Osteogenic Effect of Inducible Nitric Oxide Synthase (iNOS)-Loaded Mineralized Nanoparticles on Embryonic Stem Cells.
This study investigated the effect of inducible nitric oxide synthase-loaded mineralized nanoparticles (iNOS-MNPs) on the osteogenic differentiation of mouse embryonic stem cells (ESCs). We prepared iNOS-MNPs using an anionic block copolymer template-mediated calcium carbonate (CaCO3) mineralization process in the presence of iNOS. iNOS-MNPs were spherical and had a narrow size distribution. iNOS was stably loaded within MNPs without denaturation. In order to confirm the successful introduction of iNOS-MNPs into the cytosol of ESCs, intracellular levels of nitric oxide (NO) was determined with a fluorometric analysis. A NO effector molecule, cyclic guanosine 3',5' monophosphate (cGMP) was also quantified with a competitive enzyme immunoassay. Cell viability in response to iNOS-MNP treatment was determined using the cell counting kit-8 (CCK-8) assay. Alkaline phosphatase (ALP) activity assay, intracellular calcium quantification assay, and Alizarin red S staining for matrix mineralization were performed to investigate osteogenic differentiation of ESCs. The protein levels of Runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osterix (OSX) as osteogenic-related factors were also assessed by immunofluorescence staining and Western blot analysis. The complex pathways associated with iNOS-MNP-derived osteogenic differentiation of ESCs were evaluated by network-based analysis. Cells with iNOS-MNPs displayed a significant increase in NO and cGMP concentration compared with the control group. When cells were exposed to iNOS-MNPs, there were no adverse effects on cell viability. Importantly, iNOS-MNP uptake promoted the osteogenic differentiation of ESCs. Using transcriptome profiling, we obtained 1,836 differentially-induced genes and performed functional enrichment analysis with ClueGO and KEGG. These analyses identified significantly enriched and interconnected molecular pathways such as protein kinase activity, estrogen receptor activity, bone morphogenetic protein (BMP) receptor binding, ligand-gated ion channel activity, and phosphatidylinositol 3-phosphate binding. These findings suggest that iNOS-MNPs can induce osteogenic differentiation in ESCs by integrating complex signaling pathways.


Diet quality and risk of multiple sclerosis in two cohorts of US women.
To determine the association between measures of overall diet quality (dietary indices/patterns) and risk of multiple sclerosis (MS). Over 185,000 women in the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII) completed semiquantitative food frequency questionnaires every 4 years. There were 480 MS incident cases. Diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED) index, and Dietary Approaches to Stop Hypertension (DASH) index. Principal component analysis was used to determine major dietary patterns. We calculated the hazard ratio (HR) of MS with Cox multivariate models adjusted for age, latitude of residence at age 15, body mass index at age 18, supplemental vitamin D intake, and cigarette smoking. None of the dietary indices, AHEI-2010, aMED, or DASH, at baseline was statistically significantly related to the risk of MS. The principal component analysis identified "Western" and "prudent" dietary patterns, neither of which was associated with MS risk (HR, top vs bottom quintile: Western, 0.81 (p = 0.31) and prudent, 0.96 (p = 0.94)). When the analysis was repeated using cumulative average dietary pattern scores, the results were unchanged. There was no evidence of an association between overall diet quality and risk of developing MS among women.


Polyacrylamide hydrogel injection for breast augmentation: another injectable failure.
Increasing complications of polyacrylamide hydrogel (PAAG) augmentation mammoplasty, such as chronic persistent infection, have recently caught the attention of both the medical field and the general public. A total of 96 patients with severe chronic infection following PAAG augmentation mammoplasty were treated in the present study including 63 cases with infection confined to the breast and 33 with systemic infection. Endoscopy and surgery were performed to completely remove the materials and clear the infected tissues followed by drug-irrigation and vacuum-assisted closure for several days. In patients with severe infection there were large amounts of PAAG, fibers and infiltration of numerous neutrophils and macrophages. The infection-inducing materials were extensively dispersed in the mammary and subcutaneous tissues, pectoral fascia and intermuscular space. In addition, there was scattered distribution of PAAG materials in the armpit, chest wall and abdominal wall, which were mixed with necrotic tissues and surrounded by lymphocytes, giant cells, macrophages and other inflammatory cells, forming chronic granulomatous and fibrous lesions. Infection was controlled following surgical intervention. No residual infectious foci or recurrent infections were noted among these patients. Although the severe infection did not result in mastectomy, patients had breast atrophy and various degrees of deformation. Chronic infection following PAAG augmentation mammaplasty usually causes systemic infection and other devastating adverse reactions. This study confirms PAAG augmentation mammaplasty is another failed attempt. More attention should be paid to the injection of large doses of liquid filler.


Selective cytotoxicity of 125I-labeled monoclonal antibody T101 in human malignant T cell lines.
The radiolabeled anti-T cell antibody T101 can be used for specific tumor localization, but unlabeled T101 produces limited cytotoxicity in patients. We thus studied the in vitro cytotoxic effects of T101 labeled with 125I, a radionuclide known for its short-range, high-linear-energy electrons. We showed that 125I-T101 could be readily prepared at high specific activity with high immunoreactivity. Human malignant T cell lines HUT 102, MOLT-4, and HUT 78 were found to differ in the number of T65 determinants (the antigen recognized by T101) and the sensitivity to external x-ray radiation, which were of significance for the cytotoxicity of 125I-T101 in vitro. The cytotoxic effects of 125I-T101 were also found to be dose dependent and increased with exposure time under frozen conditions. As controls, unlabeled T101 had no cytotoxic effect, while free Na 125I or the 125I-labeled irrelevant antibody 9.2.27 exerted minor cytotoxicity. In HUT 102 and MOLT-4, more than 3 logs' cell killing was achieved within four weeks. Because considerable cytotoxicity was demonstrated in vitro by 125I-T101 on T65-positive malignant cells, and because low-dose 111In-T101 can be used successfully for tumor localization, future trials using 125I-T101 at high specific radioactivity may improve therapeutic results in patients with T65-positive malignancies.


Agar-gel precipitin-inhibition test for coccidioidomycosis. I. Preliminary evaluation of the complement-fixation and agar-gel precipitin tests in the serodiagnosis of human coccidioidomycosis.
The agar-gel precipitin-inhibition serological test for coccidioidomycosis was a more sensitive indicator of Coccidioides immitis antibodies than the tube precipitin, the agar-gel immunodiffusion, in the complement-fixation tests in assaying monkey sera, whether these sera were from prechallenge-vaccinated or postchallenged animals. When applying this technique to the assay of human sera, an analogous finding generally persisted. However, some human sera were positive by the complement-fixation test and negative by the agar-gel precipitin-inhibition test. These sera were diffused in agar-gel against various coccidioidin complement-fixation, tube precipitin, and agar-gel precipitin-inhibition test antigens with essentially negative results.


Mapping QTL Contributing to Variation in Posterior Lobe Morphology between Strains of Drosophila melanogaster.
Closely-related, and otherwise morphologically similar insect species frequently show striking divergence in the shape and/or size of male genital structures, a phenomenon thought to be driven by sexual selection. Comparative interspecific studies can help elucidate the evolutionary forces acting on genital structures to drive this rapid differentiation. However, genetic dissection of sexual trait divergence between species is frequently hampered by the difficulty generating interspecific recombinants. Intraspecific variation can be leveraged to investigate the genetics of rapidly-evolving sexual traits, and here we carry out a genetic analysis of variation in the posterior lobe within D. melanogaster. The lobe is a male-specific process emerging from the genital arch of D. melanogaster and three closely-related species, is essential for copulation, and shows radical divergence in form across species. There is also abundant variation within species in the shape and size of the lobe, and while this variation is considerably more subtle than that seen among species, it nonetheless provides the raw material for QTL mapping. We created an advanced intercross population from a pair of phenotypically-different inbred strains, and after phenotyping and genotyping-by-sequencing the recombinants, mapped several QTL contributing to various measures of lobe morphology. The additional generations of crossing over in our mapping population led to QTL intervals that are smaller than is typical for an F2 mapping design. The intervals we map overlap with a pair of lobe QTL we previously identified in an independent mapping cross, potentially suggesting a level of shared genetic control of trait variation. Our QTL additionally implicate a suite of genes that have been shown to contribute to the development of the posterior lobe. These loci are strong candidates to harbor naturally-segregating sites contributing to phenotypic variation within D. melanogaster, and may also be those contributing to divergence in lobe morphology between species.


Carcinoma of the oesophagus in the Sudan.
The histopathological reports of 135 specimens of carcinoma of the oesophagus received in the Central Research Laboratory in Khartoum during the period 1965 to 1974 and the clinical data of 14 cases treated at the University Department of Surgery in the period 1970 to 1974 are analysed. The incidence in the Sudan is 1.4% of all malignant tumours. The disease affected both sexes equally; is most common at the age of 50-69 and is commoner in patients from the North. Of the different aetiological factors mentioned in the literature the habit of placing tobacco under the tongue or in the labiodental groove seems to be associated with a high incidence of oral cancer and possibly also of oesophageal cancer in much the same way as in Russia. The low resectability rate of 16.3% is due to the high surgical risk of the patients and the lack of supportive measures. Radiotherapy and palliation by indwelling tubes are commonly used with the objective of enabling the patient to swallow.


Signal requirements for growth and differentiation of activated murine B lymphocytes.
Mouse B lymphocytes were stimulated at high cell concentrations with goat anti-IgM antibodies, which leads to the induction of B cell proliferation without the addition of any growth factors. After 48 hr, blast cells were purified and cultured at low cell concentrations. Proliferation and differentiation of purified B lymphocyte blasts is then dependent on the addition of either mitogens (e.g., LPS) or certain lymphokines derived from activated T cells or macrophages. One such lymphokine was isolated from supernatants of various activated T cells and characterized by gel filtration as a material with an apparent m.w. of 40,000 to 50,000, similar to BCGF II. It supports the proliferation of the B cell blasts and induces their differentiation into plaque-forming cells. Lymphokines such as BCGF I, interleukin 2, and BCDF gamma could neither maintain growth nor induce differentiation of B lymphocytes preactivated by goat anti-IgM.


