, along with other factors, to predict occupational status post-injury. Sixty-one TBI survivors completed a background information questionnaire, the BAFQ, and an employment status rating scale. A factor analysis of the BAFQ sub-scales revealed two factors, one related to functioning in the orbitofrontal area, and one related to dorsolateral frontal lobe functioning. These two factors, along with background information, were entered into a discriminant function analysis, revealing a 77.4% accuracy rate in predicting occupational status post-injury. Demographic variables were found to differentiate employed from unemployed survivors. The BAFQ appeared useful in differentiating survivors who may return to their pre-injury employment level from those who may require modified employment.


IQ estimate smackdown: comparing IQ proxy measures to the WAIS-III.
Brief assessments of general cognitive ability are frequently needed by neuropsychologists, and many methods of estimating intelligence quotient (IQ) have been published. While these measures typically present overall correlations with the Wechsler Adult Intelligence Scale (WAIS) Full Scale IQ, it is tacitly acknowledged that these estimates are most accurate within 1 standard deviation of the mean and that accuracy diminishes moving toward the tails of the IQ distribution. However, little work has been done to systematically characterize proxy measures at the tails of the IQ distribution. Additionally, while these measures are all correlated with the WAIS, multiple proxy measures are rarely presented in one manuscript. The current article has two goals: (1) Examine various IQ proxies against Wechsler Adult Intelligence Scale (Third Version) scores, showing the overall accuracy of each measure against the gold standard IQ measure. This comparison will assist in selecting the best proxy measure for particular clinical constraints. (2) The sample is then divided into three groups (below, average, and above-average ability), and each group is analyzed separately to characterize proxy performance at the tails of the IQ distribution. Repeated measures multivariate analysis of variance compares the different proxy measures across ability levels. All IQ estimates are represented in tables so that they can be examined side by side.


Examining emotional functioning in misophonia: The role of affective instability and difficulties with emotion regulation.
Misophonia is a newly described condition characterized by sensory and emotional reactivity (e.g., anxiety, anger, disgust) to repetitive, pattern-based sounds (e.g., throat clearing, chewing, slurping). Individuals with misophonia report significant functional impairment and interpersonal distress. Growing research indicates ineffective coping and emotional functioning broadly (e.g., affective lability, difficulties with emotion regulation) are central to the clinical presentation and severity of misophonia. Preliminary evidence suggests an association between negative emotionality and deficits in emotion regulation in misophonia. Still, little is known about (a) the relationships among specific components of emotional functioning (e.g., emotion regulation, affective lability) with misophonia, and (b) which component(s) of misophonia (e.g., noise frequency, emotional and behavioral responses, impairment) are associated with emotional functioning. Further, despite evidence that mood and anxiety disorders co-occur with misophonia, investigation thus far has not controlled for depression and anxiety symptoms. Examination of these relationships will help inform treatment development for misophonia. The present study begins to disambiguate the relationships among affective lability, difficulties with emotion regulation, and components of misophonia. A sample of 297 participants completed questionnaires assessing misophonia, emotional functioning, depression, anxiety, and COVID-19 impact. Findings indicated that misophonia severity was positively associated with each of these constructs with small to medium effect sizes. When controlling for depression, anxiety, and COVID-19 impact, results from this preliminary study suggest that (a) difficulties with emotion regulation may be correlated with misophonia severity, and (b) misophonic responses, not number of triggers or perceived severity, are associated with difficulties with emotion regulation. Overall, these findings begin to suggest that emotion regulation is important to our understanding the risk factors and treatment targets for misophonia.


[Breakthrough bleeding in adult patients with severe hemophilia A receiving low- and intermediate-dose FVIII for tertiary prophylaxis: characteristics and influencing factors].
To investigate the characteristics of breakthrough bleeding in adult patients with severe hemophilia A (SHA) receiving low- and intermediate-dose FVIII for tertiary prophylaxis and explore the factors affecting the outcomes of the treatment. Forty-nine patients (mean age 31.53∓7.33 years) with SHA receiving tertiary prophylaxis FVIII treatment were divided into low-dose group (n=15) and intermediate-dose group (n=34). The data including clinical bleeding phenotype (Pre?AJBR), 72 h FVIII trough activity, and Functional Independence Score in Hemophilia (FISH) were recorded in all the patients, and Hemophilia Steward APP was used to record the bleeding episode and the treatment data. All the patients were followed up for at least 6 months. In the low-dose and intermediate-dose groups, the number of joint bleeding (AJBR) episodes were 18.79∓13.03 and 9.28∓7.02 per year (P=0.016), and the proportions of spontaneous bleeding were 75.0% and 47.7%, respectively. The proportions of patients with target joint were 80% and 44%, target joint bleeding occurred in 59% and 41%, and cataract bleeding after 0-12 h of prophylactic injection occurred in 4.86% and 5.18% of the patients with a median breakthrough bleeding time of 40.08 h and 46.08 h (P=0.008), respectively. The proportions of patients with 72 h FVIII trough activity <1% were 44.4% and 34.8% in the two groups, respectively. AJBR was negatively correlated with the preventive dose consumed (r=-0.57, P=0.000, n=49) and FISH, but positively correlated with Pre-AJBR in the two groups (P<0.05). Tertiary prophylaxis with low- and intermediate-dose FVIII is not sufficient to achieve the goal of preventing progression of joint disease in Chinese adult patients with SHA. Although the prophylactic dose is the most important factor to affect the treatment efficacy, other non-factor approaches may also help to improve the efficacy of the treatment.


Anastomotic Aneurysm Formation after High Flow Bypass Surgery: A Case Report with Histopathological Study.
Bypass surgery is often used in the treatment of large and giant aneurysms. Major complications that often arise during the perioperative period include cranial nerve palsy, ischemic complications, and hyperperfusion. However, there have been a few reports about late onset complications such as anastomotic aneurysms. In particular, anastomotic aneurysm after high flow bypasses has never been reported. A 57-year-old woman who had been suffering from left eye pain was diagnosed with a large aneurysm of the left internal carotid artery (ICA) in the cavernous portion. She was treated with high flow bypass surgery using radial artery graft and proximal ICA ligation. One and a half year after surgery, a de novo aneurysm (7.5 mm in maximum diameter) was detected in the anastomotic site. To prevent rupture, the aneurysm was resected and the middle cerebral artery (MCA) was reconstructed via superficial temporal artery (STA)-MCA bypass. Postoperative course was uneventful and the anastomotic aneurysm did not recur until 2 years after second surgery. Histological evaluation of the anastomotic aneurysm demonstrated loss of smooth muscle cells and proliferation of neointima, features consistent with a true aneurysm. Interestingly, the above changes were prominent in the radial artery graft while the MCA was almost histologically intact. As such, intraoperative intimal damage and postoperative hemodynamic stress to the radial artery graft may be a cause of aneurysm formation. Anastomotic aneurysm may occur after high flow bypass, necessitating careful postoperative follow-up.


Selective Mutism: The Fraternal Twin of Childhood Social Phobia.
Selective mutism (SM) is an anxiety disorder with a close link to childhood social phobia (SP). Our studies compare behavioral problem profiles in children and adolescents with SM and SP and control groups and assess the comorbidity patterns of SM and SP. Participants aged 3-18 years with SM (n = 95), SP (n = 74) and internalizing disorders (INT, n = 46) and a typically developing control group (CG, n = 119) were assessed with the Child Behavior Checklist (CBCL); adolescents were additionally assessed with the Youth Self-Report (YSR). Comorbidity was assessed in SM and SP participants with a diagnostic interview. SP was detected in 94% of children with SM. SM participants showed different behavioral and psychiatric symptoms than SP: they were more frequently affected by lifetime separation anxiety disorder (SM: 45%, SP: 26%) and oppositional defiant disorder (SM: 22%, SP: 5%), and less by generalized anxiety disorder (SM: 6%, SP: 20%) and major depression (SM: 12%, SP: 26%). Adolescents with SM showed high rates of agoraphobia (SM 27%; SP 10%) and more social problems (YSR), and were more withdrawn (CBCL, YSR) than those with SP alone. Specific behavioral problems of SM and SP compared to INT and CG were observed. SM and SP represent separate but closely related disorders, distinct from other INT and CG, with specific patterns of lifetime comorbidities.


Establishment and characterization of a new human glioblastoma cell line (MGM-1) with highly motile phenotype.
A new cell line MGM-1 was established from a primary tumor of the left temporal lobe with histological diagnosis of glioblastoma multiforme, removed from a 64-year-old Japanese male. The patient died of recurrence and unusual extracranial metastases of the tumor 7 months after the surgery. The cultured MGM-1 cells are spindle or polygonal in shape. After serial passages, glial fibrillary acidic protein became negative immunocytochemically in vitro. The modal chromosome number was 61-64. Doubling time and soft agar colony forming efficiency were 42.9h and 0.4%, respectively (at 25th passage). MGM-1 is a highly motile cell line in vitro and its serum-free conditioned medium is chemotactic and chemokinetic for other glioma cells. Secretion of gelatinases (probably MMP-2/72-kDa type i.v. collagenase) and MMP-9/92-kDa type i.v. collagenase) and urokinase-type plasminogen activator were also investigated. MGM-1 would therefore be useful for studying the mechanisms regulating glioma-cell motility and invasion. The MGM-1 cell line has been propagated continuously by serial passages (more than 100 passages) during the past 4 years.


