First Report of Blueberry red ringspot virus Infecting Highbush Blueberry in Korea.
Blueberry red ringspot virus (BRRSV) of the Soymovirus genus in the family Caulimovididae causes red ringspot diseases in highbush blueberry (Vaccinium corymbosum L.) on leaves, stems, and fruits. The virus has been identified in the United States, Japan, Czech Republic, Slovenia, and Poland (1). In July 2010, highbush blueberry with red ringspots on leaves and circular blotches on ripening fruits was found in one plant of cv. Duke in Pyeongtaek, Korea. The symptoms were similar to red ringspot disease caused by BRRSV (3), although stems did not show any characteristic symptoms. Red ringspots on the upper surface of leaves were the most visible symptom and became more prominent as leaves matured in August through October. Leaves of the symptomatic plant were collected and tested for BRRSV infection by PCR, and were also embedded for electron microscopy. DNA was extracted from leaves using DNeasy Plant Mini Kit (Qiagen, Valencia, CA) according to the manufacturer's instructions. Primer pairs BR1512F/BR2377R (5'-ACAGGACGATTAGAAGATGG-3'/5'-CCTTTAGGGCAATATTTCTG-3', amplifying a fragment of the coat protein region with an expected size of 865 bp) and BR2961F/BR3726R (5'-ACCGATACATCACAGTTCAC-3'/5'-TGGTTGTGATAAGATGATTCC-3', amplifying a fragment of the reverse transcriptase region with an expected size of 766 bp) were used to amplify the indicated region of BRRV in PCR. Primers were designed on the basis of the BRRSV isolate from New Jersey (GenBank Accession No. AF404509). DNA fragments of the expected sizes were obtained from the symptomatic plant, while no amplification products were obtained from highbush blueberry without symptoms. The PCR products were cloned into pGEM-T easy vector (Promega, Madison, WI) and sequenced. BLAST analyses of obtained fragments revealed 91 to 98% nucleotide sequence identity with the coat protein gene (GenBank Accession No. JQ706341) and 96 to 98% nucleotide sequence identity with the reverse transcriptase gene (GenBank Accession No. JQ706340) of known BRRV isolates. Electron microscopy of thin sections revealed particles approximately 50 nm diameter within electron-dense inclusion bodies, characteristic of BRRSV (2) To our knowledge, this is the first report of BRRSV infection of highbush blueberry in Korea. Highbush blueberries are usually propagated by cutting, so BRRSV suspicious plants should be tested with PCR before they are propagated. References: (1) E. Kalinowska et al. Virus Genes. DOI 10.1007/s11262-011-0679-4, 2011. (2) K. S. Kim et al. Phytopathology 71:673, 1981. (3) M. Isogai et al. J. Gen. Plant Pathol. 75:140, 2009.


Atomic wave-packet dynamics and third-harmonic generation in sodium.
In femtosecond degenerate four-wave mixing experiments in sodium vapor, quantum beats are observed at the wavelength of the third harmonic when the fundamental beams are three-photon resonant. The period of beating, which corresponds to fine structure energy-level splitting, does not change with the atomic number density, buffer gas pressure, or laser intensity. Surprisingly, the third-harmonic signal is observed only at negative time delays for the transient grating pulse sequence. We relate this to the well-known interference effect between excitation pathways involving the fundamental and the third-harmonic fields, which leaves atoms virtually unexcited and prevents formation of population grating.


Mesothelioma: recent highlights.
Recent discoveries have elucidated some of the mechanisms responsible for the development of mesothelioma. These discoveries are: (I) the critical role of chronic inflammation in promoting mesothelioma growth, driven by the release of high mobility group box protein-1 (HMGB1) following asbestos deposition in tissues and its potential role as a biomarker to identify asbestos exposed individuals and mesothelioma patients; (II) the discovery that inherited heterozygous germline mutations of the deubiquitylase BRCA-associated protein 1 (BAP1) cause a high incidence of mesothelioma in some families; and that (III) germline BAP1 mutations lower the threshold of asbestos required to cause mesothelioma in mice, evidence of gene X environment interaction. These findings together with the identification of novel serum biomarkers, including HMGB1, Fibulin-3, etc., promise to revolutionize screening and treatment of this malignancy in the coming years.


Synthetic spike-in standards for RNA-seq experiments.
High-throughput sequencing of cDNA (RNA-seq) is a widely deployed transcriptome profiling and annotation technique, but questions about the performance of different protocols and platforms remain. We used a newly developed pool of 96 synthetic RNAs with various lengths, and GC content covering a 2(20) concentration range as spike-in controls to measure sensitivity, accuracy, and biases in RNA-seq experiments as well as to derive standard curves for quantifying the abundance of transcripts. We observed linearity between read density and RNA input over the entire detection range and excellent agreement between replicates, but we observed significantly larger imprecision than expected under pure Poisson sampling errors. We use the control RNAs to directly measure reproducible protocol-dependent biases due to GC content and transcript length as well as stereotypic heterogeneity in coverage across transcripts correlated with position relative to RNA termini and priming sequence bias. These effects lead to biased quantification for short transcripts and individual exons, which is a serious problem for measurements of isoform abundances, but that can partially be corrected using appropriate models of bias. By using the control RNAs, we derive limits for the discovery and detection of rare transcripts in RNA-seq experiments. By using data collected as part of the model organism and human Encyclopedia of DNA Elements projects (ENCODE and modENCODE), we demonstrate that external RNA controls are a useful resource for evaluating sensitivity and accuracy of RNA-seq experiments for transcriptome discovery and quantification. These quality metrics facilitate comparable analysis across different samples, protocols, and platforms.


Need for mental health care in adolescents and its determinants: the TRAILS Study.
Although a great deal of evidence is available on the patterns and determinants of unmet health care needs among adolescents with mental health problems, little is known about the factors that influence the need for care. The aim of this study is to assess the occurrence of need for care for mental problems in adolescents and the determinants of this need. Data were obtained from three assessment waves of TRAILS (TRacking Adolescents' Individual Lives Survey) (N = 1406). Need for care was assessed at age 16/17 (parent report). Determinants concerned previous health care utilization, emotional and behavioral problems (child behavior checklist and youth self-report) and child and family characteristics. Of the 1406 parents, 409 parents (29%) reported that their child needed help for mental problems. Of these adolescents, only 29% received specialized mental health treatment. The determinants of need for mental health care at age 16/17 were family break-up and parental internalizing problems (age 10/11), parent-reported internalizing and externalizing (age 10/11 and 13/14) and receiving specialized help (age 13/14). A substantial proportion of all adolescents need care for their mental problems, according to their parent. There is also a large group of adolescents with mental health problems according to their parents, but for whom no parental reported need for care is expressed. The findings stress the importance of early interventions focusing on raising parental and child awareness of mental health problems.


p16 Gene Transfer Induces Centrosome Amplification and Abnormal Nucleation Associated with Survivin Downregulation in Glioma Cells.
In human glioma cells, p16 gene transfer induced G1/S arrest, increased radiosensitivity and abnormal nucleation (especially bi- and multinucleation). Survivin suppression caused G2/M arrest, radiosensitization and an increase in aneuploidy accompanied by centrosome amplification. Abnormal nucleation and aneuploidy represent chromosome instability (CIN), and it is well known that centrosome amplification leads to CIN. However, little has been reported that suggests that transferring p16 causes centrosome overduplication during the G1/S phase. The p16 gene was transferred into p16-null human glioma cell lines (U251MG and D54MG) using adenovirus with or without irradiation. Centrosome amplification was evaluated by immunofluorescence. We also investigated the DNA replication licensing factor CDT1, its inhibitor geminin and survivin expression as regulators of chromosomal segregation. p16 gene transfer with radiation initiated the greatest degree of centrosome overduplication. CDT1 showed low levels, geminin was unchanged and survivin decreased in Ax-hp16-infected cells with radiation. Those changes of factors affecting DNA licensing or chromosomal segregation might contribute to CIN. p16 transfer caused centrosome amplification even in G1/S phase-arrested cells. This suggests that p16 is involved in abnormal nucleation and radiosensitization in human glioma cells. © 2015 S. Karger AG, Basel.


Glucocorticoid receptor DNA binding decoy is a gas.
The glucocorticoid receptor (GR) is a paradigmatic DNA binding transcription factor and was described over 20 years ago as one of the first proteins identified to bind the enhancer region of genes called "response elements." Since that time, an immense amount of work has revealed that GR transcriptional regulation is controlled at virtually every step of its activity: ligand binding, nuclear translocation, transcriptional cofactor binding, and DNA binding. Just when the major modes of GR regulation appear known, a new study provides yet another mechanism whereby GR transcriptional activity is controlled under conditions of cell growth arrest. In this case, GR activity is repressed by a small noncoding RNA (ncRNA) from the growth arrest-specific transcript 5 gene that folds into a soluble glucocorticoid response element-like sequence and serves as a decoy for GR DNA binding. This unexpected mode of regulation by nucleic acid molecular mimicry is probably not confined to GR and should spark interest in the hunt for other ncRNAs that regulate transcription factor binding to DNA.