Impaired central tolerance induces changes in the gut microbiota that exacerbate autoimmune hepatitis.
Medullary thymic epithelial cells (mTECs) induce T cell tolerance in the thymus through the elimination of self-reactive thymocytes. Commensal bacteria are also critical for shaping T cell responses in the gut and distal organs. We previously showed that mice depleted of mTECs (Traf6ΔTEC) generated autoreactive T cells and developed autoimmune hepatitis (AIH). In this report, we found that Toll-like receptor (TLR)-mediated microbial sensing on liver hematopoietic cells and the gut microbiota contributed to AIH development in Traf6ΔTEC mice. While adoptive transfer of thymic Traf6ΔTEC T cells in immune-deficient mice was sufficient for AIH development, colonization of germ-free mice with Traf6ΔTEC microbiota failed to induce AIH, suggesting that the gut microbiota contributes to but is not sufficient for AIH development. Microbiota-mediated exacerbation of AIH associated with increased numbers of hepatic Foxp3+ T cells and their increase was proportional to the degree of inflammation. The contribution of the gut microbiota to AIH development associated with an altered microbial signature whose composition was influenced by the qualitative nature of the thymic T cell compartment. These results suggest that aberrant selection of T cells in the thymus can induce changes in the gut microbiota that lead to exacerbation of organ-specific autoimmunity and AIH. Our results add to our understanding of the mechanisms of AIH development and create a platform towards developing novel therapeutic approaches for treating this disease.


[Susceptibility of Anopheles gambiae to insecticides in the Ivory Coast].
Studies on the susceptibility of Anopheles gambiae to insecticides were carried out in rice field areas of Côte-d'Ivoire. An. gambiae larvae populations from Côte-d'Ivoire were resistant to DDT but susceptible to organophosphorous insecticides. Adult populations from the surroundings of Bouake were resistant to DDT and permethrin. Resistance to propoxur was strongly suspected. The knock-down effect of both deltamethrin and lambdacyhalothrin was delayed and strongly decreased. The control strain from Bobo-Dioulasso and populations from rice fields of Katiola located far from the city were still susceptible to the three pyrethroids. It is likely that resistance to pyrethroids in Bouake has been promoted by the intensive use of domestic aerosol sprays.


Respiratory kinematics and the regulation of subglottic pressure for phonation of pitch jumps - a dynamic MRI study.
The respiratory system is a central part of voice production as it contributes to the generation of subglottic pressure, which has an impact on voice parameters including fundamental frequency and sound pressure level. Both parameters need to be adjusted precisely during complex phonation tasks such as singing. In particular, the underlying functions of the diaphragm and rib cage in relation to the phonation of pitch jumps are not yet understood in detail. This study aims to analyse respiratory movements during phonation of pitch jumps using dynamic MRI of the lungs. Dynamic images of the breathing apparatus of 7 professional singers were acquired in the supine position during phonation of upwards and downwards pitch jumps in a high, medium, and low range of the singer's tessitura. Distances between characteristic anatomical landmarks in the lung were measured from the series of images obtained. During sustained phonation, the diaphragm elevates, and the rib cage is lowered in a monotonic manner. During downward pitch jumps the diaphragm suddenly changed its movement direction and presented with a short inspiratory activation which was predominant in the posterior part and was associated with a shift of the cupola in an anterior direction. The magnitude of this inspiratory movement was greater for jumps that started at higher compared to lower fundamental frequency. In contrast, expiratory movement of the rib cage and anterior diaphragm were simultaneous and continued constantly during the jump. The data underline the theory of a regulation of subglottic pressure via a sudden diaphragm contraction during phonation of pitch jumps downwards, while the rib cage is not involved in short term adaptations. This strengthens the idea of a differentiated control of rib cage and diaphragm as different functional units during singing phonation.


Long-Term Outcomes of Single-Port Laparoscopic Placement of Peritoneal Dialysis Catheter.
Laparoscopic insertion of peritoneal dialysis (PD) catheter has become a preferred method compared to the traditional open technique for PD catheter insertion. We retrospectively report the outcome of 1-port laparoscopic placement PD catheters in our institution. A total of 263 patients with end-stage renal disease who underwent single-trocar laparoscopic PD catheter insertion during a recent 6-year period were reviewed. Laparoscopic technique involves introducing a PD catheter over a stiff guidewire into the abdominal cavity through a 10-mm laparoscopic port. Pertinent clinical variables, procedural complications, and follow-up outcome were analyzed. There were 182 men and 81 women. The mean age was 56 years. Technical success was 95.8%. Catheter occlusion was the most common early complications (<6 months) that occurred in 4 (1.5%) patients. Late complications (> 6 months) including catheter occlusion, cuff extrusion, catheter leakage, catheter migration, infection, and hernia occurred in 5 patients (1.9%), 2 patients (0.8%), 3 patients (1.1%), 3 patients (1.1%), 6 patients (2.3%), and 4 patients (1.5), respectively. Mean follow-up time was 39 ± 18 months. Catheter survival rate at 1, 2, 3, 4, and 5 years was 96%, 94%, 90%, 85%, and 82%, respectively. Laparoscopic PD catheter implantation via a single-trocar utilizing a stiff guidewire technique is feasible and safe. This method can result in low complication and high catheter survival rate.


Microtubule Response to Tensile Stress Is Curbed by NEK6 to Buffer Growth Variation in the Arabidopsis Hypocotyl.
Growth variability generates mechanical conflicts in tissues. In plants, cortical microtubules usually align with maximal tensile stress direction, thereby mechanically reinforcing cell walls, and channeling growth rate and direction. How this is achieved remains largely unknown and likely involves microtubule regulators. The NIMA-related microtubule-associated kinase NEK6 phosphorylates tubulin, leading to the depolymerization of a subset of microtubules. We found that cortical microtubules exhibit a hyper-response to mechanical stress in the nek6 mutant. This response contributes to local cell protrusions in slow-growing regions of the nek6 mutant hypocotyl. When growth amplitude is higher, the hyper-alignment of microtubules leads to variable, stop-and-go, phenotypes, resulting in wavy hypocotyl shapes. After gravistimulation or touch, the nek6 mutant also exhibits a hyperbent hypocotyl phenotype, consistent with an enhanced perception of its own deformation. Strikingly, we find that NEK6 exhibits a novel form of polarity, being recruited at the ends of a subset of microtubules at cell edges. This pattern can be modified after local ablation, matching the new maximal tensile stress directions. We propose that NEK6 depolymerizes cortical microtubules that best align with maximal tensile stress to generate a noisier network of microtubules. This prevents an overreaction of microtubules to growth fluctuations and, instead, promotes the buffering of growth variations.


The Arabidopsis ATNRT2.7 nitrate transporter controls nitrate content in seeds.
In higher plants, nitrate is taken up by root cells where Arabidopsis thaliana NITRATE TRANSPORTER2.1 (ATNRT2.1) chiefly acts as the high-affinity nitrate uptake system. Nitrate taken up by the roots can then be translocated from the root to the leaves and the seeds. In this work, the function of the ATNRT2.7 gene, one of the seven members of the NRT2 family in Arabidopsis, was investigated. High expression of the gene was detected in reproductive organs and peaked in dry seeds. beta-Glucuronidase or green fluorescent protein reporter gene expression driven by the ATNRT2.7 promoter confirmed this organ specificity. We assessed the capacity of ATNRT2.7 to transport nitrate in Xenopus laevis oocytes or when it is expressed ectopically in mutant plants deficient in nitrate transport. We measured the impact of an ATNRT2.7 mutation and found no difference from the wild type during vegetative development. By contrast, seed nitrate content was affected by overexpression of ATNRT2.7 or a mutation in the gene. Finally, we showed that this nitrate transporter protein was localized to the vacuolar membrane. Our results demonstrate that ATNRT2.7 plays a specific role in nitrate accumulation in the seed.


Vascular alpha1-adrenoceptors in isolated perfused rat kidney: influence of ageing.
1. The present study identifies alpha1-adrenoceptor subtype(s) involved in constrictor responses of the kidney and how ageing influences it. 2. The study was conducted on kidneys from F344BNF1 rats, which unlike F344 or Wistar rats used by many previous investigators do not exhibit glomerulonephritis at advanced age. 3. Noradrenaline (NA) and phenylephrine (PHE) (non-selective alpha1) and A61063 (selective alpha(1A)) adrenoceptor agonists elicited constriction of perfused kidneys of young and old rats. The pD2 values (index of renovascular reactivity) were significantly higher for A61603 than for either PHE or NA, and significantly decrease across age groups. 4. BMY 7378 or RS 100329, alpha(1D)- or alpha(1A)-adrenoceptor antagonists, respectively antagonized the constrictor responses and suppressed the maximal responses to all agonists in young adult rat kidneys. However, antagonism of PHE or A61063 by BMY 7378 in old rat kidneys was surmountable. 5. This study suggests that: (i) alpha(1A) and alpha(1D)-adrenoceptor subtypes mediate vasoconstriction of perfused rat kidney; (ii) alpha(1A)-adrenoceptor subtype appears to predominate in renal vasculature based on agonist relative potencies. (iii) Ageing significantly decreases alpha1-adrenoceptor-mediated vasoconstriction of rat kidney.


A real-time PCR assay for rapid detection and quantitation of canine parvovirus type 2 in the feces of dogs.
We describe a rapid, sensitive and reproducible real-time PCR assay for detecting and quantifying canine parvovirus type 2 (CPV-2) DNA in the feces of dogs with diarrhea. An exogenous internal control was added to control the assay performance from extraction to amplification. The method was demonstrated to be highly specific and sensitive, allowing a precise CPV-2 DNA quantitation over a range of eight orders of magnitude (from 10(2) to 10(9) copies of standard DNA). The reproducibility of the CPV-2 real-time PCR assay was assessed by calculating the coefficients of variation (CV) intra-assay and inter-assay for samples containing amounts of CPV-2 DNA spanning the whole range of the real-time PCR standard curve. Then, fecal specimens from diarrheic dogs were analyzed by hemagglutination (HA), conventional PCR and real-time amplification. Comparison between these different techniques revealed that real-time PCR is more sensitive than HA and conventional gel-based PCR, allowing to detect low viral titers of CPV-2 in infected dogs.


Artificial intelligence (AI) for home support interventions in dementia: a scoping review protocol.
Dementia has become one of the significant causes of disability and dependency among older people globally. The proportion of people with dementia who are cared for at home has soared. The rapid growth of technology and data has stimulated artificial intelligence (AI) in patients with dementia at home. However, there are still tremendous opportunities and challenges in applying AI to patients with dementia at home, and there is no systematic overview. The review will adopt the Unified Theory of Acceptance and Use of Technology. This scoping review will follow the Joanna Briggs Institute scoping review methodology. The structure and content of this protocol follow the Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews checklist. The proposed study will consider applying AI technology for dementia patients living at home and their families. Authors will conduct systematic searches: China National Knowledge Infrastructure, Wanfang Database, China Science and Technology Journal Database, China Biology Medicine disc, PubMed, CINAHL, Web of Science Cochrane database, EBSCO, Ovid, PsycINFO, Embase. The extracted data will be processed qualitatively and described through tables. The findings are integrated by a narrative synthesis. This review aims to evaluate the nature and extent of the application of AI technology in patients with dementia at home through a systematic search of the literature. Scoping review is an analysis of existing data and therefore does not require ethical approval. We will publish our findings in a peer-reviewed journal.Scoping review protocol registration . DOI:10.17605/OSF.IO/3NU9C.


