Expression of the transforming growth factor beta isoforms in inflammatory cells of nasal polyps.
To determine the expression and the potential role of transforming growth factor beta (TGF-beta) in nasal polyposis. Comparison of TGF-beta expression between normal and inflammatory nasal mucosa and polyps; in inflammatory nasal polyps, characterization of the TGF-beta isoforms expression and their potential location in macrophages and eosinophils. Patients and samples were selected at the Hôpital Intercommunal, Créteil, France, and immunohistochemistry and immunoblots were performed at the Institut National de la Sante et de la Recherche Medicale U296 (Universite Paris XII, France). Nasal polyps and nasal mucosa were sampled in 21 patients during ethmoidectomy, and muscosa was sampled in 6 healthy patients during rhinoplasty. Immunohistochemistry and Western blot analysis were performed using specific antibodies to TGF-beta1-3, TGF-beta1, TGF-beta2, and TGF-beta3 isoforms. Double labeling was also performed using anti-TGF-beta1 antibody together with macrophages or eosinophil-specific antibodies. The expression of TGF-beta(1-3) was significantly higher in inflammatory nasal polyps than in inflammatory nasal mucosa and higher in inflammatory nasal mucosa than in nasal mucosa from healthy patients. Transforming growth factor beta1 was the main isoform detected in inflammatory nasal polyps, and it was present in numerous macrophages and in some eosinophils. Transforming growth factor beta, mainly TGF-beta1, is strongly expressed in inflammatory nasal mucosa, where it could be produced by macrophages and eosinophils. Transforming growth factor beta could induce epithelium and connective tissue modifications and therefore be involved in the pathogenesis of nasal polyposis.


Age-Specific Transmissibility Change of COVID-19 and Associations With Breathing Air Volume, Preexisting Immunity, and Government Response.
The comprehensive impacts of diverse breathing air volumes and preexisting immunity on the host susceptibility to and transmission of COVID-19 at various pandemic stages have not been investigated. We classified the US weekly COVID-19 data into 0-4, 5-11, 12-17, 18-64, and 65+ age groups and applied the odds ratio (OR) of incidence between one age group and the 18-64 age group to delineate the transmissibility change. The changes of incidence ORs between May, 2020 and November, 2021 were 0.22-0.66 (0-4 years), 0.20-1.34 (5-11 years), 0.39-1.04 (12-17 years), and 0.82-0.73 (65+ years). The changes could be explained by age-specific preexisting immunity including previous infection and vaccination, as well as volumes of breathing air. At the early pandemic, the ratio that 0-4-year children exhaled one-fifth of air and discharge a similar ratio of viruses was closely associated with incidence OR between two age groups. While, after a rollout of pandemic and vaccination, the much less increased preexisting immunity in children resulted in rapidly increased OR of incidence. The ARIMA model predicted the largest increase of relative transmissibility in 6 coming months in 5-11-year children. The volume of breathing air may be a notable factor contributing to the infectivity of COVID-19 among different age groups of patients. This factor and the varied preexisting greatly shape the transmission of COVID-19 at different periods of pandemic among different age groups of people.


Diagnosis, treatment and long-term outcomes of autoimmune pancreatitis in Spain based on the International Consensus Diagnostic Criteria: A multi-centre study.
Autoimmune pancreatitis (AIP) is a form of chronic pancreatitis that has been reported worldwide for the last two decades. The aim of this study is to analyse the clinical profile of patients from Spain with AIP, as well as treatments, relapses and long-term outcomes. Data from 59 patients with suspected AIP that had been diagnosed in 15 institutions are retrospectively analysed. Subjects are classified according to the International Consensus Diagnostic Criteria (ICDC). Patients with type 1 AIP (AIP1) and type 2 AIP (AIP2) are compared. Kaplan-Meier methodology is used to estimate the overall survival without relapses. Fifty-two patients met ICDC, 45 patients were AIP1 (86.5%). Common manifestations included abdominal pain (65.4%) and obstructive jaundice (51.9%). Diffuse enlargement of pancreas was present in 51.0%; other organ involvement was present in 61.5%. Serum IgG4 increased in 76.7% of AIP1 patients vs. 20.0% in AIP2 (p = 0.028). Tissue specimens were obtained in 76.9%. Initial successful treatment with steroids or surgery was achieved in 79.8% and 17.3%, respectively. Maintenance treatment was given in 59.6%. Relapses were present in 40.4% of AIP1, with a median of 483 days. Successful long-term remission was achieved in 86.4%. AIP1 is the most frequent form of AIP in Spain in our dataset. Regularly, ICDC allows AIP diagnosis without the need for surgery. Steroid and chirurgic treatments were effective and safe in most patients with AIP, although maintenance was required many times because of their tendency to relapse. Long-term serious consequences were uncommon.


A new role for human dyskerin in vesicular trafficking.
Dyskerin is an essential, conserved, multifunctional protein found in the nucleolus, whose loss of function causes the rare genetic diseases X-linked dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. To further investigate the wide range of dyskerin's biological roles, we set up stable cell lines able to trigger inducible protein knockdown and allow a detailed analysis of the cascade of events occurring within a short time frame. We report that dyskerin depletion quickly induces cytoskeleton remodeling and significant alterations in endocytic Ras-related protein Rab-5A/Rab11 trafficking. These effects arise in different cell lines well before the onset of telomere shortening, which is widely considered the main cause of dyskerin-related diseases. Given that vesicular trafficking affects many homeostatic and differentiative processes, these findings add novel insights into the molecular mechanisms underlining the pleiotropic manifestation of the dyskerin loss-of-function phenotype.


ARAS: an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes.
Automated protocols for measuring and dispensing solutions containing radioisotopes are essential not only for providing a safe environment for radiation workers but also to ensure accuracy of dispensed radioactivity and an efficient workflow. For this purpose, we have designed ARAS, an automated radioactivity aliquoting system for dispensing solutions containing positron-emitting radioisotopes with particular focus on fluorine-18 ((18)F). The key to the system is the combination of a radiation detector measuring radioactivity concentration, in line with a peristaltic pump dispensing known volumes. The combined system demonstrates volume variation to be within 5 % for dispensing volumes of 20 μL or greater. When considering volumes of 20 μL or greater, the delivered radioactivity is in agreement with the requested amount as measured independently with a dose calibrator to within 2 % on average. The integration of the detector and pump in an in-line system leads to a flexible and compact approach that can accurately dispense solutions containing radioactivity concentrations ranging from the high values typical of [(18)F]fluoride directly produced from a cyclotron (~0.1-1 mCi μL(-1)) to the low values typical of batches of [(18)F]fluoride-labeled radiotracers intended for preclinical mouse scans (~1-10 μCi μL(-1)).


New insights into the suppression of inflammation and lipid accumulation by JAZF1.
Atherosclerosis is one of the leading causes of disease and death worldwide. The identification of new therapeutic targets and agents is critical. JAZF1 is expressed in many tissues and is found at particularly high levels in adipose tissue (AT). JAZF1 suppresses inflammation (including IL-1β, IL-4, IL-6, IL-8, IL-10, TNFα, IFN-γ, IAR-20, COL3A1, laminin, and MCP-1) by reducing NF-κB pathway activation and AT immune cell infiltration. JAZF1 reduces lipid accumulation by regulating the liver X receptor response element (LXRE) of the SREBP-1c promoter, the cAMP-response element (CRE) of HMGCR, and the TR4 axis. LXRE and CRE sites are present in many cytokine and lipid metabolism gene promoters, which suggests that JAZF1 regulates these genes through these sites. NF-κB is the center of the JAZF1-mediated inhibition of the inflammatory response. JAZF1 suppresses NF-κB expression by suppressing TAK1 expression. Interestingly, TAK1 inhibition also decreases lipid accumulation. A dual-targeting strategy of NF-κB and TAK1 could inhibit both inflammation and lipid accumulation. Dual-target compounds (including prodrugs) 1-5 exhibit nanomolar inhibition by targeting NF-κB and TAK1, EGFR, or COX-2. However, the NF-κB suppressing activity of these compounds is relatively low (IC50 > 300 nM). Compounds 6-14 suppress NF-κB expression with IC50 values ranging from 1.8 nM to 38.6 nM. HS-276 is a highly selective, orally bioavailable TAK1 inhibitor. Combined structural modifications of compounds using a prodrug strategy may enhance NF-κB inhibition. This review focused on the role and mechanism of JAZF1 in inflammation and lipid accumulation for the identification of new anti-atherosclerotic targets.


A cascade extraction of active phycocyanin and fatty acids from Galdieria phlegrea.
The setup of an economic and sustainable method to increase the production and commercialization of products from microalgae, beyond niche markets, is a challenge. Here, a cascade approach has been designed to optimize the recovery of high valuable bioproducts starting from the wet biomass of Galdieria phlegrea. This unicellular thermo-acidophilic red alga can accumulate high-value compounds and can live under conditions considered hostile to most other species. Extractions were performed in two sequential steps: a conventional high-pressure procedure to recover phycocyanins and a solvent extraction to obtain fatty acids. Phycocyanins were purified to the highest purification grade reported so far and were active as antioxidants on a cell-based model. Fatty acids isolated from the residual biomass contained high amount of PUFAs, more than those recovered from the raw biomass. Thus, a simple, economic, and high effective procedure was set up to isolate phycocyanin at high purity levels and PUFAs.


The purification and characterization of plasma membranes and the subcellular distribution of adenylate cyclase in mouse parotid gland.
1. Plasma membranes have been purified 17-fold from mouse parotid gland homogenates prepared in hypertonic sucrose media using differential centrifugation. The method is fast and simple. The membranes were characterised by electron microscopy, enzyme composition and chemical composition. Further purification was achieved by isopycnic centrifugation in discontinuous sucrose gradients. 2. The purified membranes contain an adenylate cyclase activity which is stimulated by isoproterenol and fluoride. Only 50% of the total adenylate cyclase activity sedimented in the plasma membrane fraction. The rest of the activity resided in the crude nuclear and mitochondrial pellets. However, this adenylate cyclase activity was not associated with these organelles but with membrane fragments in the pellets. Purified nuclei did not contain adenylate cyclase activity. 3. Adenylate cyclase activity was also localised by electron microscopic cytochemistry. Besides being found at the plasma membrane, large amounts of adenylate cyclase were found in a small proportion of the vesicles within the acinar cells, which appeared to be secondary lysosomes. 4. Adenylate cyclase activities, under standard assay conditions, are proportional to the time of incubation and the concentration of enzyme. The enzyme requires both Mg-2+ and CA-2+ for activity. Isoproterenol increased activity 2-fold and this increase is abolished by beta-adrenergic blocking agents.