[Trocar site hernias. A rare but potentially dangerous complication of laparoscopic surgery].
With increasing numbers of laparoscopic procedures more postoperative trocar site hernias can be expected. This complication of minimally invasive surgery is rare but potentially dangerous. According to the literature, the overall incidence of trocar site hernias is expected to be around 1%. Among trocar site hernias, Richter's hernias are the most frequent, accounting for two-thirds of all small intestinal hernias. The following risk factors for the development of trocar site hernias have been identified: the trocar diameter, the trocar design, preexisting fascial defects, and some operation- and patient-related factors. Peritoneal and fascial closure should be done when blunt trocars of >10 mm have been employed. Based on the literature and our own experience, some preventive recommendations are given to further reduce the risk of hernia formation at trocar sites.


Research sponsorship, financial relationships, and the process of research in pharmaceutical clinical trials.
THE EFFECTS OF SPONSORSHIP AND FINANCIAL relationships on the conduct of clinical trials were examined by surveying 321 authors who had published reports of pharmaceutical clinical trials. The survey asked about research sponsorship, financial relationships, who controlled the research, and who carried it out. W hen a commercial s ponsor w as t he e xclusive research sponsor, authors reported less control over and less contribution to the research, and more sponsor control and contribution, as compared with noncommercial or mixed sponsorship. Similarly, financial relationships with firms were associated with less author contribution to and more sponsor control over and contribution to the research. The results raise concerns about bias in the design, conduct, or reporting of research.


Loss of CclA, required for histone 3 lysine 4 methylation, decreases growth but increases secondary metabolite production in Aspergillus fumigatus.
Secondary metabolite (SM) production in filamentous fungi is mechanistically associated with chromatin remodeling of specific SM clusters. One locus recently shown to be involved in SM suppression in Aspergillus nidulans was CclA, a member of the histone 3 lysine 4 methylating COMPASS complex. Here we examine loss of CclA and a putative H3K4 demethylase, HdmA, in the human pathogen Aspergillus fumigatus. Although deletion of hdmA showed no phenotype under the conditions tested, the cclA deletant was deficient in tri- and di-methylation of H3K4 and yielded a slowly growing strain that was rich in the production of several SMs, including gliotoxin. Similar to deletion of other chromatin modifying enzymes, ΔcclA was sensitive to 6-azauracil indicating a defect in transcriptional elongation. Despite the poor growth, the ΔcclA mutant had wild-type pathogenicity in a murine model and the Toll-deficient Drosophila model of invasive aspergillosis. These data indicate that tri- and di-methylation of H3K4 is involved in the regulation of several secondary metabolites in A. fumigatus, however does not contribute to pathogenicity under the conditions tested.


Telephone versus in-person clinical and health status assessment interviews in patients with bipolar disorder.
We evaluated the correspondence between in-person- and telephone interview-derived data on affective symptoms, health-related quality of life, disability days, and medication compliance in patients with bipolar disorder. Twenty-eight outpatients with DSM-III-R-documented bipolar disorder were randomly assigned to an initial in-person or telephone interview. An average of 4.0 days later, they were reassessed by the other interview method. Results indicate good to excellent agreement between telephone and in-person interviews on measures of mania (intraclass correlation coefficient (ICC) = 0.92) and depression symptoms (ICC = 0.90), suicide risk (kappa = 0.80), and alcohol use (kappa = 0.61), scores on the Medical Outcomes Study 36-item Short-Form Health Survey (ICCs = 0.66-0.92), and medication compliance (ICCs = 0.50-0.66). Measures of bed disability days (ICC = 0.34) and restricted activity days (ICC = 0.66) showed less agreement. Telephone interviews are feasible and reliable for collecting data on psychiatric and other health-related outcomes in bipolar disorder patients.


Glioblastoma in elderly patients: solid conclusions built on shifting sand?
Management of glioblastoma in the elderly population is challenging. In the near future, more than half of patients with this tumor will be over the age of 65. Clinicians have been historically reluctant to treat such patients with the same intensity as younger patients. Due to upper age limits or poor accrual of elderly patients in clinical trials, randomized data for this patient population have been relatively sparse until recently. In this review, we will discuss the concept of an elderly patient population, describe evidence for molecular differences in glioblastoma of elderly versus young patients, evaluate recent first-line trials studying glioblastoma in elderly patients, and discuss best therapeutic practices including the value of molecular testing.


The genetic validation of heterogeneity in schizophrenia.
Schizophrenia is a heritable disorder, however clear genetic architecture has not been detected. To overcome this state of uncertainty, the SZGene database has been established by including all published case-control genetic association studies appearing in peer-reviewed journals. In the current study, we aimed to determine if genetic variants strongly suggested by SZGene are associated with risk of schizophrenia in our case-control samples of Japanese ancestry. In addition, by employing the additive model for aggregating the effect of seven variants, we aimed to verify the genetic heterogeneity of schizophrenia diagnosed by an operative diagnostic manual, the DSM-IV. Each positively suggested genetic polymorphism was ranked according to its p-value, then the seven top-ranked variants (p < 0.0005) were selected from DRD2, DRD4, GRIN2B, TPH1, MTHFR, and DTNBP1 (February, 2007). 407 Schizophrenia cases and 384 controls participated in this study. To aggregate the vulnerability of the disorder based on the participants' genetic information, we calculated the "risk-index" by adding the number of genetic risk factors. No statistically significant deviation between cases and controls was observed in the genetic risk-index derived from all seven variants on the top-ranked polymorphisms. In fact, the average risk-index score in the schizophrenia group (6.5+/-1.57) was slightly lower than among controls (6.6+/-1.39). The current work illustrates the difficulty in identifying universal and definitive risk-conferring polymorphisms for schizophrenia. Our employed number of samples was small, so we can not preclude the possibility that some or all of these variants are minor risk factors for schizophrenia in the Japanese population. It is also important to aggregate the updated positive variants in the SZGene database when the replication work is conducted.


Assessment of variability in biomonitoring data using a large database of biological measures of exposure.
Although intra- and interindividual sources of variation in airborne exposures have been extensively studied, similar investigations examining variability in biological measures of exposure have been limited. Following a review of the world's published literature, biological monitoring data were abstracted from 53 studies that examined workers' exposures to metals, solvents, polycyclic aromatic hydrocarbons, and pesticides. Approximately 40% of the studies also reported personal sampling results, which were compiled as well. In this study, the authors evaluated the intra- and interindividual sources of variation in biological measures of exposure collected on workers employed at the same plant. In 60% of the data sets, there was more variation among workers than variation from day to day. Approximately one-fourth of the data were homogeneous with small differences among workers' mean exposure levels. However, an almost equal number of data sets exhibited moderate to extreme levels of heterogeneity in exposures among workers at the same facility. In addition, the relative magnitude of the intra- to interindividual source of variation was larger for biomarkers with short compared to long half-lives, which suggests that biomarkers with half-lives of 7 days or longer exhibit physiologic dampening of fluctuations in external levels of the workplace contaminant and thereby may offer advantages when compared to short-lived biomarkers or exposures assessed by air monitoring. The use of biological indices of exposure, however, places an additional burden on the strategy used to evaluate exposures, because data may be serially correlated as evidenced in this study, which could result in biased estimates of the variance components if autocorrelation is undetected or ignored in the statistical analyses.


Serum concentrations of micronutrients, packed cell volume, and blood hemoglobin during the first two gestations and lactations of sows.
The objective of the present work was to describe the changes in serum concentrations of some micronutrients during the first 2 gestations and lactations of 33 gilts in order to establish blood reference values for a rapid assessment of nutritional status. In both parities, blood samples were taken from the jugular vein at mating, 5, 10 and 15 wk of gestation and l d and 4 wk after parturition (weaning). Reference values (mean, standard deviation, minimum, maximum) for serum folates, vitamin B12, vitamin B6 metabolites (pyridoxal and pyridoxal-5-phosphate), calcium, phosphorus, sodium, zinc, copper and iron, as well as blood hemoglobin and packed cell volume are reported for each studied time. Differences between parities and between each time are also reported. Results from the present report demonstrate that knowledge of the physiological state of the sows is critical for the assessment of nutritional status of an individual or a breeding herd by interpretation of analyses of blood constituents.


Clinical predictors of the respiratory arousal threshold in patients with obstructive sleep apnea.
A low respiratory arousal threshold (ArTH) is one of several traits involved in obstructive sleep apnea pathogenesis and may be a therapeutic target; however, there is no simple way to identify patients without invasive measurements. To determine the physiologic determinates of the ArTH and develop a clinical tool that can identify patients with low ArTH. Anthropometric data were collected in 146 participants who underwent overnight polysomnography with an epiglottic catheter to measure the ArTH (nadir epiglottic pressure before arousal). The ArTH was measured from up to 20 non-REM and REM respiratory events selected randomly. Multiple linear regression was used to determine the independent predictors of the ArTH. Logistic regression was used to develop a clinical scoring system. Nadir oxygen saturation as measured by pulse oximetry, apnea-hypopnea index, and the fraction of events that were hypopneas (Fhypopneas) were independent predictors of the ArTH (r(2) = 0.59; P < 0.001). Using this information, we used receiver operating characteristic analysis and logistic regression to develop a clinical score to predict a low ArTH, which allocated a score of 1 to each criterion that was satisfied: (apnea-hypopnea index, <30 events per hour) + (nadir oxygen saturation as measured by pulse oximetry >82.5%) + (Fhypopneas >58.3%). A score of 2 or above correctly predicted a low arousal threshold in 84.1% of participants with a sensitivity of 80.4% and a specificity of 88.0%, a finding that was confirmed using leave-one-out cross-validation analysis. Our results demonstrate that individuals with a low ArTH can be identified from standard, clinically available variables. This finding could facilitate larger interventional studies targeting the ArTH.