Impact of a new daily rapid access medical clinic in a Scottish district general hospital.
Medical admissions to hospital in the UK are rising by approximately 10% per year. A Medical Assessment Unit (MAU) was opened to help deal with the rising influx of patients. The objectives of this study were to determine if a daily rapid access medical clinic could provide a safe alternative to hospital admission and aid safe discharge for medical patients. The rapid access clinic was embedded within the MAU, utilising existing resources. Patients were allocated and reviewed by a senior acute medicine specialist registrar (SpR). Data were collected from January to September 2008. 74 patients seen in the clinic were analysed. 93% of these were managed in an ambulatory fashion, avoiding admission and saving a potential 280 bed days. The same day discharge rate of all patients seen and assessed in the MAU was increased from 17% to 26% (p<0.001), following institution of the clinic. The readmission rate fell from 8% to 4% (p=0.12). A daily rapid access medical clinic embedded within a MAU was piloted and allowed the safe management of a variety of medical complaints in an ambulatory fashion. It enabled an increase in the discharge rate of patients referred for admission by general practitioners. This seemed to be more robust than as evidenced previously by a trend towards lower readmission rates. These results were dependent on the presence of a senior clinical decision maker to facilitate safe discharges.


Phosphorylation of phospholamban at threonine-17 reduces cardiac adrenergic contractile responsiveness in chronic pressure overload-induced hypertrophy.
Physiological hemodynamic stress, such as aerobic exercise, is intermittent and requires an increase in Ca2+ -dependent contractility through sympathetic nervous system activation. Pathological hemodynamic stress, such as hypertension, is persistent and requires sustained increases in cardiac function. Over time, this causes left ventricular hypertrophy (LVH)-reduced responsiveness to sympathetic stimulation. In this study, we examined the hypothesis that blunted in vivo adrenergic contractile responsiveness in pressure overload (PO)-induced cardiac hypertrophy is caused by abnormalities in the abundance and/or basal phosphorylation state of Ca2+ regulatory proteins. PO, induced by aortic constriction, caused concentric LVH or dilated LVH. Only animals with dilation exhibited a decrease in baseline left ventricle function [fractional area change (FAC); measured with echocardiography]. All PO animals had a reduced contractile response to adrenergic agonists (increase in FAC with 40 microg.kg(-1).min(-1) dobutamine, control 0.30 +/- 0.04, n = 5 vs. banded 0.10 +/- 0.03, n = 10; P < 0.01). PO animals had reduced phospholamban (PLB) protein abundance (P = 0.07, not significant) and increased PLB phosphorylation at the calmodulin-dependent kinase II (CaMKII)-specific site (PLB-Thr17, P < 0.05) but not at the protein kinase A-specific site (PLB-Ser16). PLB-Thr17 phosphorylation was inversely correlated with dobutamine-induced increases in contractility in PO animals (r2 = 0.81, P < 0.05). Continuous induction of Ca2+ transients in isolated ventricular myocytes for 24 h increased phosphorylation at PLB-Thr17 and diminished inotropic responsiveness and PLB-Ser16 phosphorylation after exposure to isoproterenol (P < 0.05). These data show that reduced adrenergic responsiveness in feline PO hypertrophy and failure involves increases in basal PLB-Thr17 phosphorylation, suggesting that activation of CaMKII in PO hypertrophy contributes to defective adrenergic reserve in compensated LVH and early heart failure.


Inflammatory bowel disease in rats: bacterial and chemical interaction.
To develop a novel model of colitis in rats, using a combination of iodoacetamide and enteropathogenic E. coli (EPEC), and to elucidate the pathophysiologic processes implicated in the development of ulcerative colitis (UC). Male Sprague-Dawley rats (n = 158) were inoculated intrarectally on a weekly basis with 4 different combinations: (a) 1% methylcellulose (MC), (b) 100 microL of 6% iodoacetamide (IA) in 1% MC, (c) 200 microL containing 4 x 10(8) colony factor units (CFU) of EPEC, and (d) combined treatment of (IA) followed by bacteria (B) after 2 d. Thirty days post treatment, each of the four groups was divided into two subgroups; the inoculation was stopped for one subgroup and the other subgroup continued with biweekly inoculation until the end of the experiment. Colitis was evaluated by the clinical course of the disease, the macroscopic and microscopic alterations, activity of myeloperoxidase (MPO), and by TNF-alpha gene expression. Findings indicative of UC were seen in the combined treatment (IA + B) as well as the IA continued treatment groups: the animals showed slow rate of increase in body weight, diarrhea, bloody stools, high colonic ulcer score, as well as histological alterations characteristic of UC, with an extensive inflammatory reaction. During the course of the experiment, the MPO activity was consistently elevated and the TNF-alpha gene expression was upregulated compared to the control animals. The experimental ulcerative colitis model used in the present study resembles, to a great extent, the human disease. It is reproducible with characteristics indicative of chronicity.


Purification of alpha 1 proteinase inhibitor from human plasma fraction IV-1 by ion exchange chromatography.
Alpha-proteinase inhibitor (PI) protects the lungs from proteolytic damage caused by elastase and can be used to treat congenital emphysema. We describe an improved method of purification of alpha 1 PI from redissolved fraction IV-1 paste. The process used dimethylaminoethyl anion exchange chromatography, sulfopropyl cation exchange chromatography, virus inactivation by dry heat, and tri-n-butyl-phosphate/cholate treatment, followed by a second strong cation exchange chromatography. Optimizations of loading conditions for ion exchange chromatography at small scale (20-60 ml of suspension) are described. Virus inactivation was adjusted to provide the best yield of alpha 1 PI consistent with effective inactivation. The process has been effectively scaled up. The final product was approximately 90% pure by SDS-PAGE, with a 60-70% yield from starting fraction IV-1 paste. The process has been characterized by methods including nonreduced SDS-PAGE, alpha 1 PI inhibition assay, and biuret protein assay. The method described is an effective way of preparing large quantities of alpha 1 PI from fractionated plasma.


Surgical treatment of anastomotic recurrence after gastrectomy for gastric cancer.
The purpose of this study was to evaluate the outcome of reoperation with curative intent for the treatment of anastomotic recurrent gastric cancer. Ten patients with anastomotic recurrence of gastric cancer who underwent reoperation from November 1995 to February 2011 were analyzed retrospectively. The time interval between the first operation and reoperation, recurrence pattern, type of surgery, survival, and postoperative outcome were analyzed. The average time to recurrence after initial surgery was 48.8 months (median, 23.5 months). Of the ten patients, eight (80.0%) had recurrence at the esophagojejunostomy, one (10.0 %) at the esophagogastrostomy, and two (20.0%) at the esophagus. Among these patients, five had combined metastasis or invasion to major organs in addition to anastomotic recurrence. Complete resection was achieved in five patients (50.0%), and incomplete resection or bypass surgery was performed in the remaining five patients (50.0%). The overall median survival time was 7.0 months (range, 2.2 to 105.5 months). The median survival time following complete resection and palliative surgery (incomplete resection or bypass surgery) was 28.1 months (range, 4.2 to 105.5 months) and 5.5 months (range, 2.2 to 7.5 months), respectively. Surgical resection of anastomotic recurrent gastric cancer should be implemented only in selected patients in whom complete resection is possible.


Looking forward in the treatment of deep-vein thrombosis.
Clinical guidelines developed by the American College of Chest Physicians (ACCP) for the management of venous thromboembolism (VTE) are based on current evidence from randomized clinical trials and amended in response to emerging results. The standard treatment for VTE comprises in-hospital treatment with dose-adjusted unfractionated heparin (UFH) for a minimum of 5 days and oral anticoagulants for at least 3 months. Recent clinical studies show that subcutaneous low-molecular-weight heparins (LMWHs) in fixed doses according to body weight are as effective and safe as intravenous UFH in the initial treatment of deep-vein thrombosis, with or without pulmonary embolism. There is also evidence that the optimal duration of secondary thromboprophylaxis depends on assessable thromboembolic risk factors. The 1998 ACCP guidelines take account of this new evidence by advocating LMWHs as an alternative to standard UFH for the initial treatment of VTE and risk stratification of patients to guide duration of secondary thromboprophylaxis. Outpatient treatment of VTE with LMWHs has been shown to be feasible and is increasingly used in clinical practice, offering substantial economic benefits. Certain LMWHs appear to be effective at a once-daily dose. Evidence is now emerging that may clarify the role of inferior vena cava filters and thrombolysis in VTE management. Future versions of the ACCP guidelines may be expected to reflect new data from ongoing trials.


A histological survey of avian post-natal skeletal ontogeny.
Bone histology of crown-group birds is a research topic of great interest, permitting insight into the evolution of remarkably high growth rates in this clade and variation across the altricial-precocial spectrum. In this study, we describe microanatomical characteristics of the humerus and femur in partial growth series from 14 crown group birds representing ten major clades (Struthioniformes, Galliformes, Apodiformes, Columbiformes, Charadriiformes, Accipitriformes, Strigiformes, Psittaciformes, Falconiformes, and Passeriformes). Our goals were to: (1) describe the microanatomy of each individual; (2) make inter-and intra-taxonomic comparisons; (3) assess patterns that correspond with developmental mode; and (4) to further parse out phylogenetic, developmental, and functional constraints on avian osteological development. Across taxa, the femoral and humeral tissue of neonates can be broadly characterized as highly-vascularized, disorganized woven bone with great variation in cortical thickness (inter-and intrataxonomically, within an individual specimen, and within a single section). The tissue of precocial chicks is relatively more mature at hatching than in altricial, but other categories along the developmental spectrum were less easy to distinguish, thus we were unable to identify a definitive histological proxy for developmental mode. We did not find evidence to support hypotheses that precocial chicks exclusively have thicker cortices and more mature bone in the femur than the humerus at time of hatching; instead, this is a characteristic of nearly all taxa (regardless of developmental mode), suggesting deep evolutionary origins and the effects of developmental channeling. Bone tissue in adults exhibited unexpected variation, corresponding to differences in body size. Large-bodied birds have cortices of fibrolamellar bone, but organization of tissue increases and vascularity decreases with diminishing body size. The outer circumferential layer (OCL) also appears at earlier growth stages in small-bodied taxa. Thus, while the OCL is indicative of a cessation of appositional growth it is not always indicative of cortical maturity (that is, maximum organization of bony tissue for a given taxon). Small size is achieved by truncating the period of fast growth; manipulation of the timing of offset of bone growth is therefore an important factor in changing growth trajectories to alter adult body size.


