Cessation of injecting drug use among street-based youth.
Young injecting drug users (IDUs) are at high risk for a number of negative health outcomes such as hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infection. However, very little is known about injecting drug-use patterns among this population, particularly with respect to cessation of injection. We sought to identify the factors associated with cessation of injection in a population of young street-based IDUs. A prospective cohort study design was used to assess long-term (> or = 1 year) cessation of drug injection. Data was collected between January 1995 and September 2000 in Montreal, Québec, Canada. Subjects were originally recruited from various street-based outreach programs in Montreal and, for this study, had to have reported injecting drugs within the prior 6 months at baseline or during follow-up and had to have completed at least two semiannual follow-up questionnaires. Cessation incidence rates stratified by duration of injection and adjusted hazard ratios (AdjHRs) were calculated. A Cox proportional hazards regression model was used to identify risk factors independently associated with cessation of drug injection. Of 502 young IDUs, 305 subjects met the inclusion criteria. Cessation of injection for approximately 1 year or more occurred in 119 (39%) of the young IDUs. The incidence of cessation was 32.6/100 person-years but consistently declined as duration of time spent injecting increased. Independent predictors of cessation of injection were currently injecting on a less than monthly or less than weekly basis (HR = 6.4; 95% confidence interval (CI): 3.0-13.6 and HR = 2.4; 95% CI = 1.1-5.3, respectively); currently injecting two or fewer different types of drug (HR = 2.1; 95% CI = 1.1-4.0); currently employed (HR = 1.7; 95% CI = 1.1-2.7); and having at least one parent born outside of Canada (HR = 1.4; 95% CI = 1.1-1.7). Independent predictors of not ceasing injection were currently attending a needle-exchange program (HR = 0.5; 95% CI = 0.3-0.8); and current homelessness (HR = 0.6; 95% CI = 0.4-1.0). The early sharp decline in cessation of drug injection followed by a consistent decrease in this rate suggest difficulties in breaking the habit later on in the drug injecting career. Intensity of drug use and factors which may help to stabilize the social environment of the young IDU may also influence the ability to stop injecting.


Strategies for referent tracking in electronic health records.
The goal of referent tracking is to create an ever-growing pool of data relating to the entities existing in concrete spatiotemporal reality. In the context of Electronic Healthcare Records (EHRs) the relevant concrete entities are not only particular patients but also their parts, diseases, therapies, lesions, and so forth, insofar as these are salient to diagnosis and treatment. Within a referent tracking system, all such entities are referred to directly and explicitly, something which cannot be achieved when familiar concept-based systems are used in what is called "clinical coding." In this paper, we describe the components of a referent tracking system in an informal way and we outline the procedures that would have to be followed by healthcare personnel in using such a system. We argue that the referent tracking paradigm can be introduced with only minor--though nevertheless ontologically important--technical changes to existing EHR infrastructures, but that it will require a radically different mindset on the part of those involved in clinical coding and terminology development from that which has prevailed hitherto.


The effect of diabetes mellitus on aortic prostanoid synthesis and serum cholesterol levels in the rat fed a high cholesterol diet.
The effect of diabetes mellitus on serum cholesterol and aortic microsomal prostanoid synthesis was studied in cholesterol fed male Lewis rats. Normal, diabetic and diabetic rats treated with pancreatic islets were divided into three diet subgroups, control diet, control +2% cholesterol for 8 weeks and control +2% cholesterol diet for 16 weeks. Serum glucose levels were elevated three-fold in the diabetic group compared to normal. Treatment with islets restored serum glucose to normal levels in diabetic rats. The 2% cholesterol diet did not significantly alter serum glucose levels in any of the groups. Body weights in the diabetic group were significantly lower than normal or diabetic rats treated with islets. Feeding 2% cholesterol for 16 weeks significantly increased weight in normal and islet treated diabetic rats but not in the diabetic group. Aortic microsomal prostanoid synthesis was similar in all experimental groups with 6-keto-PGF1 alpha (PGI2 metabolite) being the major product synthesized in all groups. Aortic microsomal prostanoid levels were not altered by the 2% cholesterol diet. Serum cholesterol levels increased 14-fold in the diabetic group which returned to the normal level in the diabetic animals treated with islets. These data show that diabetes does not alter aortic microsomal prostanoid levels in the rat. However, diabetes significantly increased serum cholesterol levels which were reversed by islet transplantation.


Studies on synergistic toxic effects of copper and dithiocarbamate pesticides with the ciliate protozoan Colpidium campylum (Stokes).
The toxicity of seven dithiocarbamates and interactions occurring with copper were studied with the ciliate protozoan Colpidium campylum. No product was toxic at 0.1 mg liter-1. Thiram and mancozeb are the most toxic products (lethal at 1 mg liter-1) and ziram and propineb the least toxic. Concerning interactions with copper, no or slight interactions were observed with propineb and mancozeb, although a strong synergistic toxic effect was observed in a previous work with two structurally related products, maneb and zineb. On the contrary, the responses observed with alkyl-related dithiocarbamates (ferbam and ziram) and ethylene bis-related dithiocarbamates (nabam, thiram, and metiram) are in correlation with the results known in the literature. The synergistic toxic effect of copper and dithiocarbamates thus seems to be related mainly to the alkyl- or the ethylene bis-dithiocarbamate structure, but is not constant for molecules associated with metals (propineb, mancozeb, maneb, and zineb).


Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes.
Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte-specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. In this study, we demonstrated that anthocyanins (cyanidin or cyanidin 3-glucoside) have the potency of a unique pharmacological function in isolated rat adipocytes. Treated adipocytes with anthocyanins enhanced adipocytokine (adiponectin and leptin) secretion and up-regulated the adipocyte specific gene expression without activation of PPARgamma in isolated rat adipocytes. The gene expression of adiponectin was also up-regulated in white adipose tissue in mice fed an anthocyanin supplemented diet. As one of the possible mechanisms, AMP-activated protein kinase activation would be associated with these changes, nevertheless, the AMP:ATP ratio was significantly decreased by administration of the anthocyanins. These data suggest that anthocyanins have a potency of unique therapeutic advantage and also have important implications for preventing obesity and diabetes.


When inhibition goes incognito: feedback interaction between spiny projection neurons in striatal function.
Theories about basal ganglia function have always been driven by our knowledge about the spiny projection neurons of the striatum. At the core of these theories lies the question of how, precisely, spiny projection neurons process cortical inputs. Most recently, studies demonstrating the role of spiny projection neurons in local synaptic GABA transmission have provided several new avenues for exploring striatal dynamics. They have also suggested new experimental directives for examining the specific ways in which spiny projection neurons both compete and cooperate through their local axon collaterals during cortical input processing.


Delayed hypoxia during pediatric posterior spinal fusion secondary to intraoperative pneumothorax: Case report.
Rarely will a pneumothorax caused intraoperatively not manifest signs such as hypoxia, tachypnea, and tachycardia until later. If this occurs, diagnosis and treatment with needle decompression or chest tube must happen quickly for patient safety.


Noninvasive predictors of sudden cardiac death in men with coronary heart disease. Predictive value of maximal stress testing.
In a follow-up study of 1,852 men with coronary heart disease, 195 deaths occurred within the first 3 years (33 +/- 13 months [mean +/- standard deviation]). Analysis of these cases indicated that the risk of sudden cardiac death in ambulatory men with clinical manifestations of coronary heart disease may be readily estimated from noninvasive clinical and exercise criteria. The important predictors are indexes of the severity of coronary heart disease and impairment of peak left ventricular function demonstrated with symptom-limited maximal exercise. The advantages of these predictors are that they may be elicited on the initial study as well as on follow-up noninvasive examinations of ambulatory patients. The appearance of nonelectrocardiographic predictors in serial examinations may provide an indication for invasive studies and be a more important finding than the ischemic S-T reponse to exertion.


SAMHD1 transcript upregulation during SIV infection of the central nervous system does not associate with reduced viral load.
Restriction of HIV-1 in myeloid-lineage cells is attributed in part to the nucleotidase activity of the SAM-domain and HD-domain containing protein (SAMHD1), which depletes free nucleotides, blocking reverse transcription. In the same cells, the Vpx protein of HIV-2 and most SIVs counteracts SAMHD1. Both Type I and II interferons may stimulate SAMHD1 transcription. The contributions of SAMHD1 to retroviral restriction in the central nervous system (CNS) have been the subject of limited study. We hypothesized that SAMHD1 would respond to interferon in the SIV-infected CNS but would not control virus due to SIV Vpx. Accordingly, we investigated SAMHD1 transcript abundance and association with the Type I interferon response in an SIV model. SAMHD1 transcript levels were IFN responsive, increasing during acute phase infection and decreasing during a more quiescent phase, but generally remaining elevated at all post-infection time points. In vitro, SAMHD1 transcript was abundant in macaque astrocytes and further induced by Type I interferon, while IFN produced a weaker response in the more permissive environment of the macrophage. We cannot rule out a contribution of SAMHD1 to retroviral restriction in relatively non-permissive CNS cell types. We encourage additional research in this area, particularly in the context of HIV-1 infection.


Colchicine injection in the inferior olivary nucleus increases the number of Purkinje cell dendritic spines.
The number of Purkinje cell dendritic spines was evaluated in the cerebellum of rats after injection of colchicine into the inferior olivary nucleus. In these conditions, the spines situated in the proximal (inner) part of the molecular layer were increased as compared to lumicolchicine-injected or non-injected control animals. Most postsynaptic targets for climbing fibers are located in the inner molecular layer and the fact that spines in this region increased when axonal transport was blocked in the climbing fibers suggests that the latter play a role in the control of spine formation.