Association of Gray Matter and Personality Development With Increased Drunkenness Frequency During Adolescence.
Alcohol abuse correlates with gray matter development in adolescents, but the directionality of this association remains unknown. To investigate the directionality of the association between gray matter development and increase in frequency of drunkenness among adolescents. This cohort study analyzed participants of IMAGEN, a multicenter brain imaging study of healthy adolescents in 8 European sites in Germany (Mannheim, Dresden, Berlin, and Hamburg), the United Kingdom (London and Nottingham), Ireland (Dublin), and France (Paris). Data from the second follow-up used in the present study were acquired from January 1, 2013, to December 31, 2016, and these data were analyzed from January 1, 2016, to March 31, 2018. Analyses were controlled for sex, site, socioeconomic status, family history of alcohol dependency, puberty score, negative life events, personality, cognition, and polygenic risk scores. Personality and frequency of drunkenness were assessed at age 14 years (baseline), 16 years (first follow-up), and 19 years (second follow-up). Structural brain imaging scans were acquired at baseline and second follow-up time points. Increases in drunkenness frequency were measured by latent growth modeling, a voxelwise hierarchical linear model was used to observe gray matter volume, and tensor-based morphometry was used for gray matter development. The hypotheses were formulated before the data analyses. A total of 726 adolescents (mean [SD] age at baseline, 14.4 [0.38] years; 418 [58%] female) were included. The increase in drunkenness frequency was associated with accelerated gray matter atrophy in the left posterior temporal cortex (peak: t1,710 = -5.8; familywise error (FWE)-corrected P = 7.2 × 10-5; cluster: 6297 voxels; P = 2.7 × 10-5), right posterior temporal cortex (cluster: 2070 voxels; FWE-corrected P = .01), and left prefrontal cortex (peak: t1,710 = -5.2; FWE-corrected P = 2 × 10-3; cluster: 10 624 voxels; P = 1.9 × 10-7). According to causal bayesian network analyses, 73% of the networks showed directionality from gray matter development to drunkenness increase as confirmed by accelerated gray matter atrophy in late bingers compared with sober controls (n = 20 vs 60; β = 1.25; 95% CI, -2.15 to -0.46; t1,70 = 0.3; P = .004), the association of drunkenness increase with gray matter volume at age 14 years (β = 0.23; 95% CI, 0.01-0.46; t1,584 = 2; P = .04), the association between gray matter atrophy and alcohol drinking units (β = -0.0033; 95% CI, -6 × 10-3 to -5 × 10-4; t1,509 = -2.4; P = .02) and drunkenness frequency at age 23 years (β = -0.16; 95% CI, -0.28 to -0.03; t1,533 = -2.5; P = .01), and the linear exposure-response curve stratified by gray matter atrophy and not by increase in frequency of drunkenness. This study found that gray matter development and impulsivity were associated with increased frequency of drunkenness by sex. These results suggest that neurotoxicity-related gray matter atrophy should be interpreted with caution.


Terahertz wireless communications based on photonics technologies.
There has been an increasing interest in the application of terahertz (THz) waves to broadband wireless communications. In particular, use of frequencies above 275 GHz is one of the strong concerns among radio scientists and engineers, because these frequency bands have not yet been allocated at specific active services, and there is a possibility to employ extremely large bandwidths for ultra-broadband wireless communications. Introduction of photonics technologies for signal generation, modulation and detection is effective not only to enhance the bandwidth and/or the data rate, but also to combine fiber-optic (wired) and wireless networks. This paper reviews recent progress in THz wireless communications using telecom-based photonics technologies towards 100 Gbit/s.


Economic evaluations with agent-based modelling: an introduction.
Agent-based modelling (ABM) is a relatively new technique, which overcomes some of the limitations of other methods commonly used for economic evaluations. These limitations include linearity, homogeneity and stationarity. Agents in ABMs are autonomous entities, who interact with each other and with the environment. ABMs provide an inductive or 'bottom-up' approach, i.e. individual-level behaviours define system-level components. ABMs have a unique property to capture emergence phenomena that otherwise cannot be predicted by the combination of individual-level interactions. In this tutorial, we discuss the basic concepts and important features of ABMs. We present a case study of an application of a simple ABM to evaluate the cost effectiveness of screening of an infectious disease. We also provide our model, which was developed using an open-source software program, NetLogo. We discuss software, resources, challenges and future research opportunities of ABMs for economic evaluations.


Neurofibroma of the urinary bladder.
Neurofibroma of the urinary bladder is rare. Only isolated case reports have appeared. Information regarding the long term follow-up of patients with neurofibroma is limited. The authors studied 4 cases of neurofibroma of the bladder diagnosed at Mayo Clinic from 1965 through 1990. Immunostains for S-100 protein, neurofilament protein, epithelial membrane antigen (EMA), cytokeratin (CAM 5.2; AE 1/3), Type IV collagen, MIB-1, and p53 protein were performed in all cases, as was Alcian blue at pH 2.5. The mean follow-up was 9.6 years (range, 2-18 years). The mean age at diagnosis was 17 years (range, 7-28 years); the male-to-female ratio was 1:1. All four patients exhibited physical stigmata of neurofibromatosis type 1. Clinical presentations included hematuria (one patient), irritative symptoms (two patients), and pelvic mass (one patient). Long term urinary complications included bladder atony (two patients), neurogenic bladder (one patient), and recurrent urinary tract infection with hematuria (one patient). Subsequently, two patients underwent partial cystectomy and one a complete cystectomy. Involvement of the bladder was generalized in all four cases. Three tumors were transmural, showing a diffuse and plexiform pattern of growth; in the fourth case, a superficial biopsy showed only diffuse submucosal growth with conspicuous pseudo-Meissnerian corpuscle formation. An Alcian blue positive, variably collagenized matrix was present in all cases. Tumor cells displayed immunoreactivity for S-100 protein and Type IV collagen in all cases. Neurofilament protein positive axons were evident in three cases; all other immunostains were negative. The mean MIB-1 labeling index was 3.2% (range, 0.9-7.3%). No malignant transformation was observed during a mean follow-up of 9.6 years. Neurofibroma of the bladder presents early in life, is of the plexiform type with a diffuse component, and usually occurs in the setting of generalized neurofibromatosis type 1 rather than as isolated visceral neurofibromatosis. Malignant transformation did not occur in any of these 4 patients during a mean follow-up time of 9.6 years.


The origin of the red emission in n-ZnO nanotubes/p-GaN white light emitting diodes.
In this article, the electroluminescence (EL) spectra of zinc oxide (ZnO) nanotubes/p-GaN light emitting diodes (LEDs) annealed in different ambients (argon, air, oxygen, and nitrogen) have been investigated. The ZnO nanotubes by aqueous chemical growth (ACG) technique on p-GaN substrates were obtained. The as-grown ZnO nanotubes were annealed in different ambients at 600°C for 30 min. The EL investigations showed that air, oxygen, and nitrogen annealing ambients have strongly affected the deep level emission bands in ZnO. It was concluded from the EL investigation that more than one deep level defect is involved in the red emission appearing between 620 and 750 nm and that the red emission in ZnO can be attributed to oxygen interstitials (Oi) appearing in the range from 620 nm (1.99 eV) to 690 nm (1.79 eV), and to oxygen vacancies (Vo) appearing in the range from 690 nm (1.79 eV) to 750 nm (1.65 eV). The annealing ambients, especially the nitrogen ambient, were also found to greatly influence the color-rendering properties and increase the CRI of the as - grown LEDs from 87 to 96.


Role of adenosine in the gastric blood flow response to pentagastrin in the rat.
We tested the hypothesis that the increase in gastric mucosal blood flow during pentagastrin-stimulated acid secretion in the rat is mediated partly by endogenously generated adenosine. In in vivo microscopic studies, topical 10(-5) to 10(-3) M adenosine dose-dependently dilated the submucosal arterioles, the vessels that control mucosal blood flow. The adenosine receptor antagonist 8-phenyltheophylline, significantly reduced adenosine's vasodilatory response. An adenosine analog with a high A2 receptor affinity was 100 times more potent as a vasodilator than one with a high A1 receptor affinity but lower A2 receptor affinity. We then examined the effect of i.v. 8-phenyltheophylline, 10 mg/kg, on the pentagastrin-stimulated increase in gastric blood flow and gastric acid secretion. Mucosal blood flow was estimated by the hydrogen clearance technique. Pentagastrin increased mucosal blood flow from 26.6 +/- 2.6 to 42.7 +/- 4.9 ml/min/100 g and this was reduced to 31.9 +/- 3.1 ml/min/100 g upon the addition of 8-phenyltheophylline. Gastric acid secretion upon the addition of 8-phenyltheophylline. Gastric acid secretion was stimulated by pentagastrin and stimulated further by the addition of 8-phenyltheophylline from 2.06 +/- 0.34 mEq of H+ per min to 2.84 +/- 0.49 mEq/min. 8-Phenyltheophylline had no effect on basal mucosal blood flow or gastric acid secretion. In contrast, the nonmethylxanthine phosphodiesterase inhibitor RO 20-1724 stimulated acid secretion and increased gastric mucosal blood flow during pentagastrin administration. The data suggest that gastric submucosal arterioles contain adenosine receptors of the A2 subtype that vasodilate when activated.(ABSTRACT TRUNCATED AT 250 WORDS)


Successful recanalization of chronic total occlusion of the superior mesenteric artery by transradial approach.
It is a challenge to confirm chronic mesenteric ischemia (CMI) as a cause of gastrointestinal (GI) symptoms such as postprandial epigastric bloating, anorexia, and debilitating weight loss. Endovascular intervention for CMI has been gaining popularity because of the high morbidity associated with surgical revascularization. However, in EVI for superior mesenteric artery (SMA) occlusion, the transfemoral approach is limited by difficulty in coaxial alignment of the guiding catheter, which leads to insufficient back-up support. Herein, we report on a 58-year-old male patient with chronic total occlusion of the SMA, which was successfully revascularized by endovascular intervention via the left radial artery. Transradial endovascular therapy may be another treatment option for the treatment of CMI.


Phonetic and phonological errors in children with high functioning autism and Asperger syndrome.
This study involved a qualitative analysis of speech errors in children with autism spectrum disorders (ASDs). Participants were 69 children aged 5-13 years; 30 had high functioning autism and 39 had Asperger syndrome. On a standardized test of articulation, the minority (12%) of participants presented with standard scores below the normal range, indicating a speech delay/disorder. Although all the other children had standard scores within the normal range, a sizeable proportion (33% of those with normal standard scores) presented with a small number of errors. Overall 41% of the group produced at least some speech errors. The speech of children with ASD was characterized by mainly developmental phonological processes (gliding, cluster reduction and final consonant deletion most frequently), but non-developmental error types (such as phoneme specific nasal emission and initial consonant deletion) were found both in children identified as performing below the normal range in the standardized speech test and in those who performed within the normal range. Non-developmental distortions occurred relatively frequently in the children with ASD and previous studies of adolescents and adults with ASDs shows similar errors, suggesting that they do not resolve over time. Whether or not speech disorders are related specifically to ASD, their presence adds an additional communication and social barrier and should be diagnosed and treated as early as possible in individual children.