Social support in rural communities in Manabi province, Ecuador.
Social support has been found in many contexts, and in urban Ecuador, to be protective of health, particularly in the context of disaster. Fewer studies have explored the presence and impact of social support in rural Ecuador. This study engages a rural community in Ecuador to examine the general levels of social support, differences in social support based on different demographic groupings and relationships among social support and health outcomes and protective health behaviors. A cross-sectional design was used to survey 416 people in a rural Ecuadorian community that had recently experienced an earthquake. Spanish-language versions of the Multidimensional Scale of Perceived Social Support and the Interpersonal Support Evaluation List-12 were applied, as well as questions about demographics and risk reduction behaviors. Body mass index, blood pressure, and cholesterol and blood sugar levels were assessed. Analysis of variance assessed differences in social support among demographic groupings, risk reduction behaviors, and health outcomes. Levels of social support were moderate. Few statistically significant (ie p<0.05) differences in amount of social support received or in sources of social support were found. Men, people 80 years or older, divorced or widowed people, and people living in peripheral areas received less social support than women, people of all other ages, married/cohabitating people, and people living within the village, respectively. Effect sizes of these differences were small. No relationship between social support and health outcomes were found, and few were found for risk reduction factors. These findings indicate that social support may function differently in rural Ecuador than in urban contexts. Those promoting social support in rural communities may wish to focus on community-level, not individual-level, interventions. Limitations of applying an assessment of social support from urban Ecuadorian contexts to rural Ecuadorian contexts are discussed.


The correlation between bowel complications and cardiac surgery.
Although advances in knowledge and technology have improved outcomes in surgical cardiac patients over the last decade, complications following cardiac operations still remain to be potentially fatal. Gastrointestinal complications, in particular, tend to have high rates of reintervention and mortality following cardiac surgery, with ischemia and hemorrhage being two of the commonest underlying causes. The intention of this review is to identify which risk factors play important roles in predisposing patients to such complications and to gain better insight into the pathogenesis of the sequelae. Furthermore, strategies for prevention have been discussed to educate and increase awareness of how adverse cardiac surgical outcomes can be minimized.


Lung MRI at 1.5 and 3 Tesla: observer preference study and lesion contrast using five different pulse sequences.
To compare the image quality and lesion contrast of lung MRI using 5 different pulse sequences at 1.5 T and 3 T. Lung MRI was performed at 1.5 T and 3 T using 5 pulse sequences which have been previously proposed for lung MRI: 3D volumetric interpolated breath-hold examination (VIBE), true fast imaging with steady-state precession (TrueFISP), half-Fourier single-shot turbo spin-echo (HASTE), short tau inversion recovery (STIR), T2-weighted turbo spin-echo (TSE). In addition to 4 healthy volunteers, 5 porcine lungs were examined in a dedicated chest phantom. Lung pathology (nodules and infiltrates) was simulated in the phantom by intrapulmonary and intrabronchial injections of agarose. CT was performed in the phantom for correlation. Image quality of the sequences was ranked in a side-by-side comparison by 3 blinded radiologists regarding the delineation of pulmonary and mediastinal anatomy, conspicuity of pulmonary nodules and infiltrates, and presence of artifacts. The contrast of nodules and infiltrates (CNODULES and CINFILTRATES) defined by the ratio of the signal intensities of the lesion and adjacent normal lung parenchyma was determined. There were no relevant differences regarding the preference for the individual sequences between both field strengths. TSE was the preferred sequence for the visualization of the mediastinum at both field strengths. For the visualization of lung parenchyma the observers preferred TrueFISP in volunteers and TSE in the phantom studies. At both field strengths VIBE achieved the best rating for the depiction of nodules, whereas HASTE was rated best for the delineation of infiltrates. TrueFISP had the fewest artifacts in volunteers, whereas STIR showed the fewest artifacts in the phantom. For all but the TrueFISP sequence the lesion contrast increased from 1.5 T to 3 T. At both field strengths VIBE showed the highest CNODULES (6.6 and 7.1) and HASTE the highest CINFILTRATES (6.1 and 6.3). The imaging characteristics of different pulse sequences used for lung MRI do not substantially differ between 1.5 T and 3 T. A higher lesion contrast can be expected at 3 T.


On the evaluation of research software: the CDUR procedure.
Background: Evaluation of the quality of research software is a challenging and relevant issue, still not sufficiently addressed by the scientific community. Methods: Our contribution begins by defining, precisely but widely enough, the notions of research software and of its authors followed by a study of the evaluation issues, as the basis for the proposition of a sound assessment protocol: the CDUR procedure. Results: CDUR comprises four steps introduced as follows: Citation, to deal with correct RS identification, Dissemination, to measure good dissemination practices, Use, devoted to the evaluation of usability aspects, and Research, to assess the impact of the scientific work. Conclusions: Some conclusions and recommendations are finally included. The evaluation of research is the keystone to boost the evolution of the Open Science policies and practices. It is as well our belief that research software evaluation is a fundamental step to induce better research software practices and, thus, a step towards more efficient science.


Parents of children with physical disabilities - perceived health in parents related to the child's sleep problems and need for attention at night.
Approximately half of all children with moderate to severe physical disabilities have persistent sleep problems and many of these children need parental attention at night. To study whether sleep problems and need for night-time attention among children with physical disabilities are associated with perceived parental health, headache, psychological exhaustion, pain due to heavy lifting, night-time wakefulness and disrupted sleep. We asked parents of 377 children with physical disabilities aged 1-16 years to complete a questionnaire about their own health. The children all lived at home with both parents. Both parents reported poor health, psychological exhaustion, more night-time wakefulness and disrupted sleep when the child had sleep problems (P < 0.05). Mothers also reported more headache when the child had sleep problems (P = 0.001). Both parents reported more night-time wakefulness and disrupted sleep when the child needed night-time attention (P < 0.01). In general, mothers reported significantly poorer health, more night-time wakefulness, disrupted sleep, headache and psychological exhaustion than fathers (P < 0.001). Sleep problems need to be acknowledged within the paediatric setting in order to prevent psychological exhaustion and poor health in mothers and fathers of children with physical disabilities.


Texture Analysis Improves the Value of Pretreatment 18F-FDG PET/CT in Predicting Interim Response of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.
To explore the application of pretreatment 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) texture analysis (TA) in predicting the interim response of primary gastrointestinal diffuse large B-cell lymphoma (PGIL-DLBCL). Pretreatment 18F-FDG PET/CT images of 30 PGIL-DLBCL patients were studied retrospectively. The interim response was evaluated after 3-4 cycles of chemotherapy. The complete response (CR) rates in patients with different clinicopathological characteristics were compared by Fisher's exact test. The differences in the maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), and texture features between the CR and non-CR groups were compared by the Mann-Whitney U test. Feature selection was performed according to the results of the Mann-Whitney U test and feature categories. The predictive efficacies of the SUVmax, MTV, and the selected texture features were assessed by receiver operating characteristic (ROC) analysis. A prediction probability was generated by binary logistic regression analysis. The SUVmax, MTV, some first-order texture features, volume, and entropy were significantly higher in the non-CR group. The energy was significantly lower in the non-CR group. The SUVmax, volume, and entropy were excellent predictors of the interim response, and the areas under the curves (AUCs) were 0.850, 0.805, and 0.800, respectively. The CR rate was significantly lower in patients with intestinal involvement. The prediction probability generated from the combination of the SUVmax, entropy, volume, and intestinal involvement had a higher AUC (0.915) than all single parameters. TA has potential in improving the value of pretreatment PET/CT in predicting the interim response of PGIL-DLBCL. However, prospective studies with large sample sizes and validation analyses are needed to confirm the current results.


Cockayne's Syndrome A and B Proteins Regulate Transcription Arrest after Genotoxic Stress by Promoting ATF3 Degradation.
Cockayne syndrome (CS) is caused by mutations in CSA and CSB. The CSA and CSB proteins have been linked to both promoting transcription-coupled repair and restoring transcription following DNA damage. We show that UV stress arrests transcription of approximately 70% of genes in CSA- or CSB-deficient cells due to the constitutive presence of ATF3 at CRE/ATF sites. We found that CSB, CSA/DDB1/CUL4A, and MDM2 were essential for ATF3 ubiquitination and degradation by the proteasome. ATF3 removal was concomitant with the recruitment of RNA polymerase II and the restart of transcription. Preventing ATF3 ubiquitination by mutating target lysines prevented recovery of transcription and increased cell death following UV treatment. Our data suggest that the coordinate action of CSA and CSB, as part of the ubiquitin/proteasome machinery, regulates the recruitment timing of DNA-binding factors and provide explanations about the mechanism of transcription arrest following genotoxic stress.


Quantification of the steady-state plasma concentrations of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia using a novel HPLC method and the effects of CYPs and ABC transporters polymorphisms.
Background This study developed a novel high-performance liquid chromatography (HPLC) method for the simultaneous quantification of clozapine and its active metabolite, N-desmethylclozapine, in human plasma and investigated the effects of various factors, including genetic polymorphisms in cytochrome P450 (CYP) 2D6, CYP3A5, ABCB1 and ABCG2, on the steady-state plasma trough concentrations (C0) of clozapine and N-desmethylclozapine in Japanese patients with schizophrenia. Methods Forty-five patients had been receiving fixed doses of clozapine for at least four weeks. The CYP2D6 ( CYP2D6*2, CYP2D6*5, CYP2D6*10), CYP3A5 ( CYP3A5*3), ABCB1 (1236C > T, 2677G > T/A, 3435C > T) and ABCG2 (421 C > A) genotypes were identified by polymerase chain reaction. Results The within- and between-day coefficients of variation (CV) were less than 11.0%, and accuracy was within 9.0% over the linear range from 10 to 2500 ng/mL for both analytes, and their LOQs were each 10 ng/mL. The median C0/dose (C0/D) ratios of clozapine were significantly higher in patients with the ABCG2 421 A allele than in those with the 421 C/C genotype ( P = 0.010). However, there were no significant differences in C0/D ratios of clozapine and N-desmethylclozapine among ABCB1, CYP2D6 or CYP3A5 genotypes. In multiple regression analysis, including polymorphisms, age, body weight and biochemical data of patients, the ABCG2 polymorphism alone was correlated with the C0/D ratios of clozapine ( R2 = 0.139, P = 0.016). Conclusions Among the various CYPs and drug transporters, BCRP appeared to most strongly influence clozapine exposure. Knowledge of the patient's ABCG2 421 C > A genotype before initiating therapy may be useful when making dosing decisions aimed at achieving optimal clozapine exposure.