The value of a quality improvement programme for panoramic radiography: a cluster randomised controlled trial.
To assess the value of a quality improvement programme for panoramic radiography. A prospective, cluster randomised controlled trial was conducted in 40 dental practices in England. Practices were randomly assigned into two groups, an 'active' practice receiving regular feedback on film quality and a 'control' practice receiving no feedback until the completion of the study. 800 panoramic radiographs were examined for technical and processing faults. Following the first feedback to the 'active' practices, 100 films showed that the films taken were a significant predictor of a reduction in the number of technical (effect coefficient 0.51 (standard error SE 0.06); P<0.001) and processing (effect coefficient 0.42 (SE 0.08); P<0.001) faults compared to those in 'control' practices (n=400). The 'active' practices continued to benefit from the second round of feedback, showing a marked reduction in technical (effect coefficient 1.31 (SE 0.06); P<0.001) and processing (effect coefficient 1.18 (SE 0.11); P<0.001) faults. Two months after completion of the study, a further 120 panoramic radiographs from 12 practices in each group were examined for quality. Significant differences between the two groups for both technical faults (effect coefficient 0.62 (SE 0.22); P=0.02) and processing faults (effect coefficient 0.65 (SE 0.17); P<0.001) were found. This cluster randomised controlled trial showed that distance feedback is an effective method in instructing dental practitioners to correct technical and processing errors experienced in producing panoramic radiographs. This intervention was effective in the short term whilst the practitioners were actively receiving feedback and for 8 weeks afterwards. Panoramic radiography quality is often poor due to a lack of knowledge of correct patient positioning. A failure to comply with manufacturers' instructions regarding the changing frequency for processing chemistry also compounds the problem. Distant feedback is effective in improving film quality in the short term and after 8 weeks.


Association of polymorphisms of STAT6 and SO(2) with Chinese childhood asthma: a case-control study.
To investigate the association of polymorphisms of STAT6 gene and air pollutants of PM(10), NO(2), and SO(2), with asthma in Chinese children. 418 subjects aged 14 years and under were recruited in a case-control study. The association between STAT6 polymorphisms and childhood asthma were tested by allele frequency, genotype analysis, and MDR analysis. Exposure to outdoor air pollutants was estimated by a 5-day moving average level. Statistical analyses were performed with SAS 9.1 software. Only 3 alleles of GT repeats at exon 1 of STAT6 were found in Chinese children. C258T and T710C were 2 new SNPs of STAT6 at 3'-UTR. Children who carried T allele of C258T were more common in asthma children than in control subjects (P<0.05). The MDR analysis showed that GT repeats, C258T and T710C of STAT6 polymorphisms interacted together in leading to susceptibility to childhood asthma among Chinese people. After confounding factors were controlled, such as SNP C258T, family history of asthma, frequency of influenza within a year, the 5-day average of SO(2) was tested to be a key risk factor of asthma in Chinese children (P<0.05). Chinese children differed in polymorphisms of STAT6 and in its relation with childhood asthma.


(Dis)similarity in Impulsivity and Marital Satisfaction: A Comparison of Volatility, Compatibility, and Incompatibility Hypotheses.
Impulsivity is negatively associated with relationship satisfaction, but whether relationship functioning is harmed or helped when both partners are high in impulsivity is unclear. The influence of impulsivity might be exacerbated (the Volatility Hypothesis) or reversed (the Compatibility Hypothesis). Alternatively, discrepancies in impulsivity might be particularly problematic (the Incompatibility Hypothesis). Behavioral and self-report measures of impulsivity were collected from a community sample of couples. Mixed effect polynomial regressions with response surface analysis provide evidence in favor of both the Compatibility Hypothesis and the Incompatibility Hypothesis, but not the Volatility Hypothesis. Mediation analyses suggest results for satisfaction are driven by perceptions of the partner's negative behavior and responsiveness. Implications for the study of both impulsivity and relationship functioning are discussed.


Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.
Papillary thyroid carcinomas in humans are associated with the ret/PTC oncogene and, following loss of p53 function, may progress to anaplastic carcinomas. Mice with thyroid-targeted expression of ret/PTC1 developed papillary thyroid carcinomas that were minimally invasive and did not metastasize. These mice were crossed with p53-/- mice to investigate whether loss of p53 would promote anaplasia and metastasis of ret/PTC1-induced thyroid tumors. The majority of p53-/- mice died or were euthanized by 17 weeks of age due to the development of thymic lymphomas, soft tissue sarcomas, and testicular teratomas. All ret/PTC1 mice developed thyroid carcinomas, but tumors in p53-/- mice were more anaplastic, larger in diameter, more invasive, and had a higher mitotic index than tumors in p53+/+ and p53+/- mice. Thyroid tumors did not metastasize in any of the experimental p53+/+ and p53+/- mice </=28 weeks of age or p53-/- mice </= 17 weeks of age; however, an older (170-day-old) male p53-/- mouse used to maintain the colony developed anaplastic thyroid carcinoma with liver metastases. These findings demonstrate that the lack of functional p53 in ret/PTC1 mice promotes anaplasia and invasiveness of thyroid carcinomas.


OSR1 downregulation indicates an unfavorable prognosis and activates the NF-κB pathway in ovarian cancer.
Odd-skipped related 1 (OSR1) has been reported as a tumor suppressor gene in various malignant tumors. The mechanism through which OSR1 regulates ovarian cancer (OC) progression remains unclear. Immunohistochemistry was utilized to evaluate OSR1 expression in patients with ovarian cancer. We investigated the association between clinicopathological parameters and OSR1 expression in OC patients and the influence of OSR1 expression on patient survival and prognosis. OC cells with OSR1 overexpression or knockdown were established and validated using Western blot and Quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The influence of OSR1 on the NF-κB pathway was examined by analyzing the p-IκBα, IκBα, p65, and p-p65 protein expression. In vitro assays, such as cell cycle assay, Cell Counting Kit-8 (CCK-8), transwell invasion assay, wound healing migration assay, enzyme-linked immunoassay (ELISA), and Annexin V/PI flow cytometry apoptosis assay, were conducted to explore the effect of OSR1 knockdown or dual inhibition of OSR1 and the NF-κB pathway on OC malignant biological behavior. OSR1 expression was downregulated in OC tissues, with significant associations observed between its expression and The International Federation of Gynecology and Obstetrics (FIGO) stage and tissue differentiation. Low OSR1 expression in OC patients correlated with reduced overall survival (OS) rates and poor prognosis. In vitro, experiments confirmed a negative correlation between OSR1 expression and NF-κB pathway activity. OSR1 knockdown facilitated OC cell malignant biological behavior, while the NF-κB pathway inhibitor (Bay 11-0782) reversed the impacts of OSR1 knockdown on cell proliferation, migration, invasion, and apoptosis. Our findings indicate that OSR1 is downregulated and associated with OC prognosis. OSR1 suppresses NF-κB pathway activity and inhibits OC progression by targeting the NF-κB pathway.


Chronic myeloid leukemia incidence, survival and accessibility of tyrosine kinase inhibitors: a report from population-based Lithuanian haematological disease registry 2000-2013.
Currently available chronic myeloid leukaemia (CML) survival reports have originated from more affluent countries. Herein we report the entire country data on incidence and survival of CML, as well as penetrance of tyrosine kinase inhibitors (TKIs) in Lithuania. We analyzed all patients (N = 601) from the national haematological disease monitoring system who were diagnosed with CML between 2000 and 2013. Crude (CR) and age-standardized (weighted) (ASW(R)) incidence and mortality rates, as well as 1-, 5-, and 10-year relative survival rates (RSR) were calculated. Information on TKI penetration is also reported. Throughout the entire 2000-2013 period the median age at diagnosis of CML patients was 62 years. The respective incidence and mortality CRs were 1.28 and 0.78, both characterized by decreasing trends over the observation period. A 5-year RSR increased from 0.33 [95 % CI, 0.27-0.40] in 2000-2004 to 0.55 [95 % CI, 0.47-0.63] in 2005-2009. However, the respective 5-year RSRs for patients aged 65-74 and ≥75 were only 0.33 [95 % CI, 0.24-0.42] and 0.18 [95 % CI 0.07-0.23] during the entire study period. TKI penetrance for CML patients grew from 1.5 % in 2000-2004 to 30.6 % in 2005-2009 and 69.1 % in 2010-2013. TKI penetrance was low in the older age groups (60 % for the 65-74 and 19 % for the ≥75 patient group, in 2010-2013). Relative CML survival in Lithuania steadily improved and paralleled the increase in TKI treatment availability. Patients above 64 years rarely received TKIs and their relative survival remained low throughout the observation period. The latency of TKI availability may have influenced the survival trends.


Polymer Morphological Change Induced by Terahertz Irradiation.
As terahertz (THz) frequencies correspond to those of the intermolecular vibrational modes in a polymer, intense THz wave irradiation affects the macromolecular polymorph, which determines the polymer properties and functions. THz photon energy is quite low compared to the covalent bond energy; therefore, conformational changes can be induced "softly," without damaging the chemical structures. Here, we irradiate a poly(3-hydroxybutylate) (PHB) / chloroform solution during solvent casting crystallization using a THz wave generated by a free electron laser (FEL). Morphological observation shows the formation of micrometer-sized crystals in response to the THz wave irradiation. Further, a 10-20% increase in crystallinity is observed through analysis of the infrared (IR) absorption spectra. The peak power density of the irradiating THz wave is 40 MW/cm(2), which is significantly lower than the typical laser intensities used for material manipulation. We demonstrate for the first time that the THz wave effectively induces the intermolecular rearrangement of polymer macromolecules.


Cooperation between heparin-binding EGF-like growth factor and interleukin-6 in promoting the growth of human myeloma cells.
Interleukin-6 (IL-6) is a major survival and proliferation factor of human malignant plasma cells and IL-6 dependent myeloma cell lines can be obtained from patients with terminal disease. We show here that mutated diphtheria toxin, a specific inhibitor of heparin-binding epidermal growth factor-like growth factor (HB-EGF), blocked the IL-6-induced growth of two myeloma cell lines (XG-1 and XG-14) and did not significantly affect that of two other cell lines (XG-6 and XG-13). The IL-6 mediated growth of myeloma cells was also inhibited by antibodies to ErbB1, a receptor for HB-EGF. The XG-1 and XG-14 cell lines that are sensitive to HB-EGF inhibitors overexpressed HB-EGF and EGF receptor (ErbB1) genes. They also overexpressed CD9, a tetraspanin that binds to the heparin-binding domain of HB-EGF and is critical for promoting ErbB1 activation by HB-EGF. The XG-6 and XG-13 myeloma cells that were not significantly sensitive to HB-EGF antagonists, poorly expressed HB-EGF, ErbB1 and CD9 genes or proteins. We demonstrated that recombinant HB-EGF supported the long-term growth of myeloma cells, as did IL-6. The myeloma cell growth factor activity of HB-EGF was completely inhited by antibodies to ErbB1, but also by antibodies to gp130 IL-6 transducer or to IL-6. These data indicate that in the XG-1 and XG-14 IL-6-dependent myeloma cell lines, the CD9/HB-EGF/erbB1 and the IL-6/IL-6R/gp130 pathways cooperate synergistically to trigger myeloma cell growth. They suggest that inhibitors of the EGF receptor or HB-EGF may be useful for inducing myeloma cell apoptosis in patients with multiple myeloma.


