Chirped laser dispersion spectroscopy with differential frequency generation source.
A feasibility study of open-path methane detection at 3.4 μm using chirped laser dispersion spectroscopy (CLaDS) based on nonlinear differential frequency generation (DFG) laser source is performed. Application of a DFG source based on telecom laser sources and modulators allows mid-infrared CLaDS system to be optimized for measurements of gases at atmospheric conditions for which modulation in the GHz range is required. Excellent agreement between observed CLaDS signals and spectroscopic models has been observed.


Irritable aggression induced by delta 9-tetrahydrocannabinol in rats pretreated with 6-hydroxydopamine.
Administration of delta 9-tetrahydrocannabinol (THC) to grouped rats injected intraventricularly with 6-hydroxydopamine (6-OHDA) produced violent fighting accompanied by remarkable hyperirritability. This behavior was induced reproducibly from the 10th to 100th postoperative days. It was shown that this irritable aggression could be measured continuously and quantitatively in terms of degree of activity and/or vocalization using a newly designed analyzer. The effect of THC differed markedly from the action of apomorphine and methamphetamine in 6-OHDA pretreated rats. Apomorphine induced irritable aggression but not vigorous vocalization. On the other hand, methamphetamine induced much less irritable aggression than apomorphine-induced aggression. It is assumed that a THC-invoked imbalance in catecholamine agonistic and serotonin antagonistic action brought about by activation of supersensitized catecholaminergic receptor was operating to produce the aggression. Specifically, hypoactivity of serotonergic neurons might play a key role in the occurrence of THC-induced irritable aggression.


Ethanol modulation of opiate receptors in cultured neural cells.
The mouse neuroblastoma-rat glioma hybrid cell line NG108-15 was used to study the acute and chronic interaction of ethanol with intact neural cells. In the short term, ethanol inhibited opiate receptor binding, but after long-term exposure the cells exhibited an apparent adaptive increase in the number of opiate binding sites; this was reversible when ethanol was withdrawn. High concentrations of ethanol (200 mM) increased opiate binding after 18 to 24 hours, whereas lower concentrations (25 to 50 mM) produced similar changes after 2 weeks. This model system has potential for exploring the cellular and molecular mechanisms underlying ethanol intoxication, tolerance, and withdrawal.


Analysis of disparity gradient based cooperative stereo.
This paper argues that the disparity gradient subsumes various constraints for stereo matching, and can thus be used as the basis of a unified cooperative stereo algorithm. Traditionally, selection of the neighborhood support function (NSF) in cooperative stereo was left as a heuristic exercise. We present an analysis and evaluation of three families of NSFs based on the disparity gradient. It is shown that an exponential decay function with a conveniently selectable parameter is well behaved in that it yields the least error, converges steadily, and produces correctly located weak-winners. The discovery of the well-behaved function facilitates the success of the disparity gradient based approach. It is suggested that this function will help a two-pass algorithm in resolving the dilemma of surface continuity and discontinuity/occlusion. In our experiments, the unified cooperative stereo-matching algorithm is tested on random-dot stereograms containing opaque and transparent surfaces. It is also shown to be applicable to both area matching and contour matching in real-world images.


Biomechanics of Exoskeleton-Assisted Treadmill Walking.
To exploit the benefits of treadmill-based exoskeletons, it is crucial to assess possible deviations from natural walking depending on assistive parameters. This study evaluated the biomechanics of exoskeleton-assisted treadmill walking by comparing it with free gait. Five healthy participants walked freely on a treadmill and with the assistance of the Lokomat gait trainer, while changing Body Weight Support (BWS), Gait Speed (GS), and Guidance Force (GF). Results showed that the hip and knee joint kinematics depended on BWS and GS, while changes due to GF were limited. Moreover, joint kinematics and the activity of related muscles were altered with respect to free gait, for any combination of robot parameters in the case of the ankle, and especially for low GS and with BWS in the case of hip and knee. Overall, walking with the Lokomat can mostly resemble free gait at high speed and without BWS.


Correlation of extreme drug resistant assay results and progression-free survival following intraperitoneal chemotherapy for advanced ovarian cancer.
The aim of this study was to determine if in vitro extreme drug resistance (EDR) to platinum and/or taxane chemotherapy was predictive of patient response to intraperitoneal (I.P.) chemotherapy in patients with stage III or recurrent epithelial ovarian cancer (EOC). Fifty-six patients were retrospectively identified who underwent optimal cytoreductive surgery for primary or recurrent eOC and then received at least three cycles of either intravenous (I.V.) or I.P. chemotherapy with platinum and paclitaxel-based chemotherapy. EDR to platinum and/or paclitaxel was determined using a commercially available assay (Oncotech, Inc., Tustin, CA). The primary outcome measure was progression-free survival (PFS). Twenty-nine (52%) patients received I.P. chemotherapy and 27 (48%) received I.V. chemotherapy. The patients were well matched in terms of age, stage, grade and histology. Ten (35%) patients in the I.OP. arm and ten (37%) patients in the I.V. arm showed EDR to either platinum and/or paclitaxel. Median PFS for all I.P. chemotherapy patients was 23 months, compared with 13 months for those receiving I.V. chemotherapy (p = 0.04). Patients with EDR to platinum and/or taxane who underwent I.V. chemotherapy had a median PFS of 13.5 months, whereas those who underwent I.P. treatment had a median PFS of 15 months (p = 0.69). Median overall survival had not been reached at the time of analysis.No significant difference in PFS was noted between patients who underwent I.P. and those who underwent I.V. chemotherapy when EDR was predicted to either platinum or paclitaxel or both. These data suggest that the decision to offer I.P. chemotherapy, with the attendant increase in morbidity, in the setting of EDR to platinum and/or taxane chemotherapy, may not be beneficial. Prospective studies, preferably analyzing platinum or taxane EDR individually, are required to validate these observations.


Large cerebellar hemorrhage during trumpet playing: importance of blood pressure elevation during the valsalva maneuver: case report.
The authors report a case of a large intracerebellar hemorrhage that occurred in a professional musician while playing the trumpet. This is the first report of such a complication. A 60-year-old man presented with severe occipital headache accompanied by nausea, vomiting, and dizziness that occurred while he was practicing the trumpet. On presentation, he was hypertensive with a systolic blood pressure of 255 mmHg and was found to have a large left cerebellar hemorrhage. Magnetic resonance imaging and magnetic resonance angiography were performed but revealed no tumor or vascular abnormality. The patient was initially stable but, despite maximal medical therapy, deteriorated and was taken to the operating room for suboccipital craniectomy and evacuation of the hematoma. This patient likely had chronic hypertension; however, the transient increase in systolic blood pressure associated with intensive trumpet playing and the Valsalva maneuver may have contributed to his risk of hemorrhage. We suggest that hypertensive screening and therapy may be especially important in this population and emphasize the importance for neurosurgeons to understand the physiology involved in the Valsalva maneuver.


Deletions in the COL10A1 gene are not associated with skeletal changes in dogs.
Type 10 collagen alpha 1 (COL10A1) is a short-chain collagen of cartilage synthesized by chondrocytes during the growth of long bones. COL10A1 mutations, which frequently result in COL10A1 haploinsufficiency, have been identified in patients with Schmid metaphyseal chondrodysplasia (SMCD), a cartilage disorder characterized by short-limbed short stature and bowed legs. Similarities between SMCD and short stature in various dog breeds suggested COL10A1 as a candidate for canine skeletal dysplasia. We report the sequencing of the exons and promoter region of the COL10A1 gene in dog breeds fixed for a specific type of skeletal dysplasia known as chondrodysplasia, breeds that segregate the skeletal dysplasia phenotype, and control dogs of normal stature. Thirteen single nucleotide polymorphisms (SNPs), one insertion, and two deletions, one of which introduces a premature stop codon and likely results in nonsense-mediated decay and the degradation of the mutant allele product, were identified in the coding region. There appear to be no causal relationships between the polymorphisms identified in this study and short stature in dogs. Although COL10A1 haploinsufficiency is an important cause of SMCD in humans, it does not seem to be responsible for the skeletal dysplasia phenotype in these dog breeds. In addition, homozygosity for the nonsense allele does not result in the observed canine skeletal dysplasia phenotype.


Uterine Fibroid Torsion during Pregnancy: A Case of Laparotomic Myomectomy at 18 Weeks' Gestation with Systematic Review of the Literature.
Uterine myomas are the most common benign growths affecting female reproductive system, occurring in 20-40% of women, whereas the incidence rate in pregnancy is estimated from 0.1 to 3.9%. The lower incidence in pregnancy is due to the association with infertility and low pregnancy rates and implantation rates after in vitro fertilization treatment. Uterine myomas, usually, are asymptomatic during pregnancy. However, occasionally, pedunculated fibroids torsion or other superimposed complications may cause acute abdominal pain. There are many controversies in performing myomectomy during cesarean section because of the risk of hemorrhage. Nevertheless, the majority of indication arises before labor and delivery due to acute symptoms leading to a discussion regarding the need for intervention during pregnancy. Therefore, we present a case of successful multiple laparotomic myomectomy at 17 + 2 weeks of gestational age and a systematic review of the literature in order to clarify the approach to this pathologic condition and its effect on pregnancy outcome.


Increased isolation of Vibrio cholerae O1 serotype Inaba over serotype Ogawa in Pakistan.
Although the predominant Vibrio cholerae serotype in Pakistan is Ogawa and serotype Inaba is rare, there has been a significant increase in the isolation of Inaba in our referral laboratory in Karachi. This paper reports this observation and further analysis of previous cholera data from 1993 to 2005 to assess the trend of occurrence and resistance pattern of V. cholerae strains. From January to September 2005, 245/3292 (7.4%) specimens yielded growth of V. cholerae. Of these, 243 were serotype Inaba, outnumbering serotype Ogawa. This recent Inaba strain is 100% resistant to cotrimoxazole, 3% resistant to chloramphenicol and not resistant to ampicillin, tetracycline and ofloxacin. This sensitivity pattern is almost similar to that of the previous predominant serotype Ogawa.


