Locomotor disability: meaning, causes and effects of interventions.
This paper provides a synopsis of a long-term programme of MRC-funded work on locomotor disability in older people. Specifically it describes the meaning and experience of disability, examines the risk factors for disability and systematically reviews the evidence from randomized trials of complex interventions for disability. We undertook a national prospective study of a representative sample of 999 people aged 65 years or more plus in-depth interviews with a small subsample and a selected sample obtained from hospital sources. Secondary analysis of several large prospective studies was carried out and a systematic review and meta-analysis of published randomized controlled trials of the effects of complex interventions for disability. Very few participants subscribed to the constructs of longstanding illness, disability or infirmity that surveys often use. A wide range of social and psychological factors, independently of chronic diseases, were strongly associated with disability. People with greater functional reserve capacity and those with greater self-efficacy were generally less likely to suffer from catastrophic decline in ability and had better quality of life in the face of disability. In reviewing 89 trials (over 97,000 participants) of complex interventions for disability, evidence of benefits was found although no relationship with intensity of intervention was apparent. Our findings on the meaning and experience of disability suggest the need for modifications to routinely used survey questions and for different ways of understanding the need for and receipt of care among older people with disabilities. The diverse risk factors for disability suggest that novel approaches across social, psychological as well as more traditional rehabilitation and behavioural risk factor modification would be worth exploring. Complex interventions appeared to help older people to live independently and limit functional decline irrespective of age and health status.


Speckle reduction using multiple tones of illumination.
The occurrence and smoothing of speckle are studied as a function of the line width for a highly collimated illuminating source. A general theory is presented for speckling in the image of a partially diffuse, phase type of object, which has a variable number of random scattering centers per resolution element. Then, an expression is derived for the wavelength spacing required to decouple the speckle patterns arising from two monochromatic tones in an imaging system, thereby establishing that it is feasible to smooth speckle using multicolor illumination. This theory is verified in a series of experiments using both laser illumination and band-limited light from a carbon arc. With highly collimated sources, we show that speckle appears laserlike for an imaged diffuser even up to line widths of 5 A. Then, smoothing of speckle is demonstrated in the imaging of a diffuser and for a section of an optic nerve when the illumination is provided by six narrow lines spread over 1500 A. Since with color-blind, panchromatic viewing the speckle smooths, a direct extension of this method to holographic microscopy, using a multitone laser, should permit one to record and reconstruct holograms of diffraction-limited resolution that are essentially speckle-free.


Hormone therapy and the medical encounter: a qualitative analysis of women's experiences.
The aim of this article was to explore women's experiences in biomedical consultations for menopause symptoms, with a particular focus on how hormone therapy (HT) featured during the encounter. Semistructured interviews were conducted with 39 women, and data were analyzed using a qualitative strategy referred to as Thematic Networks. Several participants whose menopause started before the period of the HT "scares" described being "put on" HT as a matter of course, even when their symptoms were mild. By contrast, some of those presenting in the more recent time period with what they deemed to be severe symptoms were more likely to describe scenarios whereby they pressured their physicians for an HT prescription. Once on HT, participants were found to be far from passive recipients of a biomedical "treatment" but rather embarked on an active dialogue with themselves about how to manage the distressing aspects of menopause. Using HT did not tend to spell a transition to biomedical advocacy, despite its reported effectiveness in moderating bodily distresses. Rather, HT tended to retain a tentative status as a temporary relief and not a long-term panacea.


Hallmarks of glycogene expression and glycosylation pathways in squamous and adenocarcinoma cervical cancer.
Dysregulation of glycogene expression in cancer can lead to aberrant glycan expression, which can promote tumorigenesis. Cervical cancer (CC) displays an increased expression of glycogenes involved in sialylation and sialylated glycans. Here, we show a comprehensive analysis of glycogene expression in CC to identify glycogene expression signatures and the possible glycosylation pathways altered. First, we performed a microarray expression assay to compare glycogene expression changes between normal and cervical cancer tissues. Second, we used 401 glycogenes to analyze glycogene expression in adenocarcinoma and squamous carcinoma from RNA-seq data at the cBioPortal for Cancer Genomics. The analysis of the microarray expression assay indicated that CC displayed an increase in glycogenes related to GPI-anchored biosynthesis and a decrease in genes associated with chondroitin and dermatan sulfate with respect to normal tissue. Also, the glycogene analysis of CC samples by the RNA-seq showed that the glycogenes involved in the chondroitin and dermatan sulfate pathway were downregulated. Interestingly the adenocarcinoma tumors displayed a unique glycogene expression signature compared to squamous cancer that shows heterogeneous glycogene expression divided into six types. Squamous carcinoma type 5 (SCC-5) showed increased expression of genes implicated in keratan and heparan sulfate synthesis, glycosaminoglycan degradation, ganglio, and globo glycosphingolipid synthesis was related to poorly differentiated tumors and poor survival. Squamous carcinoma type 6 (SCC-6) displayed an increased expression of genes involved in chondroitin/dermatan sulfate synthesis and lacto and neolacto glycosphingolipid synthesis and was associated with nonkeratinizing squamous cancer and good survival. In summary, our study showed that CC tumors are not a uniform entity, and their glycome signatures could be related to different clinicopathological characteristics.


Immunological function in patients operated on with small intestinal shunts for morbid obesity.
Obese individuals, operated on with intestinal shunts, have been investigated with regard to immunological functions. After operation strong increases in skin reactions of immediate and delayed type were observed. Analysis of total WBC and differential counts, percentage T lymphocytes, immunoglobulin concentrations, and lymphocyte reactivity yielded no explanation of the findings.


Short-term cardiorespiratory adaptation to high altitude in children compared with adults.
As short-term cardiorespiratory adaptation to high altitude (HA) exposure has not yet been studied in children, we assessed acute mountain sickness (AMS), hypoxic ventilatory response (HVR) at rest and maximal exercise capacity (CPET) at low altitude (LA) and HA in pre-pubertal children and their fathers. Twenty father-child pairs (11 ± 1 years and 44 ± 4 years) were tested at LA (450 m) and HA (3450 m) at days 1, 2, and 3 after fast ascent (HA1/2/3). HVR was measured at rest and CPET was performed on a cycle ergometer. AMS severity was mild to moderate with no differences between generations. HVR was higher in children than adults at LA and increased at HA similarly in both groups. Peak oxygen uptake (VO2 peak) relative to body weight was similar in children and adults at LA and decreased significantly by 20% in both groups at HA; maximal heart rate did not change at HA in children while it decreased by 16% in adults (P < 0.001). Changes in HVR and VO2 peak from LA to HA were correlated among the biological child-father pairs. In conclusion, cardiorespiratory adaptation to altitude seems to be at least partly hereditary. Even though children and their fathers lose similar fractions of aerobic capacity going to high altitude, the mechanisms might be different.


Selective spatial attention in vision and touch: unimodal and multimodal mechanisms revealed by PET.
Two positron-emission tomography (PET) experiments explored the neural basis of selective spatial attention in vision and touch, testing for modality-specific versus multimodal activations due to attended side. In the first study, either light flashes or finger vibrations were presented bilaterally. Twelve healthy volunteers were scanned while sustaining covert attention on the left or right hemifield within each modality. The main effect for attending right minus left, across both modalities, revealed bimodal spatial attention effects in the left intraparietal sulcus and left occipitotemporal junction. Modality-specific attentional effects (again, for attending right vs. left) were found in the left superior occipital gyrus for vision, and left superior postcentral gyrus for touch. No significant activations were seen for attending left minus right. The second study presented only tactile stimuli, manipulating whether the eyes were open or closed, and including passive stimulation and rest baselines. The unimodal activation for tactile spatial attention in the left superior postcentral gyrus was replicated. The bimodal activation of the left intraparietal sulcus observed in the first study was now found for touch, but only when the eyes were open (hands visible), apparently confirming its multimodal nature. These results reveal mechanisms of sustained spatial attention operating at both modality-specific and multimodal levels.


Factors influencing the general well-being of low-income Korean immigrant elders.
This study explores factors that influence the general well-being (anxiety, depression, positive well-being, self-control, vitality, and general health) of low-income Korean immigrant elders by interviewing 206 older adults living in Los Angeles County and Orange County, California. Ordinary least squares regression results reveal that lack of English proficiency and longer residence in the United States were significant predictors of higher anxiety, higher depression,lower self-control,lower vitality, and lower general health among Korean immigrant elders. Losing a spouse was a significantly negative factor in vitality. Financial problems were significantly associated with lower positive well-being. Social support was a significant factor in lower anxiety, lower depression, higher positive well-being, higher self-control, and higher vitality. Spiritual coping was significantly associated with lower anxiety,lower depression, higher positive well-being, and higher vitality. The findings of this study show that low-income Korean immigrant elders are at high risk for psychological and physical health problems influenced by difficulties with the acculturation or adjustment and socioeconomic stress of living in a new society. The study discusses essential implications for culturally competent social work practice among low-income Korean immigrant elders.


Association between an arachnoid cyst and intracranial aneurysms misdiagnosed as a cystic tumor with a mural nodule. Case report and review of the literature.
The authors report on a 63-year-old man initially admitted to an outside hospital for altered mental status and respiratory distress. A head computed tomography scan disclosed a right frontal cystic mass, suspected to be a neoplasm. An open biopsy was performed at an outside institution, and on visualization of the cyst, an aneurysm was found incidentally. Postoperatively, an angiogram and magnetic resonance image confirmed the presence of a distal right M1 segment aneurysm. The patient was transferred to our institution where, in addition to the middle cerebral artery lesion, a right anterior choroidal artery aneurysm was found intraoperatively; the necks of both aneurysms were clipped successfully. A review of the literature revealed 14 additional cases of intracranial aneurysms associated with arachnoid cysts. Data in the present report highlight the importance of considering an intracystic aneurysm in the differential diagnosis when reviewing cases that involve a cystic mass with a mural nodule. The authors provide a comprehensive summary of documented cases of aneurysms associated with arachnoid cysts. In addition, they include a discussion of prevailing thoughts on the origin and evolution of arachnoid cysts.


