Missense mutations of the interleukin-12 receptor beta 1(IL12RB1) and interferon-gamma receptor 1 (IFNGR1) genes are not associated with susceptibility to lepromatous leprosy in Korea.
Interleukin-12 receptor beta 1 ( IL12RB1), interleukin-12 receptor beta 2 ( IL12RB2), and interferon gamma receptor 1 ( IFNGR1) perform important roles in the host defense against intracellular pathogens such as Mycobacteria. Several mutations within their genes have been confirmed as associated with increased susceptibility to mycobacterial infection. However, the association between mutations of the IL12RB1, IL12RB2, and IFNGR1 encoding genes and lepromatous leprosy has not been studied. This study screened for polymorphisms within IL12RB1, IL12RB2, and IFNGR1 encoding genes in the Korean populations using polymerase chain reaction (PCR)/single-strand conformation polymorphism (SSCP) DNA sequencing assay, and an association study was performed using the missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), and 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14M), and 1443 T/C (L467P) for the IFNGR1 encoding genes. There were no differences in the genotype and allele frequencies of IL12RB1 and IFNGR1 genes between 93 lepromatous leprosy patients and 94 control subjects. In conclusion, missense mutations of 705 A/G (Q214R), 1196 G/C (G378R), 1637 G/A (A525T), 1664 C/T (P534S) of the IL12RB1, 83 G/A (V14 M), and 1443 T/C (L467P) of the IFNGR1 encoding genes have no association with the susceptibility to lepromatous leprosy in the Korean population.


Breast-milk iodine concentration declines over the first 6 mo postpartum in iodine-deficient women.
Little is known about the iodine status of lactating mothers and their infants during the first 6 mo postpartum or, if deficient, the amount of supplemental iodine required to improve status. The objective was to determine maternal and infant iodine status and the breast-milk iodine concentration (BMIC) over the first 6 mo of breastfeeding. A randomized, double-blind, placebo-controlled supplementation trial was conducted in lactating women who received placebo (n = 56), 75 μg I/d (n = 27), or 150 μg I/d (n = 26) after their infants' birth until 24 wk postpartum. Maternal and infant urine samples and breast-milk samples were collected at 1, 2, 4, 8, 12, 16, 20, and 24 wk. Maternal serum thyrotropin and free thyroxine concentrations were measured at 24 wk. Over 24 wk, the median urinary iodine concentration (UIC) of unsupplemented women and their infants ranged from 20 to 41 μg/L and 34 to 49 μg/L, respectively, which indicated iodine deficiency (ie, UIC < 100 μg/L). Mean maternal UIC was 2.1-2.4 times higher in supplemented than in unsupplemented women (P < 0.001) but did not differ significantly between the 2 supplemented groups. BMIC in the placebo group decreased by 40% over 24 wk (P < 0.001) and was 1.3 times and 1.7 times higher in women supplemented with 75 μg I/d (P = 0.030) and 150 μg I/d (P < 0.001), respectively, than in unsupplemented women. Thyrotropin and free thyroxine did not differ significantly between groups. BMIC decreased in the first 6 mo in these iodine-deficient lactating women; supplementation with 75 or 150 μg I/d increased the BMIC but was insufficient to ensure adequate iodine status in women or their infants. The study was registered with the Australian New Zealand Clinical Trials Registry as ACTRN12605000345684.


Induction of HLA-G-restricted human cytomegalovirus pp65 (UL83)-specific cytotoxic T lymphocytes in HLA-G transgenic mice.
The non-classical major histocompatibility complex class I molecule HLA-G is expressed mainly by extravillous trophoblasts at the materno-foetal interface. HLA-G has been found to bind endogenously processed nonameric peptides but its function as a restriction element for a cytotoxic T cell response to viruses with tropism for trophoblastic cells has never been demonstrated. In this study, candidate viral peptides derived from human cytomegalovirus (HCMV) pp65 (UL83), which stabilized the HLA-G molecule on HLA-G-transfected T2 cells, were identified. The specific anti-pp65 cytotoxic T lymphocyte (CTL) response restricted by HLA-G in triple transgenic mice (HLA-G, human beta2m, human CD8alpha) was then investigated by injection of dendritic cells loaded with synthetic pp65-derived peptides or by infection with canarypox virus expressing pp65. Results showed that CTLs from HLA-G mice have the capacity to kill target cells either infected with recombinant vaccinia viruses expressing pp65 or loaded with specific pp65-derived peptides using HLA-G as an antigen-presenting molecule. It was also demonstrated that these HLA-G-restricted pp65-specific T cells are able to kill the human astrocytoma cell line U373, which was transfected with HLA-G and infected with HCMV. Moreover, using HLA-G tetramers refolded with a synthetic pp65-derived peptide, peptide-specific CD8(+) cells restricted by HLA-G have been detected in vivo. These findings provide the first evidence that HLA-G can select anti-HCMV-restricted CTLs in vivo, although the potency of this cytolytic response is limited (20-25 %). The weak HLA-G-restricted anti-HCMV response is probably due to HLA-G-mediated inhibitory signals on the development of an antiviral CTL response.


The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training.
Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake (V.O2max) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed. The search profile included: citrate, synthase, human, skeletal, muscle, training, not electrical stimulation, not in-vitro, not rats. Studies that reported changes in CS activity and V.O2max were included. Different training types and subject populations were analyzed independently to assess correlation between relative changes in V.O2max and CS activity. 70 publications with 97 intervention groups were included. There was a positive (r = 0.45) correlation (P < 0.001) between the relative change in V.O2max and the relative change in CS activity. All reported absolute values of CS and V.O2max did not correlate (r =- 0.07, n = 148, P = 0.4). Training induced changes in whole body oxidative capacity is matched by changes in muscle CS activity in a nearly 1:1 relationship. Absolute values of CS across different studies cannot be compared unless a standardized analytical method is used by all laboratories.


Fatty acids and polar lipids of extremely thermophilic filamentous bacterial masses from two Yellowstone hot springs.
The fatty acid composition of filamentous bacterial masses from two very hot Yellowstone Park springs is not unusual despite the extreme environment. Both populations have a series of C(14) to C(20) straight-chain acids with a maximum at C(18), and a series of saturated iso acids with a maximum at C(17) in one case and C(19) in the other. The fatty acid pattern of this anomalous group of organisms is like that of bacteria but not of blue-green algae. Both populations have similar polar lipids and identical carotenoids. It is speculated that these organisms may be adapted to their high-temperature environment by means of stable lipoprotein membrane systems.


Aspirin and NSAID use in older women: effect on bone mineral density and fracture risk. Study of Osteoporotic Fractures Research Group.
Prostaglandin inhibition by aspirin or nonsteroidal anti-inflammatory drug (NSAIDs) may inhibit bone loss and preserve bone mineral density (BMD) in vitro and in animal models. The effect of these agents on BMD and fracture risk in postmenopausal women in unknown. We assessed the risk factors for osteoporosis and the use of aspirin and NSAIDs in 7786 white women over age 65. Axial BMD was measured at the same time, and fractures were prospectively documented over the subsequent 4 years of follow-up. In age-adjusted analyses, daily use of aspirin or NSAIDs was associated with a 2.3-5.8% increase in BMD of the hip and spine. The relationship persisted even after adjustment for weight, a variety of medications, self-reported arthritis, and for radiographic findings of osteoarthritis, but the multiply adjusted increase in BMD was only 1.0-3.1%. Fracture risk was similar among daily users of aspirin and NSAIDs and nonusers. After adjustment for potential confounders, among daily aspirin users the relative risk of hip fracture was 1.1 (95% confidence interval [CI]: 0.7, 1.6), and among daily NSAID users the risk was 0.9 (CI: 0.6, 1.4). Considering all nonspine fractures together, the risk among aspirin users was 1.0 (CI: 0.8. 1.2), and among NSAID users the risk was also 1.0 (CI; 0.8, 1.2). Regular use of aspirin or NSAIDs may have a modest beneficial effect on BMD in postmenopausal women. This effect persists after adjustment for obesity and the presence of osteoarthritis. However, among women who take aspirin or NSAIDs regularly, there is no clinically significant protective effect on the subsequent risk of fractures.


Spatial Embryonic Origin Delineates GABAergic Hub Neurons Driving Network Dynamics in the Developing Entorhinal Cortex.
Coordinated neuronal activity is essential for the development of cortical circuits. GABAergic hub neurons that function in orchestrating early neuronal activity through a widespread net of postsynaptic partners are therefore critical players in the establishment of functional networks. Evidence for hub neurons was previously found in the hippocampus, but their presence in other cortical regions remains unknown. We examined this issue in the entorhinal cortex, an initiation site for coordinated activity in the neocortex and for the activity-dependent maturation of the entire entorhinal-hippocampal network. Using an unbiased approach that identifies "driver hub neurons" displaying a high number of functional links in living slices, we show that while almost half of the GABAergic cells single-handedly influence network dynamics, only a subpopulation of cells born in the MGE and composed of somatostatin-expressing neurons located in infragranular layers, spontaneously operate as "driver" hubs. This indicates that despite differences in the origin of interneuron diversity, the hippocampus and entorhinal cortex share similar developmental mechanisms for the establishment of functional circuits.


MR angiographic and sonographic indications for endarterectomy.
Our objective was to determine whether appropriate criteria could be developed for performing an endarterectomy on the basis of sonographic and MR angiographic findings. Fifty patients were examined prospectively with sonography, MR angiography, and conventional angiography. All three imaging studies were performed within 2 weeks of one another, and conventional angiography served as the reference standard. All 10 carotid occlusions were detected with sonography and MR angiography. Sonography accurately showed flow in two arteries, and MR angiography showed flow in one of three nearly occluded arteries with extremely slow flow. Multislab three-dimensional time-of-flight MR angiographic sequences underestimated the degree of stenosis in 12 arteries, and in two cases this resulted from high T1 signal within the atherosclerotic plaque. With conventional angiography as the reference standard for 70% to 99% stenosis, sonography had a sensitivity of 96%, a specificity of 91%, and a positive predictive value of 90%, while concordant sonographic findings and the presence of a signal void on multislab 3-D time-of-flight sequences had a sensitivity of 72%, a specificity of 98%, and a positive predictive value of 97%. Endarterectomy performed on the basis of sonographic findings of 70% to 99% stenosis and of a signal void on multislab 3-D time-of-flight MR angiographic sequences is appropriate.


