Emergency supply of prescription-only medicines to patients by community pharmacists: a mixed methods evaluation incorporating patient, pharmacist and GP perspectives.
To evaluate and inform emergency supply of prescription-only medicines by community pharmacists (CPs), including how the service could form an integral component of established healthcare provision to maximise adherence. Mixed methods. 4 phases: prospective audit of emergency supply requests for prescribed medicines (October-November 2012 and April 2013); interviews with CPs (February-April 2013); follow-up interviews with patients (April-May 2013); interactive feedback sessions with general practice teams (October-November 2013). 22 community pharmacies and 6 general practices in Northwest England. 27 CPs with experience of dealing with requests for emergency supplies; 25 patients who received an emergency supply of a prescribed medicine; 58 staff at 6 general practices. Clinical audit in 22 pharmacies over two 4-week periods reported that 526 medicines were requested by 450 patients. Requests peaked over a bank holiday and around weekends. A significant number of supplies were made during practice opening hours. Most requests were for older patients and for medicines used in long-term conditions. Difficulty in renewing repeat medication (forgetting to order, or prescription delays) was the major reason for requests. The majority of medicines were 'loaned' in advance of a National Health Service (NHS) prescription. Interviews with CPs and patients indicated that continuous supply had a positive impact on medicines adherence, removing the need to access urgent care. General practice staff were surprised and concerned by the extent of emergency supply episodes. CPs regularly provide emergency supplies to patients who run out of their repeat medication, including during practice opening hours. This may aid adherence. There is currently no feedback loop, however, to general practice. Patient care and interprofessional communication may be better served by the introduction of a formally structured and funded NHS emergency supply service from community pharmacies, with ongoing optimisation of repeat prescribing.


Regional cerebral blood flow in mood disorders. I. Comparison of major depressives and normal controls at rest.
We measured regional cerebral blood flow with the xenon 133 inhalation technique in 41 patients with major depressive disorder and 40 matched, normal controls during an eyes-closed, resting condition. The depressed group had a marked reduction in global cortical blood flow. To examine topographic abnormalities, traditional multivariate analyses were applied, as well as a new scaled subprofile model developed to identify abnormal functional neural networks in clinical samples. Both approaches indicated that the depressed sample had an abnormality in topographic distribution of blood flow, in addition to the global deficit. The scaled subprofile model identified the topographic abnormality as being due to flow reduction in the depressed patients in selective frontal, central, superior temporal, and anterior parietal regions. This pattern may reflect dysfunction in the parallel distributed cortical network involving frontal and temporoparietal polymodal association areas. The extent of this topographic abnormality, as revealed by the scaled subprofile model, was associated with both patient age and severity of depressive symptoms.


Simple sequence repeats in Helicobacter canadensis and their role in phase variable expression and C-terminal sequence switching.
Helicobacter canadensis is an emerging human pathogen and zoonotic agent. The genome of H. canadensis was sequenced previously and determined to contain 29 annotated coding regions associated with homopolymeric tracts. Twenty-one of the repeat-associated coding regions were determined to be potentially transcriptionally or translationally phase variable. In each case the homopolymeric tract was within the predicted promoter region or at the 5' end of the coding region, respectively. However, eight coding sequences were identified with simple sequence repeats toward the 3' end of the open reading frame. In these cases, the repeat tract would be too far into the coding region to be mediating translational phase variation. All of the 29 coding region-associated homopolymeric tracts display variability in tract length in the sequencing read data. Twenty-nine coding regions have been identified in the genome sequence of Helicobacter canadensis strain NCTC13241 that show variations in homopolymeric tract length in the bacterial population, indicative of phase variation. Five of these are potentially associated with promoter regions, which would lead to transcriptional phase variation. Translational phase variation usually switches expression of a gene ON and OFF due to the repeat region being located sufficiently close to the initiation codon for the resulting frame-shift to lead to a premature termination codon and stop the translation of the protein. Sixteen of the 29 coding regions have homopolymeric tracts characteristic of translational phase variation. For eight coding sequences with repeats located later in the reading frame, changes in the repeat tract length would alter the protein sequence at the C-terminus but not stop the expression of the protein. This mechanism of C-terminal phase variation has implications for stochastic switching of protein sequence in bacterial species that already undergo transcriptional and translational phase variation.


Ghrelin mediates exercise endurance and the feeding response post-exercise.
Exercise training has several well-established health benefits, including many related to body weight, appetite control, and blood glucose homeostasis. However, the molecular mechanisms and, in particular, the hormonal systems that mediate and integrate these beneficial effects are poorly understood. In the current study, we aimed to investigate the role of the hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR; ghrelin receptor), in mediating the effects of exercise on food intake and blood glucose following exercise as well as in regulating exercise endurance capacity. We used two mouse models of treadmill running to characterize the changes in plasma ghrelin with exercise. We also assessed the role of the ghrelin system to influence food intake and blood glucose after exercise, exercise endurance, and parameters potentially linked to responses to exercise. Mice lacking GHSRs (GHSR-null mice) and wild-type littermates were studied. An acute bout of exercise transiently elevated plasma acyl-ghrelin. Without the action of this increased ghrelin on GHSRs (as in GHSR-null mice), high intensity interval exercise markedly reduced food intake compared to control mice. The effect of exercise to acutely raise blood glucose remained unmodified in GHSR-null mice. Exercise-induced increases in plasma ghrelin positively correlated with endurance capacity, and time to exhaustion was reduced in GHSR-null mice as compared to wild-type littermates. In an effort to mechanistically explain their reduced exercise endurance, exercised GHSR-null mice exhibited an abrogated sympathoadrenal response, lower overall insulin-like growth factor-1 levels, and altered glycogen utilization. Exercise transiently increases plasma ghrelin. GHSR-null mice exhibit decreased food intake following high intensity interval exercise and decreased endurance when submitted to an exercise endurance protocol. These data suggest that an intact ghrelin system limits the capacity of exercise to restrict food intake following exercise, although it enhances exercise endurance.


Beam cleanup and image restoration with a photorefractive polymeric composite.
We demonstrate, for the first time to our knowledge, the use of a photorefractive polymeric composite to clean a phase-distorted laser beam and reconstruct a badly distorted image. Advantageous qualities including relatively high figures of merit, ease of processability, and low cost make this class of materials attractive when compared with their inorganic crystalline counterparts. In addition, we used four-wave-mixing and holographic techniques to obtain an internal diffraction efficiency of approximately 31% at 54.5 V/micron and a two-beam-coupling gain coefficient of gamma = 17 cm-1 at 54.5 V/micron under our experimental conditions.


Adaptive Upregulation of EGFR Limits Attenuation of Tumor Growth by Neutralizing IL6 Antibodies, with Implications for Combined Therapy in Ovarian Cancer.
Excess production of the proinflammatory IL6 has both local and systemic tumor-promoting activity in many cancers, including ovarian cancer. However, treatment of advanced ovarian cancer patients with a neutralizing IL6 antibody yielded little efficacy in a previous phase II clinical trial. Here, we report results that may explain this outcome, based on the finding that neutralizing antibodies to IL6 and STAT3 inhibition are sufficient to upregulate the EGFR pathway in high-grade serous and other ovarian cancer cells. Cell treatment with the EGFR inhibitor gefitinib abolished upregulation of the EGFR pathway. Combining neutralizing IL6 antibodies and gefitinib inhibited malignant cell growth in 2D and 3D culture. We found that ErbB-1 was localized predominantly in the nucleus of ovarian cancer cells examined, contrasting with plasma membrane localization in lung cancer cells. Treatment with anti-IL6, gefitinib, or their combination all led to partial restoration of ErbB-1 on the plasma membrane. In vivo experiments confirmed the effects of IL6 inhibition on the EGFR pathway and the enhanced activity of a combination of anti-IL6 antibodies and gefitinib on malignant cell growth. Taken together, our results offer a preclinical rationale to combine anti-IL6 and gefitinib to treat patients with advanced stage ovarian cancer.


Optical guided-wave devices.
Optical fiber is rapidly becoming the transmission medium of choice for new telecommunication systems. For a true lightwave network to evolve, however, optical control devices such as optical switches and multiplexer-demultiplexers will be essential. Optical guided-wave devices built with photolithographic fabrication techniques and electro-optic substrates are compact, low drive power devices that provide these functions. Research is particularly advanced on integrated-optic devices based on waveguides formed by titanium diffused into lithium niobate. Switch arrays, tunable filters, and high-speed modulators have been demonstrated and used in research systems experiments.


The Mitochondrial Citrate Carrier (SLC25A1) Sustains Redox Homeostasis and Mitochondrial Metabolism Supporting Radioresistance of Cancer Cells With Tolerance to Cycling Severe Hypoxia.
Pronounced resistance of lung cancer cells to radiotherapy and chemotherapy is a major barrier to successful treatment. Herein, both tumor hypoxia and the upregulation of the cellular antioxidant defense systems observed during malignant progression can contribute to radioresistance. We recently found that exposure to chronic cycling severe hypoxia/reoxygenation stress results in glutamine-dependent upregulation of cellular glutathione (GSH) levels and associated radiation resistance opening novel routes for tumor cell-specific radiosensitization. Here, we explored the role of the mitochondrial citrate carrier (SLC25A1) for the improved antioxidant defense of cancer cells with tolerance to acute and chronic severe hypoxia/reoxygenation stress and the use of pharmacologic SLC25A1 inhibition for tumor cell radiosensitization. Exposure to acute or chronic cycling severe hypoxia/reoxygenation stress triggered upregulated expression of SLC25A1 in lung cancer, prostate cancer, and glioblastoma cells in vitro. Interestingly, exposure to ionizing radiation (IR) further promoted SLC25A1 expression. Inhibition of SLC25A1 by 1,2,3-benzene-tricarboxylic acid (BTA) disturbed cellular and mitochondrial redox homeostasis, lowered mitochondrial metabolism, and reduced metabolic flexibility of cancer cells. Even more important, combining IR with BTA was able to overcome increased radioresistance induced by adaptation to chronic cycling severe hypoxia/reoxygenation stress. This radiosensitizing effect of BTA-treated cells was linked to increased reactive oxygen species and reduced DNA repair capacity. Of note, key findings could be reproduced when using the SLC25A1-inhibitor 4-Chloro-3-[[(3-nitrophenyl)amino]sulfonyl]-benzoic acid (CNASB). Moreover, in silico analysis of publically available databases applying the Kaplan-Meier plotter tool (kmplot.com) revealed that overexpression of SLC25A1 was associated with reduced survival of lung cancer patients suggesting a potential link to aggressive cancers. We show that SLC25A1 can contribute to the increased antioxidant defense of cancer cells allowing them to escape the cytotoxic effects of IR. Since upregulation of SLC25A1 is induced by adverse conditions in the tumor environment, exposure to IR, or both pharmacologic inhibition of SLC25A1 might be an effective strategy for radiosensitization of cancer cells particularly in chronically hypoxic tumor fractions.


