Diagnostic value of open and needle biopsies in tumors of the sacrum.
A retrospective study with statistical analysis of 25 percutaneous needle biopsies and 54 open biopsies performed on 60 patients with tumors located in the sacrococcygeal region. To analyze the diagnostic value of open and needle biopsies in tumors of the sacrum as well as to determine factors leading to a false or equivocal result. Although percutaneous needle biopsies of the spine are valuable for thoracolumbar levels, the benefit in the sacrococcygeal region, specifically, has not previously been shown. This region is unique because of anatomic and oncologic factors. Medical charts, imaging studies, and operative and pathologic records of patients with tumors diagnosed between 1965 and 1996 in the sacrococcygeal region reviewed were analyzed. Accuracy and effective accuracy of each procedure were then calculated. There were 54 primary lesions (17 benign, 37 malignant) and 6 metastatic tumors. The accuracy and effective accuracy of open biopsies was 87% and 81% but in percutaneous needle biopsies was only 44% and 12%, respectively. An unclear diagnosis resulted in the need for another biopsy in 12 of 21 primary percutaneous needle biopsies but only in 2 of 39 open biopsies (P < 0.0001, chi2). The average number of biopsies required to obtain a definitive diagnosis was significantly less if an open biopsy were performed first instead of a percutaneous needle biopsy, 1.1 versus 1.8, respectively (P = 0.0004, two-sample t test). There was a significant delay in treatment if the initial biopsy was a percutaneous needle biopsy compared with an open biopsy, mean 46 versus 4 days, respectively (P = 0.004, two-sample t test). We conclude that for sacral tumors, open biopsies have a higher effective accuracy, whereas needle biopsies are associated with a longer delay in treatment.


Detection and characterization of ticlopidine conjugates in rat bile using high-resolution mass spectrometry: applications of various data acquisition and processing tools.
Ticlopidine, an antiplatelet drug, undergoes extensive oxidative metabolism to form S-oxide, N-oxide, hydroxylated and dealkylated metabolites. However, metabolism of ticlopidine via conjugation has not been thoroughly investigated. In this study, multiple data acquisition and processing tools were applied to the detection and characterization of ticlopidine conjugates in rat bile. Accurate full-scan mass spectrometry (MS) and collision-induced dissociation (CID) MS/MS data sets were recorded using isotope pattern-dependent acquisition on an LTQ/Orbitrap system. In addition, mass spectral data from online H/D exchanging and high collision energy dissociation (HCD) were recorded. Data processes were carried out using extracted ion chromatography (EIC), mass defect filter (MDF) and isotope pattern filter (IPF). The total ion chromatogram displayed a few major conjugated metabolites and many endogenous components. Profiles from EIC and IPF processes exhibited multiple conjugates with no or minimal false positives. However, ticlopidine conjugates that were not predictable or lost a chorine atom were not found by EIC or IPF, respectively. MDF was able to detect almost all of ticlopidine conjugates although it led to a few more false positives. In addition to CID spectra, data from HCD, H/D exchanging experiments and isotope pattern simulation facilitated structural characterization of unknown conjugates. Consequently, 20 significant ticlopidine conjugates, including glucuronide, glutathione, cysteinylglycine, cysteine and N-acetylcysteine conjugates, were identified in rat bile, a majority of which are associated with bioactivation and not previously reported. This study demonstrates the utility and limitation of various high-resolution MS-based data acquisition and processing techniques in detection and characterization of conjugated metabolites.


Blocking LFA-1 Aggravates Cardiac Inflammation in Experimental Autoimmune Myocarditis.
The lymphocyte function-associated antigen 1 (LFA-1) is a member of the beta2-integrin family and plays a pivotal role for T cell activation and leukocyte trafficking under inflammatory conditions. Blocking LFA-1 has reduced or aggravated inflammation depending on the inflammation model. To investigate the effect of LFA-1 in myocarditis, mice with experimental autoimmune myocarditis (EAM) were treated with a function blocking anti-LFA-1 antibody from day 1 of disease until day 21, the peak of inflammation. Cardiac inflammation was evaluated by measuring infiltration of leukocytes into the inflamed cardiac tissue using histology and flow cytometry and was assessed by analysis of the heart weight/body weight ratio. LFA-1 antibody treatment severely enhanced leukocyte infiltration, in particular infiltration of CD11b+ monocytes, F4/80+ macrophages, CD4+ T cells, Ly6G+ neutrophils, and CD133+ progenitor cells at peak of inflammation which was accompanied by an increased heart weight/body weight ratio. Thus, blocking LFA-1 starting at the time of immunization severely aggravated acute cardiac inflammation in the EAM model.


A new species of Tegenaria Latreille, 1804 (Araneae, Agelenidae) from Turkey.
A new species of the spider genus Tegenaria Latreille, 1804 is described, based on newly collected specimens from Turkey. Detailed morphological descriptions, diagnosis and figures of the copulatory organs of both sexes are presented. Finally, a checklist and distribution maps for Turkish Tegenaria species are provided.


PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells.
Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium.


Black Raspberry (Rubus coreanus Miquel) Promotes Browning of Preadipocytes and Inguinal White Adipose Tissue in Cold-Induced Mice.
The alteration of white adipose tissue (WAT) "browning", a change of white into beige fat, has been considered as a new therapeutic strategy to treat obesity. In this study, we investigated the browning effect of black raspberry (Rubus coreanus Miquel) using in vitro and in vivo models. Black raspberry water extract (BRWE) treatment inhibited lipid accumulation in human mesenchymal stem cells (hMSCs) and zebrafish. To evaluate the thermogenic activity, BRWE was orally administered for 2 weeks, and then, the mice were placed in a 4 °C environment. As a result, BRWE treatment increased rectal temperature and inguinal WAT (iWAT) thermogenesis by inducing the expression of beige fat specific markers such as PR domain zinc-finger protein 16 (PRDM16), uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), and t-box protein 1 (TBX1) in cold-exposed mice. Furthermore, ellagic acid (EA), a constituent of BRWE, markedly promoted beige specific markers: UCP1, PGC1α, TBX1, and nuclear respiratory factor 1 in beige differentiation media (DM)-induced 3T3-L1 adipocytes. Our findings indicate that BRWE can promote beige differentiation/activation, and EA is the active compound responsible for such effect. Thus, we suggest the nature-derived agents BRWE and EA as potential agents for obesity treatment.


Hangover free! The social and material trajectories of PartySmart.
This paper presents three embedded episodes in the life of a polyherbal drug indicated as a preventative measure for hangovers. Invented and marketed in 2005 by a leading ayurvedic pharmaceutical company in India, PartySmart is a reformulated compound based on ayurvedic, biomedical and phytochemical sources. This creative process has involved multiple translations, resulting in hybrid pharmacological models, including, for instance, ayurvedic post-digestive tastes and biomedical effects on enzymatic activities. These modes of therapeutic action are conceptualizations of an active drug-- i.e., a digested and metabolized drug. A problem arises, however, in the fact that the ingestion of this drug is linked to alcohol consumption in a country where it is widely considered in negative terms. For this reason, PartySmart was seen as an ambivalent presence in the firm's catalogue and thus a series of interventions aiming to uphold the image of this drug transformed both its social inscription and its materiality. This transformation also took a different, global trajectory as the drug gradually developed as a transnational pharmaceutical commodity and became a new object in new latitudes. By focusing on the social and material dimensions of this drug in these contexts, this paper calls upon science studies to expand the scope of pharmaceutical anthropology. It brings together various layers of analysis to offer new perspectives on contemporary herbal formulations as they traverse material cultures, medical epistemologies, sociopolitical borders, legal environments and social practices.


A new model to produce infectious hepatitis C virus without the replication requirement.
Numerous constraints significantly hamper the experimental study of hepatitis C virus (HCV). Robust replication in cell culture occurs with only a few strains, and is invariably accompanied by adaptive mutations that impair in vivo infectivity/replication. This problem complicates the production and study of authentic HCV, including the most prevalent and clinically important genotype 1 (subtypes 1a and 1b). Here we describe a novel cell culture approach to generate infectious HCV virions without the HCV replication requirement and the associated cell-adaptive mutations. The system is based on our finding that the intracellular environment generated by a West-Nile virus (WNV) subgenomic replicon rendered a mammalian cell line permissive for assembly and release of infectious HCV particles, wherein the HCV RNA with correct 5' and 3' termini was produced in the cytoplasm by a plasmid-driven dual bacteriophage RNA polymerase-based transcription/amplification system. The released particles preferentially contained the HCV-based RNA compared to the WNV subgenomic RNA. Several variations of this system are described with different HCV-based RNAs: (i) HCV bicistronic particles (HCVbp) containing RNA encoding the HCV structural genes upstream of a cell-adapted subgenomic replicon, (ii) HCV reporter particles (HCVrp) containing RNA encoding the bacteriophage SP6 RNA polymerase in place of HCV nonstructural genes, and (iii) HCV wild-type particles (HCVwt) containing unmodified RNA genomes of diverse genotypes (1a, strain H77; 1b, strain Con1; 2a, strain JFH-1). Infectivity was assessed based on the signals generated by the HCV RNA molecules introduced into the cytoplasm of target cells upon virus entry, i.e. HCV RNA replication and protein production for HCVbp in Huh-7.5 cells as well as for HCVwt in HepG2-CD81 cells and human liver slices, and SP6 RNA polymerase-driven firefly luciferase for HCVrp in target cells displaying candidate HCV surface receptors. HCV infectivity was inhibited by pre-incubation of the particles with anti-HCV antibodies and by a treatment of the target cells with leukocyte interferon plus ribavirin. The production of authentic infectious HCV particles of virtually any genotype without the adaptive mutations associated with in vitro HCV replication represents a new paradigm to decipher the requirements for HCV assembly, release, and entry, amenable to analyses of wild type and genetically modified viruses of the most clinically significant HCV genotypes.


