Pulmonary hypertension secondary to serum hyperviscosity in a patient with rheumatoid arthritis.
A patient with rheumatoid arthritis who was evaluated for dyspnea of six months' duration is described. Although no primary cardiac or parenchymal lung disease was identified, right heart catheterization revealed marked pulmonary hypertension. The patient was presumed to have pulmonary arteritis. Evaluation of her hyperproteinemia, however, led to the discovery of a polyclonal gammopathy with a marked increase in plasma viscosity. Although the classic clinical findings of the hyperviscosity syndrome were minimal, the patient underwent plasmapheresis, resulting in a marked reduction of pulmonary artery pressures (from 53 +/- 4 mm Hg, mean +/- SD, to 30 +/- 3 mm Hg, p less than 0.05) and pulmonary vascular resistance (from 707 +/- 63 dynes/second/cm5 to 421 +/- 72 dynes/second/cm5, p less than 0.05) concomitant with a return to normal plasma viscosity. Her dyspnea completely resolved. This represents the first successful treatment of pulmonary hypertension by plasmapheresis. Protein evaluation revealed the presence of intermediate complexes of IgG rheumatoid factor. The hyperviscosity syndrome should be considered in the differential diagnosis of pulmonary hypertension in patients with rheumatoid arthritis and other disorders associated with a polyclonal or monoclonal gammopathy. Pulmonary hypertension secondary to the hyperviscosity syndrome is reversible by plasmapheresis. Immunosuppressive therapy that reduces immunoglobulin production may provide a means of long-term treatment.


Mediation of augmented monocyte adhesiveness by thromboxane.
We examined the potential contribution of thromboxanes in human monocyte adherence to plastic. Monocyte adherence to plastic could be augmented by various stimuli including lipopolysaccharide, chemotactic peptide, and supernates of antigen-stimulated lymphocytes. Increments in monocyte adhesiveness were suppressed by inhibition of cyclooxygenase, thromboxane synthetase, or by antiserum to thromboxane B2. Neither prostaglandin E2 or F2 alpha significantly affected baseline or lipopolysaccharide-stimulated monocyte adherence. Additional experiments confirmed incremental production of thromboxane B2 by monocytes after incubation with lipopolysaccharide. Thromboxane B2 itself did not stimulate monocyte adhesiveness. These data demonstrate that monocytes release thromboxane A2 following stimulation and suggest that thromboxane A2 may play a significant role in monocyte-substrate attachment.


Anomalous anisotropic behaviour of spin-triplet proximity effect in Au/SrRuO3/Sr2RuO4 junctions.
Spin-polarized supercurrents can be generated with magnetic inhomogeneity at a ferromagnet/spin-singlet-superconductor interface. In such systems, complex magnetic inhomogeneity makes it difficult to functionalise the spin-polarized supercurrents. However, spin-polarized supercurrents in ferromagnet/spin-triplet-superconductor junctions can be controlled by the angle between magnetization and spin of Copper pairs (d-vector), that can effectively be utilized in developing of a field of research known as superconducting spintronics. Recently, we found induction of spin-triplet correlation into a ferromagnet SrRuO3 epitaxially deposited on a spin-triplet superconductor Sr2RuO4, without any electronic spin-flip scattering. Here, we present systematic magnetic field dependence of the proximity effect in Au/SrRuO3/Sr2RuO4 junctions. It is found that induced triplet correlations exhibit strongly anisotropic field response. Such behaviour is attributed to the rotation of the d-vector of Sr2RuO4. This anisotropic behaviour is in contrast with the vortex dynamic. Our results will stimulate study of interaction between ferromagnetism and unconventional superconductivity.


Dental discoloration caused by bismuth oxide in MTA in the presence of sodium hypochlorite.
The aim of this research was to analyse the dental discolouration caused by mineral trioxide aggregate (MTA) induced by bismuth oxide and also assess the colour stability of other dental cements. Bismuth oxide, calcium tungstate and zirconium oxide were placed in contact with sodium hypochlorite for 24 h after which they were dried and photographed. Phase analyses were performed by X-ray diffraction (XRD) of radiopacifiers before and after immersion in sodium hypochlorite. Furthermore, teeth previously immersed in water or sodium hypochlorite were filled with MTA Angelus, Portland cement (PC), PC with 20 % zirconium oxide, PC with 20 % calcium tungstate and Biodentine. Teeth were immersed for 28 days in Hank's balanced salt solution after which they were sectioned and characterized using scanning electron microscopy (SEM) with energy-dispersive mapping and stereomicroscopy. Bismuth oxide in contact with sodium hypochlorite exhibited a change in colour from light yellow to dark brown. XRD analysis demonstrated peaks for radiopacifier and sodium chloride in samples immersed in sodium hypochlorite. The SEM images of the dentine to material interface showed alteration in material microstructure for MTA Angelus and Biodentine with depletion in calcium content in the material. The energy-dispersive maps showed migration of radiopacifier and silicon in dentine. MTA Angelus in contact with a tooth previously immersed in sodium hypochlorite resulted in colour alteration at the cement/dentine interface. MTA Angelus should not be used after irrigation with sodium hypochlorite as this will result in tooth discoloration.


Multidirectional insights into the phytochemical, biological, and multivariate analysis of the famine food plant (Calligonum polygonoides L).: A novel source of bioactive phytocompounds.
Calligonum polygonoides L. also known as famine food plant, is normally consumed in times of food scarcity in India and Pakistan and also used traditionally in the management of common diseases. The present design aims to provide an insight into the medicinal potential of four solvent extracts of C. polygonoides via an assessment of its phytochemical profile, antioxidant and enzyme inhibitory potential. Phytochemical composition was estimated by deducing total bioactive constituents, UHPLC-MS secondary metabolites profile, and HPLC phenolic quantification. Antioxidant potential was determined via six methods (radical scavenging (DPPH and ABTS), reducing power (FRAP and CUPRAC), phosphomolybdenum total antioxidant capacity and metal chelation activity). Enzyme inhibitory potential was assessed against clinical enzymes (acetylcholinesterase -AChE, butyrylcholinesterase -BChE, tyrosinase, and α-amylase). The highest amounts of phenolic contents were found in chloroform extract (76.59 mg GAE/g extract) which may be attributed to its higher radical scavenging, reducing power and tyrosinase inhibition potential. The n-butanol extract containing the maximum amount of flavonoids (55.84 mg RE/g extract) exhibited highest metal chelating capacity. Similarly, the n-hexane extract was found to be most active against AChE (4.65 mg GALAE/g extract), BChE (6.59 mg GALAE/g extract), and α-amylase (0.70 mmol ACAE/g extract) enzymes. Secondary metabolite assessment of the crude methanol extract as determined by UHPLC-MS analysis revealed the presence of 24 (negative ionization mode) and 15 (positive ionization mode) secondary metabolites, with most of them belonging to phenolic, flavonoids, terpene, and alkaloid groups. Moreover, gallic acid and naringenin were the main phenolics quantified by HPLC-PDA analysis in all the tested extracts (except n-butanol extract). PCA statistical analysis was also conducted to establish any possible relationship amongst bioactive contents and biological activities. Overall, the C. polygonoides extracts could be further considered to isolate bioactive enzyme inhibitory and antioxidant natural phytocompounds.


Microheterogeneity of paraproteins. I. Diagnostic value of isoelectric focusing followed by immunoblotting.
Isoelectric focusing (IEF) in thin-layer polyacrylamide gels followed by immunoblotting on nitrocellulose membranes is presently the most sensitive method in the routine detection of IgG paraproteins. With this technique, immunoglobulin class and light chain composition can be as reliably identified as in immunoelectrophoresis. The problem of firm adherence between IEF polyacrylamide gels and nitrocellulose membranes can be overcome by brief incubation in sodium dodecyl sulfate. After isoelectric focusing, IgG paraproteins display a characteristic pattern of limited electrophoretic heterogeneity. This pattern is easily recognized even in the few cases with a constant tendency to aggregate under IEF conditions and in the surprisingly high percentage of paraproteins with very alkaline isoelectric points in which it is altered due to a cathodal collection effect. It is independent of the total amount of IgG in serum and remains stable intraindividually over extended observation periods. On the other hand, there is a very high degree of interindividual variability while common paraprotein characteristics still remain recognizable.


Optimization of the formula and processing of a sweet potato leaf powder-based beverage.
For the development of a sweet potato leaf powder (SPLP)-based beverage, we investigated the effects of blanching methods on SPLP quality (including color, nutritional and functional compositions and antioxidant activity), and the effects of particle size and stabilizers on suspension stability of final product. The total polyphenol and antioxidant activity of SPLP of uncut group were 1.69 and 1.91 times those of cut group, respectively, and the indices of nutritional quality of copper, manganese and vitamin E of uncut group were significantly greater than cut group. The ultrafine SPLP-produced lowest gravitational sedimentation ratio (49%), indicating it had greatest suspension stability. The optimized formula of SPLP-based beverage was as follows: ultrafine SPLP of uncut group was mixed with 2.5% (w/w, powder basis) xanthan gum, 1% calcium lactate, 2% ascorbic acid, 12% maltodextrin, 20% xylitol, and 0.9% apple essence. The final product had high nutritional value along with consumer-acceptable flavor and texture.


Effects of midodrine in patients with ascites due to cirrhosis: Systematic review and meta-analysis.
Midodrine has been reported to improve systemic and renal hemodynamics in patients with cirrhotic ascites. However, the results of clinical trials are conflicting. The aim of this study is to evaluate the effects of midodrine on cirrhotic ascites through a meta-analysis and systematic review. We searched PubMed (January 1966-December 2014), EMBASE (January 1966-December 2014), the Cochrane Library (Issue 11, 2014), ScienceDirect (January 1966-December 2014), and the China National Knowledge Infrastructure (January 1979-December 2014) databases using the terms 'midodrine' AND 'cirrhosis' AND 'ascites' AND 'paracentesis' for all relevant randomized controlled trials using midodrine for treatment of cirrhotic ascites. In all, 10 trials with a total of 462 patients were included. As a novel therapy for cirrhotic ascites, midodrine was not found to improve survival [odds ratio (OR) 0.81, 95% confidence interval (CI) 0.23-2.91]; although it might improve response rates (OR 3.36, 95% CI 1.47-7.69) and reduce plasma renin activity (MD -3.10, 95% CI -5.37 to -0.84). When midodrine was used as an alternative to albumin in large-volume paracentesis, the mortality was higher for midodrine than for albumin (OR 10.76, 95% CI 1.35-85.97). However, there was no statistically significant difference in the development of paracentesis-induced circulatory dysfunction between midodrine group and albumin group (OR 1.69, 95% CI 0.43-6.72). Midodrine may have treatment effects on cirrhotic ascites. Better powered and well-designed trials are required to assess the extent of the efficacy of midodrine in specifically targeted patients.