The role of the corpus callosum in the perception of reversible figures in children.
To test the role of interhemispheric competition through the corpus callosum in the perceptual alternation of reversible figures, we compared children with callosal pathology and typically developing children on a bistable stimulus task. The children with corpus callosum pathology reported significantly less changes of percepts per minute than the age-matched typically developing children. In addition, older typically developing children reported significantly more changes of percepts than the younger ones. These results support the hypothesis that the rate of reversal between two interpretations of a bistable stimulus may be partly mediated by the corpus callosum.


Clear cell tumors of the alimentary tract and abdominal cavity.
Clear cell neoplasms of the abdominal organs are represented by a variety of epithelial and mesenchymal neoplasms, of varying malignant potential. Several varieties of clear cell carcinomas, including those with tubulopapillary, hepatoid, colloid, or neuroendocrine features, have been described, as well as several benign epithelial neoplasms. These epithelial tumors have been reported in the gastrointestinal hollow viscera, as well as the liver, pancreas, and biliary tract. A second major consideration is the mesenchymal-derived gastrointestinal stromal tumors, which also may feature clear cells, and comprise a spectrum of biological behavior. Miscellaneous lesions include clear cell variants of melanoma and mesothelioma. This review includes histological details of the various entities, as well as important histochemical, immunohistological, and ultrastructural features. Pertinent differential diagnostic points are stressed, including distinction of the primary clear lesions from relevant metastatic neoplasms.


The Epstein-Barr virus genome and phenotypic expression during lytic cycle.
The Epstein-Barr Virus (EBV) has been studied extensively as a human cancer virus. Until recently, however, little was known about the viral genes encoding for different proteins involved in the virus immortalization and replication cycles. Most of the efforts have been directed at those genes expressed in immortalized cells. However, more recently, there has also been advances in the mapping of genes encoding for polypeptides expressed in the virus replication cycle and in the characterization of the proteins encoded by these genes. The purpose of this article is to review some of these new developments in identifying viral genes and their products. In addition, the current status of the development of a subviral vaccine against this virus is discussed.


Within-group differences between native-born and foreign-born Black men on prostate cancer risk reduction and early detection practices.
To better address prostate cancer disparities, we investigated the differences among US-born, African-born, and Caribbean-born Black men on prostate cancer risk reduction and early detection behaviors. Data were collected from over 3,400 Black men in five cities in Florida. One-way analysis of variance was used to explore the ethnic variations among the three study groups. We found that there were significant differences among the three groups. The US-born Black men had the highest knowledge, were most likely to have health insurance, and consume the most meat compared to African-born, and Caribbean-born Black men. African-born Black men were most likely to use chemoprevention products and discuss prostate cancer risk-reduction and early detection with a physician. Given the significant number of foreign-born Blacks in the US, it is important to disaggregate the data of US-born and foreign-born Blacks to develop effective programs and policies to address the needs of each group.


Nanomedicines for Improved Management of Ectopic Pregnancy: A Narrative Review.
Ectopic pregnancy (EP) - the implantation of an embryo outside of the endometrial cavity, often in the fallopian tube - is a significant contributor to maternal morbidity and leading cause of maternal death due to hemorrhage in first trimester. Current diagnostic modalities including human chorionic gonadotropin (hCG) quantification and ultrasonography are effective, but may still misdiagnose EP at initial examination in many cases. Depending on the patient's hemodynamic stability and gestational duration of the pregnancy, as assessed by history, hCG measurement and ultrasonography, management strategies may include expectant management, chemotherapeutic treatment using methotrexate (MTX), or surgical intervention. While these strategies are largely successful, expectant management may result in tubal rupture if the pregnancy does not resolve spontaneously; MTX administration is not always successful and may induce significant side effects; and surgical intervention may result in loss of the already-damaged fallopian tube, further hampering the patient's subsequent attempts to conceive. Nanomaterial-based technologies offer the potential to enhance delivery of diagnostic imaging contrast and therapeutic agents to more effectively and safely manage EP. The purpose of this narrative review is to summarize the current state of nanomedicine technology dedicated to its potential to improve both the diagnosis and treatment of EP.


Emotion Generation and Emotion Regulation: One or Two Depends on Your Point of View.
Emotion regulation has the odd distinction of being a wildly popular construct whose scientific existence is in considerable doubt. In this article, we discuss the confusion about whether emotion generation and emotion regulation can and should be distinguished from one another. We describe a continuum of perspectives on emotion, and highlight how different (often mutually incompatible) perspectives on emotion lead to different views about whether emotion generation and emotion regulation can be usefully distinguished. We argue that making differences in perspective explicit serves the function of allowing researchers with different theoretical commitments to collaborate productively despite seemingly insurmountable differences in terminology and methods.


Identification and characterization of nucleotide-binding site-leucine-rich repeat genes in the model plant Medicago truncatula.
The nucleotide-binding site (NBS)-Leucine-rich repeat (LRR) gene family accounts for the largest number of known disease resistance genes, and is one of the largest gene families in plant genomes. We have identified 333 nonredundant NBS-LRRs in the current Medicago truncatula draft genome (Mt1.0), likely representing 400 to 500 NBS-LRRs in the full genome, or roughly 3 times the number present in Arabidopsis (Arabidopsis thaliana). Although many characteristics of the gene family are similar to those described on other plant genomes, several evolutionary features are particularly pronounced in M. truncatula, including a high degree of clustering, evidence of significant numbers of ectopic translocations from clusters to other parts of the genome, a small number of more evolutionarily stable NBS-LRRs, and numerous truncations and fusions leading to novel domain compositions. The gene family clearly has had a large impact on the structure of the genome, both through ectopic translocations (potentially, a means of seeding new NBS-LRR clusters), and through two extraordinarily large superclusters. Chromosome 6 encodes approximately 34% of all TIR-NBS-LRRs, while chromosome 3 encodes approximately 40% of all coiled-coil-NBS-LRRs. Almost all atypical domain combinations are in the TIR-NBS-LRR subfamily, with many occurring within one genomic cluster. This analysis shows the gene family not only is important functionally and agronomically, but also plays a structural role in the genome.


Prevalence and Risk Factors of Dry Eye Symptoms in a Saudi Arabian Population.
The information about dry eye epidemiology in Saudi Arabia is few in literature. To estimate the prevalence and identify determinants of dry eye symptoms (DES) in Al-Ahsa, Saudi Arabia. Using a multi-stage proportionate sampling technique, Saudis of both genders from 6 urban and 4 rural Primary Health Care centers in Al-Ahsa were enrolled. They were interviewed to gather data on sociodemography, symptoms of dry eye, factors potentially related to dry eye, and chronic comorbidities. If one or more of DESs present often or constantly, we labeled the person with DES. We examined 1858 Saudi adults with mean age of 39.3 ± 14.1 years. The age-adjusted prevalence of DES was 32.1% (95% confidence interval [CI] = 30.0-34.3). Multivariate logistic regression analysis showed that female gender (adjusted odds ratio [aOR] = 2.1, 95% CI = 1.7-2.6), older age (>56 years; aOR = 1.5, 95% CI = 1.0-2.1), current smoking (aOR = 1.4, 95% CI = 1.1-1.8) and history of diabetes mellitus (aOR = 1.5, 95% CI = 1.2-2.0) were significantly associated with DES. Nonsignificant variables included residence (urban/rural); work status; wearing contact lenses; multivitamin use; caffeine use; history of trachoma, hypertension, bronchial asthma, coronary artery disease, thyroid disease, arthritis, hemolytic blood diseases (sickle cell-thalassemia), gout, and osteoporosis. DES are highly prevalent among the adult population of Al-Ahsa. Females, persons more than 55 years of age, smokers and diabetics were associated to DES.


Recent advances in the self-referencing embedded strings (SELFIES) library.
String-based molecular representations play a crucial role in cheminformatics applications, and with the growing success of deep learning in chemistry, have been readily adopted into machine learning pipelines. However, traditional string-based representations such as SMILES are often prone to syntactic and semantic errors when produced by generative models. To address these problems, a novel representation, SELF-referencing embedded strings (SELFIES), was proposed that is inherently 100% robust, alongside an accompanying open-source implementation called selfies. Since then, we have generalized SELFIES to support a wider range of molecules and semantic constraints, and streamlined its underlying grammar. We have implemented this updated representation in subsequent versions of selfies, where we have also made major advances with respect to design, efficiency, and supported features. Hence, we present the current status of selfies (version 2.1.1) in this manuscript. Our library, selfies, is available at GitHub (https://github.com/aspuru-guzik-group/selfies).


A push for public health: the effect of e-bikes on physical activity levels.
Cycling is considered to have a positive effect on public health through increased physical activity. In Norway, the e-bike is seen as a way of getting more people to cycle. However, the motorized assistance of an e-bike potentially eliminates any physical activity associated with its use. It is possible that the assumed health effect of increased cycling is "erased" through a reduction in other physical activities (a substitution effect). In this paper we study the public health effects of e-bikes using a combined cross-sectional and quasi-experimental design. First, we explore the existence of potentially hedonistic values in relation to interest in acquiring an e-bike and, second, we conduct an intervention study of physical activity pre- and post-purchase. A sample of 340 people responded to a questionnaire before buying an e-bike and follow-up 4 weeks later, when 45 had bought one. A further 28 (mainly physically inactive) were recruited through a Norwegian NGO. For a comparison group, 1995 people were recruited through the Falck National Register of Bicycle Owners. All respondents were asked about the intensity of their cycling, (kilometres cycled in the previous week), walking and physical activity in addition to cycling as means of transport (days and hours). A structural equation model showed that hedonistic life values, and general physical activity, were predictive of interest in buying an e-bike. However people who already cycled a lot showed less interest. The trial showed that increased cycling - whether as a mean of transport or exercise -was related to higher levels of total physical activity in both groups compared to a comparison group (one-way ANOVA). Our findings indicate that in the Norwegian cycle population there is no substantial substitution effect of physical activity with the introduction of an e-bike. The appeal of the e-bike is strongest among those with little existing interest in, or levels of, physical activity. The net effect of the e-bike therefore seems positive from a public health perspective.