Crosstalk between Iron and Arteriosclerosis.
Iron is an important element for life; however, intracellular labile iron overload can lead to the generation of reactive oxygen species and cellular damage. Although iron is mainly utilized for heme synthesis and is incorporated into hemoglobin, body iron status is often implicated in the pathogenesis of cardiovascular diseases. In a cell, iron is used for basic processes such as cell growth, maintenance, and repair. Thus, iron is considered to be involved in the pathogenesis of arteriosclerosis. In fact, clinical and experimental studies have shown an association between iron and arteriosclerosis. These data suggest the crosstalk between iron and arteriosclerosis. However, iron metabolism in arteriosclerosis is often complicated, and the systemic and cellular mechanisms of iron homeostasis in arteriosclerosis remain completely unsolved. Thus, in this review, we aimed to examine the role of iron in arteriosclerosis.


Effects of high-fat diets rich in either omega-3 or omega-6 fatty acids on UVB-induced skin carcinogenesis in SKH-1 mice.
Our previous studies reported that caffeine or voluntary exercise decreased skin tumor multiplicity, in part, by decreasing fat levels in the dermis. These data suggest that tissue fat may play an important role in regulating ultraviolet light (UV) B-induced skin tumor development. In the present study, we explored the effects of high-fat diets rich in either omega-3 or omega-6 fatty acids on UVB-induced skin carcinogenesis. SKH-1 mice were irradiated with 30 mJ/cm(2) of UVB once a day, two times per week for 39 weeks. During UVB treatment, one group of mice was given a high-fat fish oil (HFFO) diet rich in omega-3 fatty acids and the other group of mice was given a high-fat mixed-lipids (HFMLs) diet rich in omega-6 fatty acids. The results showed that, compared with HFML diet, HFFO treatment (i) increased latency for the development of UVB-induced skin tumors; (ii) decreased the formation of papilloma, keratoacanthoma and carcinoma by 64, 52 and 46%, respectively and (iii) decreased the size of papilloma, keratoacanthoma and carcinoma by 98, 80 and 83%, respectively. Mechanistic studies with antibody array revealed that compared with HFML diet, administration of HFFO to the mice significantly decreased the UVB-induced increases in the levels of TIMP-1, LIX and sTNF R1 as well as other several proinflammatory cytokines and stimulated the UVB-induced apoptosis in the epidermis. Our results indicate that omega-3 fatty acids in HFFO diet have beneficial effects against UVB-induced skin carcinogenesis, and these effects may be associated with an inhibition on UVB-induced inflammatory response.


Chronic bronchitis in Victoria, New South Wales and Queensland.
A study of chronic bronchitis was carried out on 195 ex-servicemen from Victoria New South Wales and Queensland. Exacerbations of chest symptoms were commonly found and chronic bronchitis was in important cause of haemoptysis. Weather conditions, especially cold weather, affected chest symptoms and early age of starting to smoke affected the incidence of severe bronchitis. The clinical profiles of the cases studied were similar to those in some of the reports from Canada and Britain.


An audit of half-count myocardial perfusion imaging using resolution recovery software.
The Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine has conducted a multicentre, multivendor audit to evaluate the use of resolution recovery software from several manufacturers when applied to myocardial perfusion data with half the normal counts acquired under a variety of clinical protocols in a range of departments. The objective was to determine whether centres could obtain clinical results with half-count data processed with resolution recovery software that were equivalent to those obtained using their normal protocols. Sixteen centres selected 50 routine myocardial perfusion studies each, from which the Nuclear Medicine Software Quality Group generated simulated half-count studies using Poisson resampling. These half-count studies were reconstructed using resolution recovery and the clinical reports compared with the original reports from the full-count data. A total of 769 patient studies were processed and compared. Eight centres found only a small number of clinically relevant discrepancies between the two reports, whereas eight had an unacceptably high number of discrepancies. There were no significant differences in acquisition parameters between the two groups, although centres finding a high number of discrepancies were more likely to perform both rest and stress scans on normal studies. Half of the participating centres could potentially make use of resolution recovery to reduce the administered activity for myocardial perfusion scans without changing their routine acquisition protocols. The other half could consider adjusting the reconstruction parameters used with their resolution recovery software if they wish to use reduced activity successfully.


[Choroidal melanoma and maculopathy].
Distant macular changes were revealed in 21 of 28 patients with intraocular melanoma. In 13 eyes maculopathy was very distant from choroidal melanoma (CM), in 4 cases the tumor was located preequatorially and in 9 patients in the posterior fundus beyond the macular zone. In 8 patients bilateral AMD was found along with CM. Revealed changes are considered to be tumor-associated sign of progressing CM. Association of AMD and CM should be considered as a combination of two distinct conditions, when CM disturbs hematoretinal barrier and thus leads to AMD progression.


Some conceptual distinctions are more useful than others.
Useful distinctions in conceptual schemes lead to explanatory or descriptive metaphors that have a clear form. Muddles, on the other hand, are created when useful distinctions that could be drawn are not or when an unnecessary distinction is drawn. The field of family therapy, now involved in an explicit epistemological and paradigmatic shift, has various muddles of each kind. The purpose of this essay is to describe some of these muddles and to suggest that making a distinction between "the study of the family-as-a-system" and "the study of family-therapy-as-a-system" leads to some useful and clear metaphors.


Return to Sport and Reinjury Rates in Elite Female Athletes After Anterior Cruciate Ligament Rupture.
While there has been significant interest in the documentation of return to sport outcomes following anterior cruciate ligament (ACL) injury, the elite level female athlete has not been a focus of this research. This is despite women being at increased risk for ACL injury and considerable global growth in women participating in sport. Therefore, the focus of this review was to examine the available literature regarding return to sport outcomes in elite level women with an ACL injury. The topics of discussion focus on return to sport rates, timing and determinants of return to sport, longevity of play, return to sport performance, and further ACL injury. Knee health in the longer term is also briefly discussed along with the limitations of the existent literature.


Infant crying problems related to maternal depressive and anxiety symptoms during pregnancy: a prospective cohort study.
Infant crying may cause concerns among new parents and is a frequent reason for seeking help from their general practitioner (GP). The etiology of crying problems in infancy is not fully understood, but recent studies have found associations with maternal mental factors. It is well-established that postpartum depression is related to infant crying problems while the influence of maternal mental problems in pregnancy on infant crying is less investigated. We aimed to explore whether maternal depressive symptoms or maternal anxiety during pregnancy were related to crying problems by the newborn child. In this prospective cohort study, 1290 pregnant women and their newborn children were followed throughout pregnancy until 8 weeks postpartum. Depressive symptoms and anxiety symptoms were assessed three times during pregnancy and again 8 weeks postpartum with the Major Depressive Inventory (MDI) and the Anxiety Symptoms Scale (ASS). Eight weeks postpartum the mothers were also asked whether their child cried in a way they found problematic. Multivariable regression was used to assess the association between depressive and anxiety symptoms during pregnancy and crying problems, and to adjust for potential confounders. We found statistically significant associations between high scores of depressive symptoms and anxiety symptoms in pregnancy and infant crying problems. Previously reported strong associations postpartum between depressive symptoms, anxiety symptoms and infant crying problems were also observed in the present data. These results indicate that mental problems during pregnancy are associated with having a child with crying problems after birth. If more focus is given to maternal mental problems during pregnancy, the healthcare system might be able to detect and help these women, which would be beneficial for both mother and child.


Mean-field models for heterogeneous networks of two-dimensional integrate and fire neurons.
We analytically derive mean-field models for all-to-all coupled networks of heterogeneous, adapting, two-dimensional integrate and fire neurons. The class of models we consider includes the Izhikevich, adaptive exponential and quartic integrate and fire models. The heterogeneity in the parameters leads to different moment closure assumptions that can be made in the derivation of the mean-field model from the population density equation for the large network. Three different moment closure assumptions lead to three different mean-field systems. These systems can be used for distinct purposes such as bifurcation analysis of the large networks, prediction of steady state firing rate distributions, parameter estimation for actual neurons and faster exploration of the parameter space. We use the mean-field systems to analyze adaptation induced bursting under realistic sources of heterogeneity in multiple parameters. Our analysis demonstrates that the presence of heterogeneity causes the Hopf bifurcation associated with the emergence of bursting to change from sub-critical to super-critical. This is confirmed with numerical simulations of the full network for biologically reasonable parameter values. This change decreases the plausibility of adaptation being the cause of bursting in hippocampal area CA3, an area with a sizable population of heavily coupled, strongly adapting neurons.


An analysis of the relationship between donor and recipient biomarkers and kidney graft function, dysfunction, and rejection.
The study aimed to find predictive biomarkers to evaluate donor kidney function to predict graft dysfunction as well as to assess an early signs of acute graft rejection. Twenty-seven deceased donors and 54 recipients who underwent a successful kidney transplantation were enrolled in the study. An assessment was made in serum and urine from donors and recipients to measure the following biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase 2 (TIMP-2) and urinary N-acetyl-b-D-glucosaminidase (uNAG). These biomarkers were used to establish a model for predicting a reduced graft function (RGF) classified as either a delayed or slow graft function. Our analysis suggest that out of four tested biomarkers, the serum TIMP-2 and uNAG levels of the donors had a predictive value for RGF; the area under the receiver operating characteristic curves (AUROC) of serum TIMP-2 and uNAG were 0.714 and 0.779, respectively. The combined best fitting prediction model of serum TIMP-2, uNAG, and creatinine levels was better in predicting RGF than the serum creatinine level alone. In addition, the recipient serum TIMP-2 level on the third day post-transplantation (D3) was associated with the estimated glomerular filtration rate (eGFR) on the seventh day post-transplantation (D7; OR 1.119, 95% CI 1.016-1.233, p = 0.022). Furthermore, the ROC curve value revealed that the AUROC of TIMP-2 on D3 was 0.99 (95% CI 0.97-1, p < 0.001), and this was the best predictive value of the renal function on D7. Donor serum TIMP-2 and uNAG levels are useful predictive biomarkers because they can provide the donor-based prediction for RGF.