Prevalence and risk factors for MRSA nasal colonization among persons experiencing homelessness in Boston, MA.
Homeless individuals face an elevated risk of methicillin-resistant Staphylococcus aureus (MRSA) infection. Identifying the prevalence and risk factors for MRSA nasal colonization may reduce infection risk. A cross-sectional study was conducted at a health clinic for homeless persons in Boston, MA, USA (n=194). In-person interviews and nasal swab specimens were collected. MRSA isolates were genotyped using pulse-field gel electrophoresis (PFGE) and assessed for antibiotic susceptibility. The prevalence of MRSA nasal colonization was 8.3 %. Seventy-five percent of isolates reflected clonal similarity to USA300. USA100 (18.8 %) and USA500 (6.3 %) were also recovered. Resistance to erythromycin (81.3 %), levofloxacin (31.3 %) and clindamycin (23.1 %) was identified. Recent inpatient status, endocarditis, haemodialysis, heavy drinking, not showering daily and transience were positively associated with MRSA nasal colonization. Carriage of community-acquired MRSA strains predominated in this population, although nosocomial strains co-circulate. Attention to behavioural and hygiene-related risk factors, not typically included in MRSA prevention efforts, may reduce risk.


The effects of red clover on quality of life in post-menopausal women.
Due to symptoms and its complications, menopause influences the mental, psychological and physical health, social performance and familial relationships. Because of the undesirable side effects of hormone replacement therapy, tendency and desire toward alternative treatments in relieving menopausal symptoms have increased. Among the alternative therapies are herbs and among those, herbs with phytoestrogens are more preferable. Red clover is a rich source of phytoestrogens. The present study investigated the effect of red clover on quality of life in post-menopausal women. In a randomized, triple-blind, placebo-controlled clinical trial, 72 menopausal women who at least obtained 15 scores in Kupperman Menopausal Index, after two weeks of monitoring, were randomly allocated to receive either placebo or 45 mg of red clover isoflavones for eight weeks. Before the treatment and at the end of the study, menopause-specific quality of life questionnaire (MENQOL) was completed in the two groups. A total of 55 women completed the study, 28 subjects in red clover and 27 in placebo group. Mean score of total quality of life (p < 0.001 in both groups), mean score of quality of life in vasomotor domain (p < 0.001 in both groups), psycho-social domain (p < 0.001 in red clover and p = 0.02 in placebo group) and physical domain (p < 0.001 red clover and p = 0.01 placebo group) significantly reduced compared to the baseline values. However, the differences between two groups were significant neither for total quality of life nor for its domains. Red clover had no side effects and all the subjects in the red clover group were satisfied with the prescribed administration. In the present study, the effect of red clover supplementation on menopausal women's quality of life showed no difference with the placebo. Further clinical trials are recommended.


Detection and genotyping of human papillomavirus in urine samples from unvaccinated male and female adolescents in Italy.
The introduction of vaccination against Human Papillomavirus (HPV) in adolescent girls in 2006 has focused virological surveillance on this age group. As few studies have evaluated HPV infections in young populations, further data are needed in order to improve and extend prophylactic policy and to monitor epidemiological changes. The present study aimed at evaluating overall and type-specific HPV prevalence in both female and male adolescents in Italy. HPV DNA detection and genotyping was performed on urine samples collected from 870 unvaccinated adolescents (369 females, 501 males, 11-18 years of age) in five cities in Italy. Following DNA extraction by means of a commercial kit (NucliSENS(®)-miniMAG(®), bioMérieux), the L1 gene fragment was PCR amplified and genotyped by restriction fragment length polymorphism analysis. HPV DNA was detected in 1.5% of all samples, and in 3% and 0.4% of samples from females and males, respectively. In approximately 70% of HPV DNA positive adolescents, the infection was due to a single genotype, with 88.9% of genotypes belonging to the HR-clade. The only two HPV-positive boys (14 and 18 years old) had HPV-70 genotype. Only one of the 11 HPV-infected girls was in the 11-14 age-group. HPV prevalence was 4.2% in girls aged 15-18 years and 60% of infections were due to vaccine types HPV-16 or HPV-6/-11. This is one of the few studies, the first conducted in Italy, on HPV infection in adolescents. Urine testing is the easier way of detecting HPV infection in younger populations. Our data revealed a very low HPV prevalence, and no infections were observed in the 12-year-old vaccine target population. The majority of infections were seen in females aged 15-18 years. Overall, more than 50% and 30% of the potentially persistent HPV infections detected in this group could have been prevented by the quadrivalent and the bivalent vaccines, respectively.


[The Scope, Quality and Safety Requirements of Drug Abuse Testing].
The aim of this review is to inform about the scopes and requirements of drug abuse testing. Drug abuse testing is one of the tools for determination of drug use. It must fulfill the quality and safety requirements in judgmental legal and administrative decisions. Drug abuse testing must fulfill some requirements like selection of the appropriate test matrix, appropriate screening test panel, sampling in detection window, patient consent, identification of the donor, appropriate collection site, sample collection with observation, identification and control of the sample, specimen custody chain in preanalytical phase; analysis in authorized laboratories, specimen validity tests, reliable testing METHODS, strict quality control, two-step analysis in analytical phase; storage of the split specimen, confirmation of the split specimen in the objection, result custody chain, appropriate cut-off concentration, the appropriate interpretation of the result in postanalytical phase. The workflow and analytical processes of drug abuse testing are explained in last regulation of the Department of Medical Laboratory Services, Ministry of Health in Turkey. The clinical physicians have to know and apply the quality and safety requirements in drug abuse testing according to last regulations in Turkey.


Guidelines for the Management of Severe Traumatic Brain Injury, Fourth Edition.
The scope and purpose of this work is 2-fold: to synthesize the available evidence and to translate it into recommendations. This document provides recommendations only when there is evidence to support them. As such, they do not constitute a complete protocol for clinical use. Our intention is that these recommendations be used by others to develop treatment protocols, which necessarily need to incorporate consensus and clinical judgment in areas where current evidence is lacking or insufficient. We think it is important to have evidence-based recommendations to clarify what aspects of practice currently can and cannot be supported by evidence, to encourage use of evidence-based treatments that exist, and to encourage creativity in treatment and research in areas where evidence does not exist. The communities of neurosurgery and neuro-intensive care have been early pioneers and supporters of evidence-based medicine and plan to continue in this endeavor. The complete guideline document, which summarizes and evaluates the literature for each topic, and supplemental appendices (A-I) are available online at https://www.braintrauma.org/coma/guidelines.


Community-level consequences of density dependence and habitat association in a subtropical broad-leaved forest.
How extraordinary numbers of species can coexist in hyper-diverse communities remains unresolved. While numerous hypotheses have been proposed based on observational and theoretical investigations, little is known about which mechanisms are truly active in forest communities and less is known about their relative contributions to community assembly. In this study, generalized linear mixed models with crossed random effects were used to assess the relative contributions of density dependence and habitat association to community-level diversity maintenance. Species habitat associations were classified based on soil nutrients, topography and species composition. Local neighbourhood effects were also addressed with spatially explicit models of seedling survival. The results shown here reveal that local- and community-level seedling dynamics were consistent with density-dependent predictions, although habitat association played a more important role in shaping short-term seedling survival. We conclude that density dependence could promote species coexistence on the premise of habitat partitioning.


Shame and stigma in association with the HCV cascade to cure among people who inject drugs.
Psycho-social experiences including shame and experienced and internalized stigma have been associated with substance use, HCV infection, and reluctance to disclose HCV status and pursue treatment. These psycho-social barriers have been examined independently for many chronic diseases, including HCV, but to our knowledge have not been quantitatively explored in a large multi-site US-based sample of people who inject drugs (PWID) in HCV treatment. We examine baseline relationships with HCV-stigma and engagement across the HCV treatment cascade as well as baseline and longitudinal relationships between shame and engagement across the HCV treatment cascade including treatment initiation, adherence, completion, and sustained virologic response (SVR) among a multi-site sample of PWID with HCV, where N=755 were randomized to the pragmatic trial comparing HCV treatment outcomes in modified directly observed treatment (mDOT) or patient navigation, and N=623 initiated treatment. While cross-sectional assessments of shame and HCV-stigma were not associated with engagement across the HCV treatment cascade, those whose shame scores decreased compared to those who reported consistently high and increasing levels of shame were significantly more likely to complete HCV treatment (aOR=5.29; 95%CI: 1.56,18.00) and achieve SVR (aOR=6.32; 95%CI: 1.61, 24.87). Results underscore the relationships between lower levels of shame and health-related behavior and treatment outcomes among PWID and suggest SVR achievement may contribute to reductions in shame or that reductions in shame may contribute to continued treatment and thus SVR.


Möbius syndrome associated with obesity and precocious puberty.
Möbius syndrome is a neurological disorder involving underdevelopment of the sixth and seventh cranial nerves. Multiple associations have been described including dysfunction of other cranial nerves, limb abnormalities and hypogonadotrophic hypogonadism causing delayed puberty. We present the second reported case of Möbius syndrome associated with obesity and with precocious puberty. These features may be secondary to dysregulation of the hypothalamic-pituitary axis. We highlight the need to consider extraocular symptoms in these patients and for close liaison with physicians in their management.


γ-Glutamyltransferase catabolism of S-nitrosoglutathione modulates IL-8 expression in cystic fibrosis bronchial epithelial cells.
S-nitrosoglutathione (GSNO) is an endogenous nitrosothiol involved in several pathophysiological processes. A role for GSNO has been envisaged in the expression of inflammatory cytokines such as IL-8; however, conflicting results have been reported. γ-Glutamyltransferase (GGT) enzyme activity can hydrolyze the γ-glutamyl bond present in the GSNO molecule thus greatly accelerating the release of bioactive nitric oxide. Expression of GGT is induced by oxidative stress, and activated neutrophils contribute to GGT increase in cystic fibrosis (CF) lung exudates by releasing GGT-containing microvesicles. This study was aimed at evaluating the effect of GSNO catabolism mediated by GGT on production of IL-8 in CF transmembrane regulation protein-mutated IB3-1 bronchial cells. The rapid, GGT-catalyzed catabolism of GSNO caused a decrease in both basal and lipopolysaccharide-stimulated IL-8 production in IB3-1 cells, by modulating both NF-κB and ERK1/2 pathways, along with a decrease in cell proliferation. In contrast, a slow decomposition of GSNO produced a significant increase in both cell proliferation and expression of IL-8, the latter possibly through p38-mediated stabilization of IL-8 mRNA. Our data suggest that the differential GSNO catabolism mediated by GGT enzyme activity can downregulate the production of IL-8 in CF cells. Hence, the role of GGT activity should be considered when evaluating GSNO for both in vitro and in vivo studies, the more so in the case of GSNO-based therapies for cystic fibrosis.