DNA methylation patterns of behavior-related gene promoter regions dissect the gray wolf from domestic dog breeds.
A growing body of evidence highlights the relationship between epigenetics, especially DNA methylation, and population divergence as well as speciation. However, little is known about how general the phenomenon of epigenetics-wise separation of different populations is, or whether population assignment is, possible based on solely epigenetic marks. In the present study, we compared DNA methylation profiles between four different canine populations: three domestic dog breeds and their ancestor the gray wolf. Altogether, 79 CpG sites constituting the 65 so-called CpG units located in the promoter regions of genes affecting behavioral and temperamental traits (COMT, HTR1A, MAOA, OXTR, SLC6A4, TPH1, WFS1)-regions putatively targeted during domestication and breed selection. Methylation status of buccal cells was assessed using EpiTYPER technology. Significant inter-population methylation differences were found in 52.3% of all CpG units investigated. DNA methylation profile-based hierarchical cluster analysis indicated an unambiguous segregation of wolf from domestic dog. In addition, one of the three dog breeds (Golden Retriever) investigated also formed a separate, autonomous group. The findings support that population segregation is interrelated with shifts in DNA methylation patterns, at least in putative selection target regions, and also imply that epigenetic profiles could provide a sufficient basis for population assignment of individuals.


Trait profiling and genotype selection in oilseed rape using genotype by trait and genotype by yield*trait approaches.
Selection and breeding for high-yielding in oilseed rape have always been one of the leading objectives for oilseed rape breeders. This process becomes more complicated when all quantitative traits are considered in selection in addition to grain yield. In the present study, 18 oilseed rape genotypes along with 2 check cultivars (RGS003 and Dalgan) were evaluated across 16 environments (a combination of 2 years and eight locations) in the tropical climate regions of Iran during 2018-2019 and 2019-2020 cropping seasons. The experiments were conducted in a format of randomized complete block design (RCBD) with three replications. The obtained multienvironmental trial data were utilized to conduct multivariate analysis, genotype by trait (GT) biplot, and genotype by yield*trait (GYT) biplot (Breeding, Genetics and Genomics, 1:2019). The GT and GYT biplot accounted for 55.5% and 93.6% of the total variation in the first two main components. Based on multivariate analysis and GT biplot, pod numbers in plant (PNP) and plant height (PH) were chosen as two key traits in spring oilseed rape genotypes for indirect selection due to high variation, strong positive correlation with grain yield (GY), and their high representatively and discriminability in genotype selection. The mean × stability GT biplot represented G10 (SRL-96-17) as the superior genotype. Based on the mean × stability GYT biplot, eight above-average genotypes were identified that took high scores in stability, high-yielding, and all evaluated quantitative traits at the same time. Based on the superiority index of GYT data, G10 (SRL-96-17) and G5 (SRL-96-11) indicated the best yield-trait combinations profile and ranked above check cultivars and then selected as superior genotypes. Similarly, cluster analysis using the WARD method also separated eight superior genotypes. Based on the result of the present study, GT ad GYT methodologies are recommended for trait profiling and genotype selection in oilseed rape breeding projects, respectively.


Flebogamma(®) 5 % DIF Intravenous Immunoglobulin for Replacement Therapy in Children with Primary Immunodeficiency Diseases.
The previous studies with Flebogamma(®) 5 % DIF intravenous immunoglobulin (IVIG) contained insufficient numbers of pediatric subjects to fully warrant a pediatric indication by the FDA. The objective of this study was to evaluate the efficacy, safety, and pharmacokinetics of Flebogamma® 5 % DIF for replacement therapy in children (age 2-16) with primary immunodeficiency diseases (PIDD). IVIG was administered at eight clinical sites to 24 subjects with well-defined PIDD at a dose of 300-800 mg/kg every 21-28 days for 12 months. The pharmacokinetics endpoint in this study was the dose-adjusted increment of the serum IgG trough levels. The calculated serious bacterial infection rate was 0.05/subject/year. The incidence of adverse events considered potentially related to IVIG during or within 72 h after completing an infusion was within the FDA guidance threshold of <40 % at each time point. Dose-adjusted incremental IgG levels remained approximately equal to or slightly greater than pre-study IgG levels (between 800 and 1000 mg/dL throughout) when the subjects were treated with IVIG therapy other than Flebogamma(®) DIF 5 % indicating no evidence of a different pharmacokinetic profile in this pediatric population if compared to those profiles in previous Flebogamma studies in predominately adult populations. Flebogamma(®) 5 % DIF is efficacious and safe, has adequate pharmacokinetic properties, is well-tolerated, and maintains the profile of Flebogamma(®) 5 % for the treatment of children with primary humoral immunodeficiency diseases.


Plasmodium yoelii YM MAEBL protein is coexpressed and colocalizes with rhoptry proteins.
We have previously cloned genes from multiple rodent malaria species exhibiting characteristics of the genes encoding Duffy binding like-erythrocyte binding proteins (DBL-EBP). Homology is seen in the intron/exon structure of the genes and in the carboxyl terminal region (including the deduced carboxyl cysteine-rich domain) of the proteins they encode. However, the amino termini of these proteins are not homologous to the DBL-EBP but contain tandem cysteine-rich regions that are similar to the cysteine-rich region of AMA-1 (apical membrane antigen-1), a rhoptry protein. This new family of proteins has been termed MAEBL and these are paralogues of both AMA-1 and the DBL-EBP. Serum against the carboxyl cysteine-rich region of the Plasmodium yoelii YM MAEBL reacted to parasites with a punctate fluorescence pattern characteristic of apical organelle proteins and also localized MAEBL to the surface of merozoites within schizonts. This antiserum immunoprecipitated a protein doublet (120/128 kDa) that was unexpectedly insoluble when compared to members of the DBL-EBP. Characterization of MAEBL was extended through colocalization studies comparing the P. yoelii YM MAEBL to other parasite proteins. This protein appeared to be located in the rhoptry organelles as it colocalized with both AMA-1 and the P. yoelii 235 kDa rhoptry proteins within parasites. In addition, MAEBL is expressed relatively early in schizont development and appears on the merozoite surface after segmentation. Both the pattern and time of expression of the P. yoelii YM MAEBL are consistent with a rhoptry rather than a microneme protein.


Delineating bone's interstitial fluid pathway in vivo.
Although interstitial fluid flow has been suggested to play a role in bone adaptation and metabolism, the constituents and ultrastructure of this interstitial fluid pathway are not well understood. Bone's lacunar-canalicular porosity is generally believed to be a continuous interstitial fluid pathway through which osteocytes sense external mechanical loading as well as obtain nutrients and dispose of wastes. Recent electron microscopy studies have suggested that a fiber matrix surrounds the osteocytic cell processes and fills this pericellular fluid space. However, studies injecting tracer molecules into the bone vasculature have provided conflicting results about the pore size or the fiber spacing of the interstitial fluid pathway. In addition, whether the smaller collagen-apatite porosity in adult bone is also a continuous fluid pathway is still unclear. To delineate bone's interstitial fluid pathway, four tracers of various size were injected into rats: reactive red (approximately 1 nm), microperoxidase (MP, approximately 2 nm), horseradish peroxidase (HRP, approximately 6 nm), and ferritin (approximately 10 nm). Five minutes after injection, the tibiae were harvested and processed using histological protocols optimized to minimize processing time to reduce possible redistribution of tracer molecules. The number of blood vessels and osteocytic lacunae labeled with the tracers per unit bone area was then measured for mid-diaphysial cross-sections of the tibia. While none of the tracers was detected within the mineralized bone matrix (the collagen-apatite porosity) using light microscopy, all the tracers except ferritin were found to pass through the canaliculi and appear in the osteocytic lacunae. These results indicate that while small tracers (<6 nm) readily pass through the lacunar-canalicular porosity in the absence of mechanical loading, there appears to be an upper limit or cutoff size between 6 and 10 nm for molecular movement from bone capillaries to osteocytic lacunae in rat long bone. This range of pore size contains the most likely fiber spacing (approximately 7 nm) that has been proposed for the lacunar-canalicular annular space based on the presence of a proteoglycan fiber matrix surrounding the osteocyte.


Efficient Photo-Assisted Thermal Selective Oxidation of Toluene Using N-Doped TiO2.
Selective oxidation of toluene is a key reaction to produce high value-added products but remains a big challenge. In this study, we introduce a nitrogen-doped TiO2 (N-TiO2) catalyst to create more Ti3+ and oxygen vacancy (OV), which act as active sites for selective oxidation of toluene via activating O2 to superoxide radical (•O2-). Interestingly, the resulting N-TiO2-2 exhibited an outstanding photo-assisted thermal performance with a product yield of 209.6 mmol·gcat-1 and a toluene conversion of 10960.0 μmol·gcat-1·h-1, which are 1.6 and 1.8 times greater than those obtained under thermal catalysis. We showed that the enhanced performance under photo-assisted thermal catalysis was attributed to more active species generation by making full use of photogenerated carriers. Our work suggests a viewpoint to apply a noble-metal-free TiO2 system in the selective oxidation of toluene under solvent-free conditions.


Fluorometric lateral flow immunoassay for simultaneous determination of three mycotoxins (aflatoxin B1, zearalenone and deoxynivalenol) using quantum dot microbeads.
A fluorometric lateral flow immunoassay (LFA) is described for the simultaneous determination of the mycotoxins aflatoxin B1 (AFB1), zearalenone (ZEN) and deoxynivalenol (DON). The method is based on the use of CdSe/SiO2 quantum dot microbeads (QBs) with a mean diameter of 106 nm. These have strong red luminescence (with excitation/emission peaks at 365/622 nm) which results in enhanced sensitivity. The QBs binding with monoclonal antibodies (mAbs) as the signal probes can react specifically with AFB1, ZEN and DON, respectively. There is an inverse correlation between the fluorescence signal intensity of test line and the analyte content, which can realize the quantitative analysis of analytes within 15 min. The limits of detection in solution are 10, 80 and 500 pg mL-1 for AFB1, ZEN and DON, respectively. Besides, the average recoveries from spiked feed range from 85.5 to 119.0%, and the relative standard deviations are less than 16.4% for both intra- and inter-day assays. The method was used to analyze naturally contaminated feedstuff, and this resulted in a good agreement with data obtained by LC-MS/MS. Graphical abstractSchematic representation of a fluorometric method for the simultaneous determination of three mycotoxins. Quantum dot microbeads (QBs) binding with monoclonal antibodies (mAbs) are signal probes. There is an inverse correlation between the fluorescence intensity of test line and the analyte concentration.