Ten simple rules for making a vocabulary FAIR.
We present ten simple rules that support converting a legacy vocabulary-a list of terms available in a print-based glossary or in a table not accessible using web standards-into a FAIR vocabulary. Various pathways may be followed to publish the FAIR vocabulary, but we emphasise particularly the goal of providing a globally unique resolvable identifier for each term or concept. A standard representation of the concept should be returned when the individual web identifier is resolved, using SKOS or OWL serialised in an RDF-based representation for machine-interchange and in a web-page for human consumption. Guidelines for vocabulary and term metadata are provided, as well as development and maintenance considerations. The rules are arranged as a stepwise recipe for creating a FAIR vocabulary based on the legacy vocabulary. By following these rules you can achieve the outcome of converting a legacy vocabulary into a standalone FAIR vocabulary, which can be used for unambiguous data annotation. In turn, this increases data interoperability and enables data integration.


A molecular study of tick-borne haemoprotozoan parasites (Theileria and Babesia) in small ruminants in Northern Tunisia.
In this study, the frequency of Theileria and Babesia species in sheep and goats was assessed via reverse line blotting (RLB). A total of 263 apparently healthy sheep and goats, from 16 randomly selected flocks located in 9 localities situated in 3 bioclimatic zones in Tunisia, were investigated for the blood protozoans. RLB hybridization with polymerase chain reaction detected only Theileria ovis in sheep and goats, accounting for 22.4% (95% confidence interval [CI]: 17.6-27.1%) positive samples. The infection rate in sheep (28.1%; 95% CI: 23.8-32.3%) was higher than in goats (4.7%; 95% CI: -10.9 to 20.4%). Neither Babesia nor mixed infections were detected. Only two Ixodid tick species (Rhipicephalus turanicus and Rhipicephalus bursa) were collected from the examined sheep and goats in 5 localities. R. turanicus was the dominant species (95.5%) collected mainly in the humid zone, while apparently rare in the sub-humid zone. R. bursa was the only species collected in the semi-arid area. RLB analysis identified six different piroplasms in ticks, with an overall prevalence of 31.5% (95% CI: 28.1-34.9%). Twenty percent (95% CI: 14.4-25.5%) of the collected ticks tested positive for Theileria spp., 3% (95% CI: -5.6 to 11.6%) for Babesia spp. and 0.9% (95% CI: -8.1 to 9.9%) of the ticks harbored both genera; several of these species are not known to occur in small ruminants. This is the first report on the detection of Theileria and Babesia species DNA in small ruminants and ticks in Tunisia.


An assessment of intra-patient variability on observed relationships between wall shear stress and plaque progression in coronary arteries.
Wall shear stress (WSS) has been associated with sites of plaque localization and with changes in plaque composition in human coronary arteries. Different values have been suggested for categorizing WSS as low, physiologic or high; however, uncertainties in flow rates, both across subjects and within a given individual, can affect the classification of WSS and thus influence the observed relationships between local hemodynamics and plaque changes over time. This study examines the effects of uncertainties in flow rate boundary conditions upon WSS values and investigates the influence of this variability on the observed associations of WSS with changes in VH-IVUS derived plaque components. Three patients with coronary artery disease underwent baseline and 12 month follow-up angiography and virtual histology-intravascular ultrasound (VH-IVUS) measurements. Coronary artery models were reconstructed from the data and models with and without side-branches were created. Patient-specific Doppler ultrasound (DUS) data were employed as inflow boundary conditions and computational fluid dynamics was used to calculate the WSS in each model. Further, the influence of representative coronary artery flow waveforms upon WSS values was investigated and the concept of treating WSS using relative, rather than actual, values was explored. Models that included side-branch outflows and subject-specific DUS velocities were considered to be the reference cases. Hemodynamic differences were caused by the exclusion of side-branches and by imposing alternative velocity waveforms. One patient with fewer side-branches and a scaled generic waveform had little deviation from the reference case, while another patient with several side-branches excluded showed much larger departures from the reference situation. Differences between models and the respective reference cases were reduced when data were analyzed using relative, rather than actual, WSS. When considering individual subjects, large variations in patient-specific flow rates and exclusion of multiple side-branches in computational models can cause significant differences in observed associations between plaque evolution and ranges of computed WSS. These differences may contribute to the large variability typically found among subjects in pooled populations. Relative WSS may be more useful than actual WSS as a correlative variable when there is a large degree of uncertainty in flow rate data.


Comparison of effects of low-level laser therapy and extracorporeal shock wave therapy in calcaneal spur treatment: A prospective, randomized, clinical study.
In this study, we aimed to evaluate and compare the efficacy of low-level laser therapy (LLLT) and extracorporeal shock wave therapy (ESWT) in the treatment of calcaneal spurs. A total of 62 patients (14 males, 48 females; mean age: 47.6±11.7 years; range, 18 to 70 years) who were diagnosed with calcaneal spurs based on clinical examination and plain radiography between April 2019 and September 2019 were included in this study. A total of 15 sessions of plantar fascia gastroc-soleus stretching exercises and cold pack treatments were given to both groups. The LLLT (904 nm wavelength, 3,000 Hz, 8 J/cm2 dose to the painful heel area and insertion of the plantar fascia on the medial calcaneal area, five points for a total of 5 min for three weeks) was applied to the first group (n=31), whereas ESWT (10 Hz, 2,000 shock waves with a 2.5 bar pressure into the areas of the painful heel, insertion of the plantar fascia on the medial calcaneal area) was applied the second group (n=31). All patients were evaluated using the Visual Analog Scale (VAS) and Foot Function Index (FFI) before and after treatment. In both groups, the median VAS and FFI scores after treatment showed a significant improvement, compared to pre-treatment scores (p=0.001). There was no significant difference between the groups in terms of the median post-treatment VAS scores (p>0.05). In the ESWT group, the median FFI pain and total scores after treatment were significantly lower than in the LLLT group (p=0.033). The change in the median FFI pain and total scores were significantly higher in the ESWT group (p=0.046). Both treatment modalities are effective and not superior to each other in terms of disability and activity limitation reduction, although a greater improvement in the FFI pain and total scores can be achieved with the ESWT. Based on these findings, we recommend both non-invasive treatment methods to be used in the treatment of calcaneal spurs in the clinical practice.


Atracurium in clinical anaesthesia.
Atracurium was used on 250 occasions under normal operating conditions in patients between the ages of 18 and 86 yr; 97 patients were aged 65 yr and over, 47 were ASA Grade III, 15 were Grade IV and three were Grade V. Provided that a dose of 0.5-0.6 mgkg-1 was used, intubation was carried out in 1.5 min in 82% of patients. Good operating conditions were obtained in all patients and no complications could be attributed to atracurium even in patients giving a history of allergy or asthma. Residual blockade could be adequately antagonized and recurarization did not occur.


Usefulness of transoesophageal echocardiography before cardioversion in patients with atrial fibrillation and different anticoagulant regimens.
To evaluate the prevalence of atrial thrombi in patients with atrial fibrillation undergoing different anticoagulation regimens before cardioversion; to evaluate the usefulness of transoesophageal echocardiography (TOE) guided cardioversion to prevent thromboembolic complications; and to correlate the presence of atrial thrombi with clinical and echocardiographic data. 757 consecutive patients admitted as candidates for cardioversion of atrial fibrillation were enrolled in the study. They were divided into four groups: effective conventional oral anticoagulation, short term anticoagulation, ineffective oral anticoagulation or subtherapeutic anticoagulation, and effective oral anticoagulation with a duration of < 3 weeks for various clinical reasons. All patients underwent TOE before cardioversion; in the presence of atrial thrombi or extreme left atrial echo contrast, cardioversion was postponed. The incidence of thromboembolic events was evaluated after cardioversion. Atrial thrombi were detected in 48 of the 757 (6.3%) patients. No significant differences in the percentage of atrial thrombosis were found in the four study groups. Patients with atrial thrombosis were older and had a higher percentage of mitral prosthetic valves, lower left ventricular ejection fraction, more severe atrial spontaneous echo contrast, and lower Doppler left atrial appendage velocities. 648 patients were scheduled for cardioversion. Cardioversion was successful in 89% of patients without any major thromboembolic event. The prevalence of atrial thrombosis before cardioversion despite different treatments with anticoagulants is about 7% and a TOE guided approach may prevent the risk of embolic events.


Post-transcriptional Regulation by 3' UTRs Can Be Masked by Regulatory Elements in 5' UTRs.
In mRNA sequences, 3' UTRs are thought to contain most elements that specifically regulate localization, turnover, and translation. Although high-throughput experiments indicate that many RNA-binding proteins (RBPs) also bind 5' UTRs, much less is known about specific post-transcriptional control exerted by 5' UTRs. GLD-1 is a conserved RBP and a translational repressor with essential roles in Caenorhabditis elegans germ cell development. Previously, we showed that GLD-1 binds highly conserved sites in both 3' and 5' UTRs. Here, by targeted single-copy insertion of transgenes, we systematically tested in vivo functionality of 5' and 3' UTR binding sites individually and in combination. Our data show that sites in 5' UTRs mediate specific and strong translational repression, independent of exact position. Intriguingly, we found that the functionality of 3' UTR sites can be masked by 5' UTR sites and vice versa. We conclude that it is important to study both UTRs simultaneously.


Interaction of Vesicular-arbuscular Mycorrhizal Fungi and Phosphorus with Meloidogyne incognita on Tomato.
The influence of two vesicular-arbuscular mycorrhizal fungi and phosphorus (P) nutrition on penetration, development, and reproduction by Meloidogyne incognita on Walter tomato was studied in the greenhouse. Inoculation with either Gigaspora margarita or Glomus mosseae 2 wk prior to nematode inoculation did not alter infection by M. incognita compared with nonmycorrhizal plants, regardless of soil P level (either 3 mug [low P] or 30 mug [high P] available P/g soil). At a given soil P level, nematode penetration and reproduction did not differ in mycorrhizal and nonmycorrhizal plants. However, plants grown in high P soil had greater root weights, increased nematode penetration and egg production per plant, and decreased colonization by mycorrhizal fungi, compared with plants grown in low P soil. The number of eggs per female nematode on mycorrhizal and nonmycorrhizal plants was not influenced by P treatment. Tomato plants with split root systems grown in double-compartment containers which had either low P soil in both sides or high P in one side and low P in the other, were inoculated at transplanting with G. margarita and 2 wk later one-half of the split root system of each plant was inoculated with M. incognita larvae. Although the mycoorhizal fungus increased the inorganic P content of the root to a level comparable to that in plants grown in high P soil, nematode penetration and reproduction were not altered. In a third series of experiments, the rate of nematode development was not influenced by either the presence of G. margarita or high soil P, compared with control plants grown in low P soil. These data indicate that supplemental P (30 mu/g soil) alters root-knot nematode infection of tomato more than G. mosseae and G. margarita.