Random networks of fibres display maximal heterogeneity in the distribution of elastic energy.
Above a small length scale, the distribution of local elastic energies in a material under an external load is typically Gaussian, and the dependence of the average elastic energy on strain defines the stiffness of the material. Some particular materials, such as granular packings, suspensions at the jamming transition, crumpled sheets and dense cellular aggregates, display under compression an exponential distribution of elastic energies, but also in this case the elastic properties are well defined. We demonstrate here that networks of fibres, which form uncorrelated non-fractal structures, have under external load a scale invariant distribution of elastic energy (epsilon) at the fibre-fibre contacts proportional to 1/epsilon. This distribution is much broader than any other distribution observed before for elastic energies in a material. We show that for small compressions it holds over 10 orders of magnitude in epsilon. In such a material a few 'hot spots' carry most of the elastic load. Consequently, these materials are highly susceptible to local irreversible deformations, and are thereby extremely efficient for damping vibrations.


Adverse childhood experiences growing up in East or West Germany or abroad.
Adverse childhood experiences (ACEs) are potentially traumatic events that occur before the age of 18. The term encompasses various adverse childhood experiences, e.g., physical, psychological, and sexual abuse, physical and psychological neglect, and family dysfunction. Prevalence estimates for a broad spectrum of ACEs against the background of where childhood and adolescence were spent are scarcely available in Germany. This study examines the frequencies of adverse childhood experiences, considering growing up in East or West Germany or abroad and interacting with different age cohorts and gender. A total of 5,018 individuals (51.4% female) aged 14 years and older were retrospectively assessed on adverse childhood experiences using questionnaires "adverse childhood experiences" (ACE). Logistic regression models were used to analyze the association between birth cohort, gender, and where a person grew up. Descriptive statistics and univariate analyses were used to calculate frequencies, proportions, and unadjusted associations for each variable. 37.4% (N = 1,878) of respondents reported experiencing at least one form of ACE. Individuals who grew up abroad report significantly more adverse childhood experiences than individuals in East or West Germany. Men and women who grew up in East Germany reported a lower rate of ACEs. We found significant effects for all predictors: Where childhood and adolescence were predominantly spent, year of birth, and gender. Significant differences in the prevalence of adverse childhood experiences within the gender groups were only found for sexual and physical abuse and substance dependence in the household. The results suggest that the socio-political context plays an essential role in the experience of adverse childhood experiences, both in frequency and risk. Thus, child abuse and neglect studies should increasingly focus on societal risk and protection mechanisms.


Adaptations of hepatic amino acid uptake and net utilisation contributes to nitrogen economy or waste in lambs fed nitrogen- or energy-deficient diets.
We investigated the effect of relative changes in dietary nitrogen (N) and energy supply and the subsequent variations in net portal appearance (NPA) of nitrogenous and energy nutrients on the net amino acid (AA) uptake by the liver and net N supply to the peripheral tissues. Six lambs were catheterised across the splanchnic tissues and received, in a replicated Latin square, one of three dietary treatments. The diets were formulated to either match the requirements of N and energy (C), or supply only 0.8 of the N requirement (LN) or 0.8 of the energy requirement (LE). Net fluxes of AA and urea-N were measured across the portal-drained viscera, and estimation of arterial hepatic flow allowed the estimation of hepatic fluxes. Catheters were implanted into the portal and hepatic veins as well as in the abdominal aorta for the measurement of AA fluxes. Animals fed the LN diet showed more efficient N retention (0.59 of digested N) than did the C and LE diet (0.50 and 0.33, respectively; P < 0.001). The NPA of total AA-N for the LN diet was only 0.60 of the value measured for the control (C) diet (P < 0.01). Despite this, the total estimated AA-N net splanchnic fluxes were not significantly different across the three diets (3.3, 1.9 and 2.6 g total AA-N/day for C, LN and LE, respectively, P = 0.52). Thus, different metabolic regulations must have taken place across the liver between the three experimental diets. A combination of decreased net uptake of total AA-N by the liver of animals in the LN diet (0.61 of the C diet; P = 0.002) and reduced urinary urea-N production (0.52 of the C diet; P = 0.001) spared AA from catabolism in the LN diet relative to the other two diets. For the LE diet, the urinary urea-N output was 1.3 times the value of the C diet (P = 0.01). This may relate to an increased catabolism of AA by the muscle and/or, to a lesser extent, to an increased utilisation of AA for gluconeogenesis in the liver. These effects may explain the reduced whole body protein retention observed with the LE diet.


Size of the lower third molar space in relation to age in Serbian population.
It is considered that the shortage of space is the major cause of the third molar impaction. The aim of this study was to establish the frequency of insufficient lower third molar eruption space in Serbian population, to question the differences in this frequency in the subjects of different age, to determine the influence of the lower third molar space (retromolar space) size on third molar eruption, and to investigate a possible correlation between the size of gonial angle and the space/third molar width ratio. Digital orthopantomograms were taken from 93 patients divided into two groups: early adult (16-18 years of age) and adult (18-26) patients. Retromolar space, mesiodistal third molar crown width, gonial angle and eruption levels were measured. The space/third molar width in early adult subjects was smaller (p < 0.0001) and insufficient space was significantly more frequent (p = 0.0003) than in adult patients. Considerably more third molars erupted in case of enough space in both age groups (p < 0.0001). There was no difference between the means of gonial angle size in relations to the available space. The retromolar space/third molar width ratio is more favorable in adult subjects. Gonial angle is not in correlation with the retromolar space/third molar width ratio.


Amino acid sequence of the Pronase-released heads of neuraminidase subtype N2 from the Asian strain A/Tokyo/3/67 of influenza virus.
The amino acid sequence of the Pronase-released heads of neuraminidase subtype N2 from the A/Tokyo/3/67 strain of influenza virus was determined by a combination of peptide and nucleic acid sequence analysis. The results show that the Pronase-released heads contain 396 amino acid residues and extend from residue 74 in the original protein to the C-terminus at residue 469. The heads contain five potential glycosylation sites at asparagine residues 86, 146, 200, 234 and 402, but only the first four are glycosylated. The sequence homology with the corresponding region of the previously published sequence of the neuraminidase subtype N1 [Fields, Winter & Brownlee (1981) Nature (London) 290, 213-217] is 45%. Detailed evidence for the sequence data has been deposited as Supplementary Publication SUP 50116 (14 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies may be obtained on the terms given in Biochem. J. (1981) 193, 5.


Aquablation of the Prostate for Symptomatic Benign Prostatic Hyperplasia: 1-Year Results.
We sought to establish the safety and effectiveness of aquablation, a novel, image guided, robotic assisted, water jet tissue ablation technology, for the treatment of benign prostatic hyperplasia. We performed a prospective, single arm, multicenter trial at a total of 3 centers in Australia and New Zealand with 1-year followup. Participants were men 50 to 80 years old with moderate to severe lower urinary tract symptoms as determined by urodynamics. All patients underwent aquablation under image guidance. Primary end points included procedural and perioperative safety. The main clinical end point was the change from baseline in I-PSS (International Prostate Symptom Score). Other secondary end points included uroflow measures, prostate volume on transrectal ultrasound and detrusor pressure. Detrusor pressure at maximum flow was only measured at 6 months. A total of 21 men underwent aquablation at a mean age of 69.7 years (range 62 to 78). Prostate volume was 57.2 ml (range 30 to 102). Procedural duration averaged 38 minutes with a mean aquablation treatment time of 5 minutes. All but 1 subject were catheterized for 1 day only and 19 of 21 were discharged home the day after the procedure. Detrusor pressure at maximum flow decreased from 65 cm H2O at baseline to 39 cm H2O at 6 months (p <0.0027). Prostate volume decreased from 57 ml at baseline to 35 ml (p <0.0001). Mean I-PSS score improved from 23.0 at baseline to 6.8 at 12 months (p <0.0001) and maximum urinary flow increased from 8.7 to 18.3 ml per second (p <0.0001). There were no important perioperative adverse events. No urinary incontinence developed and sexual function was preserved postoperatively. This phase II study provides early evidence to support the safety and effectiveness of aquablation for symptomatic benign prostatic hyperplasia.


Canine parvovirus serum neutralizing antibody assay: assessment of factors responsible for disparity of results between tests.
Canine parvovirus (CPV) serum neutralization (SN) test components were evaluated to determine their effect on antibody titer results. The use of different strains of CPV and different cell substrates had little effect on assay results. Variations in SN antibody titer results were associated with the use of challenge virus preparations that differed in the ratio of hemagglutination units (HAU) to infectivity units (FAID50). Sensitivity and reproducibility can be achieved by using a standardized challenge virus preparation containing a low HAU/FAID50 ratio.


Preweaning diet affects bile lipid composition and bile acid kinetics in infant baboons.
We tested, with 14-wk-old baboons before weaning, the hypothesis that bile acid metabolism is differentially affected by breast feeding or by feeding formulas with a high polyunsaturated:saturated fatty acid ratio or with a low ratio, similar to that of breast milk. Bile lipid content, bile acid pool size, fractional turnover rate, synthetic rate and conjugate composition were measured in a single bile sample 9 d after an injection on d 1 of a mixture of [14C]cholic and [14C]chenodeoxycholic acids and an injection of a mixture of [3H]cholic acid and [3H]chenodeoxycholic acid on d 8. The principal biliary bile acid was chenodeoxycholic acid. The only difference in chenodeoxycholic acid metabolism among the infant diet groups was a lower chenodeoxycholic acid synthetic rate in baboons fed the low polyunsaturated:saturated formula compared with those fed the high polyunsaturated:saturated formula or breast-fed. Cholic acid metabolism was significantly affected by infant diet: breast-fed infants had a smaller cholic acid pool size, lower cholic acid percentage of total bile acids, higher cholic acid glycine:taurine conjugate ratio and larger cholic acid fractional turnover rate than formula-fed animals. The polyunsaturated:saturated fatty acid ratio in the formulas did not significantly affect these variables. These results show that differences in bile acid metabolism between breast- and formula-fed infant baboons are limited principally to cholic acid. These differences likely are due to factors other than fatty acid saturation.