Who Restores Hip Biomechanics More Effectively after a Femoral Neck Fracture? Comparison of Total Hip Arthroplasties Performed by Either Hip Surgeons or Orthopaedic Residents.
This study aims to analyze the ability to restore hip biomechanics in patients who undergo total hip arthroplasty for displaced femoral neck fractures operated by either hip surgeons (HSs) or orthopaedic residents (ORs). We retrospectively compared 95 patients treated by HSs (group A) with 110 patients treated by ORs (group B). Leg-length discrepancy, femoral offset (FO), center of rotation (COR), acetabular inclination, and acetabular anteversion were evaluated on postoperative radiographs using the healthy contralateral hip as control. The median leg-length discrepancy was 2 mm for both groups (P = .74). The leg length was increased in 54% of the HS group and 57% of the OR group (P = .13). The median FO difference of groups A and B were 7 mm and 5.5 mm, respectively (P = .14). FO was increased in 80% of the HS group and 69% of the OR group (P = .19). Median discrepancies of the horizontal and vertical CORs were not statistically relevant, with P-values of .69 and .14, respectively. The horizontal COR was slightly medialized in 58% of the HS group and 53% of the OR group (P = .003). The vertical COR was slightly proximal in 66% of the HS group and 76% of the OR group (P = .28). The median acetabular inclination angles of groups A and B were 41° and 40°, respectively (P = .62). The median anteversion angle was 19° for both groups (P = .89). The horizontal COR was the only measurement with statistical significance. To conclude, ORs under supervision are as reliable as HSs to properly restore hip biomechanics in patients who undergo total hip arthroplasty for displaced femoral neck fractures.


Shelf life determinants and enzyme activities of pearl millet: a comparison of changes in stored flour of hybrids, CMS lines, inbreds and composites.
Shelf life of pearl millet flour is very short because of rapid development of rancidity. This investigation was carried out in view of generating breeding material for development of low rancid pearl millet hybrids/varieties. Flour of twenty-one genotypes; seven hybrids, seven CMS lines, five inbreds and two composites stored in covered aluminium boxes at 37 °C for 30 days along with respective fresh flour was analysed for shelf life indicators/determinants. Crude fat content and fat acidity (FA) of fresh flour of the genotypes varied from 3.8 to 7.2% and 11 to 75 mg KOH/100 g d.m., respectively. FA in stored flour ranged between 180 and 330 mg KOH/100 g d.m. After storage, magnitude of decrease in pH of water extract of flour of the genotypes varied from 0.15 to 0.44. Activity of peroxidase (POX) varied from 378 to 588 units in control flour and irrespective of the genotypes decreased upon storage. Increase in FA (difference between FA of fresh and stored flour) rather total build up of FA was positively associated with crude fat content (r = 0.440*) indicated comparatively more prominent role of lipolytic enzymes. Chemical changes taking place in water soluble fraction of flour were independent of fat content as no correlation was discerned between fat content and decrease in pH. Among the hybrids, HHB 197 had lowest crude fat content (4.7%), lowest total build up FA (212 mg KOH/100 g d.m.), slowest increase in FA (191 mg KOH/100 g d.m.), least decrease in pH (0.31) of water soluble fraction flour during storage and lowest activity of POX in fresh flour (377 units/g d.m). Among all the tested CMS lines, inbreds and composites, HBL 11 showed pattern of quantitative changes in FA, pH and POX activity similar to the hybrid HHB 197 and was identified a promising inbred for developing low-rancid pearl millet variety or hybrid.


Effect of Preoperative Geriatric Evaluation on Outcomes After Elective Surgery: A Population-Based Study.
Randomized and nonrandomized single-center studies suggest that preoperative geriatric evaluation improves postoperative outcomes in older adults. The generalizability and population-level effect of preoperative geriatric evaluation has not been determined. Our objective was to measure the adjusted association between preoperative geriatric evaluation and postoperative outcomes. Multilevel multivariable regression model analysis of a population-based historical cohort. Publicly funded universal healthcare system in Ontario, Canada. All adults aged 65 and older having major, elective, noncardiac surgery from 2002 to 2014 (N = 266,499). We studied geriatric consultations and comprehensive assessments performed in the 4 months prior to surgery. These were identified using validated methods. Ninety-day survival (primary outcome), in-hospital complications, length of stay, 30-day readmissions, need for supported discharge, and 90-day costs of care. The 7,352 participants (2.8%) who had a preoperative geriatric evaluation had longer 90-day survival than those who who did not (adjusted hazard ratio = 0.81, 95% confidence interval = 0.68-0.95). Length of stay and complication rates did not differ between groups, but participants evaluated by a geriatrician preoperatively had higher rates of supported discharge, readmission rates, and costs of care. Sensitivity analyses supported the association between preoperative geriatric assessment and 90-day survival. In individuals aged 65 and older undergoing major, elective, noncardiac surgery, preoperative geriatric evaluation was associated with longer 90-day survival, but it is used infrequently. Given these results, and those of previous small studies, the influence of a geriatric evaluation on postoperative outcomes should be determined in a multicenter randomized trial.


Left atrial appendage closure: An emerging option in atrial fibrillation when oral anticoagulants are not tolerated.
Atrial fibrillation is associated with a risk of stroke, primarily from embolization of clots that form in the left atrial appendage. This structure has been targeted to reduce stroke risk in patients who have contraindications to oral anticoagulation. This article appraises the current literature describing surgical and percutaneous isolation of the left atrial appendage.


Structural features and rheological behavior of a water-soluble polysaccharide extracted from the seeds of Plantago ciliata Desf.
A water-soluble polysaccharide (PSPC) was extracted from the seeds of Plantago ciliata Desf., a spontaneous Algerian Saharan plant by a hot aqueous extraction then purified by successive ethanolic precipitations. The final extraction yield for PSPC was close to 18.6% (w/v). PSPC was then investigated regarding its global composition, structural features and rheological properties. PSPC is a neutral arabinoxylan, composed of a β-(1,3)/β-(1,4)-d-xylan backbone with side chains of Xylp, and Araf residues attached in O-2 and O-3 positions. The macromolecular characteristics of PSPC in water was determined by SEC/MALLS, with a high molecular weight (Mw) of 700 kDa, a low polydispersity index (PDI) of 1.47 and an intrinsic viscosity [η] close to 157 mL/g. PSPC showed a pseudoplastic behavior in semi-dilute media and the critical overlay concentration (C*) was estimated around 0.32-0.37% (w/v). This current research has supplied original structural information on a new arabinoxylan which could be particularly useful as a novel source of soluble fiber belonging to psyllium.


Do hypokyphotic adolescent idiopathic scoliosis patients treated with Ponte osteotomy obtain a better clinical efficacy? A preliminary retrospective study.
A retrospective case-control study. To evaluate whether Ponte osteotomy improves thoracic kyphosis and to determine its clinical efficacy in hypokyphotic adolescent idiopathic scoliosis (AIS). Eighty consecutive Lenke type 1 AIS patients with hypokyphotic curves who underwent posterior spinal fusion by one spine surgeon at a single institution were recruited. According to whether Ponte osteotomy was performed, the patients were divided into two groups. The preoperative, immediate, one-year postoperative, and two-year postoperative radiographs were analyzed. The demographic characteristics, surgical information, radiographic parameters, Scoliosis Research Societye-22 (SRS-22) questionnaire, and complications were compared. The sagittal alignment and coronal alignment were both improved in the Ponte group and the control group postoperatively. There was no significant difference in the preoperative parameters between the two groups, except the TL/L, CB, and LL. Significant differences were found in the MT (15.18° ± 2.84° vs. 20.33° ± 3.75°, P < 0.001) and TK (24.23° ± 2.71° vs. 19.93° ± 2.38°, P < 0.001) at the two-year follow-up. The Ponte group had a longer operation time and more intraoperative blood loss. No significant difference was observed between the groups in the SRS-22 scores at the final follow-up. Ponte osteotomy could obtain better coronal correction and sagittal contour restoration in AIS patients with hypokyphosis. However, Ponte osteotomies might lead to more intraoperative blood loss and longer operation time. Moreover, no discrepancy was found in the postoperative health-related quality of life of the included patients. Therefore, we considered that the Ponte osteotomy may be an alternative method to restore the desired thoracic kyphosis, which needs further study.


Litter inputs exert greater influence over soil respiration and its temperature sensitivity than roots in a coniferous forest in north-south transition zone.
The changes in carbon inputs of litter and roots to forest soils caused by climate change will result in a serious cascade effect on soil respiration and its temperature sensitivity (Q10). To differentiate and quantify the effects of surface litter and living roots on soil respiration and Q10, and further explore the role of abiotic factors and microbial properties on soil respiration and Q10, a short-term (two years) detritus input and removal treatment experiment was conducted in a coniferous forest of central China. Soil temperature, soil moisture, C/N, microbial biomass and community composition were analyzed to explore the drive mechanisms of soil respiration and Q10 in response to carbon inputs. The results showed that litter addition increased soil respiration by 22 %, while litter or roots removal did not affect soil respiration, which might be ascribed to the "priming effects" mediated by fresh plant litter. We also found that litter addition increased Q10, while litter removal decreased Q10. Litter addition significantly enhanced the microbial biomass for any single functional group and altered soil microbial community composition. Structural equation model further proved that microbial biomass and community composition exerted stronger impacts on Q10 than do soil abiotic factors. Soil moisture, microbial biomass and community structure were main factors in predicting soil respiration. The study highlights the important role of litter inputs compared with living roots in carbon cycling in short-term and deepens our understanding on the complex relationships among soil respiration, soil micro-environment and microbial community composition.


CDC recommendations for the 2018-2019 influenza season.
Vaccines will contain a new A (H3N2) component and B antigen. The live attenuated influenza vaccine returns as an option for those 2- to 49-years of age.