Identification of immune-related hub genes and construction of an immune-related gene prognostic index for low-grade glioma.
Low-grade glioma (LGG) poses significant management challenges and has a dismal prognosis. While immunotherapy has shown significant promise in cancer treatment, its progress in glioma has confronted with challenges. In our study, we aimed to develop an immune-related gene prognostic index (IRGPI) which could be used to evaluate the response and efficacy of LGG patients with immunotherapy. We included a total of 529 LGG samples from TCGA database and 1152 normal brain tissue samples from the GTEx database. Immune-related differentially expressed genes (DEGs) were screened. Then, we used weighted gene co-expression network analysis (WGCNA) to identify immune-related hub genes in LGG patients and performed Cox regression analysis to construct an IRGPI. The median IRGPI was used as the cut-off value to categorize LGG patients into IRGPI-high and low subgroups, and the molecular and immune mechanism in IRGPI-defined subgroups were analysed. Finally, we explored the relationship between IRGPI-defined subgroups and immunotherapy related indicators in patients after immunotherapy. Three genes (RHOA, NFKBIA and CCL3) were selected to construct the IRGPI. In a survival analysis using TCGA cohort as a training set, patients in the IRGPI-low subgroup had a better OS than those in IRGPI-high subgroup, consistent with the results in CGGA cohort. The comprehensive results showed that IRGPI-low subgroup had a more abundant activated immune cell population and lower TIDE score, higher MSI, higher TMB score, lower T cell dysfunction score, more likely benefit from ICIs therapy. IRGPI is a promising biomarker in the field of LGG ICIs therapy to distinguish the prognosis, the molecular and immunological characteristics of patients.


Molecular dissection of the biosynthetic relationship between phthiocerol and phthiodiolone dimycocerosates and their critical role in the virulence and permeability of Mycobacterium tuberculosis.
Phthiocerol dimycocerosates and related compounds are important molecules in the biology of Mycobacterium tuberculosis, playing a key role in the permeability barrier and in pathogenicity. Both phthiocerol dimycocerosates, the major compounds, and phthiodiolone dimycocerosates, the minor constituents, are found in the cell envelope of M. tuberculosis, but their specific roles in the biology of the tubercle bacillus have not been established yet. According to the current model of their biosynthesis, phthiocerol is produced from phthiodiolone through a two-step process in which the keto group is first reduced and then methylated. We have previously identified the methyltransferase enzyme that is involved in this process, encoded by the gene Rv2952 in M. tuberculosis. In this study, we report the construction and biochemical analyses of an M. tuberculosis strain mutated in gene Rv2951c. This mutation prevents the formation of phthiocerol and phenolphthiocerol derivatives, but leads to the accumulation of phthiodiolone dimycocerosates and glycosylated phenolphthiodiolone dimycocerosates. These results provide the formal evidence that Rv2951c encodes the ketoreductase catalyzing the reduction of phthiodiolone and phenolphthiodiolone to yield phthiotriol and phenolphthiotriol, which are the substrates of the methyltransferase encoded by gene Rv2952. We also compared the resistance to SDS and replication in mice of the Rv2951c mutant, deficient in synthesis of phthiocerol dimycocerosates but producing phthiodiolone dimycocerosates, with those of a wild-type strain and a mutant without phthiocerol and phthiodiolone dimycocerosates. The results established the functional redundancy between phthiocerol and phthiodiolone dimycocerosates in both the protection of the mycobacterial cell and the pathogenicity of M. tuberculosis in mice.


Omental mesenteric myxoid hamartoma, a subtype of inflammatory myofibroblastic tumor? Considerations based on the histopathological evaluation of four cases.
Omental mesenteric myxoid hamartoma (OMH) is a distinctive myxoid lesion of infancy, characterized by a benign clinical behavior. In the current World Health Organization (WHO) classification of soft tissue tumors, it is considered as part of the morphologic spectrum of inflammatory myofibroblastic tumors (IMT), but this relationship with IMT is still subject to debate. Four lesions with histologic features of OMH occurring in newborns and toddlers are described and compared with classic, ALK-positive IMT. All OMH showed a peculiar dot-like immunostaining for ALK, which, in one of the cases, was cytogenetically found to be associated with an inversion of the ALK gene. While OMHs were positive for smooth muscle actin (SMA), desmin, WT1, podoplanin, and cytokeratins (CAM5.2 and AE1-3), IMT were consistently positive only for SMA (10 cases). ALK-1 displayed cytoplasmic staining in IMT and characteristic paranuclear dot-like staining in OMH.


Migration of MDA-MB-231 breast cancer cells depends on the availability of exogenous lipids and cholesterol esterification.
We previously described a lipid-accumulating phenotype of estrogen receptor negative (ER(-)) breast cancer cells exemplified by the MDA-MB-231 and MDA-MB-436 cell lines. These cells had more lipid droplets, a higher uptake of oleic acid and LDL, a higher ratio of cholesteryl ester (CE) to triacylglycerol (TAG), and higher expression of acyl-CoA:cholesterol acyltransferase 1 (ACAT1) as compared to ER(+) MCF-7 breast cancer cells. LDL stimulated proliferation of ER-cells only, and proliferation was reduced by inhibition of ACAT. We hypothesized that storage of exogenous lipids would confer an energetic advantage. We tested this by depriving cells of exogenous lipids and measuring chemotactic migration, an energy-intensive behavior. MDA-MB-231 cells were grown for 48 h in medium with either 5% FBS or 5% lipoprotein-depleted (LD) FBS. Growth in LD medium resulted in visibly reduced lipid droplets and an 85% decrease in cell migration. Addition of LDL to the LD medium dose-dependently restored the ability to migrate in an ACAT-sensitive manner. LDL receptor (LDLR) mRNA was 12-fold higher in MDA-MB-231 cells compared to nontumorigenic ER-MCF-10A breast epithelial cells grown in LD medium. Addition of LDL to the LD medium reduced LDLR mRNA levels in MCF-10A cells only. We asked if ACAT1 activity was associated with the expression of the LDLR in MDA-MB-231 cells. LDLR mRNA in MDA-MB-231 cells was substantially reduced by inhibition of ACAT, demonstrating that high ACAT1 activity permitted higher LDLR expression. This data substantiates the association of lipid accumulation with aggressive behavior in an ER-breast cancer cell line.


Calculated plasma volume status predicts outcomes after transcatheter aortic valve implantation.
Congestion can worsen outcomes after transcatheter aortic valve implantation (TAVI), but can be difficult to quantify non-invasively. We hypothesised that preprocedural plasma volume status (PVS), estimated using a validated formula that enumerates percentage change from ideal PV, would provide prognostic utility post-TAVI. This retrospective cohort study identified patients who underwent TAVI (2007-2017) from a prospectively collected database. Actual ([1-haematocrit] × [a + (b × weight (Kg))] and ideal (c × weight (Kg)) PV were quantified from equations where a, b and c are sex-dependent constants. Calculated PVS was then derived (100% x [(actual - ideal PV)/ideal PV]). In 564 patients (mean age 82±7 years, 49% male), mean PVS was -2.7±10.2%, with PV expansion (PVS >0%) evident in 39%. Only logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) independently predicted a PVS >0% (OR 1.85, p=0.002). On Cox analyses, a PVS >0% was associated with greater mortality at 3 (HR 2.29, 95% CI 1.11 to 4.74, p=0.03) and 12 months (HR 2.00, 95% CI 1.23 to 3.26, p=0.006) after TAVI, independently of, and incremental to, the EuroSCORE and New York Heart Association class. A PVS >0% was also independently associated with more days in intensive care (coefficient: 0.41, 95% CI 0.04 to 0.78, p=0.03) and in hospital (coefficient: 1.95, 95% CI 0.48 to 3.41, p=0.009). Higher PVS values, calculated simply from weight and haematocrit, are associated with greater mortality and longer hospitalisation post-TAVI. PVS could help refine risk stratification and further investigations into the utility of PVS-guided management in TAVI patients is warranted.


Subcutaneous lesions and bacteraemia due to Stenotrophomonas maltophilia in three leukaemic patients with neutropenia.
Subcutaneous lesions were seen in three of 13 neutropenia patients who had Stenotrophomonas (Xanthomonas) maltophilia bacteraemia. The characteristic clinical presentation resembled leukaemic infiltrates, and were different from deep ulcers or subcutaneous nodules caused by Pseudomonas aeruginosa. The three patients had acute leukaemia and were treated with intensive combination chemotherapy. All had previously been treated with broad-spectrum antibiotics, and each patient recovered after proper combination antibiotic treatment given according to sensitivity testing.


Cell behaviour during postembryonic pattern regulation in the insect abdomen (Oncopeltus fasciatus). I. Regeneration of segment borders
The confrontation of cells from the anterior region of an abdominal segment of Oncopeltus with those from the posterior region of the same or the adjacent segment results in the generation of a segment border. The behaviour of epidermal cells during this regulation is described. It consists primarily of cell division and transverse elongation of cells at the site of confrontation. This behaviour can be separated from any associated purely with wound healing because a similar-sized wound to that used to ablate the segment border, performed within the segment, does not result in any cell division or elongation. The results are consistent with the view that there is a discontinuity in positional values at the segment border. The stability of such a discontinuity and the regeneration of segment borders are discussed in terms of there being a special population of cells at the segment border that have the property of isolating other cells with the maximum difference in positional values.


Multirobot systems: a classification focused on coordination.
Multirobot systems (MRS) are, nowadays, an important research area within robotics and artificial intelligence and a growing number of systems have recently been presented in the literature. Since application domains and tasks that are faced by MRS are of increasing complexity, the ability of the robots to cooperate can be regarded as a fundamental feature. In this paper, we present a survey of the recent work in the area by specifically examining the forms of cooperation and coordination realized in the MRS. In particular, we propose a new taxonomy for classification of the approaches to coordination in MRS and we describe some systems, which we consider representative in our taxonomy. We finally discuss the outcomes of our analysis and try to highlight future trends of the research on MRS.