Surgical local resection for early gastric cancer.
In Japan, endoscopic mucosal resection remains a familiar treatment of early gastric cancers even though long-term results of surgical local resection (SLR) including a laparoscopic or open approach have been unclear. We reviewed our SLR experiences. Laparoscopic wedge resection (LWR), laparoscopic intragastric surgery (LIS), and open local resection (OLR) were performed in 11, 7, and 11 patients, respectively. Four LIS patients were converted to open surgery. Histologically, resected specimens demonstrated that larger-sized materials were obtained in OLR and LWR. Five patients overall showed submucosal invasion; 1 patient underwent reoperation (gastrectomy). Long-term results showed no primary-lesion related death; 2 patients died of other diseases. However, 2 LWR patients showed new lesions in the remnant stomach at 29 months and 7 years later. Both patients underwent subsequent gastrectomy. In conclusion, SLR is safe and curative for properly selected cancer patients. Precise preoperative diagnosis and careful remnant stomach survey is important.


Dysregulated autophagy contributes to caspase-dependent neuronal apoptosis.
Autophagy is a regulated, intracellular degradation process that delivers unnecessary or dysfunctional cargo to the lysosome. Autophagy has been viewed as an adaptive survival response to various stresses, whereas in other cases, it promotes cell death. Therefore, both deficient and excessive autophagy may lead to cell death. In this study, we specifically attempted to explore whether and how dysregulated autophagy contributes to caspase-dependent neuronal cell death induced by the neurotoxin 6-hydroxydopamine (6-OHDA). Ultrastructural and biochemical analyses indicated that MN9D neuronal cells and primary cultures of cortical neurons challenged with 6-OHDA displayed typical features of autophagy. Cotreatment with chloroquine and monitoring autophagic flux by a tandem mRFP-EGFP-tagged LC3 probe indicated that the autophagic phenomena were primarily caused by dysregulated autophagic flux. Consequently, cotreatment with an antioxidant but not with a pan-caspase inhibitor significantly blocked 6-OHDA-stimulated dysregulated autophagy. These results indicated that 6-OHDA-induced generation of reactive oxygen species (ROS) played a critical role in triggering neuronal death by causing dysregulated autophagy and subsequent caspase-dependent apoptosis. The results of the MTT reduction, caspase-3 activation, and TUNEL assays indicated that pharmacological inhibition of autophagy using 3-methyladenine or deletion of the autophagy-related gene Atg5 significantly inhibited 6-OHDA-induced cell death. Taken together, our results suggest that abnormal induction of autophagic flux promotes apoptotic neuronal cell death, and that the treatments limiting dysregulated autophagy may have a strong neuroprotective potential.


Bcl-2 and p53 immunoprofile in Kaposi's sarcoma.
Seventy three cases of Kaposi's sarcoma (KS) from the 3 histological subtypes (patch, plaque and nodular) were assessed for bcl-2 and p53 protein expression. The aim was to determine the level of expression of these proteins in KS and in the different subtypes. Commercially available antibodies to bcl-2 and p53 were applied after both microwave and pressure cooking antigen retrieval. Bcl-2 immunoexpression increased from the patch stage (36%) to the plaque stage (45%) to the nodular stage (70.83%). Better immunostaining for bcl-2 was obtained after pressure cooking. p53 on the other hand, was not expressed in the patch or plaque stages, but 54.16% of cases in the nodular stage were immunopositive. These results show a progression of immunoexpression of both bcl-2 and p53 from the early histological stages to the late tumor stage, implying that these proteins are upregulated late in the evolution of KS.


Functional development of the cervical sympathetic pathway in the neonatal rat.
Maturation of the cervical sympathetic innervation of the levator palpebrae smooth muscle was studied physiologically in vivo in the rat. Tonic pre- and postganglionic nerve activity and responses to centrally acting stimuli, asphyxia and hypoglycemia, were recorded. Development of functional capacity of the sympathetic nerve terminal-smooth muscle complex was assessed by measuring contractions evoked by directly acting noradrenergic agonists, endogenous nerve terminal norepinephrine released by tyramine, and electrical stimulation of preganglionic axons. Tonic preganglionic activity and responses to asphyxia and hypoglycemia were fully developed by the second postnatal day. Ganglionic neurotransmission, however, is not established until the end of the first postnatal week so that sympathetic outflow from the central nervous system (CNS) does not affect the nerve terminal-smooth muscle complex before this time. Functional capacity of the complex develops in a stepwise fashion with intervening plateau periods. There is an initial rapid increase before onset of ganglionic neurotransmission, and development to the mature level is attenuated only modestly by decentralization of the ganglion on the first postnatal day. It is concluded that conduction of impulses to the postganglionic neuron is not essential to initiate maturation of this nerve terminal-smooth muscle complex, that a significant degree of maturation occurs before ganglionic transmission is established, and that maturation to the adult level is usually largely independent of neural connections between the CNS and the postganglionic neuron.


Short columns with molecularly imprinted monolithic stationary phases for rapid separation of diastereomers and enantiomers.
Three molecularly imprinted monolithic columns with different length but almost identical column volume had been prepared. It was observed that the separation factors of diastereomers and enantiomers were almost unaffected by column length. However, the short column with dimension of 38 mm x 8 mm i.d. showed much lower resistance to flow rate so that it could be operated at much higher flow rates. By combining stepwise gradient elution with elevated flow rate, the diastereomers of cinchonine and cinchonidine and the enantiomers of Cbz-DL-Trp and Fmoc-DL-Trp were successfully separated within 3 min on the short column with dimension of 38 mm x 8 mm i.d. Based on the above results, a cinchonine imprinted monolithic disk with dimension of 10mm x 16 mm i.d. was further developed. The SEM image and the pore size distribution profile showed that large flow-through pores are present on the prepared monolith, which allowed mobile phase to flow through the disk with very low resistance. Chromatographic performances on the monolithic disk were almost unchanged compared with the long columns. A rapid separation of cinchonine and cinchonidine was achieved in 2.5 min at the flow rate of 9.0 ml/min. Furthermore, it was observed that there was almost no effect of the flow rate on the dynamic binding capacity at high flow rates. In addition, the effect of the loading concentration of analytes on the dynamic binding capacity, namely adsorption isotherm, was also investigated. A non-linear adsorption isotherm of cinchonine was observed on the molecularly imprinted monolith with cinchonine as template, which might be a main reason to result in the peak tailing of template molecule.


Population pharmacokinetics of moxifloxacin, cycloserine, p-aminosalicylic acid and kanamycin for the treatment of multi-drug-resistant tuberculosis.
Control of multi-drug-resistant tuberculosis (MDR-TB) requires extensive, supervised chemotherapy because second-line anti-TB drugs have a narrower therapeutic range than first-line drugs. This study aimed to develop population pharmacokinetic (PK) models for second-line drugs in patients with MDR-TB, evaluate the recommended dosage regimens and, if necessary, suggest new dosage regimens. A prospective, single-centre PK study was performed on second-line anti-TB drugs in patients with MDR-TB. Moxifloxacin, cycloserine, p-aminosalicylic acid (PAS), kanamycin and other second-line drugs were administered to the patients. Plasma concentrations were analysed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Population PK models were developed using non-linear mixed effect modelling (NONMEM, Version 7.30; ICON Development Solutions, Ellicott City, MD, USA). Simulations were performed using the calculated PK parameters. The respective absorption rate constant, apparent clearance and apparent volume of distribution values were as follows: 0.305/h, 9.37 L/h and 56.7 L for moxifloxacin; 0.135/h, 1.38 L/h and 10.5 L for cycloserine; 0.510/h, 30.8 L/h and 79.4 L for PAS; and 1.67/h, 3.75 L/h and 15.2 L for kanamycin. The simulations showed that the following dosage regimens were more likely to be within the recommended concentration ranges than the raw data in this study: 200 mg of moxifloxacin once daily (QD) (patient weight <50 kg) and 400 mg of moxifloxacin QD (patient weight ≥50 kg), 500-750 mg of cycloserine QD, 4.95-6.6 g of PAS twice daily and 750-1000 mg of intramuscular kanamycin QD. These findings indicate that the recommended doses should be revised to improve the clinical outcomes of MDR-TB treatment.


Isolated positive anti-SS-B autoantibodies are not related to clinical features of systemic autoimmune diseases: Results from a routine population survey.
To assess in clinical practice the frequency and diagnosis associated with the SS-B-positive/SS-A negative autoantibody profile. We analyzed a one-year consecutive population of 624 patients referred by clinicians to the immunology laboratory to investigate anti-SS-A and/or anti-SS-B autoantibodies, who were detected using luminex technology. Data were analyzed for patients with isolated anti-SS-B autoantibodies. The clinical characteristics and diagnosis of connective tissue diseases (CTD) were retrieved according to the international criteria. Among 1173 sera positive for anti-SS-A and/or anti-SS-B autoantibodies from 624 patients, we identified 84 patients (13.5%) that had isolated anti-SS-B. Among the 75 patients positive for anti-SS-B with known clinical data, 15 were diagnosed with a CTD (20%) including 4 systemic lupus erythematosus (5%), 4 rheumatoid arthritis (5%), 2 idiopathic inflammatory myositis (3%), 1 primary Sjögren's syndrome pSS (1%), 1 systemic sclerosis (1%), 2 undefined CTD (3%), and 1 mixed CTD (1%). Among the 60 other patients, 18 had non-CTD autoimmune diseases and 42 had non-autoimmune diseases. Within the CTD population, the presence of isolated anti-SS-B was not significantly associated to characteristic indicating a specific syndrome. There was no association between diagnosis of CTD and level of anti-SS-B autoantibodies (p = 0.70). Arthralgia was the more frequent sign and encountered in 10 patients (67%), of whom 3 had arthritis. The presence of anti-SS-B, without anti-SS-A autoantibodies using luminex technology, was not associated with CTD, especially pSS, in daily clinical practice. Our data suggests that the SS-B serological profile is not contributive for the classification criteria of pSS.