Child Health CheckPoint: cohort summary and methodology of a physical health and biospecimen module for the Longitudinal Study of Australian Children.
'Growing Up in Australia: The Longitudinal Study of Australian Children' (LSAC) is Australia's only nationally representative children's longitudinal study, focusing on social, economic, physical and cultural impacts on health, learning, social and cognitive development. LSAC's first decade collected wide-ranging repeated psychosocial and administrative data; here, we describe the Child Health CheckPoint, LSAC's dedicated biophysical module. LSAC recruited a cross-sequential sample of 5107 infants aged 0-1 year and a sample of 4983 children aged 4-5 years in 2004, since completing seven biennial visits. CheckPoint was a cross-sectional wave that travelled Australia in 2015-2016 to reach LSAC's younger cohort at ages 11-12 years between LSAC waves 6 and 7. Parent-child pairs participated in comprehensive assessments at 15 Assessment Centres nationwide or, if unable to attend, a shorter home visit. CheckPoint's intergenerational, multidimensional measures were prioritised to show meaningful variation within normal ranges and capture non-communicable disease (NCD) phenotype precursors. These included anthropometry, physical activity, fitness, time use, vision, hearing, and cardiovascular, respiratory and bone health. Biospecimens included blood, saliva, buccal swabs (also from second parent), urine, hair and toenails. The epidemiology and parent-child concordance of many measures are described in separate papers. 1874 (54% of eligible) parent-child pairs and 1051 second parents participated. Participants' geographical distribution mirrored the broader Australian population; however, mean socioeconomic position and parental education were higher and fewer reported non-English-speaking or Indigenous backgrounds. Application of survey weights partially mitigates that the achieved sample is less population representative than previous waves of LSAC due to non-random attrition. Completeness was uniformly high for phenotypic data (>92% of eligible), biospecimens (74%-97%) and consent (genetic analyses 98%, accessing neonatal blood spots 97%, sharing 96%). CheckPoint enriches LSAC to study how NCDs develop at the molecular and phenotypic levels before overt disease emerges, and clarify the underlying dimensionality of health in childhood and mid-adulthood.


The Genetic Structure of Pseudoperonospora cubensis Populations.
Pseudoperonospora cubensis is a destructive foliar pathogen of economically important cucurbitaceous crops in the United States and worldwide. In this study, we investigated the genetic structure of 465 P. cubensis isolates from three continents, 13 countries, 19 states of the United States, and five host species using five nuclear and two mitochondrial loci. Bayesian clustering resolved six genetic clusters and suggested some population structure by geographic origin and host, because some clusters occurred more or less frequently in particular categories. All of the genetic clusters were present in the sampling from North America and Europe. Differences in cluster occurrence were observed by country and state. Isolates from cucumber had different cluster composition and lower genetic diversity than isolates from other cucurbits. Because genetic structuring was detected, isolates that represent the genetic variation in P. cubensis should be used when developing diagnostic tools, fungicides, and resistant host varieties. Although this study provides an initial map of global population structure of P. cubensis, future genotyping of isolates could reveal population structure within specific geographic regions, across a wider range of hosts, or during different time points during the growing season.


Lateral Posterior Tibial Slope in Male and Female Athletes Sustaining Contact Versus Noncontact Anterior Cruciate Ligament Tears: A Prospective Study.
Lateral posterior tibial slope (PTS) has been identified as a risk factor for primary anterior cruciate ligament (ACL) tears. The purpose was to prospectively determine if there was a difference in lateral PTS between male and female athletes sustaining contact ACL tears as compared with a group of sex-, age-, and activity-matched athletes who sustained noncontact ACL tears. It was hypothesized that there would be no difference in degree of lateral PTS between contact and noncontact mechanisms among patients sustaining primary ACL tears in sports. Cohort study; Level of evidence, 3. Data from patients who underwent primary ACL reconstruction without posterior cruciate ligament injury between 2016 and 2018 by a single surgeon were prospectively analyzed. Measurements of lateral PTS were performed on magnetic resonance imaging. Mean values of lateral PTS were compared between the ACL tear groups. Additionally, a group of patients with intact knee ligaments were matched to patients with ACL tears to serve as controls. A total of 245 patients had complete primary ACL tears during the inclusion period. Of these, 56 (23%) reported a contact mechanism of injury at the time of ACL tear, and 56 patients who sustained noncontact ACL tears were matched to the contact ACL tear group. There were no significant differences in sex (P≥ .999), age (P = .990), or body mass index (P = .450) between the patient groups. The mean lateral PTS was 9.1°± 2.9° for the ACL contact and 9.9°± 3.0° for the ACL noncontact group (P = .180). There was a significant difference in mean lateral PTS between the ACL tear groups (noncontact and contact: 9.5°± 3.0°) and matched control group (5.6°± 1.9°, P = .0001). The lateral PTS was significantly increased among patients with contact and noncontact ACL tears as compared with controls. However, there were no differences in lateral PTS between patients who sustained contact and noncontact ACL tears. Lateral PTS measured on magnetic resonance imaging does not appear to be predictive of the mechanism of injury type among patients who sustain a contact or noncontact primary ACL tear.


Common gynecological challenges in adolescents with sickle cell disease.
Sickle cell anemia is one of the most common genetic blood disorders worldwide. Individuals with sickle cell disease (SCD) experience clinical manifestations such as chronic anemia, developmental delay, vaso-occlusive pain, acute chest syndrome, and neurological complications. Adolescent girls with SCD face unique gynecological challenges including delayed puberty marked by a later onset in menarche, vaso-occlusive pain associated with their menstrual cycle, and underdiagnosed abnormal uterine bleeding. This review focuses on these challenges with particular emphasis on delayed menarche and vaso-occlusive pain episodes associated with menstruation, in addition to the evaluation and initial management of heavy menstrual bleeding for adolescents with SCD. We highlight research opportunities in this neglected area to help enhance the comprehensive care model for this population.


5-Methylcytosine in eukaryotic DNA.
A small portion of the cytosine residues in the DNA of higher eukaryotes as well as in that of many lowe eukaryotes if methylated. The resulting 5-methylcytosine residues occur in specific in the DNA, usually adjacent to guanine residues on the 3' side. This methylation of eukaryotic DNA has been proposed to function in many ways, including control of transcription, maintenance of chromosome structure, repair of DNA, establishment of preferred sites for mutation, oncogenic transformation, and, in certain systems, protection of DNA against enzymatic degradation.


Arsenite renal apoptotic effects in chickens co-aggravated by oxidative stress and inflammatory response.
The kidney is the most crucial site for the excretion of arsenic and its metabolites. In this study, Hy-line chickens exposed to different toxicologically relevant doses of arsenic (0, 7.5, 15 and 30 mg kg-1 diet) presented marked renal injury as evidenced by the increased leakage of blood urea nitrogen (up to 2.6 folds) and creatinine (up to 2.3 folds). Furthermore, increased content of renal arsenic (up to 30 folds) and malondialdehyde restrained anti-hydroxyl radical ability, and the activities of antioxidant enzymes (glutathione peroxidase, catalase) further corroborated extensive renal damage. Meanwhile, as another cellular adaptive survival strategy, inflammation responses were quickly detected upon arsenic exposure as evidenced by elevated nuclear migration of nuclear factor-κB (NF-κB) and inflammation-related phenotypes. It was further noted that arsenic-induced mitochondrial damage was accompanied by accumulation of p53 initiated mitochondrial apoptosis pathway in nephrocyte, eventually elevating the apoptosis rate (up to 9.1 folds) compared to that of the control groups. Noticeably, correlation analysis illustrated that this mitochondrial apoptotic pathway was initiated following oxidative stress and inflammatory response. This study demonstrated that As2O3 exposure induced oxidative stress and inflammatory-mediated nephrotoxicity in a dose- and time-dependent manner, eventually leading to apoptosis through a mitochondria-dependent pathway in chicken kidneys.


Synthetic delta-9-tetrahydrocannabinol (dronabinol) can improve the symptoms of schizophrenia.
We are reporting improvement of symptoms of schizophrenia in a small group of patients who received the cannabinoid agonist dronabinol (synthetic Delta-9-tetrahydrocannabinol). Before this report, cannabinoids had usually been associated with worsening of psychotic symptoms. In a heuristic, compassionate use study, we found that 4 of 6 treatment-refractory patients with severe chronic schizophrenia but who had a self-reported history of improving with marijuana abuse improved with dronabinol. This improvement seems to have been a reduction of core psychotic symptoms in 3 of the 4 responders and not just nonspecific calming. There were no clinically significant adverse effects. These results complement the recent finding that the cannabinoid blocker rimonabant does not improve schizophrenic symptoms and suggest that the role of cannabinoids in psychosis may be more complex than previously thought. They open a possible new role for cannabinoids in the treatment of schizophrenia.


Comparison of gene expression of epicardial and visceral adipocytes with regard to the differentiation stage.
Our study focused on the ability of epicardial adipocytes to produce bioactive substances and compare the extent of this production with the production of adipokines in visceral adipocytes, which are well known endocrine cells capable of contributing to the development of atherosclerosis. The gene expression of human cytokines (IL-6, IL-8, IL-18, RANTES and MCP-1) and adipokines (leptin and adiponectin) was measured in primary cell lines of epicardial and visceral adipocytes, both in undifferentiated and mature statuses, after a 21-day-long differentiation protocol. Each condition was assayed in triplicate in two independent primary cell lines obtained from two different donors. The epicardial preadipocytes showed an increased expression of IL-8 (3.25-fold, p<0.05) compared with visceral preadipocytes. The expression of the atheroprotective adiponectin in epicardial preadipocytes was minimal compared with the expression in visceral preadipocytes (p<0.0001). Moreover, the expression of the genes of interest was dependent on the differentiation degree and cell origin. We observed an altered expression of the proinflammatory genes IL-8 (0.016-fold, p<0.01) and MCP-1 (0.19-fold, p<0.05) in differentiated epicardial adipocytes compared with undifferentiated adipocytes. The epicardial adipocytes showed an increased expression of IL-6 (8.13-fold, p<0.05) compared with the visceral adipocytes. Our results suggest that epicardial adipocytes substantially differ from visceral adipocytes and might locally contribute to the pathogenesis of coronary atherosclerosis.