Intraoperative considerations in a patient with chondroblastic osteosarcoma and saddle pulmonary embolism undergoing amputation.
In patients presenting to the operating room with a saddle pulmonary embolism for noncardiac surgery, it is best to take a multidisciplinary approach and involve the cardiac and vascular surgeons.


Total decompression of the spinal cord for combined ossification of posterior longitudinal ligament and yellow ligament in the thoracic spine.
One of the causes of hyperostosis in the spinal canal, ossification of the posterior longitudinal ligament (OPLL) combined with ossification of the yellow ligament (OYL) in the thoracic spine, can result in serious myelopathy, leading to sandwich-type compression of the spinal cord from anterior and posterior. For such cases we devised a treatment of total decompression of the spinal cord and intervertebral body fusion. This operation consists of two steps. The first step is designed for posterior and lateral decompression of the spinal cord by removal of the OYL following wide laminectomy. The second step is removal of the OPLL anteriorly for anterior decompression, followed by interbody fusion. As the final procedure of the first step, two deep parallel gutters, covering the extent of the OPLL to be removed anteriorly, are drilled down from the rear into the vertebral body along both sides of the dura. This pre-treatment makes removal of the OPLL anteriorly during the second stage much easier, faster, and safer. This operation is lengthy and demanding. However, based on our experience so far, it appears to be a promising surgical procedure.


Wrapper, a novel member of the Ig superfamily, is expressed by midline glia and is required for them to ensheath commissural axons in Drosophila.
The midline glia are specialized, nonneuronal cells at the midline of the Drosophila central nervous system (CNS). During development, the midline glia provide guidance cues for extending axons. At the same time, they migrate and help separate the two axon commissures. They then wrap around and ensheath the commissural axons. In many segments, a few of the glia do not enwrap the axons, and these cells die. The wrapper gene encodes a novel member of the immunoglobulin (Ig) superfamily. Wrapper protein is expressed specifically on the surface of midline glia. In wrapper mutant embryos, the midline glia express their normal guidance cues and migrate normally. However, they do not ensheath the commissural axons, and as a result, the glia die. In the absence of Wrapper, the two axon commissures are not properly separated.


Epithelial tissue folding pattern in confined geometry.
The primordium of the exoskeleton of an insect is epithelial tissue with characteristic patterns of folds. As the insect develops from larva to pupa, the spreading of these folds produces the three-dimensional shape of the exoskeleton of the insect. It is known that the three-dimensional exoskeleton shape has already been encoded in characteristic patterns of folds in the primordium; however, a description of how the epithelial tissue forms with the characteristic patterns of folds remains elusive. The present paper suggests a possible mechanism for the formation of the folding pattern. During the primordium development, because of the epithelial tissue is surrounded by other tissues, cell proliferation proceeds within a confined geometry. To elucidate the mechanics of the folding of the epithelial tissue in the confined geometry, we employ a three-dimensional vertex model that expresses tissue deformations based on cell mechanical behaviors and apply the model to examine the effects of cell divisions and the confined geometry on epithelial folding. Our simulation results suggest that the orientation of the axis of cell division is sufficient to cause different folding patterns in silico and that the restraint of out-of-plane deformation due to the confined geometry determines the interspacing of the folds.


Investigation of biochemical changes of the ovine calpain 3 exon-10 polymorphism.
Calpain 3 (CAPN3) is a tissue specific calpain, and its mRNA is the most expressed calpain isoform in skeletal muscles. Many mutations and polymorphisms within the human CAPN3 gene have been reported and related to limb-girdle muscular dystrophy. Several reports link CAPN3 polymorphisms and meat quality. An association between three allele variants in exon-10 of ovine CAPN3 and the yield of fat trimmed meat cuts has been reported. This research investigated the biochemical significance of polymorphic variation in CAPN3. CAPN3 mRNA sequences were obtained from muscle samples collected from lambs which were homozygous for each of the three alleles. Four single base substitutions were found besides those in exon-10, but none of them, including the variations within exon-10, caused a change in amino acid sequence. The expression of CAPN3 mRNA and the amounts of CAPN3 protein were also compared among genotypes, and no significant differences were found. These results suggest that the reported association of specific allele variants within CAPN3 exon-10 to phenotype variations were not direct effects of CAPN3 polymorphisms. Interspecies analyses of the CAPN3 sequences indicated that the sequence reported here is more likely to be the correct common ovine CAPN3 sequence than the reference sequence.


Prolonged prostaglandin E1 infusion in an infant with cyanotic congenital heart disease.
A small-for-gestational-age premature infant with severe tetralogy of Fallot was treated with prostaglandin E1 to dialate the ductus arteriosus and increase pulmonary blood flow. The infusion was continued for 29 days without complication at which time surgery was performed.


Extraordinary metabolic stability of peptides containing α-aminoxy acids.
The metabolic stability of peptides containing a mixed sequence of α-aminoxy acids and α-amino acids is significantly improved compared to peptides composed of only natural α-amino acids. The introduction of an α-aminoxy acid into peptide chain dramatically improves the stability of the amide bonds immediately before and after it. These peptides containing α-aminoxy acids represent excellent structural scaffold for the design of metabolically stable and biologically active peptides.


Histological study on the fate of haptenated epidermal cells injected intradermally in guinea pigs.
The percutaneous administration of in vitro haptenated epidermal cells (EC) has become established as a procedure to produce contact sensitivity (CS) in experimental animals for routine use. The cells have also been found to elicit a significant delayed-type skin reaction by intradermal test in the animals sensitized by painting the skin with the hapten. The fate of 2,4-dinitrophenylated (DNP) isogeneic epidermal cell suspensions (EC) injected intradermally was investigated histologically in intact or 2,4-dinitrochlorobenzene (DNCB)-sensitized strain 13 guinea pigs to study the role of the cells in CS. DNP-EC were found to proliferate actively in the dermis and formed EC nests with central keratinization and then elicited inflammatory reaction associated with necrosis of the epidermal structures 7 days after injection in the intact animals. DNP-EC injected intradermally into the animals which had received and reacted against DNCB underwent a suppression of EC proliferation. These findings are discussed in relation to the role of the haptenated EC in CS.


Hypertension enhances Aβ-induced neurovascular dysfunction, promotes β-secretase activity, and leads to amyloidogenic processing of APP.
Hypertension (HTN) doubles the risk of Alzheimer's disease (AD), but the mechanisms remain unclear. Amyloid-β (Aβ), a key pathogenic factor in AD, induces cerebrovascular dysfunction. We hypothesized that HTN acts in concert with Aβ to amplify its deleterious cerebrovascular effects and to increase Aβ production. Infusion of angiotensin II (ANGII; intravenously) elevated blood pressure and attenuated the cerebral blood flow (CBF) response to whisker stimulation or the endothelium-dependent vasodilator acetylcholine (ACh) (P < 0.05). Neocortical application of Aβ in mice receiving ANGII worsened the responses to ACh (P < 0.05). The cerebrovascular dysfunction observed in Tg2576 mice, in which Aβ is elevated both in blood and in brain due to expression of mutated amyloid precursor protein (APP), was not aggravated by neocortical application of ANGII or by a 2-week administration of 'slow pressor' of ANGII (600 ng/kg per minute; subcutaneously). In contrast, ANGII aggravated the dysfunction in TgSwDI mice, in which Aβ is increased only in brain. Slow-pressor ANGII induced microvascular amyloid deposition in Tg2576 mice and enhanced β-secretase APP cleavage. In Chinese hamster ovary (CHO) cells producing Aβ, ANGII increased β-secretase activity, Aβ1-42, and the Aβ42/40 ratio. We conclude that HTN enhances amyloidogenic APP processing, effects that may contribute to the pathogenic interaction between HTN and AD.


Mouse model of plasma cell mastitis.
Plasma cell mastitis is distinct from the common form of mastitis and clinically resembles breast carcinoma. The lesion occurs in non-lactating young women, and the incidence rate is rising. Surgical resection is the main treatment, but cannot prevent recurrence of the disease. Disfigurement or removal of breast after the operations can cause marked physical and psychological distress. The etiology of plasma cell mastitis is unclear up till now. It is therefore necessary to investigate further the underlying immunological changes of the disease. The lesions of plasma cell mastitis removed from patients through aseptic operation were mixed with normal saline into homogenate tube machine (homogenate tubes were disinfected and sterilized prior to treatment). The mixture was homogenized at medium speed and grinded in ultrasonic cell disruptor. The homogenate obtained was made into oil emulsion with Freund's adjuvant. Thirty female BALB/c mice (6 weeks after sexual maturity) were divided into five groups A-E: group A was blank control; group B was normal saline control; group C was inoculated with 0.02 ml water-in-oil emulsion; group D was inoculated with 0.04 ml water-in-oil emulsion; group E was complete Freund's adjuvant control. Pathology results showed that mouse mammary gland acinar cells remained integral without any abnormal changes observed in control groups A and B. Experimental groups C and D showed dilation of mouse mammary ductal tissue with a large number of epithelial cells and debris in the lumen, and fibrosis around ducts accompanied by large duct cells, neutrophils, lymphocytes, and especially plasma cell infiltration. Pathological changes were observed in 3 (50%) mice and 5 (83.3%) mice in group C and D respectively. In group E, neutrophil infiltration in mammary gland was observed in 5 mice, but neither infiltration of plasma cells nor other abnormal pathological changes were observed. The lesions of patient with plasma cell mastitis could make the female BALB/c mice experience the similar clinical and pathological manifestation. High-dose group can successfully establish a mouse model of plasma cell mastitis.


High prevalence of 16S rRNA methylase RmtB among CTX-M extended-spectrum β-lactamase-producing Klebsiella pneumoniae from Islamabad, Pakistan.
The aim of this study was to characterise extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae isolated from urinary tract and wound infections from Pakistan (n=25). Isolates were subjected to commercially available microarray analysis to determine the presence of ESBLs and acquired AmpC enzymes. The genetic diversity of the isolates was determined by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid replicon typing and capsular serotyping were conducted by PCR. Finally, screening for virulence genes, plasmid-mediated quinolone resistance (PMQR) genes, and genes encoding 16S rRNA methylases was done using PCR. All K. pneumoniae isolates hosted blaCTX-M genes and all strains belonged to phylogroup CTX-M-1. Acquired AmpC β-lactamases (ACT/MIR and CIT group) were found in 16% of isolates. Two clusters were observed with ≥80% similarity among profiles obtained by PFGE, and two sequence types (STs) by MLST, namely ST215 and ST307, were observed in these clusters. Three ST215 isolates carried virulence factor wcaG and three ST215 isolates had capsular type K20. IncFIA, IncFIB, IncFIIK and FrepB replicons were most commonly found in this collection. Among the PMQR determinants, aac(6')-lb-cr was present in 96% (24/25) of the isolates, qnrB was found in 88% (22/25) and qepA was found in 4% (1/25). The 16S rRNA methylase-encoding gene rmtB was found in 60% (15/25) of the isolates. In conclusion, CTX-M-producing ST215 and ST307 K. pneumoniae were the two major clones detected. Of particular concern was the high prevalence of 16S rRNA methylases conferring resistance to all aminoglycosides.