Predicting use of case management support services for adolescents and adults living in community following brain injury: A longitudinal Canadian database study with implications for life care planning.
To determine factors associated with case management (CM) service use in people with traumatic brain injury (TBI), using a published model for service use. A retrospective cohort, with nested case-control design. Correlational and logistic regression analyses of questionnaires from a longitudinal community data base. Questionnaires of 203 users of CM services and 273 non-users, complete for all outcome and predictor variables. Individuals with TBI, 15 years of age and older. Out of a dataset of 1,960 questionnaires, 476 met the inclusion criteria. Eight predictor variables and one outcome variable (use or non-use of the service). Predictor variables considered the framework of the Behaviour Model of Health Service Use (BMHSU); specifically, pre-disposing, need and enabling factor groups as these relate to health service use and access. Analyses revealed significant differences between users and non-users of CM services. In particular, users were significantly younger than non-users as the older the person the less likely to use the service. Also, users had less education and more severe activity limitations and lower community integration. Persons living alone are less likely to use case management. Funding groups also significantly impact users. This study advances an empirical understanding of equity of access to health services usage in the practice of CM for persons living with TBI as a fairly new area of research, and considers direct relevance to Life Care Planning (LCP). Many life care planers are CM and the genesis of LCP is CM. The findings relate to health service use and access, rather than health outcomes. These findings may assist with development of a modified model for prediction of use to advance future cost of care predictions.


Effect of Hedyotis Diffusa Willd extract on tumor angiogenesis.
Inhibition of tumor angiogenesis has become an attractive target of anticancer chemotherapy. However, drug resistance and cytotoxicity against non-tumor associated endothelial cells limit the long-term use and the therapeutic effectiveness of angiogenesis inhibitors, thus increasing the necessity for the development of multi-target agents with minimal side effects. Traditional Chinese medicine (TCM) formulas, which have relatively fewer side effects and have been used clinically to treat various types of diseases, including cancer, for thousands of years, are considered to be multi-component and multi-target agents exerting their therapeutic function in a more holistic way. Hedyotis Diffusa Willd (EEHDW) has long been used as an important component in several TCM formulas to treat various types of cancer. Although recently we reported that EEHDW promotes cancer cell apoptosis via activation of the mitochondrial-dependent pathway, the precise mechanism of its tumoricidalactivity still remains to be clarified. In the present study, we investigated the angiogenic effects of the ethanol extract of EEHDW. Cell cycle analysis was perfomed using flow cytometry. Cell viability was analyzed using MTT assay. We found that EEHDW inhibited angiogenesis in vivo in chick embryo chorioallantoic membrane (CAM). In addition, we observed that EEHDW dose- and time-dependently inhibited the prolife-ration of human umbilical vein endothelial cells (HUVEC) by blocking the cell cycle G1 to S progression. Moreover, EEHDW inhibited the migration and tube formation of HUVECs. Furthermore, EEHDW treatment down-regulated the mRNA and protein expression levels of VEGF-A in HT-29 human colon carcinoma cells and HUVECs. Our findings suggest that inhibiting tumor angiogenesis is one of the mechanisms by which EEHDW is involved in cancer therapy.


Efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treatment of uncomplicated malaria in children in Zaire and Uíge Provinces, angola.
The development of resistance to antimalarials is a major challenge for global malaria control. Artemisinin-based combination therapies, the newest class of antimalarials, are used worldwide but there have been reports of artemisinin resistance in Southeast Asia. In February through May 2013, we conducted open-label, nonrandomized therapeutic efficacy studies of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) in Zaire and Uíge Provinces in northern Angola. The parasitological and clinical responses to treatment in children with uncomplicated Plasmodium falciparum monoinfection were measured over 28 days, and the main outcome was a PCR-corrected adequate clinical and parasitological response (ACPR) proportion on day 28. Parasites from treatment failures were analyzed for the presence of putative molecular markers of resistance to lumefantrine and artemisinins, including the recently identified mutations in the K13 propeller gene. In the 320 children finishing the study, 25 treatment failures were observed: 24 in the AL arms and 1 in the DP arm. The PCR-corrected ACPR proportions on day 28 for AL were 88% (95% confidence interval [CI], 78 to 95%) in Zaire and 97% (91 to 100%) in Uíge. For DP, the proportions were 100% (95 to 100%) in Zaire, and 100% (96 to 100%) in Uíge. None of the treatment failures had molecular evidence of artemisinin resistance. In contrast, 91% of AL late-treatment failures had markers associated with lumefantrine resistance on the day of failure. The absence of molecular markers for artemisinin resistance and the observed efficacies of both drug combinations suggest no evidence of artemisinin resistance in northern Angola. There is evidence of increased lumefantrine resistance in Zaire, which should continue to be monitored.


Expression and localization of opioid receptors during the maturation of human oocytes.
The endogenous opioid system has been characterized in some female reproductive organs, but little is known about the expression of these receptors in human oocytes. This study investigated the presence and differential distribution of the opioid receptors during the maturation of human oocytes. A total of 821 human oocytes from an intracytoplasmic sperm injection (ICSI) programme were studied including 213 at germinal-vesicle (GV) stage and 164 at metaphase-I (MI) stage and 444 failed fertilization metaphase-II (MII) oocytes. Additionally 31 MII oocytes corresponding to cases where ICSI was not attempted and 50 failed fertilization MII oocytes from the IVF programme were included. Western blot analysis revealed the presence of the delta (OPRD1), kappa (OPRK1) and mu (OPRM1) opioid receptors in human oocytes. The OPRK1 and OPRM1 immunostaining patterns changed during the maturation of the oocyte, while the OPRD1 pattern was the same throughout. In particular, OPRD1 were detected in peripheral tissue from the GV to the MII stage. OPRK1 were found peripherally at the GV stage, more internally at MI and homogeneously at MII. Finally, OPRM1 were located peripherally at the GV stage and homogeneously in MI and MII oocytes. Opioids may have a role in oocyte maturation, acting via receptors. The opioid system has been well characterized in the central nervous system, but it is now known that opioids also act in reproductive organs. However, little is known about the presence and function of this system in human oocytes and its role in their maturation. In this study, we investigated the presence and differential distribution of three (delta, kappa and mu) opioid receptors (proteins which bind the opioids) during the maturation of human oocytes. A total of 821 human oocytes (from 253 patients) not suitable for intracytoplasmic sperm injection (ICSI) or which did not develop into an embryo after ICSI were studied. Thus, we have verified the presence of the delta, kappa and mu opioid receptors in human oocytes. The kappa and mu localization changed during the maturation of the oocyte, while the Delta localization was the same throughout. In particular, the delta receptor was detected in the periphery of the oocyte. On the other hand, the kappa receptor was found peripherally at the beginning, more internally during maturation and homogeneously at the end of maturation. Finally, the Mu receptor was located peripherally at the beginning of maturation and homogeneously in the rest of the maturation stages. This finding suggests a possible role for opioids, acting via receptors, in the maturation of the oocyte.


Patellofemoral Arthroplasty Results in Better Time-weighted Patient-reported Outcomes After 6 Years than TKA: A Randomized Controlled Trial.
In a previous study, we reported the 2-year outcomes of a parallel-group, equivalence, randomized controlled trial (RCT; blinded for the first year) comparing patellofemoral arthroplasty (PFA) and TKA for isolated patellofemoral osteoarthritis (PF-OA). We found advantages of PFA over TKA for ROM and various aspects of knee-related quality of life (QOL) as assessed by patient-reported outcomes (PROs). Register data show increases in PFA revision rates from 2 to 6 years after surgery at a time when annual TKA revision rates are decreasing, which suggests rapidly deteriorating knee function in patients who have undergone PFA. We intended to examine whether the early advantages of PFA over TKA have deteriorated in our RCT and whether revision rates differ between the implant types in our study after 6 years of follow-up. (1) Does PRO improvement during the first 6 postoperative years differ between patients who have undergone PFA and TKA? (2) Does the PRO improvement at 3, 4, 5, and 6 years differ between patients who have undergone PFA and TKA? (3) Do patients who have undergone PFA have a better ROM after 5 years than patients who have had TKA? (4) Does PFA result in more revisions or reoperations than TKA during the first 6 postoperative years? We considered patients who had debilitating symptoms and PF-OA as eligible for this randomized trial. Screening initially identified 204 patients as potentially eligible; 7% (15) were found not to have sufficient symptoms, 21% (43) did not have isolated PF-OA, 21% (43) declined participation, and 1% (3) were not included after the target number of 100 patients had been reached. The included 100 patients were randomized 1:1 to PFA or TKA between 2007 and 2014. Of these, 9% (9 of 100) were lost before the 6-year follow-up; there were 12% (6 of 50) and 0% (0 of 50) deaths (p = 0.02) in the PFA and TKA groups, respectively, but no deaths could be attributed to the knee condition. There were no differences in baseline parameters for patients who had PFA and TKA, such as the proportion of women in each group (78% [39 of 50] versus 76% [38 of 50]; p > 0.99), mean age (64 ± 9 years versus 65 ± 9 years; p = 0.81) or BMI (28.0 ± 4.7 kg/m 2 versus 27.8 ± 4.1 kg/m 2 ; p = 0.83). Patients were seen for five clinical follow-up visits (the latest at 5 years) and completed 10 sets of questionnaires during the first 6 postoperative years. The primary outcome was SF-36 bodily pain. Other outcomes were reoperations, revisions, ROM, and PROs (SF-36 [eight dimensions, range 0 to 100 best, minimum clinically important difference {MCID} 6 to 7], Oxford Knee Score [OKS; one dimension, range 0 to 48 best, MCID 5], and Knee Injury and Osteoarthritis Outcome Score [KOOS; five dimensions, range 0 to 100 best, MCID 8 to 10]). Average PRO improvements over the 6 years were determined by calculating the area under the curve and dividing by the observation time, thereby obtaining a time-weighted average over the entire postoperative period. PRO improvements at individual postoperative times were compared for the patients who had PFA and TKA using paired t-tests. Range of movement changes from baseline were compared using paired t-tests. Reoperation and revision rates were compared for the two randomization groups using competing risk analysis. Patients who underwent PFA had a larger improvement in the SF-36 bodily pain score during the first 6 years than those who underwent TKA (35 ± 19 vs. 23 ± 17; mean difference 12 [95% CI 4 to 20]; p = 0.004), and the same was true for SF-36 physical functioning (mean difference 11 [95% CI 3 to 18]; p = 0.008), KOOS Symptoms (mean difference 12 [95% CI 5 to 20]; p = 0.002), KOOS Sport/recreation (mean difference 8 [95% CI 0 to 17]; p = 0.048), and OKS (mean difference 5 [95% CI 2 to 8]; p = 0.002). No PRO dimension had an improvement in favor of TKA. At the 6-year time point, only the SF-36 vitality score differed between the groups being in favor of PFA (17 ± 19 versus 8 ± 21; mean difference 9 [95% CI 0 to 18]; p = 0.04), whereas other PRO measures did not differ between the groups. At 5 years, ROM had decreased less from baseline for patients who underwent PFA than those who had TKA (-4° ± 14° versus -11° ± 13°; mean difference 7° [95% CI 1° to 13°]; p = 0.02), but the clinical importance of this is unknown. Revision rates did not differ between patients who had PFA and TKA at 6 years with competing risk estimates of 0.10 (95% CI 0.04 to 0.20) and 0.04 (95% CI 0.01 to 0.12; p = 0.24), respectively, and also reoperation rates were no different at 0.10 (95% CI 0.04 to 0.20) and 0.12 (95% CI 0.05 to 0.23; p = 0.71), respectively. Our RCT results show that the 2-year outcomes did not deteriorate during the subsequent 4 years. Patients who underwent PFA had a better QOL throughout the postoperative years based on several of the knee-specific outcome instruments. When evaluated by the 6-year observations alone and without considering earlier observations, we found no consistent difference for any outcome instruments, although SF-36 vitality was better for patients who underwent PFA. These combined findings show that the early advantages of PFA determined the results by 6 years. Our findings cannot explain the rapid deterioration of results implied by the high revision rates observed in implant registers, and it is necessary to question indications for the primary procedure and subsequent revision when PFA is in general use. Our data do not suggest that there is an inherent problem with the PFA implant type as otherwise suggested by registries. The long-term balance of advantages will be determined by the long-term QOL, but based on the first 6 postoperative years and ROM, PFA is still the preferable option for severe isolated PF-OA. A possible high revision rate in the PFA group beyond 6 years may outweigh the early advantage of PFA, but only detailed analyses of long-term studies can confirm this. Level I, therapeutic study.