The effect of bisphenol A on testicular steroidogenesis and its amelioration by quercetin: an in vivo and in silico approach.
Bisphenol A (BPA), a phenyl ring containing synthetic xenoestrogen, is widely used in the manufacture of polycarbonate plastics, epoxy resins and as a non-polymer additive to other plastics. Food is considered as the main source of exposure to BPA as it leaches out from food containers as well as surface coatings. It causes toxicity in the liver, kidney, brain, and other organs by initiating the process of lipid peroxidation. The present investigation was an attempt to evaluate the effect of BPA on steroidogenesis and its amelioration by quercetin. Inbred Swiss strain male albino mice were orally administered with 80, 120 and 240 mg per kg body weight per day of BPA for 45 days. The results revealed that BPA causes significant (p < 0.05) and dose-dependent changes in the body weight and biochemical parameters like protein, cholesterol and lipid contents as well as activities of 3β-and 17β-hydroxysteroid dehydrogenases in the testis of mice. It was also found to significantly reduce the testosterone level in serum. Oral administration of quercetin (30, 60 and 90 mg per kg body weight per day) along with a high dose of BPA (240 mg per kg body weight per day) for 45 days caused significant amelioration in the body weight and steroidogenesis as compared to the BPA alone treated group. The effect was dose-dependent. This amelioration in BPA-induced toxicity might be due to the antioxidative properties of quercetin. The reduction in the function of enzymes was confirmed by in silico bindings. BPA and quercetin show competitive binding with steroidogenic enzymes as well as binding with each other. This could be a possible mechanism to reduce the toxic effect of BPA which has been supported by molecular dynamics simulations for molecular level recognition with structural insights.


Sarcomatoid Peritoneal Mesothelioma: Clinicopathologic Correlation of 13 Cases.
Peritoneal mesothelioma is rare, and the sarcomatoid variant is more infrequent, with <30 cases reported to date in the literature. Several case series have described the morphologic features of sarcomatoid peritoneal mesothelioma (SPe); however, the clinicopathologic features are not well characterized. To our knowledge, this is the first large series reporting the clinicopathologic features of SPe. We reviewed our database of 3106 malignant mesothelioma cases. Of 248 peritoneal mesotheliomas, 15 (4%) were sarcomatoid variant (0.5% of all mesotheliomas). Only cases with 100% sarcomatoid morphology diagnosed by open surgical biopsy and/or autopsy were included. Thus, 4 cases were excluded leaving 11 cases of SPe. Two additional cases of SPe previously published by 1 of the authors (V.L.R.), not included in the database, are added yielding 13 cases total. The median age at diagnosis was 66 years (range=48 to 85 y), and there was a male predominance (M:F=3.25:1). Survival from date of diagnosis to date of death was 5 months (range=0 to 12 mo). The most common presenting symptom was abdominal pain, and 3 of 4 women were suspected to have cholecystitis/cholelithiasis. All cases stained positive for cytokeratins, and 2 contained heterologous elements. Seven cases had objective markers of asbestos exposure, and 2 additional cases had occupations strongly associated with mesothelioma. Two cases with alleged household contact exposures could not be confirmed to be asbestos related by lung fiber analysis. SPe is a rare variant of mesothelioma attributed to asbestos exposure in 69% of our cases.


Modular Ion Mobility Calibrants for Organometallic Anions Based on Tetraorganylborate Salts.
Organometallics are widely used in catalysis and synthesis. Their analysis relies heavily on mass spectrometric methods, among which traveling-wave ion mobility spectrometry (TWIMS) has gained increasing importance. Collision cross sections (CCS) obtainable by TWIMS significantly aid the structural characterization of ions in the gas phase, but for organometallics, their accuracy has been limited by the lack of appropriate calibrants. Here, we propose tetraorganylborates and their alkali-metal bound oligomers [Mn-1(BR4)n]- (M = Li, Na, K, Rb, Cs; R = aryl, Et; n = 1-6) as calibrants for electrospray ionization (ESI) TWIMS. These species chemically resemble typical organometallics and readily form upon negative-ion mode ESI of solutions of alkali-metal tetraorganylborates. By combining different tetraorganylborate salts, we have generated a large number of anions in a modular manner and determined their CCS values by drift-tube ion mobility spectrometry (DTIMS) (DTCCSHe = 81-585, DTCCSN2 = 130-704 Å2). In proof-of-concept experiments, we then applied these DTCCS values to the calibration of a TWIMS instrument and analyzed phenylcuprate and argentate anions, [Lin-1MnPh2n]- and [MnPhn+1]- (M = Cu, Ag), as prototypical reactive organometallics. The TWCCSN2 values derived from TWIMS measurements are in excellent agreement with those determined by DTIMS (<2% relative difference), demonstrating the effectiveness of the proposed calibration scheme. Moreover, we used theoretical methods to predict the structures and CCS values of the anions considered. These predictions are in good agreement with the experimental results and give further insight into the trends governing the assembly of tetraorganylborate, cuprate, and argentate oligomers.


Plasminogen alleles influence susceptibility to invasive aspergillosis.
Invasive aspergillosis (IA) is a common and life-threatening infection in immunocompromised individuals. A number of environmental and epidemiologic risk factors for developing IA have been identified. However, genetic factors that affect risk for developing IA have not been clearly identified. We report that host genetic differences influence outcome following establishment of pulmonary aspergillosis in an exogenously immune suppressed mouse model. Computational haplotype-based genetic analysis indicated that genetic variation within the biologically plausible positional candidate gene plasminogen (Plg; Gene ID 18855) correlated with murine outcome. There was a single nonsynonymous coding change (Gly110Ser) where the minor allele was found in all of the susceptible strains, but not in the resistant strains. A nonsynonymous single nucleotide polymorphism (Asp472Asn) was also identified in the human homolog (PLG; Gene ID 5340). An association study within a cohort of 236 allogeneic hematopoietic stem cell transplant (HSCT) recipients revealed that alleles at this SNP significantly affected the risk of developing IA after HSCT. Furthermore, we demonstrated that plasminogen directly binds to Aspergillus fumigatus. We propose that genetic variation within the plasminogen pathway influences the pathogenesis of this invasive fungal infection.


A focal cortical dysplasia case whose seizure focuses were detected using interhemispheric grid electrode: a technical case report.
We report an 18-year-old boy who presented with seizures at the age of 12 years. He had 3 different kinds of seizures, occurring 4 to 5 times a week, despite adequate antiepileptic treatment. Magnetic resonance imaging (MRI) showed deep paramedian focal cortical dysplasia in the left parietal lobe. Ictal video-EEG demonstrated 5 seizures originating from the left parietal lobe, left hemisphere and right hemisphere. He was submitted to invasive recordings with two frontal strips and an interhemispherical grid that was advanced to the corpus callosum. The lesion and other seizure focuses were resected subpially down to the corpus callosum approximately 1 cm posterior to the motor area. His seizures resumed after three years of quiescence. Postoperative MRI investigation revealed remnants of dysplastic tissue deep in the interhemispheric region, which were silent during the invasive EEG monitorization. We want to re-emphasize that each patient with cortical dysplasia who is a candidate for epilepsy surgery should undergo detailed neuroradiological investigations as well as EEG monitorization, whereas complete resection of the lesion on the basis of findings that are obtained from neuroradiological examination might have a superior effect on the postoperative seizure outcome compared to the findings obtained from EEG recordings.


The association among hypertension and reduced psychological well-being, anxiety and sleep disturbances: a population study.
Hypertension (HP) is a serious condition affecting about one quarter of all adults, both men and women. Genetic and environmental factors are of importance in its aetiology, while psychosocial factors may also play a role. This study focused on psychosocial factors and examined the association among reduced psychological well-being, anxiety, sleep disturbances and HP by comparing people with HP and the general population. A national survey of 12,166 individuals (hypertensives n = 2047; rest of population n = 10,119) was conducted using two-step multiple logistic regression with an odds ratio and a 95% confidence interval. The study is in accordance with Swedish legislation pertaining to ethics. Reduced psychological well-being, anxiety and sleep disturbances were higher in the HP group and, in addition, reduced psychological well-being was, still higher in the presence of severe anxiety and serious sleep disturbances. These three factors are of major importance for HP, but it is difficult to know whether they are causes or consequences. In order to prevent HP, support for people who exhibit such risk factors should be a matter of high priority.


2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children.
This guideline has been produced as the official statement of the European Thyroid Association guideline committee. Subclinical hypothyroidism (SCH) in pregnancy is defined as a thyroid-stimulating hormone (TSH) level above the pregnancy-related reference range with a normal serum thyroxine concentration. Isolated hypothyroxinaemia (defined as a thyroxine level below the 2.5th centile of the pregnancy-related reference range with a normal TSH level) is also recognized in pregnancy. In the majority of SCH the cause is autoimmune thyroiditis but may also be due to iodine deficiency. The cause of isolated hypothyroxinaemia is usually not apparent, but iodine deficiency may be a factor. SCH and isolated hypothyroxinaemia are both associated with adverse obstetric outcomes. Levothyroxine therapy may ameliorate some of these with SCH but not in isolated hypothyroxinaemia. SCH and isolated hypothyroxinaemia are both associated with neuro-intellectual impairment of the child, but there is no evidence that maternal levothyroxine therapy improves this outcome. Targeted antenatal screening for thyroid function will miss a substantial percentage of women with thyroid dysfunction. In children SCH (serum TSH concentration >5.5-10 mU/l) normalizes in >70% and persists in the majority of the remaining patients over the subsequent 5 years, but rarely worsens. There is a lack of studies examining the impact of SCH on the neuropsychological development of children under the age of 3 years. In older children, the evidence for an association between SCH and impaired neuropsychological development is inconsistent. Good quality studies examining the effect of treatment of SCH in children are lacking.