Review of dose-intense platinum and/or paclitaxel containing chemotherapy in advanced and recurrent epithelial ovarian cancer.
Ovarian cancer is the most lethal gynecological cancer in women in the western world with a 5-year survival of 49.7%. Advanced stage ovarian cancer is treated both surgically and with chemotherapy, but despite initial high response rates of 60- 75%, many women experience disease recurrence with a dismal prognosis, 5 year overall survival for FIGO stage IIIc and IV disease being only 32 and 18%. In an attempt to improve outcome for both primary and recurrent disease, dose-intense and dose-dense chemotherapy regimens have been investigated. This overview summarizes these results in first and second-line treatment. In first-line treatment, no benefit was found of dose-intense regimes in the majority of the studies, only toxicity was increased. However, results are conflicting with the recent Japanese Gynecologic Oncology Group (JGOG) trial showing an improved progression free and overall survival in patients treated with dose-dense weekly paclitaxel combined with standard 3-weekly carboplatin. For recurrent disease dose-dense weekly combination chemotherapy seems to be very effective in patients with platinum-resistant ovarian cancer. Several phase II studies showed an increase in response rate, progression free survival and overall survival for dose-dense paclitaxel and carboplatin, compared to results of nonplatinum chemotherapy. In platinum-sensitive ovarian cancer, on contrary, the results of weekly paclitaxel and carboplatin seem to be comparable with standard 3-weekly regimens.


Drosophila melanogaster as a Model for Diabetes Type 2 Progression.
Drosophila melanogaster has been used as a very versatile and potent model in the past few years for studies in metabolism and metabolic disorders, including diabetes types 1 and 2. Drosophila insulin signaling, despite having seven insulin-like peptides with partially redundant functions, is very similar to the human insulin pathway and has served to study many different aspects of diabetes and the diabetic state. Yet, very few studies have addressed the chronic nature of diabetes, key for understanding the full-blown disease, which most studies normally explore. One of the advantages of having Drosophila mutant viable combinations at different levels of the insulin pathway, with significantly reduced insulin pathway signaling, is that the abnormal metabolic state can be studied from the onset of the life cycle and followed throughout. In this review, we look at the chronic nature of impaired insulin signaling. We also compare these results to the results gleaned from vertebrate model studies.


Identifying Clinical Study Types from PubMed Metadata: The Active (Machine) Learning Approach.
We examined a process for automating the classification of articles in MEDLINE aimed at minimising manual effort without sacrificing accuracy. From 22,808 articles pertaining to 19 antidepressants, 1000 were randomly selected and manually labelled according to article type (including, randomised controlled trials, editorials, etc.). We applied a machine learning approach termed 'active learning', where the learner (machine) selects the order in which the user (human) labels examples. Via simulation, we determined the number of articles a user needed to label to produce a classifier with at least 95% recall and 90% precision in three scenarios related to evidence synthesis. We found that the active learning process reduced the number of training instances required by 70%, 19%, and 14% in the three scenarios. The results show that the active learning method may be used in some scenarios to produce accurate classifiers that meet the needs of evidence synthesis tasks and reduce manual effort.


[Enigmatic archaeal viruses].
Viruses infecting microorganisms of the third domain of life, Archaea, are still poorly characterized: to date, only about fifty of these viruses have been isolated. Their hosts are hyperthermophilic, acidothermophilic, and extreme halophilic or methanogenic archaea. Their morphotypes are highly diverse and their gene content is very specific. Some of these viruses have developed extraordinary mechanisms to open the cell wall thanks to the formation of exceptional pyramidal nanostructures. The still limited knowledge about the biology of archaeoviruses should develop rapidly in the coming years.


Progressive mechanical ventilatory constraints with aging.
To investigate the progressive nature of mechanical ventilatory constraints with aging, we studied 20 young (age 39 +/- 3 yr), 14 senior (70 +/- 2 yr), and 11 elderly (88 +/- 2 yr) men and women during exercise. All subjects had normal pulmonary function and performed graded cycle ergometry to exhaustion. Minute ventilation (V E), lung volume, and expiratory airflow limitation (EAFL) were measured during each 1-min increment in work rate. Data were analyzed by two-way analysis of variance (ANOVA; age x gender) at rest, ventilatory threshold (VTh), and peak exercise. If an interaction was present, each gender was analyzed with a one-way ANOVA. Aging resulted in an increased V E for a given submaximal work rate, although V E during peak exercise was lowest in the elderly group (p < 0.01). End-expiratory lung volume (EELV, % of TLC) in men increased progressively with age and all groups were different at VTh (p < 0.01) and peak exercise (p < 0.01). In women, EELV (% of TLC) also increased with aging, the senior and elderly subjects had a greater EELV at VTh (p < 0.01) and peak exercise (p < 0.01) than the young group. Additionally, the normal decrease in EELV during the early stages of exercise was not observed in elderly subjects. End-inspiratory lung volume (EILV) also progressively increased with aging; senior and elderly subjects had a higher EILV at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than young subjects. EAFL (% of VT) increased with aging; elderly subjects experienced greater EAFL at rest (p < 0.05), VTh (p < 0.01), and peak exercise (p < 0.01) than both young and senior subjects. We conclude that mechanical ventilatory constraints are progressive with aging, elderly subjects demonstrating marked mechanical ventilatory constraints during exercise. The impact of these constraints on exercise tolerance cannot be determined from this investigation and remains unclear.


Stochastic binding of Staphylococcus aureus to hydrophobic surfaces.
The adhesion of pathogenic bacteria to surfaces is of immense importance for health care applications. Via a combined experimental and computational approach, we studied the initiation of contact in the adhesion process of the pathogenic bacterium Staphylococcus aureus. AFM force spectroscopy with single cell bacterial probes paired with Monte Carlo simulations enabled an unprecedented molecular investigation of the contact formation. Our results reveal that bacteria attach to a surface over distances far beyond the range of classical surface forces via stochastic binding of thermally fluctuating cell wall proteins. Thereby, the bacteria are pulled into close contact with the surface as consecutive proteins of different stiffnesses attach. This mechanism greatly enhances the attachment capability of S. aureus. It, however, can be manipulated by enzymatically/chemically modifying the cell wall proteins to block their consecutive binding. Our study furthermore reveals that fluctuations in protein density and structure are much more relevant than the exact form of the binding potential.


The epidemiology of ankle sprains in the United States.
Ankle sprain has been studied in athletic cohorts, but little is known of its epidemiology in the general population. A longitudinal, prospective epidemiological database was used to determine the incidence and demographic risk factors for ankle sprains presenting to emergency departments in the United States. It was our hypothesis that ankle sprain is influenced by sex, race, age, and involvement in athletics. The National Electronic Injury Surveillance System (NEISS) was queried for all ankle sprain injuries presenting to emergency departments between 2002 and 2006. Incidence rate ratios were then calculated with respect to age, sex, and race. During the study period, an estimated 3,140,132 ankle sprains occurred among an at-risk population of 1,461,379,599 person-years for an incidence rate of 2.15 per 1000 person-years in the United States. The peak incidence of ankle sprain occurred between fifteen and nineteen years of age (7.2 per 1000 person-years). Males, compared with females, did not demonstrate an overall increased incidence rate ratio for ankle sprain (incidence rate ratio, 1.04; 95% confidence interval, 1.00 to 1.09). However, males between fifteen and twenty-four years old had a substantially higher incidence of ankle sprain than their female counterparts (incidence rate ratio, 1.53; 95% confidence interval, 1.41 to 1.66), whereas females over thirty years old had a higher incidence compared with their male counterparts (incidence rate ratio, 2.03; 95% confidence interval, 1.65 to 2.65). Compared with the Hispanic race, the black and white races were associated with substantially higher rates of ankle sprain (incidence rate ratio, 3.55 [95% confidence interval, 1.01 to 6.09] and 2.49 [95% confidence interval, 1.01 to 3.97], respectively). Nearly half of all ankle sprains (49.3%) occurred during athletic activity, with basketball (41.1%), football (9.3%), and soccer (7.9%) being associated with the highest percentage of ankle sprains during athletics. An age of ten to nineteen years old is associated with higher rates of ankle sprain. Males between fifteen and twenty-four years old have higher rates of ankle sprain than their female counterparts, whereas females over thirty years old have higher rates than their male counterparts. Half of all ankle sprains occur during athletic activity.


Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.


Quantitative optimization of emergency department's nurses of an educational hospital: a case study.
Nurses account for the majority of human resources in hospitals, as such that 62% of the workforce and 36% of hospital expenditures are related to nurses. Considering its vital role in offering round-the-clock emergency healthcare services, an Emergency Department (ED) requires adequate nurses. Therefore, this study was conducted to optimize the number of nurses in ED. This was an applied study conducted using a Linear Programming (LP) model in 2015. The study population were selected by census who were all ED nurses (n=84) and patients referred to ED (n=3342). To obtain the statistics related to the number of patients and nurses, the hospital information system and human resources database were employed respectively. To determine the optimum number of nurses per shift, LP model was created via literature review and expert advice, and it was executed in WinQSB software. Before implementing the model, the number of nurses required for ED morning shift, evening shift, and night shift (2 shifts) was 26, 24 and 34 respectively. The optimum number of nurses who worked in ED after running the model was 62 nurses, 17 in the morning shift, 17 in the evening shift and 28 in the night shift (2 shifts). This reduced to 60 nurses after conducting sensitivity analysis. The estimated number of nurses using LP was less than the number of nurses working in ED. This discrepancy can be reduced by scientific understanding of factors affecting allocation and distribution of nurses in ED and flexible organization, to reach the optimal point.