Microseizures and the spatiotemporal scales of human partial epilepsy.
Focal seizures appear to start abruptly and unpredictably when recorded from volumes of brain probed by clinical intracranial electroencephalograms. To investigate the spatiotemporal scale of focal epilepsy, wide-bandwidth electrophysiological recordings were obtained using clinical macro- and research microelectrodes in patients with epilepsy and control subjects with intractable facial pain. Seizure-like events not detectable on clinical macroelectrodes were observed on isolated microelectrodes. These 'microseizures' were sparsely distributed, more frequent in brain regions that generated seizures, and sporadically evolved into large-scale clinical seizures. Rare microseizures observed in control patients suggest that this phenomenon is ubiquitous, but their density distinguishes normal from epileptic brain. Epileptogenesis may involve the creation of these topographically fractured microdomains and ictogenesis (seizure generation), the dynamics of their interaction and spread.


[Immunotherapy of lung cancer].
Immune checkpoint inhibitor therapy in lung cancer is a new effective treatment as part of a complex treatment strategy. In the advanced stage of non-small cell non-squamous lung cancer, without actionable mutation, the immune monotherapy or combination treatment with platinum based chemotherapy is a new standard of care depending on PD-L1 status. In case of advanced squamous cell lung cancer the situation is similar. The exact role of combination PD-1 axis and CTLA-4 inhibitor treatment with or without chemotherapy is not exactly defined. Immune checkpoint inhibitor therapy can be used in second or more line treatment as well. After exhaustion of targeted treatment the efficacy of the combination of immunotherapy with angiogenesis inhibitor and platinum based chemotherapy is promising. In locally advanced non-small cell lung cancer after radiochemotherapy the consolidation PD-L1 inhibitor treatment is a new standard of care in case of PD-L1 positivity. There are Phase III trials in neoadjuvant and adjuvant setting as well. In extensive stage small cell lung cancer the platinum-etoposide treatment with PD-L1 inhibitor is a new standard, but we do not have any effective biomarkers yet.


[Surgery in bleeding stenosing pyloroduodenal ulcer].
The results of surgical treatment of 147 patients with a bleeding stenosing pyloroduodenal ulcer are presented. The operation of choice in this pathology is a selective proximal vagotomy in combination with the original methods of ulcer excision and drainage operations, and as well a selective proximal vagotomy with antrectomy. Gastric resection is indicated in patients with decompensated stenosis of gastric outlet and pronounced disorders in motor-evacuatory function of the stomach. In patients with a severe, or extremely severe state, the ulcer excision in combination with pyloroduodenoplasty dilating the lumen is expedient.


Overexpression of nucleolin and different expression sites both related to the prognosis of gastric cancer.
The aim of this study was to investigate the expression of nucleolin in tumorous tissues and corresponding non-malignant tissues in gastric cancer (GC), and the correlation of different expression sites with clinicopathologic parameters and prognosis. Immunohistochemistry was used for detecting the expression levels of nucleolin in GC tissues and corresponding non-malignant tissues from 124 gastrectomy specimens with stage I-III. Staining results were correlated with clinicopathologic features and survival. Both GC tissues and corresponding non-malignant tissues showed nucleolar staining for nucleolin. Nucleolin expression was higher in GC tissues than in non-malignant tissues. Among the 124 GCs, 85 (68.5%) were nucleolin-high. No significant correlation between nucleolin expression and other clinicopathologic parameters was found. The Cox univariate analysis indicated that both cytoplasmic staining and nucleolar staining of nucleolin expression correlated with patients' prognosis (log-rank, p < 0.0001; p = 0.0075, respectively). It was concluded in the study that nucleolin was overexpressed in GCs. A high level of nucleolar expression of nucleolin was an independent prognostic marker for better survival while high cytoplasmic staining was closely associated with worse prognosis for GC patients.


Effect of ulinastatin on myocardial ischemia reperfusion injury through ERK signaling pathway.
To study the effect of ulinastatin (UTI) on myocardial ischemia-reperfusion injury (MIRI) through the extracellular signal-regulated kinase (ERK) signaling pathway. A total of 24 Sprague-Dawley rats were randomly divided into sham group (n=8), I/R group (n=8), and UTI group (n=8), and the rat model of MIRI was established. The changes in the content of serum biochemical indexes, including superoxide dismutase (SOD) and malondialdehyde (MDA), were detected using the kits, and the changes in the expressions of serum inflammatory factors, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), were detected using the quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. Moreover, the ERK phosphorylation level in myocardial tissues was detected using the immunofluorescence method, and the ERK phosphorylation level and cleaved caspase-3 expression were detected via qRT-PCR and Western blotting. Compared with those in sham group, the serum SOD content significantly declined, while the MDA content was significantly increased in I/R group, and they were significantly improved in UTI group (p<0.01). The results of detection using qRT-PCR and ELISA kits revealed that the inflammatory factors (IL-6 and TNF-α) in UTI group were significantly improved (p<0.01). The immunofluorescence results showed that the ERK phosphorylation level in myocardial tissues was significantly increased in UTI group. The results of qRT-PCR and Western blotting manifested that both ERK phosphorylation level and cleaved caspase-3 expression were significantly improved in UTI group (p<0.01). UTI can play a protective role in MIRI through up-regulating the ERK signaling pathway.


MRC2 expression correlates with TGFβ1 and survival in hepatocellular carcinoma.
MRC2 (Mannose Receptor C Type 2) is a constitutively recycling endocytic receptor belonging to the mannose receptor family, which has been found to be closely involved with cancer metastasis. This study attempted to determine MRC2 expression on hepatocellular carcinoma (HCC) and its significance on postsurgical prognosis of HCCs. The expression of both MRC2 and transforming growth factor (TGFβ1) was detected in tumor tissues and adjacent liver tissues from 96 HCCs by immunohistochemistry staining, and it was found that MRC2 expression in HCC tissues was significantly higher than in adjacent liver tissues. HCCs with higher MRC2 expression had worse prognosis after liver resection. Univariate analysis showed that advanced TNM staging of HCC, higher Edmonson-Steiner classification, intrahepatic metastases, portal vein invasion, higher MRC2 and higher TGFβ1 were the poor prognostic factors. Furthermore, multivariate analysis revealed that intrahepatic metastases, higher MRC2 and higher TGFβ1 were the independent prognostic factors. TGFβ1 treatment up-regulated MRC2 expression, cell migration and invasion of Huh7 cells notably. In addition, knockdown of MRC2 repressed the effect of TGFβ1 on cell migration and invasion. These data suggest that MRC2 overexpression predicts poor prognosis of HCCs after liver resection and MRC2 potentially contributed to TGFβ1-driven up-regulation of cell migration and invasion in HCC.


[System analysis of metabolic profile of blood in patients with thermal trauma].
To make multiparametric analysis of blood metabolic profile in early period of burn disease. We tested blood samples of 15 healthy adults (control group) and 60 patients with thermal trauma (main group--II-4IIIA, B degree of burn, more then 15 bsp). Parameters of lipid metabolism, level of glucose, lactate, malonic dialdehyde and some enzymes in blood plasma and erythrocytes were estimated. In early period of burn disease we fixed the clear metabolic disorders, including tissues hypoxia, activation of plasma transaminases and oxidoreductases, inhibition of detoxication system, induction of oxidative stress. Connection of metabolic changes, associated with burn disease, was registered. It supported by numerous correlations between studied parameters, formed from first day after trauma. Our data expand the knowledge about mating metabolic changes of catalytic activity of blood enzymes, forming in early period of burn disease (system metabolic disadaptation), and diagnostic value of some blood biochemical parameters in estimation of burned patient metabolism.


Inhibition of tumor cell collagenolytic activity by bovine endothelial cells.
The ability of cellular vascular components including endothelial cells, smooth muscle cells, and fibroblasts to interact with the collagenolytic activity of invasive human tumor cell lines has been investigated. The human HT1080 fibrosarcoma and Bowe melanoma cells, which rapidly digest collagenous proteins in vitro, failed to dissolve them when cocultivated with bovine endothelial cells. This inhibition was not dependent on the ability of endothelial cells to form a monolayer separating the tumor cells from the collagenous substrate. In contrast, little collagenolysis inhibitory activity was detected in bovine vascular smooth muscle cells and human fibroblasts when compared to endothelial cells. Serum-free medium conditioned by endothelial cells inhibited tumor cell-mediated collagenolysis. Our data further suggest that this inhibition was mediated by secreted collagenase inhibitors, since endothelial cell-conditioned medium did not suppress the production of metalloproteinases by the tumor cells but inhibited the activities of collagenases derived from tadpole, rabbit, and human fibroblasts. Treatment of the endothelial cells with cycloheximide suppressed the collagenase inhibitory activity, demonstrating active production of collagenase inhibitors by the cells. Gel filtration chromatography of endothelial cell-conditioned medium allowed the separation of two distinct peaks with inhibitory activities for vertebrate collagenase in the molecular weight range of 70,000 to 75,000 and 30,000 to 35,000, respectively. While the inhibitor with an approximate molecular weight of 30,000 to 35,000 shared many properties with the tissue inhibitor of metalloproteinases, the high-molecular-weight inhibitor demonstrated characteristics not yet described for any collagenase inhibitor. The production and secretion of inhibitors of vertebrate collagenase by bovine endothelial cells may be of importance in the local control of collagen turnover under physiological as well as pathological conditions.