Therapeutic efficiency of rhenium-188-HEDP in human prostate cancer skeletal metastases.
Rhenium-188-HEDP ((188)Re-HEDP) is a new and attractive radiopharmaceutical for the treatment of metastatic bone pain. As a product of (188)W/(188)Re generator, it is convenient for clinical therapeutic use with a short physical half-life of 16.9 h and a maximal beta-energy of 2.1 MeV. We investigated the effect of (188)Re-HEDP on pain relief, analgesic intake and impairment of bone marrow function in 27 patients with bone metastases induced from prostate cancer. All patients were interviewed using a standardised set of questions before, and after therapy for 12 weeks. The patients were treated with 2700-3459 MBq of (188)Re-HEDP. Blood samples were taken weekly for 12 weeks, and a blood count was performed. Patients described an improvement on the Karnofsky performance scale from 74+/-7 to 85+/-9% 12 weeks after therapy (P=0.001). The pain score showed a maximum decrease from 44+/-18 to 27+/-20% in the third to the eight week after therapy (P=0.009). Seventy-six percent of the patients described a pain relief without increase of analgesic intake. Twenty percent of the patients could discontinue their analgesics and were pain free. Mean platelet count decreased from (286+/-75)*10(3) microl(-1) to (215+/-92)*10(3) microl(-1), and mean leucocyte count from (7.7+/-1.5)*10(3) microl(-1) to (6.0+/-1.9)*10(3) microl(-1) in the second to the fourth week after therapy. The maximal differences between the values of platelets and leucocytes before and after therapy were not statistically significant (P=0.021 and 0.094). In conclusion, (188)Re-HEDP is an effective radiopharmaceutical used in the palliative treatment of metastatic bone pain in prostate cancer and shows minimal bone marrow toxicity.


Direct interaction between Rab3b and the polymeric immunoglobulin receptor controls ligand-stimulated transcytosis in epithelial cells.
We have examined the role of rab3b in epithelial cells. In MDCK cells, rab3b localizes to vesicular structures containing the polymeric immunoglobulin receptor (pIgR) and located subjacent to the apical surface. We found that GTP-bound rab3b directly interacts with the cytoplasmic domain of pIgR. Binding of dIgA to pIgR causes a dissociation of the interaction with rab3b, a process that requires dIgA-mediated signaling, Arg657 in the cytoplasmic domain of pIgR, and possibly GTP hydrolysis by rab3b. Binding of dIgA to pIgR at the basolateral surface stimulates subsequent transcytosis to the apical surface. Overexpression of GTP-locked rab3b inhibits dIgA-stimulated transcytosis. Together, our data demonstrate that a rab protein can bind directly to a specific cargo protein and thereby control its trafficking.


Occurrence of extended-spectrum β-lactamase and AmpC-producing Escherichia coli in retail meat products from the Maritime Provinces, Canada.
This study was conducted to determine the occurrence of antimicrobial resistance to the extended-spectrum cephalosporins (ESC) in Escherichia coli isolates. The isolates were collected from retail meat products collected in the Maritime Provinces of Canada. Our analyses involved the use of both selective and traditional culture methods; we also conducted genotype analyses using multiplex polymerase chain reactions. ESC-resistant (ESC-R) E. coli were detected in 33 of 559 samples (5.9%) using the traditional culture method, compared with 151 of 557 samples (27.1%) using the selective culture method. We recovered more isolates of ESC-R E. coli from poultry compared with beef and pork (P < 0.001). Multidrug resistance, extended-spectrum β-lactamase (ESBL), and AmpC phenotypes were more common in chicken-derived isolates than other retail meat products (P < 0.001). From the 98 isolates examined, 76 isolates (77.6%) were positive for either ESBL and AmpC β-lactamases or both. Among the 76 isolates, blaCMY-2 (78.9%), blaCTXM (46.1%), blaTEM (21.1%), and blaSHV (1.3%) genes were detected. Among the blaCTXM-producing isolates, blaCTXM-1, blaCTXM-2, and blaCTXM-9 phylogenetic groups were detected. β-lactamase genes were more commonly detected in chicken-derived isolates compared with other meat types (P < 0.01). This study demonstrates the occurrence of ESBL- and AmpC-resistance genes in retail meat products in the Maritime Provinces of Canada. We found that selective culture significantly improved the recovery of ESC-R E. coli isolates from retail meat samples.


Competitive endogenous RNA (ceRNA) regulation network of lncRNA-miRNA-mRNA during the process of the nickel-induced steroidogenesis disturbance in rat Leydig cells.
Nickel (Ni) is a ubiquitous environmental pollutant, which can disrupt the production of steroid in rat Leydig cells. Steroidogenesis can be affected by non-coding RNAs (ncRNAs), which operate in normal physiological processes. To date, however, very few studies have focused on whether ncRNAs are involved in Ni-induced steroidogenesis disturbance. The present study was designed to investigate the impact of NiSO4 on the regulation of RNA networks including long non-coding RNA (lncRNA), microRNA (miRNA), and mRNA in rat Leydig cells. After treatment with 1000 μmol/L NiSO4 for 24 h, 372 lncRNAs, 27 miRNAs (fold change>2, p < .05) and 3666 mRNAs (fold change>2, p < .01, and FDR < 0.01) were identified to be markedly altered by high-throughput sequencing analysis in rat Leydig cells. Functional analysis showed that the differentially expressed mRNAs were annotated into some steroid-related pathways. A dysregulated competing endogenous RNA (ceRNA) network of lncRNA-miRNA-mRNA was constructed based on bioinformatic analysis. Furthermore, a ceRNA network related to steroidogenesis was selected to analyze further and after the validation by qRT-PCR. The LOC102549726/miR-760-3p/Atf6, LOC102549726/miR-760-3p/Ets1, LOC102549726/miR-760-3p/Sik1 and AABR07037489.1/miR-708-5p/MAPK14 ceRNA networks were eventually confirmed. Collectively, our study provided a systematic perspective on the potential role of ncRNAs in steroidogenesis disturbance induced by Ni in rat Leydig cells.


Dopamine excretion in benign pheochromocytoma.
Dopamine excretion is reported in 27 patients with benign pheochromocytoma. In 21 patients the tumours were in the adrenal (one patient, bilateral), four were extra-adrenal, and two were assumed to be so since they were not found at laparotomy. Dopamine excretion was found to be higher in the patients with extra-adrenal tumours and in one patient--with bilateral pheochromocytoma. Slight increase of dopamine excretion was found in two of the remaining patients. These observations--indicate that while increased dopamine excretion may be present in patients with malignant pheochromocytoma it can be also increased in some patients with benign tumours.


How available to European children and young people with cerebral palsy are features of their environment that they need?
The UN Convention on the Rights of Persons with Disabilities requires accessibility to the physical and social environments. However, individuals with cerebral palsy (CP) have many difficulties in accessing the environment they need for functional independence and social inclusion. To examine the availability of environmental features which children with CP need for optimal participation, and whether availability changed for them between ages 8-12 and 13-17 years. The sample is the 594 children with CP, born 31/07/1991-01/04/1997, who took part in the SPARCLE study at age 8-12 (SPARCLE 1) and again at 13-17 years (SPARCLE 2). Participants were randomly sampled from population registers of children with CP in eight European regions; one further region recruited from multiple sources. Data about environment were captured with the European Child Environment Questionnaire (60 items). Differences in availability of environmental features between childhood and adolescence were assessed using McNemar's test; differences between regions were assessed by ranking regions. Differences in availability between regions were assessed by ranking regions. For seven environmental features significantly (p<0.01) fewer individuals needed the feature in SPARCLE 2 than in SPARCLE 1, whilst for two features more individuals needed the feature. Nine features in SPARCLE 1 and six features in SPARCLE 2 were available to less than half the participants who needed them. Eight features showed significantly (p<0.01) higher availability in SPARCLE 2 than in SPARCLE 1 (enlarged rooms, adapted toilet, modified kitchen and hoists at home, adapted toilets and lifts at school, an adequate vehicle, grants for home modifications) while none showed significantly lower availability. The relative rankings of the better and less good regions persisted from the age 8-12year age group to the 13-17year age group. Needed environmental features are unavailable to many children at ages 8-12 and 13-17 years. This lack of availability is more pronounced in some regions than others, which probably results from their policy, legislative and statutory frameworks.


Surgical treatment of coronary sinus orifice atresia with hypoplastic left heart syndrome after total cavo-pulmonary connection.
Atresia of the coronary sinus orifice is rare. We describe the surgical treatment of coronary orifice atresia in an infant with a persistent left superior vena cava after total cavo-pulmonary connection for hypoplastic left heart syndrome. The diagnosis was made by cardiac catheterization after total cavo-pulmonary connection at 8 months of age. After surgery, cardiac performance deteriorated. At reoperation, the coronary sinus was fenestrated to the left atrium. The patient survived surgical treatment of coronary sinus ostial atresia unroofed to the left atrium, guiding the placement of the fenestration with a probe placed through the open cardiac end of left superior vena cava.