Morita-Baylis-Hillman adduct derivatives (MBHADs): versatile reactivity in Lewis base-promoted annulation.
Lewis base-promoted annulation reactions with MBHADs have emerged as a key platform for the construction of functionalized carbo- and heterocycles. MBHADs, which are economical and readily available, exert diverse and amazing reactivity when reacted with a wide range of electrophiles. A variety of carbo- and heterocycles, most of which are predominant in natural products and pharmaceuticals, could be constructed with high efficiency. This tutorial review will describe these annulation reactions, with a special emphasis on recent work regarding diverse reactivities of MBHADs.


The appearance of stippled retinal pigment epithelial detachments. A sign of occult choroidal neovascularization in age-related macular degeneration.
The clinical source of 62 eyes that had been coded for macular degeneration and fibrovascular retinal pigment epithelial (RPE) detachment on fluorescein angiography was reviewed; 17 eyes had signs of a choroidal neovascular membrane (CNVM) at initial examination, and 30 eyes developed a definite CNVM during follow-up examination. Thus, 47 of the 62 eyes (76%) developed a CNVM in association with fibrovascular RPE detachments. Features of fibrovascular RPE detachments include: 1) focal, tiny hyperfluorescent spots at the level of the RPE arising in the mid and late frames of the angiogram, which do not correspond to drusen or foci of depigmentation (stippled hyperfluorescence); 2) intensification of these spots in the later stages of the angiogram; 3) slight enlargement of the spots in the late frames of the angiogram; 4) occasional presence of scant overlying subretinal fluid; and 5) minimal elevation of the RPE. Fibrovascular RPE detachments appear to be a distinct form of an RPE detachment. It is concluded that this sign is associated with a high risk of developing a frank CNVM and is thus a reliable indicator of occult neovascularization.


Transcranial direct current stimulation modulates autonomic nervous system and reduces ambulatory blood pressure in hypertensives.
Purpose: Transcranial direct current stimulation (tDCS) seems to positively modulate the autonomic nervous system in different clinical conditions and healthy subjects; however, its effects on hypertensive (HTN) patients are not completely known. This study aimed to evaluate the effects of a tDCS or SHAM session (20 min) on blood pressure (BP) and autonomic variables of HTN patients.Materials and Methods: Subjects (n = 13) were randomly submitted to SHAM and tDCS sessions (1 week of washout). Hemodynamic and autonomic variables were measured at baseline, during, and immediately after tDCS or SHAM stimulation (Finometer®, Beatscope). Ambulatory BP measurement (ABPM) was evaluated after the experimental period.Results: Hemodynamic variables were not changed by tDCS, except for the fall in peripheral vascular resistance (Δ = -1696.51 ± 204.65 dyn.s/cm5). After the tDCS, sympathetic modulation was decreased (-61.47%), and vagal modulation was increased (+38.09%). Such acute autonomic changes may have evoked positive results observed in 24 hs-systolic blood pressure (Δ = -8.4 ± 6.2; P = .0022) and 24hs-diastolic blood pressure (Δ = -5.4 ± 4.2; P = .0010) in tDCS subjects compared with that in SHAM.Conclusion: These findings suggest that the tDCS could promote positive acute adjustments on cardiac autonomic control and reduced values on 24-hs BP of HTN patients. More than a proof-of-concept, these results may point out to the future, where brain stimulation (tDCS) can be used to HTN syndromes, such as refractory HTN.


HER2 status in advanced gastric carcinoma: A retrospective multicentric analysis from Sicily.
According to the ToGA trial, HER2 has been shown to be predictive for the success of treatment with trastuzumab in advanced gastric cancer (AGC). A number of studies have analyzed HER-2/neu overexpression in gastric carcinoma and identified the rate of HER2 positivity to be markedly varied. To date, the prevalence of HER2 overexpression in Sicilian people with AGC is unknown. Therefore, in the present study, a retrospective immunohistochemical analysis of HER2 was performed in a cohort of 304 AGC samples that were obtained from the archives of 10 Sicilian anatomopathological diagnostic units in order to verify the positive rate of HER2-positive cases. Furthermore, the characteristics of histotype, grade, stage and Ki-67 expression were also analyzed. HER2 overexpression was encountered in 17.43% of all the gastric adenocarcinomas, which was consistent with the results that have been reported elsewhere in the literature. A progressive increase in HER2 overexpression was observed, from the poorly cohesive histotype to the tubular adenocarcinomas and gastric hepatoid adenocarcinomas. HER2 overexpression was significantly associated with a high grade, advanced stage and high Ki-67 labeling index. Further investigations performed jointly by pathologists and oncologists within the geographical area of the present study should confirm that the association of trastuzumab with chemotherapy results in an improvement of survival in patients with AGC.


Nuclear magnetic resonance lipoprotein subclasses and the APOE genotype influence carotid atherosclerosis in patients with systemic lupus erythematosus.
Patients with systemic lupus erythematosus (SLE) have accelerated atherosclerosis. Since the conventional lipid profile (total plasma cholesterol, triglycerides, low and high density lipoprotein cholesterol) is not consistently altered in SLE, we hypothesized that investigation of lipoprotein subclasses would improve prediction of risk of atherosclerosis in these patients. As a quantitative index of atherosclerosis, we measured the carotid intima-media thickness (IMT) in 68 patients with SLE and related the atherosclerosis to a detailed lipoprotein profile generated using nuclear magnetic resonance (NMR). We measured the cholesterol transported by the pool of remnant lipoproteins (RLPc) and evaluated the modulatory effect of the APOE genotype on the lipoprotein subclass profile and atherosclerosis associated with SLE. Circulating lipoprotein remnant particles [RLPc and intermediate density lipoprotein (IDL)] were positively correlated with IMT, and among them, the indicator that explained 20.2% of the variability in carotid atherosclerosis measured in these patients was IDL, as assessed by NMR. Carriers of the APOE2 allele were at increased risk due to a significant accumulation of IDL particles. Lipoprotein subclasses are more associated with subclinical atherosclerosis in patients with SLE than the lipid variables that are routinely measured. The IDL fraction, which is significantly modulated by the APOE genotype, is the most strongly, significantly, and positively correlated with IMT.


Stereotactic radiosurgery (SRS) for brain metastases: a systematic review.
In many patients with brain metastases, the primary therapeutic aim is symptom palliation and maintenance of neurologic function, but in a subgroup, long-term survival is possible. Local control in the brain, and absent or controlled extracranial sites of disease are prerequisites for favorable survival. Stereotactic radiosurgery (SRS) is a focal, highly precise treatment option with a long track record. Its clinical development and implementation by several pioneering institutions eventually rendered possible cooperative group randomized trials. A systematic review of those studies and other landmark studies was undertaken. Most clinicians are aware of the potential benefits of SRS such as a short treatment time, a high probability of treated-lesion control and, when adhering to typical dose/volume recommendations, a low normal tissue complication probability. However, SRS as sole first-line treatment carries a risk of failure in non-treated brain regions, which has resulted in controversy around when to add whole-brain radiotherapy (WBRT). SRS might also be prescribed as salvage treatment in patients relapsing despite previous SRS and/or WBRT. An optimal balance between intracranial control and side effects requires continued research efforts.


Initial orthostatic hypotension and cerebral blood flow regulation: effect of α1-adrenoreceptor activity.
We examined the hypothesis that α(1)-adrenergic blockade would lead to an inability to correct initial orthostatic hypotension (IOH) and cerebral hypoperfusion, leading to symptoms of presyncope. Twelve normotensive humans (aged 25 ± 1 yr; means ± SE) attempted to complete a 3-min upright stand, 90 min after the administration of either α(1)-blockade (prazosin, 1 mg/20 kg body wt) or placebo. Continuous beat-to-beat measurements of middle cerebral artery velocity (MCAv; Doppler), blood pressure (finometer), heart rate, and end-tidal Pco(2) were obtained. Compared with placebo, the α(1)-blockade reduced resting mean arterial blood pressure (MAP) (-15%; P < 0.01); MCAv remained unaltered (P ≥ 0.28). Upon standing, although the absolute level of MAP was lower following α(1)-blockade (39 ± 10 mmHg vs. 51 ± 14 mmHg), the relative difference in IOH was negligible in both trials (mean difference in MAP: 2 ± 2 mmHg; P = 0.50). Compared with the placebo trial, the declines in MCAv and Pet(CO(2)) during IOH were greater in the α(1)-blockade trial by 12 ± 4 cm/s and 4.4 ± 1.3 mmHg, respectively (P ≤ 0.01). Standing tolerance was markedly reduced in the α(1)-blockade trial (75 ± 17 s vs. 180 ± 0 s; P < 0.001). In summary, while IOH was little affected by α(1)-blockade, the associated decline in MCAv was greater in the blockade condition. Unlike in the placebo trial, the extent of IOH and cerebral hypoperfusion failed to recover toward baseline in the α(1)-blockade trial leading to presyncope. Although the development of IOH is not influenced by the α(1)-adrenergic receptor pathway, this pathway is critical in the recovery from IOH to prevent cerebral hypoperfusion and ultimately syncope.


Effect of diabetes status and hyperglycemia on global DNA methylation and hydroxymethylation.
Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macrovascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with T2DM and compared them with healthy controls. We also analyzed microarrays of DNA methylation and gene expression of other important tissues in the context of diabetes from the GEO database repository and then compared these results with our experimental gene expression data. DNA methylation and, more importantly, DNA hydroxymethylation levels were increased in poorly controlled patients compared to well-controlled and healthy individuals. Both 5mC and 5hmC measurements were correlated with the percentage of glycated hemoglobin, indicating a direct impact of hyperglycemia on changes over the epigenome. The analysis of methylation microarrays was concordant, and 5mC levels were increased in the peripheral blood of T2DM patients. However, the DNA methylation levels were the opposite of those in other tissues, such as the pancreas, adipose tissue and skeletal muscle. We hypothesize that a process of DNA oxidation associated with hyperglycemia may explain the DNA demethylation in which the activity of ten-eleven translocation (TET) proteins is not sufficient to complete the process. High levels of glucose lead to cellular oxidation, which triggers the process of DNA demethylation aided by TET enzymes, resulting in epigenetic dysregulation of the damaged tissues.


