Depressed fractures over cranial venous sinus.
Seventeen patients with depressed fractures over cranial venous sinus who had undergone operations between 1993 and 1998 were reviewed retrospectively. There were 15 male and two female patients. Their ages ranged from 7 to 48 years. The most frequent causes of trauma were motor vehicle accident (in eight cases) followed by assault (in six cases). In the majority of cases, depressed fractures were localized over the superior sagittal sinus, and half of them were over the medial third of the sinus. In 11 cases, massive blood loss occurred intraoperatively that could be controlled by digital pressure with gelfoam or with a free muscle flap. Postoperative infection developed in one case and was treated successfully with antibiotic medication alone. Two patients died due to associated intracerebral lesions. The remaining 15 patients returned to daily living activity in the follow-up period.


Effect of dosing interval duration of intermittent ibandronate treatment on the healing process of femoral osteotomy in a rat fracture model.
The effects of bisphosphonate treatment schedule on fracture healing have not previously been tested. We evaluated the effect of ibandronate dosing interval duration on healing following surgical "fracture" (osteotomy) using a rat femoral fracture model. Six-week-old rats (n = 160) underwent osteotomy and were then allocated into vehicle control (CNT) or an ibandronate treatment group: 5 μg/kg daily (DAY, 5 days/week), 75 μg/kg once every 3 weeks (I-3), 150 μg/kg once every 6 weeks (I-6), resulting in the same total ibandronate dose over the study. Rats were killed after 6 or 18 weeks. At 18 weeks, all fracture lines had disappeared in the CNT and I-6 groups; approximately 10% of fracture lines remained in the DAY and I-3 groups. Ibandronate-treated groups showed large callus areas around the fractures, which shrank between 6 and 18 weeks after surgery; the extent of shrinkage decreased with shorter dosing interval. In histomorphometry, callus remodeling was suppressed by ibandronate; this became more apparent at shorter dose intervals. The structural properties of osteotomized femora were increased in the DAY group compared with CNT, but intrinsic material properties reduced inversely and became closer to those of CNT in response to increased dosing interval. Ibandronate induced formation of large calluses around osteotomies but delayed woven bone remodeling into lamellar bone and reduced intrinsic material properties in a rat fracture model. Extending the dosing interval of intermittent ibandronate treatment appeared to reduce the suppression of callus remodeling caused by ibandronate, which would have delayed healing after osteotomy.


On the water-fat in-phase assumption for quantitative susceptibility mapping.
To (a) define multi-peak fat model-based effective in-phase echo times for quantitative susceptibility mapping (QSM) in water-fat regions, (b) analyze the relationship between fat fraction, field map quantification bias and susceptibility bias, and (c) evaluate the susceptibility mapping performance of the proposed effective in-phase echoes in comparison to single-peak in-phase echoes and water-fat separation for regions where both water and fat are present. Effective multipeak in-phase echo times for a bone marrow and a liver fat spectral model were derived from a single voxel simulation. A Monte Carlo simulation was performed to assess the field map estimation error as a function of fat fraction for the different in-phase echoes. Additionally, a phantom scan and in vivo scans in the liver, spine, and breast were performed and evaluated with respect to quantification accuracy. The use of single-peak in-phase echoes can introduce a worst-case susceptibility bias of 0.43 $$ 0.43 $$ ppm. The use of effective multipeak in-phase echoes shows a similar quantitative performance in the numerical simulation, the phantom and in all in vivo anatomies when compared to water-fat separation-based QSM. QSM based on the proposed effective multipeak in-phase echoes can alleviate the quantification bias present in QSM based on single-peak in-phase echoes. When compared to water-fat separation-based QSM the proposed effective in-phase echo times achieve a similar quantitative performance while drastically reducing the computational expense for field map estimation.


The effect of SARS-CoV-2 variants on the plasma oxylipins and PUFAs of COVID-19 patients.
Oxylipins are important signalling compounds that are significantly involved in the regulation of the immune system and the resolution of inflammation. Lipid metabolism is strongly activated upon SARS-CoV-2 infection, however the modulating effects of oxylipins induced by different variants remain unexplored. Here, we compare the plasma profiles of thirty-seven oxylipins and four PUFAs in subjects infected with Wild-type, Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) variants. The results suggest that oxidative stress and inflammation resulting from COVID-19 were highly dependent on the SARS-CoV-2 variant, and that the Wild-type elicited the strongest inflammatory storm. The Alpha and Delta variants induced a comparable lipid profile alteration upon infection, which differed significantly from Omicron. The latter variant increased the levels of pro-inflammatory mediators and decreased the levels of omega-3 PUFA in infected patients. We speculate that changes in therapeutics, vaccination, and prior infections may have a role in the alteration of the oxylipin profile besides viral mutations. The results shed new light on the evolution of the inflammatory response in COVID-19.


Gene regulation of RMR-related DNAJC6 on adipogenesis and mitochondria function in 3T3-L1 preadipocytes.
In the pilot GWAS of children obesity, DNAJC6 gene was found as a regulator for resting metabolic rate (RMR) and obesity in children aged 8-9 years. To investigate whether DNAJC6 gene regulated obesity and energy metabolism, the physiological mechanisms during adipogenesis of 3T3-L1 preadipocytes were confirmed after DNAJC6 gene was overexpressed or inhibited. Overexpressing DNAJC6 gene maintained a 3T3-L1 preadipocyte status during cell differentiation (MTT, ORO, DAPI/BODIPY). It suppressed adipogenesis and adipokine production (leptin, adiponectin), insulin signaling with IRS-GLUT4 system (RT-PCR, Western blotting), and mitochondrial function (Mito Stress Test). DNAJC6 overexpressed cells inhibited mTOR expression, but maintained LC3 expression at a high level, indicating that autophagy occurred and energy was obtained. However, when DNAJC6 gene was inhibited, fat synthesis factor was highly expressed during differentiation (PPARr, C/EBPa, aP2, etc) and the intracellular stress level increased accordingly, which affected the reduction of reserve respiratory capacity during mitochondrial respiration. Our study confirmed gene regulation of DNAJC6, overexpression or inhibition, affects adipogenesis with energy metabolism and mitochondrial functions. This basic data can be used for clinic obesity studies to control an energy imbalance.


Preferences of pre-weanling Long-Evans rats for anal excreta of adult males and females.
Long-Evans hooded rat pups were reared with their dam alone, their dam and sire or their dam 12 hrs per day and their sire 12 hrs per day and tested for preferences for anal excreta from adult male and female rats when they were 18 to 20 days of age. In all rearing conditions the anal excreta of the rat's own dam was preferred to that of strange dams and the excreta of both own and strange dams was preferred to that of virgin females. Anal excreta from virgin females was preferred to no odor as was anal excreta of unmated males, strange sires and the rat's own sire. Only rats reared with their dam and sire preferred the odor of their own sire to that of other males. The results suggest that pre-weanling rats may attend to different dimensions of the odors of conspecifics, such as the species odor, maternal odor, and individual odor and that different rearing conditions may influence the odor dimension to which the rat attends.


Reversibility of preglomerular active vasoconstriction in the first weeks after complete unilateral ureteral obstruction by inhibition of prostaglandin synthesis.
In previous studies our group has shown that unilateral complete ureteral ligation is followed by flow reduction, which clearly precedes renal atrophy and contributes to hydronephrotic renal cortical damage by ischemia. Long-term followup studies in dogs have demonstrated that increased hydronephrotic vascular resistance could be eliminated by infusion of 2-benzyl-2-imidazole, an inhibitor of thromboxane A2 synthesis. This was shown after 1 and 4 weeks of complete renal obstruction, and there was no such effect on the vascular resistance of the contralateral, unobstructed kidney. Flow reduction and vascular resistance were not influenced by the same inhibition of prostaglandin synthesis after 8 weeks of ureteral occlusion, although renal perfusion still responded to a nonspecific vasodilator, such as dopamine. Thus, active preglomerular vasoconstriction, influenced by imidazole, is present only when renal atrophy develops. Irreversible parenchymal loss, judged by renal cortical thickness, begins after 1 to 2 weeks and is complete 6 to 8 weeks after ureteral ligation. Once renal atrophy is established (that is, after 8 weeks of ureteral occlusion), flow reduction represents loss of renal parenchyma, and not active vasoconstriction. The specificity of the possible thromboxane A2 reaction in flow reduction is shown by its absence in the kidney that has been obstructed for 5 to 8 hours when postglomerular vasoconstriction is the cause of flow reduction (indicated by high renal pelvic pressure and intrarenal pressure). If we accept that imidazole selectively inhibits thromboxane A2 synthesis, we reach 2 conclusions that are clinically relevant: 1) thromboxane A2-mediated active vasoconstriction is 1 factor in the pathophysiology of hydronephrotic atrophy, and 2) the presence of thromboxane A2-mediated active vasoconstriction indicates when hydronephrotic atrophy develops and (more importantly) when it is still reversible, with respect to renal function. These findings can be used as a physiologic basis of a clinical test to predict reversibility of hydronephrotic damage.


Weight change amongst Nauruans over 6.5 years: extent, and association with glucose intolerance.
We are reporting here the extent of weight change over 6.5 years of follow-up amongst 366 randomly selected Nauruans initially surveyed in 1975-1976. Although the initial level of obesity was high (mean body mass index: males 30.8 kg/m2, females 33.0 kg/m2), further increase in body mass index subsequently occurred in 285 subjects (78%). The weight loss that occurred amongst the other 81 subjects was generally mild (mean = 5.3 kg), and only 12 persons lost more than 10 kg. Weight loss was far more common amongst the older subjects: 40% of those older than 50 years compared with 10% of those less than 30 years showed a decrease in body mass index (P less than 0.001). After age adjustment, greater initial obesity was associated with subsequent weight loss (P less than 0.001), and higher baseline plasma glucose (P less than 0.001), and triglyceride levels (P less than 0.05) and lower plasma uric acid levels (P less than 0.01) were also predictive of some weight loss. Obesity and diabetes remained the major predictors of weight loss in the multivariate analysis. Subjects who lost weight showed similar deterioration in glucose tolerance over the 6.5 years (mean increase = 1.8 mmol/l) to those not losing weight (mean = 1.0 mmol/l) and weight loss was not associated with glucose tolerance improvement (or less deterioration) for either those diabetic, or those not diabetic initially. This result suggests that weight loss is not invariably associated with improvement in glucose tolerance amongst Nauruans.


