Ulnar variance in Kienböck's disease.
The distal extent of the radius and ulna (ulnar variance) was compared on roentgenograms of normal wrists in randomly selected black and white patients and of fifteen affected wrists in patients with Kienbock's disease. The results establish a statistically significant association between negative ulnar variance and Kienbock's disease. Blacks have more positive ulnar variance and the disease is less likely to develop in them than in whites.


Transposition and Intermingling of Galphai2 and Galphao afferences into single vomeronasal glomeruli in the Madagascan lesser Tenrec Echinops telfairi.
The vomeronasal system (VNS) mediates pheromonal communication in mammals. From the vomeronasal organ, two populations of sensory neurons, expressing either Galphai2 or Galphao proteins, send projections that end in glomeruli distributed either at the rostral or caudal half of the accessory olfactory bulb (AOB), respectively. Neurons at the AOB contact glomeruli of a single subpopulation. The dichotomic segregation of AOB glomeruli has been described in opossums, rodents and rabbits, while Primates and Laurasiatheres present the Galphai2-pathway only, or none at all (such as apes, some bats and aquatic species). We studied the AOB of the Madagascan lesser tenrec Echinops telfairi (Afrotheria: Afrosoricida) and found that Galphai2 and Galphao proteins are expressed in rostral and caudal glomeruli, respectively. However, the segregation of vomeronasal glomeruli at the AOB is not exclusive, as both pathways contained some glomeruli transposed into the adjoining subdomain. Moreover, some glomeruli seem to contain intermingled afferences from both pathways. Both the transposition and heterogeneity of vomeronasal afferences are features, to our knowledge, never reported before. The organization of AOB glomeruli suggests that synaptic integration might occur at the glomerular layer. Whether intrinsic AOB neurons may make synaptic contact with axon terminals of both subpopulations is an interesting possibility that would expand our understanding about the integration of vomeronasal pathways.


Metal specificity is correlated with two crucial active site residues in Escherichia coli alkaline phosphatase.
Escherichia coli alkaline phosphatase exhibits maximal activity when Zn(2+) fills the M1 and M2 metal sites and Mg(2+) fills the M3 metal site. When other metals replace the zinc and magnesium, the catalytic efficiency is reduced by more than 5000-fold. Alkaline phosphatases from organisms such as Thermotoga maritima and Bacillus subtilis require cobalt for maximal activity and function poorly with zinc and magnesium. Previous studies have shown that the D153H alkaline phosphatase exhibited very little activity in the presence of cobalt, while the K328W and especially the D153H/K328W mutant enzymes can use cobalt for catalysis. To understand the structural basis for the altered metal specificity and the ability of the D153H/K328W enzyme to utilize cobalt for catalysis, we determined the structures of the inactive wild-type E. coli enzyme with cobalt (WT_Co) and the structure of the active D153H/K328W enzyme with cobalt (HW_Co). The structural data reveal differences in the metal coordination and in the strength of the interaction with the product phosphate (P(i)). Since release of P(i) is the slow step in the mechanism at alkaline pH, the enhanced binding of P(i) in the WT_Co structure explains the observed decrease in activity, while the weakened binding of P(i) in the HW_Co structure explains the observed increase in activity. These alterations in P(i) affinity are directly related to alterations in the coordination of the metals in the active site of the enzyme.


[Effect of intravenous infusions of thrombin and heterogenous blood on lymph coagulability].
In dogs, i.v. administration of thrombin leads to hypocoagulation, consumption of fibrinogen, increasing fibrinolysis, and to a slight raise of antithrombin. This has no connection with appearance of natural anticoagulants and fibrinolytic agents in the lymph stream. After the heterotransfusion shock, apart from hypocoagulation and hyperfibrinolysis in the blood, the incoagulability of lymph developes due to a sharp increase of free heparin in it. The hypocoagulation after the heterotransfusion shock seems to depend on appearance of anticoagulants in the tissue fluid and lymph. Common and different features of thrombin and heterogenic blood effects on the mechanism of hypocoagulation and hyperfibrinolysis, are discussed.


[Optimization of surgical tactics in treatment of spontaneous pneumothorax].
299 patients with spontaneous pneumothorax were treated. All patients were divided in two groups. Patients of the first group (n=182) received thoracic puncture and/or drainage. The second group (n=117) has surgery, directed at liquidation of the source of pneumothorax, i.e., they received either atypical lung resection or subtotal parietal pleurectomy. The recurrent pneumothorax was registered in 24 (13.2%) patients of the first group and in 4 (3.4%) patients of the second. Authors state that radical surgical procedure for the spontaneous pneumothorax is an atypical lung resection with parietal pleurectomy. The use of active surgical tactics allows to decrease the number of recurrencies on 9.8%.


The Meyerhof quotient and the synthesis of glycogen from lactate in frog and rabbit muscle.
1. The conversion of lactate into glycogen was demonstrated in frog sartorius muscle in oxygen. The rates and amounts are highest when lactate is added to the bathing medium and are dependent on lactate and CO(2) concentration, as well as pH. The glycogen content of a resting muscle can be doubled in 4h at 24 degrees C. 2. Sartorius muscle, recovering aerobically in liquid paraffin from a period of anoxia, converts preformed lactate into glycogen at a lower rate and in smaller amounts than when lactate is added in an aqueous medium. The lower rates are similar to those Meyerhof found under the same conditions, after correction for temperature; they can be attributed partly to low muscle pH and partly to the limited amounts of lactate present. 3. Rabbit psoas muscle also shows the ability to convert added lactate into glycogen under aerobic conditions. The rates are low and similar to those in frog sartorius muscle recovering from anoxia. 4. The present experiments yield a Meyerhof quotient of 6.2, compared with Meyerhof's value of 4-5. However, these values are not significantly different from one another. 5. It is suggested that the glycogen coefficient, i.e. mol of glycogen formed/mol of lactate disappearing, is a more reliable way of assessing the resynthetic mechanism than the original quotient, i.e. mol of lactate disappearing/mol of lactate oxidized. The found coefficient is 0.419+/-0.024.


A Systematic Review of the Literature Examining the Effects of Cigarette Smoke and e-Cigarette Vapor on the Virulence of Human Pathogenic Bacteria.
The bioactive chemicals in cigarette smoke (CS) and e-cigarette vapor (EV) may affect pathogenic bacteria in the nasopharyngeal microflora, which may have implications on the pathophysiology of respiratory infections in cigarette smokers and e-cigarette users. In this systematic review, we seek to synthesize the research evidence supporting this hypothesis. To address the central research question, "what is known from the published, peer-reviewed literature about the effects of cigarette smoke or e-cigarette vapor exposure on the physiology of human pathogenic bacteria?", we screened the PubMed®, Web of ScienceTM, and ScienceDirect databases for reports examining the virulence characteristics and gene expression in human pathogenic bacteria exposed to either CS or EV. The principal conclusion from our analysis is that exposure to either CS or EV induces the virulence of respiratory pathogenic bacteria in a strain-dependent manner, which may in turn facilitate respiratory infections in cigarette smokers and e-cigarette users. In addition, we present evidence that nicotine and reactive oxygen species are the main chemicals responsible for CS/EV-mediated alterations in bacterial physiology. We note limitations that this review does not examine reports describing the alterations in host respiratory physiology or nasopharyngeal dysbiosis caused by CS/EV exposure. Future research to determine whether CS/EV-mediated augmentation of bacterial virulence indeed plays a role in human respiratory tract infections is warranted.


Sodiation and Desodiation via Helical Phosphorus Intermediates in High-Capacity Anodes for Sodium-Ion Batteries.
Na-ion batteries are promising alternatives to Li-ion systems for electrochemical energy storage because of the higher natural abundance and widespread distribution of Na compared to Li. High capacity anode materials, such as phosphorus, have been explored to realize Na-ion battery technologies that offer comparable performances to their Li-ion counterparts. While P anodes provide unparalleled capacities, the mechanism of sodiation and desodiation is not well-understood, limiting further optimization. Here, we use a combined experimental and theoretical approach to provide molecular-level insight into the (de)sodiation pathways in black P anodes for sodium-ion batteries. A determination of the P binding in these materials was achieved by comparing to structure models created via species swapping, ab initio random structure searching, and a genetic algorithm. During sodiation, analysis of 31P chemical shift anisotropies in NMR data reveals P helices and P at the end of chains as the primary structural components in amorphous Na xP phases. X-ray diffraction data in conjunction with variable field 23Na magic-angle spinning NMR support the formation of a new Na3P crystal structure (predicted using density-functional theory) on sodiation. During desodiation, P helices are re-formed in the amorphous intermediates, albeit with increased disorder, yet emphasizing the pervasive nature of this motif. The pristine material is not re-formed at the end of desodiation and may be linked to the irreversibility observed in the Na-P system.


Crocins, the active constituents of Crocus Sativus L., counteracted ketamine-induced behavioural deficits in rats.
Experimental evidence indicates that the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine impairs cognition and can mimic certain aspects of positive and negative symptoms of schizophrenia in rodents. Crocins are among the active components of the plant Crocus sativus L. and were found to be effective in different models of psychiatric disorders including anxiety and depression. The present study was designed to investigate the ability of crocins to counteract schizophrenia-like behavioural deficits produced by ketamine in rats. Crocin's ability to counteract hypermotility, stereotypies and ataxia induced by ketamine was evaluated in a motor activity cage. The ability of crocins to reverse ketamine-induced memory deficits was assessed using the novel object recognition task (NORT). The social interaction test was used in order to examine the effects of crocins on ketamine-induced social withdrawal. Crocins (50 but not 30 mg/kg, i.p.) attenuated ketamine (25 mg/kg, i.p.)-induced hypermotility, stereotypies and ataxia. In a subsequent study, post-training administration of crocins (15 and 30 mg/kg, i.p.) reversed ketamine (3 mg/kg, i.p.)-induced performance deficits in the NORT. Finally, crocins (50 but not 30 mg/kg, i.p.) counteracted the ketamine (8 mg/kg, i.p.)-induced social isolation in the social interaction test. Our findings show that crocins attenuated schizophrenia-like behavioural deficits induced by the non-competitive NMDA receptor antagonist ketamine in rats.