Regulation and function of estrogen and progesterone receptor systems.
We have developed and validated assay methods which are appropriate for studying the subcellular distribution of estrogen receptor (Re) and progesterone receptor (Rp) in hamster uterus during the estrous cycle and pregnancy. Cytosol receptors were monitored by conventional procedures, and nuclear receptors were extracted from nuclei at 2 C using 0.5 M KCl in buffer containing glycerol and measured by ligand exchange during incubation with [3H] progesterone (P) at 2 C for 24 h or [3H] estradiol-17 beta (E2) at 30 C for 1 h. The nuclear exchange assay described herein measures total receptor and also permits estimation of unlabeled steroid in the nuclear KCl extract. Nuclear Rp translocation was shown to be target-tissue specific, hormone specific, and dependent on P dosage under in vivo conditions. The duration of nuclear Rp retention was about 6 h following exogenous P treatment. During the estrous cycle, Re and Rp levels in uterine cytosol and nuclei varied in response to the changing pattern of E2 and P secretion. Our results document a positive relationship between serum E2, nuclear Re and cytosol Rp levels during the follicular phase of the cycle. Nuclear Rp remained low on cycle days 1--3, and increased abruptly on day 4 coincident with preovulatory P secretion and cytosol Rp depletion. Nuclear Rp translocation during the preovulatory period on cycle day 4 was associated with a marked decline in nuclear Re, and the latter was demonstrated to be a rapid (2--4 h) response to P action rather than serum E2 withdrawal. The negative effect of P on nuclear Re levels may represent a fundamental mechanism for P antagonism of E action. Cytosol and nuclear Rp levels in deciduomal and myometrial tissue were responsive to experimental alteration of serum P, indicating that nuclear Rp is maintained by a continuous process of P-induced Rp translocation. Of interest was the finding in pregnant animals that Re levels declined dramatically in deciduoma as compared to myometrium. The loss of cytosol and nuclear Re from deciduomal cells cannot be attributed to changes in serum E2 or P. Thus, the intracellular regulation of Re numbers may change during differentiation of certain target cells such as those found in the deciduoma.


Somatic growth and developmental functioning in children receiving prolonged home total parenteral nutrition.
Growth and psychomotor development in nine infants receiving prolonged home total parenteral nutrition (TPN) were studied longitudinally from infancy to 3 years of age. Although these children had received TPN for, on average, 79% of their lives, normalization of somatic growth occurred by 2 years of age in all of them. Three children maintained average or above average levels of developmental performance over the 3-year study period. Another four children had initially delayed development but average or above average developmental scores by 18 months. In two children the rate of development gradually slowed without obvious cause, so that by 3 years they functioned in the below average to mildly retarded range.


Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells.
CCN2/CTGF is known to be involved in tooth germ development and periodontal tissue remodeling, as well as in mesenchymal tissue development and regeneration. In this present study, we investigated the roles of CCN2/CTGF in the proliferation and differentiation of periodontal ligament cells (murine periodontal ligament-derived cell line: MPL) in vitro. In cell cultures of MPL, the mRNA expression of the CCN2/CTGF gene was stronger in sparse cultures than in confluent ones and was significantly enhanced by TGF-beta. The addition of recombinant CCN2/CTGF (rCCN2) to MPL cultures stimulated DNA synthesis and cell growth in a dose-dependent manner. Moreover, rCCN2 addition also enhanced the mRNA expression of alkaline phosphatase (ALPase), type I collagen, and periostin, the latter of which is considered to be a specific marker of the periosteum and periodontium; whereas it showed little effect on the mRNA expression of typical osteoblastic markers, e.g., osteopontin and osteocalcin. Finally, rCCN2/CTGF also stimulated ALPase activity and collagen synthesis. These results taken together suggest important roles of CCN2/CTGF in the development and regeneration of periodontal tissue including the periodontal ligament.


The respiration rate of the resting eggs of Leptodora kindti (Focke 1844) and Bythotrephes longimanus Leydig 1860 (Crustacea, Cladocera) at environmentally encountered temperatures.
Respiration rates of the resting eggs of Leptodora kindti and Bythotrephes longimanus were measured in the laboratory at temperatures between 2.4 and 6.2° C. Results are used to explore the relationships between the duration of dormancy and egg size in the natural habitat.


Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC.
Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Thus, current iPSC-based gene therapy approach reveals a limitation that is not readily applicable to iPSCs with ALK2 mutation. Here we developed a simplified one-step procedure by simultaneously introducing reprogramming and gene-editing components into human fibroblasts derived from patient with FOP syndrome, and genetically treated it. The mixtures of reprogramming and gene-editing components are composed of reprogramming episomal vectors, CRISPR/Cas9-expressing vectors and single-stranded oligodeoxynucleotide harboring normal base to correct ALK2 c.617G>A. The one-step-mediated ALK2 gene-corrected iPSCs restored global gene expression pattern, as well as mineralization to the extent of normal iPSCs. This procedure not only helps save time, labor and costs but also opens up a new paradigm that is beyond the current application of gene-editing methodologies, which is hampered by inhibitory pluripotency-maintenance requirements, or vulnerability of single-cell-dissociated iPSCs.


Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease.
Glutamine is a major fuel and an important nitrogen source for the small intestinal cell. It plays a key role in maintaining mucosal cell integrity and gut barrier function. Increased permeability may be a factor in the pathogenesis of Crohn's disease and may be an interesting parameter in the follow-up of the disease. Therefore, the aim of this study was to examine whether oral glutamine supplements are able to restore an increased intestinal permeability in patients with Crohn's disease. The inclusion criteria for the study were Crohn's disease and a disturbed small intestinal permeability for 51Cr-EDTA. Of 38 patients screened, 18 had an increased permeability (6 hours urinary excretion >1.1% of label recovered in urine). Fourteen patients were included in the study and were randomized to receive either oral glutamine (7 g three times per day; n = 7) or placebo (7 g glycine three times per day; n = 7) in addition to their normal treatment during a 4-week period. The study was performed in a double-blind manner. Baseline permeability (mean +/- SD) was 2.32%+/-0.77% dose in the glutamine group and 2.29%+/-0.67% dose in the placebo group. Permeability did not change significantly after glutamine (3.26%+/-2.15% dose) or after placebo (2.27%+/-1.32% dose). There was no significant effect on plasma glutamine, plasma glutamate, plasma ammonium, Crohn's disease activity index, C-reactive protein, or nutritional status. Oral glutamine supplements, in the dose administered, do not seem to restore impaired permeability in patients with Crohn's disease.


Responses of single auditory cortical neurons to tone sequences.
The responses of single neurons in the primary and secondary auditory cortex of cat were recorded during the presentation of sequences consisting of five tones of different frequencies. Discharges to tones within these sequences usually (84%) exhibited a dependence on the 'direction' of the sequence (ascending, descending, or mixed frequencies). For sequences consisting of 5 tones of identical frequency (monotone) the response often depended on serial position, including cases in which the neuron only responded to later tones in the sequence. Comparison of responses to heterogeneous and monotone sequences showed that response dependence on serial position was a factor in response dependence on sequence direction. Auditory cortical neurons can exhibit stronger responses to a tone presented in a sequence than to the same tone presented alone. Hence, the responses to tones within sequences may not be highly predictable from the responses to isolated tones.


Lactation after breast conserving therapy, including radiation therapy, for early breast cancer.
Two patients who underwent breast conservation including radiotherapy for early breast carcinoma are described and who subsequently delivered healthy newborn infants. One of the two patients lactated from both the irradiated and the non-irradiated breast; whereas the other patient did not lactate from the irradiated side. The treatment and implications are discussed.


Plasma homocysteine levels in noninsulin-dependent diabetes mellitus with retinopathy and neovascular glaucoma.
This study was designed to evaluate plasma homocysteine levels in noninsulin-dependent diabetes mellitus patients (NIDDM) with preproliferative retinopathy and neovascular glaucoma. The experimental goal was to determine the relationship between plasma homocysteine content and the development of microvascular lesions. Plasma homocysteine levels were assessed in three experimental groups consisting of healthy controls (n = 30), NIDDM patients with preproliferative retinopathy (n = 20) and NIDDM patients with neovascular glaucoma (n = 20). Homocysteine levels were determined via a fluorescence polarization immunoassay method by an Abbot IMX instrument. Plasma homocysteine levels in NIDDM patients with preproliferative retinopathy and neovascular glaucoma (n = 40) were found to be significantly higher than those of controls (n = 30) (p < 0.01). When statistical analysis was performed separately among the three experimental groups, no significant difference in plasma homocysteine levels were found in patients with preproliferative retinopathy compared to controls. However, homocysteine levels in patients with neovascular glaucoma were found to be significantly higher than the control group (p < 0.001). No significant difference in plasma homocysteine levels could be detected between patients with preproliferative retinopathy and neovascular glaucoma. Hyperhomocysteinemia is a risk factor for the development of microvascular lesions in patients with NIDDM but cannot be used as a marker to assess the progression of lesions observed in neovascular glaucoma.


Accuracy of CBCT measurements of a human skull.
The purpose of this study is to assess the accuracy and reproducibility of cone-beam computed tomography (CBCT) measurements of a human dry skull by comparing them to direct digital caliper measurements. Heated gutta-percha was used to mark 13 specific distances on a human skull, and the distances were directly measured using a digital caliper and on CBCT images obtained with Iluma (3M Imtec, OK, USA) and 3D Accuitomo 170 (3D Accuitomo; J Morita Mfg. Corp., Kyoto, Japan) CBCT imaging systems. Iluma images were obtained at 120 kVp and 3.8 mA and reconstructed using voxel sizes of 0.2 and 0.3 mm(3). Accuitomo images were obtained at 60 kVp and 2 mA and a voxel size of 0.250 mm(3). In addition, 3-D reconstructions were produced from images obtained from both systems. All measurements were made independently by three trained observers and were repeated after an interval of 1 week. Agreement between observers and image type was assessed by calculating Pearson correlation coefficients, with a level of significance set at p < 0.05. Pearson correlation coefficients between readings ranged from 0.995 to 1 for all image types. Correlations among observers were also very high, ranging from 0.992 to 1 for the first reading and from 0.992 to 1 for the second reading for the different image types. All CBCT image measurements were identical and highly correlated with digital caliper measurements. Accuracy of measurements of various distances on a human skull obtained from different CBCT units and image types is comparable to that of digital caliper measurements.


Fluorescence microscopical visualization of elastic fibres using basic fuchsin.
We show that fluorescence microscopy after staining of tissue sections with basic fuchsin (BF) can be used successfully for the demonstration of elastic fibres. Using double staining with BF and antibodies reacting with microfibrils of elastic fibres (anti-SAP) we showed that BF reacts with the elastin core of elastic fibres and the elastin poor terminal branches of the subepidermal elastic fibre system. Small amounts of bound BF were easily seen by fluorescence microscopy (FL) but not by ordinary light microscopy. Both frozen sections and sections of paraffin embedded tissues could be stained. The BF-FL staining procedure is simple to perform and, due to its selectivity, it may be useful for detecting elastic fibres in various tissues at the light microscopical level.