Racial and Ethnic Differences in Pediatric Readmissions for Common Chronic Conditions.
To compare the timing and magnitude of variation of pediatric readmission rates across race/ethnicity for selected chronic conditions: asthma, diabetes, seizures, migraines, and depression. Retrospective analysis of hospitalizations at 48 children's hospitals in the 2013 Pediatric Health Information System database for children (ages 0-18 years) admitted for asthma (n = 36 910), seizure (n = 35 361), diabetes (n = 12 468), migraine (n = 5882), and depression (n = 5132). Generalized linear models with a random effect for hospital were used to compare the likelihood of readmission by patients' race/ethnicity, adjusting for severity of illness, age, payer, and medical complexity. Adjusted readmission rates were calculated by week over 1 year. Significant variation in adjusted readmission rates by race/ethnicity existed for conditions aside from depression. Disparities for diabetes and asthma emerged at 3 and 4 weeks, respectively; they remained divergent up to 1 year with the highest 1-year readmission rates in non-Hispanic blacks vs other race/ethnicities (diabetes: 21.7% vs 13.4%, P < .001; asthma: 21.4% vs 14.6%, P < .001). Disparities for migraines and seizure emerged at 6 and 7 weeks, respectively; they remained up to 1 year, with the highest 1-year readmission rates in non-Hispanic whites vs other race/ethnicities (migraine: 17.3% vs 13.6%, P < .001; seizure: 23.9% vs 21.9%, P < .001). Readmission disparities behave differently across chronic conditions. They emerge more quickly after discharge for children hospitalized with asthma or diabetes than for seizures or migraines. The highest readmission rates were not consistently observed for 1 particular race/ethnicity. Study findings can impact pediatric chronic disease management to improve care for children with these conditions.


Social Workers' Views of Ways to Engage Communities in Refugee Resettlement.
The refugee crisis has been keenly felt by communities as they perceive the new arrivals as threats to the community's resources. Preparing the community for future arrivals can help, as can involving the community in the welcoming of refugees. This study explores how social workers engage communities to support refugee resettlement programs. Social workers are on the frontlines of providing services to refugees while also managing the fears and needs of the community members. A community that was once welcoming can become reactionary and xenophobic. This is a qualitative study using the content analysis of 32 social workers in four countries: the United States, Iceland, Switzerland, and Germany. Key factors influenced social workers' facilitation of community integration among new arrivals and community members: prior experiences with displaced populations, social workers' expectations, and strengths within the community. Social workers need training and support to include communities in resettlement services. Training and policy implications are discussed. Communities can be a partner in the resettlement process if care is given to work with the community before the arrival of new refugees.


Egr2 and 3 Inhibit T-bet-Mediated IFN-γ Production in T Cells.
T-bet is important for differentiation of cytotoxic CD8 and Th1 CD4 T cells. We have discovered that Egr2 and 3 are potent inhibitors of T-bet function in CD4 and CD8 effector T cells. Egr2 and 3 were essential to suppress Th1 differentiation in Th2 and Th17 conditions in vitro and also to control IFN-γ-producing CD4 and CD8 T cells in response to virus infection. Together with Egr2 and 3, T-bet is induced in naive T cells by Ag stimulation, but Egr2 and 3 expression was inhibited by Th1-inducing cytokines. We found that Egr2 and 3 physically interact with the T-box domain of T-bet, blocking T-bet DNA binding and inhibiting T-bet-mediated production of IFN-γ. Thus, Egr2 and 3 are antagonists of T-bet function in effector T cells and are important for the control of inflammatory responses of T cells.


Localization of Mn-superoxide dismutase (Mn-SOD) in cholinergic and somatostatin-containing neurons in the rat neostriatum.
We used rabbit antisera against manganese (Mn)-superoxide dismutase for immunohistochemical studies of localization in the rat neostriatum. Immunostaining was intense in large-sized neurons and several medium-sized neurons, but it was moderate to weak in other cells. Double immunostaining with monoclonal antibody to choline acetyltransferase or somatostatin demonstrated large-sized, Mn-SOD immunoreactive neurons to be cholinergic, and some medium-sized neurons which were intensely immunoreactive for Mn-SOD to contain somatostatinergic.


Coupling of free space sub-terahertz waves into dielectric slabs using PC waveguides.
The paper presents theoretical and experimental results on photonic crystal structures which work under the self-collimation condition to couple free space waves into dielectric slabs in the sub-terahertz range. Using a standard machining process, two-dimensional photonic crystal structures consisting of a square array of air holes in the dielectric medium are fabricated. One of the structures has two adjacent parallel line-defects that improve the coupling efficiency. This leads to a combination of self-collimation and directional emission of electromagnetic waves. The experimental results are in good agreement with those of the Finite- Element-Method calculations. Experimentally we achieve a coupling efficiency of 63%.


Longitudinal integration of cultural components into a physician assistant program's clinical year may improve cultural competency.
This study assessed the efficacy of longitudinal integration of cultural components into the clinical year of a 2-year master of science in physician assistant studies (MSPAS) program. Students submitted cultural reflection papers, gave a medical case/cultural presentation, and participated in cultural awareness discussion groups throughout the clinical year. Students completed the same cultural awareness survey at the conclusion of their clinical year that they had completed at benchmarked intervals during their didactic year. Additionally, cultural competency was assessed during the students' summative objective structured clinical examination (OSCE) using a combination of the program's objectives and established professional standards. Qualitative data suggested that students recognized the importance of cultural competency in providing quality patient care and recognized that remaining culturally competent is an ongoing process. Linear trend analyses revealed significant positive relationships between survey response scores and time in the program. The OSCE's cultural assessment scores indicated cultural competency in broad, general categories, but scores declined as cultural categories narrowed and became more detailed. Continued integration of cultural awareness training and assessment throughout the clinical year of a physician assistant (PA) program may have a positive impact on improving cultural competency. PA programs seeking to improve cultural competency in their students should consider continued integration of cultural components throughout the clinical year.


Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?
In 1999, the UK introduced meningococcal serogroup C conjugate (MCC) vaccination at 2, 3, 4 months of age with a single dose for children 1-18 y In 2006, the schedule was refined to a 2 dose priming schedule with a booster in the second year of life. In 2013, the number of priming doses was reduced to a single priming dose, the booster maintained at 12 months of age and an adolescent booster dose introduced. The paper presents the evidence supporting the reduction in the number of priming doses. A UK study provided evidence for reducing the priming doses of MCC-TT together with the positive correlation of lower quantity of antigen and serum bactericidal antibody (SBA) levels post-primary but a higher magnitude of the booster response. Another UK study, demonstrated one dose of MCC-TT or MCC-CRM197 at 3 months gave comparable responses to 2 doses (SBA titres ≥8) both post-primary vaccination and post-booster Hib/MCC-TT at 12 months. However, the magnitude of the SBA GMT was higher in the MCC-TT primed post-booster. A single priming dose of MCC-TT (at 4 or 6 months) compared to 2 doses (2 and 4 months) gave higher SBA titres in all groups, post-primary and post-booster at 12-13 months, with the highest SBA responses observed in the 4 month single dose group. A study in Malta, comparing one dose of MCC-TT or MCC-CRM197 at (3 months) versus 2 doses of MCC-CRM197 (3 and 4 months), showed a high proportion (>84.72%) of subjects achieving SBA titres ≥8 following a single dose. These studies show that a single-dose priming MCC vaccination in infancy is sufficient.


Nonsteroidal anti-inflammatory drugs and breast cancer risk in the National Institutes of Health-AARP Diet and Health Study.
By inhibiting cyclooxygenase-2, nonsteroidal anti-inflammatory drugs (NSAIDs) decrease aromatase activity and might reduce breast cancer risk by suppressing estrogen synthesis. Epidemiologic evidence for a protective role of NSAIDs in breast cancer, however, is equivocal. We tested NSAID use for its association with breast cancer incidence in the National Institutes of Health-AARP Diet and Health Study, where 127,383 female AARP (formerly known as the American Association of Retired Persons) members with no history of cancer, aged 51 to 72 years, completed a mailed questionnaire (1996 to 1997). We estimated relative risks of breast cancer for NSAID exposures using multivariate Cox proportional hazards regression models. The state cancer registry and mortality index linkage identified 4,501 primary incident breast cancers through 31 December 2003, including 1,439 estrogen receptor (ER)-positive cancers and 280 ER-negative cancers. Proportional hazards models revealed no statistically significant association between overall NSAIDs and total breast cancer. As cyclooxygenase inhibition by aspirin (but not other NSAIDs) is irreversible, we tested associations by NSAID type. Although we observed no significant differences in risk for daily use (versus nonuse) of aspirin (relative risk = 0.93, 95% confidence interval = 0.85 to 1.01) or nonaspirin NSAIDS (relative risk = 0.96, 95% confidence interval = 0.87 to 1.05), risk of ER-positive breast cancer was significantly reduced with daily aspirin use (relative risk = 0.84, 95% confidence interval = 0.71 to 0.98)--a relationship not observed for nonaspirin NSAIDS. Neither aspirin nor nonaspirin NSAIDs were associated with risk of ER-negative breast cancer. Breast cancer risk was not significantly associated with NSAID use, but daily aspirin use was associated with a modest reduction in ER-positive breast cancer. Our results provide support for further evaluating relationships by NSAID type and breast cancer subtype.


Identification of peripheral neural circuits that regulate heart rate using optogenetic and viral vector strategies.
Heart rate is under the precise control of the autonomic nervous system. However, the wiring of peripheral neural circuits that regulate heart rate is poorly understood. Here, we develop a clearing-imaging-analysis pipeline to visualize innervation of intact hearts in 3D and employed a multi-technique approach to map parasympathetic and sympathetic neural circuits that control heart rate in mice. We identify cholinergic neurons and noradrenergic neurons in an intrinsic cardiac ganglion and the stellate ganglia, respectively, that project to the sinoatrial node. We also report that the heart rate response to optogenetic versus electrical stimulation of the vagus nerve displays different temporal characteristics and that vagal afferents enhance parasympathetic and reduce sympathetic tone to the heart via central mechanisms. Our findings provide new insights into neural regulation of heart rate, and our methodology to study cardiac circuits can be readily used to interrogate neural control of other visceral organs.


Breastfeeding and the Development of Socio-Emotional Competencies: A Systematic Review.
Aim: To assess the current scientific evidence about the relationship between breastfeeding and the development of infant's socio-emotional competencies. Materials and Methods: A systematic review of literature was conducted through PubMed, LILACS (Literatura Latinoamericana y del Caribe en Ciencias de la Salud), and PsycINFO of population-based cohorts. Records were screened, data extracted, and a quality assessment performed by two authors independently. Results: Thirteen studies were included in the review with six finding a statistically significant association between breastfeeding and the development of socio-emotional competencies such as problem solving, agreeableness, and optimism. In five studies, no statistically significant association was found, and in three, a negative association existed. Regarding quality assessment, four studies had a strong global rating, four had a moderate rating, and five had a weak global rating. Conclusion: Almost half (6/13) of the studies found a positive association between breastfeeding and the development of social-emotional competencies in infants; however, a great heterogeneity was present in the quality of the included studies. There is a need for further and higher quality research into this field of study.