Post-suppression vestibulo-ocular reflex in man: visual and non-visual mechanisms.
The vestibulo-ocular reflex (VOR) was intermittently suppressed by fixating a head-fixed target (light on: 9 s; darkness: 2 s) during whole-body (60-100 deg/s peak; 0.01-0.17 Hz) sinusoidal and triangular oscillation about the vertical axis for about 2 min. Eye movements associated with intervals of darkness at different phases of body oscillation were stimulus-locked averaged, thereby estimating the "post-suppression VOR". The gain ( (eye velocity)/(head velocity) ) of the post-suppression VOR was generally 26-50% of the normal gain in maintained darkness. During sinusoidal body oscillation, the phase lead of the post-suppression VOR equalled or, at low frequencies, appeared to exceed the normal lead in maintained darkness. When the light was permanently extinguished after 2 min of intermittent suppression, an initially reduced VOR rapidly (e.g., 0.4 s) appeared and required 6-30 s to build up to normal again. These observations indicated that visual suppression of the VOR dissipated in darkness with rapid and slow components. During 0.17 Hz, 60 deg/s sinusoidal oscillation, the rapid (perhaps visual) component was responsible for 1/3, and the slow (perhaps non-visual) component for 2/3, of all suppressive effects.


In Utero Therapy for Congenital Diaphragmatic Hernia.
Congenital diaphragmatic hernia is an anomaly that is often prenatally diagnosed and spans a wide spectrum of disease, with high morbidity and mortality associated with fetuses with severe defects. Congenital diaphragmatic hernia is thus an ideal target for fetal intervention. We review the literature on prenatal diagnosis, describe the history of fetal intervention for congenital diaphragmatic hernia, and discuss fetal endoscopic tracheal occlusion and the Tracheal Occlusion To Accelerate Lung growth trial results. Finally, we present preclinical studies for potential future directions.


Adrenergic blocking agents and lipoprotein lipase activity.
Lipoprotein lipase activity, total serum cholesterol and triglycerides, HDL cholesterol were determined before and after two weeks of treatment with a low dose of an alpha 1-blocking agent (prazosin) or of a beta-adrenergic-blocking drug (metoprolol). Lipoprotein lipase activity was almost doubled after prazosin (p less than 0.02) and practically unchanged after metoprolol, at a time and at a drug dosage when only minor changes in blood pressure and serum lipids were detectable. HDL cholesterol was slightly but significantly increased after prazosin (p less than 0.05). Heart rate was increased after prazosin (p less than 0.05) and decreased after metoprolol (p less than 0.01).


Cytokine profiles of macular neovascularization in the elderly based on a classification from a pachychoroid/drusen perspective.
To classify macular neovascularization (MNV) based on pachychoroid and drusen features and to examine the aqueous humor cytokine signatures of each group. In total, 106 consecutive eyes with treatment-naïve MNV and 104 control eyes were examined. The aqueous humor concentrations of 15 cytokines were compared among the MNV groups classified based on the presence of drusen and/or pachychoroid features. Multidimensional scaling analysis was used to visualize the similarity level of the MNV subtypes according to their cytokine profiles. Thirty-one, 18, 43, and 10 eyes were classified into the pachychoroid-associated, drusen-associated, pachychoroid/drusen-associated, and non-drusen/non-pachychoroid MNV groups, respectively. Compared with the control group, cytokines were differently upregulated among the MNV groups. CRP and CXCL12 were significantly upregulated in all MNV groups, whereas CXCL13 and IL-8 were significantly upregulated in three MNV groups, excluding the non-pachychoroid/non-drusen-associated MNV group. Ang-2 was significantly upregulated in three MNV groups except the drusen-associated MNV group. PlGF was significantly upregulated in the pachychoroid-associated and drusen-associated MNV groups. CCL-2 was significantly upregulated in the pachychoroid-associated and pachychoroid/drusen-associated MNV groups. VEGF was downregulated in the pachychoroid-associated and drusen-associated MNV groups, respectively. Multidimensional scaling analysis showed a distinct cytokine profile for each MNV group. All MNV groups showed distinct cytokine profiles. Eyes with "neovascular age-related macular degeneration with drusen and concomitant pachychoroid" may share a similar etiology to those with "pachychoroid neovasculopathy" and "choroidal neovascularization with drusen," but have a distinct etiology to those without these. These findings suggest the importance of evaluating drusen and the choroid during the diagnosis of neovascular age-related macular degeneration.


Hypoxia-induced HIF-1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF-β-dependent EMT.
Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic malignant neoplasm and the malignant counterpart of benign epithelial odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops pulmonary metastasis in about one third of the patients and reveals a poor prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this report, we aimed to clarify the mechanisms of malignant transformation of AB or AC carcinogenesis. The relatively important genes in the malignant transformation of AB were screened by DNA microarray analysis, and the expression and localization of related proteins were examined by immunohistochemistry using samples of AB and secondary AC. Two genes of hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in AB. Both genes were closely related in hypoxia and epithelial-mesenchymal transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were significantly stronger in AC than in AB. In the cell assays using ameloblastoma cell line, AM-1, hypoxia condition upregulated the expression of transforming growth factor-β (TGF-β) and induced EMT. Furthermore, the hypoxia-induced morphological change and cell migration ability were inhibited by an antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced HIF-1α and ZEB1 were critical for the malignant transformation of AB via TGF-β-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.


Gaucher disease carrier with gestational thrombocytopenia and anemia: a case report.
Gaucher disease is an autosomal recessive inborn error of metabolism that causes disorders of blood, bone, and central nervous system as well as hepatosplenomegaly. We present the case of a carrier of Gaucher disease with gestational thrombocytopenia and anemia that required blood transfusion therapy. A 24-year-old Nepalese primipara was diagnosed with idiopathic thrombocytopenia at 12 weeks of gestation. Her platelet count had reduced to 30,000/µL at 21 weeks of gestation, and the hemoglobin content reduced to 7.6 g/dL at 27 weeks of gestation. As she did not respond to any medication, blood transfusion was performed. A female infant weighing 2677 g was delivered vaginally at 39 weeks of gestation. On the 78th day of puerperium, the platelet count of the mother recovered to 101,000/µL, and the hemoglobin content recovered to 12.5 g/dL. The infant had convulsions, respiratory depression, wheezing, systemic purpura, and exfoliation of the epidermis at birth. The infant was diagnosed with Gaucher disease at 37 days of age and passed away at 82 days of age. Subsequently, the parents were diagnosed as carriers of Gaucher disease. As carriers of this disease do not usually show symptoms, it is imperative to provide information regarding disease management for future pregnancies.


[Treatment of malignant effusions with the injection of dendritic cells derived from autologous peripheral CD34+ stem cells].
To evaluate the effect and side effects of CD34+ originated dendritic cells (DCs) infusion to treat malignant effusions. Twenty-three patients with 26 malignant effusions received chemotherapy and granulocyte colony-stimulating factor (G-CSF) or G-CSF alone to mobilize peripheral blood hematopoietic stem cells. CD34+ stem cells were induced to differentiate into DCs by cytokines interleukin 4 (IL-4), granulocyte-macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). After being cultured for 10 to 14 days to stimulate proliferation and grow mature, DCs were refused into the body cavity by drainage tube weekly for 3 weeks. The response rate was 54% (14/26) and the benefit rate 81%. The median duration of response was 20 weeks (range:4-45 weeks). Karnofsky performance score (KPS) was improved in 15 patients. The response rate was 50% for the naive patients and 57% for the refractory patients. There were no severe side-effects. This pilot study demonstrates that DCs derived in vitro can exist viably after intropleural injection and can mediate biologic activity to malignant effusions. DCs immunotherapy is promising to treat malignant effusions with good tolerance.


Pollution and electricity price in the EU Central and Eastern European countries: a sectoral approach.
Pollution and energy crisis are actual issues in Europe, including the EU Central and Eastern European states. In this context, the objective of this paper is to assess the impact of economic growth and electricity prices for non-household consumers on pollution. The empirical findings reveal the U pattern for energy industry and inverted U pattern for manufacturing in the period 2007-2021 in the EU countries from Central and Eastern Europe. Renewable energy consumption reduces the CO2 and GHG emissions in energy industry. FDI and electricity prices determine the reduction in GHG and CO2 emissions in both sectors. These results are the basis for policy recommendations.


Macular disease resembling adult foveomacular vitelliform dystrophy in older adults.
Fifty-three eyes of 31 patients over age 50 with macular disease were reviewed. Clinical appearance of the macula was of two types: a yellow slightly elevated lesion (29 eyes) and a pigmented flat lesion with surrounding atrophy (24 eyes). Drusen were found in 60% of affected eyes. No familial tendencies were documented. A reduced electro-oculogram (EOG) was present in approximately 50% of all eyes tested. Fluorescein angiographic findings and differential diagnosis are described. Visual prognosis was markedly different for the two groups: 69% of eyes with yellow elevated lesions lost two or more lines of visual acuity and 48% went on to visual acuity equal to or less than 20/200, whereas 33% of eyes with pigmented flat lesions lost two or more lines of visual acuity and 8% went on to visual acuity equal to or less than 20/200.


Pulmonary delivery of mucus-traversing PF127-modified silk fibroin nanoparticles loading with quercetin for lung cancer therapy.
The mucosal barrier remains a major barrier in the pulmonary drug delivery system, as mucociliary clearance in the airway accelerates the removal of inhaled nanoparticles (NPs). Herein, we designed and developed the inhalable Pluronic F127-modified silk fibroin NPs loading with quercetin (marked as QR-SF (PF127) NPs), aiming to solve the airway mucus barrier and improve the cancer therapeutic effect of QR. The PF127 coating on the SF NPs could attenuate the interaction between NPs and mucin proteins, thus facilitating the diffusion of SF(PF127) NPs in the mucus layer. The QR-SF (PF127) NPs had particle sizes of approximately 200 nm with negatively charged surfaces and showed constant drug release properties. Fluorescence recovery after photobleaching (FRAP) assay and transepithelial transport test showed that QR-SF (PF127) NPs exhibited superior mucus-penetrating ability in artificial mucus and monolayer Calu-3 cell model. Notably, a large amount of QR-SF (PF127) NPs distributed uniformly in the mice airway section, indicating the good retention of NPs in the respiratory tract. The mice melanoma lung metastasis model was established, and the therapeutic effect of QR-SF (PF127) NPs was significantly improved in vivo. PF127-modified SF NPs may be a promising strategy to attenuate the interaction with mucin proteins and enhance mucus penetration efficiency in the pulmonary drug delivery system.