Effects of elastase and cigarette smoke on alveolar epithelial permeability.
To determine whether instilled porcine pancreatic elastase (PPE) increases alveolar epithelial permeability, we measured alveolar epithelium permeability X surface area (PS) for [14C]sucrose and 125I-bovine serum albumin (125I-BSA) in isolated perfused lungs from hamsters previously exposed to PPE and/or cigarette smoke. Saline (0.5 ml) with 0, 5, or 20 units PPE was instilled intratracheally in anesthetized hamsters. Those exposed to smoke for 4-6 wk received 0 or 5 units; PS was measured 3 h later. Nonsmokers received 0, 5, or 20 units; PS was measured 3 h, 24 h, or 5 days later. Control PS values were (cm3/s X 10(-4), +/- SE) 0.84 +/- 0.11 for sucrose and 0.030 +/- 0.006 for BSA. Three and 24 h following 20 units PPE, (PS)sucrose was twice the control valve. (PS)BSA was four times control at 3 h but not significantly increased at 24 h. Five days after PPE both were back to control levels. Five units PPE or smoke exposure alone caused no PS changes. Smoke exposure and 5 units PPE caused (PS)sucrose to increase markedly (1.85 +/- 0.32); (PS)BSA was not significantly increased (0.076 +/- 0.026). Thus instilled PPE causes reversible increases in alveolar epithelial PS; cigarette smoking potentiates this effect.


Frequency and Pathophysiology of Post-Seizure Todd's Paralysis.
Todd's paralysis, a neurological abnormality characterized by temporary limb weakness or hemiplegia, typically occurs following a seizure, without enduring consequences. Since limb weakness or hemiplegia can also be a common symptom of an acute ischemic stroke, it is often difficult to diagnose Todd's paralysis in individuals experiencing an acute ischemic stroke if they do not have a pre-existing history of epilepsy. Given that there is a limited understanding of Todd's paralysis, this review discusses the history, prevalence, clinical manifestations, duration, etiology, and diagnosis of Todd's paralysis. A few factors that may help clinicians distinguish Todd's paralysis from other clinical indications are as follows: (1) Todd's paralysis is commonly observed after partial seizures or generalized tonic-clonic seizures. (2) The incidence of Todd's paralysis is greater if the epilepsy is associated with old age or stroke history. (3) The duration of Todd's paralysis can range from minutes to days, depending on the type of seizure or whether the patient has experienced cortical structural damage. (4) The etiology of Todd's paralysis is associated with cerebral perfusion abnormality after seizures. Further research is needed to explore factors that distinguish Todd's paralysis from other indications that may lead to limb weakness in order to improve the diagnosis of Todd's paralysis.


2017 Annual Report Digest of the Renal Epidemiology Information Network (REIN) registry.
The French Renal Epidemiology and Information Network (REIN) registry started in 2002 with the goal to provide a tool to evaluate renal replacement therapy (RRT) practices and outcomes, to provide data for research and to support public health decisions related to end-stage renal disease ESRD. This summary presents the incidence and prevalence of RRT including kidney transplantation and wait-listing activity in 2017, and patients' survival and trends over 5 years. In 2017, 11 543 patients started RRT for ESRD, that is, incidence of 172 pmp. Between 2012 and 2017, the incidence of RRT increased by 1% per year [CI 95% (0.0; +2.0)]. On 31 December 2017, 87 275 patients were receiving RRT, that is, prevalence of 1294 pmp, 55% on dialysis, 45% with a functioning transplant. In 2017, 3782 kidney transplantations have been performed including 16% from a living donor, 13% being retransplantations and 15% pre-emptive transplantations. The median time on the waiting list was 19.7 months when only taking into account active waiting periods on the list. In 2017, 5280 new patients were registered on the renal transplant waiting list (i.e. 78.7 pmp). The number of patients considered as 'inactive' represented 45% of the patients on the list.


Anti-inflammatory effect of cinnamaldehyde in Helicobacter pylori induced gastric inflammation.
Cinnamomum cassia is widely employed for gastrointestinal complaints such as dyspepsia, flatulence, diarrhea, and vomiting. Studies report cinnamaldehyde (CM) as a major active constituent of cinnamon. The aim of this study was to evaluate the anti-inflammatory mechanism of CM on Helicobacter (H.) pylori-infected gastric epithelial cells in order to validate cinnamon traditional use in gastrointestinal (GI)-related disorders. AGS/MKN-45 cells and H. pylori (193C) were employed for co-culture experiments. Anti-H. pylori cytotoxic and anti-adhesion activity of CM were determined. Enzyme linked immunosorbent assay, real time polymerase chain reaction analysis and immunoblotting were used to measure the effect on interleukin-8 (IL-8) secretion/expression. The effect on activation of nuclear factor kappa B (NF-κB) was determined by immunoblot analysis. The non-cytotoxic CM (≤125 µM) was also non-bactericidal at the given time, suggesting the effect in H. pylori/cell co-culture system was not due to alteration in H. pylori viability or the toxicity to the cells. Also, CM did not show any anti-adhesion effect against H. pylori/cell co-culture. However, pre-incubation of the cells with CM significantly inhibited the IL-8 secretion/expression from H. pylori-infected cells (p<0.01). In addition, CM suppressed H. pylori-induced NF-κB activation and prevented degradation of inhibitor (I)-κB This study provides evidence that the anti-inflammatory effect of C. cassia on H. pylori-infected gastric cells is due to blockage of the NF-κB pathway by cinnamaldehyde. This agent can be considered as a potential candidate for in vivo and clinical studies against various H. pylori related gastric pathogenic processes.


Resolution and quantification of complex mixtures of polycyclic aromatic hydrocarbons in heavy fuel oil sample by means of GC × GC-TOFMS combined to multivariate curve resolution.
Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC × GC-TOFMS) combined to multivariate curve resolution-alternating least-squares (MCR-ALS) is proposed for the resolution and quantification of very complex mixtures of compounds such as polycyclic aromatic hydrocarbons (PAHs) in heavy fuel oil (HFO). Different GC × GC-TOFMS data slices acquired during the analysis of HFO samples and PAH standards were simultaneously analyzed using the MCR-ALS method to resolve the pure component elution profiles in the two chromatographic dimensions as well as their pure mass spectra. Outstandingly, retention time shifts within and between GC × GC runs were not affecting the results obtained using the proposed strategy and proper resolution of strongly coeluted compounds, baseline and background contributions was achieved. Calibration curves built up with standard samples of PAHs allowed the quantification of ten of them in HFO aromatic fractions. Relative errors in their estimated concentrations were in all cases below 6%. The obtained results were compared to those obtained by commercial software provided with GC × GC-TOFMS instruments and to Parallel Factor Analysis (PARAFAC). Inspection of these results showed improvement in terms of data fitting, elution process description, concentration relative errors and relative standard deviations.


Joint Effects of Fragmentation and Mercury Contamination on Marsh Periwinkle (Littoraria irrorata) Movement.
There are different ways contaminants can interact and enhance the effects of habitat fragmentation, such as modifying the movement of organisms. The present study tested the hypothesis that mercury exacerbates the effects of fragmentation by affecting the movement of the marsh periwinkle Littoraria irrorata and reducing the probability of snails crossing fragmented microlandscape experimental systems. How these changes could affect the search efficiency of organisms in the long term was assessed using hidden Markov models and random walks simulations. Bayesian nonlinear models were used to analyze the effects of fragmentation and contamination on the mean speed and mean directional change of organisms. Snail movement for control and two mercury-exposure treatments were recorded in microlandscapes with six different levels of habitat cover and three landscape replicates. The results indicated that exposed organisms had lower probabilities of crossing the landscape, reduced speed, and shifts in step length distributions. Both mercury exposure and habitat fragmentation affected the movement of the marsh periwinkle. Mercury exacerbated the effects of habitat fragmentation by affecting the cognition (e.g., route planning, orientation, and spatial learning) and movement of L. irrorata. Hence, the interaction of these stressors could further reduce the functional connectivity of landscapes and reduce the search efficiency of organisms. Environ Toxicol Chem 2022;41:1742-1753. © 2022 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


Adaptions of Lichen Microbiota Functioning Under Persistent Exposure to Arsenic Contamination.
Host-associated microbiota play an important role in the health and persistence of more complex organisms. In this study, metagenomic analyses were used to reveal microbial community adaptations in three lichen samples as a response to different arsenic concentrations at the sampling sites. Elevated arsenic concentrations at a former mining site expanded the spectrum and number of relevant functions in the lichen-associated microorganisms. Apparent changes affected the abundance of numerous detoxification-related genes, they were substantially enhanced in arsenic-polluted samples. Complementary quantifications of the arsenite S-adenosylmethionine methyltransferase (arsM) gene showed that its abundance is not strictly responding to the environmental arsenic concentrations. The analyzed samples contained rather low numbers of the arsM gene with a maximum of 202 gene copies μl-1 in total community DNA extracts. In addition, bacterial isolates were screened for the presence of arsM. Positive isolates were exposed to different As(III) and As(V) concentrations and tolerated up to 30 mM inorganic arsenic in fluid media, while no substantial biotransformations were observed. Obtained data deepens our understanding related to adaptions of whole microbial communities to adverse environmental conditions. Moreover, this study provides the first evidence that the integrity of bacteria in the lichen holobiont is maintained by acquisition of specific resistances.


Functional characterization of AP3, SOC1 and WUS homologues from citrus (Citrus sinensis).
Flowering and flower formation are defining features of angiosperms and the control of these developmental processes involves a common repertoire of genes which are shared among different species of flowering plants. These genes were first identified using various homeotic and flowering time mutants of Arabidopsis and snapdragon, and homologous genes have subsequently been isolated from a wide range of different plant species based on the conservation of protein sequence and function. Using degenerate reverse-transcriptase polymerase chain reaction, we have isolated one APETALA3-like (CitMADS8) and two SOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1)-like (CsSL1 and CsSL2) homologues from sweet orange (Citrus sinensis L.). Although the translated amino acid sequence of CitMADS8 shares many similarities with other higher plant APETALA3 proteins, CitMADS8 fails to complement the floral organ identity defects of the Arabidopsis ap3-3 mutant. By contrast, the two citrus SOC1-like genes, particularly CsSL1, are able to shorten the time taken to flower in the Arabidopsis wild-type ecotypes Columbia and C24, and functionally complement the late flowering phenotype of the soc1 mutant, essentially performing the endogenous function of Arabidopsis SOC1. Once flowering has commenced, interactions between specific flowering genes and a gene required for meristem maintenance, WUSCHEL, ensure that the Arabidopsis flower is a determinate structure with four whorls. We have isolated a citrus WUSCHEL homologue (CsWUS) that is capable of restoring most of the meristem function to the shoots and flowers of the Arabidopsis wus-1 mutant, implying that CsWUS is the functional equivalent of Arabidopsis WUSCHEL.


