Glycine and other amino compounds prevent chromatin precipitation at physiological ionic strength.
Glycine, proline and taurine, when present in the range 0.1-0.60 M, inhibit chromatin precipitation by sodium chloride. Histone gel electrophoresis revealed that the linker histones H1 and H5 were largely depleted from the supernatant chromatin fraction at 0.2 M NaCl, while this depletion was absent in the presence of glycine. These observations are discussed in relation with the various factors which may be involved in the precipitation process.


Effect of everolimus initiation and early calcineurin inhibitor withdrawal on myocardial FOXP3+ regulatory T cells in heart transplantation.
Through immunosuppression CD4+FoxP3+ regulatory T-cells (Tregs) play an indispensable role in allograft rejection. Post-HTx treatment with everolimus is associated with slower progression of cardiac allograft vasculopathy (CAV) - chronic rejection - than CNI based therapy. We hypothesized treatment with everolimus reduced the risk of CAV by modulating myocardial FoxP3 levels. 15 patients from the Schedule trial comparing everolimus, MMF, steroid and early CNI (Everolimus, n=8) withdrawal to conventional CNI based immunosuppression (Controls, n=7) after de novo HTx were included and FoxP3+ cells were quantified in 56 endomyocardial biopsies, and compared in the two patient groups. CAV was evaluated invasively using coronary intravascular ultrasound (IVUS). Baseline FoxP3 biopsy levels were similar in the two groups. The Everolimus group showed a significant increase in Foxp3 densities from baseline to time of one-year follow-up (median (IQR)=4.8×10(-7)(20.4) Tregs/μm(2), P=0.046) while Controls showed no significant change (median (IQR)=3.1×10(-7)(6.5) Tregs/μm(2), P=0.116). At 1-month follow-up FoxP3 densities correlated with the observed change in TAV from baseline to time of 1-year follow-up (r=0.641, P=0.034). FoxP3 densities at 1-week predicted acute cellular rejection (ACR) levels at 1month (P=0.026). No other correlations with ACR were found. Everolimus treatment combined with early CNI elimination is associated with increased densities of Tregs 12-months post-HTx compared to patients receiving CNI based regimen. Furthermore, the density of myocardial FoxP3+ cells early after transplantation appears to predict at least one measure of CAV burden after one year.


Variable arginine vasopressin levels in neonatal congestive heart failure.
Arginine vasopressin levels in 17 neonates with cardiac disease were compared with control levels in 10 healthy newborn infants. Infants with congestive heart failure who were free of left ventricular outflow tract obstruction had a mean level of 80 +/- 18 pg/ml, which was significantly greater than the mean control level (p less than 0.001). Infants with congestive heart failure and left ventricular outflow tract obstruction had a mean vasopressin level of 3 +/- 0.7 pg/ml, which was lower than the mean control level of 6 +/- 0.7 pg/ml (p less than 0.05). The data suggest that impaired forward flow to high pressure sinoaortic and ventricular baroreceptors is necessary for vasopressin release in congestive heart failure. In left ventricular outflow tract obstruction with heart failure these receptors may be impaired or absent, leading to decreased vasopressin release. Low plasma arginine vasopressin may adversely affect circulatory homeostasis.


Ejection fraction response to upright exercise in hypertension: relation to loading conditions and to contractility.
The respective roles of peripheral and myocardial determinants of exercise ventricular performance were studied in 10 normal volunteers and in 9 mildly hypertensive patients without evidence of coronary disease. Hemodynamic measurements and equilibrium blood pool scintigraphy were simultaneously performed at rest and during maximal upright exercise. In hypertensive patients, mean systolic and diastolic blood pressure were, respectively, 199 +/- 23 and 102 +/- 12 mm Hg at rest, and 271 +/- 28 and 113 +/- 8 mm Hg at peak exercise. Ejection fraction response to exercise was normal (increase by more than 5%) in 4 hypertensive patients (normal hypertensive group: 63 +/- 4 to 77 +/- 6%) and in volunteers (65 +/- 3 to 78 +/- 4%) and abnormal in 5 hypertensive patients (abnormal hypertensive group: 66 +/- 6 to 58 +/- 10% at peak exercise). The abnormal response in the abnormal hypertensive group was not due to an inadequate decrease in systemic vascular resistance during exercise. By contrast, the ratio systolic blood pressure/end-systolic volume, an index of contractility, decreased by 2.3 +/- 4.9 in the abnormal hypertensive group, whereas it increased by 9.8 +/- 9.1 in the normal hypertensive group and by 7.3 +/- 2 in volunteers. Thus, abnormal exercise ejection fraction response in mild hypertension was not related to increased afterload but rather to intrinsic myocardial factors.


[Place of azathioprine in the treatment of giant cell arteritis].
The aim of this bicentric retrospective study was to describe the use of azathioprine in giant cell arteritis, and to appreciate its corticosteroid-sparing effect in glucocorticoid-dependent patients or with severe glucocorticoid related side effects. We retrospectively reviewed the medical records of patients diagnosed with giant cell arteritis between 2000 and 2011 in two departments of internal medicine. Only the patients treated with azathioprine were included in this study. Sociodemographic, clinical, biological, radiological and therapeutic data were collected by a standardized questionnaire. A comparative analysis of daily prednisone dose at the initiation and 1 year after the prescription of azathioprine was made. Of the 28 patients included, 21 responded to azathioprine. At 1 year of follow-up after the initiation of azathioprine, 18 patients (64%) were still in sustained response, asymptomatic, without increase in acute phase response laboratory markers, and with a daily dose of prednisone<10 mg. Three patients (11%) experienced a relapse during azathioprine treatment. Mean daily dose of prednisone were 25.4 mg at the time of initiation of azathioprine, and 4.7 mg at 1 year of treatment, suggesting a corticosteroid-sparing effect (P<0.001). Ten patients experienced azathioprine serious side effects, leading to discontinuation of treatment in seven cases. Azathioprine may be an alternative treatment for patients with giant cell arteritis requiring prolonged high dose glucocorticoid therapy or developing severe glucocorticoid related side effects. However, given the potential adverse effects of azathioprine, a close monitoring is necessary.