Analysis of potential for reducing emissions of greenhouse gases in municipal solid waste in Brazil, in the state and city of Rio de Janeiro.
This paper examines potential changes in solid waste policies for the reduction in GHG for the country of Brazil and one of its major states and cities, Rio de Janeiro, from 2005 to 2030. To examine these policy options, trends in solid waste quantities and associated GHG emissions are derived. Three alternative policy scenarios are evaluated in terms of effectiveness, technology, and economics and conclusions posited regarding optimal strategies for Brazil to implement. These scenarios are been building on the guidelines for national inventories of GHG emissions (IPCC, 2006) and adapted to Brazilian states and municipalities' boundaries. Based on the results, it is possible to say that the potential revenue from products of solid waste management is more than sufficient to transform the current scenario in this country into one of financial and environmental gains, where the negative impacts of climate change have created a huge opportunity to expand infrastructure for waste management.


Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.
The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.


Mouse liver plasma membrane redox system activity is altered by aging and modulated by calorie restriction.
Caloric restriction (CR) is known as the only non-genetic method proven to slow the rate of aging and extend lifespan in animals. Free radicals production emerges from normal metabolic activity and generates the accumulation of oxidized macromolecules, one of the main characteristics of aging. Due to its central role in cell bioenergetics, a great interest has been paid to CR-induced modifications in mitochondria, where CR has been suggested to decrease reactive oxygen species production. The plasma membrane contains a trans-membrane redox system (PMRS) that provides electrons to recycle lipophilic antioxidants, such as α-tocopherol and coenzyme Q (CoQ), and to modulate cytosolic redox homeostasis. In the present study, we have investigated age differences in the PMRS in mouse liver and their modulation by CR. Aging induced a decrease in the ratio of CoQ10/CoQ9 and α-tocopherol in liver PM from AL-fed mice that was attenuated by CR. CoQ-dependent NAD(P)H dehydrogenases highly increased in CR old mice liver PMs. On the other hand, the CoQ-independent NADH-FCN reductase activity increased in AL-fed animals; whereas, in mice under CR this activity did not change during aging. Our results suggest that liver PMRS activity changes during aging and that CR modulates these changes. By this mechanism CR maintains a higher antioxidant capacity in liver PM of old animals by increasing the activity of CoQ-dependent reductases. Also, the putative role of PMRS in the modulation of redox homeostasis of cytosol is implicated.


Formation of artifactual metabolites of doxylamine following acid hydrolysis.
This study describes the use of gas chromatographic-mass spectrometric, high-performance liquid chromatographic and capillary column gas chromatographic separation techniques in demonstrating the production of several artifactual compounds reported in the literature as metabolites of doxylamine. Rhesus monkey urinary extracts which contained doxylamine and doxylamine metabolites were examined with and without acid hydrolysis. The production of 1-phenyl-1-(2-pyridinyl)ethanol and 1-phenyl-1-(2-pyridinyl)ethylene under acid hydrolysis conditions was demonstrated. These artifactual products were shown to originate from the acid hydrolysis of 2-[1-phenyl-1-(2-pyridinyl)ethoxy] acetic acid and not from doxylamine.


Loading Rho to terminate transcription.
In bacteria, one of the major transcriptional termination mechanisms requires a hexameric RNA/DNA helicase known as Rho. One question that has remained unanswered is how the helicase loads onto a nascent transcript so that it can initiate actions on the transcript to cause termination. Recent structures of Rho bound to nucleic acid by show how the individual RNA-binding domains of the 6 subunits are organized and that the ring is split open. The opening is wide enough to accommodate single-stranded RNA and suggests that this conformation is poised to load onto mRNA.


Clear-cell sarcoma of tendons and aponeuroses studied by immunoscintigraphy.
Clear-cell sarcoma is a rare tumor that arises in association with tendons and aponeuroses. Although it shares with malignant melanoma several histologic and ultrastructural features, it has a clinical course different from that of conventional melanomas. A case of clear-cell sarcoma studied by immunoscintigraphy with 99mTc-labeled F(ab')2 fragments of the monoclonal antibody 225.28 S is reported.


The impact of ambient particulate matter on hospital outpatient visits for respiratory and circulatory system disease in an urban Chinese population.
There are limited evidence on the association between short-term exposure to ambient particulate matter (PM) and overall hospital outpatient visits for respiratory system disease (RESD) and cardio-cerebrovascular system disease (CCD) in high-polluted countries like China. Though previous epidemiological studies of RESD and CCD generally applied a linear relationship of the acute PM effects, it is unclear whether this linear exposure-response relationship holds in high pollution area. In this study, a time-series study during 2013 through 2016 was conducted to investigate 245,442 and 430,486 hospital visits for RESD and CCD respectively from Nanjing city, China. A combination of logistic generalized additive model (GAM) was used to evaluate the exposure-response associations. The results disclosed that a 10 μg/m3 increase in PM2.5 and PM10 concentration on the current day of exposure (lag 0) was associated with 0.36% (95% CI: -0.02%-0.73%) and 0.33% (0.07%-0.60%) increase in RESD; and 0.42% (0.00%-0.85%) and 0.37% (0.08%-0.67%) increase in CCD. The exposure-response association was approximately linear within 0-150 μg/m3 of PM concentration and non-linear across the full range of exposures. The effects of PM on RESD and CCD were sensitive to additional adjustment for co-pollutants, indicating the health effects of air pollution mixture in Nanjing city. There was no evidence of potential effect modification of RESD and CCD by season (cold and warm), age (5-64, 65-74, ≧75 years) and sex (male and female) groups. Though not statistically significant, the estimated risks in warm season were higher than those in cold season, suggesting potential synergistic effects of ambient PM pollution and temperature on triggering RESD and CCD.


Hospitalized patients with X-linked disease and infected with SARS-CoV-2 in Brazil: A serial case report from the first two years of the pandemic.
We described the characteristics of 18 patients with coronavirus disease (COVID)-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to COVID-19. The patients were diagnosed with Hemophilia B (one patient), Klinefelter syndrome [eight patients- three deaths occurred, one unrelated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection], and Turner syndrome (nine patients- two patients died). Half of the patients with X-linked disorders and COVID-19 (9/18) were male, the age varied from 1 to 71 years, and most patients were White (9/12; six patients had missing data). The most common symptoms were cough (13/17; one patient had missing data) and fever (12/16; two patients had missing data), whereas the most common comorbidities were diabetes mellitus (3/11; seven patients had missing data) and cardiopathy (2/12; six patients had missing data). Nearly half of the patients needed intensive care unit (8/17; one patient had missing data), and a quarter required invasive mechanical ventilation (4/16; two patients had missing data). Our study accounted for a total of five deaths, one unrelated to COVID-19. There may be several reasons for the low number of X-linked patients found in our data, such as limited access to genetic diagnosis tools causing underdiagnosis and a lack of knowledge by health professionals to identify the necessity of a genetic diagnosis or even forgetting to fill in the Brazilian database for hospitalization due to severe acute respiratory syndrome.


Ribosomal Intergenic Spacers Are Filled with Transposon Remnants.
Eukaryotic ribosomal DNA (rDNA) comprises tandem units of highly conserved coding genes separated by rapidly evolving spacer DNA. The spacers of all 12 species examined were filled with short direct repeats (DRs) and multiple long tandem repeats (TRs), completing the rDNA maps that previously contained unannotated and inadequately studied sequences. The external transcribed spacers also were filled with DRs and some contained TRs. We infer that the spacers arose from transposon insertion, followed by their imprecise excision, leaving short DRs characteristic of transposon visitation. The spacers provided a favored location for transposon insertion because they occupy loci containing hundreds to thousands of gene repeats. The spacers' primary cellular function may be to link one ribosomal RNA transcription unit to the next, whereas transposons flourish here because they have colonized the most frequently used part of the genome.


[Facioscapulohumeral muscular dystrophy type 2].
In recent years, the advances of knowledge in clinical, genetic and epigenetic features of facioscapulohumeral muscular dystrophy (FSHD) allowed the identification of two forms of FSHD, the classical autosomal dominant FSHD type 1, and FSHD type 2 characterized by an identical clinical phenotype but associated with a different (epi)genetic defect. In the large majority of FSHD1 patients, the identification of D4Z4 pathogenic contraction on a permissive chromosome 4 is sufficient for diagnosis, while FSHD2 diagnosis is complicated by the fact that the genetic defect associated with this disease is not known yet and a complete D4Z4 genotype and a D4Z4 specific methylation test are required. Indeed, FSHD2 patients display a non-contracted D4Z4 allele on chromosomes 4, at least one permissive chromosome 4QA and a profound hypomethylation of both chromosomes 4 and 10. A common pathophysiological pathway has been hypothesized for FSHD1 and FSHD2 in order to explain the identical clinical phenotype and the highly similar epigenetic changes found in patients affected by these diseases. According to this hypothesis, chromatin relaxation - due to pathogenic D4Z4 contraction in FSHD1 patients, and to important hypomethylation of this locus in FSHD2 patients - would allow the last D4Z4 unit to encode for a toxic DUX4 transcript. This transcript would be stable only when encoded from a permissive chromosome 4 carrying a polyadenylation signal immediately distal to the last D4Z4 unit on chromosome 4. Since, to express clinical phenotype, FSHD2 patients have to carry both 4QA chromosome and hypomethylated D4Z4 on chromosomes 4 and 10, digenic transmission has been hypothesized for this disease. The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene. The identification, among patients carrying a FSHD phenotype, of FSHD2, a new disease with distinct (epi)genetic features but having a common pathophysiological pathway with FSHD1, suggests the possibility of developping new therapeutic strategies suitable for both diseases.


Pleural mesothelioma of connective tissue type, localized fibrous tumour of the pleura, and reactive submesothelial hyperplasia. An immunohistochemical comparison.
Ten diffuse pleural mesotheliomas of connective tissue type have been compared with 14 examples of pleural granulation tissue and 7 localized fibrous tumours of the pleura, using immunohistochemistry to identify cytokeratins of low and high molecular weight and vimentin. Low molecular weight cytokeratin and vimentin were both detected in 8 of the 10 mesotheliomas and in 12 of the 14 reactive lesions. High molecular weight cytokeratin was rarely detected in either lesion. The seven localized fibrous tumours of the pleura were all positive for vimentin and negative for both cytokeratins. These findings support an origin of connective tissue type mesotheliomas from multipotential submesothelial spindle cells and of localized fibrous tumours of the pleura from either conventional fibroblasts or resting submesothelial spindle cells. Antibodies to cytokeratin help distinguish these two neoplasms but provide no assistance in the more difficult diagnostic problem of distinguishing mesotheliomas of connective tissue type from pleural reactions characterized by abundant granulation tissue.