Common projection of the motor cortex to the caudate nucleus and the cerebellum.
1. Stimulation of the caudate nucleus (Cd) was found to evoke early mossy fibre (MF) and late climbing fibre (CF) responses in fairly wide areas of the cerebellar cortex in cats. Points capable of eliciting the cerebellar responses were situated exclusively in the head portion of the nucleus. These responses showed a close resemblance to those induced by stimulation of the medial part of the anterior sigmoid gyrus (ASG) both in their contours and in their distributions. 2. There was a remarkable interaction between the Cd- and the medial ASG-induced field potentials in the pontine nuclei. When conditioned by the Cd stimulation at significantly short time intervals, the field potentials evoked by the medial ASG stimulation were more remarkably suppressed than those by the lateral ASG stimulation. 3. Field potentials or extracellular unitary activities in the inferior olive elicited by the Cd stimulation were closely related to those evoked by the medial ASG stimulation both in their responsiveness and in their topographical localizations. 4. When the cortical motor area had been ablated 10--14 days previously, the Cd stimulation elicited no responses in the cerebellar cortex. 5. From these findings, it was indicated that the Cd receives collaterals of the cortico-pontine and/or the cortico-olivary axons that originated almost exclusively from the neurones in the medial ASG (area 6). This suggested the existence of a common innervation of the basal ganglia and the cerebellar systems by the premotor area of the cerebral cortex.


Palladium-catalyzed synthesis of 2-substituted benzothiazoles via a C-H functionalization/intramolecular C-S bond formation process.
Catalytic synthesis of 2-substituted benzothiazoles from thiobenzanilides was achieved in the presence of a palladium catalyst through C-H functionalization/C-S bond formation. This method features the use of a novel catalytic system consisting of 10 mol % of Pd(II), 50 mol % of Cu(I), and 2 equiv of Bu4NBr that produced variously substituted benzothiazoles in high yields with good functional group tolerance.


A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: frameshifting without tRNA slippage.
Most retroviruses and retrotransposons express their pol gene as a translational fusion to the upstream gag gene, often involving translational frameshifting. We describe here an unusual translational frameshift event occurring between the GAG3 and POL3 genes of the retrotransposon Ty3 of yeast. A +1 frameshift occurs within the sequence GCG AGU U (shown as codons of GAG3), encoding alanine-valine (GCG A GUU). Unlike other programed translational frameshifts described, this event does not require tRNA slippage between cognate or near-cognate codons in the mRNA. Two features distal to the GCG codon stimulate frameshifting. The low availability of the tRNA specific for the "hungry" serine codon, AGU, induces a translational pause required for frameshifting. A sequence of 12 nt distal to the AGU codon (termed the Ty3 "context") also stimulates the event.


Phase I trial of weekly cisplatin, irinotecan and paclitaxel in patients with advanced gastrointestinal cancer.
To determine the maximum tolerated dose (MTD), toxicities, and suitable dose for weekly 1-h paclitaxel combined with weekly cisplatin and irinotecan to treat advanced gastrointestinal malignancies. Thirty patients with metastatic or locally advanced (unresectable or recurrent) gastrointestinal solid tumors were enrolled on this single-center, phase I study. Patients were treated with paclitaxel given over 1h at 1 of 4 dose levels (40, 50, 65, or 80 mg/m(2)). Paclitaxel was followed by fixed doses of cisplatin (30 mg/m(2)) and irinotecan (50 mg/m(2)). All treatment was administered sequentially, once a week, in 6-week cycles (4 weeks on, 2 weeks off). Dose-limiting toxicity (DLT) was defined as a 2-week delay in treatment for grade 3 or 4 non-hematologic toxicity, neutropenic fever, a 1-week delay for grade 4 hematologic toxicity, or a 2-week delay for grade 3 hematologic toxicity. Thirty patients were recruited; 28 patients were assessable for safety. Most of the patients (70%) had no prior chemotherapy. The primary first-cycle DLTs were neutropenia, diarrhea, and nausea. Paclitaxel at 65 mg/m(2) was defined as the MTD. The most common grade 3-4 toxicities observed during all cycles were neutropenia (57%), febrile neutropenia (11%), diarrhea (29%), fatigue (29%), and nausea (18%). No patients had G-CSF (Neupogen, Amgen Inc., Thousand Oaks, CA) support. Responses were observed in gastric, esophageal, and pancreatic cancers. Paclitaxel at 65 mg/m(2), cisplatin (30 mg/m(2)), and irinotecan (50 mg/m(2)) given weekly can be safely administered to patients with solid tumor malignancies. To improve cumulative toxicities, a schedule modification was required (3-week cycle; 2-on, 1-off) Neutropenia was the most common DLT. This combination showed substantial activity, particularly in patients with gastric and esophageal adenocarcinoma, and phase II evaluation could be considered.


Fe-based carbonitride as Fenton-like catalyst for the elimination of organic contaminants.
The Fenton-like process has been regarded as a clean and efficient approach to generate reactive oxygen species (ROS) to deal with the ever-growing environmental pollution. However, developing improved catalysts with adequate activity and stability remains a long-term goal for practical application. Herein, crystalline carbon nanotubes (CNTs) interconnected Fe/Fe3C-doped nanoporous carbonitride (Fe-NC) was easily prepared by the pyrolysis of ZIF-8 confined with Fe3+. The obtained Fe-NCs possessed high degrees of graphitic carbon and nitrogen. Such Fe-NCs can enhance the activation of peroxymonosulfate (PMS) for the removal of multiple organic contaminants. The optimized Fe-NC/PMS system exhibited impressive catalytic performance, with a TOF as high as 4.43 min-1 for 3BF degradation, and the removal efficiency of other dyes, phenols and antibiotics was up to 96.2% within 10 min. The removal efficiency of 3BF was 93.4% within 10 min with extremely low iron ions leaching (<0.052 mg/L) even after five cycles. In addition, the effects of pH on the catalytic performance demonstrated that the decomposition of 3BF exceeded 95.6% even when the initial pH varied from 5 to 10. We confirmed that SO4-, OH, O2- and 1O2 were generated in the catalytic system of Fe-NC/PMS, which played a critical role in degrading the organics. These findings provide new insights into the design of environmental-friendly Fenton-like catalysts with high efficiency and favorable stability in environmental remediation.


Dual-activity nanozyme to initiate tandem catalysis for doubly enhancing ATP-depletion anti-tumor therapy.
Nanozymes can regulate metabolism to achieve precise anti-tumor therapy. However, the application of nanozymes with single catalytic properties is limited by complex tumor microenvironment (TME). Herein, we report a rarely discovered nanozyme ruthenium (Ru), which has double catalytic activity of glucose-oxidase-like (GOx-like) activity and peroxidase-like (POD-like) activity. Importantly, the GOx-like activity of Ru was proposed for the first time, which can catalyze glucose and O2 to product H2O2. And then, Ru nanozyme can connect the tandem catalysis to enhance various tumor therapy. Firstly, the atovaquone (ATO) and Ru NPs were covered with a hybrid membrane of tumor cells and liposomes to obtain Ru@ATO-Lip/M with homologous targeting. Due to the enhanced permeability and retention (EPR) effect and the tumor targeting, the Ru@ATO-Lip/M NPs could be efficiently delivered to tumor and taken up by tumor cells. Subsequently, the acidic environment of tumor activated Ru to catalyze H2O2 producing OH (Fenton-like reaction). Meanwhile, newly discovered ability of Ru catalyzed glucose and O2 to produce gluconic acid and H2O2, which provided sufficient substrates (H2O2) for continuously generating more OH. Therefore, Ru nanozyme aggravated the starvation and chemodynamic therapy (CDT). Further, ATO improved the hypoxia of the tumor microenvironment, achieving steadily synergistic anti-tumor effect. This study verified the glucose oxidase-like properties of Ru NPs for the first time, and the strategy enhanced the synergistic anti-tumor effects by CDT and starvation therapy, which provided a basis for further exploration of Ru nanozyme activity and application on antitumor.


SWAP-70 is important for invasive phenotypes of mouse embryo fibroblasts transformed by v-Src.
SWAP-70 is a protein involved in actin rearrangement, especially in membrane ruffling. Mouse embryo fibroblasts (MEFs) deficient in SWAP-70 show impaired membrane ruffling and fail to grow in soft agar after transformation by v-Src. Here, we show that v-Src transformed MEFs expressing SWAP-70 are highly invasive. MEFs expressing SWAP-70 or v-Src alone were far less invasive, suggesting that both proteins were required for the cells to be invasive. Expression of both SWAP-70 and v-Src induced constant membrane ruffling, which may cause vigorous cell movement, probably required for invasiveness of the cells. Expression of v-Src alone morphologically transformed MEFs but formed lamellipodia rather than membrane ruffles, suggesting less aggressive nature of the cells compared with those expressing both SWAP-70 and v-Src. These results suggest that v-Src and SWAP-70 act synergistically in the invasion activity of MEFs.


Analysis of biomarker expression in severe endometriosis and determination of possibilities for targeted intraoperative imaging.
To evaluate the expression of biomarkers in endometriotic tissue in order to determine the most promising molecules for targeted intraoperative imaging. Tissue samples were obtained from 18 patients with endometriosis. The intensity and pattern of expression of the following biomarkers were assessed by immunohistochemistry: C-X-C chemokine receptor type 4 (CXCR4), epithelial cell adhesion molecule (EpCAM), estrogen receptor (ER), folate receptor α (FR-α), hypoxia-inducible factor 1-α (HIF-1α), progesterone receptor (PR), and vascular endothelial growth factor A (VEGF-A). The Target Selection Criteria scoring system was used to select the most promising biomarkers for intraoperative imaging. Expression of CXCR4, EpCAM, ER, PR, and VEGF-A was scored as strong in endometriotic epithelium. Expression of FR-α was detected in 94.4% of samples, whereas HIF-1α was expressed in just 5.6% of samples. Of note, CXCR4, ER, and VEGF-A were also expressed in surrounding healthy tissue, thus reducing the target-to-background ratio. Of the 7 biomarkers assessed in the present study, EpCAM, FR-α, and VEGF-A seem the most promising for targeted intraoperative imaging of endometriosis.