AMPD1 rs17602729 is associated with physical performance of sprint and power in elite Lithuanian athletes.
The C34T genetic polymorphism (rs17602729) in the AMPD1 gene, encoding the skeletal muscle-specific isoform of adenosine monophosphate deaminase (AMPD1), is a common polymorphism among Caucasians that can impair exercise capacity. The aim of the present study was twofold: (1) to determine the C34T AMPD1 allele/genotype frequency distributions in Lithuanian athletes (n = 204, stratified into three groups: endurance, sprint/power and mixed) and compare them with the allele/genotype frequency distributions in randomly selected healthy Lithuanian non-athletes (n = 260) and (2) to compare common anthropometric measurements and physical performance phenotypes between the three groups of athletes depending on their AMPD1 genotype. The results of our study indicate that the frequency of the AMPD1 TT genotype was 2.4% in the control group, while it was absent in the athlete group. There were significantly more sprint/power-orientated athletes with the CC genotype (86.3%) compared with the endurance-orientated athletes (72.9%), mixed athletes (67.1%), and controls (74.2%). We determined that the AMPD1 C34T polymorphism is not associated with aerobic muscle performance phenotype (VO2max). For CC genotype the short-term explosive muscle power value (based on Vertical Jump test) of athletes from the sprint/power group was significantly higher than that of the endurance group athletes (P < 0.05). The AMPD1 CC genotype is associated with anaerobic performance (Vertical Jump). The AMPD1 C allele may help athletes to attain elite status in sprint/power-oriented sports, and the T allele is a factor unfavourable for athletics in sprint/power-oriented sports categories. Hence, the AMPD1 C allele can be regarded as a marker associated with the physical performance of sprint and power. Replications studies are required to confirm this association.


Impact of a lifestyle intervention program on cardio-metabolic parameters among obese adults: A comparative population-based study in West Bengal, India.
The obesity epidemic is not only limited to high-income or urbanized societies, but has also become prevalent among rural communities, even in India. Approaches to modifiable behaviors, like unhealthy dietary habits or a sedentary lifestyle, could bring positive results among obese populations. This research aimed to assess the effectiveness of lifestyle intervention programs to prevent obesity and cardio-metabolic risks among Bengali obese adults (Body Mass Index of 25-30kg/m2). The population was selected from rural and urban communities of Hooghly district in west Bengal, India and included 121 participants (20-50 years), divided into four groups (rural male, rural female, urban male, and urban female) who underwent a 12-month intervention program. Anthropometric parameters, systolic and diastolic blood pressure, biochemical parameters (fasting blood glucose, fasting plasma insulin, Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] and lipid profile), dietary habits, and physical activity profiles were assessed before the study (baseline), after 12 months of intervention (post-intervention), and after 24 months (follow-up), among all groups, to evaluate changes in data within and between the groups (rural vs. urban). The results showed a significant decline in anthropometric parameters and fasting blood glucose levels among all intervention groups, HOMA-IR in rural females, and serum triglyceride levels in urban groups. A significant improvement was noted regarding dietary habits and physical activity, even during follow-up. The impact of the intervention program did not show any rural-urban difference. The lifestyle intervention program was effective in reducing obesity and related health risks and promoting a healthy lifestyle among the target population.


The rubber hand illusion: sensitivity and reference frame for body ownership.
When subjects view stimulation of a rubber hand while feeling congruent stimulation of their own hand, they may come to feel that the rubber hand is part of their own body. This illusion of body ownership is termed 'Rubber Hand Illusion' (RHI). We investigated sensitivity of RHI to spatial mismatches between visual and somatic experience. We compared the effects of spatial mismatch between the stimulation of the two hands, and equivalent mismatches between the postures of the two hands. We created the mismatch either by adjusting stimulation or posture of the subject's hand, or, in a separate group of subjects, by adjusting stimulation or posture of the rubber hand. The matching processes underlying body ownership were asymmetrical. The illusion survived small changes in the subject's hand posture, but disappeared when the same posture transformations were applied to the rubber hand. Mismatch between the stimulation delivered to the subject's hand and the rubber hand abolished the illusion. The combination of these two situations is of particular interest. When the subject's hand posture was slightly different from the rubber hand posture, the RHI remained as long as stimulation of the two hands was congruent in a hand-centred spatial reference frame, even though the altered posture of the subject's hand meant that stimulation was incongruent in external space. Conversely, the RHI was reduced when the stimulation was incongruent in hand-centred space but congruent in external space. We conclude that the visual-tactile correlation that causes the RHI is computed within a hand-centred frame of reference, which is updated with changes in body posture. Current sensory evidence about what is 'me' is interpreted with respect to a prior mental body representation.


Concomitant chemoradiation treatment in the management of patients with extrahepatic biliary tract recurrence of gastric carcinoma.
The aim of this study was to determine the role of concomitant chemoradiation in the alleviation of obstructive jaundice in patients with extrahepatic biliary tract metastases from gastric carcinoma. Thirteen patients with good performance status who had obstructive jaundice resulting from extrahepatic biliary metastases after gastrectomy for gastric carcinoma were treated with palliative intent. Treatment consisted of insertion of a percutaneous transhepatic choledochal drainage (PTCD) catheter followed by external radiation up to a total dose of 40-60 grays in combination with chemotherapy (cisplatin 20 mg/m(2)/day, 5-fluorouracil 600 mg/m(2)/day, and leucovorin 90 mg/m(2)/day for 96 hours during the first and fifth weeks) on an outpatient basis. The concomitant chemoradiation produced a good palliative effect in all 13 patients. Hyperbilirubinemia continued to improve after treatment, patients' clay-colored stool resolved within an average of 4 weeks (range, 2-6 weeks), and bilirubin levels returned to normal. The PTCD catheter could be removed after treatment was completed (the seventh week); the mean duration of PTCD placement was 2 months. The entire treatment course was performed on an outpatient basis; hospital admission was necessary only for PTCD insertion and chemotherapy. Ten patients died of their disease, with an average survival of 14.4 months (range, 4-31 months) from the time of PTCD insertion. Three patients are still alive at 16, 21, and 8 months. Biliary tract patency was maintained until death. No serious treatment-related complications occurred, and no endoprothesis or intraluminal brachytherapy was needed in this study. Satisfactory palliation can be achieved by concomitant chemoradiation for patients with obstructive jaundice resulting from extrahepatic biliary metastases from gastric carcinoma, providing an alternative treatment choice for these patients.


High-dose proton pump inhibitor plus amoxycillin for the treatment or retreatment of Helicobacter pylori infection.
The combination of 120 mg of omeprazole (40 mg t.d.s.) and amoxycillin has been reported to be effective for treating H. pylori infections. Normal volunteers with H. pylori infection received high-dose omeprazole (40 mg t.d.s.) or lansoprazole (60 mg t.d.s.) plus amoxycillin 750 mg t.d.s. for 14 days. The studies were open label and not randomized as those receiving omeprazole plus amoxycillin had previously failed lower dose omeprazole (20 mg b.d.) plus amoxycillin therapy more than 6 months previously. Those receiving lansoprazole plus amoxycillin had not been previously treated. Four to 6 weeks after ending antimicrobial therapy, H. pylori status was determined by Genta stain of gastric mucosal biopsies. Forty-three volunteers entered the study and 41 completed it. The overall success with high-dose proton pump inhibitor plus amoxycillin was 34.9%. For the individual regimens the per-protocol results were 48% (95% CI = 28-69%) with lansoprazole and 12.5% (95% CI = 2-38%) with omeprazole. Compliance was > 95% for both regimens. Side-effects were experienced by four lansoprazole and three omeprazole subjects, and caused two omeprazole subjects to withdraw. Cure rates were similar among different races and ethnic groups, between men and women, and between smokers and non-smokers. The level of the pre-treatment urea breath test also did not predict outcome. High-dose proton pump inhibitor plus amoxycillin combinations for treatment of H. pylori infection yielded unacceptable results, as the 95% confidence intervals did not include an 80% cure rate. These combinations do not yield consistent results worldwide and cannot be recommended as primary therapy.


Mosaic: An Architecture for Scalable & Interoperable Data Views.
Mosaic is an architecture for greater scalability, extensibility, and interoperability of interactive data views. Mosaic decouples data processing from specification logic: clients publish their data needs as declarative queries that are then managed and automatically optimized by a coordinator that proxies access to a scalable data store. Mosaic generalizes Vega-Lite's selection abstraction to enable rich integration and linking across visualizations and components such as menus, text search, and tables. We demonstrate Mosaic's expressiveness, extensibility, and interoperability through examples that compose diverse visualization, interaction, and optimization techniques-many constructed using vgplot, a grammar of interactive graphics in which graphical marks act as Mosaic clients. To evaluate scalability, we present benchmark studies with order-of-magnitude performance improvements over existing web-based visualization systems-enabling flexible, real-time visual exploration of billion+ record datasets. We conclude by discussing Mosaic's potential as an open platform that bridges visualization languages, scalable visualization, and interactive data systems more broadly.


Predictors of unsuccessful laparoscopic resection of gastric submucosal neoplasms.
While laparoscopy has become integral to the performance of foregut surgery, its optimal use in resection of gastric submucosal neoplasms, including gastrointestinal stromal tumors (GISTs), remains uncertain. Concern exists for technical feasibility related to tumor size and location, as well as oncologic outcome. From 2002 to 2012, 106 patients underwent resection for gastric submucosal neoplasms, comprising 79 laparoscopic and 27 open resections. Median follow-up was 15 months. Patients were 62 ± 14 years and 56 % male. Mean tumor size was 5.5 ± 4.3 cm, with 76 % being GISTs. A total of 8 (10 %) conversions occurred in the laparoscopic cohort. On multivariate analysis, conversion was predicted by size greater than 8 cm, while recurrence was predicted by mitotic index (p < 0.05). Laparoscopic resection resulted in better perioperative outcomes, with less morbidity, operative time, blood loss, and length of stay (p < 0.05). No significant difference was seen in survival, with 90 % and 81 % alive 3 years after laparoscopic and open resection, respectively (HR 0.4; 95 % CI 0.1-1.3; p = 0.13). Laparoscopic resection is feasible and effective in the management of gastric submucosal neoplasms, including GISTs. Caution should be reserved for tumors greater than 8 cm. Oncologic outcome appears to be predicted by tumor biology as opposed to surgical approach.