Imaging of cervical artery dissection.
Cervical artery dissection (CAD) may affect the internal carotid and/or the vertebral arteries. CAD is the leading cause of ischemic stroke in patients younger than 45 years. Specific treatment (aspirin or anticoagulants) can be implemented once the diagnosis of CAD has been confirmed. This diagnosis is based on detection of a mural haematoma on ultrasound or on MRI. The diagnosis can be suspected on contrast-enhanced MRA (magnetic resonance angiography) or CT angiography, in case of long stenosis, sparing the internal carotid bulb, or suspended, at the junction of V2 and V3 segments of the vertebral artery, in patients with no signs of atheroma of the cervical arteries. MRI is recommended as the first line imaging screening tool, including a fat suppressed T1 weighted sequence, acquired in the axial or oblique plane at 1.5T, or 3D at 3T. Complete resolution of the lumen abnormality occurred in 80% of cases, and CAD recurrence is rare, encountered in less than 5% of cases. Interventional neuroradiology (angioplasty and/or stenting of the dissected vessel) may be envisaged in rare cases of haemodynamic effects with recurring clinical infarctions in the short-term.


The influence of top-down, bottom-up and abiotic factors on the moose (Alces alces) population of Isle Royale.
Long-term, concurrent measurement of population dynamics and associated top-down and bottom-up processes are rare for unmanipulated, terrestrial systems. Here, we analyse populations of moose, their predators (wolves, Canis lupus), their primary winter forage (balsam fir, Abies balsamea) and several climatic variables that were monitored for 40 consecutive years in Isle Royale National Park (544 km2), Lake Superior, USA. We judged the relative importance of top-down, bottom-up and abiotic factors on moose population growth rate by constructing multiple linear regression models, and calculating the proportion of interannual variation in moose population growth rate explained by each factor. Our analysis indicates that more variation in population growth rate is explained by bottom-up than top-down processes, and abiotic factors explain more variation than do bottom-up processes. Surprisingly, winter precipitation did not explain any significant variation in population growth rate. Like that detected for two Norwegian ungulate populations, the relationship between population growth rate and the North Atlantic Oscillation was nonlinear. Although this analysis provides significant insight, much remains unknown: of the models examined, the most parsimonious explain little more than half the variation in moose population growth rate.


The BCL9-2 proto-oncogene governs estrogen receptor alpha expression in breast tumorigenesis.
The majority of human breast cancers express estrogen receptor alpha (ER), which is important for therapy with anti-estrogens. Here we describe the role of BCL9-2, a proto-oncogene previously characterized as co-activator of Wnt/ß-catenin signaling, for mammary tumorigenesis in mice and human. ER positive human breast cancers showed overexpression of BCL9-2 and tamoxifen treated patients with high BCL9-2 demonstrated a better survival. BCL9-2 was upregulated during puberty and pregnancy in normal mammary epithelia, but downregulated in the involuted gland. BCL9-2 overexpression in vivo delayed the mammary involution and induced alveolar hyperplasia. Moreover, aged BCL9-2 transgenic mice developed ductal-like mammary tumors with high nuclear ER expression. We found, that primary cell cultures of BCL9-2 breast tumors responded to tamoxifen treatment. Moreover, BCL9-2 regulated the expression of ER and the proliferation of human breast cancer cells independently of ß-catenin. Finally, we describe a novel mechanism, how BCL9-2 regulates ER transcription by interaction with Sp1 through the proximal ESR1 gene promoter. In summary, BCL9-2 induces ER positive breast cancers in vivo, regulates ER expression by a novel ß-catenin independent mechanism in breast cancer cells, and might predict the therapy response to tamoxifen treatment.


Expressive suppression and enhancement during music-elicited emotions in younger and older adults.
When presented with emotional visual scenes, older adults have been found to be equally capable to regulate emotion expression as younger adults, corroborating the view that emotion regulation skills are maintained or even improved in later adulthood. However, the possibility that gaze direction might help achieve an emotion control goal has not been taken into account, raising the question whether the effortful processing of expressive regulation is really spared from the general age-related decline. Since it does not allow perceptual attention to be redirected away from the emotional source, music provides a useful way to address this question. In the present study, affective, behavioral, and physiological consequences of free expression of emotion, expressive suppression and expressive enhancement were measured in 31 younger and 30 older adults while they listened to positive and negative musical excerpts. The main results indicated that compared to younger adults, older adults reported experiencing less emotional intensity in response to negative music during the free expression of emotion condition. No age difference was found in the ability to amplify or reduce emotional expressions. However, an age-related decline in the ability to reduce the intensity of emotional state and an age-related increase in physiological reactivity were found when participants were instructed to suppress negative expression. Taken together, the current data support previous findings suggesting an age-related change in response to music. They also corroborate the observation that older adults are as efficient as younger adults at controlling behavioral expression. But most importantly, they suggest that when faced with auditory sources of negative emotion, older age does not always confer a better ability to regulate emotions.


Outcomes of adult critically ill patients with hemophagocytic lymphohistiocytosis in united states-analysis from an administrative database from 2007 to 2015.
Severe infections caused by the novel coronavirus 2 display similarities to secondary hemophagocytic lymphohistiocytosis (HLH). However, HLH is a rare disease and has not been well described in critically ill patients. We used the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient care database publicly available in the United States to identify all adult discharges with Hemophagocytic syndrome (ICD-9 CM code 288.4) between 2007 and 2015. Critical illness was considered present if patient had either ICD-9 CM code indicating the requirement of invasive mechanical ventilation or the presence of shock. We used ICD-9-CM codes to identify various infections (inf-HLH), malignancies (mal-HLH) and autoimmune diseases associated with HLH (MAS-HLH) and classified them in their respective groups. Primary outcome was in-hospital mortality in critically ill patients. We developed multivariable regression model to examine variables associated with mortality in critically ill HLH patients. P value was kept at < 0.05. Of the 7420 (95% CI 6959-7881) estimated discharges with HLH, 2313 (31%) were critically ill. Of the critically ill patients, 442 (34%) were mal-HLH, 422 (43.3%) were inf-HLH, 403 (30.7%) were MAS-HLH and 1046 (27.3%) were unable to be classified. In hospital mortality rates were 6.4% in non-critically ill and 48.4% in critically ill patients. Among the subtypes of HLH, in-hospital mortality was 53% in mal-HLH, 49.4% in inf-HLH, 26% in MAS-HLH and 54.6% in unclassified group. On multivariable regression analysis, development of acute renal failure requiring hemodialysis (OR 2.06, 95% CI 1.29-3.3, P=0.002) and acute hepatic failure (OR 2.21, 95% CI 1.38-3.52, P=0.001) were significantly associated with higher mortality. Inpatient mortality of critically ill patients is remarkably high. Patients with MAS-HLH had better outcomes when compared to other groups of HLH.


Application of Size and Maturation Functions to Population Pharmacokinetic Modeling of Pediatric Patients.
Traditionally, dosage for pediatric patients has been optimized using simple weight-scaled methods, but these methods do not always meet the requirements of children. To overcome this discrepancy, population pharmacokinetic (PK) modeling of size and maturation functions has been proposed. The main objective of the present study was to evaluate a new modeling method for pediatric patients using clinical data from three different clinical studies. To develop the PK models, a nonlinear mixed effect modeling method was employed, and to explore PK differences in pediatric patients, size with allometric and maturation with Michaelis-Menten type functions were evaluated. Goodness of fit plots, visual predictive check and bootstrap were used for model evaluation. Single application of size scaling to PK parameters was statistically significant for the over one year old group. On the other hand, simultaneous use of size and maturation functions was statistically significant for infants younger than one year old. In conclusion, population PK modeling for pediatric patients was successfully performed using clinical data. Size and maturation functions were applied according to established criteria, and single use of size function was applicable for over one year ages, while size and maturation functions were more effective for PK analysis of neonates and infants.


The South African general practitioner-an overview.
The reasons for geographical maldistribution of South African doctors are discussed. Solutions are offered which involve vocational training for general practitioners in rural areas. It is believed that sophisticated primary health care is the best for all the peoples of South Africa.


Salivary peptide tyrosine-tyrosine 3-36 modulates ingestive behavior without inducing taste aversion.
Hormone peptide tyrosine-tyrosine (PYY) is secreted into circulation from the gut L-endocrine cells in response to food intake, thus inducing satiation during interaction with its preferred receptor, Y2R. Clinical applications of systemically administered PYY for the purpose of reducing body weight were compromised as a result of the common side effect of visceral sickness. We describe here a novel approach of elevating PYY in saliva in mice, which, although reliably inducing strong anorexic responses, does not cause aversive reactions. The augmentation of salivary PYY activated forebrain areas known to mediate feeding, hunger, and satiation while minimally affecting brainstem chemoreceptor zones triggering nausea. By comparing neuronal pathways activated by systemic versus salivary PYY, we identified a metabolic circuit associated with Y2R-positive cells in the oral cavity and extending through brainstem nuclei into hypothalamic satiety centers. The discovery of this alternative circuit that regulates ingestive behavior without inducing taste aversion may open the possibility of a therapeutic application of PYY for the treatment of obesity via direct oral application.