Adolescent literacy: learning and understanding content.
Learning to read--amazing as it is to small children and their parents--is one thing. Reading to learn, explains Susan Goldman of the University of Illinois at Chicago, is quite another. Are today's students able to use reading and writing to acquire knowledge, solve problems, and make decisions in academic, personal, and professional arenas? Do they have the literacy skills necessary to meet the demands of the twenty-first century? To answer these questions, Goldman describes the increasingly complex comprehension, reasoning skills, and knowledge that students need as they progress through school and surveys what researchers and educators know about how to teach those skills. Successfully reading to learn requires the ability to analyze, synthesize, and evaluate information from multiple sources, Goldman writes. Effective readers must be able to apply different knowledge, reading, and reasoning processes to different types of content, from fiction to history and science, to news accounts and user manuals. They must assess sources of information for relevance, reliability, impartiality, and completeness. And they must connect information across multiple sources. In short, successful readers must not only use general reading skills but also pay close attention to discipline-specific processes. Goldman reviews the evidence on three different instructional approaches to reading to learn: general comprehension strategies, classroom discussion, and disciplinary content instruction. She argues that building the literacy skills necessary for U.S. students to read comprehensively and critically and to learn content in a variety of disciplines should be a primary responsibility for all of the nation's teachers. But outside of English, few subject-area teachers are aware of the need to teach subject-area reading comprehension skills, nor have they had opportunities to learn them themselves. Building the capacity of all teachers to meet the literacy needs of today's students requires long-term investment and commitment from the education community as well as society as a whole.


Propofol inhibits proliferation and induces neuroapoptosis of hippocampal neurons in vitro via downregulation of NF-κB p65 and Bcl-2 and upregulation of caspase-3.
Propofol is widely used in paediatric anaesthesia and intensive care unit because of its essentially short-acting anaesthetic effect. Recent data have shown that propofol induced neurotoxicity in developing brain. However, the mechanisms are not extremely clear. To gain a better insight into the toxic effects of propofol on hippocampal neurons, we treated cells at the days in vitro 7 (DIV 7), which were prepared from Sprague-Dawley embryos at the 18th day of gestation, with propofol (0.1-1000 μM) for 3 h. A significant decrease in neuronal proliferation and a remarkable increase in neuroapoptosis were observed in DIV 7 hippocampal neurons as measured by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay respectively. Moreover, propofol treatment decreased the nuclear factor kappaB (NF-κB) p65 expression, which was accompanied by a reduction in B-cell lymphoma 2 (Bcl-2) mRNA and protein levels, increased caspase-3 mRNA and activation of caspase-3 protein. These results indicated that downregulation of NF-κB p65 and Bcl-2 were involved in the potential mechanisms of propofol-induced neurotoxicity. This likely led to the caspase-3 activation, triggered apoptosis and inhibited the neuronal growth and proliferation that we have observed in our in vitro systems.


EBNA1 partitions Epstein-Barr virus plasmids in yeast cells by attaching to human EBNA1-binding protein 2 on mitotic chromosomes.
Epstein-Barr virus (EBV) episomal genomes are stably maintained in human cells and are partitioned during cell division by mitotic chromosome attachment. Partitioning is mediated by the viral EBNA1 protein, which binds both the EBV segregation element (FR) and a mitotic chromosomal component. We previously showed that the segregation of EBV-based plasmids can be reconstituted in Saccharomyces cerevisiae and is absolutely dependent on EBNA1, the EBV FR sequence, and the human EBNA1-binding protein 2 (EBP2). We have now used this yeast system to elucidate the functional contribution of human EBP2 to EBNA1-mediated plasmid partitioning. Human EBP2 was found to attach to yeast mitotic chromosomes in a cell cycle-dependent manner and cause EBNA1 to associate with the mitotic chromosomes. The domain of human EBP2 that binds both yeast and human chromosomes was mapped and shown to be functionally distinct from the EBNA1-binding domain. The functionality and localization of human EBP2 mutants and fusion proteins indicated that the attachment of EBNA1 to mitotic chromosomes is crucial for EBV plasmid segregation in S. cerevisiae, as it is in humans, and that this is the contribution of human EBP2. The results also indicate that plasmid segregation in S. cerevisiae can occur through chromosome attachment.


(-)-Epigallocatechin gallate sensitizes breast cancer cells to paclitaxel in a murine model of breast carcinoma.
Paclitaxel (Taxol) is a microtubule-targeted agent that is widely used for cancer treatment. However, resistance to paclitaxel is frequently encountered in the clinic. There is increasing interest in identifying compounds that may increase the sensitivity to conventional chemotherapeutic agents. In this study, we investigated whether green tea polyphenol (-)-epigallocatechin gallate (EGCG) could sensitize breast carcinoma to paclitaxel in vivo. Breast cancer cells were treated with or without EGCG and paclitaxel followed by detection of cell survival and apoptosis. c-Jun NH2-terminal kinase (JNK) phosphorylation and glucose-regulated protein 78 (GRP78) expression were detected by Western blotting. For in vivo study, 4T1 breast cancer cells were inoculated into Balb/c mice to establish a transplantation model. The tumor-bearing mice were treated with or without EGCG (30 mg/kg, i.p.) and paclitaxel (10 mg/kg, i.p.). Tumor growth was monitored. Apoptosis in tumor tissues was detected. Cell lysates from tumors were subjected to Western blot analysis of GRP78 expression and JNK phosphorylation. EGCG synergistically sensitized breast cancer cells to paclitaxel in vitro and in vivo. EGCG in combination with paclitaxel significantly induced 4T1 cells apoptosis compared with each single treatment. When tumor-bearing mice were treated with paclitaxel in combination with EGCG, tumor growth was significantly inhibited, whereas the single-agent activity for paclitaxel or EGCG was poor. EGCG overcame paclitaxel-induced GRP78 expression and potentiated paclitaxel-induced JNK phosphorylation in 4T1 cells both in vitro and in vivo. EGCG may be used as a sensitizer to enhance the cytotoxicity of paclitaxel.


Anaesthesia for uterine rupture in a Nigerian teaching hospital: maternal and fetal outcome.
An observational retrospective study was conducted at the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria to determine the outcome for patients with rupture of the gravid uterus who had anaesthesia for laparotomy over a four-year period, July 2000 to June 2004. The hospital records (case files, labour ward and theatre records) of patients over a four-year period with rupture of the uterus were reviewed. A total of 2707 deliveries took place at UNTH, Enugu, Nigeria. There were 2556 live births (94.8% of deliveries) and 714 (26.4%) caesarean deliveries. Twenty-three cases of uterine rupture occurred, giving a prevalence of 8.5/1000 deliveries. In nine patents (39.1%) the uterus was already scarred. The patients' mean age was 30.2 years. No nulliparous patients suffered ruptured uterus. General anaesthesia with muscle relaxants was administered to all patients. Twenty-two patients (95.6%) received blood transfusions. All the patients received normal saline and one patient also received Haemacel. Five (21.7%) patients had preoperative hypotension and two (8.6%) had intraoperative hypotension. There was one maternal death which occurred three days after the cesarean section. Twenty-three (96.3%) fetal deaths, including the loss of a set of twins, were recorded. Fetal deaths from ruptured uterus represented 32.4% of all fetal loss following caesarean section during the study period. There were no neonatal deaths. Rupture of the gravid uterus presents the anaesthetist with the unique challenge of maintaining haemodynamic status before haemostasis is secured, often with the patient in shock. Choice of anaesthetic drugs and availability of blood are important, as well as the skill and experience of the anaesthetist. The maternal mortality rates in other West African studies reviewed were generally higher than those in this series. The maternal outcome re-emphasises the vital role of prompt intervention and availability of blood in reducing maternal mortality following rupture of the uterus.


Monkey vocal tracts are speech-ready.
For four decades, the inability of nonhuman primates to produce human speech sounds has been claimed to stem from limitations in their vocal tract anatomy, a conclusion based on plaster casts made from the vocal tract of a monkey cadaver. We used x-ray videos to quantify vocal tract dynamics in living macaques during vocalization, facial displays, and feeding. We demonstrate that the macaque vocal tract could easily produce an adequate range of speech sounds to support spoken language, showing that previous techniques based on postmortem samples drastically underestimated primate vocal capabilities. Our findings imply that the evolution of human speech capabilities required neural changes rather than modifications of vocal anatomy. Macaques have a speech-ready vocal tract but lack a speech-ready brain to control it.