Extracellular endoglucanase activity by a novel bacterium isolated from marine shipworm.
An extracellular enzyme preparation from shipworm bacterium cultures dramatically increased reducing sugar content of carboxymethylcellulose (CMC3), but did not solubilize sugar from particulate cellulose. The preparation degraded cellodextrins larger than cellotriose (G3). Only interior cellodextrin chain linkages were cleaved and the center-most bond of cellohexaose (G6) was preferentially cleaved. Activity maxima were observed at 60 degrees C and between pH 5.0 and 7.0. The activity was resistant to protease treatment and little loss of activity was observed after 14 d at 25 degrees C.


Prior Femoroacetabular Osteoplasty Does Not Compromise the Clinical Outcome of Subsequent Total Hip Arthroplasty.
Total hip arthroplasty (THA) is the most effective treatment option for patients with symptomatic osteoarthritis after a prior femoroacetabular osteoplasty (FAO). This study evaluated clinical outcomes of THA after a prior FAO and compared the results with a matched group of patients who underwent THA with no prior surgical procedures in the affected hip. By reviewing our prospectively maintained database, we identified 74 hips (69 patients) that underwent THA after previous FAO between 2004 and 2017. They were matched 1:3 to a control group of primary THA with no history of any procedures on the same hip based on age, sex, body mass index, date of surgery, Charlson comorbidity index, surgical approach, and acetabular and femoral component type. At minimum 2-year follow-up, modified Harris Hip Score, 90-day readmission, and revision THA for any reason were compared between the groups. The median time interval between FAO and subsequent THA was 1.64 years. There was no significant difference in preoperative Harris Hip Score between patients in the case and control cohorts. At the latest follow-up, the median modified Harris Hip Score was 77.6 in the case group and 96.2 in the control, and the difference was not statistically significant. None of the patients in the case group developed infection. 7 patients in the case group required additional procedures at any point, compared with 15 in the control. THA after prior FAO has similar outcomes to primary THA in patients with no prior procedures in the affected hip. THA can be performed safely with excellent outcome in patients with a history of FAO.


Cytokine expression in gingival and intestinal tissues of patients with periodontitis and inflammatory bowel disease: An exploratory study.
To evaluate the expression of the cytokines IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IL-17A, IL-17F, sCD40L, and TNF-α in gingival tissue and intestinal mucosa of patients having both periodontitis and inflammatory bowel disease (IBD) and assess how they cluster in both tissues. This cross-sectional study selected 28 patients with periodontitis (18 with Crohn's disease and 10 with ulcerative colitis) from the IBD gastroenterology outpatient clinic at the Pedro Ernesto University Hospital. Patients were assessed using questionnaire, medical chart check and periodontal examination. Gingival and intestinal biopsies were collected and homogenized using a cell disruptor. Cytokines expression was evaluated through multiplex technology. Cluster analysis was performed based on cytokinés correlation strength and presented in dendrograms. Crohn's disease and ulcerative colitis patients exhibited no significant difference between them in cytokine levels (p>0.05), so they were analysed together. Significantly higher levels of IL-17A, IL-17F, IL-22, IL-25, IL-33, IL-10, and INF-γ were found in gingival tissues in comparison with intestinal mucosa (p<0.05). In gingival tissue, cytokines formed the following clusters: IL-25/IL-10/IL-33 (r=0.775), IL-22/IL-23/IL-6 (r=0.681) and IL-6/IL-25/IL-33/IL-10 (r=0.660). In intestinal mucosa, the following clusters were formed: IL-6/IL-21/IL-10 (r=0.880), IL-17A/IL-6/IL-21/IL-10 (r=0.826), IL-I7F/IL-33/IL-25 (r=0.813) and IL-23/IL-2/IL-17A/IL-6/IL-21/IL-10 (r=0.785). Expression of IL-17A, IL-17F, IL-22, IL-25, IL-33, IL-10, and INF-γ was significantly increased in gingival tissue in comparison with intestinal mucosa of patients with periodontitis and IBD. The cytokine clustering pattern was different in gingival and intestinal tissues.


ε-Viniferin and α-viniferin alone or in combination induced apoptosis and necrosis in osteosarcoma and non-small cell lung cancer cells.
This study investigated the effects and molecular mechanisms of ε-viniferin and α-viniferin in non-small cell lung cancer cell line A549, melanoma cell line A2058, and osteosarcoma cell lines HOS and U2OS. Results showed ε-viniferin having antiproliferative effects on HOS, U2OS, and A549 cells. Compared with ε-viniferin at the same concentration, α-viniferin had higher antiproliferative effects on HOS cells, but not the same effect on U2OS and A549 cells. Lower dose combination of α-viniferin and ε-viniferin had more synergistic effects on A549 cells than either drug alone. α-Viniferin induced apoptosis in HOS cells by decreasing expression of phospho-c-Jun-N-terminal kinase 1/2 (p-JNK1/2) and increasing expression of cleaved Poly (ADP-ribose) polymerase (PARP), whereas α-viniferin in combination with ε-viniferin induced apoptosis in A549 cells by decreasing expression of phospho-protein kinase B (p-AKT) and increasing expression of cleaved PARP and cleaved caspase-3. ε-Viniferin and α-viniferin have not been studied using in vivo tumor models for cancer. This research is the first showing that ε-viniferin treatment resulted in significant inhibition of tumor growth in A549-cell xenograft-bearing nude mice compared with the control group. Consequently, ε-viniferin and α-viniferin may prove to be new approaches and effective therapeutic agents for osteosarcoma and lung cancer treatment.


Exploring the multiverse: the impact of researchers' analytic decisions on relationships between depression and inflammatory markers.
In recent years, a replication crisis in psychiatry has led to a growing focus on the impact of researchers' analytic decisions on the results from studies. Multiverse analyses involve examining results across a wide array of possible analytic decisions (e.g., log-transforming variables, number of covariates, or treatment of outliers) and identifying if study results are robust to researchers' analytic decisions. Studies have begun to use multiverse analysis for well-studied relationships that have some heterogeneity in results/conclusions across studies.We examine the well-studied relationship between peripheral inflammatory markers (PIMs; e.g., white blood cell count (WBC) and C-reactive protein (CRP)) and depression severity in the large NHANES dataset (n = 25,962). Specification curve analyses tested the impact of 9 common analytic decisions (comprising of 58,000+ possible combinations) on the association of PIMs and depression severity. Relationships of PIMs and total depression severity are robust to analytic decisions (based on tests of inference jointly examining effect sizes and p-values). However, moderate/large differences are noted in effect sizes based on analytic decisions and the majority of analyses do not result in significant findings, with the percentage of analyses with statistically significant results being 46.1% for WBC and 43.8% for CRP. For associations of PIMs with specific symptoms of depression, some associations (e.g., sleep, appetite) in males (but not females) were robust to analytic decisions. We discuss how multiverse analyses can be used to guide research and also the need for authors, reviewers, and editors to incorporate multiverse analyses to enhance replicability of research findings.


Enhanced recovery after surgery improves postdischarge recovery after pulmonary lobectomy.
Enhanced recovery after surgery protocols are known to accelerate immediate postoperative recovery and to facilitate healing. Our purpose was to further characterize benefits after discharge from the hospital. An institutional database was queried to identify patients with clinical stage I non-small cell lung cancer who were classified as Eastern Cooperative Oncology Group performance status 0 and received a lobectomy between January 1, 2000, and August 31, 2020. The presence or absence of symptoms (ie, pain, shortness of breath, fatigue, among others) and performance status were recorded by clinic staff at the time of follow-up. Cox proportional hazards regression was used to identify factors associated with postdischarge recovery, which was defined as a return to Eastern Cooperative Oncology Group performance status 0 in the follow-up clinic. A total of 935 patients were identified (pre-enhanced recovery after surgery, 523; transition period, 222; enhanced recovery after surgery, 190). Outpatient performance status data were recorded in 774 of 935 patients (83%). The number of patients reporting symptoms at the 1-month follow-up appointment decreased from the pre-enhanced recovery after surgery to transition to the enhanced recovery after surgery period (60%, 50%, and 33%, respectively, P < .001), predominately due to less pain reported (43%, 35%, and 23%, respectively, P = .001). At 6-month follow-up, these differences were no longer statistically significant. Surgery during the enhanced recovery after surgery period was independently associated with significant improvements in postdischarge recovery (hazard ratio, 1.60, 95% confidence interval, 1.29-2.00), and the presence of coronary artery disease (hazard ratio, 0.69, P = .006) and receipt of thoracotomy (hazard ratio, 0.84, P = .036) were independently associated with delayed postdischarge recovery. Enhanced recovery is associated with significant improvements in postdischarge recovery of performance status.


The Effect of a Magnetic Field on a RAPET (Reaction under Autogenic Pressure at Elevated Temperature) of MoO(OMe)(4): Fabrication of MoO(2) Nanoparticles Coated with Carbon or Separated MoO(2) and Carbon Particles.
In this article, we present results of the RAPET dissociation of MoO(OMe)4 at 700 degrees C in a closed Swagelok cell. The reaction produces molybdenum dioxide nanoparticles (20 nm) coated with carbon (20 nm). We have also carried out the same reaction under an applied magnetic field of 10 T. This reaction yielded different products. It produces a mixture of comparatively larger (50 nm) molybdenum dioxide nanoparticles and separated uncoated carbon particles (20-30 nm).


Catalytic site flexibility facilitates the substrate and catalytic promiscuity of Vibrio dual lipase/transferase.
Although enzyme catalysis is typified by high specificity, enzymes can catalyze various substrates (substrate promiscuity) and/or different reaction types (catalytic promiscuity) using a single active site. This interesting phenomenon is widely distributed in enzyme catalysis, with both fundamental and applied importance. To date, the mechanistic understanding of enzyme promiscuity is very limited. Herein, we report the structural mechanism underlying the substrate and catalytic promiscuity of Vibrio dual lipase/transferase (VDLT). Crystal structures of the VDLT from Vibrio alginolyticus (ValDLT) and its fatty acid complexes were solved, revealing prominent structural flexibility. In particular, the "Ser-His-Asp" catalytic triad machinery of ValDLT contains an intrinsically flexible oxyanion hole. Analysis of ligand-bound structures and mutagenesis showed that the flexible oxyanion hole and other binding residues can undergo distinct conformational changes to facilitate substrate and catalytic promiscuity. Our study reveals a previously unknown flexible form of the famous catalytic triad machinery and proposes a "catalytic site tuning" mechanism to expand the mechanistic paradigm of enzyme promiscuity.