Pilot Trial of an Emergency Department-based Intervention to Promote Child Passenger Safety Best Practices.
Despite demonstrated effectiveness of child restraint systems (CRSs), use remains suboptimal. In this randomized pilot trial, we sought to determine the feasibility, acceptability, and potential efficacy of "Tiny Cargo, Big Deal" an ED-based intervention to promote guideline-concordant size-appropriate CRS use. Parents of children < 11 years old were recruited in two EDs and randomized in a 2 × 2 factorial design to four conditions: 1) generic information sheet, 2) tailored brochure mailed after the ED visit, 3) a single motivational interviewing-based counseling session in the ED, and 4) full intervention (counseling session plus tailored brochure). We assessed feasibility (recruitment, completion, follow-up rates) and acceptability (parent attitudes, uptake of information) in the ED, at 1 month and at 6 months. We obtained preliminary estimates of effect sizes of the intervention components on appropriate CRS use at 6-month follow-up. Of the 514 parents assessed for eligibility, 456 met inclusion criteria and 347 consented to participate. Enrolled parents were mostly mothers (88.1%); 48.7% were 18 to 29 years old; 52.5% were non-Hispanic, white; and 65.2% reported size-appropriate CRS use. Completion rates were 97.7% for baseline survey, 81.6% for counseling, 51.9% for 1-month follow-up, and 59.3% for 6-month follow-up. In the ED, 70.5% rated thinking about child passenger safety in the ED as very helpful. At 1 month, 70.0% expressed positive attitudes toward the study. Of 132 parents who reported receiving study mailings, 78.9% reviewed the information. Parents randomized to the full intervention demonstrated an increase (+6.12 percentage points) and other groups a decrease (-1.69 to -9.3 percentage points) in the proportion of children reported to use a size-appropriate CRS at 6-month follow-up. Suboptimal CRS use can be identified and intervened upon during a child's ED visit. A combined approach with ED-based counseling and mailed tailored brochures shows promise to improve size-appropriate CRS use.


Fibroblast growth factor 23 (FGF-23) concentrations in cats with early nonazotemic chronic kidney disease (CKD) and in healthy geriatric cats.
Fibroblast growth factor (FGF-23) has an important role in phosphate regulation. Its clinical relevance in cats with CKD has not been explored previously. The study objectives were (1) to determine whether FGF-23 concentrations are increased in nonazotemic cats, cats which developed azotemia within 12 months of screening compared with cats that remained non-azotemic, and (2) to evaluate the relationships between FGF-23 and PTH and FGF-23 and glomerular filtration rate (GFR). Sixty-two healthy client-owned geriatric cats, 14 of which developed azotemia during the 12-month follow-up period. Healthy nonazotemic cats were recruited prospectively into the study and followed for 12 months. At the study end-point, cats were categorized into 3 groups according to plasma creatinine concentration. PTH, FGF-23, and additional biochemical variables were evaluated at baseline and after 12 months. GFR was measured by a corrected slope-intercept iohexol clearance method. FGF-23 concentrations at baseline were found to be significantly increased in cats that developed azotemia (P = .001) compared with cats that did not develop azotemia. A significant positive relationship was identified between FGF-23 and PTH, whereas the relationship between FGF-23 and GFR was negative. FGF-23 concentrations predicted development of azotemia in geriatric cats. Positive relationships between FGF-23 and PTH suggest an association between FGF-23 and renal secondary hyperparathyroidism.


How an electric field can modulate the metal ion selectivity of protein binding sites: insights from DFT/PCM calculations.
Selecting the "right" metal cation from the surrounding intracellular/extracellular fluids is of crucial importance for proper functioning of metalloproteins. Over the course of a few billion years of cell evolution various strategies have been developed by the host protein or cell machinery to secure the most favorable conditions for cognate cation binding. The effect of internal/external electric fields, potentially capable of influencing the process of metal selectivity in proteins, however, remains an enigmatic and unexplored area of research. Several outstanding questions remain unanswered: (1) Can, and if so, to what extent, an electric field affect the competition between different metal species for protein ligands? (2) What type of binding sites (with specific architecture, polarizability, and solvent exposure) are more susceptible to electric stimuli? (3) How do the basic parameters of the electric field - its strength and directionality - modulate the selectivity of the metal binding site? (4) What is the upper limit of the electric field magnitude that preserves the integrity of the metal binding site? Here, by employing density functional theory calculations combined with continuum dielectric method computations, we endeavor to shed light on these questions by studying the thermodynamic outcome of the competition between Mg2+ and Ca2+ in a model EF-hand motif metal binding site under the influence of a dipole electric field with variable magnitude and directionality. The calculations reveal that the electric field (either internal or external) is a potent force that can modulate the metal selectivity of the binding site and thus can be added to the list of factors governing the metal competition in metalloproteins. An oriented external electric field with a particular directionality could be used as a switch to enhance or attenuate the preference of the binding site toward given metal species.


Analysis of Thermal Field Distribution in Winter over Beijing from 1985 to 2015 Using Landsat Thermal Data.
Heat supply, automobile exhaust, industrial production and decrease of thermal inertia in winter caused by the decrease of vegetation coverage leads to an obvious difference in the distribution of the land thermal field in the winter compared with other seasons. The Urban thermal field distribution in the winter directly affects the spread of air pollutants, which has important implications for analyzing the contribution of the thermal field to particulate air pollution. Atmospheric transmissivity and atmospheric upwelling/downwelling radiance in simulations are first calculated using the moderate spectral resolution atmospheric transmittance algorithm and computer model (MODTRAN). Then, we solve the radiative transfer model of the thermal infrared band by constructing a look-up table. In addition, the accuracy estimation is performed using the simulated data, showing that when the error range of emissivity and water vapor content are confined to ±0.005 and ±0.6, respectively, the temperature retrieval error are less than 0.348 and 2.117 K, respectively indicating the high retrieval accuracy of the method. In addition, the long-term sequenced Landsat TM and ETM+ data were selected to retrieve land surface temperature (LST) during 1985-2015. The analysis of the temporal and spatial distribution of thermal fields in Beijing show that the spatial and temporal variations are observable. The spatial variation covers four levels: high temperature is distributed within the second ring, low temperature loops are distributed between the second and the fifth ring, high temperature is distributed in the outer suburb areas and the lowest temperature is distributed in the western mountainous areas. Meanwhile, the temporal variation of thermal field distribution changed a great deal during the rapid development in the past 3 decades: the low temperature loop expanded from the third to the sixth ring; the intensity and scope of the heat island effect within the second ring increased gradually.


Correlation of body mass index with serum DDTs predicts lower risk of breast cancer before the age of 50: prospective evidence in the Child Health and Development Studies.
Many suspected breast cancer risk factors, including the pesticide dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyldichloroethylene (DDE), are stored in fat where they could influence carcinogenesis. We tested the hypothesis that the relationship of DDT and DDE (DDTs) with adiposity is modified by disposition to develop breast cancer. We predicted that concentrations of serum DDTs would be inversely correlated with body mass index (BMI) during active exposure when DDTs move into the larger fat pool. We described this correlation at an average of 17 years before breast cancer was diagnosed, in a prospective nested case-control study in the Child Health and Development Studies. Women entered the study during pregnancy from 1959 to 1966 when DDT was in active use. In total, 133 breast cancer cases were diagnosed under the age of 50 as of 1998. Mean time to diagnosis was 17 years. In total, 133 controls were matched to cases on birth year. We observed the expected inverse correlation of serum DDTs with BMI only in women who remained cancer-free and not in women who ultimately developed breast cancer (p for interaction < 0.05). Findings suggest that vulnerability to breast cancer before the age of 50 may be associated with an uncoupling of the inverse correlation between BMI and serum DDTs. Investigation into mechanisms may eventually reveal early biomarkers of breast cancer risk.


Use of biologic agents in pediatric psoriasis.
Psoriasis affects approximately 2 percent of the population. Approximately 30-45 percent of those affected first experience symptoms during childhood or adolescence. Although biologics have proven to be a relatively safe and effective treatment option for adults with psoriasis, limited information is available regarding the use of biologic agents in pediatric patients with psoriasis. The authors attempt to assess and summarize the available data on the use of biologic agents in patients under the age of 18, regardless of the indication, as well as to examine the limited available data on the use of biologics for psoriasis in the pediatric population. In doing so, the authors aim to provide guidance on the safety and efficacy of biologic therapies in pediatric patients with psoriasis. The authors' findings suggest that biologic agents should be considered for use solely in children with psoriasis that is refractory to conventional therapies, including children currently with severe, widespread, refractory pustular, plaque or psoriatic arthritis. Of all the currently available biologics, etanercept appears to have resulted in fewer and less severe side effects compared to infliximab in the juvenile rheumatoid arthritis population. In addition, while biologics are generally safe and effective in the pediatric population, serious adverse events (including infection), have been reported in the literature and should be taken into account before beginning treatment with any biologic agent. The physician and parents of the patient must carefully consider the risk-benefit ratio when deciding whether to use these medications. Additional randomized, controlled trials are needed to adequately assess the safety and efficacy of biologic medications for childhood psoriasis.


The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations.
Arachnoid granulations and villi from 23 brains from subjects aged 9 to 84 years were examined post mortem by serial sections with the light microscope and as whole or fractured preparations in the scanning electron microscope. The object of the study was to investigate the pathways within the arachnoid granulations by which cerebrospinal fluid (CSF) drains from the subarachnoid space to the sinus endothelium. At the base of each granulation, a thin neck of arachnoid projects through an aperture in the dural lining of the sinus and expands to form a core of collagenous trabeculae and interwoven channels. An apical cap of arachnoid cells, about 150 microns thick, surmounts the collagenous core, and channels extend through the cap to reach subendothelial regions of the granulation. Channels within the granulation are lined by compacted collagen and may contain macrophages. Following recent subarachnoid hemorrhage, erythrocytes are found in the channels, suggesting that the channels are in continuity with the subarachnoid space and are CSF drainage pathways. The cap region of the granulation is only attached to the endothelium over an area 300 microns in diameter; the rest of the granulation core is separated from the endothelium by a subdural space and a fibrous dural cupola. Scanning electron microscopy reveals an intact endothelial surface to the granulations with small perforating venous channels present on the apex of some granulations. The differences between human arachnoid granulations and arachnoid villi in animals are discussed, together with preliminary observations regarding the transition of villi into granulations in man.