Quality optimized medical image information hiding algorithm that employs edge detection and data coding.
The present work has the goal of developing a secure medical imaging information system based on a combined steganography and cryptography technique. It attempts to securely embed patient's confidential information into his/her medical images. The proposed information security scheme conceals coded Electronic Patient Records (EPRs) into medical images in order to protect the EPRs' confidentiality without affecting the image quality and particularly the Region of Interest (ROI), which is essential for diagnosis. The secret EPR data is converted into ciphertext using private symmetric encryption method. Since the Human Visual System (HVS) is less sensitive to alterations in sharp regions compared to uniform regions, a simple edge detection method has been introduced to identify and embed in edge pixels, which will lead to an improved stego image quality. In order to increase the embedding capacity, the algorithm embeds variable number of bits (up to 3) in edge pixels based on the strength of edges. Moreover, to increase the efficiency, two message coding mechanisms have been utilized to enhance the ±1 steganography. The first one, which is based on Hamming code, is simple and fast, while the other which is known as the Syndrome Trellis Code (STC), is more sophisticated as it attempts to find a stego image that is close to the cover image through minimizing the embedding impact. The proposed steganography algorithm embeds the secret data bits into the Region of Non Interest (RONI), where due to its importance; the ROI is preserved from modifications. The experimental results demonstrate that the proposed method can embed large amount of secret data without leaving a noticeable distortion in the output image. The effectiveness of the proposed algorithm is also proven using one of the efficient steganalysis techniques. The proposed medical imaging information system proved to be capable of concealing EPR data and producing imperceptible stego images with minimal embedding distortions compared to other existing methods. In order to refrain from introducing any modifications to the ROI, the proposed system only utilizes the Region of Non Interest (RONI) in embedding the EPR data.


Inversion of the alpha-2 and alpha-1 noradrenergic control of the cortical release of acetylcholine and gamma-aminobutyric acid in morphine-tolerant guinea pigs.
In normal guinea pigs the adrenergic agonists clonidine and norepinephrine are known to inhibit directly the cortical outflow of acetylcholine (ACh) through alpha-2 receptors and to increase the cortical outflow of gamma-aminobutyric acid (GABA) through alpha-1 receptors. GABA, in turn, contributes to inhibit ACh through GABAA receptors. This scheme is changed drastically by morphine tolerance. In morphine-tolerant guinea pigs, clonidine at 7.5, 18.7 and 112 nmol/kg i.p. stimulates the cortical release of ACh through alpha-1 receptors. This effect is prevented by prazosin, 35.8 nmol/kg i.p. Clonidine reduces ACh release at high doses only (374 and 1122 nmol/kg i.p.). Furthermore, electrical stimulation of locus ceruleus also gives rise to a prazosin-sensitive increase in ACh release. In addition, locus ceruleus stimulation often causes behavioral activation rather than sedation. In morphine-tolerant guinea pigs, clonidine at 7.5 and 18.7 nmol/kg i.p. reduces GABA efflux through alpha-2 receptors, as the drug effect is prevented by idazoxan, 84 nmol/kg i.p. Clonidine increases GABA efflux at high doses only (112 and 374 nmol/kg i.p.). Locus ceruleus stimulation also gives rise to an idazoxan-sensitive reduction in GABA outflow. This new condition, evident after 7 days of morphine treatment, can be defined as inversion of the physiological norepinephrine control over ACh and GABA outflow and can represent a major part of the neurochemical derangement associated with opioid tolerance.


Immunogenic and encephalitogenic epitope clusters of myelin proteolipid protein.
To understand and develop strategies to intervene in autoimmune responses to myelin proteolipid protein (PLP), encephalitogenic epitopes must be identified. To expedite the identification of potentially immunogenic and encephalitogenic epitopes of PLP, overlapping synthetic 20-mer PLP peptides covering the whole PLP molecule were screened for their ability to bind to purified mouse I-Ad, I-Ak, and I-As molecules. The peptides that bound to the I-A molecules were tested for their ability to induce immune responses in corresponding inbred mouse strains. Immunogenic peptides were then tested for their ability to induce experimental autoimmune encephalomyelitis. Moderate to strong I-A binding was essential for development of immune responses, but immunogenicity was not sufficient for encephalitogenicity. Rather, encephalitogenic epitopes clustered in three regions of the molecule, namely within residues 40-70, 100-119, and 178-209. These were also the regions of the PLP that showed the greatest promiscuity in binding to I-A molecules. Except for PLP 139-151, which is an encephalitogenic determinant in mice expressing I-As, all encephalitogenic epitopes of PLP previously identified, regardless of their MHC class II restriction, are located within or adjacent to these epitope clusters. None of the encephalitogenic epitopes occur in regions of the molecule that have a high degree of homology with the neuronal M6a protein, a member of the DM20/PLP superfamily. Atypical clinical and histologic patterns of experimental autoimmune encephalomyelitis were observed in some strains of mice sensitized with certain PLP peptides and may reflect induction of T cells with different disease-inducing potentials.


An Overview of Research and Evaluation Designs for Dissemination and Implementation.
The wide variety of dissemination and implementation designs now being used to evaluate and improve health systems and outcomes warrants review of the scope, features, and limitations of these designs. This article is one product of a design workgroup that was formed in 2013 by the National Institutes of Health to address dissemination and implementation research, and whose members represented diverse methodologic backgrounds, content focus areas, and health sectors. These experts integrated their collective knowledge on dissemination and implementation designs with searches of published evaluations strategies. This article emphasizes randomized and nonrandomized designs for the traditional translational research continuum or pipeline, which builds on existing efficacy and effectiveness trials to examine how one or more evidence-based clinical/prevention interventions are adopted, scaled up, and sustained in community or service delivery systems. We also mention other designs, including hybrid designs that combine effectiveness and implementation research, quality improvement designs for local knowledge, and designs that use simulation modeling.


Patellar options in revision total knee arthroplasty.
There are numerous options that need to be considered by the surgeon at the time of revision total knee arthroplasty (TKA). One needs to consider the reason for the revision, the type of patella in place, and the length of time the patella has been in place. The surgeon also needs to consider the status of the patellar bone stock, the stability of the patellar component (well-fixed or loose), and the component type (cemented or metal-backed). Assuming that the existing prosthesis is not metal-backed and has minimal PE wear, then it is preferable to retain a well-fixed all-PE cemented patellar button. However, if the button is metal-backed, then it probably is best to remove the button and replace it with an all-PE domed patellar component. Assuming more than 8 mm of patellar bone stock is remaining, it usually is best to cement an all-PE dome-shaped patella. However, if less than 8 mm is remaining, then that patient can be left with a patelloplasty, recognizing that this individual is going to continue with a high likelihood of anterior knee pain, subluxation, and poor functional results. In that situation, it may be preferable to consider a bone stock augmentation.


Clinicopathological Significance of BRCAness in Resectable Pancreatic Ductal Adenocarcinoma and Its Association With Anticancer Drug Sensitivity in Pancreatic Cancer Cells.
The concept of BRCAness has been proposed as a homologous recombination repair dysfunction triggered by a genetic defect in the BRCA pathway including the BRCA1/2 mutations. A certain number of pancreatic ductal adenocarcinoma (PDAC) patients have BRCAness. However, a large-scale analysis of BRCAness in PDAC has not been performed. In addition, no basic studies have examined the significance of BRCAness in PDAC cell lines. Ninety-two patients who underwent surgery for PDAC were enrolled. Formalin-fixed and paraffin-embedded specimens of resected PDACs were used to analyze BRCAness by multiplex ligation-dependent probe amplification. We also analyzed BRCAness in pancreatic cancer cell lines and the sensitivity to cisplatin and olaparib using a colony formation assay. Of the 92 patients with PDAC, 6 were detected to have BRCAness-positive PDAC (6.5%). No significant differences in overall survival and progression-free survival were observed between the BRCAness-positive and BRCAness-negative groups. One PDAC cell line, KP-2, was positive for BRCAness and was more sensitive to cisplatin and olaparib than the BRCAness-negative cell lines. Our results revealed that a considerable number of PDACs are positive for BRCAness, suggesting that BRCAness status could be a useful biomarker for selecting anticancer treatments for advanced or relapsed PDAC.


[Intrapericardic surgical treatment of teratoma in an infant].
The intrapericardic cardiac tumors are infrequent; however, the clinical manifestations can be serious, even with symptoms of low cardiac output or cardiogenic shock, depending on the localization of the tumor. We report the case of a 3-month-old infant who progressed to cardiogenic shock due to an intrapericardic tumor compressing the right atrium and the vena cava superior. Emergent surgery for resection of the tumor mass was recommended. The patient had a 6-month uneventful postoperative course.


[Effects of detergents on neutral cholesterol esterase from porcine aorta].
Effects of detergents on hydrolysis of cholesteryl-14C-oleate by porcine aorta extracts were studied. Digitonin, cetyl pyridinium chloride and sodium taurocholate inhibited the activity of cholesterolesterase, sodium cholate enhanced slightly the hydrolysis and Triton X-100 exhibited a considerable stimulating effect. After chromatography of aorta extracts on Bio-Gel A-1.5 m two cholesterolesterase fractions were obtained with molecular weight of about 200,000 and above 1 500 000, respectively; the first fraction was active only in presence of Triton X-100 and the second--hydrolysed cholesteryl-14C-oleate both in presence and absence of the detergent. As a result of treatment of aorta extracts with digitonin (0.4%), the Triton-dependent low molecular fraction of cholesterolesterase was obtained. Since the molecular weight of the enzyme fraction was about 20,000 (as shown by elution profiles), the activating effect of Triton on cholesterolesterase appears to be not due to disaggregation of the enzyme of to destruction of the membrane-enzyme complexes.


Low-temperature water reconstruction in concanavalin A, with implications for controlled protein crystal annealing.
Flash-cooled crystals of the I222 form of concanavalin A undergo a sharp non-destructive non-reversible phase transition upon warming to between 160 and 165 K, characterized by an anomalous increase in unit-cell volume. The expansion is anisotropic and primarily affects the b and c axes. Three sets of 1.7 A X-ray diffraction data were collected from one crystal: immediately after flash-cooling (130 K), after slow warming to 170 K and after re-cooling to 130 K. Measurable changes in reflection width after the transition were apparent. Each data set was collected under very similar conditions (aside from temperature). Structures refined against each data set using a powerful phase-bias reduction algorithm indicate negligible rearrangement of the protein molecule and its first hydration shell. Further away from the protein surface, on the edge of the fully disordered solvent regions, a small number of more dramatic changes were apparent. Little is known about the behaviour of water confined within dimensionally restricted spaces, but solvent cavities and channels in protein crystals provide a rich source of reproducible nanoscale water assemblies. This paper presents information on the behaviour of water confined within protein cavities in relation to the physics of protein crystal annealing.