[Dietary intake and healthcare use among the elderly--Maccabi Healthcare Services survey].
The world population is getting older and the percentage of elderly people (over 65 years old) in Israel (November 1999) is approaching 10%. Six percent of Maccabi Healthcare Services members are older adults. Elderly people are at risk for undernutrition due to chronic diseases, decreased physical and cognitive functioning. The present study aimed to assess the dietary intake of elderly people in Tel Aviv, members of Maccabi Healthcare Services, to evaluate their intake in relation to the recommendations, as well as to determine the association between the dietary intake and the use of medical care services. A random sample of people over 70 years old, members of Maccabi Healthcare Services, were randomly selected and interviewed for their dietary intake using food frequency questionnaire. Additional questions were asked regarding lifestyle, health status and use of health care services. The interviews were conducted by trained interviewers from the surveys department of Maccabi Healthcare Services. One hundred and fifty eight people participated in the survey. Among them, 8% were consuming less than 800 calories per day and 33% less than 1200 calories per day. Over 40% of the participants had at least one chronic disease or condition and 19% had dental problems. Most of the participants (70%) visited their family physician at least once in the last 3 months, 71% visited at least one specialist in the last 6 months and 12% visited a dietitian. Over 90% of the interviewees eat 3 meals a day and over 50% participate in physical activity regularly. Significant negative association was shown between caloric intake and family physician office visits, No such association was shown for specialist office visits. Over 30% of the participants of this study have lower caloric intake. It seems that there is an increased need to improve the awareness of older people to the importance of nutrition for their health and quality of life. Larger and more detailed studies are needed to understand the scope of the problem.


Uncertainty and precaution in European environmental risk assessment of chemicals.
It is recognised that there is a need for a proper treatment and transparency of uncertainty in risk assessment and management, especially in view of the upcoming proposed new chemical policy REACH, which delegates the responsibility for conducting risk assessments to industry. The current EU risk assessment for new and existing substances is largely deterministic and prudential measures are implicitly embedded in calculation schemes and rules. In this paper, a more probabilistic approach to risk assessment is advocated. The advantage is twofold: 1) inherent variability and other uncertainty pertaining to exposure and effects are transparently taken into account, while at the same time 2) issues of caution are explicitly transferred to the risk management phase. The result of a probabilistic risk assessment as suggested is improved transparency with quantitative and qualitative uncertainty estimates. Such uncertainty information can be used to discuss precautionary measures in the context of risk management.


Prostate Cancer Aggressiveness Prediction Using CT Images.
Prostate Cancer (PCa) is mostly asymptomatic at an early stage and often painless requiring active surveillance screening. Transrectal Ultrasound Guided Biopsy (TRUS) is the principal method to diagnose PCa following a histological examination by observing cell pattern irregularities and assigning the Gleason Score (GS) according to the recommended guidelines. This procedure presents sampling errors and, being invasive may cause complications to the patients. External Beam Radiotherapy Treatment (EBRT) is presented as curative option for localised and locally advanced disease, as a palliative option for metastatic low-volume disease or after prostatectomy for prostate bed and pelvic nodes salvage. In the EBRT worflow a Computed Tomography (CT) scan is performed as the basis for dose calculations and volume delineations. In this work, we evaluated the use of data-characterization algorithms (radiomics) from CT images for PCa aggressiveness assessment. The fundamental motivation relies on the wide availability of CT images and the need to provide tools to assess EBRT effectiveness. We used Pyradiomics and Local Image Features Extraction (LIFEx) to extract features and search for a radiomic signature within CT images. Finnaly, when applying Principal Component Analysis (PCA) to the features, we were able to show promising results.


An automated sample preparation for detection of 72 doping-related substances.
Automation of sample preparation procedures in a doping control laboratory is of great interest due to the large number of samples that have to be analyzed, especially in large events where a high throughput protocol is required to process samples over 24 h. The automation of such protocols requires specific equipment capable of carrying out the diverse mechanical tasks required for accomplishing these analytical methodologies, which include pipetting, shaking, heating, or crimping. An automated sample preparation procedure for the determination of doping-related substances by gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) analysis, including enzymatic hydrolysis, liquid-phase extraction and derivatization steps, was developed by using an automated liquid handling system. This paper presents a description of the equipment, together with the validation data for 72 doping-related compounds including extraction efficiency, evaluation of carry-over, interferences, and robustness. Validation was approached as a comparison between the results obtained using the manual protocol and the transferred automated one. The described methodology can be applied for sample preparation in routine anti-doping analysis with high sample throughput and suitable performance.


The effect of dietary lipid on skin tumor promotion by benzoyl peroxide: comparison of fish, coconut and corn oil.
Fish or vegetable oils were fed during the promotion stage of a mouse skin carcinogenesis model in order to investigate the effects of dietary fat on tumor development. Two weeks after initiation with 10 nmol dimethylbenz[a]anthracene, SENCAR mice were divided into five groups and maintained on one of the following semipurified diets containing 10% total fat and varying the type of fat: 8.5% coconut oil (CT)/1.5% corn oil (CO); 1% menhaden oil (MO)/7.5% CT/1.5% CO; 4% MO/4.5% CT/1.5% CO; 8.5% MO/1.5% CO; or 10% CO. Promotion with twice-weekly applications of 40 mg benzoyl peroxide was begun 2 weeks later and continued for 52 weeks. No statistically significant differences in kcal food consumed or body weights were observed between diet groups. Papilloma latency, incidence and yield differed among the diet groups with the group fed the 8.5% CT/1.5% CO diet having the shortest latency and highest papilloma incidence and number. In addition, carcinoma latency and incidence was assessed and the first carcinoma appeared in the group fed 8.5% CT/1.5% CO after 20 weeks of benzoyl peroxide treatment; this group yielded the highest carcinoma incidence throughout the study. In comparison, the group fed the 10% CO diet had the longest latency period, and among the lowest papilloma and carcinoma incidence and fewest tumors. In parallel studies, ornithine decarboxylase activity, vascular permeability and hyperplasia were elevated in the epidermis of benzoyl peroxide-treated mice but the extent of the response did not correlate with the different rates of tumor formation observed among the diet groups. These data indicate that dietary fat modulates tumor promotion by benzoyl peroxide in this skin carcinogenesis model with the predominantly saturated fat diet producing the highest rates of papilloma and carcinogen formation and the polyunsaturated fat diet the lowest.


Initial validity and reliability of the Banff Patella Instability Instrument.
Patellofemoral instability is a well-recognized problem, but there are currently no published patient-reported quality of life outcome measures that are disease specific for the treatment of this population. To establish the content validity, initial construct validity, and initial reliability of the Banff Patella Instability Instrument (BPII). Cohort study (diagnosis); Level of evidence, 2. The content of the BPII was validated using a modified 3-stage Ebel procedure and analysis of floor and ceiling effects. As a measure of internal consistency, the Cronbach α was utilized to assess how reliably the 32 items of the questionnaire measured a similar construct. Test-retest reliability of the BPII was calculated using an intraclass correlation coefficient (ICC). Construct validity was evaluated on 150 questionnaires completed by patients with a confirmed diagnosis of patellofemoral instability. A one-way between-group analysis of variance was employed to determine if the BPII was able to differentiate between patients presenting at the initial orthopaedic consultation relative to patients presenting at 6 months and 12 months postoperatively. Content validity was clearly established as each item in the BPII achieved a minimum of 83.3% agreement (range, 83.3%-100%) for relevance among the expert panelists. The average agreement was 96.9%; 24 items achieved 100% agreement. There was no evidence of floor or ceiling effects. Reliability (internal consistency) of the BPII was established at the initial orthopaedic consultation (α = .91), 6 months postoperatively (α = .97), and 12 months postoperatively (α = .97). Test-retest analysis resulted in an ICC of 0.98 between tests. Construct validity was established as there was a statistically significant difference in BPII scores at the initial orthopaedic consultation and 6-month and 12-month postoperative appointments (F2,146 = 75.62; P < .001). The BPII demonstrates content validity, strong initial reliability, and a statistically significant level of construct validity in patients with patellofemoral instability. This population includes patients with recurrent patellofemoral instability as well as surgically stabilized patients.


Reversible replication between ordered mesoporous silica and mesoporous carbon.
Highly ordered mesoporous silica can be regenerated from a mesoporous carbon CMK-3 that is a negative replica of mesoporous silica SBA-15, indicating reversible replication between carbon and inorganic materials.