Whole brain functional connectivity using phase locking measures of resting state magnetoencephalography.
The analysis of spontaneous functional connectivity (sFC) reveals the statistical connections between regions of the brain consistent with underlying functional communication networks within the brain. In this work, we describe the implementation of a complete all-to-all network analysis of resting state neuronal activity from magnetoencephalography (MEG). Using graph theory to define networks at the dipole level, we established functionally defined regions by k-means clustering cortical surface locations using Eigenvector centrality (EVC) scores from the all-to-all adjacency model. Permutation testing was used to estimate regions with statistically significant connections compared to empty room data, which adjusts for spatial dependencies introduced by the MEG inverse problem. In order to test this model, we performed a series of numerical simulations investigating the effects of the MEG reconstruction on connectivity estimates. We subsequently applied the approach to subject data to investigate the effectiveness of our method in obtaining whole brain networks. Our findings indicated that our model provides statistically robust estimates of functional region networks. Application of our phase locking network methodology to real data produced networks with similar connectivity to previously published findings, specifically, we found connections between contralateral areas of the arcuate fasciculus that have been previously investigated. The use of data-driven methods for neuroscientific investigations provides a new tool for researchers in identifying and characterizing whole brain functional connectivity networks.


Cassini Imaging Science: initial results on Phoebe and Iapetus.
The Cassini Imaging Science Subsystem acquired high-resolution imaging data on the outer Saturnian moon, Phoebe, during Cassini's close flyby on 11 June 2004 and on Iapetus during a flyby on 31 December 2004. Phoebe has a heavily cratered and ancient surface, shows evidence of ice near the surface, has distinct layering of different materials, and has a mean density that is indicative of an ice-rock mixture. Iapetus's dark leading side (Cassini Regio) is ancient, heavily cratered terrain bisected by an equatorial ridge system that reaches 20 kilometers relief. Local albedo variations within and bordering Cassini Regio suggest mass wasting of ballistically deposited material, the origin of which remains unknown.


Involvement of reactive oxygen species in adaphostin-induced cytotoxicity in human leukemia cells.
Adaphostin (NSC 680410), an analog of the tyrphostin AG957, was previously shown to induce Bcr/abl down-regulation followed by loss of clonogenic survival in chronic myelogenous leukemia (CML) cell lines and clinical samples. Adaphostin demonstrated selectivity for CML myeloid progenitors in vitro and remained active in K562 cells selected for imatinib mesylate resistance. In the present study, the mechanism of action of adaphostin was investigated in greater detail in vitro. Initial studies demonstrated that adaphostin induced apoptosis in a variety of Bcr/abl- cells, including acute myelogenous leukemia (AML) blasts and cell lines as well as chronic lymphocytic leukemia (CLL) samples. Further study demonstrated that adaphostin caused intracellular peroxide production followed by DNA strand breaks and, in cells containing wild-type p53, a typical DNA damage response consisting of p53 phosphorylation and up-regulation. Importantly, the antioxidant N-acetylcysteine (NAC) blunted these events, whereas glutathione depletion with buthionine sulfoximine (BSO) augmented them. Collectively, these results not only outline a mechanism by which adaphostin can damage both myeloid and lymphoid leukemia cells, but also indicate that this novel agent might have a broader spectrum of activity than originally envisioned.


Clinical evaluation of angiotensin II enhanced perfusion scintigraphy in metastatic liver disease.
The hepatic perfusion index (HPI) may be of value in the diagnosis of liver micro-metastases. However, raised values of HPI also occur in some benign liver conditions (e.g. cirrhosis), thereby weakening the diagnostic power of this test. It has been suggested that infusion of the vaso-active agent angiotensin II might improve the predictive value of dynamic scintigraphy because it has been shown to alter liver perfusion in patients with metastatic liver disease. Basal HPI values were not significantly different in a group of patients with metastases (n = 10) and a group with cirrhosis (n = 9). A significant rise in HPI occurred in the metastatic group using angiotensin II enhancement (p less than 0.01, Wilcoxon test). In the cirrhotic group there was no significant increase in the HPI with angiotensin II enhancement. Within the groups, there was considerable variation in response, with eight of ten metastatic and five of nine cirrhotic patients showing a rise in HPI during an angiotensin II infusion. As a result, there was complete overlap in the angiotensin II enhanced HPI for the two groups. Angiotensin II enhancement of HPI is therefore unlikely to improve the diagnostic power of dynamic scintigraphy in individual patients with established hepatic disease.


A data set of bloodstain patterns for teaching and research in bloodstain pattern analysis: Impact beating spatters.
This is a data set of 61 blood spatter patterns scanned at high resolution, generated by controlled impact events corresponding to forensic beating situations. The spatter patterns were realized with two test rigs, to vary the geometry and speed of the impact of a solid object on a blood source - a pool of blood. The resulting atomized blood droplets travelled a set distance towards a poster board sheet, creating a blood spatter. Fresh swine blood was used; its hematocrit and temperature were measured. Main parameters of the study were the impact velocity and the distance between blood source and target sheet, and several other parameters were explored in a less systematic way. This new and original data set is suitable for training or research purposes in the forensic discipline of bloodstain pattern analysis.


Neuropathological indexes of Alzheimer's disease in demented and nondemented persons aged 80 years and older.
Subjects with clinically diagnosed senile dementia of the Alzheimer type (n = 37) and healthy controls (n = 5) were assessed clinically until death. Postmortem examination of the brain was performed at age 80 years or older. The brains of all of the group with dementia (except one that was found to have a non-Alzheimer dementia) had substantial densities of neocortical senile plaques regardless of dementia severity; the control brains had very few senile plaques. In those subjects with Alzheimer's disease, moderate correlations were found between dementia duration and severity (cognitive portion of the Blessed Dementia Scale and the Sum of Boxes from the Clinical Dementia Rating) and certain neuropathological lesions, both gross and microscopic. Densities of neocortical neurofibrillary tangles were related to degree of dementia; densities of neocortical senile plaques were unrelated. We conclude that (1) neocortical senile plaque densities differentiate very old subjects with Alzheimer's disease from nondemented controls, but there is a need for more postmortem studies of older persons who are free of dementia; and (2) among the microscopic lesions studied, densities of neocortical neurofibrillary tangles were most closely related to the degree and duration of dementia.


Minireview: human obesity-lessons from monogenic disorders.
Genetic influences on the determination of human fat mass are profound and powerful, a statement that does not conflict with the obvious influence of environmental factors that drive recent changes in the prevalence of obesity. The assertion of the importance of genetic factors has, until recently, largely been based on twin and adoption studies. However, in the last 6 yr, a number of human genes have been identified in which major missense or nonsense mutations are sufficient in themselves to result in severe early-onset obesity, usually associated with disruption of normal appetite control mechanisms. Progress in the identification of more common, subtler genetic variants that influence fat mass in larger numbers of people has been slower, but discernible. Human genetics will continue to make an invaluable contribution to the study of human obesity by identifying critical molecular components of the human energy balance regulatory systems, pointing the way toward more targeted and effective therapies and assisting the prediction of individual responses to environmental manipulations.


Innovative antifibrotic therapies in systemic sclerosis.
Fibrosis is a key feature of systemic sclerosis (SSc) and arises from excessive release of collagens by pathologically activated fibroblasts. Affecting the skin and many internal organs, fibrosis represents a major cause for the high morbidity and mortality in SSc. So far, effective therapies to treat fibrosis in SSc and other fibrotic diseases are not available in clinical routine. Nevertheless, promising antifibrotic agents are emerging from translational studies with some having already entered clinical trials. In this review, we focus on recent advances in the development of antifibrotic treatment strategies in SSc. We have selected for targeted therapeutic approaches that have proven high efficacy and tolerability in preclinical fibrosis models of SSc and/or are already in clinical evaluation. Applying these criteria, we discuss a large repertory of candidate antifibrotic therapies that block inflammatory pathways, inhibit profibrotic growth factors, modulate epigenetic signaling, and interfere with morphogenic pathways. Many antifibrotic candidate therapies have proven efficacy and tolerability in preclinical models of SSc. So far, early clinical studies have tested only few of these agents. Besides discovering novel molecular treatment strategies, SSc research will now have to translate its findings into clinical practice.


The regulation of SIRT2 function by cyclin-dependent kinases affects cell motility.
Cyclin-dependent kinases (Cdks) fulfill key functions in many cellular processes, including cell cycle progression and cytoskeletal dynamics. A limited number of Cdk substrates have been identified with few demonstrated to be regulated by Cdk-dependent phosphorylation. We identify on protein expression arrays novel cyclin E-Cdk2 substrates, including SIRT2, a member of the Sirtuin family of NAD(+)-dependent deacetylases that targets alpha-tubulin. We define Ser-331 as the site phosphorylated by cyclin E-Cdk2, cyclin A-Cdk2, and p35-Cdk5 both in vitro and in cells. Importantly, phosphorylation at Ser-331 inhibits the catalytic activity of SIRT2. Gain- and loss-of-function studies demonstrate that SIRT2 interfered with cell adhesion and cell migration. In postmitotic hippocampal neurons, neurite outgrowth and growth cone collapse are inhibited by SIRT2. The effects provoked by SIRT2, but not those of a nonphosphorylatable mutant, are antagonized by Cdk-dependent phosphorylation. Collectively, our findings identify a posttranslational mechanism that controls SIRT2 function, and they provide evidence for a novel regulatory circuitry involving Cdks, SIRT2, and microtubules.