Pedicle screws with a thin hydroxyapatite coating for improving fixation at the bone-implant interface in the osteoporotic spine: experimental study in a porcine model.
OBJECTIVE Instrumentation failure caused by the loosening of pedicle screws (PSs) in patients with osteoporosis is a serious problem after spinal surgery. The addition of a thin hydroxyapatite (HA) surface coating applied by using a sputtering process was reported recently to be a promising method for providing bone conduction around an implant without a significant risk of coating-layer breakage. In this study, the authors evaluated the biomechanical and histological features of the bone-implant interface (BII) of PSs with a thin HA coating in an in vivo porcine osteoporotic spine model. METHODS Three types of PSs (untreated/standard [STPS], sandblasted [BLPS], and HA-coated [HAPS] PSs) were implanted into the thoracic and lumbar spine (T9-L6) of 8 mature Clawn miniature pigs (6 ovariectomized [osteoporosis group] and 2 sham-operated [control group] pigs). The spines were harvested from the osteoporosis group at 0, 2, 4, 8, 12, or 24 weeks after PS placement and from the control group at 0 or 24 weeks. Their bone mineral density (BMD) was measured by peripheral quantitative CT. Histological evaluation of the BIIs was conducted by performing bone volume/tissue volume and bone surface/implant surface measurements. The strength of the BII was evaluated with extraction torque testing. RESULTS The BMD decreased significantly in the osteoporosis group (p < 0.01). HAPSs exhibited the greatest mean extraction peak torque at 8 weeks, and HAPSs and BLPSs exhibited significantly greater mean torque than the STPSs at 12 weeks (p < 0.05). The bone surface/implant surface ratio was significantly higher for HAPSs than for STPSs after 2 weeks (p < 0.05), and bonding between bone and the implant surface was maintained until 24 weeks with no detachment of the coating layer. In contrast, the bone volume/tissue volume ratio was significantly higher for HAPSs than for BLPSs or STPSs only at 4 weeks. CONCLUSIONS Using PSs with a thin HA coating applied using a sputtering process strengthens bonding at the BII, which might improve early implant fixation after spinal surgery for osteoporosis. However, the absence of increased bone mass around the screw remains a concern; prescribing osteoporosis treatment to improve bone quality might be necessary to prevent fractures around the screws.


Etiologies of acute, persistent, and dysenteric diarrheas in adults in Bangui, Central African Republic, in relation to human immunodeficiency virus serostatus.
A study of the etiologies of diarrhea in adults in relation to their human immunodeficiency virus (HIV) serostatus and number of CD4+ cells was carried out in the Central African Republic. In cases and controls, multi-parasitism was observed. Salmonella spp. were identified mainly during acute diarrhea, with 50% of the S. enteritidis isolated during the study being responsible for septicemia and/or urinary tract infection in immunodeficient patients. Enteroaggregative Escherichia coli (EAggEC) were the most frequently identified agent in HIV+ patients with persistent diarrhea; 42.8% of the patients with EAggEC as sole pathogens had bloody diarrhea, and these strains were negative for the presence of a virulence plasmid. Coccidia were found in those with acute and persistent diarrhea. Blood was observed in 53.3% of infections involving coccidia as the sole pathogen. Microsporidium spp. and Blastocystis hominis were found only in HIV+ patients with persistent diarrhea. Shigella spp., Campylobacter spp., and Entamoeba histolytica were found in HIV+ and HIV- dysenteric patients; bacteria resembling spirochetes that could not be cultivated were identified only in HIV+ cases with dysentery. Shiga-like toxin-producing E. coli O157:H- was isolated from two cases with hemolytic-uremic syndrome. Fungi were identified as the sole pathogen in 6.4% of the HIV+ patients with persistent diarrhea. Most of enteropathogenic bacteria identified were resistant to ampicillin and trimethoprim-sulfamethoxazole, remained susceptible to ampicillin plus clavulanic acid, and were susceptible to amikacin, gentamicin, and ciprofloxacin.


Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer.
The prognostic value of BRAF and KRAS mutations within microsatellite-unstable (MSI) and microsatellite-stable (MSS) subgroups of resected colon carcinoma patients remains controversial. We examined this question in prospectively collected biospecimens from stage III colon cancer with separate analysis of MSI and MSS tumors from patients receiving adjuvant FOLFOX +/- cetuximab in two adjuvant therapy trials. Three groups were defined: BRAF Mutant, KRAS Mutant, and double wild-type. The analytic strategy involved estimation of study-specific effects, assessment of homogeneity of results, and then analysis of pooled data as no differences in patient outcome were found between treatment arms in both trials. Associations of mutations with patient outcome were analyzed, and multivariable models were adjusted for treatment and relevant factors. Four thousand four hundred eleven tumors were evaluable for BRAF and KRAS mutations and mismatch repair status; 3934 were MSS and 477 were MSI. In MSS patients, all BRAF V600E mutations (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.23 to 1.92, P < .001), KRAS codon 12 alterations, and p.G13D mutations (HR = 1.60, 95% CI = 1.40 to 1.83, P < .001) were associated with shorter time to recurrence (TTR) and shorter survival after relapse (SAR; HR = 3.02 , 95% CI = 2.32 to 3.93, P < .001, and HR = 1.20, 95% CI = 1.01 to 1.44, P = .04, respectively). Overall survival (OS) in MSS patients was poorer for BRAF-mutant patients (HR = 2.01, 95% CI = 1.56 to 2.57, P < .001) and KRAS-mutant patients (HR = 1.62, 95% CI = 1.38 to 1.91, P < .001) vs wild-type. No prognostic role of KRAS or BRAF mutations was seen in MSI patients. Furthermore, no interaction was found between treatment arm (with or without cetuximab) and KRAS and BRAF mutations for TTR or OS in MSS patients. In a pooled analysis of resected stage III colon cancer patients receiving adjuvant FOLFOX, BRAF or KRAS mutations are independently associated with shorter TTR, SAR, and OS in patients with MSS, but not MSI, tumors. Future clinical trials in the adjuvant setting should consider these mutations as important stratification factors.


Immunization with a combination of integral chlamydial antigens and a defined secreted protein induces robust immunity against genital chlamydial challenge.
We have previously demonstrated the efficacy of recombinant chlamydial protease-like activity factor (rCPAF; a secreted chlamydial protein) in inducing antigen-specific CD4+ T cell/gamma interferon (IFN-gamma)-mediated but not antibody-mediated chlamydial clearance and reduction of upper genital tract (UGT) pathological sequelae. Since chlamydial integral antigens may induce neutralizing antibody protection, we further evaluated induction of protective immunity using a combination of rCPAF and UV-inactivated chlamydial elementary bodies (UV-EB) against vaginal chlamydial challenge in comparison to immunization with the individual components or live EB. The rCPAF-UV-EB immunization induced a significantly enhanced anti-UV-EB cellular and antibody response and a reduced anti-CPAF cellular and antibody response, compared to immunization with the respective individual components. Moreover, vaccination with UV-EB and rCPAF-UV-EB induced serum antibodies that neutralized chlamydial infectivity. The rCPAF-UV-EB immunization resulted in a significant reduction of vaginal chlamydial shedding and induced earlier bacterial clearance than vaccination of mice with the individual components. Importantly, the UGT sequelae were significantly reduced in mice immunized with rCPAF or rCPAF-UV-EB, but not in those immunized with UV-EB alone, and approached the levels of protection induced by live EB. These results collectively suggest that a combination of neutralizing antibodies induced by integral chlamydial antigens and cell-mediated responses induced by secreted proteins such as CPAF induces optimal protective immunity against genital chlamydial infections.


Multiscale mobility networks and the spatial spreading of infectious diseases.
Among the realistic ingredients to be considered in the computational modeling of infectious diseases, human mobility represents a crucial challenge both on the theoretical side and in view of the limited availability of empirical data. To study the interplay between short-scale commuting flows and long-range airline traffic in shaping the spatiotemporal pattern of a global epidemic we (i) analyze mobility data from 29 countries around the world and find a gravity model able to provide a global description of commuting patterns up to 300 kms and (ii) integrate in a worldwide-structured metapopulation epidemic model a timescale-separation technique for evaluating the force of infection due to multiscale mobility processes in the disease dynamics. Commuting flows are found, on average, to be one order of magnitude larger than airline flows. However, their introduction into the worldwide model shows that the large-scale pattern of the simulated epidemic exhibits only small variations with respect to the baseline case where only airline traffic is considered. The presence of short-range mobility increases, however, the synchronization of subpopulations in close proximity and affects the epidemic behavior at the periphery of the airline transportation infrastructure. The present approach outlines the possibility for the definition of layered computational approaches where different modeling assumptions and granularities can be used consistently in a unifying multiscale framework.


Calibration-free In Vitro Quantification of Protein Homo-oligomerization Using Commercial Instrumentation and Free, Open Source Brightness Analysis Software.
Number and brightness is a calibration-free fluorescence fluctuation spectroscopy (FFS) technique for detecting protein homo-oligomerization. It can be employed using a conventional confocal microscope equipped with digital detectors. A protocol for the use of the technique in vitro is shown by means of a use case where number and brightness can be seen to accurately quantify the oligomeric state of mVenus-labelled FKBP12F36V before and after the addition of the dimerizing drug AP20187. The importance of using the correct microscope acquisition parameters and the correct data preprocessing and analysis methods are discussed. In particular, the importance of the choice of photobleaching correction is stressed. This inexpensive method can be employed to study protein-protein interactions in many biological contexts.


The effect of symbiotic in the treatment of infantile colic: A double-blind, randomized, placebo-controlled clinical trial.
This study aims to evaluate the effect of symbiotic (Pedilact) on the treatment of infantile colic. In this randomized clinical trial in Zanjan, Iran, 76 infants with infantile colic were assigned to two groups of 38 cases using block randomization. The intervention group received 5 drops of Pedilact, a symbiotic containing Lactobacillus reuteri and simethicone (20 mg twice daily), and the control group received placebo in addition to simethicone for 4 weeks. Daily crying time, number of crying attacks per day, and sleep duration were recorded on days 1, 7, 14, 21, and 28, and the results were compared. Thirty-three infants in the intervention group and 35 infants in the control group were enrolled. There was no significant difference between the two groups in terms of age, gender, gestational age, maternal age, type of delivery, type of feeding, and weight at the beginning and the end of the study (all P > 0.05). Daily crying time in the control and intervention groups decreased from 240 and 210 min/day, respectively, to 0 min/day in both the groups. Daily crying attacks decreased from 5 and 4/day in the control and intervention groups, respectively, to 0/day. Sleep duration in both the groups increased from 720 to 840 and 930 min/day in the control and intervention groups, respectively, but the changes were not significant (P = 0.56, P = 0.52, and P = 0.13, respectively). We did not find a significant improvement in colic symptoms in infants receiving symbiotic compared to placebo.