Antibiotic therapy for preventing infections in people with acute stroke.
Stroke is the main cause of disability in high-income countries and ranks second as a cause of death worldwide. Infections occur frequently after stroke and may adversely affect outcome. Preventive antibiotic therapy in the acute phase of stroke may reduce the incidence of infections and improve outcome. In the previous version of this Cochrane Review, published in 2012, we found that antibiotics did reduce the risk of infection but did not reduce the number of dependent or deceased patients. However, included studies were small and heterogeneous. In 2015, two large clinical trials were published, warranting an update of this Review. To assess the effectiveness and safety of preventive antibiotic therapy in people with ischaemic or haemorrhagic stroke. We wished to determine whether preventive antibiotic therapy in people with acute stroke:• reduces the risk of a poor functional outcome (dependency and/or death) at follow-up;• reduces the occurrence of infections in the acute phase of stroke;• reduces the occurrence of elevated body temperature (temperature ≥ 38° C) in the acute phase of stroke;• reduces length of hospital stay; or• leads to an increased rate of serious adverse events, such as anaphylactic shock, skin rash, or colonisation with antibiotic-resistant micro-organisms. We searched the Cochrane Stroke Group Trials Register (25 June 2017); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 5; 25 June 2017) in the Cochrane Library; MEDLINE Ovid (1950 to 11 May 2017), and Embase Ovid (1980 to 11 May 2017). In an effort to identify further published, unpublished, and ongoing trials, we searched trials and research registers, scanned reference lists, and contacted trial authors, colleagues, and researchers in the field. Randomised controlled trials (RCTs) of preventive antibiotic therapy versus control (placebo or open control) in people with acute ischaemic or haemorrhagic stroke. Two review authors independently selected articles and extracted data; we discussed and resolved discrepancies at a consensus meeting with a third review author. We contacted study authors to obtain missing data when required. An independent review author assessed risk of bias using the Cochrane 'Risk of bias' tool. We calculated risk ratios (RRs) for dichotomous outcomes, assessed heterogeneity amongst included studies, and performed subgroup analyses on study quality. We included eight studies involving 4488 participants. Regarding quality of evidence, trials showed differences in study population, study design, type of antibiotic, and definition of infection; however, primary outcomes among the included studies were consistent. Mortality rate in the preventive antibiotic group was not significantly different from that in the control group (373/2208 (17%) vs 360/2214 (16%); RR 1.03, 95% confidence interval (CI) 0.87 to 1.21; high-quality evidence). The number of participants with a poor functional outcome (death or dependency) in the preventive antibiotic therapy group was also not significantly different from that in the control group (1158/2168 (53%) vs 1182/2164 (55%); RR 0.99, 95% CI 0.89 to 1.10; moderate-quality evidence). However, preventive antibiotic therapy did significantly reduce the incidence of 'overall' infections in participants with acute stroke from 26% to 19% (408/2161 (19%) vs 558/2156 (26%); RR 0.71, 95% CI 0.58 to 0.88; high-quality evidence). This finding was highly significant for urinary tract infections (81/2131 (4%) vs 204/2126 (10%); RR 0.40, 95% CI 0.32 to 0.51; high-quality evidence), whereas no preventive effect for pneumonia was found (222/2131 (10%) vs 235/2126 (11%); RR 0.95, 95% CI 0.80 to 1.13; high-quality evidence). No major side effects of preventive antibiotic therapy were reported. Only two studies qualitatively assessed the occurrence of elevated body temperature; therefore, these results could not be pooled. Only one study reported length of hospital stay. Preventive antibiotics had no effect on functional outcome or mortality, but significantly reduced the risk of 'overall' infections. This reduction was driven mainly by prevention of urinary tract infection; no effect for pneumonia was found.


Bioaccumulation of metals in ryegrass (Lolium perenne L.) following the application of lime stabilised, thermally dried and anaerobically digested sewage sludge.
The uptake and accumulation of metals in plants is a potential pathway for the transfer of environmental contaminants in the food chain, and poses potential health and environmental risks. In light of increased population growth and urbanisation, the safe disposal of sewage sludge, which can contain significant levels of toxic contaminants, remains an environmental challenge globally. The aims of this experiment were to apply municipal sludge, having undergone treatment by thermal drying, anaerobic digestion, and lime stabilisation, to permanent grassland in order to assess the bioaccumulation of metals (B, Al, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, As, Nb, Mo, Sb, Ba, W, Pb, Fe, Cd) by perennial ryegrass over a period of up to 18 weeks after application. The legislation currently prohibits use of grassland for fodder or grazing for at least three weeks after application of treated sewage sludge (biosolids). Five treatments were used: thermally dried (TD), anaerobically digested (AD) and lime stabilised (LS) sludge all from one wastewater treatment plant (WWTP), AD sludge from another WWTP, and a study control (grassland only, without application of biosolids). In general, there was no significant difference in metal content of the ryegrass between micro-plots that received treated municipal sludge and the control over the study duration. The metal content of the ryegrass was below the levels at which phytotoxicity occurs and below the maximum levels specified for animal feeds.


Predicting Divorce Prospect Using Ensemble Learning: Support Vector Machine, Linear Model, and Neural Network.
A divorce is a legal step taken by married people to end their marriage. It occurs after a couple decides to no longer live together as husband and wife. Globally, the divorce rate has more than doubled from 1970 until 2008, with divorces per 1,000 married people rising from 2.6 to 5.5. Divorce occurs at a rate of 16.9 per 1,000 married women. According to the experts, over half of all marriages ends in divorce or separation in the United States. A novel ensemble learning technique based on advanced machine learning algorithms is proposed in this study. The support vector machine (SVM), passive aggressive classifier, and neural network (MLP) are applied in the context of divorce prediction. A question-based dataset is created by the field specialist. The responses to the questions provide important information about whether a marriage is likely to turn into divorce in the future. The cross-validation is applied in 5 folds, and the performance results of the evaluation metrics are examined. The accuracy score is 100%, and Receiver Operating Characteristic (ROC) curve accuracy score, recall score, the precision score, and the F1 accuracy score are close to 97% confidently. Our findings examined the key indicators for divorce and the factors that are most significant when predicting the divorce.


Spatial associations among density of cattle, abundance of wild canids, and seroprevalence to Neospora caninum in a population of beef calves.
To determine the epidemiologic plausibility of a sylvatic transmission cycle for Neospora caninum between wild canids and beef cattle. Spatial analysis study. 1,009 weaned beef steers from 94 beef herds in Texas. Calves were grouped on the basis of seroprevalence for N caninum and ecologic region in Texas. The Morans I test was used to evaluate spatial interdependence for adjusted seroprevalence by ecologic region. Cattle density (Number of cattle/259 km2 [Number of cattle/100 mile2] of each ecologic region) and abundance indices for gray foxes and coyotes (Number of animals/161 spotlight-transect [census] km [Number of animals/100 census miles] of each ecologic region) were used as covariates in spatial regression models, with adjusted seroprevalence as the outcome variable. A geographic information system (GIS) that used similar covariate information for each county was used to validate spatial regression models. Results-Spatial interdependence was not detected for ecologic regions. Three spatial regression models were tested. Each model contained a variable for cattle density for the ecologic regions. Results for the 3 models revealed that seroprevalence was associated with cattle density and abundances of gray foxes, coyotes, or both. Abundances of gray foxes and coyotes were collinear. Results of a GIS-generated model validated these spatial models. In Texas, beef cattle are at increased risk of exposure to N caninum as a result of the abundance of wild canids and the density of beef cattle. It is plausible that a sylvatic transmission cycle for neosporosis exists.


The effect of rectus muscle recession, resection and plication on anterior segment circulation in humans.
Plication is an alternative tightening procedure to resection. In monkeys, plication has been shown to preserve anterior segment circulation compared with full-tendon tenotomy, but this is unconfirmed in humans. To evaluate anterior segment circulation by iris angiography before and after strabismus surgery in humans. Prospective, blinded study of 14 patients (mean age (SD), 58.6 (14.3)) undergoing plication and/or full tendon tenotomy (resection or recession) from August 2013 to March 2014. Eight patients (mean age (SD), 59.0 (13.3)) underwent plication of one muscle with or without recession of a second muscle on the same eye and six patients (mean age (SD), 58.2 (16.8)) underwent tenotomy of one to two muscles on the same eye. Preoperative and postoperative iris angiograms were compared for changes in perfusion by a masked examiner. In patients undergoing binocular surgery, one eye was chosen preoperatively to be the study eye. Postoperative iris filling defects were present in four patients (67%) after tenotomy and one patient (12.5%) after plication (p=0.09). Of the seven total vertical rectus muscles operated (three tenotomies and four plications), filling defects were present after three tenotomies and one plication (100% vs 25%; p=0.14). Of the 13 total horizontal rectus muscles operated (eight tenotomies and five plications), filling defects were present after one tenotomy and none of the plications (13% vs 0%; p=0.99). Rectus muscle plication spares the ciliary vessels and may be considered a safer alternative to resection for patients at risk for anterior segment ischaemia, especially when surgery involves a vertical rectus muscle.


Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection.
Chlamydophila pneumoniae and Mycoplasma pneumoniae are associated with acute exacerbation of bronchial asthma (AEBA). The aim of this study was to evaluate the correlation between these acute bacterial infections and the severity of AEBA. We prospectively analysed consecutive patients admitted to the Emergency Department with acute asthma exacerbation. In every patient peak expiratory flow (PEF) measurement was performed on admission, and spirometry during follow-up. Serology for Chlamydophila and Mycoplasma pneumoniae was performed on admission and after 4-8 weeks. Fifty-eight patients completed the study. Acute atypical infections (AAI) was observed in 22/58 cases; we found single acute C. pneumoniae in 19 cases, single acute M. pneumoniae in 2 cases, and double acute infection in one case. Functional impairment on admission was greater in patients with AAI than in patients without AAI (PEF 205 +/- 104 L/min vs 276 +/- 117 p = 0.02) and persisted until visit 2 (FEV1% 76.30 +/- 24.54 vs FEV1% 92.91 +/- 13.89, p = 0.002). Moreover, the proportion of patients who presented with severe AEBA was significantly greater in the group with AAI than in the group without AAI (15/22 vs 12/36, p = 0.01; OR 4.29, 95% CI 1.38-13.32). Our data suggest an association between acute atypical infection and a more severe AEBA.


Electrical detection of dengue virus (DENV) DNA oligomer using silicon nanowire biosensor with novel molecular gate control.
In this paper, a silicon nanowire biosensor with novel molecular gate control has been demonstrated for Deoxyribonucleic acid (DNA) detection related to dengue virus (DENV). The silicon nanowire was fabricated using the top-down nanolithography approach, through nanostructuring of silicon-on-insulator (SOI) layers achieved by combination of the electron-beam lithography (EBL), plasma dry etching and size reduction processes. The surface of the fabricated silicon nanowire was functionalized by means of a three-step procedure involving surface modification, DNA immobilization and hybridization. This procedure acts as a molecular gate control to establish the electrical detection for 27-mers base targets DENV DNA oligomer. The electrical detection is based on the changes in current, resistance and conductance of the sensor due to accumulation of negative charges added by the immobilized probe DNA and hybridized target DNA. The sensitivity of the silicon nanowire biosensors attained was 45.0µAM(-1), which shows a wide-range detection capability of the sensor with respect to DNA. The limit of detection (LOD) achieved was approximately 2.0fM. The demonstrated results show that the silicon nanowire has excellent properties for detection of DENV with outstanding repeatability and reproducibility performances.


Effects of surface reflectance on skylight polarization measurements at the Mauna Loa Observatory.
An all-sky imaging polarimeter was deployed in summer 2008 to the Mauna Loa Observatory in Hawaii to study clear-sky atmospheric skylight polarization. The imager operates in five wavebands in the visible and near infrared spectrum and has a fisheye lens for all-sky viewing. This paper describes the deployment and presents comparisons of the degree of skylight polarization observed to similar data observed by Coulson with a principal-plane scanning polarimeter in the late 1970s. In general, the results compared favorably to those of Coulson. In addition, we present quantitative results correlating a variation of the maximum degree of polarization over a range of 70-85% to fluctuation in underlying surface reflectance and upwelling radiance data from the GOES satellite.