Oral health-related quality of life among groups of foundling and delinquent children in comparison with mainstream children.
This study envisages understanding about the Oral Health-Related Quality of Life (OHRQoL) among groups of foundling and delinquent children and compares them with mainstream children in Riyadh, Saudi Arabia. This is a cross-sectional, observational study of a group of foundling and delinquent children aged 11 to 14 years, in care houses in Riyadh, Saudi Arabia, and mainstream school children. Variables measured for each group were demographic data (age, gender), subjective oral health condition, and OHRQoL. An interview-based questionnaire was used for collecting the relevant data. The questionnaire was divided into four parts, oral symptoms, functional limitations, emotional well-being, and social well-being, with each response scored as per the following codes: (0) never, (1) once or twice, (2) sometimes, (3) often, and (4) every day. The top possible score for the total scale was 144, and the lowest was 0. A comparison group of mainstream school children was recruited from public schools. Data were analysed using SPSS version 25.0 statistical software, and one-way ANOVA was used for the analysis of data when three levels or more were categorical, and the response was numerical. A chi-square test was used to assess the correlation between any two categorical variables. Out of the total 99 children, 33 were delinquents, 33 were foundling, and 33 were mainstream children included as a comparative group in the study. It was noted that the delinquents compared to the other children had significantly higher scores in accordance with the data collected, with a mean overall score of 30.61 compared to the score for foundling, which was 19.48, and mainstream children had a meager score of 9.18. Individual factorssuch as the oral symptoms, functional limitations, and emotional and social well-being were scored separately, with delinquents having the highest scores and mainstream children the least. Health, including oral health, is a right everyone is equally subjected to, and while the concept of OHRQoL is relatively new, delinquents and foundling are definitely subjected to poorer standards in terms of their oral hygiene, on-time treatment, and diagnosis, which further deteriorates their quality of life.


Crystal structure of (1S,2R)-6,6-dimethyl-4,8-dioxo-2-phenyl-spiro-[2.5]octane-1-carbaldehyde.
In the title compound, C17H18O3, the two non-spiro C atoms of the cyclo-propane ring bear a formyl and a phenyl substituent which are trans-oriented. In the crystal, mol-ecules are linked by weak C-H⋯O and C-H⋯π contacts resulting in a three-dimensional supra-molecular structure.


The effect of tiamulin administered by different routes and at different ages to turkeys receiving monensin in their feed.
Healthy turkeys receiving 80 ppm monensin in their feed were injected at 26, 40 and 61 days of age with tiamulin at dosages of 12.5 and 25 mg/kg body weight. The aim of the study was to develop a regime for medicating with tiamulin turkeys receiving monensin in their feed, and which would circumvent the known toxicity created by the simultaneous administration of the two drugs. One injection of 12.5 mg/kg tiamulin up to the age of 61 days or 2 injections of 12.5 mg/kg tiamulin up to 40 days of age caused no mortality or adverse reaction.


Human gene discovery through experimental definition of transcribed regions of the human genome.
The sequencing of the human genome has failed to realize its primary goal: the identification of all human genes. We have learned that genes can only be identified with certainty within this vast and information-sparse structure by comparison with transcript sequences. Significantly more sequence data of this kind is required before we can claim to have deciphered our genetic blueprint.


An Assessment of Density Functional Methods for Potential Energy Curves of Nonbonded Interactions: The XYG3 and B97-D Approximations.
A recently proposed double-hybrid functional called XYG3 and a semilocal GGA functional (B97-D) with a semiempirical correction for van der Waals interactions have been applied to study the potential energy curves along the dissociation coordinates of weakly bound pairs of molecules governed by London dispersion and induced dipole forces. Molecules treated in this work were the parallel sandwich, T-shaped, and parallel-displaced benzene dimer, (C6H6)2; hydrogen sulfide and benzene, H2S·C6H6; methane and benzene, CH4·C6H6; the methane dimer, (CH4)2; and the pyridine dimer, (C5H5N)2. We compared the potential energy curves of these functionals with previously published benchmarks at the coupled cluster singles, doubles, and perturbative triplets [CCSD(T)] complete-basis-set limit. Both functionals, XYG3 and B97-D, exhibited very good performance, reproducing accurate energies for equilibrium distances and a smooth behavior along the dissociation coordinate. Overall, we found an agreement within a few tenths of one kcal mol(-1) with the CCSD(T) results across the potential energy curves.


Local blood flow is not linked to lactate within single rabbit skeletal muscles.
A marked regional distribution in blood flow within single skeletal muscles on a non-microvascular level, i.e. at the level of large arterioles or small arteries, is present in dog, cat and rabbit. The mechanism for this perfusion pattern is not known. The goal of the present study was to see if regional blood flow was correlated to regional lactate metabolism. Anesthetized rabbits were studied. Blood flow to 0.25 g muscle samples was measured with microspheres whereas lactate content and lactate dehydrogenase activity were determined in extracts of these samples. No correlation was detected between regional blood flow and regional lactate or lactate dehydrogenase either at rest or during exercise hyperemia. Expressed as the coefficient of variation (CVc), regional blood flow showed a marked scatter, the CVc ranged from 0.32 to 0.35. The corresponding CVc for both lactate and lactate dehydrogenase activity ranged from 0.16 to 0.19. It is concluded that regional blood flow is not correlated to regional lactate metabolism. The regional distribution in blood flow was markedly more uneven than that for lactate content and for lactate dehydrogenase activity.


Pituitary adenoma, primary parathyroid hyperplasia and papillary (non-medullary) thyroid carcinoma. A case of multiple endocrine neoplasia (MEN).
An acidophilic pituitary adenoma associated with primary nodular parathyroid hyperplasia and a small papillary thyroid carcinoma was discovered at the autopsy of a 44 year old female acromegalic. The thyroid carcinoma showed evidence of lymphatic spread. Several etiopathogenetic mechanisms for the non-medullary thyroid carcinomata associated with Multiple Endocrine Neoplasia (MEN) have been postulated, since the follicular epithelium of the thyroid does not belong to the neural ectoderm derivates unlike the C-cells of the thyroid, the adenohypophysis and probably the parathyroid glands. Apart from genetic influence, or coincidence, one has to rule out carcinogenic exposure or hormonal influence. Clinically speaking, one should always consider whether malignant thyroid disease coexists with hyperplastic or neoplastic parathyroid tissue.


Glucagon Receptor Inhibition Reduces Hyperammonemia and Lethality in Male Mice with Urea Cycle Disorder.
The liver plays a critical role in maintaining ammonia homeostasis. Urea cycle defects, liver injury, or failure and glutamine synthetase (GS) deficiency result in hyperammonemia, serious clinical conditions, and lethality. In this study we used a mouse model with a defect in the urea cycle enzyme ornithine transcarbamylase (Otcspf-ash) to test the hypothesis that glucagon receptor inhibition using a monoclonal blocking antibody will reduce the hyperammonemia and associated lethality induced by a high-protein diet, which exacerbates disease. We found reduced expression of glutaminase, which degrades glutamine and increased expression of GS in livers of Otcspf-ash mice treated with the glucagon receptor blocking antibody. The gene expression changes favor ammonia consumption and were accompanied by increased circulating glutamine levels and diminished hyperammonemia. Otcspf-ash mice treated with the glucagon receptor-blocking antibody gained lean and body mass and had increased survival. These data suggest that glucagon receptor inhibition using a monoclonal antibody could reduce the risk for hyperammonemia and other clinical manifestations of patients suffering from defects in the urea cycle, liver injury, or failure and GS deficiency.


Variations of cochlear microphonic potential after sectioning efferent fibers to the cochlea.
Cochlear microphonic (CM) potentials were recorded, in guinea pig, with differential electrodes before and after sectioning the medial efferent innervation at the level of the brainstem. Sectioning the crossed part of the medial efferent innervation did not change the CM whatever the frequency or level of stimulation used. Sectioning the medial--crossed and uncrossed--efferent fibers diminished CM amplitude at frequencies above 2 kHz. Thus, the ipsilateral medial efferent tract seems to be involved, through a tonic action, in controlling outer hair cell micromechanics.


Global, regional and national trends in sex- and age-specific disability-adjusted life years of musculoskeletal disorders, 1990-2019.
To quantify the temporal trend of sex- and age-specific disability-adjusted life years (DALYs) for musculoskeletal (MSK) disorders by region and cause. Data were collected from the Global Burden of Diseases Study 2019. The estimated annual percentage change (EAPC) by sex, age, region and cause was calculated to examine the temporal trend of the age-standardized DALYs rate (ASDR). The sociodemographic index (SDI) and risk exposures were also examined. Between 1990 and 2019, the global ASDR for MSK disorders remained almost stable by sex and age group but decreased among females ages 0-14 years (EAPC = -0.27). Such age and sex patterns were nearly the same by SDI, except for high SDI regions, where ASDR increased in all subgroups except those ages 15-49 years. The trend in ASDR of MSK disorders for females and males ages 50-74 and ≥75 years increased in ∼80% of countries and territories. The greatest increase was in El Salvador for males ages 15-49 years (EAPC = 1.30), followed by Nicaragua. The association between EAPC and SDI was positive in developing regions, particularly among females ages 15-49 years, and negative in developed regions. A decreasing trend in ASDR was mainly driven by the decrease in low back pain, while the increasing trend was largely due to other MSK disorders and gout across sexes and age groups. There are great disparities in the age- and sex-specific trends in ASDR by cause on the global, regional and national levels. More differentiated prevention and management strategies are needed for MSK disorders.


Preventive care use among Hispanic adults with limited comfort speaking English: An analysis of the Medical Expenditure Panel Survey data.
Language barriers have been associated with worse access to healthcare and poorer health outcomes. To assess differences in access to care and utilization of healthcare services between Hispanic adults and non-Hispanic white adults (NHW), we used the Medical Expenditure Panel Survey (2013-2016) to compare Hispanic adults who expressed limited comfort speaking in English (LCE) with Hispanic adults who were comfortable speaking in English (CE) and NHW adults. Hispanic adults with CE were less likely than NHW adults to have a usual source of care, use preventive services, including cervical cancer screening, and healthcare services. However, after adjustment breast and cervical cancer screening exceeded that of NHW adults. Hispanic adults with LCE fared substantially worse than their Hispanic counterparts with CE in having a usual source of care, use of preventive services, breast and colorectal cancer screening, and healthcare services. After adjustment, use of all cancer screening tests were similar. Eliminating disparities for Hispanic adults will require a multi-pronged approach to address access to healthcare and other social determinants of health, including poverty, employment discrimination, and educational inequities. The public health community can help improve health literacy, address barriers to care, and provide appropriate language assistance at point of care using culturally-competent means to promote greater utilization of preventive services, including demand for and delivery of cancer screenings.


A screen of repurposed drugs identifies AMHR2/MISR2 agonists as potential contraceptives.
We identified the anti-Mullerian hormone (also known as Müllerian inhibiting substance or MIS) as an inhibitory hormone that induces long-term contraception in mammals. The type II receptor to this hormone, AMHR2 (also known as MISR2), represents a promising druggable target for the modulation of female reproduction with a mechanism of action distinct from steroidal contraceptives. We designed an in vitro platform to screen and validate small molecules that can activate MISR2 signaling and suppress ovarian folliculogenesis. Using a bone morphogenesis protein (BMP)–response element luciferase reporter cell–based assay, we screened 5,440 compounds from a repurposed drug library. Positive hits in this screen were tested for specificity and potency in luciferase dose–response assays, and biological activity was tested in ex vivo Mullerian duct regression bioassays. Selected candidates were further evaluated in ex vivo follicle/ovary culture assays and in vivo in mice and rats. Here, we report that SP600125, CYC-116, gandotinib, and ruxolitinib can specifically inhibit primordial follicle activation and repress folliculogenesis by stimulating the MISR2 pathway.