Shape-Shifting Droplet Networks.
We consider a three-dimensional network of aqueous droplets joined by single lipid bilayers to form a cohesive, tissuelike material. The droplets in these networks can be programed to have distinct osmolarities so that osmotic gradients generate internal stresses via local fluid flows to cause the network to change shape. We discover, using molecular dynamics simulations, a reversible folding-unfolding process by adding an osmotic interaction with the surrounding environment which necessarily evolves dynamically as the shape of the network changes. This discovery is the next important step towards osmotic robotics in this system. We also explore analytically and numerically how the networks become faceted via buckling and how quasi-one-dimensional networks become three dimensional.


Pathway-Specific Drive of Cerebellar Golgi Cells Reveals Integrative Rules of Cortical Inhibition.
Cerebellar granule cells (GrCs) constitute over half of all neurons in the vertebrate brain and are proposed to decorrelate convergent mossy fiber (MF) inputs in service of learning. Interneurons within the GrC layer, Golgi cells (GoCs), are the primary inhibitors of this vast population and therefore play a major role in influencing the computations performed within the layer. Despite this central function for GoCs, few studies have directly examined how GoCs integrate inputs from specific afferents, which vary in density to regulate GrC population activity. We used a variety of methods in mice of either sex to study feedforward inhibition recruited by identified MFs, focusing on features that would influence integration by GrCs. Comprehensive 3D reconstruction and quantification of GoC axonal boutons revealed tightly clustered boutons that focus feedforward inhibition in the neighborhood of GoC somata. Acute whole-cell patch-clamp recordings from GrCs in brain slices showed that, despite high GoC bouton density, fast phasic inhibition was very sparse relative to slow spillover mediated inhibition. Dynamic-clamp simulating inhibition combined with optogenetic MF activation at moderate rates supported a predominant role of slow spillover mediated inhibition in reducing GrC activity. Whole-cell recordings from GoCs revealed a role for the density of active MFs in preferentially driving them. Thus, our data provide empirical confirmation of predicted rules by which MFs activate GoCs to regulate GrC activity levels.SIGNIFICANCE STATEMENT A unifying framework in neural circuit analysis is identifying circuit motifs that subserve common computations. Wide-field inhibitory interneurons globally inhibit neighbors and have been studied extensively in the insect olfactory system and proposed to serve pattern separation functions. Cerebellar Golgi cells (GoCs), a type of mammalian wide-field inhibitory interneuron observed in the granule cell layer, are well suited to perform normalization or pattern separation functions, but the relationship between spatial characteristics of input patterns to GoC-mediated inhibition has received limited attention. This study provides unprecedented quantitative structural details of GoCs and identifies a role for population input activity levels in recruiting inhibition using in vitro electrophysiology and optogenetics.


Differences in Genetic Background Contribute to Pseudomonas Exotoxin A-Induced Hepatotoxicity in Rats.
Pseudomonas aeruginosa exotoxin A (PEA) causes severe hepatotoxicity in experimental animals and is useful in investigations of immune-mediated liver injury. However, strain differences in the sensitivity to PEA-induced hepatotoxicity in rats remains be elucidated. In this study, we determined the severity of PEA-induced hepatotoxicity in six genetically different rat strains. Male LE (Long Evans), Wistar, F344, WKY, BN/SsN and LEW rats were administered a single intravenous injection of PEA (20 μg/kg). Significantly elevated serum ALT and AST levels, massive necrosis and hemorrhage, and numerous TUNEL-positive hepatocytes were observed in BN/SsN rats. In contrast, low levels of ALT and AST as well as mild changes in liver histopathology were observed in Wistar and F344 rats. Moderate levels of hepatic injuries were observed in LE, WKY, and LEW rats. Pro-inflammatory cytokines including TNF-α, IL-2 and IL-6 serum levels were markedly increased in BN/SsN rats compared to Wistar and F344 rats. However, the hepatic levels of low density lipoprotein receptor-related protein (LRP), which functions as the PEA receptor, were not significantly different in each strain. Taken together, we suggest that BN/SsN is the most sensitive rat strain, whereas Wistar and F344 were the most resistant rat strains to PEA-induced liver damage. The different genetic background of rat strains plays an important role in the susceptibility to PEA-induced epatotoxicity that may depend on immune-regulation but not LRP receptor levels.


Physical activity and incident hypertension in black and white adults: the Atherosclerosis Risk in Communities Study.
The epidemiologic observation that physical activity reduces the risk for hypertension has only been made for white men who self-reported hypertension. This study examined physical activity and clinically determined incident hypertension in black and white men and women of the Atherosclerosis Risk in Communities (ARIC) Study. ARIC is a population-based prospective study with four U.S. clinic centers. The present analyses included 7,459 black and white adults 45-65 years of age. Hypertension (systolic/diastolic blood pressure >/= 140/90 mm Hg) was defined by blood pressure measured by a random-zero device or medication use. Physical activity was assessed with the Baecke questionnaire. After adjustment for age, baseline blood pressure, ARIC center, education, body mass index, waist-hip ratio, parental history of hypertension, cigarette smoking, alcohol consumption, and diet, white men in the highest quartile of leisure activity (primarily cycling and walking) had a 34% lower odds of developing hypertension over 6 years compared to the least active (OR = 0.66, 95% CI = 0.47-0.94; P for quartile trend = 0.01). Baseline activity was not associated with incident hypertension in white women or blacks. Leisure-time physical activity reduces the odds of hypertension in middle-aged white men. Additional studies in women and blacks are needed.


Genetic abnormalities in a large cohort of Coffin-Siris syndrome patients.
Coffin-Siris syndrome (CSS, MIM#135900) is a congenital disorder characterized by coarse facial features, intellectual disability, and hypoplasia of the fifth digit and nails. Pathogenic variants for CSS have been found in genes encoding proteins in the BAF (BRG1-associated factor) chromatin-remodeling complex. To date, more than 150 CSS patients with pathogenic variants in nine BAF-related genes have been reported. We previously reported 71 patients of whom 39 had pathogenic variants. Since then, we have recruited an additional 182 CSS-suspected patients. We performed comprehensive genetic analysis on these 182 patients and on the previously unresolved 32 patients, targeting pathogenic single nucleotide variants, short insertions/deletions and copy number variations (CNVs). We confirmed 78 pathogenic variations in 78 patients. Pathogenic variations in ARID1B, SMARCB1, SMARCA4, ARID1A, SOX11, SMARCE1, and PHF6 were identified in 48, 8, 7, 6, 4, 1, and 1 patients, respectively. In addition, we found three CNVs including SMARCA2. Of particular note, we found a partial deletion of SMARCB1 in one CSS patient and we thoroughly investigated the resulting abnormal transcripts.


Electron-spin-resonance studies of the NADH-dependent nitrite reductase from Escherichia coli K12.
The NADH-dependent nitrite reductase of Escherichia coli, which contains sirohaem, flavin, non-haem iron and labile sulphide, was examined by low-temperature e.s.r. spectroscopy. The enzyme, stored in the presence of nitrite and ascorbate, gave the spectrum of a nitrosyl derivative, with hyperfine splitting due to the nitrosyl nitrogen. On removal of these reagents, a series of signals centred around g = 6 was observed, typical of high-spin ferric haem. Cyanide converted this into a low-spin form. On reduction of the enzyme with NADH, an axial spectrum at g = 1.92, 2.01 was observed. The temperature-dependence of this signal is indicative of a [2Fe-2S] iron-sulphur cluster. The midpoint potential of this cluster was estimated to be -230 +/- 15 mV by two independent methods. Reduction of the enzyme with dithionite yielded further signals, which are at present unidentified, at g = 2.1-2.28. No signals were observed that could be assigned to a [4Fe-4S] cluster, such as is found in other sulphite reductases and nitrite reductases that contain sirohaem.


A perfect spin filtering device through Mach-Zehnder interferometry in a GaAs/AlGaAs electron gas.
A spin filtering device based on quantum spin interference is addressed, for use with a two-dimensional GaAs/AlGaAs electron gas that has both Rashba and Dresselhaus spin-orbit (SO) couplings and an applied external magnetic field. We propose an experimentally feasible electronic Mach-Zehnder interferometer and derive a map, in parameter space, that determines perfect spin filtering conditions. We find two broad spin filtering regimes: one where filtering is achieved in the original incoming quantization basis, that takes advantage of the purely non-Abelian nature of the spin rotations; and another where one needs a tilted preferential axis in order to observe the polarized output spinor. Both solutions apply for arbitrary incoming electron polarization and energy, and are only limited in output amplitude by the randomness of the incoming spinor state. Including a full account of the beam splitter and mirror effects on spin yields solutions only for the tilted basis, but encompasses a broad range of filtering conditions.


Detection of L-phenylalanine using molecularly imprinted solid-phase extraction and flow injection electrochemiluminescence.
A novel flow injection electrochemiluminescence method combined with molecularly imprinted solid-phase extraction was developed for the determination of L-phenylalanine, in which ${\rm{Ru(bpy}})_3^{2 + }$ was used as the luminophor and indium tin oxide glass was modified as the working electrode. Molecularly imprinted polymers, synthesized by self-assembly with functional monomer and crossing linker, were used for the selective extraction of L-phenylalanine. In order to overcome the drawbacks of traditional electrochemiluminescence cells such as high IR drop, high over-potential and so on, a novel electrochemiluminescence cell was developed. The enhanced electrochemiluminescence intensity was linearly related with the concentration of L-phenylalanine in the range from 1.0×10(-7) to 5.0×10(-5) g/mL with a detection limit of 2.59×10(-8) g/mL. The relative standard deviation for the determination of 1.0×10(-6) g/mL L-phenylalanine was 1.2% (n=11). The method showed higher sensitivity and good repeatability, and was successfully applied for the determination of L-phenylalanine in egg white, chicken and serum samples. A possible mechanism for the enhanced electrochemiluminescence response on indium tin oxide glass is proposed.