Estimation of Atmospheric Path Delays in TerraSAR-X Data using Models vs. Measurements.
Spaceborne synthetic aperture radar (SAR) measurements of the Earth's surface depend on electromagnetic waves that are subject to atmospheric path delays, in turn affecting geolocation accuracy. The atmosphere influences radar signal propagation by modifying its velocity and direction, effects which can be modeled. We use TerraSAR-X (TSX) data to investigate improvements in the knowledge of the scene geometry. To precisely estimate atmospheric path delays, we analyse the signal return of four corner reflectors with accurately surveyed positions (based on differential GPS), placed at different altitudes yet with nearly identical slant ranges to the sensor. The comparison of multiple measurements with path delay models under these geometric conditions also makes it possible to evaluate the corrections for the atmospheric path delay made by the TerraSAR processor and to propose possible improvements.


Patients' Perspectives of Oral and Injectable Type 2 Diabetes Medicines, Their Body Weight and Medicine-Taking Behavior in the UK: A Systematic Review and Meta-Ethnography.
The aim of this review is to identify peoples' perspectives of their glucose-lowering and anti-obesity drugs in relation to diabetes and weight control and to explore how these views affect medication adherence. Theoretical perspectives associated with medicine-taking behavior are also explored. The systematic review was based on a meta-ethnography of qualitative studies identified through a search of 12 medical and social science databases and subsequent citation searches. The quality of all studies was assessed. Sixteen studies were included with data from 360 UK individuals. No relevant studies were identified which focused on anti-obesity and non-insulin injectable drugs. The review revealed that the patients' perspectives and emotional state were influenced by starting and/or changing to a new glucose-lowering medicine. These were also influenced by prior medication experience, disease perceptions and interactions with clinicians. Despite reports of positive experiences with and positive perceptions of medicines, and of participation in strategies to regain life control, medication non-adherence was common. Accepting glucose-lowering medicines impacted on the individual's perception of lifestyle changes, and it was notable that weight loss was not perceived as a strategy to support diabetes management. Synthesis revealed that more than one theory is required to explain medicine-taking behavior. New insights into the underlying factors of poor adherence and the specific practical issues identified in this review can help in the development of patient-centered interventions. Diabetes UK.


Clinical manifestations and immunodiagnosis of gnathostomiasis in Culiacan, Mexico.
Gnathostomiasis was first described in Mexico in 1970, and endemic areas have been spreading in six states of this country. In Culiacan, Sinaloa, 300 cases of cutaneous larva migrans were recorded between January 1992 and December 1995. In addition, a Gnathostoma larva was surgically removed from the eye of one patient. Cutaneous lesions were observed mainly on the face, neck, arms, and legs. About 70% of the patients showed eosinophilia. A skin biopsy was carried out on 35 patients and the parasite was identified in histopathologic sections of 12 of these patients. In four patients, the larva migrated out spontaneously from the skin. An enzyme-linked immunosorbent assay using a crude somatic extract of adult Gnathostoma doloresi worms showed that 93% of the patients were seropositive, confirming the reliability of clinical diagnosis. A total of 14 advanced third-stage Gnathostoma larvae were found in four species of ichthyophagous birds captured on dams and dikes near the city of Culiacan. Scanning electron micrographs of human and bird larvae showed that they were morphologically indistinguishable from G. spinigerm. We conclude that the life cycle of Gnathostoma has been established in Sinaloa, and has become a serious public health issue for residents.


Color-converting bilayered composite plate of quantum-dot-polymer for high-color rendering white light-emitting diode.
Highly bright CuInS₂ quantum dots (QDs), whose emission is easily tuned in orange and greenish-yellow colors through manipulating the ZnS shelling procedure, are integrated with polymethyl methacrylate (PMMA) to obtain a free-standing composite plate of QD-polymer. The composite plate embedded with orange or greenish-yellow QDs is combined in a remote type with a blue light-emitting diode (LED). No color rendering index (CRI) value results when orange QDs are applied, whereas use of greenish-yellow QDs leads to a limited CRI of 72. A higher-color rendering QD-LED is demonstrated through a spectral extension by devising a unique bilayer-structured QD plate, where two types of QD are separately incorporated into each PMMA matrix, with a buffer layer of polymer blend inserted between them. The bilayered QD plate LED exhibits an improved CRI of 81, a high luminous efficacy of 71.2 lm/W at an input current of 20 mA, and exceptional high-stability luminescent characteristics against the variation of applied current.


Towards the measurement of food literacy with respect to healthy eating: the development and validation of the self perceived food literacy scale among an adult sample in the Netherlands.
Food literacy refers to the capability to make healthy food choices in different contexts, settings and situations. The aim of this study is to develop and validate the self-perceived food literacy (SPFL) scale, to assess individuals' level of food literacy, including a knowledge, skills and behavior to plan, manage, select, prepare and eat food healthfully. An initial set of 50 items for the SPFL scale were generated based on expert insights and literature. A cross-sectional online survey was conducted among a sample of Dutch adults (n = 755) in order to determine convergent, divergent and criterion validation against psychosocial variables that were expected to correlate with food literacy (self-control, impulsiveness) and against the expected outcome of high food literacy, namely healthy food consumption. Principal Component Analyses (PCA), Pearson correlation tests and linear regression analyses were conducted. The capacity to distinguish of the SPFL scale was determined by comparing SPFL scores of the general population with that of a sample of dieticians (n = 207). The participants in the general sample had an average age of 44.8 (SD:16.1), the majority were women (90.7%), they had a healthy weight (61.4%) and were highly educated (59.1%). Of the initial 50 items, 29 items remained after PCA and reflected eight domains of food literacy. SPFL was positively correlated with self-control (r = 0.51, p = <.001) and negatively with impulsiveness (r = - 0.31, p = <.01). Participants with higher levels of food literacy reported a significantly higher frequency of fruit consumption (≥5 times/week), vegetable consumption (≥5times/week) and fish consumption (≥1times/week) and consumed larger portions of fruit (≥2pieces/day) and vegetables ≥200 g/day) in comparison with participants who had lower levels of food literacy. Dieticians had slightly higher scores on SPFL than general adults (B = 0.08, SE = 0.03, t = 2.83, 95%-CI = 0.03 to 0.14). The 29 item SPFL scale is a validated, expert-based and theory-driven tool for measuring self-perceived food literacy with respect to healthy eating among adults. Higher levels of food literacy were associated with more self-control, less impulsiveness and healthier food consumption. Additional research is needed to validate the SPFL scale in different populations (different age groups, socioeconomic groups, male populations) and in different contexts.


A population-based survival assessment of categorizing level III and IV rural hospitals as trauma centers.
Patients injured in rural areas are hypothesized to have improved outcomes if statewide trauma systems categorize rural hospitals as Level III and IV trauma centers, though evidence to support this belief is sparse. To determine if there is improved survival among injured patients hospitalized in states that categorize rural hospitals as trauma centers. We analyzed a retrospective cohort of injured patients included in the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample from 1997 to 1999. We used generalized estimating equations to compare survival among injured patients hospitalized in states that categorize rural hospitals as Level III and IV trauma centers versus those that do not. Multivariable models adjusted for important confounders, including patient demographics, co-morbid conditions, injury severity, and hospital-level factors. There were 257,044 admitted patients from 7 states with a primary injury diagnosis, of whom 64,190 (25%) had a "serious" index injury, 32,763 (13%) were seriously injured (by ICD-9 codes), and 12,435 (5%) were very seriously injured (by ICD-9 codes). There was no survival benefit associated with rural hospital categorization among all patients with a primary injury diagnosis or for those with specific index injuries. However, seriously injured patients (by ICD-9 codes) had improved survival when hospitalized in a categorizing state (OR for mortality 0.72, 95% confidence interval [CI] 0.53-0.97; OR for very seriously injured 0.68, 95% CI 0.52-0.90). There was no survival benefit to categorizing rural hospitals among a broad, heterogeneous group of hospitalized patients with a primary injury diagnosis; however the most seriously injured patients did have increased survival in such states.


Colloidal quantum dot light-emitting devices.
Colloidal quantum dot light-emitting devices (QD-LEDs) have generated considerable interest for applications such as thin film displays with improved color saturation and white lighting with a high color rendering index (CRI). We review the key advantages of using quantum dots (QDs) in display and lighting applications, including their color purity, solution processability, and stability. After highlighting the main developments in QD-LED technology in the past 15 years, we describe the three mechanisms for exciting QDs - optical excitation, Förster energy transfer, and direct charge injection - that have been leveraged to create QD-LEDs. We outline the challenges facing QD-LED development, such as QD charging and QD luminescence quenching in QD thin films. We describe how optical downconversion schemes have enabled researchers to overcome these challenges and develop commercial lighting products that incorporate QDs to achieve desirable color temperature and a high CRI while maintaining efficiencies comparable to inorganic white LEDs (>65 lumens per Watt). We conclude by discussing some current directions in QD research that focus on achieving higher efficiency and air-stable QD-LEDs using electrical excitation of the luminescent QDs.


An immunological analysis of Ty1 virus-like particle structure.
We present an immunological characterization of the Ty1 virus-like particle (VLP). A panel of monoclonal and polyclonal antibodies were raised against the TYA particle-forming protein. Using these antibodies in epitope availability assays two N-terminal regions of the TYA protein were mapped projecting from or at the surface of the proteinaceous shell of the VLP. Two different C-termini of the TYA protein, corresponding to the C-terminus of the full-length and truncated forms, were seen to be buried within the particle core and not available for antibody binding. RNase accessibility studies demonstrated a difference in the porosity of the protein shell surrounding the Ty1 nucleic acid between different particle types, suggesting differences in subunit organization.