Preventing stroke in patients with atrial fibrillation: current treatments and new concepts.
Atrial fibrillation (AF) is common, and it increases the risk of stroke. Placebo-controlled trials consistently showed that warfarin reduces the risk of stroke by two thirds, and a meta-analysis of trials of aspirin show a one-fifth reduction. Meta-analysis of trials directly comparing warfarin and aspirin shows that warfarin reduces the risk of stroke compared with aspirin by about one third. Major advisory bodies recommend risk stratification of patients with AF and prophylactic therapy with warfarin for patients at higher risk. There are several problems with warfarin therapy, which have resulted in a widely documented underuse. These problems include a narrow therapeutic window, marked variability in pharmacokinetics, and contraindications. There are new promising approaches to stroke prevention in AF. One of these is combination antiplatelet therapy. In a large randomized trial, the combination of dipyridamole and aspirin has been shown to have additive benefits against stroke. The combination of clopidogrel and aspirin results in additive benefits against vascular events, with only a modest increase in bleeding. A trial of combined antiplatelet therapy in AF is warranted. Occlusion of the left atrial appendage, either with a transvenous device or with surgery, is another strategy that is being explored. A direct thrombin inhibitor, ximelagatran, has been shown to have an excellent pharmacokinetic profile and is being developed as an oral agent for stroke prevention in AF, and it will not need regular monitoring.


Open and Arthroscopic Elbow Contracture Release: Tips and Pearls.
Elbow stiffness is a common consequence of trauma and can significantly limit the functionality of the affected arm. Intervention may be necessary for those with a motion arc less than 100°, but the decision to intervene should be based on individual patient needs. Restoration of joint motion in a stiff elbow can be challenging, time consuming, and costly. Nonsurgical treatment is the primary management option, and surgical intervention is considered for refractory stiffness. However, recurrent stiffness is a common issue following surgical elbow contracture release. An overview of relevant elbow anatomy, principles and technical pearls of arthroscopic and open contracture release, and postoperative rehabilitation methods to reduce the risk of recurrent stiffness is provided. It is important to tailor the treatment plan to each patient's unique needs and functional expectations.


[Evaluation of the usefulness of ultrasonography in the insertion and control of the intrauterine device].
The usefulness of ultrasonography in IUD insertion and control, was evaluated. A follow up of IUD localization, placed at the end of puerperium and in non puerperal patients, was done. The copper T IUD 200 was used, and was placed in 50 patients. Ultrasonographic study was done right after IUD placement, at one month and at three months; uterine longitudinal sections, as well as transversal ones, for adequate localization of IUD; data were taken for control and followup. There were no IUD expulsion, pregnancy, or uterine perforation. Conclusions were: 1. Ultrasonography is useful for IUD control. 2. IUD placement at the hospital is adequate. 3. There were no complications. 4. Alterations produced by IUD insertion are more frequent during the first month, and very scarce at third month. 5. Dysmenorrhea was most frequent after IUD insertion. 6. Echosonographic control of IUD is the most accurate method in order to know its localization within the uterine cavity.


Arterial Stiffness and Cardiorespiratory Fitness Impairment in the Community.
Background During exercise, a healthy arterial system facilitates increased blood flow and distributes it effectively to essential organs. Accordingly, we sought to understand how arterial stiffening might impair cardiorespiratory fitness in community-dwelling individuals. Methods and Results Arterial tonometry and maximum effort cardiopulmonary exercise testing were performed on Framingham Heart Study participants (N=2898, age 54±9 years, 53% women, body mass index 28.1±5.3 kg/m2). We related 5 arterial stiffness measures (carotid-femoral pulse wave velocity [CFPWV]: a measure of aortic wall stiffness; central pulse pressure, forward wave amplitude, characteristic impedance: measures of pressure pulsatility; and augmentation index: a measure of relative wave reflection) to multidimensional exercise responses using linear models adjusted for age, sex, resting heart rate, habitual physical activity, and clinical risk factors. Greater CFPWV, augmentation index, and characteristic impedance were associated with lower peak oxygen uptake (VO2; all P<0.0001). We observed consistency of associations of CFPWV with peak oxygen uptake across age, sex, and cardiovascular risk profile (interaction P>0.05). However, the CFPWV-peak oxygen uptake relation was attenuated in individuals with obesity (P=0.002 for obesity*CFPWV interaction). Higher CPFWV, augmentation index, and characteristic impedance were also related to cardiopulmonary exercise testing measures reflecting adverse O2 kinetics and lower stroke volume and peripheral O2 extraction but not to ventilatory efficiency, a prognostic measure of right ventricular-pulmonary vascular performance. Conclusions Our findings delineate relations of arterial stiffness and cardiorespiratory fitness in community-dwelling individuals. Future studies are warranted to evaluate whether the physiological measures implicated here may represent potential targets for improving cardiorespiratory fitness in the general population.


Residual Psychomotor Skills of Orderlies After a Novel Chest Compression Training Intervention.
High-quality chest compressions are essential to favorable patient outcomes after in-hospital cardiac arrest. Without frequent training, however, skill in performing compressions declines considerably. The Timely Chest Compression Training (T-CCT) intervention was introduced in 2019 as a quality improvement initiative to address this problem. The long-term impact of the T-CCT is unknown. A cohort study was conducted at a university-affiliated hospital in Quebec, Canada. Chest compression performance among orderlies was measured by using a subtractive scoring model and mannequins. The association of exposure to the T-CCT 10 months earlier with having an excellent chest compression performance (score ≥90 out of 100), after adjusting for potential confounders, was examined. A total of 412 orderlies participated in the study. More than half (n = 232, 56%) had been exposed to the T-CCT, and the rest (n = 180, 44%) had not. Nearly half (n = 106, 46%) of orderlies exposed to the T-CCT had an excellent performance, compared with less than one-third (n = 53, 30%) of nonexposed orderlies. In univariable analysis, previous exposure to the T-CCT was associated with 1.53 times greater risk of having an excellent performance (risk ratio, 1.53; 95% CI, 1.17-1.99). This effect remained after adjustment for potential confounders (risk ratio, 1.57; 95% CI, 1.19-2.07). The results of this study suggest that the T-CCT has a lasting effect on the psychomotor skills of orderlies 10 months after initial exposure. Further research should investigate the impact of the intervention on patient outcomes after in-hospital cardiac arrest.


A plate reader-compatible microchannel array for cell biology assays.
The use of microfluidic devices for studying cell biology holds considerable promise when compared to canonical culture systems. However, the lack of compatibility with existing infrastructure hinders the application of microfluidic devices in the life sciences. Here, we present a microchannel cell culture platform having both operational (compatible with plate readers and pipetting) and performance (lower detection limits, controlled microenvironment) advantages. We demonstrated rapid growth assays and immunocytochemistry on mammary epithelial cells (both a cell line and primary cells) in the microchannel arrays. The utilization of ubiquitous pipetting methods and plate reader endpoints lowers the barriers to use. The simplicity and flexibility of the platform, combined with the throughput of automated detection systems, will facilitate the adoption of microfluidic culture systems in biological laboratories.


Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer's disease.
Matrix metalloproteinases (MMPs) may play a role in the pathophysiology of Alzheimer's disease (AD). MMP-9 and tissue inhibitors of metalloproteinases (TIMPs) are elevated in postmortem brain tissue of AD patients. MMPs and TIMPs are found in neurons, microglia, vascular endothelial cells and leukocytes. The aim of this study was to determine whether circulating levels of MMP-2, MMP-9, TIMP-1 and TIMP-2 are elevated in the plasma of AD patients. We compared AD patients to age- and gender-matched controls as well as to Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) patients. There was constitutive expression of gelatinase A (MMP-2), and gelatinase B (MMP-9), in all the samples as shown by zymographic analysis. Levels of MMP-9 were significantly (P=0.003) elevated in the plasma of AD patients as compared to controls. Plasma levels of MMP-2, TIMP-1 and TIMP-2 were unchanged. There were no significant changes of MMP-2, MMP-9, TIMP-1 and TIMP-2 levels in PD and ALS samples. TIMP-1 and TIMP-2 were significantly correlated with MMP-9 in the AD patients. ApoE genotyping of plasma samples showed that levels of MMP-2, TIMP-1 and TIMP-2 and MMP-9 were not significantly different between the ApoE subgroups. These findings indicate that circulating levels of MMP-9 are increased in AD and may contribute to disease pathology.


UMD-CFTR: a database dedicated to CF and CFTR-related disorders.
With the increasing knowledge of cystic fibrosis (CF) and CFTR-related diseases (CFTR-RD), the number of sequence variations in the CFTR gene is constantly raising. CF and particularly CFTR-RD provide a particular challenge because of many unclassified variants and identical genotypes associated with different phenotypes. Using the Universal Mutation Database (UMD) software we have constructed UMD-CFTR (freely available at the URL: http://www.umd.be/CFTR/), the first comprehensive relational CFTR database that allows an in-depth analysis and annotation of all variations identified in individuals whose CFTR genes have been analyzed extensively. The system has been tested on the molecular data from 757 patients (540 CF and 217 CBAVD) including disease-causing, unclassified, and nonpathogenic alterations (301 different sequence variations) representing 3,973 entries. Tools are provided to assess the pathogenicity of mutations. UMD-CFTR also offers a number of query tools and graphical views providing instant access to the list of mutations, their frequencies, positions and predicted consequences, or correlations between genotypes, haplotypes, and phenotypes. UMD-CFTR offers a way to compile not only disease-causing genotypes but also haplotypes. It will help the CFTR scientific and medical communities to improve sequence variation interpretation, evaluate the putative influence of haplotypes on mutations, and correlate molecular data with phenotypes.