Evaluation of a one-parameter flow analysis of cervical samples for gynecology cancer screening.
A total of 246 endocervical samples were collected for Papanicolaou staining and one-parameter flow cytometric DNA analysis (FCDA) using 4',6-diamidino-2-phenylindole as a DNA stain. Typical histograms derived from FCDA analysis were designated class I, II, III, and V. Two groups of patients were studied: 135 women referred for colposcopy (COLPO), and 79 women exposed to diethylstilbestrol (DES). The remaining 32 samples were evaluated and found unsatisfactory. In the colposcopy group FCDA assigned 38 patients normal, 62 mild to moderate dysplasia, 33 moderate to severe dysplasia, and 2 carcinoma in situ and invasive carcinoma. Agreement of Pap smear and FCDA occurred in 56, 59, 72, and 100%, respectively. In the diethylstilbestrol group 57 patients were normal and 12 had mild to moderate dysplasia according to Pap diagnosis. Agreement between FCDA and Pap diagnosis were 45 and 58%, respectively. However, FCDA did not falsely assign severe dysplasia or carcinoma in situ to any DES patient. This preliminary study based on FCDA appears to clearly differentiate patients with normal Pap smears from those patients with invasive cancer.


ATRA sensitized the response of hepatocellular carcinoma to Sorafenib by downregulation of p21-activated kinase 1.
Sorafenib resistance greatly reduces the efficacy of treatments in advanced hepatocellular carcinoma (HCC) patients, but the underlying mechanisms are not thoroughly understood. All-trans retinoic acid (ATRA), an anti-leukaemia agent, has attracted considerable attention due to its role in sensitizing cells to other anticancer treatments. We aimed to investigate the combined effect of ATRA and Sorafenib on HCC and the underlying mechanisms. CCK-8, cell sphere formation, trans-well migration, and wound-healing assays were used to analyse the biological behaviours of HCC cells in vitro. Western blotting and qRT-PCR analysis were conducted to measure the expression of p21 activated kinase 1 (PAK1) and phospho-p21 activated kinase 1 (pPAK1). Xenograft models were established to confirm the synergistic effects of ATRA and Sorafenib in vivo. TUNEL assays and immunohistochemistry were utilized to determine apoptosis, proliferation, PAK1 and pPAK1 levels in tumour tissues. We observed that PAK1 was overexpressed in HCC, and its expression was negatively correlated with the survival of patients. PAK1 promoted the proliferation, self-renewal and epithelial-mesenchymal transition of HCC cells. Correlation analysis indicated that the IC50 of Sorafenib was positively correlated with the level of pPAK1 in HCC cell lines. ATRA inhibited the progression of HCC and sensitized HCC response to Sorafenib by downregulation of PAK1, as shown by the calculated coefficient of drug interaction and the data obtained from xenograft models. Our findings indicated that instead of treatment with Sorafenib alone, the combination of ATRA and Sorafenib provides a more effective treatment for HCC patients. Video Abstract.


Tolerance of intraoperative hemoglobin decrease during cardiac surgery.
It has been suggested that a decrease of at least 50% from the preoperative hemoglobin (Hb) level during cardiac surgery is associated with adverse outcomes even if the absolute Hb level remains above the commonly used transfusion threshold of 7.0 g/dL. In this study the relation between intraoperative Hb decline of at least 50% and a composite endpoint was analyzed. This single-center study comprised 11,508 patients who underwent cardiac surgery and had normal preoperative Hb levels (12.0-16.0 g/dL in women, 13.0-18.0 g/dL in men) between January 2001 and December 2011. Logistic regression modeling was used. The composite endpoint comprised in-hospital mortality, stroke, myocardial infarction, and renal failure. Patients whose Hb did not decrease at least 50% and remained above 7 g/dL were used as reference (n = 9672). A total of 363 (3.2%) patients had an intraoperative Hb of less than 7 g/dL during surgery but a Hb decrease of less than 50%; 876 patients (7.4%) showed both a nadir Hb less than 7 g/dL and a Hb decrease of at least 50%, while 597 (5.2%) had a Hb decrease of at least 50% and a nadir Hb of at least 7 g/dL. In this last group the incidence of the composite endpoint was higher than in patients in the reference group (adjusted odds ratio, 1.27; 95% confidence interval, 1.14-1.41). Our findings show that a decrease of at least 50% from baseline Hb during cardiac surgery is associated with adverse outcomes, even if the absolute Hb level remains higher than the commonly used transfusion threshold of 7.0 g/dL.


Non-parametric graphnet-regularized representation of dMRI in space and time.
Effective representation of the four-dimensional diffusion MRI signal - varying over three-dimensional q-space and diffusion time τ - is a sought-after and still unsolved challenge in diffusion MRI (dMRI). We propose a functional basis approach that is specifically designed to represent the dMRI signal in this qτ-space. Following recent terminology, we refer to our qτ-functional basis as "qτ-dMRI". qτ-dMRI can be seen as a time-dependent realization of q-space imaging by Paul Callaghan and colleagues. We use GraphNet regularization - imposing both signal smoothness and sparsity - to drastically reduce the number of diffusion-weighted images (DWIs) that is needed to represent the dMRI signal in the qτ-space. As the main contribution, qτ-dMRI provides the framework to - without making biophysical assumptions - represent the qτ-space signal and estimate time-dependent q-space indices (qτ-indices), providing a new means for studying diffusion in nervous tissue. We validate our method on both in-silico generated data using Monte-Carlo simulations and an in-vivo test-retest study of two C57Bl6 wild-type mice, where we found good reproducibility of estimated qτ-index values and trends. In the hopes of opening up new τ-dependent venues of studying nervous tissues, qτ-dMRI is the first of its kind in being specifically designed to provide open interpretation of the qτ-diffusion signal.


Immunogenicity of self tumor associated proteins is enhanced through protein truncation.
We showed previously that therapy with Vesicular Stomatitis Virus (VSV) expressing tumor-associated proteins eradicates established tumors. We show here that when cellular cDNA were cloned into VSV which retained their own poly-A signal, viral species emerged in culture which had deleted the cellular poly-A signal and also contained a truncated form of the protein coding sequence. Typically, the truncation occurred such that a Tyrosine-encoding codon was converted into a STOP codon. We believe that the truncation of tumor-associated proteins expressed from VSV in this way occurred to preserve the ability of the virus to replicate efficiently. Truncated cDNA expressed from VSV were significantly more effective than full length cDNA in treating established tumors. Moreover, tumor therapy with truncated cDNA was completely abolished by depletion of CD4+ T cells, whereas therapy with full length cDNA was CD8+ T cell dependent. These data show that the type/potency of antitumor immune responses against self-tumor-associated proteins can be manipulated in vivo through the nature of the self protein (full length or truncated). Therefore, in addition to generation of neoantigens through sequence mutation, immunological tolerance against self-tumor-associated proteins can be broken through manipulation of protein integrity, allowing for rational design of better self-immunogens for cancer immunotherapy.


Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial.
To find a subset of patients with suspected central venous catheter (CVC)-related infection (CRI) in whom CVC removal is not needed. Randomized controlled trial. Thirty-three-bed ICU. One hundred and forty four patients with suspected CRI in which a change of CVCs was planned were evaluated for inclusion. Hemodynamically stable patients without proven bacteremia, no insertion site infection, and no intravascular foreign body were randomized to a standard-of-care group (SOC, all CVCs were changed as planned) or a watchful waiting group (WW, CVCs changed when bacteremia was subsequently confirmed or hemodynamic instability occurred). Study groups were compared for incidence of CVC-related bloodstream infection (CR-BSI), resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and mortality. Of 144 patients with suspected CRI, 80 patients met exclusion criteria. Sixty-four were randomized. Forty-seven of 80 excluded patients were shown to be bacteremic, 20 (25%) of whom had a CR-BSI. Five of 64 (8%) included patients had a CR-BSI during their subsequent ICU stay (two in SOC and three in WW group). All 38 CVCs were changed in the SOC group versus 16 of 42 in the WW group (62% reduction, P<0.01). Resolution of fever, C-reactive protein, SOFA score, duration of ICU stay, and ICU mortality did not differ between SOC and WW group ( P>0.1 for all). The use of a simple clinical algorithm permits a substantial decrease in the number of unnecessarily removed CVCs without increased morbidity.


Eating, mood, and gender in a noneating disorder population.
Recently, eating in relation to emotions has been the focus of much research. The present study evaluates the role of mood, gender, and tendency for emotions to impact on eating (as measured by a revised form of the Emotional Eating Scale-II, EES II) within an analogue mood-related eating paradigm, e.g., Baucom & Aiken [J. Pers. Soc. Psychol. 41 (1981) 577], with a nonclinical population. The results indicate that there is a complex relationship that exists between gender and mood. Males appeared to experience a reduction in the negative component of their overall mood after eating, while females appeared to be more emotionally responsive to eating overall. This effect is not dependent on tendency for emotions to impact on eating as measured by the EES II. This suggests that there is a need to examine the impact of mood on eating in both clinical and nonclinical populations as there appears to be important differences between the populations.


A consultative itinerant approach to service delivery: considerations for the early childhood community.
This article, written by experts in itinerant early childhood special education, describes and differentiates approaches to itinerant early childhood special education as a primary service delivery option. Consultative itinerant early childhood special education services, in particular, are a means of ensuring that young children with disabilities have access to the general early childhood curriculum as offered in community-based programs. A discussion of the empirical literature that supports a consultative approach, literature that focuses on behavioral consultation and principles of distributed practice and embedded learning opportunities, is included. In addition, this article outlines a set of assumptions that program personnel make when implementing a consultative itinerant approach to service delivery. The need for and challenges associated with a consultative itinerant approach are discussed. Itinerant early childhood special educators face similar challenges as speech-language pathologists with regard to providing high-quality interventions to children in inclusive settings.