Combination of High-frequency Electrocautery Therapy and ALA-PDT in Hyperkeratotic Vulvar Lichen Sclerosus: series of seven cases.
ALA-PDT effectively treats Vulvar lichen sclerosus et atrophicus (VLSA), but it requires multiple repetitions for satisfactory results. To enhance efficacy, we employed a combination of high-frequency electrocautery therapy and ALA-PDT in treating seven VLSA patients. Lesions and leukoplakia in the seven women with VLSA were removed using a high-frequency generator. PDT was administered after wound healing, and it was repeated six times. Follow-up assessments were carried out at 1, 3, and 6 months to evaluate the severity of pruritus and investigate lesion repigmentation. Following the combined therapy, the disappearance of pruritus was observed in all patients, and normal color and thickness were restored to their skin. Two patients reported mild pruritus with a score of 2 one month after treatment, which persisted until the 6-month follow-up, while the remaining patients remained free from pruritus. No recurrence of skin lesions was observed in any of the patients. The combined therapy for the treatment of VLSA is found to be convenient, effective, and easily promotable.


Dimethyl Fumarate Targets MSK1, RSK1, 2 and IKKα/β Kinases and Regulates NF-κB /p65 Activation in Psoriasis: A Demonstration of the Effect on Peripheral Blood Mononuclear Cells, Drawn from Two Patients with Severe Psoriasis Before and After Treatment with Dimethyl Fumarate.
Dimethyl fumarate (DMF) has an inhibitory effect on the production of pro-inflammatory proteins from different cells which participate in the immune reaction in psoriatic skin. Most recently it was shown that DMF is an allosteric covalent inhibitor of the p90 ribosomal S6 kinases (RSK1, 2), determined by X-ray crystallography. DMF binds to a specific cysteine residue in RSK2 and in the closely related mitogen and stress-activated kinases 1 (MSK1) which inhibits further downstream activation. The aim of this study was to review the literature on the effects of DMF on activation of MSK1, RSK1, 2 kinases, and downstream transcription factors NF-κB/p65 and IκBα in cells contributing to the pathogenesis of psoriasis. We also hypothesized and studied if treatment with DMF would inhibit the activation of MSK1, RSK1, 2 kinases in peripheral blood mononuclear cells (PBMCs) in psoriatic patients. PBMCs were purified from patients with severe psoriasis before and after 90 days of treatment with DMF. Cells were stimulated with anisomycin, IL-1β or EGF for 10 and 20 minutes. The levels of phosphorylation of MSK1, RSK1, 2 or NF-κB/p65, IκBα were analyzed by Western blotting. Our case study showed that treatment with DMF inhibited the activation of MSK1 and RSK1, 2 kinases in PBMCs in patients. This supports that DMF is the active metabolite in vivo in psoriatic patients during DMF treatment. Pro-inflammatory proteins are induced through activation of MSK1 and NF-κB/p65 at (S276). The extracellular signal-regulated kinases (ERK1/2) control cell survival by activating both MSK1 and RSK1, 2 kinases. P-RSK1, 2 activates P-κBα and NF-κB/p65 at (S536). The phosphorylation of NF-κB/p65 at (S276) and (S536) controls different T cell and dendritic cell functions. DMF´s inhibitory effect on MSK1 and RSK1, 2 kinase activations reduces multiple immune reactions in psoriatic patients.


Conflict and synergy in health promotion partnerships: a Danish case study.
Intersectoral partnerships constitute a central approach in health promotion. By combining different perspectives, knowledge and resources from different sectors, partnerships are important for addressing complex health problems. When successful, intersectoral partnerships create synergy, which is suggested to be a proximal outcome that links partnership functioning to health effects. Nonetheless, partnerships are also difficult and time-consuming and may result in conflicts, hostility and power struggles. Such antagonist outputs are expected to produce negative results. However, conflicts may also be a source of valuable learning. This article explores the relationship between conflict and synergy in health promotion partnerships. The empirical material is derived from an evaluation of a 4-year Danish government partnership program. Data consist of survey data collected from 35 partnerships and in-depth qualitative case studies of 10 partnerships. The analysis was inspired by realist evaluation. The qualitative data were coded, and cases written up. Cross-case analysis was conducted and triangulated with survey data. Surprisingly, disagreements and conflicts of interests between partners were common and associated with synergy creation. Moreover, the partnerships' experiences of synergy were often linked to their attribution of differences rather than to common goals or value congruences. The study identifies that a potential for synergy lays in the productive confrontation between partners different perspectives. Moreover, a key mechanism enabling productive conflicts was inclusive dialog, in which the partners' differences were valued, and all voices were included. The study thus builds on the existing synergy literature and adds nuance to the understanding of conflicts in health promotion partnerships.


Development of blood-based biomarker tests for early detection of colorectal neoplasia: Influence of blood collection timing and handling procedures.
Blood-based, cancer-associated biomarkers are susceptible to a variety of well-known preanalytical factors. The influence of bowel preparation before a diagnostic colonoscopy on biomarker levels is, however, poorly investigated. The present study assessed the influence of bowel preparation on colorectal cancer-associated biomarkers. In addition, the effect of single versus double centrifugation of plasma biomarkers was assessed. Blood samples were collected pre- and post-bowel preparation from 125 subjects scheduled for first time diagnostic colonoscopy due to symptoms attributable to CRC. The samples were separated into serum and EDTA plasma, and analyzed by four independent collaborators for: 1) the proteins AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1, 2) the proteins BAG4, IL6ST, vWF, CD44 and EGFR, 3) the glycoprotein Galectin-3 ligand, and 4) cell-free DNA (cfDNA). Statistical analysis of biomarker data has been performed using mixed modelling, including repeated measures. The biomarkers generally showed negligible variation between pre- and post-bowel preparation except for CyFra21-1, Ferritin, BAG4 and cfDNA. CyFra21-1 levels were systematically reduced with 29% (95% CI 21-36%) by bowel preparation (p ≤ 0.0001). Ferritin was not significantly different between pre- and post-bowel preparation (p = 0.07), however the estimated difference (increase) was 18%. BAG4 was systematically reduced by 12% (95% CI 1-22%, p = 0.04), while cfDNA showed a significant increase of 28% (95% CI 17-39%, p < 0.0001). Double centrifugation compared to single centrifugation showed reduced vWF (ratio 0.86, p ≤ 0.0001) and CD44 (ratio 0.85, p = 0.016), but increased IL6ST levels (ratio 1.18, p = 0.014). Results of the present study demonstrated systematic, statistically significant differences between pre-bowel and post-bowel preparation levels for three independent blood-based biomarkers (BAG4, CyFra21-1, cfDNA), illustrating the importance of timing of sample collection for biomarker analyses.


In vitro metabolism of benzo[a]pyrene-7,8-dihydrodiol and dibenzo[def,p]chrysene-11,12 diol in rodent and human hepatic microsomes.
Polycyclic aromatic hydrocarbons (PAHs) are contaminants that are ubiquitously found in the environment, produced through combustion of organic matter or petrochemicals, and many of which are procarcinogens. The prototypic PAH, benzo[a]pyrene (B[a]P) and the highly carcinogenic dibenzo[def,p]chrysene (DBC) are metabolically activated by isoforms of the P450 enzyme superfamily producing benzo[a]pyrene-7,8-dihydrodiol (B[a]P diol), dibenzo[def,p]chrysene-11,12 diol (DBC diol). Each of these diols can be further metabolized by cytochrome P450 enzymes to highly reactive diol-epoxide metabolites that readily react with DNA or by phase II conjugation facilitating excretion. To complement prior in vitro metabolism studies with parent B[a]P and DBC, both phase I metabolism and phase II glucuronidation of B[a]P diol and DBC diol were measured in hepatic microsomes from female B6129SF1/J mice, male Sprague-Dawley rats, and female humans. Metabolic parameters, including intrinsic clearance and Michaelis-Menten kinetics were calculated from substrate depletion data. Mice and rats demonstrated similar B[a]P diol phase I metabolic rates. Compared to rodents, human phase I metabolism of B[a]P diol demonstrated lower overall metabolic capacity, lower intrinsic clearance at higher substrate concentrations (>0.14μM), and higher intrinsic clearance at lower substrate concentrations (<0.07μM). Rates of DBC diol metabolism did not saturate in mice or humans and were highest overall in mice. Higher affinity constants and lower capacities were observed for DBC diol glucuronidation compared to B[a]P diol glucuronidation; however, intrinsic clearance values for these compounds were consistent within each species. Kinetic parameters reported here will be used to extend physiologically based pharmacokinetic (PBPK) models to include the disposition of B[a]P and DBC metabolites in animal models and humans to support future human health risk assessments.


Catechol-Based Antimicrobial Polymers.
Catechol is a key constituent in mussel adhesive proteins and is responsible for strong adhesive property and crosslinking formation. Plant-based polyphenols are also capable of chemical interactions similar to those of catechol and are inherently antimicrobial. This review reports a series of catechol-based antimicrobial polymers classified according to their antimicrobial mechanisms. Catechol is utilized as a surface anchoring group for adhering monomers and polymers of known antimicrobial properties onto various types of surfaces. Additionally, catechol's ability to form strong complexes with metal ions and nanoparticles was utilized to sequester these antimicrobial agents into coatings and polymer matrices. During catechol oxidation, reactive oxygen species (ROS) is generated as a byproduct, and the use of the generated ROS for antimicrobial applications was also introduced. Finally, polymers that utilized the innate antimicrobial property of halogenated catechols and polyphenols were reviewed.