Assessment of multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in Sudan; findings and implications.
Background: Multidrug-resistant tuberculosis (MDR-TB) has a socioeconomic impact and threatens global public health. We assessed treatment outcomes of MDR-TB and predictors of poor treatment outcomes in Sudan given current high prevalence rates.Methods: Combined retrospective and prospective cohort study at Abu-Anga hospital (TB specialized hospital in Sudan). All patients with MDR-TB between 2013 and 2017 were targeted.Results: A total of 156 patients were recruited as having good records, 117 (75%) were male, and 152 (97.4%) had pulmonary TB. Patients were followed for a median of 18 months and a total of 2108 person-months. The overall success rate was 63.5% and the mortality rate was 14.1%. Rural residency (P < 0.05) and relapsing on previous treatments (P < 0.05) were determinants of time to poor MDR-TB treatment outcomes.Conclusion: Overall, more attention needs to be given to special MDR-TB groups that are highly susceptible to poor outcomes, i.e. rural patients. As a result, it is highly recommended to maintain total coverage of medicines for all MDR-TB patients for the entire period of treatment in Sudan. It is also recommended to instigate more treatment centers in rural areas in Sudan together with programs to enhance adherence to treatments including patient counseling to improve future outcomes.


Clonality Studies in the Analysis of Adrenal Medullary Proliferations: Application Principles and Limitations.
Clonality remains as the hallmark of neoplasms. A dual genetic approach using markers nonrelated (e.g., X-chromosome inactivation assays) and related to the malignant transformation (such as loss of heterozygosity analyses of tumor-suppressor genes) would provide useful clonality information from early and advanced tumor stages, respectively. Tumor progression and clonal selection would result in genetic instability and heterogeneous expression of those molecular markers related to the malignant pathway. Therefore, only the coexistence of multiple genetic abnormalities would support the clonal nature as an expression of convergent cell selection. Considering those facts, the currently available evidence on tumorigenesis and clonality in the adrenal medulla can be summarized as follows: 1. Multistep tumorigenesis defines the evolution of pheochromocytomas, as evidenced by the presence of several genetic alterations. 2. Both the significant association of nonrandom genetic alterations (specially 1p and 22q interstitial deletions) and the topographic accumulation of genetic deletions at the peripheral tumor compartment support a convergent clone selection for these neoplasms. 3. Although many genetic loci show nonrandom abnormalities, the most frequently involved locates on chromosome 1p regardless of genetic tumor background (sporadic or inherited predisposition). 4. Most pheochromocytomas should begin as monoclonal proliferations that do not always correlate with histopathologic features, particularly in inherited tumor syndromes. 5. Early histopathologic stages, described as adrenal medullary hyperplasias, are defined by hyperproliferative features in animal models and monoclonal patterns in the adrenal nodules from patients with MEN-2a.


A novel optical film to provide a highly collimated planar light source.
In this paper, we proposed a novel optical film 'Collimation Film with Equivalent Focal Reflective Aperture' (CFEFRA) that can collocate with the proper light guide plate (LGP) to provide a highly collimated planar light source (HCPLS) that not only has high intensity peak but also good uniformity. The CFEFRA has micro-cylindrical lenses and inverted-prism-like micro-teeth on its upper surface and lower surface, respectively. The lower micro-teeth that are aligned with the upper lenses can deflect the light emitting from the LGP at large declination into the normal, and then the deflected light with transverse fan-out is further converged by the upper lens to become the collimated light. The exact alignment between the upper and lower micro-structures is fulfilled by the method 'auto-secure-alignment by focusing of a collimated exposure beam'. The vertical and horizontal full width at half maximum (FWHM) of angular intensity of the HCPLS for the optimal case are of 14 and 6 degrees, respectively. Moreover, it still has high optical efficiency with light output of over 90% despite the resultant emitting light is such collimated. Most importantly, CFEFRA just needs to collocate with a relatively low-cost and easily-manufactured LGP so the HCPLS adopting the CFEFRA can be extended for large-sized application. Both optical model and experimental samples are demonstrated in this paper, and the simulation results are consistent with the experimental results. The consistency proves our design concept and optical model are convincible and feasible.


Climate change impacts on activated sludge wastewater treatment: a case study from Norway.
We present an investigation on climate change effects on a wastewater treatment system that receive sewage collected in a combined sewer system in Oslo, Norway, during winter operation. Results obtained, by contrasting meteorological data with sewage data, show that wastewater treatment plant (WWTP) influent flow rates are significantly increased during temporary snow melting periods above a critical daily air mean temperature of approx. -1.5 degrees C degree (T(Crit)) identified in the area. In order to assess melting patterns, the number of days above and below T(Crit) was assessed, and the annual number of melting periods was additionally evaluated using meteorological data obtained in the last decade. A striking thing about the daily air temperature pattern is that, despite the progressively warmer winter temperatures in the last decade, an increasing number of days with temperatures below -1.5 degrees C could be observed. The frequency of melting periods is shown to increase in wintertime, and it is identified as an additional climate change related factor in the Oslo region. We demonstrate that these impacts can deteriorate the WWTP operation through progressively increasing the relative frequencies of very high influent flow rate and of the very low influent sewage temperature. Such climate change related effects on sewage treatment processes can be characterised as shock-conditions, i.e. significant changes in a system's boundary conditions, occurring in a relatively short period of time. In the six year period examined, biological nitrogen removal and secondary clarification processes are shown to be significantly affected by the climate factors. A striking thing about using the state-of-the-art mathematical models of wastewater treatment processes in decision support systems is their inability of describing, and thus predicting the effects of such shock-loading events, as they have not been studied so far. Adaptation and optimisation of process models, also for use in design, optimisation as well as in real-time automation and process control schemes, are thus critical to meet the challenges of climatic changes in the future.


Pupil function design algorithm for bipolar incoherent spatial filtering.
A two-step iterative algorithm is described for designing pupil functions for synthesis of bipolar point spread functions in a two-channel incoherent spatial filtering system. The first step uses the method of projections onto convex sets to determine an appropriate bias for the system pupil functions. This bias determines the complementary point spread functions and therefore the magnitude of the corresponding coherent spread functions. The phase of the coherent spread functions is obtained in the second step via iterative application of a magnitude constraint and a finite support constraint. With both magnitude and phase of the coherent spread functions established, the corresponding pupil functions are realized via Fourier transformation. Results are presented for a 2-D bandpass filter and compared with analytically obtained results. The comparison suggests that the iterative algorithm yields bias functions having less energy than bias functions determined by previously proposed analytic methods.


Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.
To test whether ovarian stimulation for in-vitro fertilization (IVF) affects oocyte quality and thus chromosome segregation behaviour during meiosis and early embryo development, preimplantation genetic screening of embryos was employed in a prospective, randomized controlled trial, comparing two ovarian stimulation regimens. Infertile patients under 38 years of age were randomly assigned to undergo a mild stimulation regimen using gonadotrophin-releasing hormone (GnRH) antagonist co-treatment (67 patients), which does not disrupt secondary follicle recruitment, or a conventional high-dose exogenous gonadotrophin regimen and GnRH agonist co-treatment (44 patients). Following IVF, embryos were biopsied at the eight-cell stage and the copy number of 10 chromosomes was analysed in 1 or 2 blastomeres. The study was terminated prematurely, after an unplanned interim analysis (which included 61% of the planned number of patients) found a lower embryo aneuploidy rate following mild stimulation. Compared with conventional stimulation, significantly fewer oocytes and embryos were obtained following mild stimulation (P < 0.01 and < 0.05, respectively). Consequently, both regimens generated on average a similar number (1.8) of chromosomally normal embryos. Differences in rates of mosaic embryos suggest an effect of ovarian stimulation on mitotic segregation errors. Future ovarian stimulation strategies should avoid maximizing oocyte yield, but aim at generating a sufficient number of chromosomally normal embryos by reduced interference with ovarian physiology.


Structural Brain Connectivity in Childhood Disruptive Behavior Problems: A Multidimensional Approach.
Studies of white matter connectivity in children with disruptive behavior have yielded inconsistent results, possibly owing to the trait's heterogeneity, which comprises diverse symptoms like physical aggression, irritability, and delinquency. This study examined associations of global and specific white matter connectivity with childhood disruptive behavior problems, while accounting for their complex multidimensionality. In a large cross-sectional population-based study of 10-year-old preadolescents (n = 2567), we assessed four previously described empirically derived dimensions of disruptive behavior problems using the Child Behavior Checklist: physical aggression, irritability, disobedient behavior, and delinquent behavior. Global and specific white matter microstructure was assessed by diffusion tensor imaging. Global fractional anisotropy and mean diffusivity were not associated with broad measures of disruptive behavior, e.g., Child Behavior Checklist externalizing problems scale. Global fractional anisotropy was negatively associated with delinquent behavior (β = -.123, pfalse discovery rate adjusted = .028) and global mean diffusivity was positively associated with delinquent behavior (β = .205, pfalse discovery rate adjusted < 0.001), suggesting reduced white matter microstructure in preadolescents with higher levels of delinquent behavior. Lower white matter microstructure in the inferior longitudinal fasciculus, superior longitudinal fasciculus, cingulum, and uncinate underlie these associations. Global white matter microstructure was not associated with physical aggression, irritability, or disobedient behavior. Delinquent behavior, a severe manifestation of childhood disruptive behavior, was associated with lower white matter microstructure in tracts connecting frontal and temporal lobes. These brain regions are involved in decision making, reward processing, and emotion regulation. This study demonstrated that incorporating the multidimensional nature of childhood disruptive behavior traits shows promise in advancing the search for elucidating neurobiological correlates of disruptive behavior.


An etiological role for aeroallergens and eosinophils in experimental esophagitis.
Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.


Identification and functional characterization of TMEM16A, a Ca2+-activated Cl- channel activated by extracellular nucleotides, in biliary epithelium.
Cl(-) channels in the apical membrane of biliary epithelial cells (BECs) provide the driving force for ductular bile formation. Although a cystic fibrosis transmembrane conductance regulator has been identified in BECs and contributes to secretion via secretin binding basolateral receptors and increasing [cAMP](i), an alternate Cl(-) secretory pathway has been identified that is activated via nucleotides (ATP, UTP) binding apical P2 receptors and increasing [Ca(2+)](i). The molecular identity of this Ca(2+)-activated Cl(-) channel is unknown. The present studies in human, mouse, and rat BECs provide evidence that TMEM16A is the operative channel and contributes to Ca(2+)-activated Cl(-) secretion in response to extracellular nucleotides. Furthermore, Cl(-) currents measured from BECs isolated from distinct areas of intrahepatic bile ducts revealed important functional differences. Large BECs, but not small BECs, exhibit cAMP-stimulated Cl(-) currents. However, both large and small BECs express TMEM16A and exhibit Ca(2+)-activated Cl(-) efflux in response to extracellular nucleotides. Incubation of polarized BEC monolayers with IL-4 increased TMEM16A protein expression, membrane localization, and transepithelial secretion (I(sc)). These studies represent the first molecular identification of an alternate, noncystic fibrosis transmembrane conductance regulator, Cl(-) channel in BECs and suggest that TMEM16A may be a potential target to modulate bile formation in the treatment of cholestatic liver disorders.


Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices.
The computations performed within cortex are likely to be determined by its internal dynamics in addition to its pattern of afferent input. As a step toward characterizing these dynamics, we have imaged electrical activity in slices from rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In response to electrical stimulation two fluorescence signals of similar maximum amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is dependent on membrane voltage, and has a significant presynaptic component. This signal can be used to image electrical activity ratiometrically. (ii) A slow signal that peaks a few seconds after stimulation, does not reflect voltage changes, and may originate from changes in scattering properties of the slice and from interactions of the dye with the cells. The spatial pattern of fast signals obtained in response to focal stimulation of coronal slices is consistent with known interlaminar projection patterns. In tangential slices, imaging of fast signals reveals clustered horizontal responses. Finally, imaging of fast signals during epileptiform activation of the disinhibited circuit reveals propagating responses, without evidence for modular activation.


Evaluation of Comparative Efficacy and Safety of Surgical Approaches for Total Hip Arthroplasty: A Systematic Review and Network Meta-analysis.
Each approach for primary total hip arthroplasty (THA) has a long learning curve, so a surgeon's choice to change their preferred approach needs to be guided by clear justifications. However, current evidence does not suggest that any of the THA approaches are more beneficial than others, and the choice of approach is mainly based on the knowledge and experience of the surgeon and individual patient characteristics. To assess the efficacy and safety associated with different surgical approaches for THA. A comprehensive search of PubMed, EMBASE, and Cochrane databases from inception to March 26, 2022; reference lists of eligible trials; and related reviews. Randomized clinical trials (RCTs) comparing different surgical approaches, including the 2-incision approach, direct anterior approach (DAA), direct lateral approach (DLA), minimally invasive direct lateral approach (MIS-DLA), minimally invasive anterolateral approach (MIS-ALA), posterior approach (PA), minimally invasive posterior approach (MIS-PA), and supercapsular percutaneously assisted total hip arthroplasty (SuperPath), for primary THA. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, 2 reviewers independently extracted data on study participants, interventions, and outcomes as well as assessed the risk of bias using the Cochrane risk of bias tool and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation framework. A frequentist framework was used to inform a series of random-effects network meta-analyses. The outcomes were hip score (range, 0-100, with higher scores indicating better overall hip condition), pain score (range, 0-100, with higher scores indicating more pain), hospitalization time, operation time, quality of life score, blood loss, cup abduction angle, and cup anteversion angle. Of 2130 retrieved studies, 63 RCTs including 4859 participants (median [IQR] age, 64.0 [60.3-66.5] years; median [IQR] percentage male, 46.74% [38.64%-54.74%]) were eligible for analysis. Eight surgical approaches were evaluated. For hip score, DAA (mean difference [MD], 4.04; 95% CI, 1.92 to 6.16; moderate certainty), MIS-ALA (MD, 3.00; 95% CI, 0.43 to 5.59; moderate certainty), MIS-DLA (MD, 3.37; 95% CI, 1.05 to 5.68; moderate certainty), MIS-PA (MD, 4.46; 95% CI, 1.60 to 7.31; moderate certainty), PA (MD, 4.37; 95% CI, 1.87 to 6.88; high certainty), and SuperPath (MD, 5.00; 95% CI, 0.58 to 9.42; high certainty) were associated with greater improvement in hip score compared with DLA. DLA was associated with lower decrease in pain score than SuperPath (MD, 1.16; 95% CI, 0.13 to 2.20; high certainty) and MIS-DLA (MD, 0.90; 95% CI, 0.04 to 1.76; moderate certainty). PA was associated with shorter operation times compared with 2-incision (MD, -23.85 minutes; 95% CI, -36.60 to -11.10 minutes; high certainty), DAA (MD, -13.94 minutes; 95% CI, -18.79 to -9.08 minutes; moderate certainty), DLA (MD, -10.50 minutes; 95% CI, -16.07 to -4.94 minutes; high certainty), MIS-ALA (MD, -6.76 minutes; 95% CI, -12.86 to -0.65 minutes; moderate certainty), and SuperPath (MD, -13.91 minutes; 95% CI, -21.87 to -5.95 minutes; moderate certainty). The incidence of 6 types of complications did not differ significantly between the approaches. In this study, moderate to high certainty evidence indicated that compared with PA, all surgical approaches except DLA were associated with similar improvements of hip score but longer operation time. DLA was associated with smaller improvement of hip score. The safety of the different approaches did not show significant differences. These findings will help health professionals and patients with better clinical decision-making and also provide references for policy makers.


Efficacy, safety, and dose-response characteristics of glipizide gastrointestinal therapeutic system on glycemic control and insulin secretion in NIDDM. Results of two multicenter, randomized, placebo-controlled clinical trials. The Glipizide Gastrointestinal Therapeutic System Study Group.
To investigate the efficacy, safety, and dose-response characteristics of an extended-release preparation of glipizide using the gastrointestinal therapeutic system (GITS) on plasma glucose, glycosylated hemoglobin (HbA1c), and insulin secretion to a liquid-mixed meal in NIDDM patients. Two prospective, randomized, double-blind, placebo-controlled, multicenter clinical trials were performed in 22 sites and 347 patients with NIDDM (aged 59 +/- 0.6 years; BMI, 29 +/- 0.3 kg/m2; known diabetes duration, 8 +/- 0.4 years) were studied. Each clinical trial had a duration of 16 weeks with a 1-week washout, 3-week single-blind placebo phase, 4-week titration to a fixed dose, and 8-week maintenance phase at the assigned dose. In the first trial, once-daily doses of 5, 20, 40, or 60 mg glipizide GITS were compared with placebo in 143 patients. In the second trial, doses of 5, 10, 15, or 20 mg of glipizide GITS were compared with placebo in 204 patients. HbA1c, fasting plasma glucose (FPG), insulin, C-peptide, and glipizide levels were determined at regular intervals throughout the study. Postprandial plasma glucose (PPG), insulin, and C-peptide also were determined at 1 and 2 h after a mixed meal (Sustacal). All doses of glipizide GITS in both trials produced significant reductions from placebo in FPG (range -57 to -74 mg/dl) and HbA1c (range -1.50 to -1.82%). Pharmacodynamic analysis indicated a significant relationship between plasma glipizide concentration and reduction in FPG and HbA1c over a dose range of 5-60 mg, with maximal efficacy achieved at a dose of 20 mg for FPG and at 5 mg for HbA1c. PPG levels were significantly lower, and both postprandial insulin and C-peptide levels significantly higher in patients treated with glipizide GITS compared with placebo. The percent reduction in FPG was comparable across patients with diverse demographic and clinical characteristics, including those with entry FPG > or = 250 mg/dl, resulting in greater absolute decreases in FPG and HbA1c in patients with the most severe hyperglycemia. Despite the forced titration to a randomly assigned dose, only 11 patients in both studies discontinued therapy because of hypoglycemia. Glipizide GITS did not alter lipids levels or produce weight gain. The once-daily glipizide GITS 1) lowered HbA1c, FPG, and PPG over a dose range of 5-60 mg, 2) was maximally effective at 5 mg (using HbA1c) or 20 mg (using FPG) based on pharmacokinetic and pharmacodynamic relationships, 3) maintained its effectiveness in poorly controlled patients (those with entry FPG > or = 250 mg/dl), 4) was safe and well tolerated in a wide variety of patients with NIDDM, and 5) did not produce weight gain or adversely affect lipids.


Differential apoptosis gene expressions of rhabdomyosarcoma cells in response to enterovirus 71 infection.
Enterovirus 71 (EV71) infection can induce the apoptosis of infected cells. The aim of this study is to explore the effect of EV71 infection on apoptosis mechanisms in virus-infected human rhabdomyosarcoma (RD) cells. The apoptosis of RD cells was examined using annexin V-FITC/PI by flow cytometry and cytokines were detected by ELISA. Cellular RNA was extracted and transcribed to cDNA. PCR array was employed to analyze the expressions of 84 apoptotic genes from EV71-infected RD cells at 8 and 20 h postinfection, respectively. In addition, the expressions of FasL, caspase, AKT2, JNK1/2, c-Jun and NF-κB proteins were detected by western blotting. Flow cytometry demonstrated that the apoptosis or death of EV71-infected RD cells was increased by 37.1% with a multiplicity of infection (MOI) of 5 at 20 h postinfection. The production of IL-4, IL-10 and TNF-α was enhanced by the subsequent EV71 infection. PCR array revealed significant changes in the expressions of apoptotic genes. Among 84 genes, 42 genes were down-regulated after EV71 infection at 8 h, whereas 32 genes were up-regulated at 20 h postinfection. Moreover, the ligands of TNF superfamily such as FasL, CD40L and TNF-α were significantly up-regulated and enhanced the expressions of apoptosis-related cysteine peptidases, including caspase-10, -8, -7 and -3. In addition, EV71 infection induces the phosphorylation of AKT2, JNK1/2, c-Jun and NF-κB at 20 h postinfection. PCR array for the determination of apoptosis gene expressions is an informative assay in elucidating biological pathways. During the early stage of EV71 infection, the apoptotic process of RD cells is significantly delayed. EV71 infection can also induce the expressions of FasL, TNF-α and CD40L, which contribute to the apoptosis of RD cells.