A strain of Fusarium kyushuense is able to produce aflatoxin B1 and G 1.
A strain of F. kyushuense is able to produce aflatoxin B1 and G1 under certain growth conditions. This was ultimately demonstrated by LC-MS analysis. By using a microarray covering oligonucleotides specific for the aflatoxin pathway genes of A. flavus, the expression of homologues of nearly the complete aflatoxin biosynthesis gene cluster was detected in F. kyushuense under producing conditions, e.g., after growth in liquid YES medium. In contrast, after growth of F. kyushuense on solid YES medium, only a very low transcription level of one of the homologues (nor-1) could be observed by microarray and Real Time PCR demonstrating differential gene expression. The cross-hybridization of the F. kyushuense mRNA to the A. flavus aflatoxin biosynthesis gene oligonucleotides of the array indicates homology between the sequences. PCR analyses with primers deduced from the nor-1 gene sequence of the aflatoxin biosynthesis gene cluster from A. flavus revealed the presence of a homologue of this gene in F. kyushuense. Sequencing of PCR fragments of the nor-1 homologue revealed a sequence similarity of >90% to the nor-1 gene of A. flavus.


Draft genome sequence of Pantoea ananatis B1-9, a nonpathogenic plant growth-promoting bacterium.
Pantoea ananatis B1-9 is an endophytic Gram-negative rhizobacterium that was isolated for its ability to promote plant growth and improve crop yield in the field. Here we report the draft genome sequence of P. ananatis B1-9. Comparison of this sequence to the sequenced genome of a plant-pathogenic P. ananatis strain, LMG20103, indicated that the pathogenesis-related genes were absent, but a subset of gene functions that may be related to its plant growth promotion were present.


Food protein induced enterocolitis syndrome in adults.
Food protein induced enterocolitis syndrome (FPIES) belongs to a group of IgE-independent food allergies. It is the domain of paediatric patients, but it can also occur in adults. In this disease there is a life-threatening risk resulting from the possibility of a severe course of the disease and the development of hypovolemic shock. The disease was first defined in the mid-1970s. Knowledge about this disease is extremely low, we do not know its exact frequency, and the disease itself usually appears between 2 and 7 months of age. FPIES occurs mainly in formula-fed infants, typically 1-4 weeks after formula introduction, very rarely in breastfed infants, but may also develop in adults.


Facilitation of drug evaluation in children by population methods and modelling.
The pharmacokinetics and pharmacodynamics of drugs are different in adult and paediatric populations, the latter being particularly heterogeneous. These differences in pharmacokinetics and pharmacodynamics justify specific studies but raise a number of ethical and practical issues. The main practical difficulties to circumvent while performing clinical studies in children are the invasiveness of the procedures and the obstacles to patient recruitment. The invasiveness related to pain/anxiety and blood loss precludes the performance of classical pharmacokinetic studies in children in many instances, particularly in neonates and infants. Population approaches, which rely on pharmacokinetic-pharmacodynamic modelling, are particularly appealing in paediatric populations because these models can cope with sparse data. The relevance of population approaches to investigation of the dose-concentration-effect relationships and to qualitative/quantitative assessment of factors that may explain interindividual variability has already been emphasized. The aims of this review are to summarize the currently available literature on population pharmacokinetic-pharmacodynamic studies in children and to discuss a number of recent methodological developments that may facilitate the evaluation of drugs in this population by alleviating invasiveness and, subsequently, facilitating recruitment of patients. The present survey confirms that population approaches in paediatrics have already reached a large audience and that they are mostly used for analysis of sparse data. However, pharmacokinetic-pharmacodynamic studies in children are still scarce. New classes of models may extend the scope of the use of population models in paediatrics. Kinetic-pharmacodynamic models, where use of the term 'kinetic' rather than 'pharmacokinetic' emphasizes the absence of pharmacokinetic data, are indirect models where the (unobserved) drug kinetics are described by a single compartment involving a single rate constant. These models, which alleviate the need for blood samples used for the measurement of drug concentration, may be very useful in paediatric studies. Physiological and physiopathological models also have potential applications but require further development. Because the number of measurements in a single individual needs to be limited in children, it is crucial to optimize the design of the experiment in order to avoid inaccurate and unreliable results. In this review, formal optimization and simulation to evaluate a design are presented, and specific problems raised by the application of these techniques in paediatrics are addressed. Finally, the related technique of clinical trial simulation and its applications are presented and discussed.


Pathogenesis of viral encephalitis: demonstration of viral antigen(s) in the brain endothelium.
One of the enigmas in the pathogenesis of inflammation is why the white cells adhere to the endothelium. In trying to define the pathogenic mechanism, we carried out experiments on ferrets infected with an SSPE strain of measles virus. Using immunoperoxidase labeling techniques, viral antigens were demonstrated on the luminal surface and in the cytoplasm of endothelial cells, irrespective of the presence or absence of inflammatory changes. The degree of inflammation corresponded well with antibody titer. These data suggest that the viral antigen in the endothelial cells is the site of interaction between these cells and sensitized lymphoid cells.


Antioxidant and anti-inflammatory effects of fractions from ripe fruits of Solanum lycocarpum St. Hil. (Solanaceae) and putative identification of bioactive compounds by GC-MS and LC-DAD-MS.
Brazilian biodiversity includes species of the genus Solanum that have several biological activities, in addition to their relevance to agriculture, economics and popular medicine. The ripe fruits of Solanum lycocapum are an important nutritional food source, since they have levels of vitamin C, total soluble sugars, sucrose, phosphorus, and iron comparable or exceed the levels present in fruits such as pineapples, bananas, oranges, and mangoes. The pulp of the fruit is consumed by the population, and it is also used to produce jellies; to make marmalade, replacing the quince, and it can also be mixed with peaches in the preparation of peach. The objective of this study was to evaluate the anti-inflammatory and antioxidant activities of fractions obtained from the ripe fruits and to identify the constituents with these biological properties. The ripe fruits were collected, dried, crushed, and subjected to extraction by exhaustive percolation, obtaining an ethanol extract that was partitioned with solvents of increasing polarities, obtaining hexane (HEX), ethyl acetate (AC), and hydroethanol (HE) fractions. The AC fraction showed higher antioxidant potential compared to BHT (2,6-di-tert-butyl-4-methylphenol) and similar activity to AA (ascorbic acid) by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical assay, while HEX and HE fractions exhibited of IC50 values similar to BHT. The AC fraction also presented similar activity to BHT by FRAP (Ferric Reducing Antioxidant Power) test. Intraperitoneal treatment with HEX (100 and 300 mg/kg) and HE (100 mg/kg) fractions caused significant inhibition of paw edema induced by carrageenan, 4 and 6 h after the inflammatory stimuli. When analyzed by GC-MS, fatty acids, phytosterols, and triterpenoid were identified in the HEX fraction, whilst 31 compounds were annotated in the AC and HE fractions analyzed by LC-DAD-MS, being phenylpropanoid derivatives, chlorogenic acids, and steroidal glycoalkaloids. The ripe fruits of S. lycocarpum have antioxidant and anti-inflammatory activities, and the detected chemical compounds, especially caffeoylquinic acid derivatives, spermidine, stigmasterol, and β-sitosterol, may be correlated with these activities. The ripe fruits of this species can be a food alternative rich in bioactive compounds and with benefits for human health.


Significance of complement activation in autoimmune haemolytic anaemia of "warm type".
To study possible relationships between serum C3 and C4 levels and fixation of complement components (C) on red cells, 79 patients of autoimmune haemolytic anaemia of warm type (AIHA) and 7 patients of various diseases with positive direct antiglobulintest (DAT) but without haemolysis were investigated. 23 out of 79 patients with AIHA were analyzed repeatedly during the course of the disease. There were no significant differences of C levels between the various clinical types. However, the number of patients with reduced levels of C3 and C4 was significantly higher among cases with C fixation on the red cells than among those with fixation of immunoglobulins alone. Changes were more pronounced for C4 than C3 and mean values of serum C4 were significantly lower in the group with C fixation. If incomplete warm haemolysins were demonstrable, C4 levels were lower than in cases without warm haemolysins. During the clinical course, C3 and C4 concentrations showed a close correlation to the severity of haemolysis.


Hemispheric lateralization in preattentive processing of speech sounds.
Event-related magnetoencephalographic (MEG) responses to infrequently presented spoken deviant syllables [di] and [ba] among repetitive standard [da)]syllables were recorded in subjects who either attended to these stimuli in order to discriminate the [ba] syllables or ignored them while attending a silent movie. In both conditions, the deviant syllables elicited a mismatch response (MMNm, the magnetic counterpart of mismatch negativity), which was stronger in the left than in the right auditory cortex, indicating left-hemispheric dominance in speech processing already at a preattentive processing level.


Antiviral activity of the new DAAs for the treatment of hepatitis C virus infection: virology and resistance.
The treatment of chronic hepatitis C virus (HCV) infection has substantially evolved over the past decade, following the Consensus Conference organized by the European Association for the Study of the Liver in 1999. Since then, the standard of care (SoC) for patients with chronic hepatitis C has been the combination of pegylated interferon (pegIFN) alpha-2a or -2b and ribavirin. In patients infected with HCV genotype 1, by far the most frequent HCV genotype worldwide, such treatment leads to a cure of infection in only 40-50% of cases. After a decade in which pegIFN alpha and ribavirin therapy was the only available option, triple therapy with HCV protease inhibitors (PIs; boceprevir and telaprevir) in combination with pegIFN alpha and ribavirin has become the new SoC for genotype-1-infected patients. With PI therapy, higher cure rates can be achieved, but specific issues are also raised, such as the emergence of resistance to PIs. For this reason, the present report examines the antiviral activity of PIs and what is currently known about resistance to them, while focusing on telaprevir and boceprevir, two HCV PIs recently licensed for the treatment of treatment-naïve and treatment-experienced genotype-1 patients with chronic hepatitis C. The clinical relevance of resistance testing is also discussed.


Studies on the use of antimitotic drugs entrapped within liposomes and of their action on a human glioma cell line.
The optimal conditions have been determined for producing the maximum incorporation within liposomes of two cell cycle-specific antimitotic drugs (bleomycin and vincristine) used in the treatment of human cerebral gliomas. Under these conditions the subsequent rate of release of these two drugs was studied in vitro. Neither cell fusion nor endocytosis could be demonstrated between liposomes of the size distribution used in these experiments (0.1-15 micron) and a human glioma cell line (U.251-MG) using a variety of marker techniques. Dose-response curves were similar for the two drugs whether free or entrapped within liposomes when applied to this cell line. These results suggest that drugs entrapped within liposomes may be useful as a potential depot preparation in the treatment of human gliomas.