Clinical and microbiological efficacy of MDT in the treatment of diabetic foot ulcers.
To assess the clinical and microbiological efficacy of maggot debridement therapy (MDT) in the management of diabetic foot ulcers unresponsive to conventional treatment and surgical intervention. Consecutive diabetic patients with foot wounds presenting at the vascular surgery unit and the diabetic foot unit of Alexandria Main University Hospital were selected for MDT. Lucilia sericata medicinal maggots were applied to the ulcers for three days per week. Changes in the percentage of necrotic tissue and ulcer surface area were recorded each week over the 12-week follow-up period. Semiquantitative swab technique was used to determine the bacterial load before and after MDT. The sample comprised 10 patients with 13 diabetic foot ulcers. The mean baseline ulcer surface area was 23.5cm2 (range 1.3-63.1), and the mean percentage of necrotic tissue was 74.9% (range 29.9-100). Complete debridement was achieved in all ulcers in a mean of 1.9 weeks (range 1-4). Five ulcers (38.5%) were completely debrided with one three-day MDT cycle. The mean reduction in ulcer size was significant at 90.2%, and this occurred in a mean of 8.1 weeks (range 2-12). The mean weekly reduction in ulcer size was 16.1% (range 8.3-50). Full wound healing occurred in 11 ulcers (84.6%) within a mean of 7.3 weeks (range 2-10). The bacterial load of all ulcers reduced sharply after the first MDT cycle to below the 10(5) threshold, which facilitates healing. The results highlight the potential benefits of MDT in diabetic wound care in developing countries. MDT was proved to be a rapid, simple and efficient method of treating these ulcers.


Laparascopic Splenectomy Due to Splenic Injury after Colonoscopy.
Colonoscopy, which is routinely performed in diagnosis and treatment of colorectal disorders, is a reliable procedure. Its most frequent complications are bleeding and perforation. Splenic rupture is a very rarely met complication of colonoscopy, and delay in its diagnosis leads to increased morbidity and mortality. We presented a 69 years old female patient, who was diagnosed by computerized abdominal tomography, performed for her abdominal pain, which started following the colonoscopy. After 15 days of medical treatment and follow-up, laparoscopic splenectomy was performed one month after her colonoscopy. The patient was discharged on her 4(th) postoperative day, with uneventful recovery. In patients who have complaint of abdominal pain following colonoscopy, an intraabdominal pathological condition should be considered and computerized abdominal tomography should be performed. If there is no detected intraperitoneal bleeding, in other words, if there is a sub-capsular hematoma of the spleen, medical management by monitoring the vital signs may be preferred. Then, splenectomy should be performed at an appropriate time.


Extracorporeal shock wave therapy is effective in treating chronic plantar fasciitis: A meta-analysis of RCTs.
Plantar fasciitis (PF) is the most common reason for heel pain. The efficacy of extracorporeal shock wave therapy (ESWT) as an ideal alternative to conservative treatments and surgery is controversial, and almost all previous articles compared general ESWT with placebo without indicating the kind of shock wave. We undertook a meta-analysis to compare the efficacy of general ESWT, focused shock wave (FSW), and radial shock wave (RSW) with placebo, to assess their effectiveness in chronic PF. The PubMed, Medline, EmBase, Web of Science, and Cochrane library databases were searched for studies comparing FSW or RSW therapy with placebo in chronic PF. Clinical outcomes included the odds ratios (ORs) of pain relief, pain reduction, and complications. Relevant data were analyzed using RevMan v5.3. Nine studies involving 935 patients were included. ESWT had higher improvement rates than the placebo group (OR 2.58, 95% confidence interval [CI] 1.97-3.39, P < .00001). ESWT had markedly lower standardized mean difference than placebo, with heterogeneity observed (standardized mean difference 1.01, 95% CI -0.01 to 2.03, P = .05, I = 96%, P < .00001). FSW and RSW therapies had greater therapeutic success in pain relief than the placebo group (OR 2.17, 95% CI 1.49-3.16, P < .0001; OR 4.63, 95% CI 1.30-16.46, P = .02), but significant heterogeneity was observed in RSW therapy versus placebo (I = 81%, P = .005). This meta-analysis suggested that FSW therapy can relieve pain in chronic PF as an ideal alternative option; meanwhile, no firm conclusions of general ESWT and RSW effectiveness can be drawn. Due to variations in the included studies, additional trials are needed to validate these conclusions.


Measuring the impact of quality improvement efforts.
Healthcare organizations are looking to quality programs as a key to survival, but many financial managers are unaware of the measurement methods they can use to quantify the results of quality management efforts. These methods can tell what impact quality initiatives have had on corporate culture, systems operations, and the bottom line.


Cyclooxygenase 2: protein-protein interactions and posttranslational modifications.
Numerous studies implicate the cyclooxygenase 2 (COX2) enzyme and COX2-derived prostanoids in various human diseases, and thus, much effort has been made to uncover the regulatory mechanisms of this enzyme. COX2 has been shown to be regulated at both the transcriptional and posttranscriptional levels, leading to the development of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX2 inhibitors (COXIBs), which inhibit the COX2 enzyme through direct targeting. Recently, evidence of posttranslational regulation of COX2 enzymatic activity by s-nitrosylation, glycosylation, and phosphorylation has also been presented. Additionally, posttranslational regulators that actively downregulate COX2 expression by facilitating increased proteasome degradation of this enzyme have also been reported. Moreover, recent data identified proteins, located in close proximity to COX2 enzyme, that serve as posttranslational modulators of COX2 function, upregulating its enzymatic activity. While the precise mechanisms of the protein-protein interaction between COX2 and these regulatory proteins still need to be addressed, it is likely these interactions could regulate COX2 activity either as a result of conformational changes of the enzyme or by impacting subcellular localization of COX2 and thus affecting its interactions with regulatory proteins, which further modulate its activity. It is possible that posttranslational regulation of COX2 enzyme by such proteins could contribute to manifestation of different diseases. The uncovering of posttranslational regulation of COX2 enzyme will promote the development of more efficient therapeutic strategies of indirectly targeting the COX2 enzyme, as well as provide the basis for the generation of novel diagnostic tools as biomarkers of disease.


Plant Growth Promoting of Endophytic Sporosarcina aquimarina SjAM16103 Isolated from the Pneumatophores of Avicennia marina L.
Endophytic Sporosarcina aquimarina SjAM16103 was isolated from the inner tissues of pneumatophores of mangrove plant Avicennia marina along with Bacillus sp. and Enterobacter sp. Endophytic S. aquimarina SjAM16103 was Gram variable, and motile bacterium measured 0.6-0.9 μm wide by 1.7-2.0 μm long and light orange-brown coloured in 3-day cultures on tryptone broth at 26°C. Nucleotide sequence of this strain has been deposited in the GenBank under accession number GU930359. This endophytic bacterium produced 2.37 μMol/mL of indole acetic acid and siderophore as it metabolites. This strain could solubilize phosphate molecules and fixes atmospheric nitrogen. Endophytic S. aquimarina SjAM16103 was inoculated into four different plants under in vitro method to analyse its growth-promoting activity and role inside the host plants. The growth of endophytic S. aquimarina SjAM16103 inoculated explants were highly significant than the uninoculated control explants. Root hairs and early root development were observed in the endophytic S. aquimarina SjAM16103 inoculated explants.


Erratum.
The caption for a series of head scans shown in the News & Comment article "AZT reverses AIDS dementia in children" (6 Oct., p. 21) was in error. The pictures of the brain, obtained by a CAT scan, indicate brain physiology but not metabolism. The latter would be revealed by a PET scan.


FANCD2 influences replication fork processes and genome stability in response to clustered DSBs.
Fanconi Anemia (FA) is a cancer predisposition syndrome and the factors defective in FA are involved in DNA replication, DNA damage repair and tumor suppression. Here, we show that FANCD2 is critical for genome stability maintenance in response to high-linear energy transfer (LET) radiation. We found that FANCD2 is monoubiquitinated and recruited to the sites of clustered DNA double-stranded breaks (DSBs) specifically in S/G2 cells after high-LET radiation. Further, FANCD2 facilitated the repair of clustered DSBs in S/G2 cells and proper progression of S-phase. Furthermore, lack of FANCD2 led to a reduced rate of replication fork progression and elevated levels of both replication fork stalling and new origin firing in response to high-LET radiation. Mechanistically, FANCD2 is required for correct recruitment of RPA2 and Rad51 to the sites of clustered DSBs and that is critical for proper processing of clustered DSBs. Significantly, FANCD2-decifient cells exhibited defective chromosome segregation, elevated levels of chromosomal aberrations, and anchorage-independent growth in response to high-LET radiation. These findings establish FANCD2 as a key factor in genome stability maintenance in response to high-LET radiation and as a promising target to improve cancer therapy.


Neurological symptoms among Sri Lankan farmers occupationally exposed to acetylcholinesterase-inhibiting insecticides.
In many agricultural districts in Sri Lanka, pesticide poisoning is a leading cause of death. This study aims to evaluate the impact of pesticide use on Sri Lankan farmers' health. A total of 260 subjects were surveyed in both a low and a high exposure period. Acetylcholinesterase activity was measured and data on symptoms were collected with questionnaires. Twenty-four percent of surveyed farmers had suffered at least once from acute pesticide poisoning. Farmers showed significantly more inhibition of cholinesterase activity than controls. Acute symptoms indicative for exposure to cholinesterase-inhibiting pesticides were associated with farming and a higher degree of cholinesterase suppression (more than 13% inhibition). Integrated Pest Management (IPM) training seemed to result in less insecticide use, and less cholinesterase inhibition. Our results suggest that occupational acetylcholinesterase-inhibiting insecticide exposures have a negative impact on Sri Lankan farmers' health. Overall reduction in pesticide use seems the best option to protect farmers from the adverse effects of pesticides.


Effect of fatigue on performance measured by a driving simulator in automobile drivers.
To identify risk factors of performance decrement in automobile drivers. 114 drivers (age <30 years, n=57; age > or =30 years, n=57) who stopped at a rest stop area on a freeway were recruited for the study. They filled out a questionnaire on their journey, sleep/wake patterns and performed a 30-min test on a driving simulator. The test evaluates, by computerized analysis, the lateral deviation of a virtual car from an appropriate trajectory on a virtual road. A sex/age matched control group was recruited in the community. Control subjects were studied at the same time of day as the index case driver. Controls had normal sleep wake schedule, absence of long driving and performed the same driving test. Drivers performed significantly worse than controls on the driving test. Age and duration of driving were the main factors associated with decreased performance. Our driving simulator can identify fatigue generated by driving but results must be considered in relation with age of subjects.