Association between C-Reactive Protein Levels and Functional Disability in the General Older-Population: The Takashima Study.
High-sensitivity C-reactive protein (hsCRP) associates with atherosclerotic diseases such as stroke. However, previous results on the association between hsCRP levels and functional disability were controversial. We analyzed 2,610 men and women who did not exhibit functional disability or death within the first 3 years of the baseline survey and those aged 65 years or older at the end of follow-up. The levels of hsCRP were assessed using latex agglutination assay at baseline survey from 2006 to 2014. Functional disability was followed up using the long-term care insurance (LTCI) program until November 1, 2019. Functional disability was defined as a new LTCI program certification. Cox proportional hazards model with competing risk analysis for death was used to evaluate the association between hsCRP levels and future functional disability. During a 9-year follow-up period, we observed 328 cases of functional disability and 67 deaths without prior functional disability incidence. The multivariable-adjusted hazard ratio (HR, 95% confidence interval [CI]) of functional disability in log-transferred hsCRP levels was 1.43 (1.22-1.67) in men and 0.97 (0.81-1.15) in women. When hsCRP level was analyzed as a categorical variable, low hsCRP levels (<1.0 mg/l) as the reference, the multivariable-adjusted HR (95% CI) of functional disability in high hsCRP levels (≥ 3.0 mg/l) was 2.37 (1.56-3.62). Similar results were observed when stratified by sex, but it was not significant in women. This study demonstrates that low-grade systemic inflammation to assess hsCRP might predict the future incidence of functional disability, especially in men.


Analysis of quantitative methods for rib seriation using the Spitalfields documented skeletal collection.
Accurate rib seriation is essential in forensic anthropology and bioarchaeology for determination of minimum numbers of individuals, sequencing trauma patterns to the chest, and identification of central ribs for use in age estimation. We investigate quantitative methods for rib seriation based on three metric variables: superior (anterior) costo-transverse crest height (SCTCH), articular facet of the tubercle-to-angle length (AFTAL), and head-to-articular facet length (HAFL). The sample consists of complete but unseriated sets of ribs from 133 individuals from the documented (known age and sex) and undocumented skeletal collections of Christ Church Spitalfields, London. This research confirms the results of an earlier study (Hoppa and Saunders [1998] J. Forensic. Sci. 43:174-177) and extends it with the application of two new metric traits and further analyses of sex differences. Analyses of variance showed that SCTCH and AFTAL are significantly associated (P < 0.001) with rib number. Tukey tests of pairwise rib comparisons revealed that for two dimensions (SCTCH and AFTAL), the central ribs (3rd-6th) are significantly distinct from each other (P < 0.05). Using simple ranking of either the SCTCH or AFTAL traits, the proportion of correctly identified ribs within +/-1 position was 80%, compared to initial seriation using morphological methods (Dudar [1993] J. Forensic. Sci. 28:788-797; Mann [1993] J. Forensic. Sci. 28:151-155). Significant sex dimorphism was also identified for these two traits. Analysis of the HAFL trait produced somewhat equivocal results, suggesting that this variable is not reliable for rib seriation. The variable SCTCH proves to be the most useful dimension for seriation, and shows that all but the 7th-9th ribs can be distinguished from others in the sequence, with important results for the 4th rib, where ranking allowed identification in 86% of cases, consistent with morphological methods for intact ribs.


An Information Theory Approach to Aesthetic Assessment of Visual Patterns.
The question of beauty has inspired philosophers and scientists for centuries. Today, the study of aesthetics is an active research topic in fields as diverse as computer science, neuroscience, and psychology. Measuring the aesthetic appeal of images is beneficial for many applications. In this paper, we will study the aesthetic assessment of simple visual patterns. The proposed approach suggests that aesthetically appealing patterns are more likely to deliver a higher amount of information over multiple levels in comparison with less aesthetically appealing patterns when the same amount of energy is used. The proposed approach is evaluated using two datasets; the results show that the proposed approach is more accurate in classifying aesthetically appealing patterns compared to some related approaches that use different complexity measures.


Synthesis and properties of (triptycenedicarboxylatio)zinc coordination networks.
(Triptycenedicarboxylato)zinc metal-organic frameworks (MOFs) based on paddle wheel secondary building units (SBUs) with different axial ligands have been prepared. The reproducible formation of the layered paddle-wheel structures from triptycenedicarboxylic acid (H(2)TDC) and zinc nitrate under various conditions seems to be characteristic of this acid and is utilized for the construction of 3D frameworks by a pillaring approach. We attempted to bring additional functionalities into MOFs by employing the appropriate pillaring ligands, for example, bis(4-pyridyl)-s-tetrazine and bis(4-pyridyl)-dimethoxy-p-phenylenedivinylene, and investigated certain properties of some MOF materials, such as guest-exchange behavior, luminescence, microporosity, and stability.


Ultrastructural analysis of ICP34.5- herpes simplex virus 1 replication in mouse brain cells in vivo.
Replication-competent forms of herpes simplex virus 1 (HSV-1) defective in the viral neurovirulence factor infected cell protein 34.5 (ICP34.5) are under investigation for use in the therapeutic treatment of cancer. In mouse models, intratumoral injection of ICP34.5-defective oncolytic HSVs (oHSVs) has resulted in the infection and lysis of tumor cells, an associated decrease in tumor size, and increased survival times. The ability of these oHSVs to infect and lyse cells is frequently characterized as exclusive to or selective for tumor cells. However, the extent to which ICP34.5-deficient HSV-1 replicates in and may be neurotoxic to normal brain cell types in vivo is poorly understood. Here we report that HSV-1 defective in ICP34.5 expression is capable of establishing a productive infection in at least one normal mouse brain cell type. We show that γ34.5 deletion viruses replicate productively in and induce cellular damage in infected ependymal cells. Further evaluation of the effects of oHSVs on normal brain cells in animal models is needed to enhance our understanding of the risks associated with the use of current and future oHSVs in the brains of clinical trial subjects and to provide information that can be used to create improved oHSVs for future use.


Simple analytical expression for crosstalk estimation in homogeneous trench-assisted multi-core fibers.
An analytical expression for the mode coupling coefficient in homogeneous trench-assisted multi-core fibers is derived, which has a simple relationship with the one in normal step-index structures. The amount of inter-core crosstalk reduction (in dB) with trench-assisted structures compared to the one with normal step-index structures can then be written by a simple expression. Comparison with numerical simulations confirms that the obtained analytical expression has very good accuracy for crosstalk estimation. The crosstalk properties in trench-assisted multi-core fibers, such as crosstalk dependence on core pitch and wavelength-dependent crosstalk, can be obtained by this simple analytical expression.


The production and characterization of thyroid-derived T-cell lines in Graves' disease and Hashimoto's thyroiditis.
Although the thyroid gland itself is a major site of the autoimmune response, the study of T-cell function in autoimmune thyroid disease has usually relied on peripheral blood as a source of cells. In this study, we have established thyroid-derived T-cell lines from six patients with Graves' disease and one patient with Hashimoto's thyroiditis by culturing the thyroid lymphocytes on an autologous thyroid follicular cell monolayer in the presence of exogenous interleukin 2 (IL-2). These T-cell lines have allowed in vitro investigation of thyroid-derived T-cell function, an approach which was previously limited by the number of lymphocytes obtained from the gland. The lines were predominantly OKT3, OKT4, and HLA-DR positive but showed heterogeneous proliferative responses. Some lines gave autologous or allogeneic mixed lymphocyte reactions but other did not. Only one of the seven lines responded well to the thyroid antigens thyroglobulin and microsomes presented by autologous monocytes. However, six of the lines proliferated in the presence of live but not dead autologous thyroid follicular cells, particularly when interferon-gamma (IFN-gamma) was added. This treatment has been shown to enhance HLA-DR and -DQ antigen expression by thyroid follicular cells in vitro. Furthermore, the proliferation induced by IFN-gamma-treated thyroid follicular cells was increased when thyroglobulin was also added. Together these results support the hypothesis that the expression of Ia antigens such as HLA-DR by thyroid follicular cells in autoimmune thyroid disease may be important in enhancing the autoimmune response, conferring on these cells the ability to present thyroid autoantigens to T cells. The use of thyroid-derived T-cell lines should permit a more detailed evaluation of the disordered immuno-regulation in Graves' disease and Hashimoto's thyroiditis than has been possible previously.


Sequence-dependent inhibition of human colon cancer cell growth and of prosurvival pathways by oxaliplatin in combination with ZD6474 (Zactima), an inhibitor of VEGFR and EGFR tyrosine kinases.
To date, clinical studies combining the new generation of targeted therapies and chemotherapy have had mixed results. Preclinical studies can be used to identify potential antagonism/synergy between certain agents, with the potential to predict the most efficacious combinations for further investigation in the clinical setting. In this study, we investigated the sequence-dependent interactions of ZD6474 with oxaliplatin in two human colon cell lines in vitro. We evaluated the in vitro antitumor activity of ZD6474, an inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR) and RET tyrosine kinase activity, and oxaliplatin using three combination schedules: ZD6474 before oxaliplatin, oxaliplatin before ZD6474, and concurrent exposure. Cell proliferation studies showed that treatment with oxaliplatin followed by ZD6474 was highly synergistic, whereas the reverse sequence was clearly antagonistic as was concurrent exposure. Oxaliplatin induced a G(2)-M arrest, which was antagonized if the cells were previously or concurrently treated with ZD6474. ZD6474 enhanced oxaliplatin-induced apoptosis but only when added after oxaliplatin. The sequence-dependent antitumor effects appeared, in part, to be based on modulation of compensatory prosurvival pathways. Thus, expression of total and active phosphorylated EGFR, as well as AKT and extracellular signal-regulated kinase, was markedly increased by oxaliplatin. This increase was blocked by subsequent treatment with ZD6474. Furthermore, the synergistic sequence resulted in reduced expression of insulin-like growth factor-I receptor and a marked reduction in secretion of vascular endothelial growth factor protein. ZD6474 in combination with oxaliplatin has synergistic antiproliferative properties in human colorectal cancer cell lines in vitro when oxaliplatin is administered before ZD6474.