Differential diagnosis between splenic nodules and peritoneal metastases with contrast-enhanced ultrasound based on signal-intensity characteristics during the late phase.
This study was done to assess the enhancement characteristics of splenic implants and to evaluate whether contrast-enhanced ultrasound (CEUS) after SonoVue injection allows the differential diagnosis with peritoneal metastases. Thirteen consecutive patients with splenosis and 13 consecutive patients with peritoneal metastases were investigated with CEUS after injection of 2.4 ml of SonoVue. Lesion enhancement was evaluated in real time for 240 s. All examinations were recorded digitally and analysed retrospectively. Frames were selected at different time intervals ranging from 0 to 4 min after injection. Average signal intensity was evaluated by measuring the average grey level in a region of interest encompassing the entire nodule. Results were evaluated using the Mann-Whitney test and interobserver variability using the Bland and Altmann method. Splenic grafts presented with intense enhancement and without significant washout. Metastases presented with variable enhancement and progressive washout. Signal intensity values were significantly higher for splenic grafts, starting from 40 s after microbubble administration. Starting from 90 s after injection, there was no overlapping between enhancement of splenic grafts and peritoneal metastases, and only splenic grafts showed a percent of enhancement higher than 60% of the maximum enhancement. CEUS after SonoVue injection may be considered a valuable alternative to scintigraphy for characterising peritoneal splenic grafts without radiation.


Nonylphenol-induced thymocyte apoptosis involved caspase-3 activation and mitochondrial depolarization.
Although the effect of 4-nonylphenol on cells of immune system have long been recognized, little is known about the effect of 4-nonylphenol on the induction of apoptosis and related signaling events in the lymphoid cells. In the present study, we used cultured thymocytes of mice to investigate the ability of 4-nonylphenol to induce the apoptosis of thymocytes and to explore the role of signal transduction pathway leading to apoptosis. The results showed that the cytotoxic effects of 4-nonyphenol involved DNA fragmentation (DNA ladder), characteristic of apoptosis. Staining of 4-nonyphenol-treated thymocytes with DNA-binding fluorochrome Hoechst 33258 showed the typical apoptotic nuclei condensation and fragmentation of chromatin. The rates of apoptosis of the 4-nonylphenol-treated thymocytes increased significantly at 4 and 6 h, which were determined by analysis of hypodiploid cells and FITC-Annexin V and PI double staining. Flow cytometer analysis also revealed that the loss of mitochondrial membrane potential and increased activity of caspase-3 occurred concomitantly with the onset of 4-nonyphenol-induced apoptosis. Furthermore, a caspase-3 inhibitor, z-DEVD-fmk protected thymocytes from apoptosis induced by 4-nonyphenol. These results suggest that 4-nonylphenol induces thymocyte apoptosis via caspase-3 activation and mitochondrial depolarization.


Thyroid-stimulating hormone-secreting pituitary adenoma presenting with recurrent hyperthyroidism in post-treated Graves' disease: a case report.
The coexistence of autoimmune hyperthyroid disease and thyroid-stimulating hormone-secreting pituitary adenoma is rare. The simple presumption of coincidence of these two diseases has a calculated incidence of less than one/several hundred million, and only four cases with histological confirmation have been reported. A rapid decrease in thyroid-stimulating hormone level after pituitary tumor removal may induce subsequent activation of autoimmune responses against the thyroid gland. We report the first case of a sequential and paradoxical occurrence of Graves' disease and a thyroid-stimulating hormone-secreting pituitary adenoma. A 32-year-old Japanese woman had recurrent hyperthyroidism. She had a history of Graves' hyperthyroidism, which had been successfully treated with propylthiouracil. A head magnetic resonance imaging showed a less enhanced area in the left lateral wing of her sella turcica. Transsphenoidal surgery was performed, and the diagnosis was established as thyroid-stimulating hormone-secreting plurihormonal adenoma. A rapid reduction in thyroid hormone levels was achieved, and her blood pressure was normalized after the operation. Although incidental occurrence is the most probable etiology, long and repeated followup examinations of both thyroid and pituitary gland should be performed in patients with an atypical clinical course.


Isolation of the Maclura pomifera hemagglutinin on a deoxymelibiotol affinity support and preliminary characterization by buffer electrofocusing and high-performance liquid chromatography.
Maclurin, the potent non-specific blood-group hemagglutinin present in extracts of Maclura pomifera, has been purified by a new biospecific affinity-chromatographic procedure. Additional studies have indicated that this hemagglutinin occurs as five closely related tetrameric protein isoforms derived from two non-covalently-linked polypeptide chains, mol. wts. ca. 10,000 and 13,000 respectively. Buffer electrofocusing fractionated the lectin into 12 components; the major isolectin exhibited an isoelectric point at pH 4.8.


Satisfaction with care provided by home-based palliative care service to the cancer patients in Dhaka City of Bangladesh: A cross-sectional study.
Patient satisfaction is an important quality indicator of health care service. The concept of home-based palliative care has been recently introduced in Bangladesh, but the patients' satisfaction with this care remained unexplored. This study aimed to assess the satisfaction of the cancer patients receiving this care. This cross-sectional study was conducted among 51 surviving cancer patients above 18 years of age registered under the home-based care service of the Department of Palliative Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh. Data were collected by face-to-face interviews using a structured questionnaire based on the FAMCARE P16 questionnaire from February to March 2019. Descriptive analysis was done for the sociodemographic and satisfaction-related indicators. A correlation matrix was done to see the correlation among the satisfaction indicators. The majority of the patients (88.2%) were satisfied with the service provided by the home care team. Most (76.5%) of the patients were women, and the mean age was 56.25 ± 14.8 years. The median duration of getting home-based care was 4 months. Main satisfaction indicators were-assessment of physical symptoms (70.6%), providing information about pain management (70.6%), the inclusion of the family in decision making (76.5%), coordination of care between the members of the home care team (84.3%) and availability of doctors, nurses and palliative care assistants (74.5%). A high correlation was observed between satisfaction regarding the care of physical symptoms and provision of information (R = 0.814, p < 0.001). Also, satisfaction regarding the provision of information and support provided to the family is highly correlated (R = 0.722, p < 0.001). Despite the limitations, the overall satisfaction level of the patients regarding home-based palliative care services in Bangladesh is very high. Home-based palliative can be a solution to provide palliative care to patients who are unable to access institution-based care and improve their quality of life.


Getting real in interprofessional clinical placements: patient-centeredness in student teams' collaborative learning.
Collaboration between healthcare providers helps tackle the increasing complexity of healthcare. When learning teamwork, interprofessional students are expected to work patient-centered; recognizing the patient's expertise and partnering with them. Research on interprofessional education (IPE) for undergraduates has illuminated learning outcomes, organization of learning activities, change in attitudes, etc. But, we know little about the interaction between patients and interprofessional student teams. This study aimed to explore how interprofessional student teams and patients interact in interprofessional clinical placements. With a focused ethnographic approach, participant observation and qualitative interviews were conducted in two contexts; a physical and an online arrangement. Central ideas in Goffman's dramaturgy constituted a theoretical lens. A reflexive thematic analysis generated three themes: (1) Preparing safe and comfortable encounters with patients, (2) Including and excluding the patient in the encounter, and (3) Adjusting to the patient's situation. We identified students' intentions of patient-centeredness when preparing encounters, but patients did not always feel included and listened to in encounters. After encountering patients, student teams adjusted their teamwork, by changing the team composition or the planned clinical interventions to better meet the patients' needs. Notably, team-based patient encounters led to a different view of the patient, their health issues, and how to collaborate. Our findings can inform educators of the importance of addressing patient-centered care in interprofessional learning arrangements. Today, clinical interprofessional placements may not exploit the potential for learning about patient-centeredness. A thematization of this, e.g., in supervision in future clinical placements can ensure an enhanced focus on this in interprofessional teamwork.


Ivabradine inhibits the production of proinflammatory cytokines and inducible nitric oxide synthase in acute coxsackievirus B3-induced myocarditis.
The role of β-adrenergic stimulation on viral myocarditis has been investigated in animal models. The beneficial action of the β-blocker carvedilol in murine viral myocarditis can be explained partly by the resulting heart rate reduction and the inhibition of proinflammatory cytokine production. The modulation of myocardial necrosis and contractile dysfunction by proinflammatory cytokines may be partially mediated by the production of nitric oxide (NO). The selective I(f) current inhibitor ivabradine reduces the heart rate without affecting cardiac contractility and has been shown to be cardioprotective in failing hearts. However, little is known about the effects of ivabradine in viral myocarditis, and in particular, its effects on inducible NO synthase (iNOS) have not been investigated. This study was therefore designed to examine the effects of ivabradine in murine viral myocarditis. In a coxsackievirus B3 murine myocarditis model, the effects of ivabradine and carvedilol on the myocardial histopathological changes and fibrosis, NO production, iNOS protein and cytokine levels were studied. Both ivabradine and carvedilol similarlyattenuated myocardial lesions and fibrosis, inhibited NO synthesis by iNOS, and decreased the production of TNF-α and IL-6. These results show that ivabradine has a therapeutic benefit in murine CVB3-induced myocarditis. The beneficial effects of ivabradine in viral myocarditis are partially mediated by the inhibition of both the production of proinflammatory cytokines and the synthesis of NO by iNOS.


Moderate Intensity Endurance and Resistance Exercise Attenuates Cachexia in Tumor-bearing Mice.
Cancer cachexia encompasses several deleterious physiological alterations associated with functional impairments, poor quality of life, and increased mortality. The aim of this study was to examine the effects of chronic moderate intensity exercise training on markers of cachexia. Balb/c mice were randomly assigned to sedentary (SED) or exercise (EX) groups and EX mice were further randomly assigned to one of three exercise modalities (aerobic, resistance, combined). Cachexia was induced in SED animals inoculated with C26 cells, as evidenced by significant changes in numerous markers. All cachexia-related perturbations were significantly attenuated in EX versus SED animals. Systemic inflammation was significantly decreased in all EX groups, as evident by a normalization of spleen mass and plasma IL-6. Multiple moderate intensity exercise modalities can provide significant benefits in cachectic mice, and this may be due, at least in part, to decreased systemic inflammation.