Performance measures for in-hospital care of acute ischemic stroke in public hospitals in Chile.
The aim of this study were to describe acute care of ischemic stroke patients and adherence to performance measures, as well as the outcomes of these events, in a sample of patients treated in public hospitals in Chile. We retrospectively reviewed the medical charts of patients with ischemic stroke from a sample of seven public hospitals in the Metropolitan Region of Santiago. We analyzed adherence to the following evidence-based measures: clinical evaluation at admission, use of intravenous thrombolysis, dysphagia screening and prescription of antithrombotic therapy at discharge. As outcome measures we analyzed post-stroke pneumonia and 30-day case-fatality. We used a logistic regression model by each outcome with generalized estimating equations, which accounted for clustering of patients within hospitals and included sex, age (years), clinical status at admission (reduced level of consciousness, speech disturbance, aphasia and hemiplegia), comorbidities, dysphagia screening and neurological evaluation at admission as measures of acute stroke care. We reviewed the charts of 677 patients, of which 52.3% were men. The mean age was 69.8 years in women and 66.3 years in men. Diagnosis of stroke was confirmed by a computed tomography scan within 4.5 hours of symptom onset in only 9.6% of the patients. Intravenous thrombolysis was administered in 1.7%. Dysphagia screening was performed in 12.1% (95% CI 9.7-15.0) and antithrombotic therapy was prescribed in 68.9% (95% CI 64.6-72.9). Pneumonia was diagnosed in 23.6% (95% CI 20.4-27.2). Thirty-day fatality was 8.7% (95% CI 6.7-11.3). The variables independently associated with 30-day case fatality were age (OR 1.08, 95% 1.06-1.10), pneumonia (OR 7.7, 95% 95% CI 4.0-14.7), aphasia (OR 2.4, 95% CI 1.1-5.6), reduced level of consciousness (OR 2.4, 95% CI 1.3-4.4), and speech disturbance (OR 1.4, 95% CI 1.0-1.9). No association was found between 30-day case fatality and dysphagia screening or neurological evaluation at admission. The factors associated with post-stroke pneumonia were female sex (OR 1.6, 95% CI 1.0-2.3), age (OR 1.04 95% CI 1.03-1.05), diagnosis of diabetes (OR 1.8, 95% CI 1.4-2.4), aphasia (OR 2.0, 95% CI 1.5-2.7), hemiplegia (OR 1.6, 95% CI 1.1-2.4), and reduced level of consciousness on admission (OR 3.4, 95% CI 2.1-5.5). No association was found between pneumonia and dysphagia screening or neurological evaluation at admission. Adherence to evidence-based performance measures was low. Administration of intravenous thrombolysis was particularly low and diagnostic confirmation of ischemic stroke was delayed. The occurrence of post-stroke pneumonia was frequent and should be reduced. To improve acute stroke care in Chile, organizational change in the health service is urgently needed.


Unusual patterns of IgG avidity in some young children following two doses of the adjuvanted pandemic H1N1 (2009) influenza virus vaccine.
During the 2009-2010 H1N1 influenza pandemic, an adjuvanted monovalent vaccine containing ∼25% of the normal antigen dose and AS03 adjuvant was widely used in Canada. This vaccine was found to be well-tolerated and immunogenic in young children (D. W. Scheifele et al., Pediatr. Infect. Dis. J. 30:402-407, 2011). We report here additional analyses to further characterize the humoral response to this vaccine. We measured standard hemagglutination inhibition (HAI) and microneutralization (MN) titers, as well as influenza virus-specific IgG avidity and subclass distribution by enzyme-linked immunosorbent assay in 73 subjects. Sera were collected before (day 0) and 3 weeks after each dose of vaccine (days 21 and 42). Most children (55/73) had undetectable HAI and MN titers at day 0 (presumed to be antigen naive) and mounted good responses at days 21 and 42. The majority of these children (43/55) had the expected pattern of an increasing IgG avidity index (AI) after each dose of vaccine (not detected [ND], 0.30, and 2.97 at days 0, 21, and 42, respectively). The avidity responses in the remaining children (12/55) were quite different, with AIs increasing abruptly after the first dose and then declining after the second dose of vaccine (ND, 8.83, and 7.15, respectively). These children also had higher concentrations of influenza virus-specific IgG1 and IgG3 antibodies at day 21. Although the antibody titers were similar, some antigen-naive children demonstrated an unusual pattern of avidity maturation after two immunizations with AS03-adjuvanted, low-dose influenza virus vaccine. These data suggest the presence of subtle differences in the quality of the antibodies produced by some subjects in response to this vaccine.


Hodgkin's disease survivors more fatigued than the general population.
To estimate the level of fatigue and frequency of fatigue cases among Hodgkin's disease survivors (HDS) and compare them with normative data from the general population. A cross-sectional follow-up study was done of 557 HDS (age range, 19 to 74 years) treated at the Norwegian Radium Hospital from 1971 to 1991. The sample was approached by mail, and their data were compared with normative data from 2,214 controls (age range, 19 to 74 years) representative of the general Norwegian population. Of the 557 HDS, 459 (82%) responded. The mean age (+/- SD) at the time of study was 44+/-12 years, and the mean observation time was 12+/-6 years. The Fatigue Questionnaire (11 items) measures physical and mental fatigue. Two systems of scoring were used, dichotomized (0, 0, 1, and 1) and Likert (0, 1, 2, and 3). Total fatigue (TF) constitutes the sum of all the Likert scores. Caseness was defined as a total dichotomized score of > or =4 and fatigue that lasted 6 months or longer. The HDS had significantly higher levels of TF than the controls (14.3 v 12.2) (P < .001). Fatigue among the HDS equaled that of the controls in poorest health. More HDS (61%) than controls (31%) reported fatigue symptoms lasting 6 months or longer (P < .001). Fatigue cases were more frequent among HDS (men, 24%; women, 27%) than among the controls (men, 9%; women, 12%) (P < .001). Disease stage/substage IB/IIB predicted fatigue caseness (P = .03). No significant associations were found between treatment characteristics and fatigue. Hodgkin's disease survivors are considerably more fatigued than the general population and report fatigue of a substantially longer duration.


A Community-Based Study of Sleep and Cognitive Development in Infants and Toddlers.
To examine the prevalence and correlates of nighttime awakenings and to explore the association between sleep and cognitive development in a community sample of infants and toddlers. A total of 590 healthy infants (aged 2-11 months) and 512 toddlers (aged 12-30 months) from 8 provinces of China were assessed for their sleep and cognitive development. Data on sleep duration and nighttime awakenings were collected through the Brief Infant Sleep Questionnaire. Cognitive development was assessed by trained pediatricians using the Bayley Scales of Infant Development. Prevalence of no nighttime awakening, and nighttime awakening(s) for 1×/night, 2×/night, and ≥ 3×/night was 6.8%, 20.2%, 33.2%, and 39.3% in infants, and was 25.8%, 34.6%, 23.8%, and 15.8% in toddlers, respectively. Nighttime awakenings were generally associated with younger age, lower maternal education level, and being currently breastfed. In addition, nighttime awakenings were associated with being boys in toddlers. After controlling for potential confounders, infants with nighttime awakenings for 2×/night were found to have significantly higher Mental Development Index (MDI) score, as compared to those without and those with more frequent nighttime awakenings. However, toddlers with nighttime awakenings for ≥ 3×/night had significantly lower MDI, as compared to those with fewer nighttime awakenings. Total sleep duration was not associated with any developmental indices in both infants and toddlers. Frequent nighttime awakenings are associated with poor cognitive functions in toddlers. Meanwhile, a nonlinear association between nighttime awakenings and cognitive performance was found among infants. The findings provide a developmental context for the effect of sleep on cognitive abilities in young children. Further longitudinal studies and interventional studies on the effects of parent-based sleep-focused intervention on cognitive abilities among young children are warranted.


[Formation of quasilinear domain structures in lipid membranes].
The process of domain lipid structure formation in phoshatidylcholine layer is studied in the context of phase separation theory for two-component mixtures. Computer simulation has shown that as the result of distinctions of structure of hydrocarbon chain-in all-trans and gauche states phase separation of different lipid conformers occurs and quasilinear domain structure is formed in the region of pretransition. The repeat distance of obtained domain structure is reasonable agreement with the experimental data of the ripple mode in phase P beta, of phoshatidylcholine bilayer. Possible role of the In-plane quasilinear lipid structure in biomembranes is discussed.


Neuropsychological performance in treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom Veterans with a history of mild traumatic brain injury.
Clinical neuropsychological presentation of treatment-seeking Veterans with a remote history of mild traumatic brain injury (mTBI) is widely variable. This manuscript seeks to better characterize cognitive concerns in the post-acute phase following mTBI and to identify the neuropsychological profiles of a large sample of clinically referred Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) Veterans with a history of mTBI and current cognitive complaints. We hypothesized that a minority of cases would exhibit valid and widespread neuropsychological deficits. Retrospective chart reviews of neuropsychological testing and mental health symptoms and diagnoses were conducted on 411 clinically referred OEF/OIF/OND Veterans with a history of mTBI. Groups were created based on scores on performance validity measures and based on overall neuropsychological performance. A total of 29.9% of the sample performed below normative expectations on at least one performance validity test (PVT). Of those Veterans performing adequately on PVTs, 60% performed within normal limits on virtually all neuropsychological measures administered, leaving only 40% performing below expectations on two or more measures. Mood and neurobehavioral symptoms were significantly elevated in Veterans performing below cutoff on PVTs compared to Veterans who performed within normative expectations or those with valid deficits. Neurobehavioral symptoms were significantly correlated with mental health symptom reports but not with injury variables. In summary, in a large sample of clinically referred Veterans with persistent cognitive complaints after mild TBI, a third demonstrated invalid clinical neuropsychological testing, and, of those performing at or above cutoff on PVTs, over half performed within normative expectations across most neuropsychological tests administered. Results highlight the importance of objective assessment of cognitive functioning in this population as subjective reports do not correspond to objective assessment in the majority of cases.