Electrospinning Fabrication Methods to Incorporate Laminin in Polycaprolactone for Kidney Tissue Engineering.
Today's treatment options for renal diseases fall behind the need, as the number of patients has increased considerably over the last few decades. Tissue engineering (TE) is one avenue which may provide a new approach for renal disease treatment. This involves creating a niche where seeded cells can function in an intended way. One approach to TE is combining natural extracellular matrix proteins with synthetic polymers, which has been shown to have many positives, yet a little is understood in kidney. Herein, we investigate the incorporation of laminin into polycaprolactone electrospun scaffolds. The scaffolds were enriched with laminin via either direct blending with polymer solution or in a form of emulsion with a surfactant. Renal epithelial cells (RC-124) were cultured on scaffolds up to 21 days. Mechanical characterization demonstrated that the addition of the protein changed Young's modulus of polymeric fibres. Cell viability and DNA quantification tests revealed the capability of the scaffolds to maintain cell survival up to 3 weeks in culture. Gene expression analysis indicated healthy cells via three key markers. Our results show the importance of hybrid scaffolds for kidney tissue engineering.


Isolation of growth suppressors from a cDNA expression library.
We describe an experimental procedure for the isolation of growth inhibitory sequences from a complex cDNA library. This approach first takes advantage of the SETGAP technique (selectable expression of transient growth arrest phenotype) to enrich for growth inhibitory sequences, followed by a screening procedure to identify individual cDNAs that inhibit cell proliferation. Here we provide a detailed description of the experimental protocol and report the characterization of two cDNA sequences isolated in our initial screen of a mouse cDNA library. One of these cDNAs encodes the mouse ubiquitin-conjugation enzyme UbcM2. The other encodes a truncated form of a novel WD40 repeat protein, named Bopl, which is conserved from yeast to human. Together, these results demonstrate a new approach for the isolation of growth suppressors from cDNA libraries, and identify a previously unknown gene likely to be involved in growth control.


Further supporting evidence of beneficial subthalamic stimulation in Parkinson's patients.
Twenty-two patients with Parkinson's disease were treated by implanting electrodes in the subthalamic nucleus. The follow-up evaluation was conducted at one (22 patients) and two years (9 patients). Significant improvement in the Unified PD Rating Scale scores was found. Tremor diminished 100% in the on drug/on stimulation and 70% off drug/on stimulation state. Rigidity decreased by 68% in the on drug/on stimulation and by 52% in off drug/on stimulation state. Subthalamic stimulation is reliable.


Contralateral suppression of transient-evoked otoacoustic emissions in children with sickle cell disease.
In previous studies, otoacoustic emissions (OAEs) have been found to be larger in normal-hearing children with sickle cell disease (SCD). It was hypothesized that some dysfunction or reduction in the medial olivocochlear efferent suppression of outer hair cell activity was responsible for this phenomenon. To test this hypothesis, contralateral suppression of transient-evoked otoacoustic emissions (TEOAEs) was examined in children with and without SCD. Thirteen African American school-aged normal-hearing children with homozygous SCD and 13 age- and gender-matched control children participated. TEOAEs were obtained bilaterally with 80 dB peSPL nonlinear click stimuli. To examine contralateral suppression, TEOAEs were obtained with 60 dB peSPL linear click stimuli with and without a contralateral 65 dB SPL white noise suppressor. Overall and half-octave band TEOAE levels were found to be larger in children with SCD relative to the normal control children (p < 0.05), consistent with previous reports of increased OAE levels. There was no significant difference (p > 0.05) in the absolute or proportional amount of TEOAE suppression as a function of group and ear. There were also no significant correlations or linear predictive relationships between TEOAE suppression and TEOAE level for either ear or group (p > 0.05). These findings do not support the notion that increased OAE levels in children with SCD are a consequence of abnormal medial olivocochlear system function as assessed with contralateral suppression of TEOAEs.


Erythrocyte sodium-lithium countertransport activity is inversely correlated to adiponectin, retinol binding protein 4 and body height.
We have previously described that the sodium/lithium countertransport (SLC) in the erythrocyte cell membrane is closely linked to obesity and insulin resistance. Adiponectin and retinol-binding protein 4 (RBP-4) are believed to affect obesity and insulin resistance. In the present study, we aimed to further characterize the relationship between SLC, inflammatory markers, adiponectin and RBP-4. We included 93 clinically healthy 58-year-old men selected to display variations in insulin sensitivity. High sensitivity C-reactive protein (hs-CRP), TNF-alpha, soluble TNF-alpha-receptors (sTNFR) 1 and 2, IL-6 and RBP-4 were measured using antibody-based techniques. Adiponectin was determined by a radioimmunoassay kit. The lithium concentration in the special flux medium was measured by atomic absorption spectrophotometry. In univariate analyses, SLC correlated negatively with RBP-4 (r(s) = -0.256, p = -0.017) and to adiponectin (r(s) = -0.316, p = 0.003) and positively with TNF-alpha (r(s) = 0.346, p = 0.001) and hs-CRP (r(s) = 0.288, p = 0.005). There were no statistically significant correlations with sTNFR 1 or 2 or IL-6. SLC was negatively associated to body height (r(s) = -0.256, p = 0.013). We are the first to report that SLC correlates negatively with adiponectin and RBP-4. This finding is intriguing, as adiponectin is anti-inflammatory and anti-diabetic whereas RBP-4 supposedly decreases insulin sensitivity. We also observed a negative association between SLC activity and body height indicating that SLC activity is not primarily influenced by fat mass. The positive association of SLC with markers of inflammatory activity such as TNF-alpha and hs-CRP is in line with the proposed link between inflammation and insulin resistance.


Fusidic acid-dependent ribosomal complexes protect Escherichia coli ribosomes from the action of the type 1 ribosome-inactivating protein crotin 2.
The type 1 ribosome-inactivating protein crotin 2 depurinated Escherichia coli ribosomes which, upon treatment of the isolated rRNA with acid aniline, released a fragment of around 240 nucleotides whose 5'-end sequence was 5'-GAGGACCGGAGUGGAC-3'. The formation of fusidic acid-dependent ribosomal complexes completely prevented release of the fragment. Ribosomes from crotin 2-pretreated fusidic acid complexes were insensitive to acid aniline. They released the RNA fragment only after a second treatment with crotin 2 and acid aniline whereas unprotected ribosomes released the fragment directly after acid aniline.


Dupuytren contracture: using qualitative data to inform a conceptual framework for shared decision-making.
Multiple treatment options are available to patients with Dupuytren contracture, making shared decision-making complex. Our rigorous qualitative analysis sought to understand patient perceptions of shared decision-making in Dupuytren contracture treatment and create a conceptual framework to optimize patient-physician communication. We interviewed 30 patients with Dupuytren contracture to learn about their experience with treatment selection. The following themes were integral to shared decision-making for Dupuytren contracture treatment: discussing disease progression and treatment initiation, presenting all available treatment options, assessing patients' pre-existing biases towards treatment, patient values and preferences for treatment trade-offs, treatment risks and benefits, physician recommendation and active patient participation. This model can optimize communication about treatment options and expectations for relevant outcomes including, recovery time, contracture recurrence, complications, and treatment-related expenses.Level of evidence: V.


[Sjögren's syndrome and non-Hodgkin's lymphoma: from pathophysiology to treatment].
Although infrequent, the development of non-Hodgkin's lymphoma (NHL) during the course of Sjögren's syndrome represents a major complication. Nethertheless, most NHL developing in patients with Sjögren's syndrome are B cell lymphomas involving the marginal zone, localized to extranodal sites. Predictive factors include lymphadenopathy, splenomegaly, neutropenia, cryoglobulinemia and low C4 levels. The treatment of B cell lymphomas depends on its nature and localization. Biotherapies targeting the B lymphocyte, such as rituximab, a chimeric monoclonal anti-CD20 antibody, or more recently targeting BAFF can be proposed.


The effects of timing and application of vibration on muscular contractions.
The effect of vibration stimulation on muscular strength is an emerging field of research and very little comprehensive work has been conducted at this stage. There will be no effects of timing or application of vibration stimulation on muscular strength and activation across isometric, isokinetic and concentric isotonic contractions. There were 28 recreational athletes who participated in this study. Their characteristics were: (mean +/- SD) age, 22.8 +/- 5.6 yr; height, 174.1 +/- 8.8 cm; and body mass, 78.0 +/- 13.6 kg. The vibration stimulation was delivered at 50.42 +/- 1.16 Hz with an acceleration of 13.24 +/- 0.18 ms(-2). A series of one-way ANOVAs revealed significant (p < 0.05) improvements of 14.7 +/- 2.9% and 15.3 +/- 3.1% above normal contraction levels for concentric isotonic strength during and after the vibration stimulation, respectively. No significant improvements in isometric and isokinetic strength were evident. Concurrent measurement of electromyography (EMG) presented significant improvements during stimulation of 30.1 +/- 14.6%, 43.0 +/- 13.0%, and 107.1 +/- 44.4% in mean activation of rectus femoris (RF) for the isometric, isokinetic, and concentric isotonic contractions, respectively. Synchronous collection of vibromyography (VMG) during stimulation displayed a significant decrease of -6.4 +/- 1.5%, -5.1 +/- 1.2%, and -4.1 +/- 1.7% in mean VMG activity of RF for the isometric, isokinetic, and concentric isotonic contractions, respectively. Significant improvements in muscular strength and activation for concentric isotonic contractions performed during an applied vibration suggest that the optimal timing of a vibratory stimulation would be while the participant is contracting isotonically. However, further research needs to be conducted to establish the exact mechanism behind these improvements.


Datasets for characterizing extreme events relevant to hydrologic design over the conterminous United States.
Despite the close linkage between extreme floods and snowmelt, particularly through rain-on-snow (ROS), hydrologic infrastructure is mostly designed based on standard precipitation Intensity-Duration-Frequency curves (PREC-IDF) that neglect snow processes in runoff generation. For snow-dominated regions, such simplification could result in substantial errors in estimating extreme events and infrastructure design risk. To address this long-standing problem, we applied the Next Generation IDF (NG-IDF) technique to estimate design basis extreme events for different durations and return periods in the conterminous United States (CONUS) to distinctly represent the contribution of rain, snowmelt, and ROS events to the amount of water reaching the land surface. A suite of datasets were developed to characterize the magnitude, trend, seasonality, and dominant mechanism of extreme events for over 200,000 locations. Infrastructure design risk associated with the use of PREC-IDF was estimated. Accuracy of the model simulations used in the analyses was confirmed by long-term snow data at over 200 Snowpack Telemetry stations. The presented spatially continuous datasets are readily usable and instrumental for supporting site-specific infrastructure design.