Experimental antibiotic treatment identifies potential pathogens of white band disease in the endangered Caribbean coral Acropora cervicornis.
Coral diseases have been increasingly reported over the past few decades and are a major contributor to coral decline worldwide. The Caribbean, in particular, has been noted as a hotspot for coral disease, and the aptly named white syndromes have caused the decline of the dominant reef building corals throughout their range. White band disease (WBD) has been implicated in the dramatic loss of Acropora cervicornis and Acropora palmata since the 1970s, resulting in both species being listed as critically endangered on the International Union for Conservation of Nature Red list. The causal agent of WBD remains unknown, although recent studies based on challenge experiments with filtrate from infected hosts concluded that the disease is probably caused by bacteria. Here, we report an experiment using four different antibiotic treatments, targeting different members of the disease-associated microbial community. Two antibiotics, ampicillin and paromomycin, arrested the disease completely, and by comparing with community shifts brought about by treatments that did not arrest the disease, we have identified the likely candidate causal agent or agents of WBD. Our interpretation of the experimental treatments is that one or a combination of up to three specific bacterial types, detected consistently in diseased corals but not detectable in healthy corals, are likely causal agents of WBD. In addition, a histophagous ciliate (Philaster lucinda) identical to that found consistently in association with white syndrome in Indo-Pacific acroporas was also consistently detected in all WBD samples and absent in healthy coral. Treatment with metronidazole reduced it to below detection limits, but did not arrest the disease. However, the microscopic disease signs changed, suggesting a secondary role in disease causation for this ciliate. In future studies to identify a causal agent of WBD via tests of Henle-Koch's postulates, it will be vital to experimentally control for populations of the other potential pathogens identified in this study.


Perinatal depressive symptoms in HIV-infected versus HIV-uninfected women: a prospective study from preconception to postpartum.
Depression is common among HIV-infected women, predicts treatment nonadherence, and consequently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women. We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ≥16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Women's Interagency HIV Study (WIHS). The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p=0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p<0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p=0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p=0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p=0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p=0.03). Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIV-uninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.


The Daily Functionality in a Major Depressive Episode Cohort of Romanian Patients - a Non-Interventional Study.
The aim of this non-interventional, investigator driven study was to assess the functionality of patients with major depression under treatment with agomelatine in real life clinical practice. The study was multicenter, non-interventional and evaluated the functionality of the adult patients with a DSM-IV diagnosis of MDD (single or recurrent episode and no treatment in the previous 6 months). It took place in Romania and it was a 10-weeks study. After the clinicians took the medical decision of treatment with agomelatine and if the patient agreed to be evaluated more accurate in this study, in order to assess functionality, patients completed at each visit the Sheehan Disability Scale (SDS). Patients were assessed also with QIDS-C (Quick Inventory of Depressive Symptomatology), a measure of depression symptoms severity and CGI scale severity (CGI-S), CGI scale improvement (CGI-I) and therapeutic index. Also, data about demographics and disease were collected during clinical interviews and from medical records. The functionality as assessed with SDS showed a significant functional impairment at baseline with scores >6 for each of the 3 inter-related domains of work/school, social and family life. At the end of the study, all functional aspects were improved although a mild impairment still persist requiring further treatment. A total of 1191 patients were analyzed (mean age: 47 years, 68% female). Mean QIDS-16 total score at baseline was 14.3 and decreased over the 10-week prospective period to 2.3. Most patients were treated with agomelatine. This study outcome confirms the fast on set of functionality improvement of agomelatine and further treatment need for the total remission of clinical depressive symptomatology after 10 weeks of treatment.


Thrombocytopenia in critically ill patients receiving thromboprophylaxis: frequency, risk factors, and outcomes.
Thrombocytopenia is the most common hemostatic disorder in critically ill patients. The objective of this study was to describe the incidence, risk factors, and outcomes of thrombocytopenia in patients admitted to medical-surgical ICUs. Three thousand seven hundred forty-six patients in 67 centers were enrolled in a randomized trial in which unfractionated heparin was compared with low-molecular-weight heparin (LMWH) for thromboprophylaxis. Patients who had baseline platelet counts < 75 × 10(9)/L or severe coagulopathy at screening were excluded. We analyzed the risk of developing mild (100-149 × 10(9)/L), moderate (50-99 × 10(9)/L), and severe (< 50 × 109/L) thrombocytopenia during an ICU stay. We also assessed independent and time-varying predictors of thrombocytopenia and the effect of thrombocytopenia on major bleeding, transfusions, and death. The incidences of mild, moderate, and severe thrombocytopenia were 15.3%, 5.1%, and 1.6%, respectively. The predictors of each category of thrombocytopenia were APACHE (Acute Physiology and Chronic Health Evaluation) II score, use of inotropes or vasopressors, and renal replacement therapy. The risk of moderate thrombocytopenia was lower in patients who received LMWH thromboprophylaxis but higher in surgical patients and in patients who had liver disease. Each category of thrombocytopenia was associated with subsequent bleeding and transfusions. Moderate and severe thrombocytopenia were associated with increased ICU and hospital mortality. A high severity of illness, prior surgery, use of inotropes or vasopressors, renal replacement therapy, and liver dysfunction are associated with a higher risk of thrombocytopenia developing in the ICU, whereas LMWH thromboprophylaxis is associated with a lower risk. Patients who develop thrombocytopenia in the ICU are more likely to bleed, receive transfusions, and die.


Stature estimation for Bosnian male population.
Since 1996, the Trotter and Gleser formulae to determine the stature of recovered missing persons in Bosnia and Herzegovina have been used. The purpose of this study is to develop appropriate stature estimation formulae from the length of the femur, tibia and fibula for use in the Bosnia and Herzegovina to help in identifications of the victims. Research was undertaken on 50 male cadavers, of individuals who died between the ages of 23 to 54 years. The cadaver length was measured and the length of the long bones was obtained from X-ray photographs. The length of the cadavers of the individuals who died after age of 45 years was corrected according to Giles' table. This study established that using Trotter and Gleser's formulae underestimate stature of tall people in the current population of Bosnia and Herzegovina. Smallest standard error of estimate is observed in the formula that uses the sum of the length of femur and fibula. There are no statistically significant differences between the length of the bones from the left and right sides of the body. Therefore, formulae developed from the average length of bone pairs are recommended for use.


Irradiation abolishes smooth muscle investment into vascular lesions in specific vascular beds.
The long-term adverse effects of radiotherapy on cardiovascular disease are well documented. However, the underlying mechanisms responsible for this increased risk are poorly understood. Previous studies using rigorous smooth muscle cell (SMC) lineage tracing have shown abundant SMC investment into atherosclerotic lesions, where SMCs contribute to the formation of a protective fibrous cap. Studies herein tested whether radiation impairs protective adaptive SMC responses during vascular disease. To do this, we exposed SMC lineage tracing (Myh11-ERT2Cre YFP+) mice to lethal radiation (1,200 cGy) followed by bone marrow transplantation prior to atherosclerosis development or vessel injury. Surprisingly, following irradiation, we observed a complete loss of SMC investment in 100% of brachiocephalic artery (BCA), carotid artery, and aortic arch lesions. Importantly, this was associated with a decrease in multiple indices of atherosclerotic lesion stability within the BCA. Interestingly, we observed anatomic heterogeneity, as SMCs accumulated normally into lesions of the aortic root and abdominal aorta, suggesting that SMC sensitivity to lethal irradiation occurs in blood vessels of neural crest origin. Taken together, these results reveal an undefined and unintended variable in previous studies using lethal irradiation and may help explain why patients exposed to radiation have increased risk for cardiovascular disease.


Odontogenic effects of two calcium silicate-based biomaterials in human dental pulp cells.
The goal of treating exposed pulp with an appropriate pulp capping material is to promote the dentinogenic potential of the pulpal cells. There have been recent attempts to develop more effective pulp-capping materials. The aim of this study was to evaluate the effect of newly developed calcium silicate-based material on odontogenic differentiation of primary human dental pulp cells (HDPCs), in comparison with a contemporary calcium silicate-based material. Human dental pulp cells isolated from dental pulps were cultured in standard culture conditions in Dulbecco's Modified Eagle's Medium (DMEM) and then the effects of Micro-Mega mineral trioxide aggregate (MM-MTA) (Micro-Mega, Besançon, France) and ProRoot MTA (MTA) (Dentsply Sirona, Tulsa, USA) (positive control) were evaluated on HDPCs at 1, 7 and 14 days. Untreated cells were used as a negative control. Odontoblastic differentiation was assessed by alkaline phosphatase (ALP) activity. Runtrelated transcription factor 2 (RUNX2), alkaline phosphatase liver/bone/kidney (ALPL), bone morphogenetic protein 2 (BMP2), dentin sialophosphoprotein (DSPP), and Distal-less homeobox 3 (DLX3), as odontoblastic/ osteoblastic expression markers, were evaluated by semi-quantitative real-time polymerase chain reaction (RT-PCR) analysis. Calcium levels of culture media were also determined. The MM-MTA group significantly increased the expression of BMP2 compared with that of the MTA group at 3 different time periods (p < 0.05). The up-regulation of ALPL between day 1 and 14 and the up-regulation of DSPP between day 7 and 14 were significant in both groups (p < 0.05). Micro-Mega MTA and MTA exhibited similar messenger RNA (mRNA) expression levels of ALPL, DSPP, RUNX2, DLX3, and ALP activities, as well as calcium levels. Based on the cell responses observed in this study, MM-MTA might be used efficiently in dental pulp therapy as a potential alternative to MTA.


Mycobacterium tuberculosis in the acquired immunodeficiency syndrome.
Patients with human immunodeficiency virus (HIV) infection, with or without the diagnosis of acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), have an increased incidence of tuberculosis, especially of an extrapulmonary nature. The condition is associated with significant morbidity and mortality. The reported incidence of the combination of tuberculosis and AIDS varies between 4% and 10% of AIDS patients, with a higher incidence noted in the male, inner-city, intravenous-drug-abuser population. Clinical findings may reflect the site of infection, but are often nondiagnostic. Diagnosis often requires biopsy for histopathologic evaluation and tissue culture to document the presence of granulomas and mycobacterial organisms. Universal body fluid precautions among these patients are mandatory, and respiratory isolation should be maintained during diagnostic evaluation and early treatment. These patients usually respond to standard antituberculosis therapy. Physicians should maintain a high index of suspicion of tuberculosis in patients with HIV infection. Conversely, the diagnosis of HIV infection should be considered in patients with unusual manifestations of tuberculosis. Because tuberculosis is one of the few potentially curable infections in the AIDS patient, recognition of its presence is crucial.