Case report: a 37-year-old male with telangiectasias, polycythemia vera, perinephric fluid collections, and intrapulmonary shunting.
The TEMPI syndrome was recently described in 2011, and is characterized by the constellation of five hallmarks: Telangiectasias, Erythrocytosis and elevated Erythropoietin, Monoclonal gammopathy, Perinephric fluids collections, and Intrapulmonary shunting. The underlying pathophysiology is unknown, though it has been postulated that the monoclonal gammopathy may play a causal role. A 37-year-old non-smoking male presented to our institution with a fever and the sensation of fullness in the right flank. His exam was notable for telangiectasias, clubbing of the fingernails, plethora, and a palpable bulge in the right flank. Renal ultrasound demonstrated bilateral perinephric fluid collections. Laboratory evaluation revealed erythrocytosis with low serum erythropoietin, and testing for the JAK2V617F mutation was positive, confirming a diagnosis of polycythemia vera. Though his room air saturation was normal at rest, it decreased dramatically with exercise, felt to be secondary to microscopic intrapulmonary shunting. The patient's presentation is very similar to that of the TEMPI syndrome, a very rare syndrome of which there have been six published cases. In contrast to the TEMPI syndrome where the erythrocytosis is driven by highly elevated serum erythropoietin, our patient was found to have polycythemia vera. Also in contrast to the other patients with TEMPI syndrome, our patient did not have an identifiable monoclonal gammopathy. Our patient responded to treatment with hydroxyurea. His erythrocytosis, perinephric fluid collections, and telangiectasias resolved over the course of six months. The intrapulmonary shunting has continued to gradually improve with treatment, suggesting that this is an entirely reversible process. Our case is the first to describe the combination of polycythemia vera, telangiectasias, perinephric fluid collections, and intrapulmonary shunting. The presentation is highly similar to the previously described TEMPI syndrome, though calls into question the potential importance of the monoclonal gammopathy. Our patient demonstrated a response to treatment with hydroxyurea, while patients with the TEMPI syndrome have shown responses to plasma-cell directed therapies such as bortezomib.


The microalgae's ability to accumulate selected trace elements studied by ICP-MS/MS and chemometric methods.
Microalgae can be used in different branches of industry, including cosmetology, pharmaceutics and the food industry, information on their ability to accumulate different elements becomes more important. The microalgae biomass grown in the media enriched in elements can increase the accumulation of different ions and give a possibility to control the contents of the various elements. The aim of the study was to determine the total content of metals in microalgae by tandem mass spectrometry with inductively coupled plasma (ICP-MS/MS) and analysis of the contents of particular metals as a function of the type of microalgae and conditions of cultivation. As the adverse effects of metals on the health of humans and animals have been well-documented and the use of microalgae has increased, the knowledge of metal contents in them is of particular importance in control of their quality. Analysis of results permitted distinction of three main groups of microalgae with similar total metal content levels. Moreover, the results revealed the ways of stimulating more significant accumulation of selected elements (for example, Se concentration in control algae 0.279 µg g-1, in the algae cultivated in enriched medium - 219.7 µg g-1). They indicated the possible correlations between the accumulation of different ions. The result obtained shows a significant effect of metal accumulation and has a considerable impact on the differentiation of Arthrospira platensis grown in the medium enriched in different elements (selenium, zinc, chromium) (p ≤ 0.05). Particular impact on the content of selected elements had the conditions of cultivation (type of support) and the microalgae species. Although the one species as the most significant source of selected elements cannot be indicated, it is possible to control the accumulation by the composition of the medium.


Meta-analyses comparing theory of mind abilities of individuals with autism, individuals with mental retardation, and normally developing individuals.
A deficit in theory of mind (ToM) abilities has been described as the core deficit in autism. The authors performed 3 meta-analyses, comparing ToM abilities of individuals with autism, individuals with mental retardation (MR), and normally developing individuals. Results indicated that individuals with autism and MR have impaired ToM abilities. The etiology associated with MR (i.e., Down syndrome, undifferentiated etiology) was found to be an important moderator variable. Chronological age (CA) and verbal mental age (VMA) of the normally developing children and CA, VMA, and performance mental age of individuals with MR, and type of matching between the groups were also found to be moderator variables. Discussion focuses on the implication of the findings and emphasizes the need to consider the specific etiology of comparison groups when studying abilities and impairments of individuals with autism and MR.


Perceived patient burden and acceptability of whole body MRI for staging lung and colorectal cancer; comparison with standard staging investigations.
To evaluate perceived patient burden and acceptability of whole body MRI (WB-MRI) compared to standard staging investigations, and identify predictors of reduced tolerance. Patients recruited to multicentre trials comparing WB-MRI with standard staging scans for lung and colorectal cancer were invited to complete two questionnaires: a baseline questionnaire at recruitment, measuring demographics, comorbidities, and distress; and a follow-up questionnaire after staging, measuring recovery time, comparative acceptability/satisfaction between WB-MRI and CT (colorectal cancer) and PET-CT (lung cancer), and perceived scan burden (scored 1, low; 7, high). Results: 115 patients (median age 66.3 years; 67 males) completed follow up and 103 baseline questionnaires. 69 (63.9%) reported "immediate" recovery from WB-MRI and 73 (65.2%) judged it "very acceptable". Perceived WB-MRI burden was greater than for CT (p < 0.001) and PET-CT (p < 0.001). High distress and comorbidities were associated with greater WB-MRI burden in adjusted analyses, with deprivation only approaching significance (adjusted regression β = 0.223, p = 0.025; β = 0.191, p = 0.048; β = -0.186, p = 0.059 respectively). Age (p = 0.535), gender (p = 0.389), ethnicity (p = 0.081) and cancer type (p = 0.201) were not predictive of WB-MRI burden. WB-MRI is marginally less acceptable and more burdensome than standard scans, particularly for patients with pre-existing distress and comorbidities. Advances in knowledge: This research shows that WB-MRI scan burden, although low, is higher than for current staging modalities among patients with suspected colorectal or lung cancer. Psychological and physical comorbidities adversely impact on patient experience of WB-MRI. Patients with high distress or comorbid illness may need additional support to undergo a WB-MRI.


Evaluation of a Cost-Effective Ammonia Monitoring System for Continuous Real-Time Concentration Measurements in a Fattening Pig Barn.
Ammonia (NH3) emission is one of the major environmental issues in livestock farming. Gas measurements are required to study the emission process, to establish emission factors, and to assess the efficiency of emission reduction techniques. However, the current methods for acquiring reference measurements of NH3 are either high in cost or labor intensive. In this study, a cost-effective ammonia monitoring system (AMS) was constructed from a commercially-available gas analyzing module based on tunable diode laser absorption (TDLA) spectroscopy. To cope with the negative measurement biases caused by differing inlet pressures, a set of correction equations was formulated. Field validation of the AMS on NH3 measurement was conducted in a fattening pig barn, where the system was compared to a Fourier-transform infrared (FTIR) spectroscopy analyzer. Under two test conditions in a fattening pig barn, the absolute error of the AMS measurements with respect to the average obtained values between the AMS and the FTIR was respectively 0.66 and 0.08 ppmv, corresponding to 5.9% and 0.5% relative error. Potential sources of the measurement uncertainties in both the AMS and FTIR were discussed. The test results demonstrated that the AMS was capable of performing high-quality measurement with sub-ppm accuracy, making it a promising cost-effective tool for establishing NH3 emission factors and studying NH3 emission processes in pig houses.


A prospective 1-year clinical and radiographic study of implants placed after maxillary sinus floor augmentation with synthetic biphasic calcium phosphate or deproteinized bovine bone.
The technique of using bone grafts or different biomaterials for augmentation of the maxillary sinus prior to implant placement is well accepted by clinicians. However, clinical documentation of some bone substitutes is still lacking. This prospective study was designed to evaluate the success rate of implants placed after maxillary sinus augmentation with a novel synthetic biphasic calcium phosphate (BCP) or deproteinized bovine bone (DBB), the latter acting as control. Nine edentulous patients and two partially edentulous patients with a mean age of 67 years with a bilateral need for sinus augmentation, < 5 mm residual bone in the floor of the sinus and a crestal width ≥ 4 mm, were included in the study. After bilateral elevation of the Schneiderian membrane, all patients were randomized for augmentation with synthetic BCP in one side and DBB in the contralateral side. After 8 months of graft healing, 62 implants with an SLActive surface were placed. Implant survival, graft resorption, plaque index, bleeding on probing, sulcus bleeding index, probing pocket depth, and implant success rate were evaluated after 1 year of functional loading. After a mean of 118 days, all patients received their fixed prosthetic constructions. One implant was lost in each biomaterial, giving an overall survival rate of 96.8%. Success rates for implants placed in BCP and DBB were 91.7 and 95.7%, respectively. No significant difference in marginal bone loss was found around implants placed in BCP, DBB, or residual bone, respectively. The mean graft resorption was 0.43 mm (BCP) and 0.29 mm (DBB). In this limited study, implant success rate was not dependent on the biomaterial used for maxillary sinus augmentation. Similar results were found after 1 year of functional loading for implants placed after sinus augmentation using BCP or DBB.


Epidemiological Characteristics of Dorsal and Lumbar Spine Trauma Presenting to a Trauma Hospital in Kathmandu, Nepal: Formulation of a National Spine Policy.
Outcome of spine injury treated in resource constrained regions may not be the same as in developed nations. The aim of the present study was to study the epidemiological characteristics, delay, complications, and outcome of surgically treated dorsal and lumbar trauma. Retrospective study of dorsal and lumbar spine injury patients treated between December 2015 and August 2017. Patients were segregated into four groups based on the timing of surgery: 0-2 days, 3-7 days, 8-30 days, and more than 31 days. Only one operating room twice a week was allotted to spine surgery, and spine had to compete with orthopedic and surgical trauma for admission and surgery. Ninety-one patients (male 61) with mean age 33 years were operated for dorsal and lumbar spine injuries. 84% of the total patients sustained a fall, and 86.8% were from the periphery. Though 69.2% presented within 2 days, only 4.4% were operated within 2 days. Majority of the delay was due to unavailability of the operating room followed by financial constraints. Twenty-seven patients had complete deficit, 32 incomplete deficit, and 32 normal neurology. Four patients operated within 2 days improved their neurology, 7 incomplete deficit patients in 3-7 days group improved, 6 in 8-30 days group improved, whereas no patient in more than 31 days group improved. Overall 53.1% of neurologically incomplete deficit patients improved if operated within 30 days. No neurological improvement was seen in the 27 complete deficit patients. Wound infection, pulmonary contusion, and deep vein thrombosis were seen in 3 patients. As expected 95.6% of our patients were treated more than 3 days after injury and 60% more than a week later, which may not be acceptable in advanced countries. Despite the delay, 53.1% had an improvement in neurology when operated within 30 days. Hence, surgery still holds the hope of neurological recovery and quicker rehabilitation.