Hemocytes from the tobacco hornworm Manduca sexta have distinct functions in phagocytosis of foreign particles and self dead cells.
Phagocytosis is an important innate immune response against microbial infections and an effective mechanism to eliminate apoptotic cells. In vertebrates, phagocytes such as macrophages and dendritic cells are involved in phagocytosis. We demonstrate here that insect hemocytes have distinct functions in phagocytosis of foreign particles and self dead cells. Plasmatocytes from the tobacco hornworm Manduca sexta were major hemocytes involved in phagocytosis of non-self microsphere beads, whereas granulocytes were apparently the only hemocytes that phagocytose self dead cells. We also showed that M. sexta immulectin-2, a pattern recognition receptor that protects larvae from bacterial infection, has an opsonic activity in phagocytosis. Immulectin-2 bound to the surface of granulocytes from the naïve larvae, but more immulectin-2 bound to plasmatocytes when larvae were injected with microsphere beads. Coupling of immulectin-2 onto microsphere beads enhanced in vitro phagocytosis of the beads. Our results suggest that insect hemocytes can have specialized functions similar to vertebrate phagocytes in phagocytosis, and pattern recognition receptors may function as opsonins to enhance phagocytosis.


Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27.
To study the local and systemic levels of the tumour necrosis factor-alpha in patients with active uveitis and to determine the implication of TNF-alpha in rheumatological uveitis and to observe if this relationship is more significant in the B27 positive patients. Patients were selected on the basis of a diagnosis of uveitis of any aetiology. Data from 23 patients were stratified into two categories according to the presence or absence of systemic rheumatic disease. The first group comprised nine patients with rheumatic disease; the second group contained 14 patients without rheumatic disease. The patients were also sub-classified into those who were HLA-B27 positive (14 patients) and those who were not. TNF-alpha levels in serum and aqueous humour from a group of 16 patients with uncomplicated cataracts were analysed as a control group. In the control group (n = 16) the serum TNF-alpha concentration was 13.1 +/- 2.9 pg/ml and the aqueous humour concentration of TNF-alpha was 0.56 +/- 1.53 pg/ml. In uveitis patients (n = 23) the serum TNF-alpha concentration was 35.35 +/- 26.77 pg/ml and the aqueous humour concentration of TNF-alpha was 15.1 +/- 1.70 pg/ml (p < 0.01). In HLA-B27 positive patients (n = 9) the serum TNF-alpha concentration was 45.56 +/- 34.17 pg/ml and the aqueous humour concentration of TNF-alpha was 15.89 +/- 0.93 pg/ml. In HLA-B27 negative patients (n = 14) the serum TNF-alpha concentration was 28.79 +/- 19.38 pg/ml and aqueous humour concentration of TNF-alpha was 14.57 +/- 1.91 pg/ml (p < 0.01). The concentration of TNF-alpha in aqueous humour in patients who are HLA-B27 positive is significantly greater than in those who are B27 negative. No significant differences in the concentrations of TNF-alpha in serum or aqueous humour in patients with or without rheumatic diseases were detected. TNF-alpha is a cytokine that may participate actively in the pathogenesis of clinical uveitis.


Noble metal targeting of thioredoxin reductase--covalent complexes with thioredoxin and thioredoxin-related protein of 14 kDa triggered by cisplatin.
Palladium (Pd), platinum (Pt), and gold (Au) are noble metals, two of which have established medical use. Pt has anticancer efficacy, predominantly as cisplatin, whereas the gold compound auranofin is used against arthritis. Both compounds inhibit the selenoprotein thioredoxin reductase (TrxR), but Pd has not been studied in this regard. Using salts of Pd, Pt, and Au as well as cisplatin and auranofin we found that Pd and Au were strikingly more potent inhibitors of recombinant TrxR1 than Pt. The TrxR-related nonselenoprotein glutathione reductase in pure form (but less so in a cellular context), as well as cellular thioredoxin (Trx) activities, were inhibited by the gold salt KAuCl(4) but were little affected by auranofin or the other compounds. In an analysis of three cancer cell lines, the extent of inhibition of TrxR activity and decrease in cell viability depended upon the choice of both noble metal and ligand and also seemed independent of p53 status. During treatment of cells with cisplatin, covalent complexes of TrxR1 with either Trx1 or TRP14 (Trx-related protein of 14kDa) were formed, as verified by Western blot analyses and mass spectrometry. These results reveal that Au and Pd are strong inhibitors of TrxR, but Pt and cisplatin trigger highly specific cellular effects on the Trx system, including covalent cross-linking of TrxR1 with Trx1 and TRP14.


α-Lipoic acid increases tolerance of cardiomyoblasts to glucose/glucose oxidase-induced injury via ROS-dependent ERK1/2 activation.
α-Lipoic acid (LA) has been shown to improve the diabetic cardiac symptoms. However, the underlying mechanisms have not been elucidated precisely. We have reported recently that LA potentially protected neurons from substance-induced apoptosis. We hypothesized that LA could attenuate cardiac cells death induced by oxidative stress derived from high glucose. To test this possibility, we examined the effects of LA on d-glucose/glucose oxidase (DG/GO, 30mM/5mU)-induced injury in rat cardiomyoblast H9c2 cells. We observed that LA pretreatment significantly increased cell viability in DG/GO-challenged cells. LA pretreatment also attenuated DG/GO-induced apoptosis as evidenced by decreases in both nuclear condensation and loss of mitochondrial potential. In addition, LA activated ERK1/2 and moderately increased ROS production. Blockade of ERK1/2 activation by PD98059 completely abolished LA-induced protection against DG/GO challenge. Inhibition of ROS by N-acetylcysteine abrogated LA-induced ERK1/2 activation and cytoprotection. Furthermore, we observed that the ROS production induced by LA was significantly slower and milder than that by DG/GO. Our results suggest that pretreatment with LA moderately increased ROS production to induce a preconditioning-like effect by ERK1/2 activation thereby increased tolerance of H9c2 cells to DG/GO challenge.


Selected immunological reactions to measles virus in immunosuppressed guinea pigs.
Cyclophosphamide and hydrocortisone treatment of measles virus infected guinea pigs resulted in suppression of cele- and antibody mediated immune reactions although a high dose of measles virus (10(5.5) TCID50) was used for infection: MIT was delayed and depressed; HI serum antibody response was almost completely inhibited.


Should patients have cardiac catheterization prior to long-term oxygen treatment?
Pulmonary arterial pressure predicts survival in patients with hypoxic chronic obstructive pulmonary disease as does the presence of cor pulmonale. Thus, cardiac catheterization has been performed prior to treatment for long-term oxygen therapy (LTOT) in order to 1) assess the suitability of patients for LTOT, 2) predict survival in patients receiving LTOT and 3) for research in cor pulmonale. In this review I will submit the evidence which suggests that these indications for measurement of pulmonary haemodynamics are not justified, and measurements of arterial blood gas values and assessment of airflow limitation are all that is necessary prior to LTOT.


Evaluation of biological activities and in vivo amelioration of CCl4 induced toxicity in lung and kidney with Abutilon pannosum (G.Forst.) Schltdl. in rat.
Abutilon pannosum is used in Pakistan for bladder inflammation, diuretic, lung disorders, diabetes and in lowering pyrexia. Amount of total phenolic content, total flavonoid content and HPLC analysis of APM for the presence of polyphenolics were carried out. Antioxidant activity was determined by using different in vitro antioxidant assays. Amelioration effects of APM (200 mg/kg body weight and 400 mg/kg body weight) against CCl4 induced kidney and lung toxicity in rat was assessed by determining level of antioxidant enzymes, lipid peroxidation products, cytokines (TNF-α, IL-1β and IL-2), comet assay and histological analysis. HPLC-DAD studies of APM indicated the presence of rutin (0.635 ± 0.011 μg/mg dry extract), gallic acid (1.07 ± 0.043 μg/mg dry extract) and catechin (0.246 ± 0.08 μg/mg dry extract) and considerable quantity of total phenolic (55.485 ± 0.85 mg GAE/g dry extract) and total flavonoid content (19.90 ± 0.58 mg Rutin/g dry extract). During in vitro antioxidant assays APM showed significant (p < 0.05) activity for iron chelation, reducing potential, inhibition of β-carotene oxidation while moderate potential for scavenging of DPPH, hydroxyl, nitrite and phosphomolybdenum radical. Administration of CCl4 to rat severely depleted the activity level of catalase (CAT), peroxidase (POD) and superoxide dismutase (SOD), and reduced glutathione (GSH) concentration while appreciably increased the concentration of thiobarbituric acid reactive substances (TBARS), H2O2, nitrite, TNF-α, IL-1β and IL-2 in lung and kidney tissues of rat. Comet length, % DNA in tail and tail moment significantly (p < 0.01) increased in lung and kidney cells of CCl4 intoxicated rat. Further, injuries in lung and kidney tissues were recorded with CCl4 induced toxicity in rat. The rats treated with APM along with CCl4 exhibited an appreciable level of restoration of the altered parameters towards the control animals. The results of this study suggested the protective potential of APM in CCl4 intoxicated rats for kidney and lung injuries.


Systemic Gene Therapy for Targeting the CNS.
Systemic gene delivery is useful for modeling and treatment of a body-wide disease. Recently, it has been shown that certain agents, when delivered systemically, can efficiently target the central nervous system. This technique has been used to model and treat rodent models of neurological disease with unprecedented success. Here, we describe intravenous delivery in neonate and adult mice. These techniques are easily learned and have minimal equipment requirements.