Magnetic nanoparticle-based mass spectrometry for the detection of biomolecules in cultured cells.
We prepared functionalized magnetic nanoparticles (d = 3.5 nm) to serve as a laser desorption/ionization material for mass spectrometry. The obtained nanoparticles consisteds of a macaulayite core conjugated with hydroxyl and amino groups, and showed superparamagnetism at room temperature. The nanoparticles by themselves could ionize the sample peptide, drug and proteins (approx. 5000 Da) without causing background peaks. In the detection of biomolecules by mass spectrometry, the analytes are generally extracted from biological samples, and undergo futher purification and desaltation. However, these processing steps cause analyte loss. In the present study, we tried to detecting biomolecules in cultured cells without extraction or desaltation, but by using nanoparticles and a permanent magnet. The nanoparticles were introduced into living cells cultured on indium tin oxide-coated glass slides and accumulated on the surface of the cultured cells using an external magnetic field. The direct mass spectrometry of the cultured cells showed that we successfuly profiled the phospholipids of the cells. Our new nanoparticle-assisted laser desorption/ionization mass spectrometry technique is a quick and convenient way to profile biomolecules in cultured cells.


Transplanted astrocytes derived from BMP- or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury.
Two critical challenges in developing cell-transplantation therapies for injured or diseased tissues are to identify optimal cells and harmful side effects. This is of particular concern in the case of spinal cord injury, where recent studies have shown that transplanted neuroepithelial stem cells can generate pain syndromes. We have previously shown that astrocytes derived from glial-restricted precursor cells (GRPs) treated with bone morphogenetic protein-4 (BMP-4) can promote robust axon regeneration and functional recovery when transplanted into rat spinal cord injuries. In contrast, we now show that transplantation of GRP-derived astrocytes (GDAs) generated by exposure to the gp130 agonist ciliary neurotrophic factor (GDAs(CNTF)), the other major signaling pathway involved in astrogenesis, results in failure of axon regeneration and functional recovery. Moreover, transplantation of GDA(CNTF) cells promoted the onset of mechanical allodynia and thermal hyperalgesia at 2 weeks after injury, an effect that persisted through 5 weeks post-injury. Delayed onset of similar neuropathic pain was also caused by transplantation of undifferentiated GRPs. In contrast, rats transplanted with GDAs(BMP) did not exhibit pain syndromes. Our results show that not all astrocytes derived from embryonic precursors are equally beneficial for spinal cord repair and they provide the first identification of a differentiated neural cell type that can cause pain syndromes on transplantation into the damaged spinal cord, emphasizing the importance of evaluating the capacity of candidate cells to cause allodynia before initiating clinical trials. They also confirm the particular promise of GDAs treated with bone morphogenetic protein for spinal cord injury repair.


Physicians in health care management: 3. Case Mix Groups and Resource Intensity Weights: an overview for physicians.
In the first of two articles on the subject, the authors explain what Case Mix Groups (CMGs) and Resource Intensity Weights (RIWs) are and how they are used. The former categorize hospital patients into groups. The latter are ratios showing the relative use of hospital resources for a typical case (successful course of treatment in an acute care hospital and discharge when the patient no longer requires the hospital's services) and atypical cases (death, transfer, sign-out and substantially longer than average stay) in each CMG. As such, CMGs and RIWs define the relation between the medical and financial dimensions of hospital cases for use in planning and management. Ontario and Alberta are the first provinces to use them to adjust hospital funding. CMGs are limited by the number of diagnoses contained in each category, and RIWs are limited by the use of New York cost data due to the lack of Canadian data.


Ductal epithelial cells cultured from human foetal epididymis and vas deferens: relevance to sterility in cystic fibrosis.
A tissue culture system for epithelial cells derived from male human foetal genital ducts has been established. The cells show morphological and biochemical characteristics of ductal epithelial cells, and can be passaged and maintained in culture for considerable periods of time. These cells will provide a suitable system for investigating, by electrophysiological, biochemical and molecular biological methods, the cause of sterility in cystic fibrosis.


Serum aminotransferase levels in healthy population from western India.
Serum alanine aminotransferase (ALT) level is most commonly used as a marker for the assessment of various liver diseases. Currently upper limits of normal for aspartate aminotransferase (AST) or ALT levels used are based on the western literature. This study was conducted to determine the ALT and AST levels in healthy blood donors from western India and to determine the relation with body mass index (BMI) and waist-to-hip ratio (WHR). A total of 5077 voluntary blood donors were selected with strict routine inclusion and exclusion criteria. Weight, height, BMI and WHR were determined along with AST and ALT levels. BMI and WHR were correlated with liver enzymes. Of the 5077 donors, 160 were excluded due to positive serological results. In the remaining 4917 individuals, 4643 (94.4%) were males and 274 (5.6%) were females. Majority 3024 (61.5%) showed BMI more than 23 kg/m2. WHR > 0.85 and 0.80 was found in 4046 (87.0%) males and 250 (91.2%) females. Mean AST and ALT levels in males were 23.4 ± 9.9 IU/l and 27.0 ± 17.3 IU/l and in females 19.1 ± 9.8 IU/l and 17.7 ± 11.2 IU/l, respectively. With increase in BMI, there was a significant increase in AST and ALT levels. Similar increase was also seen with WHR. Majority of voluntary blood donors showed high BMI and WHR which was directly related to AST and ALT levels. This study highlights the magnitude of obesity in general healthy population of western India and a need to revise the current normal limits of serum ALT.


Bonding of mild self-etching primers/adhesives to dentin with thick smear layers.
To compare the microtensile bond strength (microTBS) and the ultrastructure of resin-dentin interfaces of four self-etching systems that were applied to dentin with thick smear layers. Human third molars were ground with 180-grit silicon carbide papers to expose deep coronal dentin. A 3-mm vertical slit was made along the diameter of each tooth to fit a glass cover slip, dividing each tooth into two bonding surfaces. Two 2-step, self-etching primers (ABF experimental system and Imperva Fluoro Bond) and two single-step, self-etching adhesives (One-Up Bond F and AQ Bond) were examined. Adhesives were applied to one side of the teeth passively, and to the other side with continuous agitation for the same self-etching period. Incremental composite buildups were performed and beams with cross-sectional areas of 0.81 mm2 were prepared for microTBS evaluation. Demineralized, bonded specimens were processed for TEM examination. Two-way ANOVA showed that both the adhesive type and the application mode significantly affected microTBS results. However, the interaction of these two factors was not statistically significant (P > 0.05). For each adhesive, agitation produced significantly higher microTBS than passive application. With passive application, all systems diffused through thick smear layers and formed thin hybrid layers in intact dentin. With continuous agitation, smear layers were completely dispersed or dissolved, and thicker hybrid layers with upstanding collagen fibrils were observed.


The human phosphatidylinositol phosphatase SAC1 interacts with the coatomer I complex.
The Saccharomyces cerevisiae SAC1 gene encodes an integral membrane protein of the endoplasmic reticulum (ER) and the Golgi apparatus. Yeast SAC1 mutants display a wide array of phenotypes including inositol auxotrophy, cold sensitivity, secretory defects, disturbed ATP transport into the ER, or suppression of actin gene mutations. At present, it is not clear how these phenotypes relate to the finding that SAC1 displays polyphosphoinositide phosphatase activity. Moreover, it is still an open question whether SAC1 functions similarly in mammalian cells, since some phenotypes are yeast-specific. Potential protein interaction partners and, connected to that, possible regulatory circuits have not been described. Therefore, we have cloned human SAC1 (hSAC1), show that it behaves similar to ySac1p in terms of substrate specificity, demonstrate that the endogenous protein localizes to the ER and Golgi, and identify for the first time members of the coatomer I (COPI) complex as interaction partners of hSAC1. Mutation of a putative COPI interaction motif (KXKXX) at its C terminus abolishes interaction with COPI and causes accumulation of hSAC1 in the Golgi. In addition, we generated a catalytically inactive mutant, demonstrate that its lipid binding capacity is unaltered, and show that it accumulates in the Golgi, incapable of interacting with the COPI complex despite the presence of the KXKXX motif. These results open the possibility that the enzymatic function of hSAC1 provides a switch for accessibility of the COPI interaction motif.


Polyglandular autoimmune syndrome type I among Iranian Jews.
Polyglandular autoimmune syndrome (PAS) has been well characterised and the accepted criteria for diagnosis are the presence of at least two of the three major components: hypoparathyroidism (HPT), candidiasis, and adrenal insufficiency (AI). HPT may, however, be the only manifestation of the syndrome. Iranian Jews, having a high rate of consanguinity, appear to be a community in which PAS type I is frequent. We report on 19 families of patients with HPT from the Iranian Jewish community assuming that they are in fact affected with PAS type I. In the 19 families, 23 patients were affected, including 11 males and 12 females. All the patients but one had HPT (96%), and most were diagnosed by the age of 20 years (91%). AI was diagnosed in five of our patients; in all cases but one it appeared after HPT. Mild oral candidiasis was present in four patients and six of the patients (three males and three females) had hypogonadism. Other features of the syndrome found in some of our patients were pernicious anaemia, hypothyroidism, and alopecia. The disease is autosomal recessive and the calculated prevalence among the Iranian Jews is 1:6500 to 1:9000. The disease is also found with a very high incidence among Finns. A comparison of the symptoms between the two groups showed clinical differences including the relative rarity of candidiasis and absence of keratopathy among the Iranian Jews.