Civil war: is it all about disease and xenophobia? A comment on Letendre, Fincher & Thornhill.
Letendre, Fincher & Thornhill (2010) argue that pathogen intensity provides the ultimate explanation for why some countries are more prone to civil war than others. They argue that the economic and political factors highlighted in previous research on civil war are largely caused by underlying differences in pathogen intensity, and contend that disease proneness increases the risk of civil war through its effects on resource competition and xenophobia. They present empirical evidence that they interpret as consistent with their argument: a statistically significant correlation between pathogen intensity and civil war onset. In this comment, we raise concerns over their interpretation of the empirical evidence and their proposed causal mechanisms. We find that the data provide stronger evidence for the reverse causal relationship, namely that civil war causes disease to become more prevalent. This finding is consistent with the literatures on the public health effects of civil war as well as research on state capacity and public health.


NKG2D-Fc fusion protein promotes antitumor immunity through the depletion of immunosuppressive cells.
A major factor impeding the success of numerous therapeutic approaches in cancer is the immunosuppressive nature of the tumor microenvironment (TME). Hence, methods capable of reverting tumor immunosuppression through depletion or reprogramming of myeloid-derived suppressive cells (MDSCs) and regulatory T cells (Tregs) are of great clinical need. Here, we explore NKG2D-Fc as a modality to modulate antitumor immunity through the depletion of immunosuppressive MDSCs and Tregs in the TME. We have generated the NKG2D-Fc fusion protein and characterized its potential to mediate tumor control and overall survival in LL2 and MC38 murine models. Upon treatment of LL2 or MC38 tumor-bearing mice with NKG2D-Fc, we observe significant tumor control and enhanced survival compared to Fc control. When characterizing MDCSs and Tregs from tumor-bearing mice, we observe clear expression of NKG2D-ligand RAE1γ and subsequent binding of NKG2D-Fc fusion protein to both MDSCs and Tregs. Examining the immune profile of mice treated with NKG2D-Fc reveals significant depletion of MDSCs and Tregs in the TME, as well as an increase in NK cells likely due to the reversed suppressive TME. In conclusion, NKG2D-Fc induces antitumor immunity and tumor control through the depletion of MDSCs and Tregs, subsequently providing a niche for the infiltration and expansion of proinflammatory cells, such as NK cells. Strategies capable of modulating the immunosuppressive state in cancer are in high clinical demand. NKG2D-Fc is a simple, single tool capable of depleting both MDSCs and Tregs and should be further investigated as a therapeutic agent for the treatment of cancer.


The validity of computed tomographic scan findings for the localization of cerebral functions. The relationship between computed tomography and hemiparesis.
We studied recovery from hemiparesis in 52 patients who participated in the Hennepin County (Minnesota) Recovery From Aphasia Study. Our intent was to determine the anatomic correlates of recovery from hemiparesis and then to contrast computed tomography (CT)-hemiparesis relationships with CT-aphasia relationships in this same population. Hemiparesis was assessed at one month after onset and again at six months after onset. Computed tomographic scans were obtained five months after onset and analyzed quantitatively for lesion location. The presence or absence of arm paresis was strongly predicted by CT scan findings in the supratentorial corticospinal pathway. However, three of 25 nonparetic patients had lesions in the corticospinal pathway, and one of 22 severely paretic patients lacked an appropriate lesion. This study demonstrated that a small but inherent lack of specificity and sensitivity existed in the predictive power of CT localization of lesions potentially affecting the motor system, suggesting that some caution is necessary in interpreting the lesion-deficit relationships in less well-localized functions, eg, language. Besides considering the lack of precision in localizing with CT, the existence of individual differences both in anatomy and localization of function must be taken into account.


Associations between 24 hour movement behaviours and global cognition in US children: a cross-sectional observational study.
Childhood and adolescence are crucial periods for brain development, and the behaviours during a typical 24 h period contribute to cognitive performance. The Canadian 24-Hour Movement Guidelines for Children and Youth recommend at least 60 min physical activity per day, 2 h or less recreational screen time per day, and 9-11 h sleep per night in children aged 8-11 years. We investigated the relationship between adherence to these recommendations and global cognition. In this cross-sectional observational study, we obtained data from the first annual curated release of the Adolescent Brain Cognitive Development study, a 10-year longitudinal, observational study. Data were collected from 21 study sites across the USA between Sept 1, 2016, and Sept 15, 2017. The participants were 4524 US children aged 8-11 years from 20 study sites. Exposures of interest were adherence to the physical activity, recreational screen time, and sleep duration guideline recommendations. The primary outcome was global cognition, assessed with the NIH Toolbox (National Institutes of Health, Bethesda, MD, USA), which we analysed with multivariable linear mixed-effects models to examine the relations with movement behaviour variables. Complete movement behaviour data were available for 4520 participants. The mean number of guideline recommendations met was 1·1 (SD 0·9). Overall, 2303 (51%) participants met the sleep recommendation, 1655 (37%) met screen time, and 793 (18%) met the physical activity recommendation. 3190 (71%) participants met at least one recommendation, whereas 216 (5%) of participants met all three recommendations. Global cognition was positively associated with each additional recommendation met (β=1·44, 95% CI 0·82-2·07, p<0·0001). Compared with meeting none of the recommendations, associations with superior global cognition were found in participants who met all three recommendations (β=3·89, 95% CI 1·43 to 6·34, p=0·0019), the screen time recommendation only (β=4·25, 2·50-6·01, p<0·0001), and both the screen time and the sleep recommendations (β=5·15, 3·56-6·74, p<0·0001). Meeting the 24 h movement recommendations was associated with superior global cognition. These findings highlight the importance of limiting recreational screen time and encouraging healthy sleep to improve cognition in children. National Institutes of Health.


Encoding of progesterone stimulus intensity by intracellular [Ca2+] ([Ca2+]i) in human spermatozoa.
Progesterone induces a biphasic Ca(2+) influx and consequent acrosome reaction in human spermatozoa. We have used two procedures to vary the stimulus (dosage and prior receptor desensitization) to investigate the encoding of stimulus strength by intracellular [Ca(2+)] ([Ca(2+)](i)). Acrosome reaction and amplitude (but not kinetics) of the transient [Ca(2+)](i) response (population measurement) showed sigmoidal dose sensitivity over the range 0.3 nM-3 microM, saturating at approximately 300 nM (ED(50) approximately 30 nM). The amplitude of the sustained response saturated at 3 microM. Single-cell imaging showed that the amplitudes of both transient and sustained [Ca(2+)](i) responses were highly dose-dependent, but that their frequency of occurrence and kinetics were largely dose-independent. Fluorimetric measurements confirmed that progesterone-induced [Ca(2+)](i) influx was subject to desensitization, with second and subsequent applications of 3 microM progesterone being ineffective. However, sequential additions of 3 nM, 30 nM and 3 microM progesterone generated transient [Ca(2+)](i) responses at each concentration, the amplitude and duration of the response to 3 microM progesterone being reduced compared with non-pretreated cells. Single-cell imaging revealed that pretreatment had no effect on the proportion of responsive cells, but single-cell responses, similarly to population responses, were smaller and markedly reduced in duration, consistent with an effect of desensitization on a late component of the [Ca(2+)](i) transient. We conclude that the strength of the progesterone stimulus, when varied by dosage or by desensitization, is encoded by an analogue [Ca(2+)](i) signal. Dose dependency of the acrosome reaction is therefore determined not by the number of progesterone-responsive cells but by variation in the probability of exocytosis in a 'constant' responsive population.


Children Reading to Dogs: A Systematic Review of the Literature.
Despite growing interest in the value of human-animal interactions (HAI) to human mental and physical health the quality of the evidence on which postulated benefits from animals to human psychological health are based is often unclear. To date there exist no systematic reviews on the effects of HAI in educational settings specifically focussing on the perceived benefits to children of reading to dogs. With rising popularity and implementation of these programmes in schools, it is essential that the evidence base exploring the pedagogic value of these initiatives is well documented. Using PRISMA guidelines we systematically investigated the literature reporting the pedagogic effects of reading to dogs. Because research in this area is in the early stages of scientific enquiry we adopted broad inclusion criteria, accepting all reports which discussed measurable effects related to the topic that were written in English. Multiple online databases were searched during January-March 2015; grey literature searches were also conducted. The search results which met the inclusion criteria were evaluated, and discussed, in relation to the Oxford Centre for Evidence Based Medicine levels of evidence; 27 papers were classified as Level 5, 13 as Level 4, 7 as Level 2c and 1 as Level 2b. The evidence suggests that reading to a dog may have a beneficial effect on a number of behavioural processes which contribute to a positive effect on the environment in which reading is practiced, leading to improved reading performance. However, the evidence base on which these inferences are made is of low quality. There is a clear need for the use of higher quality research methodologies and the inclusion of appropriate controls in order to draw causal inferences on whether or how reading to dogs may benefit children's reading practices. The mechanisms for any effect remain a matter of conjecture.


Serum autoantibodies that bind citrullinated fibrinogen are frequently found in patients with rheumatoid arthritis.
Autoantibodies that bind citrullinated antigens are a sensitive and specific marker for rheumatoid arthritis (RA). While synthetic cyclic citrullinated peptides (CCP) are typically used to identify these antibodies, little is known about antibody reactivity to the predominant citrullinated protein found in the inflamed synovium, citrullinated fibrinogen (CitFib). We assessed the prevalence of anti-CitFib antibodies in patients with various rheumatic diseases. In total, 65 patients with established RA and 63 patients with other rheumatic diseases were tested for serum IgM rheumatoid factor (RF), IgG anti-CCP2, and IgG anti-CitFib antibodies. This cohort was used to determine optimal positive cutoff values for antibody reactivity to CitFib through receiver operating characteristic curve analysis. The specificity of these assays was confirmed with sera from 49 patients with psoriatic arthritis. Antibodies to both citrullinated antigens were identified in the majority of RA patients tested. The overall sensitivity and specificity of the assays were: CCP 82%, 96%, CitFib 75%, 98%, and IgM RF 80%, 64%, respectively. All but one patient that was positive for CitFib was also positive for CCP2, and close to half the RF-negative RA patients were positive for CitFib and CCP2. These results suggest that autoimmunity to CitFib is common in patients with RA and may play a role in disease pathogenesis.