CTSC-Net: an effectual CT slice classification network to categorize organ and non-organ slices from a 3-D CT image.
Computed tomography (CT) is a non-invasive diagnostic imaging modality that reveals more insight into human organs than conventional X-rays. In general, the CT output is a 3-D image that is formed by combining multiple 2D images or slices together. It is essential to keep in mind that not all of the slices provide significant information to detect tumours. Usually, a 3-D CT image obtained from the CT scanners has a significant number of unwanted non-organ slices in it. Radiologists typically devote a significant amount of time to select the slices with organ from a 3-D CT image. The presence of a tumour is only evident in the organ slice; hence, radiologists must be cautious not to skip any organ slices. This work is evaluated on the LITS, 3DIRCADb and COVID-19 CT datasets. The three datasets collectively contain 22,435 organ slices and 53,661 non-organ slices, and there is a huge gap between the number of organ and non-organ slices. There is a need for the automatic elimination of non-organ slices in 3-D CT volumes to assist the physicians, and hence, this work focuses on the automatic recognition of organ slices from 3-D CT volumes. In this paper, a new deep model called the computed tomography slice classification network (CTSC-Net) is proposed for CT slice classification between organ and non-organ slices. The model is trained on 77,980 CT slices, validated on 9748 slices and tested on 12,571 slices. Nine CNN architectures with different layer settings are trained and tested to arrive at the final optimal model. The performance measures are computed in terms of true positive rate, true negative rate, sensitivity, specificity and accuracy. The 20-layer CTSC-Net achieves a validation accuracy of 95.04% and an overall testing accuracy of 99.96%. The proposed model is compared to eight different pre-trained CNN models, and the results of the proposed CTSC-Net surpassed all the comparable models. The activation feature maps of different layers of the CTSC-Net are visualized to verify the discriminative features learned by the network. Hence, the proposed CTSC-Net can be employed as a computer-aided diagnosis tool to help physicians discard unnecessary non-organ slices from the 3-D CT volume and to speed up the CT diagnosis process.


Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter.
To evaluate the consequences of inactivation of the serotonin transporter (SERT) gene on 5-HT homeostasis and function, 5-HT synthesis and turnover rates were measured using the decarboxylase inhibition method in multiple brain regions (frontal cortex, striatum, brainstem, hippocampus and hypothalamus) from mice with a genetic disruption of SERT. 5-HT synthesis rates were increased 30-60% in the different brain regions of SERT -/- mice compared to littermate +/+ control mice despite 55-70% reductions in tissue 5-HT concentrations. Brain regions that possessed a greater capacity to increase synthesis and turnover (frontal cortex, striatum) demonstrated lesser reductions in tissue 5-HT. Female SERT -/- mice had greater increases (79%) in brain 5-HT synthesis than male -/- mice did (25%), a finding associated with higher brain tryptophan concentrations in females. Despite increased 5-HT synthesis, there was no change in either TPH2 or TPH1 mRNA levels or in maximal in vitro TPH activity in the brainstem of SERT -/- mice. Catecholamine homeostasis as reflected in brain tissue concentrations and in synthesis and turnover of dopamine and norepinephrine was unchanged in SERT -/- mice. Taken together, the results demonstrate a markedly altered homeostatic situation in SERT -/- mice that lack 5-HT reuptake, resulting in markedly depleted tissue stores that are inadequately compensated for by increased 5-HT synthesis, with brain region and gender specificity observed.


Thinking aloud on the road: Thematic differences in the experiences of drivers, cyclists, and motorcyclists.
This study takes a qualitative approach to exploring the experiences (and differences therein) of individuals using either their car, bicycle, or motorcycle to navigate a ∼10.5 km urban route in a provincial UK city, with the aim of contributing to our understanding of the needs and requirements of different road users. Forty-six individuals provided concurrent verbal reports, using the 'think aloud' method, whilst using their vehicle to navigate the test route, the transcripts of which were subjected to a theory-agnostic, inductive, thematic analysis. A number of group differences were observed, revealing (among other factors) the importance of road surface quality to cyclists, the focus on vigilant observation in motorcyclists, and the heightened emotionality experienced by both two-wheeled groups, particularly those on bicycles. This affective component has, as yet, been under-explored in the academic domain and under-utilised in road transport policy and strategy; this is discussed, with attention drawn to the cyclists' greater tendency to make negatively valenced value judgements. Results are also discussed in terms of the potential to improve road users' experiences, foster inter-group empathy and understanding, and encourage a shift in mobility towards more sustainable modes.


[Stereopsis of the patients after cataract extraction and intraocular lens implantation].
To understand the stereopsis of the patients after cataract extractation and intraocular lens implantation and the related factors. In this study were examined the stereopsis of 30 patients who had undergone cataract extraction and intraocular lens implantation and whose post-operative vision acuity measurements were 0.5 or higher. These patients' steroacuity, anisometropia, aniseikonia and scotoma were: 407.67" +/- 390.19", 1.53D +/- 1.96D, 3.93% +/- 3.51%, 3.17" +/- 1.98" respectively. There was no significant correlation between steroacuity anisometropia and aniseikonia. There was siganificant positive correlation between steroacuity and scotoma. Intraocular lens implantation may ameliorate anisometropia and aniseikonia of the patients after cataract extraction and reduce the damage to stereopsis.


Flow behaviour of pharmaceutical powders during rotary die filling with a paddle feeder.
Rotary tabletting presses are widely used to produce tablets in the pharmaceutical industry. In the tabletting process using a rotary press, rotary die filling is one of critical process steps, as powder behaviour during die filling dictates the quality of final products, such as dosage and weight variations. It is hence of importance to understand powder flow behaviour during rotary die filling. The purpose of this study is to identify the critical process parameters and material attributes that determine the die filling performance. For this purpose, a model rotary die filling system with a paddle feeder was constructed to mimic the powder feeding process in a typical rotary press. Using this model system, the effects of powder properties, turret speed and paddle speed on die filling behaviour were investigated. Three grades of microcrystalline cellulose powders were considered. It was found that the turret speed has a more pivotal role in controlling the die filling performance than the paddle speed. In addition, it is demonstrated that powder flowability has a great impact on the fill weight variation, and a higher weight variation is induced for the powders with poorer flowability.


On the evaluation of the carbon dioxide solubility in polymers using gene expression programming.
Evaluation, prediction, and measurement of carbon dioxide (CO2) solubility in different polymers are crucial for engineers in various chemical applications, such as extraction and generation of novel materials. In this paper, correlations based on gene expression programming (GEP) were generated to predict the value of carbon dioxide solubility in three polymers. Results showed that the generated correlations could represent an outstanding efficiency and provide predictions for carbon dioxide solubility with satisfactory average absolute relative errors of 9.71%, 5.87%, and 1.63% for polystyrene (PS), polybutylene succinate-co-adipate (PBSA), and polybutylene succinate (PBS), respectively. Trend analysis based on Henry's law illustrated that increasing pressure and decreasing temperature lead to an increase in carbon dioxide solubility. Finally, outlier discovery was applied using the leverage approach to detect the suspected data points. The outlier detection demonstrated the statistical validity of the developed correlations. William's plot of three generated correlations showed that all of the data points are located in the valid zone except one point for PBS polymer and three points for PS polymer.


[The effect of ion pair formation on the pharmacokinetics of drugs. 2. The effect of hexylsalicylic acid on the pharmacokinetics of quinine].
The influence of the hexylsalicylic acid (2) on the pharmacokinetic of the quinine (1), was studied using rabbits. It could be observed that after i.v. application the mean resistance time (MRT) of 1 was increased by means of ion-pair-formation with 2. But the AUC of 1 was not influenced. After rectal application of the combination 1/2 an acceleration of the 1 absorption could be pointed out. The kinetic parameters of 2 were not increased significantly if 1 was applicated simultaneously.


MEIS1 promotes expression of stem cell markers in esophageal squamous cell carcinoma.
MEIS1 (Myeloid ecotropic viral integration site 1) as a homeobox (HOX) transcription factor plays regulatory roles in a variety of cellular processes including development, differentiation, survival, apoptosis and hematopoiesis, as well as stem cell regulation. Few studies have established pluripotency and self-renewal regulatory roles for MEIS1 in human esophageal squamous cell carcinoma (ESCC), and our aim in this study was to evaluate the functional correlation between MEIS1 and the stemness markers in ESCC patients and cell line KYSE-30. Expression pattern of MEIS1 and SALL4 gene expression was analyzed in different pathological features of ESCC patients. shRNA in retroviral vector was used for constantly silencing of MEIS1 mRNA in ESCC line (KYSE-30). Knockdown of MEIS1 gene and the expression pattern of selected stemness markers including SALL4, OCT4, BMI-1, HIWI, NANOG, PLK1, and KLF4 were evaluated using real-time PCR. Significant correlations were observed between MEIS1 and stemness marker SALL4 in different early pathological features of ESCC including non-invaded tumors, and the tumors with primary stages of progression. Retroviral knockdown of MEIS1 in KYSE-30 cells caused a noteworthy underexpression of both MEIS1 and major involved markers in stemness state of the cells including SALL4, OCT4, BMI-1, HIWI and KLF4. The results highlight the important potential role of MEIS1 in modulating stemness properties of ESCCs and cells KYSE-30. These findings may confirm the linkage between MEIS1 and self-renewal capacity in ESCC and support probable oncogenic role for MEIS1 in the disease.


Adipocyte cell size enlargement involves plasma membrane area increase.
The adipocyte enlargement is associated with an increase in the cytoplasmic lipid content, but how the plasma membrane area follows this increase is poorly understood. We monitored single-cell membrane surface area fluctuations, which mirror the dynamics of exocytosis and endocytosis. We employed the patch-clamp technique to measure membrane capacitance (C(m)), a parameter linearly related to the plasma membrane area. Specifically, we studied whether insulin affects membrane area dynamics in adipocytes. A five-minute cell exposure to insulin increased resting C(m) by 12 ± 4%; in controls the change in C(m) was not different from zero. We measured cell diameter of isolated rat adipocytes microscopically. Twenty-four hour exposure of cells to insulin resulted in a significant increase in cell diameter by 5.1 ± 0.6%. We conclude that insulin induces membrane area increase, which may in chronic hyperinsulinemia promote the enlargement of plasma membrane area, acting in concert with other insulin-mediated metabolic effects on adipocytes.


Persistently elevated hCG in a patient with no clear evidence of pregnancy.
We describe a case of a female patient with a complex medical history, including squamous cell carcinoma of the tongue, and persistent elevation in serum hCG and no confirmed intrauterine or extrauterine pregnancy. The clinical chemistry laboratory was called upon to help clarify the situation and reach a diagnosis. Multiple potential sources of elevated hCG were considered and excluded. This case shows a rare example of paraneoplastic hCG expression and highlights the role of the clinical chemistry laboratory in resolving diagnostic dilemmas and interpreting laboratory results in patients with multiple medical comorbidities.