Genetic control of anastomosis in Podospora anserina.
We developed a new microscopy procedure to study anastomoses in the model ascomycete Podospora anserina and compared it with the previous method involving the formation of balanced heterokaryons. Both methods showed a good correlation. Heterokaryon formation was less quantifiable, but enabled to observe very rare events. Microscopic analysis evidenced that anastomoses were greatly influence by growth conditions and were severely impaired in the IDC mutants of the PaMpk1, PaMpk2, IDC1 and PaNox1 pathways. Yet some mutants readily formed heterokaryons, albeit with a delay when compared to the wild type. We also identified IDC(821), a new mutant presenting a phenotype similar to the other IDC mutants, including lack of anastomosis. Complete genome sequencing revealed that IDC(821) was affected in the orthologue of the Neurospora crassa So gene known to control anastomosis in several other ascomycetes.


Spinal cord protection during a thoracoabdominal aortic repair for a chronic type B aortic dissection using the aortic tailoring strategy.
This study evaluated the clinical advantage of a novel technique to reconstruct a true lumen with aortic wall tailoring for aortic repair (aortic tailoring) or the reimplantation of intercostal arteries (vascular tube) in a chronic type B aortic dissection. Thirty-three consecutive extended thoracoabdominal aortic repairs have been performed for chronic type B dissection since 2000. The novel strategy was applied in 17 cases since 2004 including eight cases of aortic repair (group A) and nine cases of a vascular tube (group B). The other 16 cases were graft interposition in five and no reimplantation in 11 for group C. There were no surgical deaths in either group A or B, and only one late death in group C. No patients sustained transient or permanent paraplegia in group A and B, while three cases of paraplegia occurred in group C (18.8%). All of the intercostal arteries were well preserved in group A and an average of 9.8 intercostal arteries for nine patients were reimplantated in group B. The present technique can optimally preserve the intercostal arteries maximally and showed an excellent surgical mortality and morbidity, especially with regard to the protection of the spinal cord.


Reauthorization of the Temporary Assistance for Needy Families (TANF) program. Final rule.
This final rule implements changes to the Temporary Assistance for Needy Families (TANF) program required by the Deficit Reduction Act of 2005 (DRA) (Pub. L. 109-171). The DRA reauthorized the TANF program through fiscal year (FY) 2010 with a renewed focus on work, program integrity, and strengthening families through healthy marriage promotion and responsible fatherhood. On June 29, 2006, ACF published an interim final rule implementing the required statutory changes with a 60-day comment period that ended on August 28, 2006. We have considered all comments received during this period and made necessary changes as reflected in this final rule.


Long-term clinical remission of a patient with chronic lymphocytic leukemia using alternative treatment option: cottonseed oil (gossypol).
Chronic lymphocytic leukaemia (CLL) results from the accumulation of malignant immunologically incompetent lymphocytes. A routine full blood count of a single patient revealed that he had CLL. The daily intake of 700ml of fresh bovine milk resulted in a decrease in the lymphocyte count from 85.5x10(9)/l to 12.5x10(9)/l over a period of 5 years. The aim was to establish which constituent(s) in milk would be responsible for the decline of the lymphocyte count. It was found that the higher vitamin D constituent in the milk, the lower the lymphocyte count. Whilst the milk from large dairy farms which use supplements in the feed in order to increase milk production, considerably decreased the lymphocyte count, the milk from small dairy farms, which do not supplement, had hardly any effect. The present study indicates that gossypol in cottonseed cake and oil are potentially responsible for the decrease in white blood cell count. It appears that gossypol is a very powerful anti-neoplastic agent. Free gossypol (Fig. 1) is a toxic phenolic compound which becomes detoxified in ruminants by binding to milk proteins, but gossypol is still an active inhibitor of tumour growth in the excreted milk.


Porcelain laminate veneers. A retrospective evaluation after 1 to 10 years of service: Part II--Clinical results.
The objective of this study was to evaluate the clinical quality of 191 porcelain laminate veneers and to explore the gingival response in a long-term survey. The clinical examination was made by two calibrated examiners following modified California Dental Association/Ryge criteria. In addition, margin index, papillary bleeding index, sulcus probing depth, and increase in gingival recession were recorded. Two age groups were formed to evaluate the influence of wearing time upon the clinical results. The results were statistically evaluated using the Kaplan-Meier survival estimation method, Chi-squared test, and Kruskal-Wallis test. A failure rate of 4% was found. Six of the total of seven failures were seen when veneers were partially bonded to dentin. Marginal integrity was acceptable in 99% and was rated as excellent in 63%. Superficial marginal discoloration was present in 17%. Slight marginal recession was detected in 31%, and bleeding on probing was found in 25%. Porcelain laminate veneers offer a predictable and successful treatment modality that preserves a maximum of sound tooth structure. An increased risk of failure is present only when veneers are partially bonded to dentin. The estimated survival probability over a period of 10 years is 91%.


Transmission of 2009 pandemic influenza A (H1N1) virus among healthcare personnel-Southern California, 2009.
In April 2009, 2009 pandemic influenza A (H1N1) (hereafter, pH1N1) virus was identified in California, which caused widespread illness throughout the United States. We evaluated pH1N1 transmission among exposed healthcare personnel (HCP) and assessed the use and effectiveness of personal protective equipment (PPE) early in the outbreak. Cohort study. Two hospitals and 1 outpatient clinic in Southern California during March 28-April 24, 2009. Sixty-three HCP exposed to 6 of the first 8 cases of laboratory-confirmed pH1N1 in the United States. Baseline and follow-up questionnaires were used to collect demographic, epidemiologic, and clinical data. Paired serum samples were obtained to test for pH1N1-specific antibodies by microneutralization and hemagglutination-inhibition assays. Serology results were compared with HCP work setting, role, and self-reported PPE use. Possible healthcare-associated pH1N1 transmission was identified in 9 (14%) of 63 exposed HCP; 6 (67%) of 9 seropositive HCP had asymptomatic infection. The highest attack rates occurred among outpatient HCP (6/19 [32%]) and among allied health staff (eg, technicians; 8/33 [24%]). Use of mask or N95 respirator was associated with remaining seronegative (P = .047). Adherence to PPE recommendations for preventing transmission of influenza virus and other respiratory pathogens was inadequate, particularly in outpatient settings. pH1N1 transmission likely occurred in healthcare settings early in the pandemic associated with inadequate PPE use. Organizational support for a comprehensive approach to infectious hazards, including infection prevention training for inpatient- and outpatient-based HCP, is essential to improve HCP and patient safety.


Multidisciplinary Guidance Regarding the Use of Immunomodulatory Therapies for Acute Coronavirus Disease 2019 in Pediatric Patients.
Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.


Edge Effect in Electronic and Transport Properties of 1D Fluorinated Graphene Materials.
A systematic examination of the electronic and transport properties of 1D fluorine-saturated zigzag graphene nanoribbons (ZGNRs) is presented in this article. One publication (Withers et al., Nano Lett., 2011, 11, 3912-3916.) reported a controlled synthesis of fluorinated graphene via an electron beam, where the correlation between the conductivity of the resulting materials and the width of the fluorinated area is revealed. In order to understand the detailed transport mechanism, edge-fluorinated ZGNRs with different widths and fluorination degrees are investigated. Periodic density functional theory (DFT) is employed to determine their thermodynamic stabilities and electronic structures. The associated transport models of the selected structures are subsequently constructed. The combination of a non-equilibrium Green's function (NEGF) and a standard Landauer equation is applied to investigate the global transport properties, such as the total current-bias voltage dependence. By projecting the corresponding lesser Green's function on the atomic orbital basis and their spatial derivatives, the local current density maps of the selected systems are calculated. Our results suggest that specific fluorination patterns and fluorination degrees have significant impacts on conductivity. The conjugated π system is the dominate electron flux migration pathway, and the edge effect of the ZGNRs can be well observed in the local transport properties. In addition, with an asymmetric fluorination pattern, one can trigger spin-dependent transport properties, which shows its great potential for spintronics applications.


Arginine vasotocin stimulates glucocorticoid secretion in male rats.
The endocrine effects of the putative pineal peptide arginine vasotocin (AVT) were compared with those of the pineal indoleamines melatonin and N-acetylserotonin and passive immunization against these indoleamines in male rats injected at 1200 hr or 2400 hr. A pharmacologic dose of AVT markedly enhanced both day and night serum glucocorticoid levels but lowered prolactin levels at both time points. Melatonin decreased night prolactin and corticosterone levels whereas passive immunization against circulating melatonin and N-acetylserotonin elevated night levels of these hormones. Preliminary evidence that AVT (10 microM) produces a guanosine triphosphate (GTP)-dependent stimulation of adenylate cyclase activity in the hypothalamus, anterior pituitary and adrenal gland suggests that the endocrine effects of this peptide may involve alterations in cAMP levels at one or more of these sites.


Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor.
Resveratrol, a compound present in a variety of plants, was recently shown to have potent chemopreventive activity against aryl hydrocarbon-induced tumorigenesis in mice. Therefore, in the present study, we examined the effect of resveratrol on the function of the aryl hydrocarbon receptor (AHR) and the transcription of CYP1A1 in human HepG2 hepatoma cells. Resveratrol inhibited the increase in cytochrome P450 (CYP) 1A1 mRNA caused by the AHR ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a concentration-dependent manner. The induction of transcription of an aryl hydrocarbon-responsive reporter vector containing the CYP1A1 promoter by TCDD was likewise inhibited by resveratrol. Resveratrol also inhibited the constitutive level of CYP1A1 mRNA and reporter vector transcription in HepG2 cells. The increase in CYP1A1 enzyme activity induced by TCDD was inhibited by resveratrol. Resveratrol prevented the TCDD-induced transformation of the cytosolic AHR to its nuclear DNA-binding form. However, resveratrol had no effect on the binding of TCDD to the cytosolic AHR. These data demonstrate that resveratrol inhibits CYP1A1 expression in vitro, and that it does this by preventing the binding of the AHR to promoter sequences that regulate CYP1A1 transcription. This activity may be an important part of the chemopreventive activity of resveratrol.