Effects of citraconylation on enzymatic modification of human proinsulin using trypsin and carboxypeptidase B.
Insulin is a polypeptide hormone which is produced by the beta-cell of pancreas and controls the blood glucose level in the human body. Enzymatic modification of human proinsulin using trypsin and carboxypeptidase B generally causes high accumulation of insulin derivatives, leading to more complicated purification processes. A simple method including citraconylation and decitraconylation in the enzymatic modification process was developed for the reduction of a major derivative, des-threonine human insulin. Addition of 3.0 g citraconic anhydride per g protein into the reaction solution led to the citraconylation of lysine residues in human proinsulin and reduction of relative des-threonine insulin content from 13.5 to 1.0%. After the enzymatic hydrolysis of the citraconylated proinsulin, 100% of lysine residues can be decitraconylated and restored by adjusting pH to 2-3 at 25 degrees C. Combination of hydrogen peroxide addition and citraconylation of proinsulin expressed in recombinant Escherichia coli remarkably improved the conversion yield of insulin from 52.7 to 77.7%. Consequently, citraconylation of lysine residues blocked the unexpected cleavage of human proinsulin by trypsin, minimized the formation of des-threonine insulin and hence increased the production yield of active insulin.


Relative importance of psychologic traits and severity of ischemia in causing angina during treadmill exercise. Canadian Amlodipine/Atenolol in Silent Ischemia Study (CASIS) Investigators.
This study was conducted to compare the influence of psychologic traits versus ischemia severity on the occurrence of angina during treadmill exercise. Some studies suggest that angina is associated with certain psychologic traits, whereas others show an association with more severe ischemia. The relative influence of these two factors and the extent to which they interact are not known. Off-drug treadmill exercise testing and a battery of psychologic tests were performed on 122 patients with known coronary artery disease. Psychologic tests measured sensitivity to physical symptoms, denial and deception, type A behavior, anger, hostility, depression, marital adjustment and amount of external stress. Stepwise logistic regression was used to determine the independent association of psychologic traits, ischemic threshold and exercise tolerance with the occurrence of angina. Angina during treadmill exercise was reported by 66 of 122 patients. On univariate testing, angina was positively associated with sensitivity to physical symptoms (p < 0.001), type A behavior (p = 0.021) and depression (p = 0.032) and was negatively associated with exercise tolerance (p < 0.001) and work load threshold for ischemia (p < 0.01). Multivariate analysis revealed independent and additive associations of angina with sensitivity to physical symptoms (p = 0.003), exercise capacity (p = 0.003) and work load threshold for ischemia (p = 0.018). Once these were included in a logistic model, depression and type A behavior were no longer significant. Other psychologic traits showed no association with angina. Sensitivity to physical symptoms, ischemic threshold and exercise tolerance are independently associated with angina, with sensitivity to physical symptoms having the stronger influence. The physiologic and psychologic mechanisms underlying symptom perception have an influence on angina that is independent of and additive to the severity of underlying ischemia.


The prognostic importance of glucose-to-lymphocyte ratio and uric acid in metastatic breast cancer patients treated with Cdk 4/6 inhibitors.
Aim: To demonstrate the prognostic importance of glucose-to-lymphocyte ratio (GLR) and uric acid (UA) in patients with metastatic breast cancer (MBC) receiving Cdk 4/6 inhibitors. Materials & methods: Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, GLR, UA and CA15-3 were analyzed to assess their prognostic value using Kaplan-Meier curves and Cox regression analysis in 101 patients with MBC, retrospectively. Results: Importantly, both progression-free survival and overall survival were shorter in the group with high neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), GLR and UA. In the multivariate analysis, GLR and UA levels were independent prognostic factors for both progression-free survival and overall survival. Conclusion: In patients with MBC, GLR and UA are independent factors that predict survival times.


Nutritional status of patients with cystic fibrosis with meconium ileus: a comparison with patients without meconium ileus and diagnosed early through neonatal screening.
This study was pursued as an extension of a randomized clinical investigation of neonatal screening for cystic fibrosis (CF). The objective was to determine if CF patients with meconium ileus (MI) were more likely to be malnourished compared with those without MI who were diagnosed during early infancy through neonatal screening. Nutritional status was evaluated from early infancy to 13 years of age based on anthropometric, biochemical, and dietary assessments. MI patients (n = 32) were smaller at birth (3117 g compared with 3413 g) and were shorter (22nd percentile compared with 48th percentile) and thinner (24th percentile compared with 49th percentile) compared with non-MI early diagnosed patients (n = 50) up to 13 years of age. Poor growth was particularly evident in 26 MI patients who required surgery for MI (height and weight at the 20th percentile), whereas those treated without surgery (n = 6) showed better height (45th percentile) and weight (37th percentile). Abnormal essential fatty acid profiles were significantly more prevalent in MI compared with non-MI early-diagnosed patients before 3 years of age. Daily intakes of calorie (130% compared with 111% recommended dietary allowances) and protein (339% compared with 279% recommended dietary allowances) were higher but the percentage of fat (37% compared with 38%) and linoleic acid (4.5% compared with 4.7%) in the diet were similar between the two groups. These results demonstrated a clear association of MI with malnutrition in CF. The observed poor growth among our MI patients was not because of poor dietary intakes, but was related to surgical treatment for MI and poor essential fatty acid status. These findings present new challenges regarding the optimal medical treatment and nutritional intervention for CF patients with MI.


Synergistic effects of risk factors.
Risk factors for coronary heart disease (CHD), stroke, congestive heart failure and total mortality were analysed in two random population samples of men in Gothenburg, Sweden, aged 50 and 47-55 years, respectively, at entry. A series of potential risk factors for the above mentioned end-points have been analysed in univariate and multivariate logistic analyses. Population attributable risks were also calculated. Significant risk factors in multivariate analyses are summarized. For CHD they were: family history of CHD, hypercholesterolemia, hypertension, tobacco smoking, psychologic stress, low social class and diabetes mellitus. In hypertensives, proteinuria was measured and found to be significant also. Stroke risk factors were: family history of stroke, blood pressure, smoking, high waist/hip ratio, high plasma fibrinogen, psychologic stress, proteinuria, atria fibrillation and transitory ischemic attacks. Hypertension, smoking, high waist/hip ratio and psychologic stress were risk factors for congestive heart failure.


Review of hair cell synapse defects in sensorineural hearing impairment.
To review new insights into the pathophysiology of sensorineural hearing impairment. Specifically, we address defects of the ribbon synapses between inner hair cells and spiral ganglion neurons that cause auditory synaptopathy. Here, we review original publications on the genetics, animal models, and molecular mechanisms of hair cell ribbon synapses and their dysfunction. Hair cell ribbon synapses are highly specialized to enable indefatigable sound encoding with utmost temporal precision. Their dysfunctions, which we term auditory synaptopathies, impair audibility of sounds to varying degrees but commonly affect neural encoding of acoustic temporal cues essential for speech comprehension. Clinical features of auditory synaptopathies are similar to those accompanying auditory neuropathy, a group of genetic and acquired disorders of spiral ganglion neurons. Genetic auditory synaptopathies include alterations of glutamate loading of synaptic vesicles, synaptic Ca influx or synaptic vesicle turnover. Acquired synaptopathies include noise-induced hearing loss because of excitotoxic synaptic damage and subsequent gradual neural degeneration. Alterations of ribbon synapses likely also contribute to age-related hearing loss.


Observations on carbon and nitrogen content of suspended matter in a headwater stream in Hong Kong.
The total carbon(C) and total nitrogen(N) content of suspended matter in a small undisturbed headwater drainage basin in the New Territories of Hong Kong has been monitored. Mean C and N contents were 12.85% and 0.99% respectively for 132 samples. Samples collected under stableflow conditions had mean C and N contents of 12.81% and 1.06% respectively. Stormflow samples had mean C and N values of 12.86% and 0.97% respectively, which were very similar to the levels observed under stableflow conditions. The mean C:N ratios of 12.47 and 13.39 for stableflow and stormflow also reveal little difference according to hydrologic conditions. When all the data is considered little difference is observed in C and N according to the season. However, in winter there is a significant difference in C and N content between stable and stormflow samples. When C and N are plotted against water level the scattergraphs suggested that as stage increases the percentage of C and N in the suspended matter declines. Scattergraphs of C and N against suspended sediment concentration reveal a negative association. Comparison has been made between fresh leaf C, N and C/N ratio for trees and shrubs and the suspended matter. Fresh leaves do not appear to contribute significantly to suspended matter. The C/N ratio of suspended matter would also seem to exclude woody material and algae as sources of suspended matter.