Activity limitations and participation restrictions experienced by people with stroke in Musanze district in Rwanda.
Stroke is a major cause of long-term disability. Information regarding the limitations in activity and participation experienced by patients with stroke in a specific setting such as Musanze district in Rwanda would assist to develop the rehabilitation programmes that would take into consideration the functional challenges experienced post stroke. To explore the activity limitations and participation restrictions experienced by people with stroke in Musanze district in Rwanda. A qualitative phenomenological approach using in-depth face-to-face interviews with 10 participants was employed to gather the data that was analyzed using a qualitative thematic approach. The themes that arose as activity limitations included limitations in walking, self care, and domestic life activities. The themes related to participation restrictions as expressed by the participants were inability to return to previous occupation, decreased social interactions and inability to participate in religious activities. The current study findings highlight the need for interventions to improve the functional status of stroke survivors.


Clinicoepidemiological profile of trauma patients admitting to the emergency department of a tertiary care hospital in eastern India.
Trauma is an immediate cause of patients flowing to the emergency department of any hospital. Besides epidemiology, clinical profile and treatment strategy forms an important aspect to reflect the gap in the existing public sector health-care system and the requirement. To evaluate the clinicoepidemiological profile of trauma patients admitting to an apex trauma hospital in east India. A prospective observational study was performed during the time period of December 2018 to July 2019 on trauma patients admitted to the Trauma and Emergency department. Patient's demographic profile, injury type, mechanism, the vehicle involved in the accident, and transportation were recorded. Various trauma scores (clinical) and outcome measures were recorded. Statistical analysis was done by R version 3.6.1. Male: female ratio was 407:93 with the 21-30 age group predominantly. 2-6 PM was the most common time of injury and ambulance was the predominant mode of transport (58%). Road traffic injury (RTI) accounted for 75% victims; two-wheelers (68%) dominated over others. Thirty percent (drivers 18%, pillion riders 12%) were wearing helmet; 41% were wearing seat belts (drivers 34%, passenger 12%). Twenty-five percent of drivers consumed alcohol. The median ± Interquartile range of injury severity score (ISS), revised trauma and trauma score and injury severity score were 17 (11-26), 7.8 (4.1-7.8), and 98.41 (95.95-99.30), respectively. Extremity injury (54% fractures) and head injury (50%) were the frontrunners in the pattern of injury, with half of the victims were polytrauma (ISS > 15). The injury was prominently RTI and the trauma victims/patients were young male drivers on two wheelers. The focus should be directed to make use of safety measures among the youth.


A giant orbital solitary fibrous tumor treated by surgical excision: a case report and literature review.
Spindle cell tumors, called solitary fibrous tumors (SFTs), are of mesenchymal origin, and can develop in the orbit. As 'intermediate malignancy' tumors, only a small percentage show malignant behavior, such as invasion of surrounding tissue. A 57-year-old woman presented with a 19-year history of a giant right orbital mass. Orbital computed tomography (CT) revealed an inhomogeneously-enhancing mass compressing and engulfing the eyeball and optic nerve. She underwent lid-sparing orbital exenteration. Microscopic characteristics and immunohistochemistry (IHC) tests were indicative of a benign SFT. No recurrence was observed at the 4-year follow-up. Early and complete tumor resection is recommended.


The histopathology of septic acute kidney injury: a systematic review.
Sepsis is the most common trigger of acute kidney injury (AKI) in critically ill patients; understanding the structural changes associated with its occurrence is therefore important. Accordingly, we systematically reviewed the literature to assess current knowledge on the histopathology of septic AKI. A systematic review of the MEDLINE, EMBASE and CINHAL databases and bibliographies of the retrieved articles was performed for all studies describing kidney histopathology in septic AKI. We found six studies reporting the histopathology of septic AKI for a total of only 184 patients. Among these patients, only 26 (22%) had features suggestive of acute tubular necrosis (ATN). We found four primate studies. In these, seven out of 19 (37%) cases showed features of ATN. We also found 13 rodent studies of septic AKI. In total, 23% showed evidence of ATN. In two additional studies performed in a dog model and a sheep model there was no evidence of ATN on histopathologic examination. Overall, when ATN was absent, studies reported a wide variety of kidney morphologic changes in septic AKI - ranging from normal (in most cases) to marked cortical tubular necrosis. There are no consistent renal histopathological changes in human or experimental septic AKI. The majority of studies reported normal histology or only mild, nonspecific changes. ATN was relatively uncommon.


Citrate synthase and pyruvate kinase activities during early life stages of the shrimp Farfantepenaeus paulensis (Crustacea, Decapoda, Penaeidae): effects of development and temperature.
Energy metabolism in early life stages of the shrimp Farfantepenaeus paulensis subjected to temperature reduction (26 and 20 degrees C) was determined using the activities of citrate synthase (CS) and pyruvate kinase (PK). At both temperatures, weight-specific activity of CS decreased throughout the ontogenetic development from protozoea II (PZ II) to postlarva XII-XIV (PL XII-XIV). PK activity reached a pronounced peak in PL V-VI, followed by a further decrease in PL XII-XIV. Temperature reduction produced variation in oxygen consumption rates (QO(2)), ammonia-N excretion and in enzyme activities. Ammonia-N excretion was higher at 20 degrees C in mysis III (M III), PL V-VI and PL XII-XIV, resulting in substantially lower O:N ratios in these stages. QO(2) was increased in protozoea II (PZ II) and mysis I (M I) at 26 degrees C, while no difference in QO(2) was detected in the subsequent stages at either temperature. This fact coincided with higher CS and PK activities in M III, PL V-VI and PL XII-XIV at 20 degrees C compared with 26 degrees C. Regressions between individual enzyme activities and dry weight exhibited slope values of 0.85-0.92 for CS and 1.1-1.2 for PK and temperature reduction was reflected by higher slope values at 20 than at 26 degrees C for both enzymes. Weight-specific CS activity was positively correlated with QO(2) at 20 and 26 degrees C, and may thus be used as an indicator of aerobic metabolic rate throughout the early stages of F. paulensis. The variation in enzyme activities is discussed in relation to possible metabolic adaptations during specific ontogenetic events of the F. paulensis life cycle. Here, the catalytic efficiency of energy-metabolism enzymes was reflected in ontogenetic shifts in behaviour such as larval settlement and the adoption of a benthic existence in early postlarvae. In most cases, enhanced enzyme activities appeared to counteract negative effects of reduced temperature.


Nucleopolyhedroviruses (NPV) induce the expression of small heat shock protein 25.4 in Antheraea pernyi.
Nucleopolyhedroviruses (NPVs) is one group of Baculoviruses. The infection of NPV in silkworm is often lethal. To investigate the effective measures to stop the infection of NPV, we cloned cDNA encoding small heat shock protein 25.4 in Antheraea pernyi (Ap-HSP25.4). The translated amino acid sequence consisted of 223 residues with a calculated molecular mass of 25.4kDa and an isoelectronic point (pI) of 4.93. Quantitative real-time PCR was used to investigate the expression patterns and distribution profiles of Ap-sHSP25.4 before and after challenged with NPV. We found that the inhibitors of eicosanoid synthesis could suppress the transcription of Ap-sHSP25.4 in the fat body in a dose dependent manner. And arachidonic acid induced the expression of Ap-sHSP25.4. Thus, we concluded that sHSPs may be promising candidates to boost insect immunity in practice.


Increase in synaptosomal acidic phospholipids after intermittent but not continuous ethanol exposure.
The aim of this study was to compare the effects of different ethanol administration procedures on synaptosomal concentrations of acidic phospholipids. The concentrations of phosphatidylinositol and phosphatidylserine were significantly increased after intermittent ethanol exposure for one week but were unaltered after one or three weeks of continuous ethanol administration. The results indicate the importance of drinking pattern for changes in synaptosomal acidic phospholipids.


Ciprofloxacin releasing gellan gum/polydopamine based hydrogels with near infrared activated photothermal properties.
In this work, with the aim to obtain a wound dressing hydrogel, an amine derivative of gellan gum was crosslinked in the presence of 4arm-polyethylenglycole-vinylsulfone. Through this easy and reproducible chemical procedure, a hydrogel with advanced elastic properties and hydrolytic resistance under physiological conditions was obtained. The incorporation of different quantities of polydopamine in the gelling solutions allows to obtain different hydrogels with marked photothermal properties when irradiated with a laser in the near infrared at 810 nm. The organic nanoparticles, reacting with the amino groups of the polysaccharide derivative, contribute to increase the storage moduli of the hydrogels. Ciprofloxacin was loaded into the hydrogel with higher amount of polydopamine and drug delivery experiments were performed to investigate the effect of irradiation on the antibiotic release profile. Antimicrobial studies, evaluated against S. aureus and P. aeruginosa, revealed that generated hyperthermia exerts a direct inhibition on the pathogens growth and, in the case of S. aureus, adjuvates the ciprofloxacin antimicrobial effect.


Partial Purification and Characterization of Bacteriocin-Like Inhibitory Substances Produced by Streptomyces sp. Isolated from the Gut of Chanos chanos.
Bacteriocin-like inhibitory substances (BLIS) have sparked great interest because of their promising use in food as natural antimicrobial agents. In this work, six Streptomyces isolates obtained from the gut of Chanos chanos demonstrated their ability to produce extracellular metabolites with inhibitory activity against Salmonella enterica serovar Typhimurium, Escherichia coli, Listeria monocytogenes, and Staphylococcus aureus. Exposure of the extracellular metabolites to proteolytic enzymes (i.e., proteinase-K, trypsin, and pepsin) revealed high sensitivity and confirmed their proteinaceous nature. The metabolites were stable at high temperatures (up to 100°C for 30 min) and a wide range of pH (pH 2.0-7.0). Fractionation of the crude BLIS by filtration yielded three fractions based on molecular weight: <3 kDa, 3-10 kDa, and >10 kDa. Analysis of the antibacterial activity of these fractions showed increased specific activity, especially in the fraction with a molecular weight (MW) of <3 kDa, relative to the crude sample. The fraction with MW < 3 kDa had minimum inhibitory and bactericidal concentrations in ranges 0.04-0.62 mg·mL-1 and 0.08-1.25 mg·mL-1, respectively. This fraction also showed better temperature and pH stability compared with crude BLIS. Brine shrimp toxicity assay revealed that this fraction has moderate toxicity with a 50% lethal concentration of 226.975 μg·mL-1 (i.e., moderate toxicity) to Artemia salina. Identification of the peptide sequences of this fraction by liquid chromatography-tandem mass spectrometry yielded 130 proteins with retention times of 15.21-19.57 min. Eleven proteins with MWs of 1345.66-2908.35 Da and composed of less than 30 amino acid residues with high hydrophobicity (15.34-26.22 kcal·mol-1) appeared to be responsible for the antibacterial activity of the fraction. This study revealed the potential application of BLIS from Streptomyces, especially BLIS SCA-8, as antibacterial agents.