Instability of mRNA expression signatures of drug transporters in chronic myeloid leukemia patients resistant to imatinib.
Despite the success of imatinib mesylate (IM) in the treatment of chronic myeloid leukemia (CML), approximately 30% of patients are resistant to therapy, mostly due to unknown causes. To profile the expression signatures of drug transporters throughout IM therapy and correlate them with resistance, we quantified mRNA expression levels of the SLC22A12, ABCB1, ABCC1, ABCG2 and MVP genes in consecutive samples from peripheral blood or bone marrow of CML patients who were either responsive or resistant to IM. Additionally we identified and quantified BCR-ABL1 transcript variants and analyzed 1236T>C ABCB1 and 480G>C SLC22A1 polymorphisms. A relationship between the type of BCR-ABL1 transcript or ABCB1 or SLC22A1 genotype and response to treatment was not discovered. However, the studied genes had higher expression levels in follow-up compared to the diagnostic samples, demonstrating a possible induction in expression. IM-sensitive patients presented significantly higher values of SLC22A1 expression, suggesting higher drug influx. Most importantly, while responding patients demonstrated stable expression signatures in consecutive samples, there was considerable variation in IM-resistant patients, indicating that single point sampling expression signatures are not reliable in predicting clinical outcomes or prognostic features in these patients. Studies that assessed consecutive samples from CML patients in order to evaluate the variation in expression levels of transporter genes are limited yet our study emphasizes the importance of such approaches.


Numerical solutions of the Rayleigh equations for the scattering of light from a two-dimensional randomly rough perfectly conducting surface.
We present rigorous, nonperturbative, purely numerical solutions of the Rayleigh equations for the scattering of p- and s-polarized light from a two-dimensional randomly rough perfectly conducting surface. The solutions are used to calculate the reflectivity of the surface, the mean differential reflection coefficients, and the full angular distribution of the intensity of the scattered field. These results are compared with previously published rigorous numerical solutions of the Stratton-Chu equations, and very good agreement is found.


Interviewer versus self-administered questionnaires in developing a disease-specific, health-related quality of life instrument for asthma.
We wished to determine the extent to which respondents provided the same answers to a health-related quality of life (HRQL) questionnaire in self- and interviewer-administered forms. One hundred and fifty patients with asthma who were symptomatic or required treatment at least once a week, and had airway hyperresponsiveness to methacholine aerosol (PC20 < 8.0 mg/ml) participated. Patients completed a 152-item HRQL questionnaire in both interviewer and self-administered forms, separated by a 2-week interval, the order determined by random allocation. The percentage of items endorsed by the self-administered approach was significantly higher than that of the interviewer-administered approach overall (46.9 vs 35.8%) (p < 0.0001). The difference was consistent across all six domains; the absolute difference in the proportion of items endorsed varied from 8.9 to 12.3%. The intraclass correlations for the proportion of subjects endorsing an item was 0.84. Self- and interviewer-administered questionnaires yield very similar results in discriminating between subjects, but the self-administered version shows systematically greater HRQL impairment.


Piplartine Analogues and Cytotoxic Evaluation against Glioblastoma.
Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma.


Measles Outbreak in a Highly Vaccinated Population - Israel, July-August 2017.
On August 6, 2017, the Israeli Defense Force Public Heath Branch (IDFPHB) was notified of two suspected measles cases. IDFPHB conducted an epidemiologic investigation, which identified nine measles cases in a population with high measles vaccination coverage. All measles patients had signs and symptoms consistent with modified measles (i.e., less severe disease with milder rash, fever, or both, with or without other mild typical measles symptoms). A total of 1,392 contacts were identified, and 162 received postexposure prophylaxis (PEP) with measles-mumps-rubella (MMR) vaccine; the remaining contacts were followed for 21 days (one incubation period). No tertiary cases were identified.


[Risk factors associated with hospitalization for bronchiolitis in the post-neonatal period].
To investigate the relationship between socioeconomic factors, maternal characteristics, breastfeeding, and hospitalization for bronchiolitis in the post-neonatal period. A nested case-control study with a cohort of 5,304 children born in the city of Pelotas, Brazil, was conducted. The cohort study consisted of four sub-studies with their own methods and logistics. Mothers were interviewed using a standard questionnaire during in-hospital and home visits. Cases were defined as any child aged 28 to 364 days who had been hospitalized for bronchiolitis. Among 5,304 cohort children, 113 (2.1%) were hospitalized for bronchiolitis. The hierarchical multivariate analysis performed using logistic regression showed the following results: family income and gestational age were inversely associated with the risk of hospitalization for bronchiolitis. Breastfeeding showed to have a protective effect; children who were breastfed for less than one month had 7 times less risk for being hospitalized for acute bronchiolitis in the first three months of life. The risk for hospitalization for bronchiolitis is 57% higher in those exposed to maternal smoking than in those non-exposed. Hospitalization for acute bronchiolitis is inversely associated with family income, gestational age and duration of breastfeeding and positively associated with maternal smoking. There was not an association with either parity or maternal history of asthma.


Brain tissue oxygen saturation increases during the night in adolescents.
How does the oxygen metabolism change during sleep? We aimed to measure the change in brain tissue oxygen saturation (StO2) before and after sleep with near-infrared spectroscopy (NIRS) using an in-house developed sensor. According to the synaptic homeostasis hypothesis [1], synaptic downscaling during sleep would result in reduced energy consumption. Thus, this reduced energy demands should be reflected in the oxygen metabolism and StO2. Thirteen nights of 7 male subjects (age 11-16 years, one subject contributed only one night, all others two) were included in the analysis. We performed NIRS measurements throughout the entire night. The NIRS sensor was placed close to electrode position Fp1 (international 10/20 system), over the left frontal cortex. Absolute StO2 and total haemoglobin (tHb) were calculated from the NIRS measurements using a self-calibrating method [2]. StO2 and tHb during the awake period prior to sleep and after awakening were compared. The subjects were instructed to lie in bed in the same position before and after sleep. Values of the two nights were averaged for each subject. Furthermore, a linear regression line was fit through the all-night StO2 recordings. We found an increase in StO2 by 4.32 ± 1.76 % (mean ± SD, paired t-test p < 0.001, n = 7) in the morning compared to evening, while tHb did not change (1.02 ± 6.81 μM p = 0.704, n = 7). Since the tHb remained at a similar level after sleep, this increase in StO2 indicates that in the morning more oxygenated blood and less deoxygenated blood was present in the brain compared to the evening. The slope of the regression line was 0.37 ± 0.13 % h(-1) leading to a similar increase of StO2 in the course of sleep. This may be interpreted as a reduced oxygen consumption or energy metabolism after sleep.


Vitamin D concentrations, endothelial progenitor cells, and cardiovascular risk factors.
Our study aimed to establish the association of vitamin D status with the level of circulating endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) and to demonstrate the effect of vitamin D on the level of lipoproteins responsible for increased cardiovascular risk and high blood pressure. 41 healthy adults were selected. EPCs were defined as CD34+/KDR+ cells, and CACs were defined as cells that expressed endothelial markers after incubation of mononuclear blood cells with endothelial growth factors during 5 days. We found a positive association between EPCs, CACs and the level of vitamin D and an inverse correlation between several subclasses of lipoproteins. The level of vitamin D higher than 40 ng/ml demonstrated a positive effect on regulation of blood pressure, and there was significant difference in cholesterol/HDL ratio, very low-density lipoproteins, and triglycerides for groups of subjects with varying levels of vitamin D.


A comparative baseline of coral disease in three regions along the Saudi Arabian coast of the central Red Sea.
Coral disease is a growing problem for coral reefs globally and diseases have been linked to thermal stress, excess nutrients, overfishing and other human impacts. The Red Sea is a unique environment for corals with a strong environmental gradient characterized by temperature extremes and high salinities, but minimal terrestrial runoff or riverine input and their associated pollution. Yet, relatively little is known about coral diseases in this region. Disease surveys were conducted at 22 reefs within three regions (Yanbu, Thuwal, Al Lith) in the central Red Sea along the Saudi Arabian coast. Surveys occurred in October 2015, which coincided with a hyperthermal-induced bleaching event. Our objectives were to 1) document types, prevalence, and distribution of coral diseases in a region with minimal terrestrial input, 2) compare regional differences in diseases and bleaching along a latitudinal gradient of environmental conditions, and 3) use histopathology to characterize disease lesions at the cellular level. Coral reefs of the central Red Sea had a widespread but a surprisingly low prevalence of disease (<0.5%), based on the examination of >75,750 colonies. Twenty diseases were recorded affecting 16 coral taxa and included black band disease, white syndromes, endolithic hypermycosis, skeletal eroding band, growth anomalies and focal bleached patches. The three most common diseases were Acropora white syndrome (59.1% of the survey sites), Porites growth anomalies (40.9%), and Porites white syndrome (31.8%). Sixteen out of 30 coral genera within transects had lesions and Acropora, Millepora and Lobophyllia were the most commonly affected. Cell-associated microbial aggregates were found in four coral genera including a first report in Stylophora. Differences in disease prevalence, coral cover, amount of heat stress as measured by degree heating weeks (DHW) and extent of bleaching was evident among sites. Disease prevalence was not explained by coral cover or DHW, and a negative relationship between coral bleaching and disease prevalence was found. The northern-most sites off the coast of Yanbu had the highest average disease prevalence and highest average DHW values but no bleaching. Our study provides a foundation and baseline data for coral disease prevalence in the central Red Sea, which is projected to increase as a consequence of increased frequency and severity of ocean warming.