What children and young people learn about ADHD from youth information books: A text analysis of nine books on ADHD available in Dutch.
Attention Deficit Hyperactivity Disorder (ADHD) is not a singular concept. For the purposes of this study, understandings of ADHD are assumed also to spread along a conceptual dimension that includes some combination of biomedical and psychosocial knowledge. Biomedically, ADHD may be considered a somatic affliction causing inattention and hyperactivity, amenable to pharmaceutical treatment. Psychosocially, ADHD ranks among adverse behaviour patterns that are amenable to psychosocial and pedagogical intervention. Considering both biomedical and psychosocial factors are associated with the ADHD construct, it seems self-evident that young people should be offered information that gives equal consideration to both ways of addressing ADHD, but the question is just how balanced the information available to young people is. This study investigated nine information books on ADHD available in the Netherlands in Dutch, aimed at children and young people up to age 17. Thirteen perspective-dependent text elements were identified in qualitative content analysis. Eight attributes associate with a biomedical view: ADHD as cause, biological factors, clinical diagnosis, brain abnormality, medication, neurofeedback, heritability and persistence. Five text elements associate with a psychosocial view: ADHD as perceived behaviour, environmental factors, descriptive diagnosis, behavioural intervention and normalisation. The most frequent text passages encountered describe ADHD as a brain abnormality, along with medical and behavioural treatment. Providing the main focus for information in eight out of nine books, biomedical information about ADHD predominates in the available youth information books, while psychosocial information about ADHD is far less well covered.


[Prevalence of FTLV (feline T-lymphotropic lentivirus) infections in cats in The Netherlands and in West Germany].
The prevalence in the Netherlands and the Free Republic of Germany (FRG) of the newly discovered retrovirus of cats, which causes an immunodeficiency syndrome in this species and is termed feline T-lymphotropic lentivirus (FTLV), was estimated by conducting a serological survey among cats with different histories of disease. In an enzyme-linked immunosorbent assay (Petcheck, Agritech Trademark, Portland, USA) 265 samples of cats with chronic disease symptoms, and 78 samples of clinically healthy cats in the Netherlands, and 138 samples of cats with chronic disease symptoms in the FRG, were tested for the presence of FTLV-specific antibodies. All these samples had been taken from cats which were negative for FeLV antigen in the immunofluorescence test. In the groups of chronically ill animals 18 (7%) and 6 (4.5%) seropositive animals were found respectively, whereas in the group of clinically healthy cats no seropositive animals could be demonstrated.


The zinc repository of Cupriavidus metallidurans.
Zinc is a central player in the metalloproteomes of prokaryotes and eukaryotes. We used a bottom-up quantitative proteomic approach to reveal the repository of the zinc pools in the proteobacterium Cupriavidus metallidurans. About 60% of the theoretical proteome of C. metallidurans was identified, quantified, and the defect in zinc allocation was compared between a ΔzupT mutant and its parent strain. In both strains, the number of zinc-binding proteins and their binding sites exceeded that of the zinc ions per cell, indicating that the totality of the zinc proteome provides empty binding sites for the incoming zinc ions. This zinc repository plays a central role in zinc homeostasis in C. metallidurans and probably also in other organisms.


Effect of hydrogen peroxide on color and whiteness of resin-based composites.
To evaluate the influence of a 35% hydrogen peroxide gel on color and whiteness changes of resin-based composites (RBC). Discs (n = 10; shade A3.5 enamel; and 8 mm diameter and 2 mm thick) were fabricated from three RBC (DF- Durafill, Heraeus Kulzer; ED- IPS Empress Direct, Ivoclar Vivadent; and AP- Amelogen Plus, Ultradent Products). Three subgroups were obtained for each RBC: before bleaching (T0 ) and after first (T1 ) and second (T2 ) bleaching applications. A dental spectrophotometer (VITA Easyshade, Vita Zahnfabrik) was used to obtain CIELAB color coordinates and whiteness index for dentistry (WID ) in all periods. CIELAB ( ΔEab* ) and CIEDE2000 (ΔE00 ) color differences were also obtained. Perceptibility (PT) and acceptability (AT) thresholds were used to analyze values of ΔEab* , ΔE00 , and ΔWID . Two-way analysis of variance (ANOVA; for L*, a*, b*, and WID ) and one-way ANOVA and Tukey tests (for ΔEab* and ΔE00 ) were used to analyzed the results (α = 0.05). L* and WID values from all RBC did not change after bleaching applications (T1 and T2 ) (P > .05). There were no significant differences in color differences ( ΔEab* and ΔE00 ) among all RBC evaluated after bleaching applications (T1 -T0 and T2 -T0 ; P > .05). Regardless of the RBC, mean values of ΔE00 between all different periods were always below 50%:50% PT value. The 35% hydrogen peroxide bleaching gel influences on color and whiteness of resin-based composites. However, color changes were not clinically perceived and whiteness variations were clinically acceptable. Patients should be advised that existing composite restorations might not match the natural tooth color after bleaching, and their replacement may be required.


Does aspirin-induced oxidative stress cause asthma exacerbation?
Aspirin-induced asthma (AIA) is a distinct clinical syndrome characterized by severe asthma exacerbations after ingestion of aspirin or other non-steroidal anti-inflammatory drugs. The exact pathomechanism of AIA remains unknown, though ongoing research has shed some light. Recently, more and more attention has been focused on the role of aspirin in the induction of oxidative stress, especially in cancer cell systems. However, it has not excluded the similar action of aspirin in other inflammatory disorders such as asthma. Moreover, increased levels of 8-isoprostanes, reliable biomarkers of oxidative stress in expired breath condensate in steroid-naïve patients with AIA compared to AIA patients treated with steroids and healthy volunteers, has been observed. This review is an attempt to cover aspirin-induced oxidative stress action in AIA and to suggest a possible related pathomechanism.


Pre-exposure prophylaxis state of the science: empirical analogies for research and implementation.
Pre-exposure prophylaxis (PrEP) has the potential to become a powerful biomedical approach to HIV prevention; however, its success depends on behavioral and social factors that may determine its appropriate use. This article is designed to facilitate interdisciplinary empirical analogies relevant to PrEP implementation, reviewing behavioral and social science findings that may provide lessons critical to the success of PrEP as a biomedical-behavioral prevention strategy. As we prepare for the dissemination of new biomedical approaches to HIV prevention, integrating the state of the science across disciplines may result in innovative strategies for implementation that can enhance their success.


Cerebral amyloid angiopathy as a cause of recurrent intracerebral hemorrhage.
Cerebral amyloid angiopathy is a largely untreatable disease often not diagnosed until autopsy. Severe cerebral amyloid angiopathy can cause lobar cerebral hemorrhage, transient neurological symptoms, and dementia with leukoencephalopathy. Several outcome studies have suggested lower mortality and better functional recovery in lobar compared with deep hemorrhage. Recurrence of lobar hemorrhage however is relatively common. We describe a case of recurrent spontaneous intracerebral hemorrhage in a 72-year-old woman requiring surgical evacuations. A review of the literature summarizing the diagnosis and treatment of cerebral amyloid angiopathy is presented.


Correlation between plasma and saliva adrenocortical hormones in response to submaximal exercise.
This study examined the relationships between plasma and saliva adrenocortical hormones in response to long-duration submaximal exercise. In nine healthy, physically active, female volunteers, blood and saliva samples were taken at rest and every 30 min during a 120-min cycling trial at 50-55% VO(2max) for cortisol and dehydroepiandrosterone (DHEA) analysis. Correlation analysis revealed a moderate but significant relationship between plasma and saliva cortisol (r = 0.35, P < 0.02) and plasma and saliva DHEA (r = 0.47, P < 0.001) during the submaximal exercise. When expressed in percent of resting values, the correlations between the plasma and saliva concentrations were higher for both hormones during the exercise (cortisol: r = 0.72; DHEA: r = 0.68, P < 0.001). The results thus suggest that, even under prolonged exercise conditions, non-invasive saliva samples may offer a practical approach to assessing pituitary-adrenal function, especially when compared with individual basal values.


Gadobenate dimeglumine 0.5 M solution for injection (MultiHance) pharmaceutical formulation and physicochemical properties of a new magnetic resonance imaging contrast medium.
To characterize the proton-magnetic relaxation properties and complexation equilibria of gadobenate dimeglumine and to develop a pharmaceutical formulation for injection. Proton-magnetic relaxivities were determined at 20 MHz and 39 degrees C. Metal complexation was studied potentiometrically. Degradation pathways were identified through prolonged exposure to elevated temperature. Because of its size and very weak interaction with serum albumin, gadobenate dimeglumine has proton-magnetic relaxivities that are larger than those of gadopentetate dimeglumine in both water and biological fluids. With regard to metal complexation, the two products are indistinguishable. The metal complexation behavior and thermal stability of the product allowed a pharmaceutical formulation for injection containing 0.5 M gadobenate dimeglumine without excipients. The physicochemical properties of the formulated product were determined. Gadobenate dimeglumine has an elevated T1-relaxivity, especially in blood plasma. The high stability of the complex guarantees a negligible release of gadolinium ion. Gadobenate dimeglumine 0.5 M solution for injection has a shelf life of three years.