The specificity of reactive synaptogenesis: a comparative study in the adult rat hippocampal formation.
The CA1 region of the hippocampus in the mature rat is shown to possess the capacity to form new synapses following a lesion of either the commissural afferents, which removes 41% of the synaptic input to stratum radiatum, or commissural and associational afferents, which destroys 74% of the synaptic input. With both types of lesion, extensive reinnervation occurs without obvious changes in lamination of afferent fibers and without accompanying changes in the acetylcholinesterase-(AChE) staining pattern. This is in contrast to what is known to occur in the hippocampal dentate gyrus following an ipsilateral entorhinal lesion where afferent lamination is reordered and where AChE-staining intensifies. A comparison between the disparate patterns of reinnervation in these closely related structures affords the opportunity to examine some of the specific factors that may regulate synaptic readjustments in brain.


Studies of histamine in the rheumatoid joint.
Fragments of synovial membranes from three patients with rheumatoid arthritis were incubated in Dulbecco's modified Eagle's medium (DMEM). Histamine was released into the medium at rates up to 649.3 ng/g synovium/day. To investigate whether histamine in synovial fluid may have more than a vasoactive role, cells cultured from human trabecular bone adjacent to a rheumatoid joint and human adherent rheumatoid synovial cells were incubated with different concentrations of histamine for 5 min. Histamine increased the intracellular content of cyclic AMP up to three fold in a dose-related manner but had no effect on synovial cells. This offers preliminary evidence that cells grown from human trabecular bone have histamine receptors.


Urban inequities; urban rights: a conceptual analysis and review of impacts on children, and policies to address them.
This paper explores current conceptual understanding of urban social, environmental, and health inequality and inequity, and looks at the impact of these processes on urban children and young people in the 21st century. This conceptual analysis was commissioned for a discussion paper for UNICEF's flagship publication: State of the World's Children 2012: Children in an Urban World. The aim of the paper is to examine evidence on the meaning of urban inequality and inequity for urban children and young people. It further looks at the controversial policies of targeting "vulnerable" young people, and policies to achieve the urban MDGs. Finally, the paper looks briefly at the potential of concepts such as environment justice and rights to change our understanding of urban inequality and inequity.


A hybrid mobile approach for population-wide HIV testing in rural east Africa: an observational study.
Despite large investments in HIV testing, only an estimated 45% of HIV-infected people in sub-Saharan Africa know their HIV status. Optimum methods for maximising population-level testing remain unknown. We sought to show the effectiveness of a hybrid mobile HIV testing approach at achieving population-wide testing coverage. We enumerated adult (≥15 years) residents of 32 communities in Uganda (n=20) and Kenya (n=12) using a door-to-door census. Stable residence was defined as living in the community for at least 6 months in the past year. In each community, we did 2 week multiple-disease community health campaigns (CHCs) that included HIV testing, counselling, and referral to care if HIV infected; people who did not participate in the CHCs were approached for home-based testing (HBT) for 1-2 months within the 1-6 months after the CHC. We measured population HIV testing coverage and predictors of testing via HBT rather than CHC and non-testing. From April 2, 2013, to June 8, 2014, 168,772 adult residents were enumerated in the door-to-door census. HIV testing was achieved in 131,307 (89%) of 146,906 adults with stable residence. 13,043 of 136,033 (9·6%, 95% CI 9·4-9·8) adults with and without stable residence had HIV; median CD4 count was 514 cells per μL (IQR 355-703). Among 131,307 adults with stable residence tested, 56,106 (43%) reported no previous testing. Among 13,043 HIV-infected adults, 4932 (38%) were unaware of their status. Among 105,170 CHC attendees with stable residence 104,635 (99%) accepted HIV testing. Of 131,307 adults with stable residence tested, 104,635 (80%; range 60-93% across communities) tested via CHCs. In multivariable analyses of adults with stable residence, predictors of non-testing included being male (risk ratio [RR] 1·52, 95% CI 1·48-1·56), single marital status (1·70, 1·66-1·75), age 30-39 years (1·58, 1·52-1·65 vs 15-19 years), residence in Kenya (1·46, 1·41-1·50), and migration out of the community for at least 1 month in the past year (1·60, 1·53-1·68). Compared with unemployed people, testing for HIV was more common among farmers (RR 0·73, 95% CI 0·67-0·79) and students (0·73, 0·69-0·77); and compared with people with no education, testing was more common in those with primary education (0·84, 0·80-0·89). A hybrid, mobile approach of multiple-disease CHCs followed by HBT allowed for flexibility at the community and individual level to help reach testing coverage goals. Men and mobile populations remain challenges for universal testing. National Institutes of Health and President's Emergency Plan for AIDS Relief.


[The nitrazine yellow test. A simple clinical method for diagnosing epidermal wound healing].
Nitrazine yellow test has proved successful in determining toxic degenerative hand eczema. Additionally, it may be regarded as helpful in the quantitative registration of kinetic data on epidermal wound healing.


Alzheimer's disease patients display gender dimorphism in circulating anorectic adipokines.
Among neurodegenerative diseases, Alzheimer's disease (AD) is a leading cause of death in elderly individuals. AD is characterized, among other clinical findings, by unexplained weight loss, cachexia and altered immune function. To explore whether any relationship between gender and circulating levels of several eating-controlling metabolites exist, we evaluated leptin, tumor necrosis factor (TNF)-alpha, triiodothyronine (T(3)), free (F) thyroxine (T(4)), TSH, PRL, insulin (INS), and cortisol in 15 AD-treated patients (age range 55-82 years): 9 postmenopausal females (without hormone replacement therapy) and 6 males. The results (mean +/- SEM) indicated that circulating leptin levels were significantly (p < 0.05) higher in female AD (40.34 +/- 11.1 ng/ml) than in male AD (6.07 +/- 1.39 ng/ml) patients. The difference found in circulating leptin levels was noticed regardless of BMI (26.75 +/- 1.77 and 24.55 +/- 1.93 kg/m(2), in females and males, respectively) and waist:hip ratios (0.91 +/- 0.03 and 0.94 +/- 0.02, in females and males, respectively). Moreover, serum TNF-alpha concentrations were also significantly (p < 0.02) higher in AD females (12.24 +/- 1.47 pg/ml) than in AD males (6.62 +/- 1.44 pg/ml), regardless of TNF-alpha:BMI ratios (0.50 +/- 0.09 and 0.28 +/- 0.08, in females and males, respectively; p > 0.05). Finally, no differences were observed between gender (in female and male AD patients, respectively) in circulating levels of T(3) (151.33 +/- 9.91 vs. 116 +/- 17.04 ng/dl), FT(4) (1.26 +/- 0.08 vs. 1.24 +/- 0.06 ng/dl), TSH (1.28 +/- 0.16 vs. 2.46 +/- 0.67 microIU/ml), PRL (10.53 +/- 2.47 vs. 12.61 +/- 2.37 ng/ml), INS (11.76 +/- 1.95 vs. 8.59 +/- 1.34 microIU/ml) and cortisol (15.71 +/- 1.23 vs. 12.63 +/- 1.47 microg/dl). These results indicate that our AD group of patients, with normal corticoadrenal and thyroid functions and normoprolactinemia, displayed a gender-related characteristic in the circulating levels of two very important anorectic signals, leptin and TNF-alpha, being both higher in female than in male AD patients, regardless of BMI. Our study suggests that increased circulating levels of both anorexigenic adipokines may contribute to the metabolic changes observed in AD females.


Resting-state functional connectivity predicts longitudinal change in autistic traits and adaptive functioning in autism.
Although typically identified in early childhood, the social communication symptoms and adaptive behavior deficits that are characteristic of autism spectrum disorder (ASD) persist throughout the lifespan. Despite this persistence, even individuals without cooccurring intellectual disability show substantial heterogeneity in outcomes. Previous studies have found various behavioral assessments [such as intelligence quotient (IQ), early language ability, and baseline autistic traits and adaptive behavior scores] to be predictive of outcome, but most of the variance in functioning remains unexplained by such factors. In this study, we investigated to what extent functional brain connectivity measures obtained from resting-state functional connectivity MRI (rs-fcMRI) could predict the variance left unexplained by age and behavior (follow-up latency and baseline autistic traits and adaptive behavior scores) in two measures of outcome--adaptive behaviors and autistic traits at least 1 y postscan (mean follow-up latency = 2 y, 10 mo). We found that connectivity involving the so-called salience network (SN), default-mode network (DMN), and frontoparietal task control network (FPTCN) was highly predictive of future autistic traits and the change in autistic traits and adaptive behavior over the same time period. Furthermore, functional connectivity involving the SN, which is predominantly composed of the anterior insula and the dorsal anterior cingulate, predicted reliable improvement in adaptive behaviors with 100% sensitivity and 70.59% precision. From rs-fcMRI data, our study successfully predicted heterogeneity in outcomes for individuals with ASD that was unaccounted for by simple behavioral metrics and provides unique evidence for networks underlying long-term symptom abatement.


Dipeptidyl-aminopeptidases and aminopeptidases in Dictyostelium discoideum.
Extracts prepared from culminating cells of Dictyostelium discoideum have been found to contain dipeptidyl-aminopeptidases I (EC 220.127.116.11), II (EC 18.104.22.168), III (EC 220.127.116.11), arginine aminopeptidase (EC 220.127.116.11) and valine aminopeptidase. Dipeptidyl-aminopeptidase III was the most active of the dipeptidyl-aminopeptidases; its molecular weight was 158,000, with a pH optimum of 10.2 and gave a single peak of activity on gel-filtration or when fractionated by chromatofocusing. The specific activities of dipeptidyl-aminopeptidases I and III increased during development being highest during the culmination stage before decreasing during sorocarp formation; dipeptidyl-aminopeptidase II and arginine aminopeptidase decreased progressively throughout development. The presence of these dipeptidyl-aminopeptidases suggests the possibility that processing of peptides may be necessary during the development of Dictyostelium.