The spatial representation of time can be flexibly oriented in the frontal or lateral planes from an early age.
The perception of time is strongly influenced by spatial context. The longer the distance of a stimulus' trajectory, the longer its duration is perceived to be. This effect has primarily been investigated in the lateral (left-right) axis despite the fact that spatial metaphors for time most commonly invoke the frontal (front-back) axis. We therefore explored how spatial distance, depth, and direction influenced perceived duration of stimuli moving in the frontal or lateral axes. Moreover, we compared the developmental trajectories of frontal versus lateral representations of time by testing children (5, 7, or 10 years old) and adults. Results showed that perceived duration of the interval between 2 consecutive stimuli in a temporal bisection task was biased by distance in the frontal, as well as lateral, plane across all age groups. Even the mere impression of distance in depth (Ponzo illusion), was sufficient to produce these effects. These findings indicate that the spatial representation of time can be oriented flexibly in either frontal or lateral planes from the age of 5 years and even precedes the development of explicit timing mechanisms. Motion direction in the frontal plane (looming/receding) had little effect on perceived duration in adults, though children temporally underestimated looming stimuli, possibly due to attentional mechanisms. (PsycINFO Database Record


Heart rate variability in left ventricular hypertrophy.
Electrocardiographic left ventricular hypertrophy and strain are associated with increased cardiac morbidity and mortality. Impaired cardiac autonomic function, assessed non-invasively by spontaneous heart rate variability on Holter monitoring, is associated with an increased risk of sudden death after myocardial infarction. To study the effect of left ventricular hypertrophy on heart rate variability. 36 controls and 154 patients with left ventricular hypertrophy (94 with hypertension and 60 with aortic valve disease). Tertiary referral centre. Heart rate variability was measured on 24 h Holter recordings by non-spectral methods. Left ventricular mass index and fractional shortening were measured by echocardiography. Patients with left ventricular hypertrophy had a higher left ventricular mass index (P < 0.001) and reduced heart rate variability (P < 0.001) compared with those of the controls. A continuous inverse relation was apparent between heart rate variability and left ventricular mass index (r = -0.478, P < 0.001). Heart rate variability was not affected by age, the presence of coronary artery disease in patients with left ventricular hypertrophy, or beta blocker treatment for hypertension. Multivariate analysis showed that left ventricular mass index is the most important determinant of heart rate variability. Heart rate variability is significantly reduced in patients with left ventricular hypertrophy secondary to hypertension or aortic valve disease. A continuous inverse relation exists between heart rate variability and left ventricular mass index. Impaired cardiac autonomic function in left ventricular hypertrophy may contribute to the mechanism of sudden death.


Guidelines for the conduct of clinical trials in spinal cord injury: Neuroimaging biomarkers.
Traumatic spinal cord injury (SCI) leads to immediate neuronal and axonal damage at the focal injury site and triggers secondary pathologic series of events resulting in sensorimotor and autonomic dysfunction below the level of injury. Although there is no cure for SCI, neuroprotective and regenerative therapies show promising results at the preclinical stage. There is a pressing need to develop non-invasive outcome measures that can indicate whether a candidate therapeutic agent or a cocktail of therapeutic agents are positively altering the underlying disease processes. Recent conventional MRI studies have quantified spinal cord lesion characteristics and elucidated their relationship between severity of injury to clinical impairment and recovery. Next to the quantification of the primary cord damage, quantitative MRI measures of spinal cord (rostrocaudally to the lesion site) and brain integrity have demonstrated progressive and specific neurodegeneration of afferent and efferent neuronal pathways. MRI could therefore play a key role to ultimately uncover the relationship between clinical impairment/recovery and injury-induced neurodegenerative changes in the spinal cord and brain. Moreover, neuroimaging biomarkers hold promises to improve clinical trial design and efficiency through better patient stratification. The purpose of this narrative review is therefore to propose a guideline of clinically available MRI sequences and their derived neuroimaging biomarkers that have the potential to assess tissue damage at the macro- and microstructural level after SCI. In this piece, we make a recommendation for the use of key MRI sequences-both conventional and advanced-for clinical work-up and clinical trials.


Sciatica of nondisc origin and piriformis syndrome: diagnosis by magnetic resonance neurography and interventional magnetic resonance imaging with outcome study of resulting treatment.
Because lumbar magnetic resonance (MR) imaging fails to identify a treatable cause of chronic sciatica in nearly 1 million patients annually, the authors conducted MR neurography and interventional MR imaging in 239 consecutive patients with sciatica in whom standard diagnosis and treatment failed to effect improvement. After performing MR neurography and interventional MR imaging, the final rediagnoses included the following: piriformis syndrome (67.8%), distal foraminal nerve root entrapment (6%), ischial tunnel syndrome (4.7%), discogenic pain with referred leg pain (3.4%), pudendal nerve entrapment with referred pain (3%), distal sciatic entrapment (2.1%), sciatic tumor (1.7%), lumbosacral plexus entrapment (1.3%), unappreciated lateral disc herniation (1.3%), nerve root injury due to spinal surgery (1.3%), inadequate spinal nerve root decompression (0.8%), lumbar stenosis (0.8%), sacroiliac joint inflammation (0.8%), lumbosacral plexus tumor (0.4%), sacral fracture (0.4%), and no diagnosis (4.2%). Open MR-guided Marcaine injection into the piriformis muscle produced the following results: no response (15.7%), relief of greater than 8 months (14.9%), relief lasting 2 to 4 months with continuing relief after second injection (7.5%), relief for 2 to 4 months with subsequent recurrence (36.6%), and relief for 1 to 14 days with full recurrence (25.4%). Piriformis surgery (62 operations; 3-cm incision, transgluteal approach, 55% outpatient; 40% with local or epidural anesthesia) resulted in excellent outcome in 58.5%, good outcome in 22.6%, limited benefit in 13.2%, no benefit in 3.8%, and worsened symptoms in 1.9%. This Class A quality evaluation of MR neurography's diagnostic efficacy revealed that piriformis muscle asymmetry and sciatic nerve hyperintensity at the sciatic notch exhibited a 93% specificity and 64% sensitivity in distinguishing patients with piriformis syndrome from those without who had similar symptoms (p < 0.01). Evaluation of the nerve beyond the proximal foramen provided eight additional diagnostic categories affecting 96% of these patients. More than 80% of the population good or excellent functional outcome was achieved.


Single-molecule electronics: from chemical design to functional devices.
The use of single molecules in electronics represents the next limit of miniaturisation of electronic devices, which would enable us to continue the trend of aggressive downscaling of silicon-based electronic devices. More significantly, the fabrication, understanding and control of fully functional circuits at the single-molecule level could also open up the possibility of using molecules as devices with novel, not-foreseen functionalities beyond complementary metal-oxide semiconductor technology (CMOS). This review aims at highlighting the chemical design and synthesis of single molecule devices as well as their electrical and structural characterization, including a historical overview and the developments during the last 5 years. We discuss experimental techniques for fabrication of single-molecule junctions, the potential application of single-molecule junctions as molecular switches, and general physical phenomena in single-molecule electronic devices.


Targeted loss of Arx results in a developmental epilepsy mouse model and recapitulates the human phenotype in heterozygous females.
Mutations in the X-linked aristaless-related homeobox gene (ARX) have been linked to structural brain anomalies as well as multiple neurocognitive deficits. The generation of Arx-deficient mice revealed several morphological anomalies, resembling those observed in patients and an interneuron migration defect but perinatal lethality precluded analyses of later phenotypes. Interestingly, many of the neurological phenotypes observed in patients with various ARX mutations can be attributed, in part, to interneuron dysfunction. To directly test this possibility, mice carrying a floxed Arx allele were generated and crossed to Dlx5/6(CRE-IRES-GFP)(Dlx5/6(CIG)) mice, conditionally deleting Arx from ganglionic eminence derived neurons including cortical interneurons. We now report that Arx(-/y);Dlx5/6(CIG) (male) mice exhibit a variety of seizure types beginning in early-life, including seizures that behaviourally and electroencephalographically resembles infantile spasms, and show evolution through development. Thus, this represents a new genetic model of a malignant form of paediatric epilepsy, with some characteristics resembling infantile spasms, caused by mutations in a known infantile spasms gene. Unexpectedly, approximately half of the female mice carrying a single mutant Arx allele (Arx(-/+);Dlx5/6(CIG)) also developed seizures. We also found that a subset of human female carriers have seizures and neurocognitive deficits. In summary, we have identified a previously unrecognized patient population with neurological deficits attributed to ARX mutations that are recapitulated in our mouse model. Furthermore, we show that perturbation of interneuron subpopulations is an important mechanism underling the pathogenesis of developmental epilepsy in both hemizygous males and carrier females. Given the frequency of ARX mutations in patients with infantile spasms and related disorders, our data unveil a new model for further understanding the pathogenesis of these disorders.


Incidence and prevalence of amyotrophic lateral sclerosis in urban China: a national population-based study.
Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative disease and information on disease burden of ALS in mainland China was limited. We aimed to estimate the prevalence and incidence of ALS in China. We used 2012-2016 data from China's Urban Employee Basic Medical Insurance and Urban Residence Basic Medical Insurance, covering approximately 0.43 billion individuals. ALS cases were identified by the primary diagnosis (International Classification of Diseases code or text of diagnosis) in the insurance database. The crude prevalence and incidence in 2016 were 2.91 per 100 000 person-years (95% CI 2.31 to 3.58) and 1.65 (95% CI 1.33 to 2.01), respectively. The standardised prevalence and incidence based on 2010 Chinese census data were 2.97 (95% CI 2.91 to 3.03) and 1.62 (95% CI 1.58 to 1.67), respectively. The annual prevalence between 2013 and 2016 remained relatively constant, ranging from 2.91 (95% CI 2.31 to 3.58) in 2016 to 3.29 (95% CI 2.51 to 4.17) in 2014 (linear regression: β=-0.129, p=0.104). Both rates peaked in the group aged 75-79 years. The prevalence and incidence of ALS in mainland China were lower than those in developed countries, and maintained a relatively stable trend. The age at onset and age at diagnosis for ALS patients were younger than those in developed countries. Further research is expected to clarify the potential pathophysiological mechanism of ALS.