An electrophysiological investigation of cross-language effects of orthographic neighborhood.
In Experiment 1 ERPs were recorded while French-English bilinguals read pure language lists of French and English words that differed in terms of the number of orthographic neighbors (many or few) they had in the other language. That is the number of French neighbors for English target words was varied and the number of English neighbors for French target words was varied. These participants showed effects of cross-language neighborhood size in the N400 ERP component that arose earlier and were more widely distributed for English (L2) target words than French (L1) targets. In a control experiment that served to demonstrate that these effects were not due to any other uncontrolled for item effects, monolingual L1 English participants read only the list of English targets that varied in the number of French (an unknown L) neighbors. These participants showed a very different pattern of effects of cross-language neighbors. These results provide further crucial evidence showing cross-language permeability in bilingual word recognition, a phenomena that was predicted and correctly simulated by the bilingual interactive-activation model (BIA+).


Assessing errors in the determination of base excess.
We compared estimates for base excess of extracellular fluid (BE(ecf); mmol/L) obtained in five clinically used blood gas analyzers: AVL Compact 2 (Roche Diagnostics, Mannheim, Germany), Ciba-Corning 860 (Bayer Diagnostics, Fernwald, Germany), IL 1620 (Instrumentation Laboratories, Lexington, MA), Stat Profile Ultra (Nova Biomedical, Waltham, MA), and ABL 510 (Radiometer, Copenhagen, Denmark). A total of 134 measurements per analyzer were obtained in arterial and venous blood samples from 10 patients undergoing cardiac surgery and 65 measurements per analyzer in venous blood samples from 2 healthy volunteers. The blood samples were equilibrated in a tonometer with gases of known composition (37 degrees C). Additional theoretical studies were performed to evaluate the relationship between pH and calculated BE(ecf) value (with varied PCO(2)) using the formulas of the various analyzers. The standard deviations of repeated measurements were 0.24 mmol/L for ABL 510 and approximately 0.45 mmol/L for the other 4 analyzers. The maximal systematic difference between the average of all measurements of each analyzer was 3.7 mmol/L; this was primarily attributable to differences in measuring pH, and, to a lesser extent, to differences in calculation and determination of PCO(2). Comparison of the results from samples with different oxygen saturation showed that the relative alkalinity of deoxygenated hemoglobin (Haldane effect) can also influence the determinations of BE(ecf). A clinically useful way to quantify nonrespiratory disturbances of the acid-base balance is calculation of the base excess of extracellular fluid by using blood gas analyzers. In this study, we found significant variability in estimates of base excess of extracellular fluid obtained with five analyzers from different manufacturers. This variability is attributable to multiple factors, including lack of correction for deoxygenated hemoglobin (Haldane effect).


Impact of one-year treatment with biotechnological drugs on work ability in patients with rheumatoid arthritis in Italy: a prospective real-life study.
We aimed to evaluate the impact of biologic therapy on work productivity outcomes in an Italian real-life cohort of biologic-naïve patients with active rheumatoid arthritis (RA). This observational prospective multicentre study enrolled RA patients in working age with an active disease who started their first biologic agent. Every patient completed the RA-specific Work Productivity Survey (WPS-RA) at each clinical evaluation (baseline, 6 and 12 months). The primary outcome of the study was the productivity gain at 12 months from the beginning of the biologic treatment, compared to baseline, assessed in terms of absenteeism and presenteeism reduction, both for employed and unemployed subjects. Linear regression analyses were performed to assess the impact of patient- and disease-related variables on productivity gain. Overall, 100 patients were enrolled and 85 completed the study. All indexes of disease activity and functional ability were significantly improved from baseline already at 6 months. At 12 months, the 55 employed subjects showed a significant reduction in the mean number of days of work missed (absenteeism) and of reduced productivity (presenteeism). A significant reduction in the mean number of days of household work missed was observed for all patients. At multivariate analysis, functional disability had a significant negative impact on all parameters of household work productivity, while the achievement of a low disease activity or remission was inversely correlated with presenteeism. One year of treatment with a biological drug significantly impacts on the disease activity and work ability of RA patients and allows economic gains due to productivity improvement.


Crouzon disease in twins. Clinical and pathological contribution.
After a survey of cases in the literature reported, two cases of Crouzon disease, in monovular twins are described. The observation in twins and the opportunity of histologic examination of optic nerve, permitted some considerations in order to help in understanding this syndrome.


The 5-HT2C receptor antagonist RO 60-0491 counteracts rats' retention deficits in a recognition memory task.
The effects of the 5-HT2C receptor antagonist RO 60-0491 on recognition memory were investigated in the rat by using the object recognition task. Post-training administration of RO 60-0491 at 3 mg/kg, but not at 1 mg/kg, counteracted rats' performance deficits in the object recognition task, suggesting that this 5-HT2C receptor antagonist compound modulates storage and/or retrieval of information.


Self-absorption correction on 2D X-ray fluorescence maps.
X-ray fluorescence mapping (XRF) is a highly efficient and non-invasive technique for quantifying material composition with micro and nanoscale spatial resolutions. Quantitative XRF analysis, however, confronts challenges from the long-lasting problem called self-absorption. Moreover, correcting two-dimensional XRF mapping datasets is particularly difficult because it is an ill-posed inverse problem. Here we report a semi-empirical method that can effectively correct 2D XRF mapping data. The correction error is generally less than 10% from a comprehensive evaluation of the accuracy in various configurations. The proposed method was applied to quantify the composition distribution around the grain boundaries in an electrochemically corroded stainless steel sample. Highly localized Cr enrichment was found around the crack sites, which was invisible before the absorption correction.


5-Substituted 4-anilinoquinazolines as potent, selective and orally active inhibitors of erbB2 receptor tyrosine kinase.
Starting from a 6,7-substituted quinazoline lead 4, optimisation of 5-substituted quinazolines containing an extended aniline motif led to potent and selective inhibitors of erbB2 receptor tyrosine kinase, and a representative compound 12a inhibited tumour growth in a mouse xenograft model.


Superchaotropic Nano-ion Binding as a Gelation Motif in Cellulose Ether Solutions.
Nanometer-sized anions (nano-ions) like polyoxometalates and boron clusters exhibit so-called superchaotropic behavior, which describes their strong binding to hydrated non-ionic matter in water. We show here that nano-ions, at millimolar concentrations, dramatically enhance the viscosity and induce gelation of aqueous solutions of non-ionic cellulose ethers (CEs), a class of widely utilized polymers known for their thickening and gel-forming ability. These phenomena arise from an interplay of attractive forces and repulsive electrostatic forces between CE-chains upon nano-ion binding. The attractive forces manifest themselves as aggregation of CE-chains into a physically crosslinked polymer network (gel). In turn, the electrostatic repulsions hamper the viscosity increase and gelation. Superchaotropic nano-ion binding emerges as a novel and general physical crosslinking motif for CE-solutions and exceeds by far the conventional thickening effects of classical salts and ionic surfactants.


Transesophageal and contact ultrasound echographic assessments of pulmonary vessels in bilateral lung transplantation.
Intraoperative transesophageal echocardiographic visualization of the vascular anastomosis of lung grafts can be difficult. The goal of this prospective study was to compare intraoperative transesophageal echocardiography and contact ultrasound. Vessel imaging and Doppler analysis obtained before chest closure by both techniques were compared in 18 bilateral lung transplant recipients. Twenty-four arteries in 36 and 45 pulmonary veins in 72 were recorded using transesophageal echocardiography versus 34 and 60 by contact ultrasound (p = 0.05). Views of the left pulmonary artery (p = 0.04) and of the left superior and inferior pulmonary veins (p = 0.04 and p = 0.02, respectively) were more often obtained with contact ultrasound. Measurements of vessel diameters were similar by both methods except for the left superior vein, which was smaller by the transesophageal approach (p = 0.002). In 1 patient, inferior venous diameters could not be obtained by either method. Nine arterial and 47 venous velocities were recorded by transesophageal echocardiography versus 21 and 33 by contact ultrasound (p = 0.001). Contact ultrasound produced better left pulmonary artery recordings (p = 0.02), whereas transesophageal echocardiography was more effective on venous velocities. Left inferior vein velocity was twofold higher using transesophageal echocardiography (p < 0.001). These results suggest clinicians should exercise caution when making treatment decisions when using transesophageal echocardiography alone.


Two-dimensional echocardiographic studies during sustained ventricular tachycardia.
We evaluated left ventricular function in patients with recurrent sustained ventricular tachycardia (VT) using two-dimensional echocardiography (2DE). Thirteen patients, 11 men and 2 women, age range 42-77 (mean 62 +/- 12) years were studied in sinus rhythm (SR) and immediately after VT induction. 2DE parameters analyzed included wall motion, mitral valve leaflet motion, and ejection fraction (EF). In SR, 21 segments/walls in 12 patients showed wall motion abnormalities (WMA) ranging from hypokinesis to dyskinesis and one patient had generalized LV hypokinesis. In VT, new WMA were noted in 2 patients. Thirteen segments/walls in 8 patients showed further worsening of pre-existing WMA. In 1 patient there was worsening of generalized LV hypokinesis. Three patients showed apparent improvement in pre-existing WMA during VT. In 2 patients large apical aneurysms showed a reduction of dyskinesis in VT. Mitral valve opening was intermittent in patients with shorter VT cycle lengths and was maximal when atrial systole preceded or coincided with ventricular depolarization. Doppler echocardiography in 1 patient confirmed the pattern of intermittent mitral flow, with greatest flow occurring when mitral valve opening occurred well before the QRS peak. In 5 patients, 2DE permitted EF measurements. EF in SR ranged from 24-56% (mean 36 +/- 13), decreased to 6-33% (mean 21 +/- 11) within the first ten beats of VT and 6-25% (mean 19 +/- 8) after twenty beats of VT. EF decreased more in patients with shorter VT cycles as compared to those with longer VT cycle lengths.(ABSTRACT TRUNCATED AT 250 WORDS)


Biophysical Characterization of Chromatin Remodeling Protein CHD4.
Chromatin-remodeling ATPases modulate histones-DNA interactions within nucleosomes and regulate transcription. At the heart of remodeling, ATPase is a helicase-like motor flanked by a variety of conserved targeting domains. CHD4 is the core subunit of the nucleosome remodeling and deacetylase complex NuRD and harbors tandem plant homeo finger (tPHD) and chromo (tCHD) domains. We describe a multifaceted approach to link the domain structure with function, using quantitative assays for DNA and histone binding, ATPase activity, shape reconstruction from solution scattering data, and single molecule translocation assays. These approaches are complementary to high-resolution structure determination.