Synthetic biology approaches for the production of plant metabolites in unicellular organisms.
Synthetic biology is the repurposing of biological systems for novel objectives and applications. Through the co-ordinated and balanced expression of genes, both native and those introduced from other organisms, resources within an industrial chassis can be siphoned for the commercial production of high-value commodities. This developing interdisciplinary field has the potential to revolutionize natural product discovery from higher plants, by providing a diverse array of tools, technologies, and strategies for exploring the large chemically complex space of plant natural products using unicellular organisms. In this review, we emphasize the key features that influence the generation of biorefineries and highlight technologies and strategic solutions that can be used to overcome engineering pitfalls with rational design. Also presented is a succinct guide to assist the selection of unicellular chassis most suited for the engineering and subsequent production of the desired natural product, in order to meet the global demand for plant natural products in a safe and sustainable manner.


Wheat straw vinegar: A more cost-effective solution than chemical fungicides for sustainable wheat plant protection.
Fusarium head blight (FHB), caused by the fungal pathogen Fusarium graminearum, is a destructive and widespread wheat disease. Chemical fungicides are becoming less effective at reducing the disease severity of FHB, and there is a need to find a more effective, low-cost natural product. A by-product of the pyrolysis of wheat straw is a condensate known as wheat straw vinegar, which was hypothesized to be an effective F. graminearum inhibitor in wheat. The organic and mineral compositions of wheat straw vinegar were analyzed. The results of GC-MS indicated that the major organic compounds in wheat straw vinegar are phenolics and acetic acid. The main inorganic elements in the liquid were K, Ca, S and Mg. A bio-test of wheat straw vinegar showed strong antifungal activity on F. graminearum growth and production of deoxynivalenol (DON) with an EC50 (concentration for 50% of maximal effect) value of 3.1 μl ml-1. Field tests showed that the application of wheat straw vinegar diluted 200-fold significantly decreased the wheat FHB infection rate and DON content by 66% and 69%, respectively. The control efficacy of wheat straw vinegar at a dilution of 200-fold was similar to that of typical chemical fungicide applications. The use of wheat straw vinegar may increase farmers' income by reducing the net fungicide costs. Therefore, wheat straw vinegar has high potential as a natural fungicide for the control of FHB and can reduce the dependence on synthetic fungicides.


Intervention of multi-modal activities for older adults with dementia translation to rural communities.
A Language-Enriched Exercise Plus Socialization (LEEPS) Program for older adults with Alzheimer's disease and related disorders (ADRD) was implemented in rural Wisconsin communities. Patterned after a university-based research intervention, (1) the LEEPS protocol entailed ongoing weekly to biweekly sessions with a trained volunteer and an individual with dementia, with exercise and language stimulation sessions interspersed with social or volunteer outings. Of 64 persons with ADRD who enrolled, 29 completed an initial follow-up assessment at an average of 10.65 months, and 8 completed a second follow-up at an average of 20.55 months. Results generally show stability in cognition, mood, and physical performance. Improvement was noted at the initial retest on 1 of the 3 physical fitness measures (arm curls; t = 2.61, P = .015), but self-rated quality of life declined slightly from baseline to the first retest (t = -2.09, P = .048). Change in the Mini-Mental State Examination at the first and second follow-ups (mean = +0.18 and -1.0, respectively) was negligible. The maintenance of function observed with LEEPS is an encouraging outcome, given the progressive nature of ADRD, but controlled investigations are needed to establish the efficacy of LEEPS. Barriers to implementation of an intensive activities-focused intervention in rural communities are discussed.


Biases in the identification of risk factor thresholds and J-curves.
For some diseases, there has been controversy about whether key risk factors are related linearly to the occurrence of disease events. This issue has important implications for strategies to modify risk factors, since nonlinear threshold or J-curve associations imply that risk factor modification is not beneficial beyond a certain level. This paper considers whether nonlinear risk factor associations can arise spuriously from selection mechanisms common in prospective cohort studies. Using theory, simulation, and cohort data, the authors show that selecting individuals based on their prior disease status leads to the primary risk factor being negatively confounded with other residual risk factors. If this confounding combines with effect modification between the primary and residual risk factors, as exists in cardiovascular disease, then the aggregate effect is nonlinear distortion of the risk factor relation. Such distortion can produce an apparent threshold or J-curve relation, even if the true underlying relation is linear. The authors conclude that nonlinear risk factor associations observed in primary or secondary prevention cohorts should be interpreted with caution because they may be consistent with an underlying linear lower-is-better relation. Randomized studies provide an important complement to prospective cohort studies when choosing between intensive and moderate risk factor modification strategies in high-risk populations.


Labour market participation after sickness absence due to cancer: a dynamic cohort study in Catalonia (Spain).
The consequences of cancer on working until retirement age remain unclear. This study aimed to analyse working life considering all possible labour market states in a sample of workers after sickness absence (SA) due to cancer and to compare their working life paths to those of a sample of workers without SA and with an SA due to other diseases. This was a retrospective dynamic cohort study among social security affiliates in Catalonia from 2012-2018. Cases consisted of workers with an SA due to cancer between 2012-2015 (N = 516) and were individually age- and sex-matched with those of affiliates with an SA due to other diagnoses and workers without an SA. All workers (N = 1,548, 56% women) were followed up from entry into the cohort until the end of 2018 to characterise nine possible weekly labour states. Sequence analysis, optimal matching, and multinomial logistic regression were used to identify and assess the probability of future labour market participation patterns (LMPPs). All analyses were stratified by sex. Compared with workers with an SA due to cancer, male workers with no SA and SA due to other causes showed a lower probability of being in the LMPP of death (aRRR 0.02, 95% CI: 0.00‒0.16; aRRR 0.17, 95% CI: 0.06‒0.46, respectively) and, among women, a lower probability of permanent disability and death (aRRR 0.24, 95% CI: 0.10‒0.57; aRRR 0.39, 95% CI: 0.19‒0.83, respectively). Compared to workers with SA due to cancer, the risk of early retirement was lower among workers with no SA (women, aRRR 0.60, 95% CI: 0.22‒1.65; men, aRRR 0.64, 95% CI: 0.27‒1.52), although these results were not statistically significant. Workplaces, many of which have policies common to all diagnoses, should be modified to the needs of cancer survivors to prevent an increasing frequency of early retirement and permanent disability when possible. Future studies should assess the impact of cancer on premature exit from the labour market among survivors, depending on cancer localisation and type of treatment.


The Determinants of Market Participation and Its Effect on Food Security of the Rural Smallholder Farmers in Limpopo and Mpumalanga Provinces, South Africa.
Addressing the disproportionate burden of food insecurity in South Africa requires targeted efforts to help smallholder farmers to access markets. The purpose of this study was to assess determinants of market participation and its contribution to household food security. The secondary data used in this study were collected from 1520 respondents; however, 389 smallholder farmers participated in the market. The Household Food Insecurity Access Scale revealed that out of the total sample size, 85% of the households were food insecure while 15% were food secure. Gender of household head, receiving social grants and higher wealth index positively impacted market participation. Having a family member with HIV had a negative impact on market participation among smallholder farmers. The results from the extended ordered probit regression model showed that household size, having a family member with HIV and agricultural assistance had a positive and significant contribution to the household food insecurity situation of the smallholder farmers. On the other hand, the educational level of household head, ownership of livestock, age of household head, gender of household head, and having access to social grants had a negative and significant effect on the food insecurity status. Access to education and the market can improve household food security. Linking smallholder farmers, particularly women and aged farmers, to markets should form an intrinsic part of the government's efforts to improve farming and food security and increase access to diversified food.


Hyperthermophilic DNA methyltransferase M.PabI from the archaeon Pyrococcus abyssi.
Genome sequence comparisons among multiple species of Pyrococcus, a hyperthermophilic archaeon, revealed a linkage between a putative restriction-modification gene complex and several large genome polymorphisms/rearrangements. From a region apparently inserted into the Pyrococcus abyssi genome, a hyperthermoresistant restriction enzyme [PabI; 5'-(GTA/C)] with a novel structure was discovered. In the present work, the neighboring methyltransferase homologue, M.PabI, was characterized. Its N-terminal half showed high similarities to the M subunit of type I systems and a modification enzyme of an atypical type II system, M.AhdI, while its C-terminal half showed high similarity to the S subunit of type I systems. M.PabI expressed within Escherichia coli protected PabI sites from RsaI, a PabI isoschizomer. M.PabI, purified following overexpression, was shown to generate 5'-GTm6AC, which provides protection against PabI digestion. M.PabI was found to be highly thermophilic; it showed methylation at 95 degrees C and retained at least half the activity after 9 min at 95 degrees C. This hyperthermophilicity allowed us to obtain activation energy and other thermodynamic parameters for the first time for any DNA methyltransferases. We also determined the kinetic parameters of kcat, Km, DNA, and Km, AdoMet. The activity of M.PabI was optimal at a slightly acidic pH and at an NaCl concentration of 200 to 500 mM and was inhibited by Zn2+ but not by Mg2+, Ca2+, or Mn2+. These and previous results suggest that this unique methyltransferase and PabI constitute a type II restriction-modification gene complex that inserted into the P. abyssi genome relatively recently. As the most thermophilic of all the characterized DNA methyltransferases, M.PabI may help in the analysis of DNA methylation and its application to DNA engineering.


Carcinoid crisis with fatal coronary spasm in a small localized peripheral bronchial carcinoid.
Presumptive coronary artery spasm, with characteristic ST-segment elevation followed by ventricular arrhythmia and cardiac arrest, is a very uncommon manifestation of the carcinoid crisis and has been shown on angiography only once in a patient with co-existing extensive atheromatous disease. We present the history of a 70-year-old man with angiographically documented fatal diffuse coronary spasm in the absence of significant atheromatosis, related to an unprovoked carcinoid crisis caused by a small peripheral atypical carcinoid tumour in the absence of metastasis.