A comparison of open surgery versus endovascular repair of unstable ruptured abdominal aortic aneurysms.
Two randomized trials to date have compared open surgery (OS) and endovascular (EVAR) repair for ruptured abdominal aortic aneurysm (rAAA); however, neither addressed optimal management of unstable patients. Single-center reports have produced conflicting data regarding the superiority of one vs the other, with the lack of statistical power due to low patient numbers. Furthermore, previous studies have not delineated between the outcomes of stable patients with a contained rupture vs those patients with instability. Our objective was to compare 30-day outcomes in patients undergoing OS vs EVAR for all rAAAs, focusing specifically on patients with instability. Patients who underwent repair of rAAA were identified from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database (2005 to 2010). Unstable patients with rupture were identified as those who were American Society of Anesthesiologists Physical Status Classification 4 or 5 requiring emergency repair with at least one of the following: preoperative shock, preoperative transfusion of >4 units, preoperative intubation, or preoperative coma or impaired sensorium. Univariable and multivariable logistic regression analyses were performed. Of the 1447 patients with rAAA, 65.5% underwent OS and 34.5% EVAR. Forty-five percent were unstable, and for these patients, OS was performed in 71.3% and EVAR in 28.7%. The 30-day mortality rate was 47.9% (OS, 52.8%; EVAR, 35.6%; P < .0001) for unstable rAAAs and was 22.4% for stable rAAAs (OS, 26.3%; EVAR, 16.4%; P = .001). Amongst patients with unstable rAAA, 26% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 29.0%; EVAR, 19.1%; P = .006), and 17% needed postoperative dialysis (OS, 18.7%; EVAR, 12.8%; P = .04). Amongst patients with stable rAAA, 13.6% had a myocardial infarction or cardiac arrest ≤ 30 days (OS, 14.9%; EVAR, 11.6%; P = .20), and 11.5% needed postoperative dialysis (OS, 13.3%; EVAR, 8.7%; P = .047). Multivariable analyses showed OS was a predictor of 30-day mortality for unstable rAAA (odds ratio, 1.74; 95% confidence interval, 1.16-2.62) and stable rAAA (odds ratio, 1.64; 95% confidence interval, 1.10-2.43). Approximately one-third of patients treated for rAAA undergo EVAR in NSQIP participating hospitals. Not surprisingly, unstable patients have less favorable outcomes. In both stable and unstable rAAA patients, EVAR is associated with a diminished 30-day mortality and morbidity.


Discrete element modelling of under sleeper pads using a box test.
It has recently been reported that under sleeper pads (USPs) could improve ballasted rail track by decreasing the sleeper settlement and reducing particle breakage. In order to find out what happens at the particle-pad interface, discrete element modelling (DEM) is used to provide micro mechanical insight. The same positive effects of USP are found in the DEM simulations. The evidence provided by DEM shows that application of a USP allows more particles to be in contact with the pad, and causes these particles to transfer a larger lateral load to the adjacent ballast but a smaller vertical load beneath the sleeper. This could be used to explain why the USP helps to reduce the track settlement. In terms of particle breakage, it is found that most breakage occurs at the particle-sleeper interface and along the main contact force chains between particles under the sleeper. The use of USPs could effectively reduce particle abrasion that occurs in both of these regions.


Future warming and acidification result in multiple ecological impacts to a temperate coralline alga.
Coralline algae are a crucial component of reef systems, stabilising reef substrate, providing habitat and contributing to accretion. Coralline algae and their surface microbial biofilms are also important as settlement cues for marine invertebrates, yet few studies address the impact of future environmental conditions on interactions between coralline algae, reef microbes and settlement by larvae of marine invertebrates. We exposed the temperate coralline algal species Amphiroa gracilis to warming and/or acidification scenarios for 21 days. Algae became bleached but photosystem II function was not measurably impacted. Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and the structure of the prokaryotic community associated with A. gracilis was altered. Coralline algae in ambient conditions were dominated by Alphaproteobacteria from the Rhodobacteraceae including Loktonella; those under warming were dominated by Bacteroidetes and Verrucomicrobia; acidification resulted in less Loktonella and more Planctomycetes and a combination of warming and acidification caused increases in Bacteroidetes, Verrucomicrobia and the Alphaproteobacteria family Hyphomonadaceae. These experiments indicate that predicted future environmental change may reduce the ability of some temperate reef coralline algae and associated reef microbes to facilitate settlement of invertebrate larvae as well as having a direct impact to algae via bleaching.


Inversion of pop-out for a distracting feature dimension in monkey visual cortex.
During visual search, it is important to reduce the interference of distracting objects in the scene. The neuronal responses elicited by the search target stimulus are typically enhanced. However, it is equally important to suppress the representations of distracting stimuli, especially if they are salient and capture attention. We trained monkeys to make an eye movement to a unique "pop-out" shape stimulus among an array of distracting stimuli. One of these distractors had a salient color that varied across trials and differed from the color of the other stimuli, causing it to also pop-out. The monkeys were able to select the pop-out shape target with high accuracy and actively avoided the pop-out color distractor. This behavioral pattern was reflected in the activity of neurons in area V4. Responses to the shape targets were enhanced, while the activity evoked by the pop-out color distractor was only briefly enhanced, directly followed by a sustained period of pronounced suppression. These behavioral and neuronal results demonstrate a cortical selection mechanism that rapidly inverts a pop-out signal to "pop-in" for an entire feature dimension thereby facilitating goal-directed visual search in the presence of salient distractors.


Size-dependent kinetics of hydriding and dehydriding of Pd nanoparticles.
Using a new indirect nanoplasmonic sensing method with subsecond resolution, we have studied hydriding and dehydriding kinetics of Pd nanoparticles in the size range 1.8-5.4 nm. Strong particle-size effects are observed. The scaling of the hydriding and dehydriding time scales satisfies power and power-exponential laws. The former (with an exponent of 2.9) is in perfect agreement with Monte Carlo simulations of diffusion-controlled hydriding kinetics. The latter is explained by the effect of surface tension on hydrogen desorption from the surface layer. The approach is generalizable to other reactant-nanoparticle systems.


Identification and characterization of alternative promoters of zebrafish Rtn-4/Nogo genes in cultured cells and zebrafish embryos.
In mammals, the Nogo family consists of Nogo-A, Nogo-B and Nogo-C. However, there are three Rtn-4/Nogo-related transcripts were identified in zebrafish. In addition to the common C-terminal region, the N-terminal regions of Rtn4-n/Nogo-C1, Rtn4-m/Nogo-C2 and Rtn4-l/Nogo-B, respectively, contain 9, 25 and 132 amino acid residues. In this study, we isolated the 5'-upstream region of each gene from a BAC clone and demonstrated that the putative promoter regions, P1-P3, are functional in cultured cells and zebrafish embryos. A transgenic zebrafish Tg(Nogo-B:GFP) line was generated using P1 promoter region to drive green fluorescent protein (GFP) expression through Tol2-mediated transgenesis. This line recapitulates the endogenous expression pattern of Rtn4-l/Nogo-B mRNA in the brain, brachial arches, eyes, muscle, liver and intestines. In contrast, GFP expressions by P2 and P3 promoters were localized to skeletal muscles of zebrafish embryos. Several GATA and E-box motifs are found in these promoter regions. Using morpholino knockdown experiments, GATA4 and GATA6 were involved in the control of P1 promoter activity in the liver and intestine, while Myf5 and MyoD for the control of P1 and P3 promoter activities in muscles. These data demonstrate that zebrafish Rtn4/Nogo transcripts might be generated by coupling mechanisms of alternative first exons and alternative promoter usage.


Neuromuscular function in limb girdle dystrophy.
The contractile properties of ankle dorsiflexor and plantarflexor muscles in 20 patients with limb girdle muscular dystrophy have been compared with those in matched controls. Twitch and voluntary torques were significantly smaller in the patient population and in nine patients it was impossible to record a twitch from tibialis anterior, a dorsiflexor muscle studied in detail. The disease process evidently ran a more rapid course in tibialis anterior than in plantarflexor muscles and this susceptibility was related to some aspect of the muscle other than its fibre type composition. Surviving fibres in dorsiflexor and plantarflexor muscles did not reveal evidence of excitation-contraction uncoupling; they exhibited normal post-activation potentiation and fatigue properties. Some patients were initially incapable of exciting their motor units maximally during voluntary contractions. A finding of possible pathogenetic significance was that one patient, with prominent calves, developed exceptionally large voluntary torque in his plantarflexor muscles.


Exactly solvable model for self-assembly of hard core-soft shell particles at interfaces.
A generic model for self-assembly of a monolayer of hybrid core-shell particles at an interface is developed. We assume that for distances larger than the size of the incompressible core a soft repulsion appears, and the repulsion is followed by an attraction at larger separations. The model is solved exactly in a one-dimensional lattice version. One, two or three periodic structures and variety of shapes of the pressure-density isotherms may occur in different versions of the model. For strong interactions the isotherm consists of nearly vertical segments at densities optimal for the periodic structures that are connected by segments with a small slope. The range of order depends very strongly on the strength of attraction and on the density. Our results agree with experimental observations.


Meat and mental health: A meta-analysis of meat consumption, depression, and anxiety.
In this meta-analysis, we examined the quantitative relation between meat consumption or avoidance, depression, and anxiety. In June 2020, we searched five online databases for primary studies examining differences in depression and anxiety between meat abstainers and meat consumers that offered a clear (dichotomous) distinction between these groups. Twenty studies met the selection criteria representing 171,802 participants with 157,778 meat consumers and 13,259 meat abstainers. We calculated the magnitude of the effect between meat consumers and meat abstainers with bias correction (Hedges's g effect size) where higher and positive scores reflect better outcomes for meat consumers. Meat consumption was associated with lower depression (Hedges's g = 0.216, 95% CI [0.14 to 0.30], p < .001) and lower anxiety (g = 0.17, 95% CI [0.03 to 0.31], p = .02) compared to meat abstention. Compared to vegans, meat consumers experienced both lower depression (g = 0.26, 95% CI [0.01 to 0.51], p = .041) and anxiety (g = 0.15, 95% CI [-0.40 to 0.69], p = .598). Sex did not modify these relations. Study quality explained 58% and 76% of between-studies heterogeneity in depression and anxiety, respectively. The analysis also showed that the more rigorous the study, the more positive and consistent the relation between meat consumption and better mental health. The current body of evidence precludes causal and temporal inferences.