A prospective observational cohort study and systematic review of 40 patients with mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome.
Mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome is characterized by overlapping features of relapsing polychondritis (RP) and Behcet's disease (BD). To date, no studies have defined the clinical spectrum of disease in a cohort of patients with MAGIC syndrome. Adult patients within an ongoing prospective, observational cohort study in RP were clinically assessed for MAGIC syndrome. A systematic review was conducted to identify additional cases of MAGIC syndrome by searching four databases: PubMed (US National Library of Medicine), Embase (Elsevier), Scopus (Elsevier) and Web of Science: Core Collection (Clarivate Analytics). The inclusion criteria used were: [1] patients of any age or gender who were diagnosed with MAGIC syndrome, or both RP and BD; [2] case report or case series study; [3] published from 1985 - July 2020; and [4] in English language. Risk of bias was assessed using a checklist developed by the authors and based on the Consensus-based Clinical Case Reporting (CARE) Guidelines. Search results screening, article inclusion, data extraction and risk of bais assessment was performed independently by two investigators. Clinical characteristics, particularly BD-related features, were compared between patients with MAGIC syndrome and cases of non-MAGIC RP. The performance characteristics of different criteria to classify MAGIC syndrome were also evaluated. Out of 96 patients with RP, 13 (14%) patients were diagnosed with MAGIC syndrome. For the systematic review, 380 articles were retrieved of which 90 were screened at title and abstract levels. Of these screened, 60 were excluded and 30 proceeded to full text review where an additional 8 were excluded. Twenty-two articles were included in our review and from which 27 additional cases of MAGIC syndrome were identified. Pooling all 40 cases together and comparing them with non-MAGIC RP, there was a significantly higher prevalence of ocular involvement (28% vs 4%, p<0.01), cutaneous involvement (35% vs 1%, p<0.01), GI involvement (23% vs 4%, p<0.01), and CNS involvement (8% vs 0, p = 0.04) in MAGIC syndrome. A higher prevalence of aortitis (23% vs 1%, p<0.01), Raynaud's phenomenon (54% vs 11%, p<0.01), and elevated anti-collagen II antibodies (50% vs 9%, p = 0.04) were observed in MAGIC syndrome. Fulfillment of either McAdam's or Damiani's Criteria for RP plus the International Criteria for Behçet's Disease had excellent sensitivity (98%) to classify cases of MAGIC syndrome. A substantial proportion of patients with RP can be clinically diagnosed with MAGIC syndrome. These patients have features of RP, BD, and other unique features including aortitis, Raynaud's phenomenon and elevated anti-collagen II antibodies.


Mineralocorticoid hormone action in plant cells.
The multiplication of Chlamydomonas reinhardtii wild type cells can be arrested by the spirolactone RU 26752 and this is fully reversible by the natural mineralocorticoid aldosterone. Evidence is presented for a 52 kDa protein that possesses functional DNA and ligand binding domains and tests positive for mineralocorticoid receptor-like activity by immuneprecipitation, macroaggregation, and photoaffinity. The regulation of trans-activation by steroid hormones in the animal world would therefore appear to be just as valid for the plant kingdom, thereby providing a new model for genetic analysis.


Sono-catalytic degradation and fast mineralization of p-chlorophenol: La(0.7)Sr(0.3)MnO3 as a nano-magnetic green catalyst.
La0.7Sr0.3MnO3 (LSMO) nanoparticles with a perovskite structure were prepared by a combination of ultrasound and co-precipitation method. The synthesized catalyst was characterized by X-ray diffraction, transmission electron microscopy, Fourier transform infrared spectroscopy. The catalytic performance of the catalyst was evaluated for the degradation of 4-chlorophenol in the presence and in the absence of ultrasound. The degradation has been studied at different temperatures, pH, catalyst dosage, and initial concentration of 4-chlorophenol. The results have shown that the degradation efficiency was higher in the presence of ultrasound than its absence under the mild conditions. More than 88% decrease in the concentration and 85% decrease in the TOC for 4-chlorophenol could be achieved in a short time of sonication with respect to the conventional method. This behavior could be attributed to the cavitation process which followed by a high mass transfer on the catalyst with high surface area. These conditions led to facilitate the removal of pollutant from aqueous solution. The results also indicated that the catalyst without recalcination can be used successfully up to five consecutive cycles without any significant loss in activity in the presence and in the absence of ultrasound. In addition, the most important is the magnetic property of the nanoparticles which separated easily from aqueous solution by an external magnetic field.


Menstrual hygiene management and associated factors among adolescent school girls in gursum district, Eastern Ethiopia: Institution-based a cross-sectional study.
In 2017 WHO reported that due to a lack of menstrual hygiene management (MHM) facilities, high costs, and ignorance, 2.3 billion girls and women worldwide do not manage their menstruation properly. This leads to the use of other options, such as old clothes or other unhygienic materials, which may make them a risk group for infections and other health consequences. Despite the significant role of appropriate menstrual hygiene practices, it is still a missed opportunity to address the hygienic practice of menstruation among girls in many low-and middle-income countries, including Ethiopia. Primarily, this study was aimed at investigating menstrual hygiene management (MHM) practice and determinant factors among young adolescent school girls in eastern Ethiopia, Gursum District 2021. An institutional-based cross-sectional survey was conducted among adolescent school girls in Gursum, Eastern Ethiopia, in 2021. 577 girls participated in this study and a multi-stage sampling procedure was employed so as to select a fair and representative sample of female students who experienced menarche. After controlling for confounding variables, binary logistic regression was fitted to identify factors affecting MHM among adolescent girls. This study revealed that 58.41% of adolescent school girls practice unsafe MHM practices. It was also reported that 193(33.45%) of the girls use reusable sanitary pads. Of those, 182(31.5%) of them keep the pads in hidden places as it is a shame to be seen Seventy-six (13.17%) of the respondents had experienced vaginal infections during menarche. Having knowledge about menstruation prior to experiencing menstruation [AOR 0.28 CI: (0.1476132, 0.5613692)], being over 15 years old [AOR 1.56, CI: (1.020577, 2.387646)], living in rural areas [AOR 1.23 CI: (1.1563013, 1.3562546)], and having infection around their vagina during menarche [AOR 4.6 CI: (2.633405, 8. 273,883)] were significant determinants of MHM practice. The majority of the adolescent girls who participated in this study practice unsafe MHM practices. Results suggest that school health education focusing on improving the hygienic practices of adolescent girls during menstruation should be provided.


Antibiotic regimens for postpartum endometritis.
Postpartum endometritis occurs when vaginal organisms invade the endometrial cavity during the labor process and cause infection. This is more common following cesarean birth. The condition warrants antibiotic treatment. Systematically, to review treatment failure and other complications of different antibiotic regimens for postpartum endometritis. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 November 2014) and reference lists of retrieved studies. We included randomized trials of different antibiotic regimens after cesarean birth or vaginal birth; no quasi-randomized trials were included. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The review includes a total of 42 trials, and 40 of these trials contributed data on 4240 participants.Regarding the primary outcomes, seven studies compared clindamycin plus an aminoglycoside versus penicillins and showed fewer treatment failures (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.46 to 0.90). There were more treatment failures in those treated with an aminoglycoside plus penicillin when compared to those treated with gentamycin/clindamycin (RR 2.57, 95% CI 1.48 to 4.46). There were more treatment failures (RR 1.66, 95% CI 1.01 to 2.74) and wound infections (RR 1.88, 95% CI 1.08 to 3.28) in those treated with second or third generation cephalosporins (excluding cephamycins) versus those treated with clindamycin plus gentamycin. In four studies comparing once-daily with thrice-daily dosing of gentamicin, there were fewer failures with once-daily dosing. There were more treatment failures (RR 1.94, 95% CI 1.38 to 2.72) and wound infections (RR 1.88, 95% CI 1.17 to 3.02) in those treated with a regimen with poor activity against penicillin-resistant anaerobic bacteria as compared to those treated with a regimen with good activity against penicillin-resistant anaerobic bacteria. There were no differences between groups with respect to severe complications and no trials reported any maternal deaths.Regarding the secondary outcomes, three studies that compared continued oral antibiotic therapy after intravenous therapy with no oral therapy, found no differences in recurrent endometritis or other outcomes. Four trials that compared clindamycin plus aminoglycoside versus cephalosporins identified fewer wound infections in those treated with clindamycin plus an aminoglycoside (RR 0.53, 95% CI 0.30 to 0.93). There were no differences between groups for the outcomes of allergic reactions. The overall risk of bias was unclear in the most of the studies. The quality of the evidence using GRADE comparing clindamycin and an aminoglycoside with another regimen (compared with cephalosporins or penicillins) was low to very low for therapeutic failure, severe complications, wound infection and allergic reaction. The combination of clindamycin and gentamicin is appropriate for the treatment of endometritis. Regimens with good activity against penicillin-resistant anaerobic bacteria are better than those with poor activity against penicillin-resistant anaerobic bacteria. There is no evidence that any one regimen is associated with fewer side-effects. Following clinical improvement of uncomplicated endometritis which has been treated with intravenous therapy, the use of additional oral therapy has not been proven to be beneficial.


The effect of metabolic inhibition on rat uterine intracellular pH and its role in contractile failure.
Although intracellular pH (pHi) is expected to change during inhibition of oxidative phosphorylation and to affect force, there have been no simultaneous measurements of its effect on pHi and force in smooth muscle. Therefore, we have investigated the relationship between force and pHi in strips of longitudinal rat myometrium, loaded with the pH-sensitive indicator carboxy-SNARF and simultaneously measured tension. The application of cyanide produced an abolition of spontaneous contractions and a rapid initial fall in pHi. In 9/19 preparations pHi then started to return to resting values but there was no corresponding restoration of force. Cyanide and weak base were simultaneously added to uterine preparations to prevent any acidification; force still fell. Addition of cyanide to depolarized preparations also produced an acidification and a fall in force. Depolarization of preparations in which spontaneous force had been abolished by cyanide often produced a transient rise in force, despite further acidification of the cytoplasm. Cyanide produced an acidification in zero Ca(2+)-containing solution, similar to that in the presence of Ca2+ indicating little role for changes in [Ca2+] in producing the acidification. It is concluded that cyanide decreases pHi and force in the uterus, but that there is not a simple relationship between the two.


Investigation of somatostatin receptor profile of neuroendocrine carcinomas of the breast.
Carcinomas of the breast with neuroendocrine features are rare primary neoplasms positive for neuroendocrine markers. According to the WHO classification of tumours of the breast they are divided into three morphologically distinct categories. They comprise neuroendocrine tumour (NET), neuroendocrine carcinoma (NEC) and carcinoma with neuroendocrine differentiation (NED). The purpose of this study was to investigate for the first time the full spectrum of sstr expression status in breast carcinomas with neuroendocrine features. Fifteen primary breast carcinomas with histological and immunohistochemical neuroendocrine features were studied. Four of them were classified as NETs and two as NECs, and the remaining 9 as carcinomas with NED. All six types of somatostatin receptor (sstr) types (sstr1, sstr 2A, sstr2B, sstr3, sstr4 and sstr5) were investigated by immunohistochemistry. To assess the distribution and intensity of membranous receptor immunoreactivity, a four-scale scoring system was used. Overall predominant receptors were sstr2A, sstr2B, sstr3 and sstr5 showing the highest membranous staining scores 3+ and 2 + . The sstr1 was not detected. Given that carcinomas with neuroendocrine features represent distinct entities, patients with such tumours may benefit from sstr targeting therapies. Immunohistochemistry for sstrs can predict the effectiveness of administration of SST analogues to those patients, thus contributing to achieve the maximum therapeutic outcome, particularly in NETs and NECs with scores 2+ and 3 + .