A Single-centre Study of COVID-19 Antibody.
ABSTARCT Four hundred and fifty-three SARS CoV-2 antibodies tests were conducted using Roche Elecsys® Anti SARS CoV-2 kits (detecting total antibodies) between June 13 to July 8, 2020 (25 days) on Cobas® e411 automatic analyser, based on electrochemiluminescence immunoassay (ECLIA) principle. Samples were collected from walk-in patients at our facility. Among them, 2 (0.4%) were found equivocal, 289 (63.8%) were found reactive, while 162 (35.8%) were found non-reactive. Moreover, reactive (symptomatic) cases were 262 (57.8%), reactive (asymptomatic) were 27 (6.0%), non-reactive (symptomatic) were 34 (7.5%), while non-reactive (asymptomatic) were 128 (28.3%). Most common symptom was fever, found in 262 (87.9%) individuals, followed by dry cough 146 (49.0%). Most number of reactive cases, i.e. 110 (42.6%) were those who got themselves tested between 15-21 days after onset of first symptom. Key Words: COVID-19, Coronavirus, Antibodies testing.


Impairment of cell-mediated immunity in mutation diabetic mice (db/db).
Mutation diabetes in the mouse occurs in the C57BL/Ks strain. All homozygous animals (db/db) develop obesity, elevated blood sugar levels and increased or normal blood insulin concentration. The defects in cellular immunity in db/db mice and their littermate controls were examined both in vivo and in vitro. Significant suppression of delayed footpad swelling and first and second set skin allograft rejection time were observed. In addition, DNA synthesis in spleen cells after nonspecific mitogen stimulation was markedly inhibited. Diabetic animals with a mean blood sugar of 512 +/- 101 mg/100 ml did not respond to exogenous insulin therapy by lowering their blood sugar levels or reversing the defect in DNA synthesis. Adding insulin to spleen cell culture in vitro had no demonstrable effect on their response to mitogens. Thus, mutation diabetic mice with their known defect in the peripheral utilization of insulin have markedly suppressed cell-mediated immune mechanisms.


Photic and pineal modulation of food anticipatory circadian activity rhythms in rodents.
Restricted daily feeding schedules entrain circadian oscillators that generate food anticipatory activity (FAA) rhythms in nocturnal rodents. The location of food-entrainable oscillators (FEOs) necessary for FAA remains uncertain. The most common procedure for inducing circadian FAA is to limit food access to a few hours in the middle of the light period, when activity levels are normally low. Although light at night suppresses activity (negative masking) in nocturnal rodents, it does not prevent the expression of daytime FAA. Nonetheless, light could reduce the duration or magnitude of FAA. If so, then neural or genetic ablations designed to identify components of the food-entrainable circadian system could alter the expression of FAA by affecting behavioral responses to light. To assess the plausibility of light as a potential mediating variable in studies of FAA mechanisms, we quantified FAA in rats and mice alternately maintained in a standard full photoperiod (12h of light/day) and in a skeleton photoperiod (two 60 min light pulses simulating dawn and dusk). In both species, FAA was significantly and reversibly enhanced in the skeleton photoperiod compared to the full photoperiod. In a third experiment, FAA was found to be significantly attenuated in rats by pinealectomy, a procedure that has been reported to enhance some effects of light on behavioral circadian rhythms. These results indicate that procedures affecting behavioral responses to light can significantly alter the magnitude of food anticipatory rhythms in rodents.


A comparison of cardiovascular disease associations of time-domain oximetry parameters in sleep apnoea cases from the Sleep Heart Health Study.
Polysomnograms (PSGs) contain a wealth of physiological information that is routinely recorded but not utilised in sleep studies. Intermittent hypoxia arising from obstructive sleep apnoea (OSA) events is an important risk in the later development of cardiovascular disease (CVD). Analysis of oximetry patterns from PSG studies may enable early assessment of CVD risk. The aim of this study was to compare associations of different time-domain oximetry patterns with incident CVD in OSA patients. All participants with OSA and no pre-existing CVD at baseline or within the first two years of follow-up, were selected from the Sleep Heart Health Study data and used for analysis (N=2878). We examined oximetry parameters that are calculated from desaturation events and from time series analysis and compared them to incident CVD outcomes using proportional hazards regression models adjusted for age, race, smoking, BMI, and sex. Our results show that were no associations between OSA oximetry parameters and incident CVD for OSA patients.


Effectiveness and toxicity of several DTPA broadening agents for biological ESR spectroscopy.
The effectiveness of a standard ESR broadening agent, potassium trioxalatochromiate (CrOx), for use with the spin-label tempone, was compared to that of diethylenetriaminepentaacetic acid (DTPA) containing an ion (Gd, Cr, Mn, Fe) with a large magnetic moment. Signal attenuation, line broadening, toxicity, and cell membrane permeability were compared. As a broadening agent, CrOx was most effective, followed by Fe-DTPA. CrOx proved mildly toxic while Gd-DTPA and Fe-DTPA were virtually non-toxic. The human red blood cell membrane was tested for permeability to Fe- and Gd-DTPA and found to be impermeable to both. In situations where toxicity to cells is critical, the DTPA chelates, particularly Fe-DTPA, may prove an acceptable substitute for CrOx.


The effect of hyperbaric oxygen on ischemia-reperfusion injury: an experimental study in a rat musculocutaneous flap.
The effect of hyperbaric oxygen is known to increase survival of ischemic tissue but its mechanism is not fully understood. The purpose of this study was to evaluate the effect of hyperbaric oxygen on a rat musculocutaneous flap versus ischemia-reperfusion injury, focusing on the mechanism involving the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) of endothelial cells and CD18 of neutrophils. A transverse rectus abdominis musculocutaneous (TRAM) flap (6 x 5 cm) supplied by a single superior epigastric vascular pedicle was elevated in 100 Sprague-Dawley rats. The rats were divided into 4 groups: group 0, sham (n = 10); group I, 4 hours of ischemia followed by reperfusion (n = 30); group II, 4 hours of ischemia and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, during the last 90 minutes of ischemia before reperfusion) followed by reperfusion (n = 30); and group III, 4 hours of ischemia followed by reperfusion and hyperbaric oxygen (100% oxygen, 2.5 atm absolute, after reperfusion for 90 minutes; n = 30). The study consisted of gross examination for flap survival, histology, immunohistochemical staining, myeloperoxidase assay, flow cytometric study of CD18, and Northern blot analysis on ICAM-1 messenger ribonucleic acid expression. Gross measurement of the flap showed increased survival in groups II and III compared with group I (P < 0.05). The leukocytes adherent to the endothelium were counted at 24 hours and on day 5. Group I leukocytes were significantly increased compared with groups II and III (P < 0.05). The myeloperoxidase assay of TRAM flaps at 24 hours revealed a significant increase in group I compared with groups II and III (P < 0.05). The expression of CD18 was similar between groups I, II, and III. Immunohistochemical staining for ICAM-1 and Northern blot analysis on ICAM-1 messenger ribonucleic acid showed decreased expression in groups II and III compared with group I. Throughout the analysis, groups II and III did not show any significant differences. These results suggests that hyperbaric oxygen reduces the accumulation of leukocytes in the TRAM flap, but not enough to prevent adhesion of neutrophils on endothelial cells; ischemia-reperfusion injury increases the expression of CD18 and ICAM-1 and causes increased adhesion of leukocytes on the endothelium; hyperbaric oxygen does not alter the expression of CD18 but decreases the expression of ICAM-1; and the point of application for hyperbaric oxygen, whether applied before or after reperfusion, did not show any differences in outcome. In conclusion, the application of hyperbaric oxygen against ischemia-reperfusion injury increases flap survival and the beneficial effect may be explained by a protective mechanism involving downregulation of ICAM-1 on endothelial cells.


A comprehensive immunotopographic map of human thymus.
We have achieved a comprehensive immunotopographic mapping of human thymus by using a large battery of monoclonal antibodies and the methodological refinement of comparative serial tissue section immunohistochemistry, allowing analysis of multiple phenotypes in the same tissue site. Previous immunohistochemical studies of thymus have concentrated on the majority T-cell and epithelial cell populations. Besides demonstrating the complexity of T-cell antigenic expression (e.g., simultaneous cortical expression of Leu 2, Leu 3, CALLA, Tdt, and Leu 6), we delineate surprisingly complex B-cell zones (e.g., septal B-follicles with DRC+C3d+ dendritic cells and zonal maturation of B-cells). Whereas septal B-follicles were found in 25% of cases, medullary B-cells were universally present as a substantial minority component. This expanded immunotopographic knowledge of the complex T-, B-, epithelial, and reticulum cell neighborhoods suggests that the thymus is an organ capable of a broad repertoire of immunological responses, not limited to T-cell development.


Activation of rat frizzled-1 promotes Wnt signaling and differentiation of mouse F9 teratocarcinoma cells via pathways that require Galpha(q) and Galpha(o) function.
The frizzled gene family of putative Wnt receptors encodes proteins that have a seven transmembrane-spanning motif characteristic of G-protein-linked receptors, although no loss-of-function studies have demonstrated a requirement for G-proteins for Wnt signaling by the gene product of frizzled-1. Medium conditioned by mouse F9 teratocarcinoma stem cells stably transfected to express either Xenopus Wnt-5a or Wnt-8 was used to test primitive endoderm formation of F9 stem cells. F9 stem cells expressing the rat Frizzled-1 receptors demonstrated endoderm formation in response to conditioned medium containing Wnt-8 but not to medium containing Wnt-5a. Primitive endoderm formation stimulated by Wnt-8 acting on the rat Frizzled-1 receptor was blocked by treatment with pertussis toxin by depletion of either Galpha(o) or Galpha(q) via antisense oligodeoxynucleotides, as well as by inhibitors of protein kinase C (bisindoylmaleimide) and of mitogen-activated protein kinase kinase (PD98059). Our results demonstrate the requirement for G-protein subunits Galpha(o) (a pertussis toxin substrate) and Galpha(q) for signaling by Frizzled-1, and an obligate role for the protein kinase C (likely mediated through stimulation of Galpha(q)) and mitogen-activated protein kinase network at the level of mitogen-activated protein kinase kinase.