Intra-peritoneal interleukin-6 system is a potent determinant of the baseline peritoneal solute transport in incident peritoneal dialysis patients.
Interleukin-6 (IL-6) is a key player in modulating inflammation. IL-6 and soluble IL-6 receptor (sIL-6R) complex induces the synthesis and secretion of various chemokines, adhesion molecules and angiogenic molecules. We hypothesized that the baseline peritoneal solute transport rate (PSTR) early after commencing peritoneal dialysis (PD) may depend largely on the IL-6/sIL-6R system. We also hypothesized that the dialysate concentrations of IL-6/sIL-6R could be closely related to local inflammation or angiogenesis in the peritoneal cavity. Fifty incident patients with a modified peritoneal equilibration test result within 3 months after commencing PD and without a previous history of peritonitis were enrolled. Clinical parameters such as age, sex, comorbid disease, body mass index, residual renal function and C-reactive protein were assessed. Serum and dialysate markers including CA125, IL-6, sIL-6R, monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) were measured and correlated with PSTR. Dialysate concentrations of IL-6 (r = 0.576, P < 0.001), MCP-1 (r = 0.408, P = 0.003) and Ang-2 (r = 0.408, P = 0.003) correlated with mass transfer area coefficient for creatinine (MTAC(cr)), respectively. Dialysate appearance rate (AR) of albumin correlated with dialysate concentrations of CA125 (r = 0.751, P < 0.001), IL-6 (r = 0.303, P = 0.039), sIL-6R (r = 0.497, P < 0.001), MCP-1 (r = 0.488, P < 0.001), VEGF (r = 0.443, P = 0.004) and Ang-2 (r = 0.488, P < 0.001). Neither MTAC(cr) nor AR of albumin was associated with systemic markers. Multivariate analysis showed that MTAC(cr) is independently associated with dialysate IL-6 and serum albumin. It also showed that AR of albumin is independently predicted by dialysate sIL-6R. Dialysate IL-6 correlated with dialysate concentrations of CA125 MCP-1, VEGF and Ang-2. Our study from incident PD patients suggested that (i) dialysate the IL-6 system is a potent determinant of baseline PSTR and (ii) elevation of IL-6 in the dialysate is associated with up-regulation of intra-peritoneal inflammatory and angiogenic molecules.


Passive smoking and attitudes towards tobacco control programs among Iranian dental students.
Conclusive evidence exists about associations between several life-threatening diseases and passive smoking. The objective of our study was to investigate the prevalence of passive smoking among Iranian dental students, to assess their attitudes towards tobacco control programs, and to explore the association between these two and tobacco use. In eight randomly selected dental schools, all fourth-year students were surveyed by means of a self-administered anonymous questionnaire in December 2010. The Global Health Professions Student Survey (GHPSS) questionnaire served as the data collection instrument. Exposure to environmental tobacco smoke (ETS) was assessed during the previous week. Chi-square test, logistic regression, and linear regression served for statistical analyses. The response rate was 84% (325 students, 66% female). Exposure to ETS was reported by 74% of the participants. Men were significantly more exposed to ETS at home, and in other places than were women. Most of the students agreed on queried tobacco control policies. The lowest agreement (72%) was for banning smoking in coffee shops and teahouses. A logistic regression model showed that adjusted for gender, passive smoking at home is significantly associated with current tobacco use. A linear regression model suggested that the total score of attitudes is significantly associated with passive smoking at home, passive smoking in other places, tobacco use experience, and current tobacco use. The study reports high exposure to ETS among dental students, and its association with current tobacco use and attitudes towards tobacco control.


Consciousness of the first order in blindsight.
At suprathreshold levels, detection and awareness of visual stimuli are typically synonymous in nonclinical populations. But following postgeniculate lesions, some patients may perform above chance in forced-choice detection paradigms, while reporting not to see the visual events presented within their blind field. This phenomenon, termed "blindsight," is intriguing because it demonstrates a dissociation between detection and perception. It is possible, however, for a blindsight patient to have some "feeling" of the occurrence of an event without seeing per se. This is termed blindsight type II to distinguish it from the type I, defined as discrimination capability in the total absence of any acknowledged awareness. Here we report on a well-studied patient, D.B., whose blindsight capabilities have been previously documented. We have found that D.B. is capable of detecting visual patterns defined by changes in luminance (first-order gratings) and those defined by contrast modulation of textured patterns (textured gratings; second-order stimuli) while being aware of the former but reporting no awareness of the latter. We have systematically investigated the parameters that could lead to visual awareness of the patterns and show that mechanisms underlying the subjective reports of visual awareness rely primarily on low spatial frequency, first-order spatial components of the image.


Neutrophil activation by monomeric interleukin-8.
Interleukin-8 (IL-8), a pro-inflammatory protein, has been shown by nuclear magnetic resonance (NMR) and x-ray techniques to exist as a homodimer. An IL-8 analog was chemically synthesized, with the amide nitrogen of leucine-25 methylated to selectivity block formation of hydrogen bonds between monomers and thereby prevent dimerization. This analog was shown to be a monomer, as assessed by analytical ultracentrifugation and NMR. Nevertheless, it was equivalent to IL-8 in assays of neutrophil activation, which indicates that the monomer is a functional form of IL-8.


Performance of a multi leaf collimator system for MR-guided radiation therapy.
The purpose of this study was to investigate and characterize the performance of a Multi Leaf Collimator (MLC) designed for Cobalt-60 based MR-guided radiation therapy system in a 0.35 T magnetic field. The MLC design and unique assembly features in the ViewRay MRIdian system were first reviewed. The RF cage shielding of MLC motor and cables were evaluated using ACR phantoms with real-time imaging and quantified by signal-to-noise ratio. The dosimetric characterizations, including the leaf transmission, leaf penumbra, tongue-and-groove effect, were investigated using radiosensitive films. The output factor of MLC-defined fields was measured with ionization chambers for both symmetric fields from 2.1 × 2.1 cm2 to 27.3 × 27.3 cm2 and asymmetric fields from 10.5 × 10.5 cm2 to 10.5 × 2.0 cm2 . Multi leaf collimator (MLC) positional accuracy was assessed by delivering either a picket fence (PF) style pattern on radiochromic films with wire-jig phantom or double and triple-rectangular patterns on ArcCheck-MR (Sun Nuclear, Melbourne, FL, USA) with gamma analysis as the pass/fail indicator. Leaf speed tests were performed to assess the capability of full range leaf travel within manufacture's specifications. Multi leaf collimator plan delivery reproducibility was tested by repeatedly delivering both open fields and fields with irregular shaped segments over 1-month period. Comparable SNRs within 4% were observed for MLC moving and stationary plans on vendor-reconstructed images, and the direct k-space reconstructed images showed that the three SNRs are within 1%. The maximum leaf transmission for all three MLCs was less than 0.35% and the average leakage was 0.153 ± 0.006%, 0.151 ± 0.008%, and 0.159 ± 0.015% for head 1, 2, and 3, respectively. Both the leaf edge and leaf end penumbra showed comparable values within 0.05 cm, and the measured values are within 0.1 cm with TPS values. The leaf edge TG effect indicated 10% underdose and the leaf end TG showed a shifted dose distribution with 0.3 cm offset. The leaf positioning test showed a 0.2 cm accuracy in the PF style test, and a gamma passing rate above 96% was observed with a 3%/2 mm criteria when comparing the measured double/triple-rectangular pattern fluence with TPS calculated fluence. The average leaf speed when executing the test plan fell in a range from 1.86 to 1.95 cm/s. The measured and TPS calculated output factors were within 2% for squared fields and within 3% for rectangular fields. The reproducibility test showed the deviation of output factors were well within 2% for square fields and the gamma passing rate within 1.5% for fields with irregular segments. The Monte Carlo predicted output factors were within 2% compared to TPS values. 15 out of the 16 IMRT plans have gamma passing rate more than 98% compared to the TPS fluence with an average passing rate of 99.1 ± 0.6%. The MRIdian MLC has a good RF noise shielding design, low radiation leakage, good positioning accuracy, comparable TG effect, and can be modeled by an independent Monte Carlo calculation platform.


Introducing asymmetric functionality into MOFs via the generation of metallic Janus MOF particles.
Herein we report a versatile methodology for engineering metallic Janus MOF particles based on desymmetrization at interfaces, whereby each MOF particle is partially coated with a desired metal. We demonstrate that it enables the fabrication of homogeneous Janus MOF particles according to the MOF (ZIF-8, UiO-66 or UiO-66-SH), the metal (Au, Co or Pt), the MOF particle size (from the micrometer to the submicrometer regime) and the metal-film thickness (from 5 nm to 50 nm) employed. We anticipate that our strategy could be applied to impart new functionalities to MOFs, including asymmetric functionalization, magnetic-guidance and motorization.


Reconnecting tile drainage to riparian buffer hydrology for enhanced nitrate removal.
Riparian buffers are a proven practice for removing NO from overland flow and shallow groundwater. However, in landscapes with artificial subsurface (tile) drainage, most of the subsurface flow leaving fields is passed through the buffers in drainage pipes, leaving little opportunity for NO removal. We investigated the feasibility of re-routing a fraction of field tile drainage as subsurface flow through a riparian buffer for increasing NO removal. We intercepted an existing field tile outlet draining a 10.1-ha area of a row-cropped field in central Iowa and re-routed a fraction of the discharge as subsurface flow along 335 m of an existing riparian buffer. Tile drainage from the field was infiltrated through a perforated pipe installed 75 cm below the surface by maintaining a constant head in the pipe at a control box installed in-line with the existing field outlet. During 2 yr, >18,000 m (55%) of the total flow from the tile outlet was redirected as infiltration within the riparian buffer. The redirected water seeped through the 60-m-wide buffer, raising the water table approximately 35 cm. The redirected tile flow contained 228 kg of NO. On the basis of the strong decrease in NO concentrations within the shallow groundwater across the buffer, we hypothesize that the NO did not enter the stream but was removed within the buffer by plant uptake, microbial immobilization, or denitrification. Redirecting tile drainage as subsurface flow through a riparian buffer increased its NO removal benefit and is a promising management practice to improve surface water quality within tile-drained landscapes.