Long-Term Outcomes After Hybrid Coronary Revascularization Versus Coronary Artery Bypass Grafting: Meta-Analysis of Kaplan-Meier-Derived Data.
Hybrid coronary revascularization (HCR) is an alternative option to conventional coronary artery bypass grafting (CABG), but the long-term outcomes of HCR versus CABG remain unclear. We aimed to analyze the long-term outcomes after HCR and CABG for patients with multivessel coronary artery disease using meta-analysis. A systemic literature search of PubMed and EMBASE was performed from inception to March 2023. Studies reporting Kaplan-Meier curves with follow-up ≥1 year were included. The primary outcome was all-cause mortality, and the secondary outcomes were major adverse cardiac and cerebrovascular events (MACCEs) and repeat revascularization. In total, 13 studies (1 randomized controlled trial and 12 propensity-score matched observational studies) were analyzed. The mean follow-up period was 5.1 ± 3.1 years. HCR was associated with similar overall mortality (hazard ratio [HR] 1.09, 95% confidence interval [CI] 0.87 to 1.36), significantly higher incidence of MACCEs (HR 1.49, 95% CI 1.07 to 2.06), and repeat revascularization (HR 2.01, 95% CI 1.53 to 2.64) compared with CABG. In phase-specific analysis, the mortality rate was similar, and the incidence of repeat revascularization was higher in HCR regardless of phases. The incidence of MACCEs was higher in HCR during the mid-term phase (1 to 5 years), but it was similar during the long-term phase (long-term: ≥5 years). In conclusion, despite the higher incidence of MACCEs and repeat revascularization compared with CABG, HCR offered a similar long-term survival. Even longer-term follow-up and randomized controlled trials with a large population are warranted to investigate the role of HCR for multivessel coronary artery disease.


Clinical efficacy and patients' perception of virtual reality during wound care in adults: A systematic review with meta-analysis of randomised clinical trials.
This study was aimed to review Virtual Reality's (VR) impact on pain, anxiety, opioid usage, physiological and behavioural responses, and patients' experience during wound care (WC) in adults. We searched multiple databases (Embase, Medline ALL, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, CINAHL, Scopus and Google Scholar) from inception until January 27th, 2023. Included studies compared VR alone or as an adjunct to standard WC with standard WC or other distraction methods, in adults with burn or non-burn-related wounds. The risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomised parallel-group and crossover trials. The review followed PRISMA guidelines for reporting. Fourteen studies were eligible for inclusion. The meta-analysis was limited to studies comprising solely of adult participants. VR reduced pain intensity compared to standard WC in all study designs. Despite not being included in the meta-analysis due to reasons such as mixed population or lack of sufficient statistical data, other studies showed significant pain reduction using VR. Additionally, VR improved patients' experience of WC. No clear effect was found on other outcomes including anxiety, opioid usage and physiological and behavioural responses. VR shows promise in reducing acute pain and enhancing patients' experience of WC. The observed variations in the effects of VR at group and individual levels indicate the need for a personalised treatment plan by selecting the right VR for the right patient given at the right time.


Proline 235 plays a key role in the regulation of the oligomeric states of Thermotoga maritima Arginine Binding Protein.
The Arginine Binding Protein isolated from Thermotoga maritima (TmArgBP) is a protein endowed with several peculiar properties. We have previously shown that TmArgBP dimerization is a consequence of the swapping of the C-terminal helix. Here we explored the structural determinants of TmArgBP domain swapping and oligomerization. In particular, we report a mutational analysis of the residue Pro235, which is located in the hinge region of the swapping dimer. This residue was either replaced with a Gly-Lys dipeptide (TmArgBP(P235GK)) or a Gly residue (TmArgBP(P235G)). Different forms of these mutants were generated and extensively characterized using biophysical techniques. For both TmArgBP(P235GK) and TmArgBP(P235G) mutants, the occurrence of multiple oligomerization states (monomers, dimers and trimers) was detected. The formation of well-folded monomeric forms for these mutants indicates that the dimerization through C-terminal domain swapping observed in wild-type TmArgBP is driven by conformational restraints imposed by the presence of Pro235 in the hinge region. Molecular dynamics studies corroborate this observation by showing that Gly235 assumes conformational states forbidden for Pro residues in the TmArgBP(P235G) monomer. Unexpectedly, the trimeric forms present: (a) peculiar circular dichroism spectra, (b) a great susceptibility to heating, and (c) the ability to bind the Thioflavin T dye. The present findings clearly demonstrate that single-point mutations have an important impact on the TmArgBP oligomerization process. In a wider context, they also indicate that proteins endowed with an intrinsic propensity to swap have an easy access to states with altered structural and, possibly, functional properties.


Influence of Irrigation Protocol on Peroxide Penetration into Dentinal Tubules Following Internal Bleaching: A Confocal Laser Scanning Microscopy Study.
Discoloration of anterior teeth can result in cosmetic impairment in young children. The walking bleach technique stands out because of its esthetic results with minor side effects. Little information is available regarding the influence of various irrigation solutions on peroxide penetration. The aim of this study is to evaluate the influence of different irrigation protocols on peroxide penetration into dentinal tubules using confocal laser scanning microscopy (CLSM). Cavity preparations were made in 50 extracted permanent premolars. The teeth went through different irrigation sequences: A. control B. saline C. EDTA, NaOCl D. phosphoric acid E. EDTA, NaOCl, phosphoric acid. Then, mixture of fluorescent dyed sodium perborate paste was placed along the pulp chamber and the coronal access cavity, and was refilled at days 7, 14 and 21. The minimal and maximal penetration depths were 324 and 3045 μm, respectively, with a mean of 1607μm. The stained areas were significantly larger in the buccal and lingual directions (P<0.05). Groups B and C showed significantly larger penetration in weeks 2 and 3 compared to week 1 (P<0.05). Group D and E showed significantly larger penetration compared to groups B and C at all times (P<0.05). Bleaching agents penetrate to the extra-radicular region of teeth; however, the level of peroxide penetration is significantly higher when the irrigation sequence consists of phosphoric acid prior the bleaching agent placement.


Palliative resection of primary site in advanced gastroenteropancreatic neuroendocrine tumors improves survivals.
Gastroenteropancreatic neuroendocrine tumors are rarely seen and have heterogeneous clinical outcomes. Mostly half of the patients had metastatic disease at presentation. Palliative resection of primary site in metastatic disease is still controversial. The aim of this study was to find out the influence of resection of primary tumor site on progression-free survival and overall survival in metastatic non-functioning gastroenteropancreatic neuroendocrine tumors. The secondary end point is to determine the prognostic factors influencing the survivals. This study was conducted at a single medical oncology center, Antalya Education and Research Hospital. Patients who had non-functioning metastatic gastroenteropancreatic neuroendocrine tumors with primary site resected or unresected were compared retrospectively. Resection of metastases was excluded. Fifty-three patients were included in the study and 29 patients had primary tumor resection. The primary site resected group had favorable outcomes with the overall survival (median unreached) compared to the median overall survival of 30 months in the unresected group (p=0.001). Median progression-free survival was also better in the primary site resected group than the unresected group (60 months vs. 14 months, respectively) (p=0.013). In multivariate analysis, unresected primary site and high-grade tumors were found to be independent prognostic factors on low survivals (Hazard ratio (HR): 4.6; 95% CI: 1.21-17.47 and HR: 10.1; 95% CI: 1.15-88.84, respectively). Age (p=0.131), gender (p=0.051), chromogranin A level (p=0.104), Ki-67 index (p=0.550), tumor size (p=0.623), and primary tumor area (p=0.154) did not influence the overall survival. Gastroenteropancreatic neuroendocrine tumors with primary site resected had improved survivals when compared to the unresected group.


Suppressive Effect of Ginsenoside Rg3 against Lipopolysaccharide-Induced Depression-Like Behavior and Neuroinflammation in Mice.
Ginsenoside Rg3 (Rg3), a major active ingredient enriched in red ginseng, possesses well-confirmed immunoregulatory effects. Immune disturbance is a common trigger and aggravating factor of depression. The aim of this study was to explore the effects of Rg3 on lipopolysaccharide (LPS)-induced depression-like behavior in mice and the involvement of immune regulation. Pretreatment with Rg3 (i.g., 20 and 40 mg/kg) effectively ameliorated LPS (i.p., 0.83 mg/kg) induced body weight loss, anorexia, and immobility time in both the tail suspension test and the forced swimming test. Rg3 attenuated the disturbed turnover of tryptophan and serotonin in the hippocampus, accompanied by decreased mRNA expression of pro-inflammatory cytokines and indoleamine-2,3-dioxygenase (IDO). These central benefits were partially linked to the regulation of microglia activation and nuclear factor kappa B (NF-κB) pathway. In addition, Rg3 significantly reduced LPS-induced elevation of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in plasma, and restored the systemic balance of tryptophan-kynurenine metabolism. Taken together, our results demonstrated that Rg3 was effective in ameliorating depressive-like behavior induced by immune activation, adding new evidence to support its health benefits by immunoregulation.


Emended descriptions of Tilletiopsis washingtonensis, Tilletiopsis cremea and Tilletiopsis lilacina.
For species discrimination, DNA relatedness, nuclear DNA (nDNA) base compositions and internal transcribed spacer (ITS) regions were studied in strains of the 'washingtonensis group' consisting of the type strains of Tilletiopsis washingtonensis, Tilletiopsis cremea and Tilletiopsis lilacina as wells as nine strains previously identified as any one of the three species. T. washingtonensis is the neotype of the genus Tilletiopsis while T. cremea and T. lilacina are currently recognized as conspecific with T. washingtonensis. The G + C content of the DNA of the strains examined in this study was 66-68 mol%. The type strains of T. washingtonensis, T. cremea and T. lilacina were clearly discriminated on the basis of DNA complementarity. These genospecies should be treated as species. Moreover, an unrooted dendrogram constructed from ITS nucleotide sequences showed that the 'washingtonensis group' was divided into three clusters, corresponding to the three species T. washingtonensis, T. cremea and T. lilacina, respectively. The species descriptions of T. washingtonensis, T. cremea and T. lilacina are emended accordingly.