Family structure and children's television viewing and physical activity.
This study aimed to examine how physical activity (PA) and television (TV) viewing time of children varied according to family structure. In 2001, 5- to 6-yr-old (N = 296) and 10- to 12-yr-old (N = 919) children and their parents were recruited from 19 state elementary schools in Melbourne, Australia. Children's PA was objectively assessed using accelerometers worn for 8 d. Sociodemographic and family structure information and time spent watching TV was collected via questionnaire completed by parents. ANCOVA revealed that, after controlling for socioeconomic status and age of child, boys without any siblings spent more minutes per day watching TV (153.2 +/- 71.3) compared with those who have siblings (129.0 +/- 64.4, P < 0.05). There were also significant differences in TV viewing time between boys with one sibling (125.5 +/- 59.9), two siblings (141.9 +/- 70.1), or three or more siblings (111.6 +/- 62.6, P < 0.001). Girls from single-parent families (145.7 +/- 85.1) spent significantly more minutes per day watching TV compared with girls from two-parent families (125.1 +/- 67.7, P < 0.05). Girls with siblings spent more minutes per day in PA (148.3 +/- 67.7) compared with those who were an only child (131.0 +/- 58.9, P < 0.05). There were significant interactions between parental status and having a sibling, with PA, and also with TV viewing for girls and between parental status and having a brother with PA for boys. There were also significant interactions between having an older sibling and child's sex with PA and between number of siblings and sex with TV viewing. Family structure may be an important source of influence on children's PA and TV viewing time. Aspects of family structure interact differently with PA and TV viewing, suggesting interventions may need to be tailored with consideration of the family structure of children.


Biochronological, taphonomical, and paleoenvironmental background of the fossil great ape Pierolapithecus catalaunicus (Primates, Hominidae).
The Late Aragonian (late middle Miocene) stratigraphic sequence of Abocador de Can Mata (ACM) from Els Hostalets de Pierola (Vallès-Penedès Basin, Catalonia, Spain), rich in fossil vertebrate localities, provides a unique opportunity to study the evolution of western Eurasian hominoids. Among these sites, Barranc de Can Vila 1 (BCV1) recently delivered a well-preserved hominoid partial skeleton of a new genus and species, Pierolapithecus catalaunicus. On the basis of the small-mammal fauna recovered at BCV1, we infer an early MN 7+8 age, between 12.5 and 12Ma, for this site. The spatial distribution of macromammal fossils, the relative abundances of skeletal elements, and their state of preservation suggest that different agents were involved in the accumulation of the P. catalaunicus individual and the remaining taxa. Carnivore marks occur on some bones of the P. catalunicus skeleton, documenting the action of predators and/or scavengers in this case. In contrast, carnivore marks are extremely rare on other macromammal remains, which seem to be derived from adjacent alluvial-fan plain areas. The small-mammal fauna from BCV1 and the large-mammal fauna from the ACM series, indicate the presence of considerably humid and warm forest environments. The compositions of the small-mammal fauna from BCV1 and from other Late Aragonian sites from the Vallès-Penedès area are similar to those from France and central Europe. The former are clearly distinct from those of Iberian inner basins, where the environment appears to have been drier, thus precluding the dispersal of hominoids into that area.


Template-directed ligation of tethered mononucleotides by t4 DNA ligase for kinase ribozyme selection.
In vitro selection of kinase ribozymes for small molecule metabolites, such as free nucleosides, will require partition systems that discriminate active from inactive RNA species. While nucleic acid catalysis of phosphoryl transfer is well established for phosphorylation of 5' or 2' OH of oligonucleotide substrates, phosphorylation of diffusible small molecules has not been demonstrated. This study demonstrates the ability of T4 DNA ligase to capture RNA strands in which a tethered monodeoxynucleoside has acquired a 5' phosphate. The ligation reaction therefore mimics the partition step of a selection for nucleoside kinase (deoxy)ribozymes. Ligation with tethered substrates was considerably slower than with nicked, fully duplex DNA, even though the deoxynucleotides at the ligation junction were Watson-Crick base paired in the tethered substrate. Ligation increased markedly when the bridging template strand contained unpaired spacer nucleotides across from the flexible tether, according to the trends: A(2)>A(1)>A(3)>A(4)>A(0)>A(6)>A(8)>A(10) and T(2)>T(3)>T(4)>T(6) approximately T(1)>T(8)>T(10). Bridging T's generally gave higher yield of ligated product than bridging A's. ATP concentrations above 33 microM accumulated adenylated intermediate and decreased yields of the gap-sealed product, likely due to re-adenylation of dissociated enzyme. Under optimized conditions, T4 DNA ligase efficiently (>90%) joined a correctly paired, or TratioG wobble-paired, substrate on the 3' side of the ligation junction while discriminating approximately 100-fold against most mispaired substrates. Tethered dC and dG gave the highest ligation rates and yields, followed by tethered deoxyinosine (dI) and dT, with the slowest reactions for tethered dA. The same kinetic trends were observed in ligase-mediated capture in complex reaction mixtures with multiple substrates. The "universal" analog 5-nitroindole (dNI) did not support ligation when used as the tethered nucleotide. Our results reveal a novel activity for T4 DNA ligase (template-directed ligation of a tethered mononucleotide) and establish this partition scheme as being suitable for the selection of ribozymes that phosphorylate mononucleoside substrates.


Controlling for endogeneity in attributable costs of vancomycin-resistant enterococci from a Canadian hospital.
Decisions regarding the optimal provision of infection prevention and control resources depend on accurate estimates of the attributable costs of health care-associated infections. This is challenging given the skewed nature of health care cost data and the endogeneity of health care-associated infections. The objective of this study is to determine the hospital costs attributable to vancomycin-resistant enterococci (VRE) while accounting for endogeneity. This study builds on an attributable cost model conducted by a retrospective cohort study including 1,292 patients admitted to an urban hospital in Vancouver, Canada. Attributable hospital costs were estimated with multivariate generalized linear models (GLMs). To account for endogeneity, a control function approach was used. The analysis sample included 217 patients with health care-associated VRE. In the standard GLM, the costs attributable to VRE are $17,949 (SEM, $2,993). However, accounting for endogeneity, the attributable costs were estimated to range from $14,706 (SEM, $7,612) to $42,101 (SEM, $15,533). Across all model specifications, attributable costs are 76% higher on average when controlling for endogeneity. VRE was independently associated with increased hospital costs, and controlling for endogeneity lead to higher attributable cost estimates.


Characteristics, Prognostic Factors, and Survival of Patients with NK/T-Cell Lymphoma of Non-upper Aerodigestive Tract: A 17-Year Single-Center Experience.
The extranodal natural killer (NK)/T-cell lymphoma (NKTCL) of non-upper aerodigestive tract (NUAT) was found to have clinical heterogeneity compared with NKTCL of the upper aerodigestive tract (UAT) in small scale studies. We conducted this study in a much larger cohort to analyze the clinical characteristics, prognostic factors, treatment modality, and clinical outcomes of patients with NUAT-NKTCL. From January 2001 to December 2017, a total of 757 NKTCL patients were identified and included in this study, including 92 NUAT-NKTCL patients (12.2%) and 665 UAT-NKTCL patients (87.8%). NUAT-NKTCL patients had relatively poorer performance status, more unfavorable prognostic factors, and more advanced stage, compared with UAT-NKTCL patients. The 5-year overall survival (OS) was 34.7% for NUAT-NKTCL, which was significantly worse than UAT-NKTCL (64.2%, p<0.001). The median OS duration was 30.9 months for NUAT-NKTCL. Multivariate analysis showed that presence with B symptoms and elevated serum lactate dehydrogenase independently predicted worse OS. International prognostic index score and prognostic index of natural killer lymphoma score still had prognostic values in NUAT-NKTCL, while the Ann Arbor system could not accurately predict the OS. NUAT-NKTCL is a distinctive subtype of NKTCL in many aspects. Patients with NUAT-NKTCL have relatively poorer performance status, more unfavorable prognostic factors, more advanced stage, and poorer prognosis.


Water binders in beef patties increase yield and extend shelf life.
Identifying nonallergenic, natural water binders to increase beef patty juiciness and extend shelf life would be beneficial to the beef industry. The objective of this study was to determine the effect of integrating water binders into beef hamburger patties on cooking yield, shelf life, and pH. Five water binder treatments were added at 2% of the meat block. Treatments included potato extract, citrus fiber, dried refried beans, potato peel, or no binder (control). Six batches of each treatment were made and two patties from each batch were analyzed for each parameter. Fluid yield and lipid oxidation were measured on cooked, frozen (210 d), and reheated patties. Raw patties were used to evaluate color, fluid loss, and lipid oxidation over 4 d of retail display. Patties containing citrus fiber improved reheat yield (P = 0.03) and overall yield (P < 0.01). Citrus patties had the lowest pH (P < 0.01) at 5.45. On days 0 and 4 of retail display, patties containing a water binder treatment had less lipid oxidation than the control patties (P < 0.01). Additionally, the cooked, frozen, and reheated patties, had less lipid oxidation when containing a water binder treatment than the control patties (P < 0.01). Citrus fiber improved water retention in reheated patties, and all water binders delayed lipid oxidation in raw, cooked, frozen, and reheated patties. Increasing patty juiciness and delaying lipid oxidation will improve consumers' eating experience of reheated, precooked patties in settings such as school or hospital cafeterias.