Comparison of cortical folding measures for evaluation of developing human brain.
We evaluated 22 measures of cortical folding, 20 derived from local curvature (curvature-based measures) and two based on other features (sulcal depth and gyrification index), for their capacity to distinguish between normal and aberrant cortical development. Cortical surfaces were reconstructed from 12 term-born control and 63 prematurely-born infants. Preterm infants underwent 2-4 MR imaging sessions between 27 and 42weeks postmenstrual age (PMA). Term infants underwent a single MR imaging session during the first postnatal week. Preterm infants were divided into two groups. One group (38 infants) had no/minimal abnormalities on qualitative assessment of conventional MR images. The second group (25 infants) consisted of infants with injury on conventional MRI at term equivalent PMA. For both preterm infant groups, all folding measures increased or decreased monotonically with increasing PMA, but only sulcal depth and gyrification index differentiated preterm infants with brain injury from those without. We also compared scans obtained at term equivalent PMA (36-42weeks) for all three groups. No curvature-based measured distinguished between the groups, whereas sulcal depth distinguished term control from injured preterm infants and gyrification index distinguished all three groups. When incorporating total cerebral volume into the statistical model, sulcal depth no longer distinguished between the groups, though gyrification index distinguished between all three groups and positive shape index distinguished between the term control and uninjured preterm groups. We also analyzed folding measures averaged over brain lobes separately. These results demonstrated similar patterns to those obtained from the whole brain analyses. Overall, though the curvature-based measures changed during this period of rapid cerebral development, they were not sensitive for detecting the differences in folding associated with brain injury and/or preterm birth. In contrast, gyrification index was effective in differentiating these groups.


Combination therapy of menstrual derived mesenchymal stem cells and antibiotics ameliorates survival in sepsis.
Sepsis is a clinical syndrome associated with a severe systemic inflammation induced by infection. Although different anti-microbial drugs have been used as treatments, morbidity and mortality rates remain high. Mesenchymal stem cells (MSCs) derived from the bone marrow have demonstrated a partial protective effect in sepsis. Menstrual derived MSCs (MenSCs) emerge as an attractive candidate because they present important advantages over other sources, including improved proliferation rates and paracrine response under specific stress conditions. Here, we evaluate their therapeutic effect in a polymicrobial severe sepsis model. The antimicrobial activity of MenSCs was determined in vitro through direct and indirect bacterial growth assays and the measurement of the expression levels of different antimicrobial peptides (AMPs) by quantitative reverse transcription-polymerase chain reaction. The therapeutic effect of MenSCs was determined in the cecal ligation and puncture (CLP) mouse model. Mice were then treated with antibiotics (AB) or MenSCs alone or in combination. The survival rates and histological and biochemical parameters were evaluated, and the systemic levels of pro- and anti-inflammatory cytokines as well as the response of specific lymphocyte subsets were determined by flow cytometry. MenSCs exerted an important antimicrobial effect in vitro, mediated by a higher expression of the AMP-hepcidin. In the CLP mouse model, MenSCs in synergy with AB (a) improved the survival rate (95 %) in comparison with saline (6 %), AB (73 %), and MenSCs alone (48 %) groups; (b) enhanced bacterial clearance in the peritoneal fluids and blood; (c) reduced organ injuries evaluated by lower concentrations of the liver enzymes alanine aminotransferase and aspartate aminotransferase; and (d) modulated the inflammatory response through reduction of pro- and anti-inflammatory cytokines without significant loss of T and B lymphocytes. We conclude that MenSCs in combination with AB enhance survival in CLP-induced sepsis by acting on multiples targets. MenSCs thus constitute a feasible approach for the future clinical treatment of sepsis.


Intimate partner violence and HIV infection among married Indian women.
Despite reductions in prevalence of human immunodeficiency virus (HIV) infection among the general population of India, women account for a rising percentage of all HIV cases with husbands' risk behavior described as the major source of women's infection. Intimate partner violence (IPV) has been described as being associated with heterosexual transmission of HIV to women in India and elsewhere. To assess the relationship between experiencing IPV and the occurrence of HIV infection in a nationally representative sample of married Indian women tested for HIV. The Indian National Family Health Survey 3 was conducted across all Indian states in 2005 through 2006. The nationally representative sample included 124,385 married women; analyses conducted in 2007 and 2008 were limited to 28,139 married women who provided IPV data and HIV test results via systematic selection into respective subsamples. Prevalence estimates of lifetime IPV and HIV infection were calculated and demographic differences assessed. Intimate partner violence was conceptualized as physical violence with or without sexual violence and then was further categorized as physical violence only vs physical and sexual violence. Regression models were used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for HIV infection among Indian women based on experiences of IPV after adjusting for demographics and women's HIV risk behaviors. One-third of married Indian women (35.49%) reported experiencing physical IPV with or without sexual violence from their husbands; 7.68% reported both physical and sexual IPV, and 27.80% reported experiencing physical IPV in the absence of sexual violence. Approximately 1 in 450 women (0.22%) tested positive for HIV. In adjusted models, married Indian women experiencing both physical and sexual violence from husbands demonstrated elevated HIV infection prevalence vs those not experiencing IPV (0.73% vs 0.19%; adjusted OR, 3.92; 95% CI, 1.41-10.94; P = .01). Physical IPV alone was not associated with risk of HIV infection. Women's personal sexual risk behaviors were not associated with HIV infection. Among married Indian women, physical violence combined with sexual violence from husbands was associated with an increased prevalence of HIV infection. Prevention of IPV may augment efforts to reduce the spread of HIV/AIDS.


Gene discovery for the bark beetle-vectored fungal tree pathogen Grosmannia clavigera.
Grosmannia clavigera is a bark beetle-vectored fungal pathogen of pines that causes wood discoloration and may kill trees by disrupting nutrient and water transport. Trees respond to attacks from beetles and associated fungi by releasing terpenoid and phenolic defense compounds. It is unclear which genes are important for G. clavigera's ability to overcome antifungal pine terpenoids and phenolics. We constructed seven cDNA libraries from eight G. clavigera isolates grown under various culture conditions, and Sanger sequenced the 5' and 3' ends of 25,000 cDNA clones, resulting in 44,288 high quality ESTs. The assembled dataset of unique transcripts (unigenes) consists of 6,265 contigs and 2,459 singletons that mapped to 6,467 locations on the G. clavigera reference genome, representing ~70% of the predicted G. clavigera genes. Although only 54% of the unigenes matched characterized proteins at the NCBI database, this dataset extensively covers major metabolic pathways, cellular processes, and genes necessary for response to environmental stimuli and genetic information processing. Furthermore, we identified genes expressed in spores prior to germination, and genes involved in response to treatment with lodgepole pine phloem extract (LPPE). We provide a comprehensively annotated EST dataset for G. clavigera that represents a rich resource for gene characterization in this and other ophiostomatoid fungi. Genes expressed in response to LPPE treatment are indicative of fungal oxidative stress response. We identified two clusters of potentially functionally related genes responsive to LPPE treatment. Furthermore, we report a simple method for identifying contig misassemblies in de novo assembled EST collections caused by gene overlap on the genome.


Theoretical foundations of the Study of Latino (SOL) Youth: implications for obesity and cardiometabolic risk.
This article describes the conceptual model developed for the Hispanic Community Health Study/Study of Latino Youth, a multisite epidemiologic study of obesity and cardiometabolic risk among U.S. Hispanic/Latino children. Public health, psychology, and sociology research were examined for relevant theories and paradigms. This research, in turn, led us to consider several study design features to best represent both risk and protective factors from multiple levels of influence, as well as the identification of culturally relevant scales to capture identified constructs. The Socio-Ecological Framework, Social Cognitive Theory, family systems theory, and acculturation research informed the specification of our conceptual model. Data are being collected from both children and parents in the household to examine the bidirectional influence of children and their parents, including the potential contribution of intergenerational differences in acculturation as a risk factor. Children and parents are reporting on individual, interpersonal, and perceived organizational and community influences on children's risk for obesity consistent with Socio-Ecological Framework. Much research has been conducted on obesity, yet conceptual models examining risk and protective factors lack specificity in several areas. Study of Latino Youth is designed to fill a gap in this research and inform future efforts.


A functional variant of Fcgamma receptor IIIA is associated with rheumatoid arthritis in individuals who are positive for anti-glucose-6-phosphate isomerase antibodies.
Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic autoantibodies in K/BxN mice, although some groups have reported that few healthy humans retain these antibodies. The expression of Fcgamma receptors (FcgammaRs) is genetically regulated and has strong implications for the development of experimental arthritis. The interaction between immune complexes and FcgammaRs might therefore be involved in the pathogenesis of some arthritic conditions. To explore the relationship between functional polymorphisms in FcgammaRs (FCGR3A-158V/F and FCGR2A-131H/R) and arthritis in individuals positive for anti-GPI antibodies, we evaluated these individuals with respect to FCGR genotype. Genotyping for FCGR3A-158V/F and FCGR2A-131H/R was performed by PCR amplification of the polymorphic site, followed by site specific restriction digestion using the genome of 187 Japanese patients with rheumatoid arthritis (including 23 who were anti-GPI antibody positive) and 158 Japanese healthy individuals (including nine who were anti-GPI antibody positive). We report here on the association of FCGR3A-158V/F functional polymorphism with anti-GPI antibody positive status. Eight out of nine healthy individuals who were positive for anti-GPI antibodies possessed the homozygous, low affinity genotype FCGR3A-158F (odds ratio = 0.09, 95% confidence interval 0.01-0.89; P = 0.0199), and probably were 'protected' from arthritogenic antibodies. Moreover, among those who were homozygous for the high affinity genotype FCGR3A-158V/V, there were clear differences in anti-human and anti-rabbit GPI titres between patients with rheumatoid arthritis and healthy subjects (P = 0.0027 and P = 0.0015, respectively). Our findings provide a molecular model of the genetic regulation of autoantibody-induced arthritis by allele-specific affinity of the FcgammaRs.


Cardiac evaluation of collegiate student athletes: a medical and legal perspective.
Physicians participate in the screening, routine medical supervision, and disqualification process of collegiate student athletes today. Physicians and universities evaluating collegiate student athletes for athletic participation should understand the meticulous medical process necessary to make eligibility/disqualification decisions and the associated liability issues. It is the responsibility of a team physician to take the lead role in the college sports medical evaluation process. The first duty of a team physician and institution is to protect the health and well-being of their collegiate student athletes. The potential liability associated with the evaluation process requires institutions of higher education and physicians to develop sound and reasonable administrative strategies regarding college athletes and their participation in intercollegiate athletics. Reducing this liability risk requires an understanding of the evolving judicial framework and compliance with standard case law and available guidelines. As medical professional standards evolve, so will responsibilities under legal standards.