Relationship of obesity and physical activity with C-peptide, leptin, and insulin-like growth factors in breast cancer survivors.
Obese and physically inactive breast cancer patients may have poorer survival compared with lighter weight and more active women. Several obesity-related and physical activity-related hormones and peptides may explain this association, including insulin, leptin, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3. Few studies have examined the associations between obesity, physical activity, and these hormones/peptides among breast cancer survivors. To determine whether obesity and physical activity are associated with insulin, IGFs, and leptin levels in a population-based sample of 710 women diagnosed with in situ to stage IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. We collected a blood sample and information on physical activity among women diagnosed 2 to 3 years earlier using an interview-administered questionnaire. Trained staff measured weight. C-peptide, leptin, and IGFs were assayed by RIA. Mean hormone levels within body mass index and physical activity categories were adjusted for confounders using analysis of covariance methods. We observed higher C-peptide (P for trend = 0.0001) and leptin (P for trend = 0.0001) levels and lower IGF-I levels (P for trend = 0.0001) with higher levels of body mass index. We observed lower C-peptide (P for trend = 0.001) and leptin (P for trend = 0.001) levels and higher IGF-I (P for trend = 0.0037) and IGF-binding protein-3 (P for trend = 0.055) levels with higher levels of physical activity. Increasing physical activity and decreasing body fat may be a reasonable intervention approach toward changing insulin and leptin, thereby potentially influencing breast cancer prognosis.


Effects of climate changes on skin diseases.
Global climate is changing at an extraordinary rate. Climate change (CC) can be caused by several factors including variations in solar radiation, oceanic processes, and also human activities. The degree of this change and its impact on ecological, social, and economical systems have become important matters of debate worldwide, representing CC as one of the greatest challenges of the modern age. Moreover, studies based on observations and predictive models show how CC could affect human health. On the other hand, only a few studies focus on how this change may affect human skin. However, the skin is the most exposed organ to environment; therefore, it is not surprising that cutaneous diseases are inclined to have a high sensitivity to climate. The current review focuses on the effects of CC on skin diseases showing the numerous factors that are contributing to modify the incidence, clinical pattern and natural course of some dermatoses.


Sperm mobility: mechanisms of fertilizing efficiency, genetic variation and phenotypic relationship with male status in the domestic fowl, Gallus gallus domesticus.
When females are sexually promiscuous, sexual selection continues after insemination through sperm competition and cryptic female choice, and male traits conveying an advantage in competitive fertilization are selected for. Although individual male and ejaculate traits are known to influence paternity in a competitive scenario, multiple mechanisms co-occur and interact to determine paternity. The way in which different traits interact with each other and the mechanisms through which their heritability is maintained despite selection remain unresolved. In the promiscuous fowl, paternity is determined by the number of sperm inseminated into a female, which is mediated by male social dominance, and by the quality of the sperm inseminated, measured as sperm mobility. Here we show that: (i) the number of sperm inseminated determines how many sperm reach the female sperm-storage sites, and that sperm mobility mediates the fertilizing efficiency of inseminated sperm, mainly by determining the rate at which sperm are released from the female storage sites, (ii) like social status, sperm mobility is heritable, and (iii) subdominant males are significantly more likely to have higher sperm mobility than dominant males. This study indicates that although the functions of social status and sperm mobility are highly interdependent, the lack of phenotypic integration of these traits may maintain the variability of male fitness and heritability of fertilizing efficiency.


Cancer risk in diethylstilbestrol-exposed offspring.
The occurrence of columnar epithelium in the vagina (vaginal adenosis) in young women with intrauterine exposure to diethylstilbestrol (DES) during the first trimester of pregnancy was observed in 231 patients (82 per cent of 280 cases who underwent colposcopic study). Extension of columnar epithelium onto the portio of the cervix was present in the remaining 18 per cent of the cases. Abnormal colposcopic findings were present in the transformation zone in 96 per cent of the patients with vaginal adenosis. Directed biopsy revealed four cases of vaginal and/or cervical squamous carcinoma in situ (CIS), two cases of severe dysplasia, five cases of moderate, and 29 cases of mild dysplasia. The prevalence of CIS in DES-exposed girls (1.4 per cent) was nearly five times the prevalence rate of CIS in a control group of 5,808 DES-unexposed women (0.44 per cent). This finding correlates well with the hypothesis that the genesis of squamous intraepithelial neoplasia is specifically related to the extent and surface area of the vaginal transformation zone. An unusual case of invasive squamous carcinoma in a DES-exposed young girl is presented, which represents the initial observation of this association to date.


Shorter telomeres in peripheral blood mononuclear cells from older persons with sarcopenia: results from an exploratory study.
Telomere shortening in peripheral blood mononuclear cells (PBMCs) has been associated with biological age and several chronic degenerative diseases. However, the relationship between telomere length and sarcopenia, a hallmark of the aging process, is unknown. The aim of the present study was therefore to determine whether PBMC telomeres obtained from sarcopenic older persons were shorter relative to non-sarcopenic peers. We further explored if PBMC telomere length was associated with frailty, a major clinical correlate of sarcopenia. Analyses were conducted in 142 persons aged ≥65 years referred to a geriatric outpatient clinic (University Hospital). The presence of sarcopenia was established according to the European Working Group on Sarcopenia in Older People criteria, with bioelectrical impedance analysis used for muscle mass estimation. The frailty status was determined by both the Fried's criteria (physical frailty, PF) and a modified Rockwood's frailty index (FI). Telomere length was measured in PBMCs by quantitative real-time polymerase chain reaction according to the telomere/single-copy gene ratio (T/S) method. Among 142 outpatients (mean age 75.0 ± 6.5 years, 59.2% women), sarcopenia was diagnosed in 23 individuals (19.3%). The PF phenotype was detected in 74 participants (52.1%). The average FI score was 0.46 ± 0.17. PBMC telomeres were shorter in sarcopenic subjects (T/S = 0.21; 95% CI: 0.18-0.24) relative to non-sarcopenic individuals (T/S = 0.26; 95% CI: 0.24-0.28; p = 0.01), independent of age, gender, smoking habit, or comorbidity. No significant associations were determined between telomere length and either PF or the FI. PBMC telomere length, expressed as T/S values, is shorter in older outpatients with sarcopenia. The cross-sectional assessment of PBMC telomere length is not sufficient at capturing the complex, multidimensional syndrome of frailty.


Phytoscreening with SPME: Variability Analysis.
Phytoscreening has been demonstrated at a variety of sites over the past 15 years as a low-impact, sustainable tool in delineation of shallow groundwater contaminated with chlorinated solvents. Collection of tree cores is rapid and straightforward, but low concentrations in tree tissues requires sensitive analytics. Solid-phase microextraction (SPME) is amenable to the complex matrix while allowing for solvent-less extraction. Accurate quantification requires the absence of competitive sorption, examined here both in laboratory experiments and through comprehensive examination of field data. Analysis of approximately 2,000 trees at numerous field sites also allowed testing of the tree genus and diameter effects on measured tree contaminant concentrations. Collectively, while these variables were found to significantly affect site-adjusted perchloroethylene (PCE) concentrations, the explanatory power of these effects was small (adjusted R(2) = 0.031). 90th quantile chemical concentrations in trees were significantly reduced by increasing Henry's constant and increasing hydrophobicity. Analysis of replicate tree core data showed no correlation between replicate relative standard deviation (RSD) and wood type or tree diameter, with an overall median RSD of 30%. Collectively, these findings indicate SPME is an appropriate technique for sampling and analyzing chlorinated solvents in wood and that phytoscreening is robust against changes in tree type and diameter.


Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro.
The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3β and β-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/β-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/β-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused reduced GSK 3β and β-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI.


Conjugated polyene fatty acids as fluorescent probes: synthetic phospholipid membrane studies.
The preparation of polyene fatty acid membrane probes cis- and trans-parinaric acid and parinaroylphosphatidylcholines and their use in studies of several one- and two- component lipid systems are described. The fluorescence quantum yield of trans-parinaric acid in dipalmitoylphosphatidylcholine at 20 degrees C is approximately 0.3; the quantum yield in aqueous solution is negligibly small. Thermal-phase transitions in single-component phospholipid dispersions are monitored with absorption and fluorescence excitation peak position, fluorescence intensity, lifetime, and polarization. The transition temperatures observed are consistent with previous determinations. Shifts in the absorption peak position are related to the bilayer expansion as it undergoes the gel to liquid-crystalline transition, while fluorescence depolarization provides semiquantitative information concerning molecular motion of the probe in the bilayer. A long fluorescence lifetime component is observed for parinaric acid in the solid phase (up to 50 ns), and a short lifetime component is observed (ca. 5 ns) in the fluid phase of dipalmitoylphosphatidylcholine; both lifetime components are observed in the transition region. In most phospholipids, cis-parinaric acid detects the melting transition at about 1 degree C lower than trans-parinaric acid. Partitioning experiments involving mixed populations of phospholipid vesicles show that trans-parinaric acid preferentially associates with solid-phase lipids, while cis-parinaric acid shows a more equal distribution between solid and fluid lipids. The binding of cis-parinaric acid to dipalmitoylphosphatidylcholine at 25 degrees C is described as partitioning of parinaric acid between lipid vesicles and the aqueous phase with a partition coefficient of 5 X 10(5). Several rates are observed in the binding process which are interpreted as rapid outer monolayer uptake and a much slower process of interlamellar exchange. The phase diagram of the binary lipid mixture dipalmitoylphosphatidylcholine-dipalmitoylphosphatidylethanolamine has also been examined and found to be essentially identical to the one constructed using a nitroxide probe.