Analgesics and asthma.
The incidence of asthma is increasing throughout the world, which presents both public health and economic concerns. It is widely recognized that in some adult patients with asthma, aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit cyclooxygenase (COX)-1 exacerbate the condition. This is a distinct clinical syndrome called aspirin-induced asthma (AIA). The disease develops according to a characteristic pattern of symptoms. Persistent eosinophilic rhinosinusitis precedes development of nasal polyposis, aspirin hypersensitivity, and asthma. There is no in vitro test, and diagnosis can only be established by provocation tests with aspirin. At the biochemical level, AIA is characterized by a chronic overproduction of cysteinyl leukotrienes. The key enzyme, leukotriene C4 synthase, is overexpressed in bronchi, and its messenger RNA is upregulated in peripheral blood eosinophils. This can be partly related to the genetic polymorphism of the enzyme. The disease runs a protracted course, even if COX-1 inhibitors are avoided. The course of AIA is often severe, and at least half of the patients need systemic corticosteroids to control their asthma. To prevent life-threatening reactions, patients with AIA should avoid aspirin and other analgesics that inhibit COX-1. The incidence of cross-sensitivity to paracetamol in AIA patients is low and, when a reaction does occur, the symptoms experienced are shorter and milder than if the reactions were evoked by an NSAID. Rapidly growing evidence indicates that highly specific COX-2 inhibitors, known as coxibs, are well tolerated and can be safely used by AIA patients.


'We know what we should eat but we don't …': a qualitative study in Irish secondary schools.
Healthy eating opportunities for young people need to be provided in the school setting. Links between formal education and local policies and practices, and active involvement of students are emphasized in whole school approaches to health promotion. In many jurisdictions, schools struggle to provide nutritious food that is acceptable to students. The aim of this study was to conduct an in-depth exploration of school food and students' food choice with students, teachers and principals in six Irish secondary schools. Students conducted their own focus groups with peers, and a researcher conducted focus groups with teachers and one-to-one interviews with principals. Students, teachers and principals expressed dissatisfaction with food provision within their respective schools and reported unhealthy dietary behaviours among the student body as the norm. Divergent views, however, emerged regarding education, knowledge and the primary drivers of food choice. Teachers and principals saw a role for more education modules and students believed environmental infrastructures, practices and policies needed to be addressed to improve behaviours. This consultation with students, teachers and principals highlight that, in addition to education, the social and environmental aspects of food choice and eating at school deserve attention in future research and policy.


Maternal depressive symptoms and sensitivity are related to young children's facial expression recognition: the Generation R Study.
A vast body of literature shows that maternal depression has long-term adverse consequences for children. However, only very few studies have documented the effect of maternal depression on children's ability to process emotional expressions and even fewer incorporated measures of observed maternal sensitivity to further tease apart whether it is the symptoms per se or the associated impact via maternal sensitivity that affects children's developing emotion-processing abilities. In a large community sample of Dutch preschoolers (N = 770), we examined independent and mediated effects of maternal depressive symptoms and sensitivity on children's ability to recognize emotional expressions using a nonverbal and a verbal task paradigm. Maternal depressive symptoms predicted less accurate emotion labeling in children, while maternal sensitivity was associated with more accurate emotion matching, especially for sadness and anger. Maternal sensitivity did not mediate the observed associations between mothers' depressive symptoms and children's emotion recognition, and effects were similar for boys and girls. Given that maternal depressive symptoms and sensitivity affected nonoverlapping areas of young children's emotion recognition, prevention and intervention efforts should focus on both alleviating maternal depressive symptoms and improving maternal sensitivity at the same time in order to maximize benefit.


Relationships between fecal consistency and colonic microstructure and absorptive function in dogs with and without nonspecific dietary sensitivity.
To determine relationships between fecal consistency and colonic microstructure and absorptive function in dogs with and without nonspecific dietary sensitivity. 12 dogs with nonspecific dietary sensitivity (affected) and 9 healthy dogs (controls). Affected dogs were fed 4 test diets and control dogs, 3 diets for 4 weeks each in a crossover design. Fecal consistency was assessed daily. At the end of each feeding period, electrolyte and water transport were assessed, and colonic biopsy specimens were obtained for histologic examination and measurement of crypt water uptake by use of confocal microscopy. Feces were consistently looser in affected dogs. In control dogs, we detected net colonic absorption of sodium and chloride and secretion of potassium and bicarbonate. Absorption of sodium and chloride was less in affected dogs, compared with controls, indicating that electrolyte transport was disrupted in affected dogs. This disruption was accentuated during feeding of diets associated with significantly poorer fecal consistency (ie, loose feces). Fecal consistency was inversely correlated with crypt water absorption, which was reduced in affected dogs. Colonic crypts were shorter and less dense in affected dogs fed diets associated with poor fecal consistency, compared with affected dogs fed other diets or with control dogs. Colonic transport function is a major determinant of fecal consistency in dogs. Dogs with nonspecific dietary sensitivity are particularly susceptible to diet-induced changes in absorptive function. Such changes are associated with damage to colonic microstructure, disrupted electrolyte transport, and failure to dehydrate luminal contents.


Creation and properties of histocompatibility antigen-cell conjugates. II. Antibody tolerance after treatment with donor histocompatibility antigen chemically coupled to recipient spleen cells.
Histocompatibility (HC) antigens from Lewis (RT-11) and ACI (RT-1a) rats were solubilized and their tolerogenic potential alone or when conjugated to cellular carriers was investigated. The tolerogenic carrier potential of whole cells, crude membranes, and deoxycholate (DOC)-solubilized membranes was first determined by conjugating trinitrophenyl (TNP) groups to them and measuring their ability to prevent an anti-TNP plaque-forming cell response in rats after immunogenic challenge. Since whole lymphoid cells proved to be most effective in this system, DOC-solubilized allogeneic histocompatibility antigens were coupled to syngeneic lymphocytes, using carbodiimide cross-linking. Animals pretreated with this conjugate produced no alloantibody upon challenge with allogeneic cells. These results suggest that tolerance to allogeneic histocompatibility antigen can be produced by association of alloantigens on a tolerogenic self-carrier.


Evidence that CD147 modulation of beta-amyloid (Abeta) levels is mediated by extracellular degradation of secreted Abeta.
Cerebral deposition of beta-amyloid (Abeta) peptides is a pathological hallmark of Alzheimer disease. Intramembranous proteolysis of amyloid precursor protein by a multiprotein gamma-secretase complex generates Abeta. Previously, it was reported that CD147, a glycoprotein that stimulates production of matrix metalloproteinases (MMPs), is a subunit of gamma-secretase and that the levels of secreted Abeta inversely correlate with CD147 expression. Here, we show that the levels and localization of CD147 in fibroblasts, as well as postnatal expression and distribution in brain, are distinct from those of integral gamma-secretase subunits. Notably, we show that although depletion of CD147 increased extracellular Abeta levels in intact cells, membranes isolated from CD147-depleted cells failed to elevate Abeta production in an in vitro gamma-secretase assay. Consistent with an extracellular source that modulates Abeta metabolism, synthetic Abeta was degraded more rapidly in the conditioned medium of cells overexpressing CD147. Moreover, modulation of CD147 expression had no effect on epsilon-site cleavage of amyloid precursor protein and Notch1 receptor. Collectively, our results demonstrate that CD147 modulates Abeta levels not by regulating gamma-secretase activity, but by stimulating extracellular degradation of Abeta. In view of the known function of CD147 in MMP production, we postulate that CD147 expression influences Abeta levels by an indirect mechanism involving MMPs that can degrade extracellular Abeta.


Update on the safety and efficacy of clomiphene citrate as a therapeutic agent.
Fifteen years have passed since our group first proposed the use of clomiphene citrate as an ovulation-inducing agent. Our 15-year experience with over 2,000 patients has not dampened our enthusiasm for this drug. The benefits have far outweighted the minor side effects or the possibility of multiple births. Serious birth defects were minimal and have been no greater than what one may expect in the general population. Clomiphene citrate has been a boon to womankind and deserves the confidence of both patient and physician: it is a drug with a record of utility and with but minor risks.


Unravelling the Role of Metallothionein on Development, Reproduction and Detoxification in the Wall Lizard Podarcis sicula.
Metallothioneins (MTs) are an evolutionary conserved multigene family of proteins whose role was initially identified in binding essential metals. The physiological role of MT, however, has been revealed to be more complex than expected, since not only are MTs able to bind to toxic heavy metals, but many isoforms have shown specialized and alternative functions. Within this uncertainty, the information available on MTs in non-mammalian vertebrates, particularly in neglected tetrapods such as the reptiles, is even more scant. In this review, we provide a summary of the current understanding on metallothionein presence and function in the oviparous lizard Podarcis sicula, highlighting the results obtained by studying MT gene expression in most representative adult and embryonic tissues. The results demonstrate that in adults, cadmium induces MT transcription in a dose- and tissue-specific manner. Thus, the MT mRNAs appear, at least in some cases, to be an unsuitable tool for detecting environmental ion contamination. In early embryos, maternal RNAs sustain developmental needs for MT protein until organogenesis is well on its way. At this time, transcription starts, but again in a tissue- and organ-specific manner, suggesting an involvement in alternative roles. In conclusion, the spatiotemporal distribution of transcripts in adults and embryos definitively confirms that MT has deserved the title of elusive protein.


Thermoelasticity of Silicate Perovskite and Magnesiowustite and Stratification of the Earth's Mantle.
Analyses of x-ray-diffraction measurements on (Mg,Fe)SiO(3) perovskite and (Mg,Fe)O magnesiowüstite at simultaneous high temperature and pressure are used to determine pressure-volume-temperature equations of state and thermoelastic properties of these lower mantle minerals. Detailed comparison with the seismically observed density and bulk sound velocity profiles of the lower mantle does not support models of this region that assume compositions identical to that of the upper mantle. The data are consistent with lower mantle compositions consisting of nearly pure perovskite (>85 percent), which would indicate that the Earth's mantle is compositionally, and by implication, dynamically stratified.