Delayed postoperative radiotherapy might improve the long-term prognosis of locally advanced esophageal squamous cell carcinoma.
There is no consensus on the optimal timing of postoperative radiotherapy (PORT) for locally advanced esophageal squamous cell carcinoma (ESCC). We aimed to determine whether the timing of PORT affects the long-term prognosis of ESCC, and plotted nomograms to predict survival. We retrospectively analyzed 351 ESCC patients who underwent radical surgery and PORT. Receiver operating characteristic curves were used to estimate the optimal cutoff point of the time interval between surgery and PORT. Cox proportional hazards regression was used to identify prognostic predictors. Overall survival (OS) and progression-free survival (PFS) were predicted using nomograms. The median follow-up was 53 months (range: 3-179 months). Compared to early PORT, PORT at >48 days after surgery was associated with better OS (adjusted hazard ratio [HR]: 1.406, p = 0.037) and PFS (adjusted HR: 1.475, p = 0.018). In the chemotherapy subgroup, incorporation of chemotherapy timing into the analysis suggested that 2-4 chemotherapy cycles followed by PORT was the optimal treatment schedule as compared to 0-1 chemotherapy cycle followed by PORT and concurrent chemoradiotherapy (5-year PFS: 65.9% vs. 51.0% vs. 50.1%; p = 0.049). The nomograms for OS and PFS were superior to the TNM classification (concordance indices: 0.721 vs. 0.626 and 0.716 vs. 0.610, respectively). Delayed PORT (>48 days) provides better survival benefit than early PORT among ESCC patients. PORT following 2-4 chemotherapy cycles might lead to the best survival rate. The nomogram plotted in this study effectively predicted survival and may help guide treatment.


Understanding the hidden relations between pro- and anti-inflammatory cytokine genes in bovine oviduct epithelium using a multilayer response surface method.
An understanding gene-gene interaction helps users to design the next experiments efficiently and (if applicable) to make a better decision of drugs application based on the different biological conditions of the patients. This study aimed to identify changes in the hidden relationships between pro- and anti-inflammatory cytokine genes in the bovine oviduct epithelial cells (BOECs) under various experimental conditions using a multilayer response surface method. It was noted that under physiological conditions (BOECs with sperm or sex hormones, such as ovarian sex steroids and LH), the mRNA expressions of IL10, IL1B, TNFA, TLR4, and TNFA were associated with IL1B, TNFA, TLR4, IL4, and IL10, respectively. Under pathophysiological + physiological conditions (BOECs with lipopolysaccharide + hormones, alpha-1-acid glycoprotein + hormones, zearalenone + hormones, or urea + hormones), the relationship among genes was changed. For example, the expression of IL10 and TNFA was associated with (IL1B, TNFA, or IL4) and TLR4 expression, respectively. Furthermore, under physiological conditions, the co-expression of IL10 + TNFA, TLR4 + IL4, TNFA + IL4, TNFA + IL4, or IL10 + IL1B and under pathophysiological + physiological conditions, the co-expression of IL10 + IL4, IL4 + IL10, TNFA + IL10, TNFA + TLR4, or IL10 + IL1B were associated with IL1B, TNFA, TLR4, IL10, or IL4 expression, respectively. Collectively, the relationships between pro- and anti-inflammatory cytokine genes can be changed with respect to the presence/absence of toxins, sex hormones, sperm, and co-expression of other gene pairs in BOECs, suggesting that considerable cautions are needed in interpreting the results obtained from such narrowly focused in vitro studies.


Control of enantioselectivity in the photochemical conversion of alpha-oxoamides into beta-lactam derivatives.
[reaction: see text]. Several approaches to asymmetric induction in the alpha-oxoamide (1) to beta-lactam (2) photorearrangement are described. Best results are obtained via irradiation of ionic and covalent chiral auxiliary-containing reactants in the crystalline state and in the interior supercages of zeolites.


Conditioning-based outcomes after allogeneic transplantation for myeloma following a prior autologous transplant (1991-2012) on behalf of EBMT CMWP.
The aim of this study was to compare the effect of the intensity of conditioning approaches used in allogeneic transplantation in myeloma-reduced intensity conditioning (RIC), non-myeloablative (NMA), myeloablative conditioning (MAC) or Auto-AlloHCT-on outcomes in patients who had had a prior autologous transplant. A retrospective analysis of the EBMT database (1991-2012) was performed. A total of 344 patients aged between 40 and 60 years at the time of alloHCT were identified: 169 RIC, 69 NMA, 65 MAC and 41 Auto-Allo transplants. At a median follow-up of 54 months, the probabilities of overall survival (OS) at 5 years were 39% (95% CI 31%-47%), 45% (95% CI 32%-57%), 19% (95% CI 6%-32%) and 34% (95% CI 17%-51%), respectively. Status at allogeneic HCT other than CR or PR conferred a 70% higher risk of death and a 40% higher risk of relapse. OS was markedly lower in the MAC group (P = .004). MAC alloHCT was associated with a higher risk of death than RIC alloHCT until 2002 (HR = 4.1, P < .001) but not after 2002 (HR = 1.2, P = .276). From 1991 to 2002, MAC was associated with poorer OS. Between 2003 and 2012, there were no significant differences in outcomes based on these different approaches.


Spread of spinal anaesthesia with plain 0.5% bupivacaine: influence of the vertebral interspace used for injection.
Three millilitre of plain 0.5% bupivacaine was injected intrathecally at two different levels in two groups of 20 patients. Injection at the L2/3 space produced a significantly higher spread of analgesia (mean T7 (SD 3.9)) than injection at L4/5 (T11(1.8)). The range of the cephalad spread of the block was less in the L4/5 group (P less than 0.001 at 60 min). The spread of anaesthesia continued beyond 30 min in both groups. In all patients anaesthesia sufficient for surgery of the knee and the foot was achieved. One patient had a final block level of T1 after injection at L2/3, accompanied by transient arterial hypotension.


The expression of glia maturation factors and the effect of glia maturation factor-γ on angiogenic sprouting in zebrafish.
Angiogenesis is a vital process for proper embryonic development, wound healing, malignant tumor growth and metastasis. Two glia maturation factor genes, glia maturation factor-β (GMFB) and glia maturation factor-γ (GMFG), presenting different expression patterns and distinct biological functions are found in vertebrates. But, the role of GMFB and GMFG in vascular development remains largely unknown. Here, we showed that both GMFB and GMFG are highly conserved in vertebrates. Whole-mount in situ hybridization and quantitative RT-PCR results revealed that GMFB and GMFG were differently expressed during zebrafish embryogenesis. GMFB was highly enriched in brain and GMFG was predominantly expressed in endothelial cells. By gene specific MO, knockdown of GMFG, but not GMFB, severely disrupted angiogenic sprouting of intersegmental vessels (ISVs), but this angiogenic defects were prevented by overexpression of a MO-resistant form of zebrafish GMFG mRNA. In addition, the expressions of angiogenic factors VEGF-A, STAT3, MMP2, MMP9, and MMP13 were significantly decreased in endothelial cells of GMFG morphants. Our findings provide the first in vivo evidence that GMFG is an important regulator for angiogenic sprouting during angiogenesis in zebrafish and suggest that GMFG may act as a novel potential target for anti-angiogenesis therapy in clinical settings.


Increasing the affinity of selective bZIP-binding peptides through surface residue redesign.
The coiled-coil dimer is a prevalent protein interaction motif that is important for many cellular processes. The basic leucine-zipper (bZIP) transcription factors are one family of proteins for which coiled-coil mediated dimerization is essential for function, and misregulation of bZIPs can lead to disease states including cancer. This makes coiled coils attractive protein-protein interaction targets to disrupt using engineered molecules. Previous work designing peptides to compete with native coiled-coil interactions focused primarily on designing the core residues of the interface to achieve affinity and specificity. However, folding studies on the model bZIP GCN4 show that coiled-coil surface residues also contribute to binding affinity. Here we extend a prior study in which peptides were designed to bind tightly and specifically to representative members of each of 20 human bZIP families. These "anti-bZIP" peptides were designed with an emphasis on target-binding specificity, with contributions to design-target specificity and affinity engineered considering only the coiled-coil core residues. High-throughput testing using peptide arrays indicated many successes. We have now measured the binding affinities and specificities of anti-bZIPs that bind to FOS, XBP1, ATF6, and CREBZF in solution and tested whether redesigning the surface residues can increase design-target affinity. Incorporating residues that favor helix formation into the designs increased binding affinities in all cases, providing low-nanomolar binders of each target. However, changes in surface electrostatic interactions sometimes changed the binding specificity of the designed peptides.


Interlimb coordination and academic performance in elementary school children.
The specific mechanisms linking motor ability and cognitive performance, especially academic achievement, are still unclear. Whereas the literature provides an abundance of information on fine and visual-motor skill and cognitive attributes, much less has been reported on gross motor ability. This study examined interlimb coordination and its relationship to academic performance in children aged 8-11 years. Motor and academic skills were examined in 100 Brazilian children using the Bruininks-Oseretsky Test of Motor Proficiency and the Academic Performance Test. Participants were grouped into low (<25%) and high (>75%) academic achievers. There was a significant difference between groups for Total Motor Composite (P < 0.001) favoring the high group. On regression analysis there was a significant association between academic performance and Body Coordination. Of the subtests of Body Coordination (Bilateral Coordination and Balance), Bilateral Coordination accounted for the highest impact on academic performance. Of interest here, that subtest consists primarily of gross motor tasks involving interlimb coordination. Overall, there was a positive relationship between motor behavior, in particular activities involving interlimb coordination, and academic performance. Application of these findings in the area of early assessment may be useful in the identification of later academic problems.


Formal learning theory dissociates brain regions with different temporal integration.
Learning can be characterized as the extraction of reliable predictions about stimulus occurrences from past experience. In two experiments, we investigated the interval of temporal integration of previous learning trials in different brain regions using implicit and explicit Pavlovian fear conditioning with a dynamically changing reinforcement regime in an experimental setting. With formal learning theory (the Rescorla-Wagner model), temporal integration is characterized by the learning rate. Using fMRI and this theoretical framework, we are able to distinguish between learning-related brain regions that show long temporal integration (e.g., amygdala) and higher perceptual regions that integrate only over a short period of time (e.g., fusiform face area, parahippocampal place area). This approach allows for the investigation of learning-related changes in brain activation, as it can dissociate brain areas that differ with respect to their integration of past learning experiences by either computing long-term outcome predictions or instantaneous reinforcement expectancies.