Salvage chemotherapy in recurrent cervical cancer with biweekly pegylated liposomal Doxorubicin (lipo-dox).
To investigate the objective response rate to and tolerance of biweekly Lipo-Dox (TTY Biopharm Co. Ltd., Taipei, Taiwan) at a dosage of 20 mg/m(2) in previously treated patients with recurrent cervical cancer. This study was performed as a Simons two-stage phase II clinical trial. Ten patients with recurrent cervical cancer were enrolled between April 2003 and December 2005 at the Mackay Memorial Hospital. Lipo-Dox (20 mg/m(2) intravenous) diluted in 250 mL of 5% dextrose solution was administered at 2-weekly intervals. The mean age of the patients was 51 +/- 11.1 years. The mean number of cycles of Lipo-Dox injection was 4.6 (range, 1-12 cycles). Nine patients (90%) had disease progression. Only one patient (10%) achieved a partial response, and this was also the only patient who experienced WHO grade 2 palmar-plantar erythrodysesthesia, which led to treatment delay for 2 months. The median survival time was 2 months (range, 2-6 months). The majority of patients experienced grade 1 or 2 anemia (30%), leukopenia (20%) or thrombocytopenia (20%), and others exhibited symptoms of nausea and vomiting (30%). Salvage chemotherapy with Lipo-Dox at a dose of 20 mg/m(2) administered at 2-weekly intervals produced limited responses in patients with recurrent cervical cancer. This trial will not proceed to the second stage. These results may discourage the management of recurrent cervical cancer with single-agent Lipo-Dox in future clinical trials.


Smaller is Plastic: Polymorphic Structures and Mechanism of Deformation in Nanoscale hcp Metals.
Using first-principles calculations, we establish the existence of highly stable polymorphs of hcp metals (Ti, Mg, Be, La and Y) with nanoscale structural periodicity. They arise from heterogeneous deformation of the hcp structure occurring in response to large shear stresses localized at the basal planes separated by a few nanometers. Through Landau theoretical analysis, we show that their stability derives from nonlinear coupling between strains at different length scales. Such multiscale hyperelasticity and long-period structures constitute a new mechanism of size-dependent plasticity and its enhancement in nanoscale hcp metals.


[Reflux esophagitis: operative procedures in children: fundoplication (author's transl)].
Hiatus hernia and peptic esophagitis in children lead in 20% of the cases to peptic stenosis, thus rendering a reflux-preventing operation mandatory in many patients. We consider fundoplication as the operation of choice and have used it for 17 years. The early and late mortality varies between 1.2% and 1.4% and can be lowered even further through improvement of treatment. Functional complications such as "gas bloat syndrome," dysphagia, diarrhea, disappear spontaneously in the first 2-3 months after surgery. The only severe late complication is the development of a paraesophageal hernia months after surgery: This complication can be avoided through better technique. Out of 61 patients who were examined 10 or more years after operation, 58 are totally free of symptoms.


Laboratory-based surveillance of Candida auris in Colombia, 2016-2020.
Since the first report of Candida auris in 2016, the Colombian Instituto Nacional de Salud (INS) has implemented a national surveillance of the emerging multidrug-resistant fungus. This report summarises the findings of this laboratory-based surveillance from March 2016 to December 2020. A total of 1720 C. auris cases were identified, including 393 (23%) colonisation cases and 1327 (77%) clinical cases. Cases were reported in 20 of 32 (62%) departments of Colombia and involved hospitals from 33 cities. The median age of patients was 34 years; 317 (18%) cases were children under 16 years, 54% were male. The peak number of cases was observed in 2019 (n = 541). In 2020, 379 (94%) of 404 cases reported were clinical cases, including 225 bloodstream infections (BSI) and 154 non-BSI. Among the 404 cases reported in 2020, severe COVID-19 was reported in 122 (30%). Antifungal susceptibility was tested in 379 isolates. Using CDC tentative breakpoints for resistance, 35% of isolates were fluconazole resistant, 33% were amphotericin B resistant, and 0.3% isolates were anidulafungin resistant, 12% were multidrug resistant, and no pan-resistant isolates were identified. For five years of surveillance, we observed an increase in the number and geographic spread of clinical cases and an increase in fluconazole resistance. These observations emphasise the need for improved measures to mitigate spread.


Microinteraction Ecological Momentary Assessment Response Rates: Effect of Microinteractions or the Smartwatch?
Mobile-based ecological-momentary-assessment (EMA) is an in-situ measurement methodology where an electronic device prompts a person to answer questions of research interest. EMA has a key limitation: interruption burden. Microinteraction-EMA(μEMA) may reduce burden without sacrificing high temporal density of measurement. In μEMA, all EMA prompts can be answered with 'at a glance' microinteractions. In a prior 4-week pilot study comparing standard EMA delivered on a phone (phone-EMA) vs. μEMA delivered on a smartwatch (watch-μEMA), watch-μEMA demonstrated higher response rates and lower perceived burden than phone-EMA, even when the watch-μEMA interruption rate was 8 times more than phone-EMA. A new 4-week dataset was gathered on smartwatch-based EMA (i.e., watch-EMA with 6 back-to-back, multiple-choice questions on a watch) to compare whether the high response rates of watch-μEMA previously observed were a result of using microinteractions, or due to the novelty and accessibility of the smartwatch. No statistically significant differences in compliance, completion, and first-prompt response rates were observed between phone-EMA and watch-EMA. However, watch-μEMA response rates were significantly higher than watch-EMA. This pilot suggests that (1) the high compliance and low burden previously observed in watch-μEMA is likely due to the microinteraction question technique, not simply the use of the watch versus the phone, and that (2) compliance with traditional EMA (with long surveys) may not improve simply by moving survey delivery from the phone to a smartwatch.


Effect of commercial Rhodiola rosea on CYP enzyme activity in humans.
The aim of the present study was to evaluate the effect of the herbal drug Rhodiola rosea on the activity of the cytochrome P-450 (CYP) enzymes CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 in humans. In a randomized cross-over study, 13 healthy volunteers were given a cocktail with single doses of the CYP substrates caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4) with and without 14 days of pretreatment with a commercially available R. rosea product (Arctic Root, produced by the Swedish Herbal Institute). Four hours after intake of the drug cocktail, a blood sample was obtained, the serum concentrations of the drugs and their metabolites were analyzed, and the metabolic ratios were calculated as a measure of CYP enzyme activity. A statistically significant 21% decrease in the EXP-3174/losartan ratio was found after pretreatment with R. rosea (p = 0.023), indicating a reduced CYP2C9 metabolic activity. The effect was more pronounced in CYP2C9 extensive metabolizers than in CYP2C9 intermediate and poor metabolizers. For the other CYP enzymes tested, no significant effects were observed. This study indicates that R. rosea inhibits the metabolic capacity of CYP2C9 in humans. Although the effect is modest, it might be clinically relevant during treatment with CYP2C9 substrates with a narrow therapeutic index, such as phenytoin and warfarin.


Osteoblasts up-regulate the expression of extracellular proteases following attachment to Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate).
MC3T3-E1 cells demonstrate a lag in osteogenic development when seeded onto Poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) (PHBV), a biomaterial with substantial potential for bone tissue repair. To determine if this was due to the priority of extracellular matrix (ECM) remodelling over other developmental processes, gene expression levels of proteins involved in the production, maintenance and turnover of the ECM were compared between cells grown on PHBV and tissue culture plastic (TCP) 24 h after seeding. When grown on PHBV, MC3T3-E1 cells up-regulated proteins such as the matrix metalloproteinases and down-regulated the expression of proteins such as collagens that are involved in cell-substrate interactions, but in later-stage processes. The results also suggest that proteins such as fibronectin and aggrecan, and particularly osteopontin, may be more suitable candidates for PHBV functionalization for optimal MC3T3-E1 cell growth than proteins like osteonectin, periostin, vitronectin or collagen. This study confirms the importance of understanding the specific response of therapeutically-relevant cells, such as human stem cells, to candidate biomaterial surfaces in order to achieve optimal regenerative therapies.


Developmental changes in proteins of purified membranes of chicken lenses and evidence for contamination by cytoplasmic delta-crystallin.
Urea-washed membranes from embryonic chick lenses (15 days old) and from the cortical and nuclear regions of adult chicken lenses (1 year) have been prepared by repeated centrifugation through discontinuous density gradients. The protein components of the isolated membranes have been examined by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate and urea. Proteins with molecular weights of 75 000, 56 000, 54 000, 48 000, 34 000, 32 000, 25 000, and 22 000 were present in all the membrane preparations, although their proportions changed during development. One additional protein, molecular weight 70 000, was seen only in the embryonic lens membranes. The greatest developmental change was the increase in 25 000 molecular weight protein from 12% in the embryonic lens to about 45% in the adult lens. Since it has been suggested that this protein is associated with gap junctions, its increase during development may reflect a corresponding increase in the number of gap junctions in the lens. The 50 000 molecular weight protein of embryonic lens membranes and membranes of adult nuclear lens fibers consisted at least partly of delta-crystallin, since delta-crystallin peptides could be identified in tryptic peptide maps of the isolated protein after in vitro radioiodination. Peptide maps of the 50 000 molecular weight protein of cortical lens fiber membranes contained no identifiable delta-crystallin peptides, although it is possible that modified delta-crystallin peptides may be present. The level of cytoplasmic contamination of the membrane fraction was estimated by preparing lens membranes in the presence of added delta-[35S]crystallin. The results indicated that cytoplasmic contamination contributes significantly to the presence of delta-crystallin in lens membrane preparations.