[The development of a finger joint phantom for the optical simulation of early inflammatory rheumatic changes].
In the field of rheumatology, conventional diagnostic methods permit the detection only of advanced stages of the disease, which is at odds with the current clinical demand for the early diagnosis of inflammatory rheumatic diseases. Prompted by current needs, we developed a finger joint phantom that enables the optical and geometrical simulation of an early stage of rheumatoid arthritis (RA). The results presented here form the experimental basis for an evaluation of new RA diagnostic systems based on near infrared light. The early stage of RA is characterised mainly by a vigorous proliferation of the synovial membrane and clouding of the synovial fluid. Using a double-integrating-sphere technique, the absorption and scattering coefficients (mua, mus') are experimentally determined for healthy and pathologically altered synovial fluid and capsule tissue. Using a variable mixture of Intralipid Indian ink and water as a scattering/absorption medium, the optical properties of skin, synovial fluid or capsule can be selected individually. Since the optical and geometrical properties of bone tissue remain constant in early-stage RA, a solid material is used for its simulation. Using the finger joint phantom described herein, the optical properties of joint regions can be adjusted specifically, enabling an evaluation of their effects on an optical signal--for example, during fluorography--and the investigation of these effects for diagnostically useful information. The experimental foundation for the development of a new optical system for the early diagnosis of RA has now been laid.


The human minor histocompatibility antigen 1 is a RhoGAP.
The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells.


Emergency department boarding and adverse hospitalization outcomes among patients admitted to a general medical service.
Overcrowding in the emergency department (ED) has been associated with patient harm, yet little is known about the association between ED boarding and adverse hospitalization outcomes. We sought to examine the association between ED boarding and three common adverse hospitalization outcomes: rapid response team activation (RRT), escalation in care, and mortality. We conducted an observational analysis of consecutive patient encounters admitted from the ED to the general medical service between February 2013 and June 2015. This study was conducted in an urban, academic hospital with an annual adult ED census over 90,000. We defined boarding as patients with greater than 4h from ED bed order to ED departure to hospital ward. The primary outcome was a composite of adverse outcomes in the first 24h of admission, including RRT activation, care escalation to intensive care, or in-hospital mortality. A total of 31,426 patient encounters were included of which 3978 (12.7%) boarded in the ED for 4h or more. Adverse outcomes occurred in 1.92% of all encounters. Comparing boarded vs. non-boarded patients, 41 (1.03%) vs. 244 (0.90%) patients experienced a RRT activation, 53 (1.33%) vs. 387 (1.42%) experienced a care escalation, and 1 (0.03%) vs.12 (0.04%) experienced unanticipated in-hospital death, within 24h of ED admission. In unadjusted analysis, there was no difference in the composite outcome between boarding and non-boarding patients (1.91% vs. 1.91%, p=0.994). Regression analysis adjusted for patient demographics, acuity, and comorbidities also showed no association between boarding and the primary outcome. A sensitivity analysis showed an association between ED boarding and the composite outcome inclusive of the entire inpatient hospital stay (5.8% vs. 4.7%, p=0.003). Within the first 24h of hospital admission to a general medicine service, adverse hospitalization outcomes are rare and not associated with ED boarding.


Glutaraldehyde test for the rapid diagnosis of pulmonary and extra-pulmonary tuberculosis in an area with high tuberculosis incidence.
Tuberculosis (TB) remains one of the leading causes of morbidity and mortality worldwide. The primary method for controlling TB is the rapid and accurate identification of infected individuals. Immune response exploitation represents one of the main methods used for early TB diagnosis; however, few studies have reported that whole blood originating from TB-infected patients gels faster in the presence of aldehyde than blood originating from healthy subjects, which is the focus of the current study. The study objectives are to determine the diagnostic value of a glutaraldehyde test (GT) in pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB) and to assess its performance compared with light-emitting diode fluorescence microscopy (LED-FM). This study included 272 specimens (176 suspected PTB specimens and 96 suspected EPTB specimens). Of the 272 patients, 98 patients had TB infection confirmed by culture (64 PTB cases and 34 EPTB cases), and 174 patients had no TB infection. The gold standard technique (culture) was used as reference to verify the GT's performance. The GT showed a high sensitivity (96.9%) and specificity (82.1%) for PTB with a good positive predictive value (PPV = 75.6%) and negative predictive value (NPV = 97.9%). For EPTB, the GT showed a sensitivity of 91.2% and a specificity of 77.4%, with PPV = 68.9% and NPV = 94.1%. LED-FM had lower sensitivities for PTB (65.6%) and EPTB (42.1%) and an excellent specificity of 100%, with PPV = 100% and NPV = 100%. We concluded that GT is rapid, easy, simple and cost-effective and does not require qualified personnel with a specific background or sophisticated equipment like molecular biology or mycobacterium-specific genotyping techniques. These qualities make the GT attractive for use in low- and high-income countries in addition to other conventional methods, particularly culture, which continues to be the gold standard.


A Cadaveric Study of Metatarsal Length and Its Function in the Metatarsal Formula and Forefoot Pathology.
The metatarsal parabola or formula is an important principle in assessing normal foot structure and pathology. To understand what effect the positions of the distal ends of the metatarsals have on foot function, the relative length of each metatarsal must be considered. The purpose of this study was to investigate what the normal metatarsal formula is and compare these findings with previous research. Measurements of metatarsal lengths were taken from 20 feet of five male and five female cadavers. The mean lengths were used to identify each donor's metatarsal formula. On average, the most common formula presented was in the order of metatarsals II>III>IV>V>I. These findings differ from historic measurements and raise questions regarding which metatarsal formula is considered normal. Further investigation is needed to standardize a more reliable method of measuring metatarsal lengths for evaluating foot biomechanics and planning forefoot surgeries.


ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR are associated with alcoholism in Mexican American men living in Los Angeles.
The aim of the present study was to use a candidate gene approach to identify the genetic risk factors for alcoholism in Mexican Americans residing in the Los Angeles area. The genes selected include alcohol metabolizing genes and neurotransmitter genes, which have been shown in the literature to be associated with alcoholism in other ethnic groups. Thirteen allelic variants from seven genes were evaluated for their role in alcoholism using alcoholic (n = 200) and nonalcoholic (n = 251) Mexican Americans. Those polymorphic sites include alcohol dehydrogenase (ADH1B, ADH1C), aldehyde dehydrogenase (ALDH2), cytochrome P-450 2E1 (CYP2E1) TaqI, DraI, RsaI, dopamine D2 receptor (DRD2) TaqI A, B, intron 6, exon 7, -141C Ins/Del, serotonin transporter (5-HTTLPR), and GABAA receptor beta3 subunit (GABRbeta3). The results demonstrate that Mexican Americans have extremely low allele frequency for both ALDH2*2 and ADH1B*2 and a relatively high frequency of ADH1C*2 and CYP2E1 c2 alleles. ADH1B*1, ADH1C*2, DRD2 (-141C Ins), and 5-HTTLPR were associated with alcoholism in Mexican Americans (p < 0.05). DRD2 Ins was associated with alcoholism in those alcoholics who carried the ADH1B*2 or ADH1C*1 protective alleles (p = 0.032 in genotype level and p = 0.015 in allele level). DRD2 TaqI A and B alleles were associated with early age of onset for drinking (p = 0.016 for TaqI A1 and p = 0.049 for TaqI B1 allele). Together, the data reveal unique genetic patterns in Mexican Americans that may be in part responsible for the heightened risk for alcoholism and alcohol-associated health problems in this population.


Effects of Salt and Fat Combinations on Taste Preference and Perception.
Fat and salt are a common and attractive combination in food and overconsumption of either is associated with negative health outcomes. The major aim was to investigate contributions and interactions of salt and fat on taste pleasantness and perception. The minor aim was to investigate individual fat taste sensitivity (detection threshold of oleic acid [C18:1]) on pleasantness for fat. In a complete factorial design, 49 participants (18-54 years, 12 males) tasted tomato soups with 4 different fat concentrations (0-20%) and 5 different salt concentrations (0.04-2.0%). The preferred concentration and the discrimination ability for both fat and salt were determined by ranking tests. Results show that salt and fat affected pleasantness separately (P < 0.01), with salt having the strongest effect. Fat concentrations 0%, 5%, and 10% did not differ in pleasantness, whereas 20% was less pleasant (P < 0.05). There were no interactions for fat and salt on pleasantness or saltiness and fattiness intensity. Fat taste sensitive participants preferred lower fat concentrations than less sensitive participants (P = 0.008). In conclusion, the strong effect of salt on pleasantness in this study suggests that salt, rather than fat, play a major role in the attraction to savory fatty foods.


Anti-inflammatory effects of three kinds of traditional Mongolian medicine monomer and its combination on LPS-stimulated RAW264.7 macrophages.
Traditional Mongolian Medicine (TMM) exhibits useful biological activities including antifungal, antibacterial, and anti-inflammatory actions. The mechanisms of TMM in anti-inflammation were still unclear. The aim of this study was to investigate the effects of the three main monomers (geniposide, gallate, berberine hydrochloride and a mixture of them) of a traditional Mongolian medicine on cell survival and the proinflammatory cytokines signaling pathways which are activated by bacterial lipopolysaccharides (LPS). Mouse macrophage-like cell line RAW264.7 was used as a model of inflammation to investigate the anti-inflammatory effects of three TMM momomers and their combination. RT-PCR and Western blot was used to quantify the change of mRNA and protein levels of cytokines, Toll-like receptor-4 (TLR4) and Nuclear Factor-κB (NF-κB) and its inhibitor IκB. The non-radioactive electrophoresis mobility shift assay (EMSA) was used to evaluate the binding activity of NF-κB. The monomers and their combination exhibited a potent anti-inflammatory effect for suppressing the LPS-evoked secretion of proinflammatory cytokines IL-1β, IL-6 and TNFα. Furthermore, the monomers and their combination attenuated activation of NF-κB and expression of TLR4 at both mRNA and protein levels, the upstream player of the LPS-TLR4-cytokines/ NF-κB signaling pathway. The Mongolia herbal compound exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemo-prevention of inflammatory diseases.