Rich context information for just-in-time adaptive intervention promoting physical activity.
Sedentary lifestyle and inadequate levels of physical activity represent two serious health risk factors. Nevertheless, within developed countries, 60% of people aged over 60 are deemed to be sedentary. Consequently, interest in behavior change to promote physical activity is increasing. In particular, the role of emerging mobile apps to facilitate behavior change has shown promising results. Smart technologies can help in providing rich context information including an objective assessment of the level of physical activity and information on the emotional and physiological state of the person. Collectively, this can be used to develop innovative persuasive solutions for adaptive behavior change. Such solutions offer potential in reducing levels of sedentary behavior. This work presents a study exploring new ways of employing smart technologies to facilitate behavior change. It is achieved by means of (i) developing a knowledge base on sedentary behaviors and recommended physical activity guidelines, and (ii) a context model able to combine information on physical activity, location, and a user's diary to develop a context-aware virtual coach with the ability to select the most appropriate behavior change strategy on a case by case basis.


Care--beyond virtue and command.
The academic turn in the field of health care has placed the study of health within the confines of a logocentric or scientistic framework. This development has led to the devaluation of many issues important to professional practice. One of these is the issue of care. In this article, different ways to enhance caring qualities are discussed. It is shown that the key to care lies not within abstract theories and principles, but rather in reflecting over our own life-world experience.


Bidirectional scattering distribution function measurements from volume diffusers: correction factors and associated uncertainties.
We consider the effect of volume diffusion on measurements of the bidirectional scattering distribution function when a finite distance is used for the solid angle defining aperture. We derive expressions for correction factors that can be used when the reduced scattering coefficients and the index of refraction are known. When these quantities are not known, the expressions can be used to guide the assessment of measurement uncertainty. We find that some measurement geometries reduce the effect of volume diffusion compared to their reciprocal geometries.


Effects of chewing on appetite, food intake and gut hormones: A systematic review and meta-analysis.
To seek insights into the relationship between chewing, appetite, food intake and gut hormones, and to consider potentially useful recommendations to promote benefits of chewing for weight management. Papers were obtained from two electronic databases (Medline and Cochrane), from searches of reference lists, and from raw data collected from the figures in the articles. A total of 15 papers were identified that detailed 17 trials. All 15 papers were included in the systematic review; however, a further five studies were excluded from the meta-analysis because appropriate information on hunger ratings was not available. The meta-analysis was conducted on a total of 10 papers that detailed 13 trials. Five of 16 experiments found a significant effect of chewing on satiation or satiety using self-report measures (visual analogue scales, VASs). Ten of 16 experiments found that chewing reduced food intake. Three of five studies showed that increasing the number of chews per bite increased relevant gut hormones and two linked this to subjective satiety. The meta-analysis found evidence of both publication bias and between study heterogeneity (IA(2) = 93.4%, tau(2) = 6.52, p < 0.001) which decreased, but remained, when covariates were considered. Analysis of the heterogeneity found a substantial effect of the fasting period where the duration of fasting influenced the decrease in hunger due to chewing. Prolonged mastication significantly reduces self-reported hunger levels (hunger: − 2.31 VAS point, 95% CI [− 4.67, − 1.38], p < 0.001). Evidence currently suggests that chewing may decrease self-reported hunger and food intake, possibly through alterations in gut hormone responses related to satiety. Although preliminary, the results identify a need for additional research in the area. Focused, uniform, experimental designs are required to clearly understand the relationships that exist between mastication, appetite, satiety, food intake and, ultimately, body weight.


Palladium-Catalyzed Ring-Opening Coupling of gem-Difluorocyclopropanes for the Construction of 2-Fluoroallylic Sulfones.
A Pd-catalyzed ring-opening sulfonylation of gem-difluorocyclopropanes is reported. This protocol involves C-C bond cleavage, β-F elimination, and allylic coupling to form corresponding 2-fluoroallylic sulfones efficiently with Z-selectivity. Different substrates bearing diverse functional groups are tolerated. Moreover, this method is successfully used for the late-stage derivation of several bioactive molecules.


[Lasik, PRK and quality of vision: a study of prognostic factors and a satisfaction survey].
To confirm the clinical interest of pupillary diameter measurement for selecting indications and determining surgical protocols, to look for clinical factors predisposing to night vision symptoms, and to the assess patient satisfaction level for photoablation techniques not based on aberrometry. This retrospective study was conducted on 111 consecutive myopic patients (219 eyes, with a mean spherical equivalent of -4.25+/-1.84 D); they underwent Lasik (91.3% of cases) or photorefractive keratectomy, after having their pupillary diameter measured by the Colvard pupillometer. Clinical data were collected from medical files, and an anonymous questionnaire was sent in order to assess quality of vision and postoperative satisfaction. Preoperative aims were reached (r=0.41, p<0.0001). The response rate for the questionnaire was 81.1%. Daytime vision was the same or better for 91.1% of the patients, but 25.6% had worse night vision than before. Night vision symptoms were mentioned by 46.7% of the patients, and the most frequent complaint was halos. However, 97.8% of the patients declared themselves as satisfied and would recommend such surgery to their family and friends. A preoperative myopia greater than 4.50D (RR=1.52, p<0.05) and a postoperative keratometry greater than 8.44 mm (RR=1.62, p<0.05) were risk factors for having night vision symptoms, but pupillary diameter was not a risk factor. This survey gives an indirect confirmation of the interest of scotopic pupillary diameter measurement and taking it into account in photoablation protocols. However, night vision symptoms remain frequent but do not influence patient satisfaction. Knowledge of risk factors and technical progress should provide a better quality of vision after Lasik.


Impaired production of interleukin 6 and tumour necrosis factor alpha in whole blood cell cultures of patients with multiple myeloma.
Cytokine production in whole blood cell cultures can be an indicator of immune cellular status in neoplastic patients. Production of interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) after stimulation with lipopolysaccharide was measured in 1/10 diluted whole blood culture of patients with monoclonal gammopathies [monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM)]. With this system, lower production of IL-6 and TNF-alpha at 4, 24 and 48 h in total blood cultures in patients with symptomatic MM was observed. Thus, the capacity of cytokine production was greater in control subjects and in patients with MGUS and MM in response than in symptomatic MM (P=0.005 at 4 h and P=0. 006 at 24 and 48 h for IL-6 and P<0.0001 at 24 h and P<0.001 at 48 h for TNF-alpha). These differences remained significant after adjustment on the basis of the lymphocyte count (P<0.001 for IL-6 and TNF-alpha at 24 and 48 h). The impaired IL-6 and TNF-alpha production in patients with symptomatic MM is probably due to a tumour-related immunosuppressive status.


[Current state of laparoscopic hepatic surgery: results of a survey of DGAV-members].
To date laparoscopic hepatic surgery is only common in a few centres for a specific selected patient group. The intention of this survey was to estimate the current state of affairs for laparoscopic hepatic surgery in Germany at 2008. A questionnaire was prepared and sent out by e-mail in May 2009 to the members of the DGAV (German Society of General and Visceral Surgery). The feedback was evaluated anonymously. A total of 181 answers were received by 31st July 2009 (return rate of 15.9%). The return rate of basic and standard care hospitals was 9.2%, specialized hospitals 23.6%, hospitals with maximum care 50% and university hospitals had a return rate of 71.9%. The question whether laparoscopic hepatic surgery had been performed in 2008 was answered with YES by 125 (69.1%) and NO by 54 (29.8%) members. The number of laparoscopic hepatic surgery interventions (laparoscopic ultrasound, laparoscopic radiofrequency ablation and resection) in 2008 was given as more than 50 by 4 (2.2%) hospitals, between 20 and 50 by 11 (6.1%) hospitals, between 10 and 20 by 23 (12.7%) hospitals, between 5 and 10 by 45 (24.9%) hospitals and between 0 and 5 by 54 (29.8%) hospitals. In 2008 the frequency of laparoscopic ultrasound during intraoperative staging to confirm the diagnosis ranged from 2 to 250, whereby 96.4% of the hospitals had less than 50 and only 2 hospitals (2.7%) had 211 and 250 examinations, respectively. 50 hospitals carried out laparoscopic radiofrequency ablation (RFA). 69 (38.1%) of the interviewed hospitals reported hepatic laparoscopic resections (n=551). Laparoscopic liver surgery has been done in Germany in patients with benign or malignant liver lesions. Pure laparoscopy is the most common access. Atypical resections are the primarily indication followed by left lateral resections. All further types of resection have been done in a very small number. Laparoscopic liver surgery has been performed in all types of hospitals.


Cope elimination: elucidation of solvent effects from QM/MM simulations.
The Cope elimination reactions for threo- and erythro-N,N-dimethyl-3-phenyl-2-butylamine oxide have been investigated using QM/MM calculations in water, THF, and DMSO. The aprotic solvents provide up to million-fold rate accelerations. The effects of solvation on the reactants, transition structures, and rates of reaction are elucidated here using two-dimensional potentials of mean force (PMF) derived from free-energy perturbation calculations in Monte Carlo simulations (MC/FEP). The resultant free energies of activation in solution are in close agreement with experiment. Ab initio calculations at the MP2/6-311+G-(2d,p) level using the PCM continuum solvent model were also carried out; however, only the QM/MM methodology was able to reproduce the large rate increases in proceeding from water to the dipolar aprotic solvents. Solute-solvent interaction energies and radial distribution functions are also analyzed and show that poorer solvation of the reactant in the aprotic solvents is primarily responsible for the observed rate enhancements. It is found that the amine oxide oxygen is the acceptor of three hydrogen bonds from water molecules for the reactant but only one to two weaker ones at the transition state. The overall quantitative success of the computations supports the present QM/MM/MC approach, featuring PDDG/PM3 as the QM method.