Increase in the activity of tryptophan hydroxylase from cortex and midbrain of male Fischer 344 rats in response to acute or repeated sound stress.
Exposure of male Fischer 344 rats to an acute sound stress consisting of 100 dB tones of 2-s duration presented at random 60-s intervals for 2 h, increased cortical and midbrain tryptophan hydroxylase activity, measured in vitro, 50% over that from sham-stressed animals. This increase in enzyme activity was observed when animals were killed immediately, but not 1 h, after termination of the sound stress. It was non-additive with the increase in activity induced by incubation of enzyme under phosphorylating conditions and could be reversed in vitro with alkaline phosphatase. Graded increases in enzyme activity were obtained with increments of sound intensity (90-120 dB). In contrast to acute stress, chronic sound stress (110 dB) repeated over a period of 1, 2 or 6 weeks (3 sessions per week each of 2-h duration) produced a 50% increase in cortical enzyme activity that persisted 24 h after the termination of the stress and was not reversed by alkaline phosphatase. However, a further increase in enzyme activity could be produced if the chronically stressed animals were exposed to an acute 2-h stress (110 dB) immediately before being killed. This additional increase in activity was reversible in vitro by alkaline phosphatase and non-additive with that produced by incubation under phosphorylating conditions. In summary, acute sound stress produced a prompt, reversible activation of tryptophan hydroxylase. Repeated exposure to sound stress induced a persistent increase in enzyme activity that was detected 24 h after the last stress.


Accuracy of core needle biopsy compared to fine needle biopsy for the diagnosis of neoplasm in patients with suspected head and neck cancers: a systematic review protocol of diagnostic test accuracy.
The objective of this review is to determine the difference in diagnostic accuracy of core needle biopsy and fine needle aspiration for patients with a head and neck mass using surgical histopathology as a reference test. The risks and adverse events associated with each technique will also be compared. Tissue diagnosis is critical in evaluation of head and neck lesions to guide management. Options for tissue biopsy include surgical biopsy, fine needle aspiration and core needle biopsy. Studies that compare ultrasound-guided core needle biopsy and/or fine needle aspiration to investigate lumps in the thyroid, cervical lymph nodes, or salivary glands for malignancy in adult patients will be included. The comparator test will be definitive histology in form of surgical biopsy/excision. MEDLINE, Emcare, Embase, Web of Science and Cochrane Register of Diagnostic Accuracy Studies will be searched. Studies will be critically appraised by two independent reviewers for methodological quality, using the modified critical appraisal instrument QUADAS-2 and JBI SUMARI software. Two independent reviewers will extract data from papers included in the review using the standardized data extraction tool available in the JBI Reviewer's Manual. PROSPERO CRD42020140005.


Hypervolemia and Sleep Apnea in Kidney Disease.
In end-stage renal disease (ESRD) and heart failure, conditions characterized by fluid overload, both obstructive sleep apnea (OSA) and central sleep apnea (CSA) are highly prevalent. This observation suggests that fluid overload may be a unifying mechanism in the pathogenesis of both OSA and CSA in these conditions. An overnight rostral fluid shift from the legs to the neck and lungs has been shown to contribute to the pathogenesis of OSA and CSA, respectively, in various different patient populations. This article reviews the evidence that supports a role for fluid overload and overnight fluid shift in the pathogenesis of sleep apnea in ESRD. The diagnosis, epidemiology, and clinical features of sleep apnea in patients with ESRD also are considered.


Time to health-related quality of life improvement analysis was developed to enhance evaluation of modern anticancer therapies.
Major advances have recently been made in the treatments of cancer, which now also have the potential to improve patients' health-related quality of life (HRQOL). We propose the time to HRQOL improvement (TTI) and the time to sustained HRQOL improvement (TTSI) as potentially important cancer outcomes to be used in longitudinal HRQOL analyses. As proof of principle, we defined TTI and TTSI, using the Fine-Gray model to include competing risks in estimates, in a case study in real life of a cohort of newly diagnosed patients with cancer receiving a targeted therapy. HRQOL was evaluated before and during therapy with six assessments over a 24-month period, using the well-validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. For each assessed HRQOL domain, we assessed TTI and TTSI and estimated the cumulative incidence of patients' clinically meaningful improvements, also accounting for the occurrence of competing events. TTI and TTSI are potentially important outcomes in the era of modern anticancer therapies. The analysis of TTI and TTSI by competing risks approach will further add to the statistical methods that can be used to inform on the impact of cancer therapies on patients' HRQOL.


Black children with high preferences for fruits and vegetables are at less risk of being at risk of overweight or overweight.
Food preferences play a central role in food choices and consumption. The primary objective of this study was to examine the relationship between children's preferences for fruits and vegetables and their weight status. A total of 341 black children (43% boys; 68% fourth graders) attending low-income, public elementary schools in southeastern Louisiana volunteered to participate. Children were measured for height and weight and completed a survey that sought their preferences for 38 different fruits and vegetables during the fall of 2005. Results indicated that children preferred fruits more than vegetables and that there was a negative association between children's mean fruit and vegetable preference score and their body mass index for age percentile (r=-0.26; P=0.01). Children who reported a very low preference for fruits and vegetables were 5.5 times more likely to be categorized as at risk for overweight or overweight than were those who reported a high preference for fruits and vegetables (odds ratio: 5.5; confidence interval: 1.97 to 15.44; P<0.01). It is believed that food preferences are established early in life; therefore, nutritionists and other health care professionals should promote children's acceptance and intake of fruits and vegetables as a measure to reduce the prevalence of overweight among children.


Early androgen influences on human neural and behavioural development.
Gonadal hormones, particularly androgens, influence sexual differentiation of the body, as well as the brain and behaviour. Antenatal exposure to atypical hormone environments leads to alterations in human behaviours that show sex differences. These include childhood play, sexual orientation, gender identity, and personality characteristics, such as empathy and aggression. Individual variability among healthy children in antenatal hormone exposure show similar relationships to individual variability in postnatal behaviour. As in studies of atypical exposure, higher levels of androgen predict more male-typical, and less female-typical, behaviour. Hormone-induced alterations in brain development are thought to underlie these behavioural outcomes, although there is little information on specific neural differences associated with early hormone differences. Notable, however, is evidence relating early androgen exposure to activation of the medial amygdaloid nucleus in women. Other emerging research areas include the role of neonatal hormones in infant development and interactions between hormone-induced predispositions and postnatal experience in producing behavioural outcomes.


Acute angular origin of left coronary artery from aorta: an unusual cause of left ventricular failure in infancy.
An unusual congenital anomaly of the left coronary artery, consisting of ostial stenosis caused by an acute angular origin of the vessel from the aorta in an infant, is presented. This anomaly resulted in progressive myocardial fibrosis and development of left ventricular congestive heart failure. The clinical state mimicked anomalous origin of the left coronary artery from the pulmonary artery.


Glycosylphosphatidylinositol-induced cardiac myocyte death might contribute to the fatal outcome of Plasmodium falciparum malaria.
Glycosylphosphatidylinositol (GPI) purified from Plasmodium falciparum has been shown to play an important role as a toxin in the pathology of malaria. Previous studies demonstrated cardiac involvement in patients suffering from severe malaria due to P. falciparum. Therefore, we tested the hypothesis that GPI induces apoptosis in cardiomyocytes. By using TUNEL and caspase activity assays, we provided evidence for apoptosis induction in cardiomyocytes by P. falciparum GPI after 48 h of incubation. A similar result was obtained in heart cells of mice 48 h after in vivo injection of GPI. Gene expression analyses in GPI-treated cardiomyocytes showed an up-regulation of apoptotic genes (apaf-1, bax) and of a myocardial damage marker bnp (brain natriuretic peptide), while a down-regulation was observed for the anti-apoptotic gene bcl-2 and for the heat shock protein hsp70. In spite of inflammatory cytokine gene up-regulation by GPI, co-culture with peripheral mononuclear cells (PMNCs) did not change the results obtained with cardiomyocytes alone, indicating a direct effect of GPI on cardiac myocytes. Co-culture with non-myocytic cardiac cells (NMCCs) resulted in up-regulation of Hsp70 and Bcl-2 genes in GPI-treated cardiomyocytes but without repercussion on the apoptosis level. A malaria-infected patient, presenting fulminant heart failure showed typical signs of cardiac myocyte apoptosis demonstrating the clinical relevance of toxin induced heart damage for the lethality of malaria. Our studies performed in vitro and in mice suggest that the GPI could be responsible for cardiomyocyte apoptosis that occurred in this patient. Plasmodium falciparum GPI-induced apoptosis might participate in the lethality of malaria.


In vitro and in vivo susceptibility to sulfadiazine and pyrimethamine of Toxoplasma gondii strains isolated from Brazilian free wild birds.
Little is known about the existence of drug-resistant Toxoplasma gondii strains and their possible impact on clinic outcomes. To expand our knowledge about the existence of natural variations on drug susceptibility of T. gondii strains in Brazil, we evaluated the in vitro and in vivo susceptibility to sulfadiazine (SDZ) and pyrimethamine (PYR) of three atypical strains (Wild2, Wild3, and Wild4) isolated from free-living wild birds. In vitro susceptibility assay showed that the three strains were equally susceptible to SDZ and PYR but variations in the susceptibility were observed to SDZ plus PYR treatment. Variations in the proliferation rates in vitro and spontaneous conversion to bradyzoites were also accessed for all strains. Wild2 showed a lower cystogenesis capacity compared to Wild3 and Wild4. The in vivo analysis showed that while Wild3 was highly susceptible to all SDZ and PYR doses, and their combination, Wild2 and Wild4 showed low susceptibility to the lower doses of SDZ or PYR. Interestingly, Wild2 presented low susceptibility to the higher doses of SDZ, PYR and their combination. Our results suggest that the variability in treatment response by T. gondii isolates could possibly be related not only to drug resistance but also to the strain cystogenesis capacity.


Subcostal M-mode echocardiography of the right atrial wall in the diagnosis of cardiac arrhythmias.
The M-mode echocardiogram of the right atrial (RA) wall can be easily recorded in each person from the subcostal location. In a normal RA wall motion pattern, atrial contraction is represented by a markedly prominent posterior motion. The presence or absence of atrial contractions in the subcostal RA wall echocardiogram, their amplitude, and their timing may help in the diagnosis of cardiac arrhythmias with the simultaneously recorded non-diagnostic electrocardiogram. Flat and hidden P waves can be accurately identified throughout the cardiac cycle. It is possible to distinguish between atrial, ventricular, and nodal premature beats and to recognize atrial fibrillation, atrial flutter, paroxysmal atrial tachycardia, paroxysmal atrial tachycardia with block, atrioventricular (AV) nodal tachycardia, and supraventricular tachycardias with aberrant ventricular conduction. The diagnosis of wandering pacemaker, AV dissociation, sinoatrial block, and AV block is facilitated. On the basis of study of 60 patients with various rhythm disturbances, it was concluded that analysis of the subcostal RA wall echocardiogram is a new, helpful noninvasive approach in the diagnosis of cardiac arrhythmias.