Space and contact networks: capturing the locality of disease transmission.
While an arbitrary level of complexity may be included in simulations of spatial epidemics, computational intensity and analytical intractability mean that such models often lack transparency into the determinants of epidemiological dynamics. Although numerous approaches attempt to resolve this complexity-tractability trade-off, moment closure methods arguably offer the most promising and robust frameworks for capturing the role of the locality of contact processes on global disease dynamics. While a close analogy may be made between full stochastic spatial transmission models and dynamic network models, we consider here the special case where the dynamics of the network topology change on time-scales much longer than the epidemiological processes imposed on them; in such cases, the use of static network models are justified. We show that in such cases, static network models may provide excellent approximations to the underlying spatial contact process through an appropriate choice of the effective neighbourhood size. We also demonstrate the robustness of this mapping by examining the equivalence of deterministic approximations to the full spatial and network models derived under third-order moment closure assumptions. For systems where deviation from homogeneous mixing is limited, we show that pair equations developed for network models are at least as good an approximation to the underlying stochastic spatial model as more complex spatial moment equations, with both classes of approximation becoming less accurate only for highly localized kernels.


In vivo consequences of deleting EGF repeats 8-12 including the ligand binding domain of mouse Notch1.
Notch signaling is highly conserved in the metazoa and is critical for many cell fate decisions. Notch activation occurs following ligand binding to Notch extracellular domain. In vitro binding assays have identified epidermal growth factor (EGF) repeats 11 and 12 as the ligand binding domain of Drosophila Notch. Here we show that an internal deletion in mouse Notch1 of EGF repeats 8-12, including the putative ligand binding domain (lbd), is an inactivating mutation in vivo. We also show that maternal and zygotic Notch1(lbd/lbd) mutant embryos develop through gastrulation to mid-gestation. Notch1(lbd/lbd) embryos died at mid-gestation with a phenotype indistinguishable from Notch1 null mutants. In embryonic stem (ES) cells, Notch1(lbd) was expressed on the cell surface at levels equivalent to wild type Notch1, but Delta1 binding was reduced to the same level as in Notch1 null cells. In an ES cell co-culture assay, Notch signaling induced by Jagged1 or Delta1 was reduced to a similar level in Notch1(lbd) and Notch1 null cells. However, the Notch1(lbd/lbd) allele was expressed similarly to wild type Notch1 in Notch1(lbd/lbd) ES cells and embryos at E8.75, indicating that Notch1 signaling is not essential for the Notch1 gene to be expressed. In addition, maternal and zygotic Notch1 mutant blastocysts developed through gastrulation. Mouse Notch1 lacking the ligand binding domain is expressed at the cell surface but does not signal in response to the canonical Notch ligands Delta1 and Jagged1. Homozygous Notch1(lbd/lbd) mutant embryos die at approximately E10 similar to Notch1 null embryos. While Notch1 is expressed in oocytes and blastocysts, Notch1 signaling via canonical ligands is dispensable during oogenesis, blastogenesis, implantation and gastrulation.


A statistical procedure useful in evaluating time of onset and termination of response in clinical trials.
A statistical model jointly characterizing the onset and termination of treatment response of a subject over a fixed observed time period is presented. The model requires that the observations for each subject are made at a set of pre-selected time points during the observed time period. A useful index characterizing the probability of being in response is developed along with maximum likelihood estimates and variances. A likelihood ratio test is developed to simultaneously compare two treatment groups with respect to this index for all times. The proposed procedure is applied to a set of data from a clinical trial of two bronchodilator drugs from which our procedure is motivated.


Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual desire in men with organic erectile dysfunction.
To assess the safety, erectogenic properties, and effect on sexual desire of Melanotan II, a synthetic melanotropic initiator of erection, in men with erectile dysfunction and organic risk factors. Ten subjects were enrolled in a double-blind, placebo-controlled, crossover study. Melanotan II (0.025 mg/kg) and vehicle were each administered twice by subcutaneous injection; real-time RigiScan monitoring and a visual analog were used to quantify the erections during a 6-hour period. The level of sexual desire and side effects were recorded with a questionnaire. Melanotan II initiated subjectively reported erections in 12 of 19 injections versus only 1 of 21 doses of placebo. The mean rigidity score of the responders was 6.9 on a scale of 0 to 10. The mean duration of tip rigidity greater than 80% was 45.3 minutes with Melanotan II versus 1.9 for placebo (P = 0.047). The level of sexual desire after injection was significantly higher after Melanotan II administration than after placebo. Nausea and stretching/yawning occurred more frequently with Melanotan II, and 4 of 19 injections were associated with severe nausea. The erectogenic properties of Melanotan II are not limited to cases of psychogenic erectile dysfunction; men with a variety of organic risk factors developed penile erections. The finding of increased sexual desire warrants further investigation of centrally acting agents on disorders of sexual desire.


Epidemiology of Huntington disease in Cyprus: A 20-year retrospective study.
Huntington disease (HD) is most prevalent among populations of western European descent and isolated populations where founder effects may operate. The aim of this study was to examine the epidemiology of HD in Cyprus, an island in southern Europe with extensive western European colonization in the past. All registered HD patients in the Cyprus, since 1994, were included. Detailed pedigrees and clinical information were recorded and maps, showing the geographic distribution of HD, were constructed. Requests for genetic testing were also examined. The project identified 58 clinically manifested cases of HD belonging to 19 families. The 16 families of Cypriot origin were concentrated in a confined geographical cluster in southeast Cyprus. In 2015, prevalence of symptomatic HD was 4.64/100 000 population, while incidence was 0.12/100 000 person-years. Prevalence displayed a marked increase during the past 20 years. Disease characteristics of HD patients were similar to those reported in western European populations. Lastly, the uptake of predictive and/or prenatal testing was limited. HD disease characteristics, incidence and prevalence in Cyprus were comparable to western European populations. Together with the geographical clustering observed, these results support the possibility for a relatively recent founder effect of HD in Cyprus, potentially of western European origin.


Characterization of gp70 and anti-gp70 monoclonal antibodies in Paracoccidioides brasiliensis pathogenesis.
Paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis whose agent is Paracoccidioides brasiliensis. In the culture supernatant, the fungus expresses glycoproteins of from 13 to 148 kDa. A cell surface glycoprotein of 43 kDa is the major antigenic component of P. brasiliensis. Another expressed glycoprotein, gp70, is recognized by 96% of sera from PCM patients and is able to induce lymphoproliferation. Since, little is known about this glycoprotein, we produced monoclonal antibodies (MAbs) against gp70 to isolate the molecule from total fungus extracts and to investigate its possible role in the pathogenesis of PCM. Using these MAbs, it was observed by confocal microscopy that gp70 is located mainly in the intracellular compartment of the fungus, although it was also detected in the culture supernatant. Based on observations showing that gp43 has a down-regulatory effect on mouse peritoneal macrophages, we tested the effects of gp70 on their phagocytic ability. Purified gp70 was able to inhibit the activity of macrophages through the mannose receptors and also through the Fc receptors; the latter effect was not observed with gp43. gp70 inhibits NO and H(2)O(2) liberation by peritoneal macrophages in vitro, as does gp43. Results obtained with gp43 led us to hypothesize that gp70 could act as an escape mechanism for fungal establishment in primary infections. To corroborate this hypothesis, we analyzed the effect of passive immunization of mice during infection with P. brasiliensis using anti-gp70 MAbs. This treatment almost completely abolished granuloma formation in the lungs, suggesting that the protein facilitates fungal establishment and progression of lesions in primary infection.


CARM1/PRMT4 is necessary for the glycogen gene expression programme in skeletal muscle cells.
CARM1 (co-activator-associated arginine methyltransferase 1)/PRMT4 (protein arginine methyltransferase 4), functions as a co-activator for transcription factors that are regulators of muscle fibre type and oxidative metabolism, including PGC (peroxisome-proliferator-activated receptor γ co-activator)-1α and MEF2 (myocyte enhancer factor 2). We observed significantly higher Prmt4 mRNA expression in comparison with Prmt1-Prmt6 mRNA expression in mouse muscle (in vitro and in vivo). Transfection of Prmt4 siRNA (small interfering RNA) into mouse skeletal muscle C2C12 cells attenuated PRMT4 mRNA and protein expression. We subsequently performed additional qPCR (quantitative PCR) analysis (in the context of metabolism) to examine the effect of Prmt4 siRNA expression on >200 critical genes that control (and are involved in) lipid, glucose and energy homoeostasis, and circadian rhythm. This analysis revealed a strikingly specific metabolic expression footprint, and revealed that PRMT4 is necessary for the expression of genes involved in glycogen metabolism in skeletal muscle cells. Prmt4 siRNA expression selectively suppressed the mRNAs encoding Gys1 (glycogen synthase 1), Pgam2 (muscle phosphoglycerate mutase 2) and Pygm (muscle glycogen phosphorylase). Significantly, PGAM, PYGM and GYS1 deficiency in humans causes glycogen storage diseases type X, type V/McArdle's disease and type 0 respectively. Attenuation of PRMT4 was also associated with decreased expression of the mRNAs encoding AMPK (AMP-activated protein kinase) α2/γ3 (Prkaa2 and Prkag3) and p38 MAPK (mitogen-activated protein kinase), previously implicated in Wolff-Parkinson-White syndrome and Pompe Disease (glycogen storage disease type II). Furthermore, stable transfection of two PRMT4-site-specific (methyltransferase deficient) mutants (CARM1/PRMT4 VLD and CARM1E267Q) significantly repressed the expression of Gys1, Pgam2 and AMPKγ3. Finally, in concordance, we observed increased and decreased glycogen levels in PRMT4 (native)- and VLD (methylation deficient mutant)-transfected skeletal muscle cells respectively. This demonstrated that PRMT4 expression and the associated methyltransferase activity is necessary for the gene expression programme involved in glycogen metabolism and human glycogen storage diseases.


Fibrosing mediastinitis mimicking sarcoidosis.
Fibrosing mediastinitis (FM), also called sclerosing mediastinitis or mediastinal fibrosis, is a rare disease characterized by excessive fibrotic reaction in the mediastinum and may compromise the airway, the great vessels and other mediastinal structures, with a morbidity directly related to the location and extent of fibrosis. The cause is not always known but is often the result of a granulomatous disease, most often the histoplasmosis. We report a 43-year-old woman with a history of tuberculosis infection 23 years ago. She attended the pulmonology clinic for cough and dyspnea. Physical examination revealed jugular venous distention at 90°. In computed tomography scan of the chest with contrast (c/c), we observed a mediastinal nodal cast provoking cava compression and obliteration of main and intermediary right lobar bronchus. The pathological examination was FM.


Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012.
Cancer incidence and mortality estimates for 25 cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for the European Union (EU-27) for 2012. We used statistical models to estimate national incidence and mortality rates in 2012 from recently-published data, predicting incidence and mortality rates for the year 2012 from recent trends, wherever possible. The estimated rates in 2012 were applied to the corresponding population estimates to obtain the estimated numbers of new cancer cases and deaths in Europe in 2012. There were an estimated 3.45 million new cases of cancer (excluding non-melanoma skin cancer) and 1.75 million deaths from cancer in Europe in 2012. The most common cancer sites were cancers of the female breast (464,000 cases), followed by colorectal (447,000), prostate (417,000) and lung (410,000). These four cancers represent half of the overall burden of cancer in Europe. The most common causes of death from cancer were cancers of the lung (353,000 deaths), colorectal (215,000), breast (131,000) and stomach (107,000). In the European Union, the estimated numbers of new cases of cancer were approximately 1.4 million in males and 1.2 million in females, and around 707,000 men and 555,000 women died from cancer in the same year. These up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe. The important role of cancer registries in disease surveillance and in planning and evaluating national cancer plans is becoming increasingly recognised, but needs to be further advocated. The estimates and software tools for further analysis (EUCAN 2012) are available online as part of the European Cancer Observatory (ECO) (http://eco.iarc.fr).


Sea urchin vault structure, composition, and differential localization during development.
Vaults are intriguing ribonucleoprotein assemblies with an unknown function that are conserved among higher eukaryotes. The Pacific coast sea urchin, Strongylocentrotus purpuratus, is an invertebrate model organism that is evolutionarily closer to humans than Drosophila and C. elegans, neither of which possesses vaults. Here we compare the structures of sea urchin and mammalian vaults and analyze the subcellular distribution of vaults during sea urchin embryogenesis. The sequence of the sea urchin major vault protein (MVP) was assembled from expressed sequence tags and genome traces, and the predicted protein was found to have 64% identity and 81% similarity to rat MVP. Sea urchin MVP includes seven approximately 50 residue repeats in the N-terminal half of the protein and a predicted coiled coil domain in the C-terminus, as does rat MVP. A cryoelectron microscopy (cryoEM) reconstruction of isolated sea urchin vaults reveals the assembly to have a barrel-shaped external structure that is nearly identical to the rat vault structure. Analysis of the molecular composition of the sea urchin vault indicates that it contains components that may be homologs of the mammalian vault RNA component (vRNA) and protein components (VPARP and TEP1). The sea urchin vault appears to have additional protein components in the molecular weight range of 14-55 kDa that might correspond to molecular contents. Confocal experiments indicate a dramatic relocalization of MVP from the cytoplasm to the nucleus during sea urchin embryogenesis. These results are suggestive of a role for the vault in delivering macromolecules to the nucleus during development.


Performance of the 32 mm Myval transcatheter heart valve for treatment of aortic stenosis in patients with extremely large aortic annuli in real-world scenario: First global, multicenter experience.
Extremely large aortic valve anatomy is one of the remaining limitations leading to exclusion of patients for transcatheter aortic valve replacement (TAVR). The newly approved Myval 32 mm device is designed for use in aortic annulus areas up to 840 mm2 . Here we want to share the initial worldwide experience with the device. Retrospective data were collected from 10 patients with aortic stenosis and very large annular anatomy (mean area 765.5 mm2 ), who underwent implantation with 32 mm Myval transcatheter heart valve at eight centers. Valve Academic Research Consortium-2 device success was achieved in all cases. Mild paravalvular leak was observed in three patients and two patients required new pacemaker implantation. One patient experienced retroperitoneal hemorrhage caused by the contralateral 6 F sheath and required surgical revision. No device-related complications, stroke, or death from any cause occurred within the 30-day follow-up period. In a studied cohort of 2219 consecutive TAVR-screened patients from a central European site, only 0.27% of patients showed larger anatomy than covered by the 32 mm Myval device by instructions for use without off-label use of overexpansion. This rate was significantly higher for the 34 mm Evolut Pro (1.8%) and 29 mm Sapien 3 (2.1%) devices. The Myval 32 mm prosthesis showed promising initial results in a cohort of patients who previously had to be excluded from TAVR. It is desirable that all future TAVR systems accommodate larger anatomy to allow optimal treatment of all patients.


[Duodenal Crohn's disease: diagnostic and therapeutic complexity].
Crohn's disease may involve any area of the digestive tract, but its localization in the duodenum is rare. The clinical, radiological or endoscopic findings may simulate those of peptic ulcer and histologic examination is not diagnostic. In contrast with Crohn's disease of any other localization, the formation of fistulas is exceptional. The authors present one case of duodenal Crohn's disease the unspecific symptomatology of which deviated the original orientation towards the more common diseases. Steroid treatment was not sufficient to control the disease which led to complications with the formation of an enterocutaneous fistula. The association of azathioprine was very effective not only in achieving remission of the process, but also in resolving the complications.


An eye tracking investigation of attentional biases towards affect in young children.
This study examines attentional biases in the presence of angry, happy and neutral faces using a modified eye tracking version of the dot probe task (DPT). Participants were 111 young children between 9 and 48 months. Children passively viewed an affective attention bias task that consisted of a face pairing (neutral paired with either neutral, angry or happy) for 500 ms that was followed by a 1,500-ms asterisk probe on 1 side of the screen. Congruent trials were trials in which the probe appeared on the same side of the screen as the emotional face and incongruent trials were trials in which the probe appeared on the opposite side of the emotional face. The latency to fixate on the probe, rather than the traditional task's button press latency, was measured for both types of trials and a bias score was calculated by subtracting the latency to the probe on congruent trials from that on incongruent trials. The results of the current study indicate positive internal reliability of this modified version of the DPT as well as the presence of a bias toward both angry and happy faces during the first 4 years of life. The successful use of the modified version of the DPT for use on the eye tracker presents a promising methodological tool for research on early attentional behavior and provides a tool for comprehensive longitudinal studies of identified risk factors for anxiety. (PsycINFO Database Record


Trait Mindfulness Helps Explain the Relationships Between Job Stress, Physiological Reactivity, and Self-Perceived Health.
The aim of this study was to assess, for the first time, the associations among work stress as measured by the job-demands resources (JD-R) model, trait mindfulness, and indices of the physiological stress response. Dairy farmers (N = 79) completed job stress (using the JD-R model), trait mindfulness, burnout, and self-reported health questionnaires and provided physiological indices of the stress response. Our findings suggest that those reporting higher mindfulness have better physical and mental health, and that being more mindful may buffer the effects of a large cortisol awakening response on poor physical health. Although assessments of both psychological and physiological indicators of stress and ill-health will inform the underlying mechanisms of the associations between work stress and disease, assessing the role of trait mindfulness in this relationship may prove useful.


Application of nanotechnology to control bacterial adhesion and patterning on material surfaces.
Bacterial adhesion and biofilm formation on surfaces raises health hazard issues in the medical environment. Previous studies of bacteria adhesion have focused on observations in their natural/native environments. Recently, surface science has contributed in advancing the understanding of bacterial adhesion by providing ideal platforms that attempt to mimic the bacteria's natural environments, whilst also enabling concurrent control, selectivity and spatial control of bacterial adhesion. In this review, we will look at techniques of how nanotechnology is used to control cell adhesion on a planar scale, in addition to describing the use of nanotools for cell micropatterning. Additionally, it will provide a general background of common methods for nanoscale modification enabling biologist unfamiliar with nanotechnology to enter the field.


Flaws in the LNT single-hit model for cancer risk: An historical assessment.
The LNT single-hit model was derived from the Nobel Prize-winning research of Herman J. Muller who showed that x-rays could induce gene mutations in Drosophila and that the dose response for these so-called mutational events was linear. Lewis J. Stadler, another well-known and respected geneticist at the time, strongly disagreed with and challenged Muller's claims. Detailed evaluations by Stadler over a prolonged series of investigations revealed that Muller's experiments had induced gross heritable chromosomal damage instead of specific gene mutations as had been claimed by Muller at his Nobel Lecture. These X-ray-induced alterations became progressively more frequent and were of larger magnitude (more destructive) with increasing doses. Thus, Muller's claim of having induced discrete gene mutations represented a substantial speculative overreach and was, in fact, without proof. The post hoc arguments of Muller to support his gene mutation hypothesis were significantly challenged and weakened by a series of new findings in the areas of cytogenetics, reverse mutation, adaptive and repair processes, and modern molecular methods for estimating induced genetic damage. These findings represented critical and substantial limitations to Muller's hypothesis of X-ray-induced gene mutations. Furthermore, they challenged the scientific foundations used in support of the LNT single-hit model by severing the logical nexus between Muller's data on radiation-induced inheritable alterations and the LNT single-hit model. These findings exposed fundamental scientific flaws that undermined not only the seminal recommendation of the 1956 BEAR I Genetics Panel to adopt the LNT single-hit Model for risk assessment but also any rationale for its continued use in the present day.


Central mechanisms IV: conscious control of cough and the placebo effect.
Early animal experiments on cough developed the concept that cough was an involuntary reflex controlled from areas in the brainstem and that cough could be inhibited by centrally acting medicines such as codeine. Studies on the voluntary control of cough, the urge to cough and the placebo effect of cough medicines have demonstrated that human cough is more complex than a brainstem reflex. The efficacy and mechanism of action of centrally acting cough medicines such as codeine and dextromethorphan is now in dispute, and codeine is no longer accepted as a gold-standard antitussive. This review puts forward a cough model that includes three types of cough: (1) reflex cough, caused by the presence of food or fluid in the airway--this type of cough is not under conscious control and can occur in the unconscious subject during general anaesthesia; (2) voluntary cough--under conscious control that is abolished with general anaesthesia; (3) cough in response to sensation of airway irritation--this type of cough causes an urge to cough that initiates voluntary cough and may only be present in the conscious subject. The review proposes that human cough associated with respiratory disease is under conscious control and is mainly related to a sensation of airway irritation and an urge to cough (type 3). The review discusses the summation of sensory input from the airway in a brainstem integrator that reaches a threshold to cause reflex cough. Subthreshold conditions in the cough integrator may be perceived as an urge to cough that is under voluntary control. The cough model presented in the review has implications for the development of cough medicines as it indicates that the older view of cough medicines acting in the brainstem area to inhibit the cough reflex may need to be revised to include conscious control of cough as an important mechanism of cough in man.