Unprecedented binary Cu(I)/Cu(II) catalyzed one-pot, three-component synthesis and evaluation of luminescent property of 2-amino-3-iminoethenylidene-2-indolones: a new class of merocyanine dye analogues.
A facile and efficient binary Cu(I)/Cu(II) catalyzed one-pot, three-component synthesis of 2-amino-3-iminoethenylidene-2-indolones in excellent yield has been achieved. Remarkably, these newly synthesized, stable merocyanine dye analogues showed strong luminescence in the blue region with large Stokes shifts.


A novel encapsulation of N,N-diethyl-3-methylbenzamide (DEET) favorably modifies skin absorption while maintaining effective evaporation rates.
N,N-diethyl-3-methylbenzamide (DEET) is popular insect repellent which is considered safe and effective, yet is subject to considerable skin absorption. Skin absorption decreases effective repellency since less DEET is available for evaporation. We have investigated the extent to which DEET skin absorption can be reduced and evaporation sustained through encapsulation. DEET permeation through human skin in vitro was measured for an ethanolic solution standard and for two novel topical controlled-release formulations in which the DEET active material was temporarily sequestered within a permeable, charged-film microcapsule. Evaporation measurements were gathered using Tenax TA cartridges and a sampling pump drawing air over the skin. Three formulations were studied: a previously reported microcapsule formulation (Formulation A); a newly-developed microcapsule formulation (Formulation B); and a non-encapsulated ethanol control solution. Formulation B led to a 30% reduction in DEET permeation versus control. The two microcapsule DEET formulations exhibited 36-40% higher cumulative evaporation from the skin than did the control. The vapor trapping measurements in vitro show that Formulation B provided more than 48h of effective evaporation rate for repellency, while Formulation A provided less than 35h and the ethanol control less than 15h. This establishes a technical advantage for the controlled-release approach.


Practice variation in treatment of suspected asymptomatic bacteriuria prior to cardiac surgery: are there differences in postoperative outcome? A retrospective cohort study.
It is unclear whether postoperative infections can be prevented by treating asymptomatic bacteriuria, or whether, on the other hand, such treatment will increase the risk of more serious infection by pathogenic bacteria different from the ones causing bacteriuria. This study aimed to support future treatment decisions for preoperative cardiothoracic surgery patients with asymptomatic bacteriuria, by examining current preoperative practice, in relation to postoperative outcome. A retrospective cohort study was conducted. All patients who underwent cardiothoracic surgery in 2011-2013 using extracorporeal circulation in St. Antonius Hospital Nieuwegein, and who preoperatively had nitrituria and/or leucocyturia were included. Exclusion criteria were C-reactive protein level higher than 10 mg/l, emergency surgery, critical preoperative state and/or antibiotic treatment because of other infections. Outcomes were postoperative infections and length of stay. Furthermore, we compared culture results of preoperative urine with postoperative infection sites in order to study the hypothesis of haematogenous spread. One thousand and two patients with leucocyturia or nitrituria were eligible, of whom 3.9% had been treated with antibiotics preoperatively (AB+). Of the 96.1% of patients who had not been treated (AB-), 8.3% had an infection postoperatively, compared with 5.1% in the treatment (AB+) group. This was not statistically significant {odds ratio, corrected for EuroSCORE, 0.53 [95% confidence interval (CI) 0.12-2.24, P = 0.39]}. Length of stay, corrected for EuroSCORE, between the treated (AB+) and the non-treated (AB-) group did not differ, with a hazard ratio of 1.05 (95% CI 0.63-1.75, P = 0.85). As regards bacterial culture results, none of patients not treated with antibiotics preoperatively (AB-) seemed to have a postoperative infection due to haematogenous spread of bacteria from the urinary tract present preoperatively. The risk of haematogenous spread of bacteria seems to be non-existent in this large cohort of non-treated patients, under our local clinical practice. Based on this current, best available evidence, it seems therefore safe not to treat patients with asymptomatic bacteriuria prior to cardiothoracic surgery. This could also imply that it is safe not to perform routine preoperative urine testing.


Soluble receptor for advanced glycation end products inhibits disease progression in autosomal dominant polycystic kidney disease by down-regulating cell proliferation.
Autosomal polycystic kidney disease (ADPKD) is a highly prevalent genetic renal disorder in which epithelial-lining fluid-filled cysts appear in kidneys. It is accompanied by hyperactivation of cell proliferation, interstitial inflammation, and fibrosis around the cyst lining cells, finally reaching end-stage renal disease. Previously, we found high expression of ligands stimulating the receptor for advanced glycation end products (RAGE) in ADPKD mice. Furthermore, gene silencing of RAGE was revealed to cause reduction of cystogenesis via down-regulation of cell proliferation in vitro, and intravenous administration of anti-RAGE adenovirus in vivo also displayed alleviation of the disease. Here, we attempted to identify the role of soluble RAGE (sRAGE) in inhibiting the progression of ADPKD using 2 different ADPKD mouse models. sRAGE is an endogenously expressed form of RAGE that has no membrane-anchoring domain, thereby giving it the ability to neutralize the ligands that stimulate RAGE signals. Both overexpression of sRAGE and sRAGE treatment blocked RAGE-mediated cell proliferation in vitro. In addition, sRAGE-injected ADPKD mice showed reduced cysts accompanied by enhanced renal function, inhibition of cell proliferation, inflammation, and fibrosis. These positive therapeutic effects of sRAGE displayed little liver toxicity, suggesting it as a new potential therapeutic target of ADPKD with low side effects.


Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.
The association between autonomic dysfunction and long-COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long-COVID syndrome in a large population are lacking. To evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome. We administered the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire to a sample of post-COVID-19 patients who were referred to post-COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long-COVID syndrome. Participants were asked to complete the COMPASS-31 questionnaire referring to the period of more than 4 weeks after acute COVID-19. We included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS-31 score was 26.29 (0-76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS-31 score and long-COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post-COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty-seven patients (76.7%) had a high score of COMPASS-31 >16.4. Patients with COMPASS-31 >16.4 had a longer duration of long-COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001). Symptoms of dysautonomia are common in long-COVID syndrome. The most common COMPASS-31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.


Protein turnover in cardiac cell growth and survival.
Protein turnover represents the balance between protein synthesis and degradation. It can be controlled quantitatively, for instance by an activation of protein synthesis during cardiac hypertrophy or by activating protein degradation during ventricular unloading. It can also be regulated qualitatively by changing the steady state concentration of specific proteins and enzymes. The recent literature points to an emerging role for the mammalian target of rapamycin (mTOR) and for the ubiquitin-proteasome system (UPS) in this process, and both pathways interact in the regulation of cell growth and survival. We highlight the critical role played by such interaction in different cellular functions, including insulin signaling, stress response to hypoxia, adaptation to variations in workload, regulation of protein phosphatase activity, apoptosis and post-ischemic recovery. A deregulation of these pathways participates in the mechanisms of cardiac ischemia, hypertrophy and failure, and controlling their activity represents an opportunity for novel therapeutic avenues.


Childhood victimization: desensitization effects in the later lifespan.
The hypothesis tested in this study was that young adults who report having been abused by parents or guardians as children would report less concern when confronted with hypothetical situations similar to the type of abuse they had reportedly experienced during childhood. In our study of nonclinical adults those who reported childhood victimization experiences showed diminished concern toward the specific kind of abuse situation encountered earlier in their lifespan.


Racial differences in cervical cytokine concentrations between pregnant women with and without bacterial vaginosis.
We have examined the association between cervical cytokine, chemokine and growth factor concentrations with bacterial vaginosis (BV) in pregnant white and black women. A nested case-control analysis was performed to examine 28 cervical cytokine, chemokine and growth factor concentrations in 83 white women (55 with normal flora and 28 with BV) and 81 black women (39 with normal flora and 42 with BV). White women with BV had significantly lower IP10 (P=0.001) and MCP1 (P=0.006) concentrations compared to women with normal flora. Black women with BV had higher IL-1alpha (P<0.001) concentrations than those with normal flora. In women with normal flora, whites had significantly higher levels of IL-1alpha (P=0.047), IL-6 (P=0.010), IL-10 (P=0.016) and PDGF-BB (P=0.010) than blacks. There were no significant concentration differences between white and black women with BV. These results demonstrate significant differences in cytokine and chemokine concentrations between women with and without BV. Ethnic differences in cytokine concentrations were also observed in women with normal flora, indicating that white and black women with normal flora have different cytokine levels, but respond to BV in a similar manner.


Hepatitis C Virus Elimination Using Direct Acting Antivirals after the Radical Cure of Hepatocellular Carcinoma Suppresses the Recurrence of the Cancer.
It remains unclear whether hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients can be suppressed by the elimination of the virus using direct-acting antivirals (DAAs) after radical HCC treatment. We evaluated the sustained inhibitory effect of DAAs on HCC recurrence after curative treatment. This multicenter retrospective study included 190 HCV-positive patients after radical treatment for early-stage HCC. Patients were classified into the DAA treatment group (n = 70) and the non-DAA treatment group (n = 120) after HCC treatment. After propensity score matching (PSM), 112 patients were assessed for first and second recurrences using the Kaplan-Meier method and analyzed using a log-rank test. The first recurrence rates at 1 and 3 years were 3.6% and 42.1% in the DAA treatment group and 21.7% and 61.9% in the non-DAA treatment group, respectively (p = 0.0026). Among 85 patients who received radical treatment, the second recurrence rate at 3 years was 2.2% in the DAA treatment group and 33.9% in the non-DAA treatment group (p = 0.0128). In HCV-positive patients with early-stage HCC, the first and second recurrences were suppressed by DAA therapy after radical treatment, suggesting that the inhibitory effect of DAA therapy on HCC recurrence was sustained.


How to guard against impostor JCAHO surveyors.
Proper security procedures are an important quality concern, asserts JCAHO official. JCAHO now providing same-day advanced warning of unannounced survey visits. Reporting incidents is critical to the development of new interagency database.