Evaluation of noninvasive hemoglobin monitoring in children with congenital heart diseases.
Noninvasive measurement of blood hemoglobin could save time and decrease the risk of anemia and infection. The accuracy of CO-oximetry-derived noninvasive hemoglobin (Sp-Hb) had been evaluated in pediatric population; however, its accuracy in children with congenital heart disease has not been studied till date. We evaluated the accuracy of Sp-Hb in relation to laboratory-measured hemoglobin (Lab-Hb) in children with congenital heart disease. This prospective observational study included children with congenital heart disease undergoing procedural intervention. Sp-Hb measurements were obtained using Radical-7 Masimo pulse CO-oximeter and were compared against simultaneous Lab-Hb measurements obtained from the arterial line. Children were divided in cyanotic and acyanotic, and separate analysis was performed for each group. The values of both measurements were analyzed using Spearman's correlation coefficient and Bland-Altman analysis. Correlation was performed between Sp-Hb and Lab-Hb bias and each of arterial oxygen saturation and perfusion index. One-hundred and eleven pairs of readings were obtained from 65 children. The median (quartiles) age and weight of the children were 1 (1.2-4) years and 11 (8-17) kg, respectively. There was moderate correlation between Lab-Hb and Sp-Hb with a correlation coefficient (95% confidence interval [CI]) of 0.75 (0.63-0.83) in acyanotic children and 0.62 (0.37-0.79) in cyanotic children. The mean bias (95% limits of agreements) was -0.4 g/dL (-2.4 to 1.6 g/dL) and 1 g/dL (-2.7 to 4.6 g/dL) in acyanotic and cyanotic children, respectively. The mean bias between Sp-Hb and Lab-Hb showed a weak negative correlation with oxygen saturation (r [95% CI]): (-0.36 [-0.51--0.18]), and a weak positive correlation with the perfusion index (r [95% CI]): (0.19 [0.01-0.37]). The large bias and the wide limits of agreement between Sp-Hb and Lab-Hb denote that Masimo-derived Sp-Hb is not accurate in children with congenital heart disease especially in the cyanotic group; the error in Sp-Hb increases when oxygen saturation decreases.


Quantitative correlation between promoter methylation and messenger RNA levels of the reduced folate carrier.
Methotrexate (MTX) uptake is mediated by the reduced folate carrier (RFC). Defective drug uptake in association with decreased RFC expression is a common mechanism of MTX resistance in many tumor types. Heavy promoter methylation was previously identified as a basis for the complete silencing of RFC in MDA-MB-231 breast cancer cells, its role and prevalence in RFC transcription regulation are, however, not widely studied. In the current study, RFC promoter methylation was assessed using methylation specific PCR in a panel of malignant cell lines (n = 8), including MDA-MB-231, and M805, a MTX resistant cell line directly established from the specimen of a patient with malignant fibrohistocytoma, whom received multiple doses of MTX. A quantitative approach of real-time PCR for measuring the extent of RFC promoter methylation was developed, and was validated by direct bisulfite genomic sequencing. RFC mRNA levels were determined by quantitative real-time RT-PCR and were related to the extent of promoter methylation in these cell lines. A partial promoter methylation and RFC mRNA down-regulation were observed in M805. Using the quantitative approach, a reverse correlation (correlation coefficient = -0.59, p < 0.05) was identified between the promoter methylation and RFC mRNA levels in this a panel of malignant cell lines. This study further suggests that promoter methylation is a potential basis for MTX resistance. The quantitative correlation identified in this study implies that promoter methylation is possibly a mechanism involved in the fine regulation of RFC transcription.


Thyroid hormone's role in regulating brain glucose metabolism and potentially modulating hippocampal cognitive processes.
Cognitive performance is dependent on adequate glucose supply to the brain. Insulin, which regulates systemic glucose metabolism, has been recently shown both to regulate hippocampal metabolism and to be a mandatory component of hippocampally-mediated cognitive performance. Thyroid hormones (TH) regulate systemic glucose metabolism and may also be involved in regulation of brain glucose metabolism. Here we review potential mechanisms for such regulation. Importantly, TH imbalance is often encountered in combination with metabolic disorders such as diabetes, and may cause additional metabolic dysregulation and hence worsening of disease states. TH's potential as a regulator of brain glucose metabolism is heightened by interactions with insulin signaling, but there have been relatively few studies on this topic or on the actions of TH in a mature brain. This review discusses evidence for mechanistic links between TH, insulin, cognitive function, and brain glucose metabolism, and reaches the conclusion that TH may modulate memory processes, likely at least in part by modulation of central insulin signaling and glucose metabolism.


Impact of production systems on swine confinement buildings bioaerosols.
Hog production has been substantially intensified in Eastern Canada. Hogs are now fattened in swine confinement buildings with controlled ventilation systems and high animal densities. Newly designed buildings are equipped with conventional manure handling and management systems, shallow or deep litter systems, or source separation systems to manage the large volumes of waste. However, the impacts of those alternative production systems on bioaerosol concentrations within the barns have never been evaluated. Bioaerosols were characterized in 18 modern swine confinement buildings, and the differences in bioaerosol composition in the three different production systems were evaluated. Total dust, endotoxins, culturable actinomycetes, fungi, and bacteria were collected with various apparatuses. The total DNA of the air samples was extracted, and quantitative polymerase chain reaction (PCR) was used to assess the total number of bacterial genomes, as a total (culturable and nonculturable) bacterial assessment. The measured total dust and endotoxin concentrations were not statistically different in the three studied production systems. In buildings with sawdust beds, actinomycetes and molds were found in higher concentrations than in the conventional barns. Aspergillus, Cladosporium, Penicillium, and Scopulariopsis species were identified in all the studied swine confinement buildings. A. flavus, A. terreus, and A. versicolor were abundantly present in the facilities with sawdust beds. Thermotolerant A. fumigatus and Mucor were usually found in all the buildings. The culturable bacteria concentrations were higher in the barns with litters than in the conventional buildings, while real-time PCR revealed nonstatistically different concentrations of total bacteria in all the studied swine confinement buildings. In terms of workers' respiratory health, barns equipped with a solid/liquid separation system may offer better air quality than conventional buildings or barns with sawdust beds. The impact of ventilation rates, air distribution, or building design still has to be explored.


Gender-selective toxicity of thimerosal.
A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4-76.8mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.


Cancer disease predictive diagnosis: BAT/CD3-positive lymphocytes in cancer patients.
BAT is an immune-activating monoclonal antibody produced against Daudi cell membranes and selected for stimulating lymphocyte proliferation. The anti-tumor activity of BAT is related to its immunostimulatory properties. Both T and NK cells mediate the anti-tumor activity of BAT. CD4-positive T cells respond to BAT activation by proliferation and INF-gamma production. The aim of the study was to assess the probability that the BAT monoclonal antibody binding capacity to T cells is a marker for different cancers. Human peripheral blood T cells from colon, breast and prostate cancer patients, as well as healthy volunteer donors, were tested for the percentage of binding to BAT mAb (BAT/CD3 cells) by FACS analysis. All patients were tested before undergoing surgery or treatment, and their diagnosis was confirmed by histology. The results showed that the percentage of BAT monoclonal antibody binding to CD3-positive T cells in the peripheral blood was different in cancer patients with diverse tumor types. We found that lymphocytes from the blood of healthy donors contained 25% BAT/CD3 cells. In colon and breast cancer patients, a significant decrease to 13 and 11% of BAT/CD3 cells was found. In contrast, these cells increased ><50% in patients with prostate cancer. These findings may have a potential diagnostic significance and also assist in the evaluation of strategies for the therapeutic use of BAT for different cancer patients.


Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets.
Intratumor subsets with tumor-initiating features in glioblastoma are likely to survive treatment. Our goal is to identify the key factor in the process by which cells develop temozolomide (TMZ) resistance. Resistant cell lines derived from U87MG and A172 were established through long-term co-incubation of TMZ. Primary tumors obtained from patients were maintained as patient-derived xenograft for studies of tumor-initating cell (TIC) features. The cell manifestations were assessed in the gene modulated cells for relevance to drug resistance. Among the mitochondria-related genes in the gene expression databases, superoxide dismutase 2 (SOD2) was a significant factor in resistance and patient survival. SOD2 in the resistant cells functionally determined the cell fate by limiting TMZ-stimulated superoxide reaction and cleavage of caspase-3. Genetic inhibition of the protein led to retrieval of drug effect in mouse study. SOD2 was also associated with the TIC features, which enriched in the resistant cells. The CD133+ specific subsets in the resistant cells exhibited superior superoxide regulation and the SOD2-related caspase-3 reaction. Experiments applying SOD2 modulation showed a positive correlation between the TIC features and the protein expression. Finally, co-treatment with TMZ and the SOD inhibitor sodium diethyldithiocarbamate trihydrate in xenograft mouse models with the TMZ-resistant primary tumor resulted in lower tumor proliferation, longer survival, and less CD133, Bmi-1, and SOD2 expression. SOD2 plays crucial roles in the tumor-initiating features that are related to TMZ resistance. Inhibition of the protein is a potential therapeutic strategy that can be used to enhance the effects of chemotherapy.


Neural Variability Is Quenched by Attention.
Attention can be subdivided into several components, including alertness and spatial attention. It is believed that the behavioral benefits of attention, such as increased accuracy and faster reaction times, are generated by an increase in neural activity and a decrease in neural variability, which enhance the signal-to-noise ratio of task-relevant neural populations. However, empirical evidence regarding attention-related changes in neural variability in humans is extremely rare. Here we used EEG to demonstrate that trial-by-trial neural variability was reduced by visual cues that modulated alertness and spatial attention. Reductions in neural variability were specific to the visual system and larger in the contralateral hemisphere of the attended visual field. Subjects with higher initial levels of neural variability and larger decreases in variability exhibited greater behavioral benefits from attentional cues. These findings demonstrate that both alertness and spatial attention modulate neural variability and highlight the importance of reducing/quenching neural variability for attaining the behavioral benefits of attention.SIGNIFICANCE STATEMENT Attention is thought to improve perception by increasing the signal-to-noise ratio of the neuronal populations that encode the attended stimulus. Signal-to-noise ratio can be enhanced by increasing neural response (signal) and/or by reducing neural variability (noise). The ability of attention to increase neural responses has been studied extensively, but the effects of attention on neural variability have rarely been examined in humans. Here, we demonstrate that modulating different components of attention, including alertness and spatial attention, reduces neural variability in humans. Furthermore, we show that subjects with larger reductions in neural variability exhibit greater behavioral benefits from attention. These results demonstrate that reduction of neural variability is a fundamental feature of attentional processes in humans with clear behavioral importance.