Overall linkage map of the nonstructural proteins of Aichi virus.
Aichi virus (AiV), which is associated with acute gastroenteritis in humans, is a member of the genus Kobuvirus of the family Picornaviridae. Picornavirus genome replication occurs in replication complexes that include viral nonstructural proteins, host proteins and viral RNA. In poliovirus, all nonstructural proteins are found in the replication complexes, suggesting the ability of the viral nonstructural proteins to interact with each other. In this study, we examined the interactions between the AiV nonstructural proteins using a mammalian two-hybrid system. The results showed that all of the tested proteins could interact with more than one protein. We observed homodimerization of five proteins, bidirectional heterodimerization of six protein pairs, and unidirectional heterodimerization of eighteen protein pairs. Among the interactions detected in this study, the 2A-2BC, 2A-2BC, 2A-2C, 2BC-3CD, 2BC-3C, 2C-3C, 2C-3CD and 3AB-3C interactions have not been observed in the previous two-hybrid studies with other picornaviruses. The strongest interaction was observed between 2A and 3CD. AiV 2A has already been shown to be involved in genome replication. Domain mapping of the 2A and 3CD interaction in mammalian two-hybrid analysis revealed that the C-terminal quarter of 2A is not required for the interaction with 3CD.


Human papillomavirus vaccine administration behaviors and influences among Arizona pharmacists and pharmacy interns.
This study assessed 27 Arizona community pharmacists' and pharmacy interns' human papillomavirus (HPV) vaccine administration behaviors and influences. We recruited community pharmacists and pharmacy interns from a statewide pharmacy conference to complete a 40-item cross-sectional survey. Informed by the Theory of Planned Behavior, the survey assessed pharmacists' HPV vaccine-related behaviors, intentions, attitudes, subjective norms, and perceived behavioral control to vaccinate against HPV. We analyzed all data using descriptive statistics and correlations. Overall, most pharmacists held positive attitudes about the HPV vaccine. However, the majority rarely administered the HPV vaccine. Intentions to vaccinate and subjective norms positively correlated with vaccine administration behavior. Pharmacists' positive attitudes about the vaccine, subjective norm to vaccinate, and behavioral control or self-efficacy to recommend the vaccine impacted their intentions to vaccinate against HPV. Most surveyed pharmacists believed that the most substantial HPV vaccine administration barriers include parental consent and parental stigma against the vaccine. The most common pharmacy-related barrier was the lack of a tracking and reminder system to encourage patients to return for additional HPV vaccine doses. This work highlights the need to increase public awareness that pharmacists can administer vaccines to adolescents. Study authors recommend offering communication training to increase pharmacists' perceived behavioral control to recommend the HPV vaccine.


[Open laparoscopy in patients at risk].
A variant of the technique of open laparoscopy is reported. The principal feature of this technique is that creation of a pneumoperitoneum is simplified. No additional instruments are required, nor sharp instruments, except for the skin incision and splitting of the fascia. The modified open laparoscopy technique was used on 23 high-risk patients in a group of 224 patients on whom laparoscopy was performed at Ludwigshafen Gynecological Clinic. The technique is discussed with reference to the literature.


A clinical evaluation of the Sulcabrush.
The purpose of this study was to compare the effectiveness of a unituft brush in combination with a conventional brush for plaque removal and maintenance of gingival health. Thirty patients presenting for routine dental care were examined and scored for plaque deposits and gingival inflammation. All subjects received a dental prophylaxis consisting of removal of all supragingival and subgingival deposits and polishing of the clinical crowns. Subjects were subsequently evaluated at 1 week, 6 weeks and 12 weeks. The addition of a unituft brush to the patient's regimen of oral hygiene procedures resulted in significant reductions at 12 weeks in both plaque scores (p less than .05) and gingival inflammation (p less than .01) when compared to the use of the conventional brush alone.


Bioanalysis of tucatinib and metabolite, and a five-way cross-validation to support clinical pharmacokinetic analysis.
Tucatinib, a tyrosine kinase inhibitor of HER2, is approved in multiple regions for metastatic breast cancer and is being evaluated in metastatic colorectal and gastric cancers. During clinical development, quantification of tucatinib plasma concentrations for pharmacokinetic analysis was performed using MS/MS analysis by three laboratories using five different methods. Cross-validation was required to confirm data across laboratories were comparable. A five-way cross-validation procedure was developed where bioanalysis performed by one laboratory and method was used as a 'base' against which the other methods were validated. This cross-validation method provides an alternative to multiple head-to-head comparisons between two methods, and enabled combination of data from multiple tucatinib clinical trials for a single population pharmacokinetic analysis.


Depression, stress and self-stigma towards seeking psychological help in veterinary students.
Previous research indicates that the prevalence of depression among veterinarians and veterinary students is high. Although self-stigma in seeking psychological help is reportedly elevated in veterinary students, its impact on mental health has been largely unexplored. The aim of this study was to compare the levels of study-related stress, depression symptoms and self-stigma in veterinary students with those of non-veterinary students, and examine whether stress and self-stigma positively predicted depression symptoms in veterinary students. A total of 287 veterinary students and 317 non-veterinary students from Australian universities completed an online questionnaire measuring study-related stress, self-stigma and depression symptoms. Results showed that veterinary students reported significantly higher levels of stress and self-stigma than non-veterinary students, but there was no significant difference between veterinary and non-veterinary students in depression symptoms. Multiple regression analysis indicated that stress and self-stigma both predicted depression symptoms in veterinary students. These findings suggest that reducing stress and help-seeking self-stigma in veterinary students may be important in improving their wellbeing levels. These findings are important in developing a whole-of-career life course approach to understanding the professional and psychological experiences of veterinarians.


Fatigue data for laser beam powder bed fused 17-4 PH stainless steel specimens in different heat treatment and surface roughness conditions.
This article presents the data demonstrating the synergistic effect of surface roughness and heat treatment on the fatigue behavior of 17-4 PH stainless steel (SS) fabricated via laser beam powder bed fusion (LB-PBF) [1]. Two sets of specimens, in as-built and machined surface conditions, were heat treated using five different recommended procedures for 17-4 PH SS by ASTM A693. Axial fully-reversed fatigue tests (R = -1) were conducted on heat treated as-built and machined specimens. The stable hysteresis stress-strain data, as well as the maximum and minimum stress and strain values for the cycle in a log10 increment are included for all conducted fatigue experiments. In addition, fractography images are provided for selected set of specimens.


Advising parents to stop smoking. Opportunities and barriers in pediatric practice.
All pediatricians in Maine were surveyed by mail to assess their beliefs and attitudes about parental smoking and their current activities concerning advice on smoking cessation. The response rate to three mailings was 86%. Most pediatricians (91%) reported advising parents who smoke to quit and estimated spending an average of almost 5 minutes giving advice on how to quit smoking. Almost all pediatricians (94%) felt moderately or very confident in addressing passive smoking issues. However, only 46% felt moderately or very confident in advising parents how to stop smoking. Important barriers to providing advice on smoking cessation to parents included negative parental expectations and not having enough time. Only 6% of the pediatricians noted lack of reimbursement as a barrier. The majority of respondents (84%) were moderately or very willing to learn brief methods of giving advice on how to stop smoking to parents.


Protothecal granulomatous meningoencephalitis in a dog.
A case of central nervous system protothecosis in a dog is reported. A three-year-old male Maremma sheepdog was referred with a two month history of diarrhoea associated with progressive tetraparesis, depression and right circling. Stupor, severe proprioceptive deficits, bilateral decreased thoracic limb flexor reflexes and bilateral deficit of the menace reaction were detected on neurological examination and a multi-focal neurological localisation was suspected. Histopathological evaluation revealed multi-focal granulomatous foci in the thalamus, hippocampus and caudal brainstem containing numerous oval-rounded organisms with a thick, periodic acid-Schiff-positive and Gomori's methenamine silver-positive cell wall, a basophilic cytoplasm and one nucleus. Scattered sporangia containing two to four endospores were also observed. Morphological features were consistent with Prototheca species. Ultrastructurally, numerous degenerated algae were present within macrophages mainly lacking nuclei and cytoplasmic organelles. Generally, protothecosis in dogs is characterised by systemic signs because of a multi-organ involvement, and haemorrhagic colitis or ophthalmologic signs are the most frequent presenting signs. However, protothecosis should be added, also in Europe, to the list of the differential diagnoses in adult dogs with a multi-focal neurological localisation even in absence of other clinical signs.