Results of laparoscopic intragastric surgery.
Technological and operative advancements have allowed laparoscopic intragastric surgery (LIGS) to be applied in the treatment of superficial gastric or submucosal lesions. The aim of this study was to evaluate short- and long-term outcomes following LIGS. From 2000 to 2013, 25 LIGSs were performed for superficial gastric lesions. Clinical records were reviewed retrospectively for peri-operative course and long-term outcomes with particular attention to the oncological follow-up for patients with malignant lesions. Nineteen (76%) lesions were located close to the EGJ, three (12%) in the lesser curvature, two (8%) in the posterior wall and one (4%) in the prepyloric-antral region. A multiport technique was used in 15 (60%) patients and a single-access approach in 10 (40%) patients. The median operative time was 140 (50-210) minutes. No conversion to open or conventional laparoscopic surgery was needed. Mortality was nil, and severe morbidity occurred in one (4%) patient. The median length of stay was 6 (3-10) days. Indications of LIGS were adenocarcinoma in 11 (44%) patients, gastrointestinal stromal tumors (GISTs) in 6 (24%) patients and benign lesions in eight (32%) patients. En bloc resection was obtained in 24 (96%) patients with R0 margins in 23 (92%) patients. After a median follow-up of 76 (26-171) months, recurrence was detected in 4 (36%) patients with advanced malignant adenocarcinoma. LIGS provides an interesting alternative to major gastric and EGJ resection when endoscopic resection is not suitable for highly selected patients with superficial gastric lesions.


Nutritional factors influencing microbiota-mediated colonization resistance of the oral cavity: A literature review.
The oral cavity is a key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems. The oral microbiota is a vital part of the human microbiome. It has been developed through mutual interactions among the environment, host physiological state, and microbial community composition. Indigenious microbiota of the oral cavity is one of the factors that prevent adhesion and invasion of pathogens on the mucous membrane, i.e., the development of the infectious process and thereby participating in the implementation of one of the mechanisms of local immunity-colonization resistance. The balance between bacterial symbiosis, microbial virulence, and host resistance ensures the integrity of the oral cavity. In this review we have tried to address how nutritional factors influence integrity of the oral indigenous microbiota and its involvement in colonization resistance.


Isoflurane's enhancement of chloride flux through rat brain gamma-aminobutyric acid type A receptors is stereoselective.
Recent evidence is consistent with the view that volatile anesthetics interact directly with excitable membrane-bound channel proteins. If these agents interact directly with chiral centers in the neuronal cell membrane, then their effects should be stereoselective. Using rat brain membranes enriched in gamma-aminobutyric acid type A (GABAA) receptors, we investigated the hypothesis that the permeability response of this well-characterized central nervous system channel protein to stereoisomers of isoflurane is stereoselective. Rat brain synaptic microvesicles were prepared by differential centrifugation. Agonist-stimulated 36Cl- flux through membrane-bound GABAA receptors was assayed in the presence of (+)- and (-)-isoflurane and compared with control conditions. Both isomers increased the potency and efficacy of GABA; however, (+)-isoflurane was significantly more potent and efficacious than the (-)-isomer. For example, the (+)-isomer (140 microM) reduced the median effective concentration of GABA from 12.7 +/- 1.0 to 5.4 +/- 0.5 microM, whereas the (-)-isomer reduced it to 9.6 +/- 1.0 microM (P < 0.001). The (+)-isomer also was 1.6 times as potent as the (-)-isomer in augmenting 5 microM GABA-gated flux (79 +/- 11 vs. 130 +/- 17 microM, respectively; P = 0.01). In addition, the (+)-isomer produced significantly greater maximal enhancement of flux (9.4 +/- 0.4 vs. 7.0 +/- 0.3 nmol.mg-1.3 s-1; P < 0.001). Isoflurane's effects on GABA-gated chloride flux were stereoselective. This result supports direct interaction with a stereoselective site, possibly the GABAA channel protein itself, rather than a nonspecific perturbation of the surrounding membrane lipid. In addition, these findings, from a functional assay using mammalian brain, agree with recent observations in invertebrate ion channels and mammalian neuronal cell cultures.


Risk-benefit analysis of adalimumab versus traditional non-biologic therapies for patients with Crohn's disease.
Adalimumab is indicated for the treatment of moderately to severely active Crohn's disease (CD). A systematic analysis of risks and benefits of adalimumab versus traditional non-biologic therapies for patients refractory to non-biologic therapy is lacking. A base-case analysis compared expected benefits of adalimumab therapy with a 12-week stopping rule for non-responders versus non-biologic therapies using data from clinical trials (CHARM, CLASSIC I). Adverse events (AEs) recorded in clinical trials (CHARM, CLASSIC I, CLASSIC II, GAIN, open-label extensions) were compiled. Sensitivity analyses incorporated all observed benefits of adalimumab and placebo (CHARM, CLASSIC I, GAIN) and observed AEs from a systematic literature review of non-biologic therapies (MEDLINE search of randomized trials 1990-2007). Distributional information from maintenance clinical trial observations and benefit model predictions were used in a probabilistic simulation. Incremental net benefits were estimated based on utility estimates from the literature. Average time in remission (i.e., CDAI <150) over 1 year of therapy was 39.9% for adalimumab versus 6.6% for traditional non-biologic therapies. Adalimumab was associated with fewer expected hospitalizations, better fistula closure rates, and lower AE rates. These findings were robust in sensitivity analyses. In the probabilistic simulation, with serious AEs as a composite of risks, adalimumab provided greater benefits with fewer AEs versus non-biologic therapies (P < 0.01). Adalimumab demonstrated greater incremental net quality-adjusted life-years (0.12) versus non-biologic therapies. Adalimumab demonstrated greater benefits and lower rates of AEs versus traditional non-biologic therapies for patients with moderately to severely active CD who were refractory to non-biologic therapies.


Expansion of the indication of transcatheter aortic valve implantation--feasibility and outcome in "off-label" patients compared with "on-label" patients.
We compare the feasibility and outcomes of "off-label" transcatheter aortic valve implantation (TAVI) patients with a standard "on-label" TAVI population. A total of 591 high-risk patients (pts) underwent a TAVI procedure at our institution. Of these, 435 pts (73.6%) were treated for an on-label indication (group A) and 156 pts (26.4%) were treated for an off-label indication (group B). Group B was further subdivided into patients with pure aortic regurgitation (n = 22; group B.1), anatomical considerations (n = 26; group B.2), very low ejection fraction ≤20% (n = 12; group B.3), concomitant severe mitral regurgitation >2+ (n = 44; group B.4), degenerated aortic bioprosthesis (n = 30; group B.5), and hemodynamic instability with the need for cardiopulmonary bypass (n = 22; group B.6). Outcome parameters were classified according to the Valve Academic Research Consortium-2 criteria. The mean log EuroSCORE of the entire study group was 25 ± 16% (33 ± 21% in group B vs 22 ± 14% in group A; P<.001). Overall device success was 90% (91.3% in group A vs 86.5% in group B; P=.02). Overall 30-day mortality was 9.7%. Group B had a higher 30-day mortality compared with group A (14.7% vs 7.8%, respectively; P=.01). Group B.5 had the lowest 30-day mortality (3.3%). Corresponding to the higher surgical risk of group B, 30-day mortality was higher for off-label pts. Patients treated as valve-in-valve had the lowest 30-day mortality, emphasizing its great potential as opposed to redo open-heart surgery.


Paraneoplastic syndrome in malignant lymphoma: A case report.
Hypercalcaemia associated with malignancy is a complication of advanced tumors. Lactic acidosis is also an extremely rare paraneoplastic syndrome of malignancy, and the presence of both usually indicates an extremely poor prognosis for the tumour. Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma and is also a common aggressive lymphoma. It is extremely rare for patients with diffuse large B-cell lymphoma to develop both hypercalcaemia and severe lactic acidosis. In this article, we report a case of CD5 positive diffuse large B-cell lymphoma with hypercalcaemic crisis and persistent lactic acidosis, in which calcium was rapidly reduced to normal after rehydration, diuresis, calcitonin and zoledronate, and continuous renal replacement therapy (CRRT). After correction of acidosis with sodium bicarbonate, diuresis, vitamin B1 and CRRT, the patient's lactate remained at a high level. The aim of this article is to analyse the experience of the combination of hypercalcaemia and intractable lactic acidosis, which should be considered as a serious electrolyte disorder possibly associated with abnormal metabolism of malignant tumors, and to identify and treat the primary lesion as early as possible.


Subexponential-Time Algorithms for Finding Large Induced Sparse Subgraphs.
Let C and D be hereditary graph classes. Consider the following problem: given a graph G ∈ D , find a largest, in terms of the number of vertices, induced subgraph of G that belongs to C . We prove that it can be solved in 2 o ( n ) time, where n is the number of vertices of G, if the following conditions are satisfied:the graphs in C are sparse, i.e., they have linearly many edges in terms of the number of vertices;the graphs in D admit balanced separators of size governed by their density, e.g., O ( Δ ) or O ( m ) , where Δ and m denote the maximum degree and the number of edges, respectively; andthe considered problem admits a single-exponential fixed-parameter algorithm when parameterized by the treewidth of the input graph. This leads, for example, to the following corollaries for specific classes C and D :a largest induced forest in a P t -free graph can be found in 2 O ~ ( n 2 / 3 ) time, for every fixed t; anda largest induced planar graph in a string graph can be found in 2 O ~ ( n 2 / 3 ) time.


Performance assessment model development and parameter acquisition for analysis of the transport of natural radionuclides in a Mediterranean watershed.
This paper describes the methodology developed to construct a model for predicting the behaviour of the natural radioisotopes of U, Th and Ra in a Mediterranean watershed. The methodology includes the development of the performance assessment model, obtaining water flow and radiological parameters based on experimental data and analysis of results. The model, which accounts for both water flows and mass balances of the radionuclides in a semi-natural environment, provides assessments of radionuclide behaviour in grassland and agricultural soils, rivers and reservoirs, including the processes of radionuclide migration through land and water and interactions between both. From field and laboratory data, it has been possible to obtain parameters for the driving processes considered in the model, water fluxes, source term definition, soil to plant transfer factors and distribution coefficient values. Ranges of parameter values obtained have shown good agreement with published literature data. This general methodological approach was developed to be extended to other radionuclides for the modelling of a biosphere watershed in the context of performance assessment of a High Level Waste (HLW) repository under Mediterranean climate conditions, as well as for forecasting radionuclide transport under similar Mediterranean conditions that will occur in the future in other areas. The application of sensitivity and uncertainty analysis was intended to identify key uncertainties with the aim of setting priorities for future research. The model results for the activity concentration in the reservoir indicate that for (238)U and (230)Th the most relevant parameter is the initial concentrations of the radionuclides in the reservoir sediments. However, for (226)Ra the most important parameter is the precipitation rate over the whole watershed.


Immunohistochemical demonstration of contractile proteins in astrocytes, marginal glial and ependymal cells in rat diencephalon.
Actin and myosin were located in astrocytes, marginal glial and ependymal cells in rat diencephalon by using antibodies against highly purified chicken gizzard actin and myosin. On the basis of these findings it is suggested that glial cell motility in vovo and in vitro is due to the presence of an intracellular actin/myosin system.