Regulation of tPA in endothelial cells exposed to cyclic strain: role of CRE, AP-2, and SSRE binding sites.
We have previously reported that exposure of cultured bovine aortic endothelial cells (EC) to 10% average strain resulted in an increase in tissue plasminogen activator (tPA) mRNA, immunoreactive tPA protein, and tPA activity in the medium. The present study was designed to examine the regulation of tPA gene expression in EC by cyclic strain. We performed a functional analysis of the tPA promoter by transfecting bovine aortic EC with a 1.4-kilobase (kb) construct of the human tPA promoter coupled to chloramphenicol acetyltransferase. We found that subjecting the EC to 10% average strain (and not 6% average strain) resulted in a 2.6-fold increase in activity of the 1.4-kb tPA promoter by 4 h. Analysis of deletion mutants of the promoter transfected into EC demonstrated a 60% drop-off in activity between position -145 and -105. Deoxyribonuclease I protection analysis of the segment downstream of position -196 suggested involvement of activator protein-2 (AP-2) and adenosine 3',5'-cyclic monophosphate-responsive element (CRE)-like binding sites, which was confirmed by electrophoretic mobility shift assays. Site-directed mutants of either the AP-2 or CRE-like regions resulted in a 65% decrease in activity compared with the wild type. Double mutations abolished basal transcription and any strain-induced activity. A shear stress responsive element (SSRE) binding site is present at -945, but site-directed mutants did not show any drop in activity compared with wild type by cyclic strain. These studies demonstrate that cyclic strain regulates tPA gene transcription in bovine aortic EC and that this transcriptional activation is dependent on factors that are similar to those activated with phorbol ester.


Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.
Exposure to arsenic in drinking water is a global health problem and arsenic-induced skin lesions are hallmark of chronic arsenic toxicity. We and others have reported germline genetic variations as risk factors for such skin lesions. The role of copy number variation (CNV) in the germline DNA in this regard is unknown. From a large prospectively followed-up cohort, exposed to arsenic, we randomly selected 2171 subjects without arsenic-induced skin lesions at enrollment and genotyped their whole blood DNA samples on Illumina Cyto12v2.1 SNP chips to generate DNA copy number. Participants were followed up every 2 years for a total of 8 years, especially for the development of skin lesions. In Cox regression models, each CNV segment was used as a predictor, accounting for other potential covariates, for incidence of skin lesions. The presence of genomic deletion(s) in a number of genes (OR5J2, GOLGA6L7P, APBA2, GALNTL5, VN1R31P, PHKG1P2, SGCZ, ZNF658) and lincRNA genes (RP11-76I14.1, CTC-535 M15.2, RP11-73B2.2) were associated with higher risk [HR between 1.67 (CI 1.3-2.1) and 2.15 (CI 1.5-2.9) for different CNVs] for development of skin lesions independent of gender, age, and arsenic exposure. Some deletions had stronger effect in a specific gender (ZNF658 in males, SGCZ in females) and some had stronger effect in higher arsenic exposure (lincRNA CTD-3179P9.1) suggesting a possible gene-environment interaction. This first genome-wide CNV study in a prospectively followed-up large cohort, exposed to arsenic, suggests that DNA deletion in several genes and lincRNA genes may predispose an individual to a higher risk of development of arsenic-induced skin lesions.


Gulf War veterans and Iraqi nerve agents at Khamisiyah: postwar hospitalization data revisited.
Chemical warfare agents were demolished by US soldiers at Khamisiyah, Iraq, in March 1991. The authors investigated postwar morbidity for Gulf War veterans, contrasting those who may have been exposed to low gaseous levels of nerve agents and those unlikely to have been exposed. Cox regression modeling was performed for hospitalizations from all causes and hospitalizations from diagnoses within 15 categories during the period March 10, 1991, through December 31, 2000, for the duration of active-duty status. After adjustment for all variables in the model, only two of 37 models suggested that personnel possibly exposed to subclinical doses of nerve agents might be at increased risk for hospitalization from circulatory diseases, specifically cardiac dysrhythmias. Of the 724 hospitalizations for cardiac dysrhythmias, 203 were in the potentially exposed group, slightly higher than expected (risk ratio = 1.23, 95% confidence interval: 1.04, 1.44). The increase was small in comparison with potential observational variability, but the findings are provocative and warrant further evaluation. Veterans possibly exposed to nerve agents released by the Khamisiyah demolition were not found to be at increased risk for hospitalizations from any other chronic diseases nearly 10 years after the Gulf War.


Emergency department presentations in infants: Predictors from an Australian birth cohort.
Infants under 12 months of age are disproportionately represented amongst emergency department (ED) presentations, and infants are more likely to be frequent ED users. This study aimed to describe and identify psychosocial predictors of ED presentation in infants. A prospective birth cohort from Queensland and New South Wales (Environments for Healthy Living) was used to understand infant health service use. Baseline and 12-month questionnaire data pertaining to children born between 2006 and 2011 were used to identify predictors of ED presentation, using multiple regression analysis. Of the 2184 children in the cohort with available baseline and 12-month data, 579 (27%) presented at least once to an ED during their first 12 months of life. Statistically significant predictors of ED presentation in the multivariate analysis included the mother having asthma (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.15-2.39) and a higher Kessler-6 score (a measure of psychological distress) of the primary carer at baseline (OR 1.04, 95% CI 1.01-1.08). Maternal education level was not associated with ED presentations of infants. This study describes maternal and child factors of children who present to the ED in the first year of life. Factors related to an infant's support system were found to be predictors for an ED presentation in the first year of life. This study emphasises the need to review the maternal medical history and psychosocial situation. There may be benefits for health-care practitioners to take the opportunity (such as during routine childhood immunisation) to perform a brief screening tool (such as the Kessler-6) to understand psychological distress experienced by mothers. This may influence the likelihood of a child presenting to an ED within the first 12 months of life.


Right brain is important for students' achievements in science.
Relations between the hearing durations of right and left ears and points on the introductory examination for entrance to the Science School of Ataturk University in Erzurum were investigated in 31 male and 13 female students. The hearing duration of the left ear was significantly associated with the scores of the examination for the university entrance, the hearing duration for the right ear being not significantly related to the examination scores. The results suggest that the right brain would be beneficial for the students' achievements in science.


Combination therapy of radiation and immunomodulators in the treatment of MM46 tumor transplanted in C3H/He mice.
Female C3H/He mice aged 10 weeks with transplanted MM46 tumor were used in an investigation of the timing of administration of immunomodulators, such as PSK (a protein-bound polysaccharide prepared from Coriolus versicolor), OK-432 (streptococcal preparation), bestatin (inhibitor of aminopeptidase B) combined with two fractionated local irradiation with the total dose of 3,000 rad. The daily dose of 250 mg/kg of PSK, 1.0 KE/mouse of OK-432, or 300 micrograms/mouse of bestatin were injected intraperitoneally for 4 consecutive days before or after irradiation. The antitumor effect was evaluated by the changes of tumor volume and survival curves. When PSK or OK-432 was administered after irradiation, tumor growth was decreased and 60-day survival rate and survival curve were significantly elongated compared with the control group and the group to which PSK or OK-432 were administered before irradiation (p less than 0.025, p less than 0.05, respectively). As for bestatin, no remarkable difference was observed irrespective of the timing of administration. These results suggested that some immunomodulators show different antitumor activity depending on the combined timing relative to radiotherapy.


EpiSouth: a network for communicable disease control in the Mediterranean region and the Balkans.
The countries around the Mediterranean Sea share epidemiological characteristics and public health problems. In 2006 the EpiSouth Project was started as a framework for collaboration for communicable diseases surveillance and training in the Mediterranean Basin. As of December 2008, 26 countries from southern Europe, the Balkans, North Africa and the Middle-East are members of EpiSouth and several international organisations and institutions collaborate: the European Commission (EC), the European Centre for Disease Prevention and Control (ECDC), the Italian Ministry of Work, Health and Social Policies and the World Health Organization (WHO). The project is coordinated by the Italian national public health institute and three work packages (WPs) Cross-border epidemic intelligence, vaccine preventable diseases and migrants and Cross-border emerging zoonoses are operated by the national institutes of France, Bulgaria and Greece. These WPs constitute technical pillars on which the project develops. Networking and Training are WPs dedicated to capacity building and are run by the Padua Teaching Hospital (Italy) and the Spanish national public health institute. A steering committee guides EpiSouth's activities while all countries collaborate through WP steering teams and focal points. A number of outcomes have been accomplished and documents with results are available from the EpiSouth website which hosts a public website and a restricted area for direct sharing of information among the participants. Five electronic bulletins were published, two trainings for 63 participants performed, national epidemic intelligence systems were evaluated, a preliminary survey on vaccine-preventable diseases and migrants performed, and a list of priorities for emerging zoonoses in the Mediterranean area was selected. Overall the network succeeded in creating cohesion, mutual trust and concrete collaboration on cross-border public health issues in a geographical area that is not addressed as a whole by any other initiative or organisation.


Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus.
Patients with Doublecortin (DCX) mutations have severe cortical malformations associated with mental retardation and epilepsy. Dcx knockout (KO) mice show no major isocortical abnormalities, but have discrete hippocampal defects. We questioned the functional consequences of these defects and report here that Dcx KO mice are hyperactive and exhibit spontaneous convulsive seizures. Changes in neuropeptide Y and calbindin expression, consistent with seizure occurrence, were detected in a large proportion of KO animals, and convulsants, including kainate and pentylenetetrazole, also induced seizures more readily in KO mice. We show that the dysplastic CA3 region in KO hippocampal slices generates sharp wave-like activities and possesses a lower threshold for epileptiform events. Video-EEG monitoring also demonstrated that spontaneous seizures were initiated in the hippocampus. Similarly, seizures in human patients mutated for DCX can show a primary involvement of the temporal lobe. In conclusion, seizures in Dcx KO mice are likely to be due to abnormal synaptic transmission involving heterotopic cells in the hippocampus and these mice may therefore provide a useful model to further study how lamination defects underlie the genesis of epileptiform activities.