Polyethersulfone as suitable passive sampler for waterborne hydrophobic organic compounds - Laboratory calibration and field test in the Sosiani river, Kenya.
We report the application of polyethersulfone (PES) membrane as a cost-saving and less labour-intensive single-phase passive sampler for waterborne hydrophobic organic compounds (HOCs) like organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), polyaromatic hydrocarbons (PAHs). The uptake kinetics of 31 HOCs from water to porous polyethersulfone (PES) membranes and their partitioning behaviour were investigated in laboratory studies. Sampling rates (Rs) of HOCs with PES were determined in a range from 1.15 to 12.9 L/d. The uptake of test chemicals and the elimination of analogous (pre-loaded) performance reference compounds (PRCs) showed anisotropy, both under laboratory and field conditions, implying that PRCs are not suitable for determining in situ sampling rates with PES. The PES-water partition coefficients (Kpw) are, on average, ten times higher than the related Kow. A Linear Solvation Energy Relationship for modelling the measured log Kpw with PES under inclusion of all available published data yields a poor fit in comparison to what is usually obtained with homogeneous polymers like polydimethylsiloxane or low-density polyethylene. At least a strong linear relationship was found between log Rs and log Kpw for the narrow log Kow range of HOCs investigated in this work which can be used for interpolation to other HOCs in this range. The PES membranes were also tested in a field trial in a tropical river against the well-established silicone rubber (SR) sheets. With laboratory-based Rs for PES generated under field-relevant temperature and water flow velocity it was possible to obtain time-weighted average concentrations in the lower ng/L range which are comparable (within a factor of two) with those derived from accumulated amounts in SR sheets (using in situ sampling rates).


Immigration Policy Mismatches and Counterproductive Outcomes: Unauthorized Migration to the U.S. in Two Eras.
The world appears to be moving into a new era of international migration during which gaps between policies needed to manage migratory flows and those enacted in practice will widen. Whereas immigrants in the late 20th century were motivated by a desire to improve their wellbeing by accessing opportunities in richer countries, in the early 21st century they are increasingly motivated by a desire to escape threats at places of origin, yielding very different patterns of migration and selectivity. Using the United States as an example, this paper reviews how mismatches between the underlying realities of international migration and the policies adopted to manage them, in both eras have produced and continue to produce dysfunctional outcomes. Although deleterious policy outcomes might be avoided in the future by combining a well-grounded conceptual understanding of the forces producing immigration with a clear statement of the goals to be achieved through specific policy interventions, the avoidance of further dysfunctional outcomes is unlikely to be achieved in an age of rising populism, disinformation, and xenophobia.


Rapid detection of IgG and IgM antibodies for cytomegalovirus by the enzyme linked immunosorbent assay (ELISA).
A simple solid phase enzyme immunoassay for the detection of immunoglobulin G and M to cytomegalovirus (CMV) is described. Using this test IgM antibodies to CMV were detected in 0.7 per cent of newborns and regularly after CMV infection in transplant patients, furthermore in these latter patients IgM production was prolonged for several months. For the determination of IgG the enzyme immunoassay was more sensitive than the complement fixation test (CF) and the antibody titres were 4 to 8 fold higher. Since the ELISA test is rapid, specific and unexpensive it can become an acceptable routine diagnostic procedure.


Increased HIV in Greater Kinshasa Urban Health Zones: Democratic Republic of Congo (2017-2018).
Diagnosis of people living with HIV (PLHIV) is the first step toward achieving the new Fast Track Strategy to end AIDS by 2030: 95-95-95. However, reaching PLHIV is especially difficult in resource-limited settings such as the Democratic Republic of Congo (DRC), where reliable prevalence data is lacking. This study evaluated the prevalence of HIV in patients in the urban Kinshasa area. Individuals seeking healthcare were tested for HIV between February 2017 and July 2018 at existing Kinshasa urban clinics. The study was conducted in two phases. Case finding was optimized in a pilot study phase using a modified cell phone-based Open\Data Kit (ODK) collection system. HIV prevalence was then determined from data obtained between March-July of 2018 from 8320 individuals over the age of 18 years receiving care at one of 47 clinics in Kinshasa. The prevalence of HIV in our study was 11.0% (95% CI 10.3-11.6%) overall and 8.14% in the subset of N = 1240 participants who were healthy mothers seeking prenatal care. These results are in sharp contrast to President's Emergency Plan for AIDS Relief (PEPFAR) estimates of 2.86%, but are consistent with data from surrounding countries. While this data is sub-national and reflects an urban healthcare setting, given the large population of Kinshasa and rapidly changing age demographics, the results suggest that HIV prevalence in the DRC is substantially higher than previously reported.


Three new species of Axinulus (Bivalvia: Thyasiridae) from the Japan and Kuril-Kamchatka trenches and abyssal zone of the northern Pacific Ocean.
The Thyasiridae is one of the most species-rich families of bivalves in the deep-sea areas of the northern Pacific Ocean. Many thyasirid species form abundant populations in these regions and play an important role in the functioning of deep-sea benthic communities. However, most of these deep-sea thyasirid species have not been identified and many of them are new to science. Based on the material of bivalves collected by eight deep-sea expeditions in the northern Pacific Ocean during the period from 1954 to 2016, three new species of the genus Axinulus (Axinulus krylovae sp. nov., A. alatus sp. nov., and A. cristatus sp. nov.) are described from the Kuril-Kamchatka and Japan trenches, the Bering Sea, and other deep-water regions of the northern Pacific Ocean (3,200-9,583 m depth). The new species are distinguished due to a unique and complex sculpture of the prodissoconch, including tubercles and numerous thin folds of varying length and shape, as well as due to a thickening of the shell in the adductor scar areas, thus rendering the scars raised above the inner surface of the shell. Comparisons with all species of the genus Axinulus are provided.


Identification and assessment of the drift velocity of green tides using the maximum cross-correlation method in the Yellow Sea.
The green tides outbreak events seriously threaten the ecological balance of the coastal areas. Quickly and accurately obtaining the spatial distribution and drift state of green tides is key to early warning. Based on Landsat 8 (L8) and Sentinel-2 (S2) image pair, the green tides drift velocity was extracted using the maximum cross-correlation (MCC) method, and windage was calculated by combining ocean current and wind data. The results of the MCC method were validated. Ulva's drift in the Yellow Sea is shaped by both ocean currents and wind, closely aligning with the direction of the currents. Notably, the northward drift velocity of Ulva exhibits a clear boundary around 34°40'N. Windage shows similar characteristics with the Ulva drift velocity, as its values vary with time and space. This study will enhance our comprehension of the dynamic mechanism of green tides drift.


The Natural Tendency for Wide and Careful Listening: Exploring the Relationship Between Open-Mindedness and Psychological Science.
We take open-mindedness to be a component of intellectual humility, as much of the recent empirical literature regarding intellectual humility does but contrary to what some philosophers think. More particularly, we understand intellectual humility as having a self-directed component, which is concerned primarily with the regulation of confidence we have on our own epistemic goods and capacities, and an other-directed component, which is concerned primarily with one's epistemic openness to others so to improve one's epistemic situation. Given that the open-minded person is disposed give new ideas serious consideration, it is crucial that she both listens widely and carefully to other's ideas. In this paper, we examine whether there is evidence to suggest that we have a natural, evolved tendency for this wide and careful listening related to open-mindedness. We conclude that there is indication of a natural tendency for wide listening, especially an in-group tendency. However, careful listening lacks more substantive empirical studies. It seems that human infants are much more inclined to be charitable and attentive to in-group cues or opinions. This is important evidence to deconstruct the idea of a natural tendency of virtuous intellectual humility that opens up the discussion for the role of social learning in cultivating and maintaining a virtuous life.


Different parental origins of supernumerary X chromosomes in brothers with Klinefelter syndrome: A case report.
Recurrence of Klinefelter syndrome (KS) in non-twin brothers is very rare. This study examined the inheritance pattern of supernumerary X chromosomes in non-twin brothers. A 16-year-old man presented with small-sized testicles. During his diagnostic work-up, his brother, in his late 20's, also complained of small testes and erectile dysfunction. Chromosome analysis in peripheral blood revealed non-mosaic 47,XXY karyotype in both brothers. Their mother showed a normal 46,XX karyotype. To examine the inheritance pattern of supernumerary X chromosomes, quantitative-fluorescence PCR was performed with small tandem repeat markers. It revealed that their supernumerary X chromosomes were inherited from different parents. After the diagnosis of KS, 2 brothers started to receive testosterone treatment. This case report is the first to report differences in the origins of supernumerary X chromosomes in brothers with KS and furthers the current understanding of the cytogenetic mechanisms in KS.


Detection of antiviral antibodies using enzyme-linked immunosorbent assay.
Following retroviral infection, specific antibodies against viral proteins may be detected in the blood, urine, milk, or saliva of an infected animal. Enzyme-linked immunosorbent assay (ELISA) is the most commonly used method to screen for antiviral antibodies, as the technique is sensitive, reproducible, relatively inexpensive, and easily adapted to large-scale screening. This chapter describes two independent ELISA techniques. The first uses a recombinant biotinylated viral protein antigen expressed in E. coli that is purified directly on streptavidin-coated plastic wells. The second uses fixed "virus-infected" cultured cells and can be used either as a second confirmatory assay or initially in a small-scale screening to identify potentially infected individuals for further study.


Multifractal structure of the ¹³⁷Cs fallout at small spatial scales.
Regardless of the surface area of the site, the spatial distribution of radioactive contamination of soils with ¹³⁷Cs for Chernobyl fallout is described by a lognormal distribution. Moreover, the spatial pattern of the radioactive contamination of soil is random geometrical multifractal field. Due to that, any contamination spot, when studied in detail, decomposes into a multitude of small spots decomposing further into a multitude of smaller spots etc. Similar patterns are apparently characteristic for fallout of other radionuclides, the Fukushima fallout, as well as atmospheric fallout of non-radioactive dust and aerosols.


Validation and application of an analytical method for monomethylmercury quantification in aquatic plant tissues.
An analytical methodology for monomethylmercury (MMHg) determination in aquatic plant tissues with low detection limit (346 pg g(-1)) is proposed. It consists of acid digestion (HBr/CuSO4), cleanup step with a Na2S solution, pre-concentration procedure using a dithizone solution in toluene and quantification by GC-ECD. The performance of the methodology has been tested by determining the MMHg concentrations in the certified reference material Fucus Sea Plant Homogenate--IAEA-140/TM (CRM) and in leaves, stems and roots of the salt marsh plants Sarcocornia fruticosa and Halimione portulacoides. The results obtained for CRM were not statistically different (alpha=0.056) from the certified value and repeatability was lower than 2.5% for the plant samples analyzed. This coefficient of variation was similar to those obtained in the externally quality control using within-batch and between-batch (<1.4%).


Integrating spatial gene expression and breast tumour morphology via deep learning.
Spatial transcriptomics allows for the measurement of RNA abundance at a high spatial resolution, making it possible to systematically link the morphology of cellular neighbourhoods and spatially localized gene expression. Here, we report the development of a deep learning algorithm for the prediction of local gene expression from haematoxylin-and-eosin-stained histopathology images using a new dataset of 30,612 spatially resolved gene expression data matched to histopathology images from 23 patients with breast cancer. We identified over 100 genes, including known breast cancer biomarkers of intratumoral heterogeneity and the co-localization of tumour growth and immune activation, the expression of which can be predicted from the histopathology images at a resolution of 100 µm. We also show that the algorithm generalizes well to The Cancer Genome Atlas and to other breast cancer gene expression datasets without the need for re-training. Predicting the spatially resolved transcriptome of a tissue directly from tissue images may enable image-based screening for molecular biomarkers with spatial variation.


Salvage of a difficult situation: method for conversion of failed endograft.
Complications of endovascular aneurysm repair can be difficult to manage. One of the more difficult situations is conversion to open surgery because of a failed endograft. We describe a technique for conversion that allows the proximal attachment system to remain intact. It may also enable infrarenal clamping of the aorta during the operation. The anastomosis is performed by incorporating the proximal attachment system of the endograft. This technique simplifies both vascular control of the aorta and the necessary reconstruction during creation of the proximal anastomosis. We believe this technique has important advantages when conversion of a failed endograft is required.


The effect of pre-eclampsia on retinal microvascular caliber at delivery and post-partum.
The retinal microcirculation provides a unique view of microvessel structure by means of non-invasive, retinal image analysis. The aim of the study was to compare the retinal vessel caliber at delivery and one-year post-partum between women who have had pre-eclampsia during pregnancy to a normotensive control group. Digital photos of the eye were taken at delivery and one-year post-partum. Retinal vessels were analysed and summarised as the corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent. The corrected central retinal arteriolar equivalent and corrected central retinal venular equivalent were significantly lower in the pre-eclamptic group compared to the control group both at delivery and one-year post-partum (p < 0.001). Retinal artery and venular caliber changes that occur during pregnancies affected by pre-eclampsia persist for up to one-year post-partum. These changes may reflect a permanent, long-term microvascular dysfunction and may be useful as a biomarker of future vascular risk.


Enhanced contractile responses of arteries from diabetic rats to alpha 1-adrenoceptor stimulation in the absence and presence of extracellular calcium.
The purpose of this study was to determine the receptor subtype mediating enhanced contractile responses of aortae and mesenteric arteries from diabetic rats to the alpha-adrenoceptor agonists, norepinephrine, clonidine, and methoxamine and to establish whether the enhanced responses are associated with increased release of intracellular Ca2+ or are dependent on the presence of extracellular Ca2+. The pA2 values calculated for the alpha 1-selective antagonist prazosin were similar in arteries from control and diabetic rats and were 2.5-3 log units greater than pA2 values calculated for the alpha 2-selective antagonist yohimbine. Contractile responses of aortae incubated in Ca2(+)-free Krebs' solution containing 1 mM EGTA to maximal but not to ED50 concentrations of the alpha-adrenoceptor agonists were significantly greater in preparations from diabetic than from control rats. Following readdition of Ca2+, contractile responses of diabetic aortae to all concentrations of the agonists tested were significantly greater than control. Similar results were obtained in mesenteric arteries, except that no clonidine response could be detected in preparations from either diabetic or control rats in the absence of extracellular Ca2+. These data indicate that enhanced responses of arteries from diabetic rats to alpha-adrenoceptor agonists are mediated by alpha 1 adrenoceptors, and are largely dependent on the presence of extracellular Ca2+. However, increased release of intracellular Ca2+ appears to contribute to enhanced responses to high concentrations of these agonists.


Reduction in health service use for whiplash injury after motor vehicle accidents in 2000-2009: results from a defined population.
To establish trends in whiplash-related health service use and cost in Victoria, Australia. Administrative data analysis. Whiplash patients claiming Transport Accident Commission (TAC) compensation for accidents dating between 1 January 2000 and 31 December 2009 (n = 51,263). Injury-related health service use during one year following the accident was determined from claim payment records. The incidence of whiplash claims in Victoria was calculated, as were inflation-adjusted health care costs. In 2000-2009, the incidence of compensable whiplash decreased from 1.56 to 1.14 per 1,000 person-years. Physiotherapy, pharmaceuticals, general practitioner, chiropractic, radiology and osteopathy sessions were the most commonly claimed services. General practitioner, allied health and radiology services decreased, but analgesic use increased. Per person-years in the population, whiplash-related medical expenses were 71% greater for women than men. Overall, population burden decreased by 38%; the decline was most pronounced in persons aged 18-24 (54% decrease) and least pronounced in those aged ≥ 55 (23% decrease). The population-based health service cost of whiplash decreased between 2000 and 2009. The overall reduction was related to a decrease in incidence and a reduction in service use per whiplash claim.


Evaluation of the toll-like receptor 6 Ser249Pro polymorphism in patients with asthma, atopic dermatitis and chronic obstructive pulmonary disease.
For allergic disorders, the increasing prevalence over the past decade has been attributed in part to the lack of microbial burden in developed countries ('hygiene hypothesis'). Variation in genes encoding toll-like receptors (TLRs) as the receptor system for the first innate immune response to microbial stimuli has been implicated in various inflammatory diseases. We evaluated here the role of a coding variation, Ser249Pro, in the TLR6 gene in the pathogenesis of asthma, atopic dermatitis (AD) and chronic obstructive pulmonary disease (COPD). Genotyping of the Ser249Pro polymorphism in 68 unrelated adult patients and 132 unrelated children with asthma, 185 unrelated patients with COPD, 295 unrelated individuals with AD and 212 healthy control subjects was performed by restriction enzyme digestion. We found a weak association of the 249Ser allele with childhood asthma (p = 0.03). Yet, significance was lost after Bonferroni correction. No association was evident for AD or COPD. Variation in TLR6 might play a role in the pathogenesis of childhood asthma.


Biomonitoring of heavy metals and air quality in Cordoba City, Argentina, using transplanted lichens.
The objective of the present study was to test the concentrations of some elements in the transplanted lichen Usnea amblyoclada transplanted in Córdoba, Argentina, and to investigate the relative air quality of the area as indicated by a Pollution Index. Analyses of Cu, Co. Pb, Fe, Ni, Mn, S and Zn in addition to analyses of physiological parameters were performed after the transplantation period. No significant differences were observed among the sampling stations for the physiological parameters, except the dry weight/fresh weight ratio. The concentration of most elements was similar to or lower than those found in non-polluted and even polluted areas. The significant correlation found between Cu, Pb and Zn with the content of hydroperoxy conjugated dienes suggests an important oxidative effect probably caused by these ions. The distribution patterns of the elements were quite similar, with maximum values around a cement plant and the metallurgical industries. The Pollution Index distribution pattern does not coincide with the elements distribution, due to the fact that the index values probably reflected the emissions of gaseous phytotoxic pollutants.


Hospital versus home treatment of deep vein thrombosis in a tertiary care hospital in Saudi Arabia: Are we ready?
Treatment of DVT with LMWHs has been shown recently to be as effective as UFH with suggested lower costs. This study was conducted to determine and compare the cost of in-patient hospital treatment versus outpatient hospital treatment of patients with DVT. All adult patients with acute proximal DVT referred to the Emergency Department of King Khalid University Hospital, Riyadh, Saudi Arabia between August 2009 and August 2010 were invited to the study. An economic analysis was performed to compare the cost impact of outpatients versus hospital treatment. Sixty-one patients were included in the study, 31 were followed in the outpatient setting and 30 as the control group (inpatients). There were no significant differences in the outcome between the outpatient and inpatient group; three patients (9.7%) in the outpatient group and four patients (13.3%) in the inpatient group had recurrent DVT. Mean nursing cost was $55 for the outpatient group and $215 for the inpatient group, mean laboratory monitoring cost was $638 for outpatient group and $1511 for the inpatient group. Hospital stay and doctor's fees amounted to a mean of $1000 for outpatient treatment and $2387 for inpatient treatment, p < 0.0001. The mean outpatient cost was significantly lower than the inpatient cost ($1750 vs. $4338, p < 0.0001). Outpatient treatment of patients with DVT using LMWHs is cost-effective with no significant differences in the outcome of patients. OPD treatment of DVT is feasible in Saudi Arabia provided there is enough logistic support from thrombosis clinics and those involved in DVT care.


Anti-thyroid antibodies and underlying generalized immunologic aberrations in patients with reproductive failures.
The link between autoimmune thyroid diseases and reproductive failures, including implantation failure and pregnancy loss, has been attracted a great deal of attention in the last two decades. In this regard, a considerable progress has been achieved in understanding the etiopathogenesis of the adverse pregnancy consequences related to the presence of anti-thyroid antibodies, however, the exact action mechanisms of these antibodies are not fully comprehended. Thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs) and TSH receptor antibodies (TRAbs) are the anti-thyroid antibodies which are present in autoimmune thyroid disorder (AITD) patients, such as Hashimoto's thyroiditis. In this condition, the thyroid hormones production, which are essential for normal implantation and pregnancy, are disrupted, and compromise the embryo or fetus development. In addition, a hypothesis suggests that there is underlying generalized immune abnormalities behind the presence of these antibodies. On the other hand, similar immunologic aberrations have been observed in thyroid autoimmunity and reproductive complications, which are postulated to be the proper answer for the scientists who seek for the pathophysiology behind the presence of these antibodies. Elevated inflammatory responses and decreased immunoregulatory actions, seem to be the main interfering pathologic factors in maternal tolerance toward fetus. In addition, cross reactivity of these antibodies with antigenic determinants of egg, embryo and placenta is another suggested mechanism, causing implantation and pregnancy complications. The ability of anti-thyroid antibodies in passing through the placental barrier and affecting the fetal thyroid gland, makes them more threatening for maintenance of a pregnancy.


Episodic hypothermia with hyperhidrosis in a pregnant woman.
Episodic hypothermia with hyperhidrosis is a disorder of thermoregulation, believed to be secondary to a hypothalamic dysfunction, which affects the body's thermoregulatory centers. During this rare condition, the body may sweat profusely in an attempt to maintain a lowered body temperature set point. The exact cause of episodic hypothermia with hyperhidrosis is not known. A multigravida at 35 weeks' gestation presented with symptoms consistent with hypothermia, although she was diaphoretic. Her basal body temperature was 91.2F, with a lowered blood pressure and heart rate. The fetal heart rate was 130 beats per minute and reassuring. Assisted rewarming occurred over a period of 3 hours, after which her temperature stabilized at 97.9F. The remainder of the pregnancy was uneventful, and the patient delivered a term infant with no apparent adverse effects from this episode. Episodic hypothermia with hyperhidrosis should be considered as a potential cause of hypothermia during pregnancy.