Changing educational paradigms in transfusion medicine and cellular therapies: development of a profession.
The transfusion medicine profession can be easily compared and contrasted with an early 1900 ironclad ship operating in the rough seas of the 21st century. Without modifying the old ship to today's standards, even the captain and crew will begin to expect the ship to meet its demise. The unfortunate passengers, on the other hand, do not expect that they are on an old obsolete ship and, instead, are innocent victims stuck on a doomed course. The old ironclad ship must change into a sleek cruiser and utilize the latest available technology so that its well-educated and competent captain and crew can safely navigate even the most challenging waters. The transfusion medicine profession must transform itself into a state-of-the-art ship so that it, like the refurbished ironclad ship, can be set on cruise control through the open seas. The question facing our industry is do we have the courage to utilize modern technology and to commit the funds necessary to develop, implement, and maintain our existence? It is difficult to plot a steady course into the future because of existing challenges that stand ready to sink our profession, including economic wrangling over regulation, technologic changes, generation conflict, and political differences that threaten our excellence. The primary purpose of this article is to focus on the educational needs that affect all personnel involved in transfusion medicine. In addition, this article will address potential adverse outcomes and investigate possible resolutions to avoid the "sinking ship." Within the next 5 to 7 years, without a corrective course of action, our profession will be at the bottom of the clinical ladder, remembered more for its demise and tragic ending than for its accomplishments. It is hoped, successful implementation of changes in educational paradigms in transfusion medicine may lead to a renaissance within our workforce-generations working together, each sharing and learning from one another.


Impact of freeze drying on drug resistance pattern of few Escherichia coli strains.
Drug resistant strains of E. coli were freeze dried for long term preservation. Certain drug resistance markers were maintained after freeze drying while others were not. Streptomycin and sulphonamide resistance markers resisted freeze drying. Ampicillin, cephelaxin and neomycin resistances developed very frequently and except gentamicin all the markers were lost in varying percentage after freeze drying.


Brain: biomedical knowledge manipulation.
Brain is a Java software library facilitating the manipulation and creation of ontologies and knowledge bases represented with the Web Ontology Language (OWL). The Java source code and the library are freely available at https://github.com/loopasam/Brain and on the Maven Central repository (GroupId: uk.ac.ebi.brain). The documentation is available at https://github.com/loopasam/Brain/wiki.


Does statin monotherapy address the multiple lipid abnormalities in type 2 diabetes?
Lipid abnormalities, which are common in type 2 diabetes, predispose to a greatly increased risk of coronary heart disease. This characteristic dyslipidaemia includes decreased concentrations of high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, and a small, dense, atherogenic form of low-density lipoprotein cholesterol (LDL-C). Insulin resistance and obesity, which is commonly present in type 2 diabetes, act in concert to disrupt normal lipoprotein metabolism; reverse cholesterol transport in particular. The proatherogenic changes, which result from this process include enrichment of very-low-density lipoprotein with cholesteryl esters and enrichment of LDL with triglycerides. Results from both the Pravastatin Pooling Project and the Heart Protection Study demonstrate that, although people with diabetes obtain the same relative risk reduction with statin therapy, the absolute benefit derived is much lower than for comparable individuals without diabetes. In order to achieve improved outcomes in diabetes patients, it will be important to address other abnormalities in their lipid profiles, including elevated triglycerides and low HDL-C.


Potentially inappropriate medications in Chinese older adults: a comparison of two updated Beers criteria.
Background Beers criteria have been into the mainstay to characterize the potentially inappropriate medication since its first publication, but the recent version, Beers 2019, is yet to be validated by clinical studies nationally. Objective To identify the prevalence and the predictors of potentially inappropriate medications in hospitalized geriatric patients based on the Beers 2019 and 2015 criteria. Setting Nanjing Drum Tower Hospital, a 3000-bed tertiary care teaching hospital in China. Method We conducted a cross-sectional study from July 1, 2018 to December 31, 2018. Data from all hospitalized patients aged ≥ 65 years were collected from the hospital database. Inappropriate prescriptions were identified using the Beers 2019 criteria and the Beers 2015 criteria. Main outcome measure Prevalence Ratio (PR) and predictors of potentially inappropriate medications. Results The prevalence of inappropriate prescriptions based on the Beers 2019 criteria was 64.80%. This result was slightly higher than that of the Beers 2015 criteria (64.31%). The most commonly encountered inappropriate prescriptions identified using the two criteria were proton-pump inhibitors. The kappa coefficient was 0.826 (p < 0.001) indicating a strong coherence between the two criteria. The most important factor associated with inappropriate medications use was the number of prescribed drugs (PR 5.17, 95% CI 2.89-8.43; PR 4.58, 95% CI 1.93-7.25). Conclusion This study showed a high prevalence of potentially inappropriate medication in the Chinese geriatric population, which was associated with the number of prescribed drugs. The predictors identified in this research might help pharmacists to detect high-risk drugs and intervene in time.


Impact of mediolateral segmentation on a multi-segment foot model.
MacWilliams et al. report their progress on a multi-segment foot model, including mediolateral segmentation, from which they calculate kinematics and kinetics [MacWilliams BA, Cowley M, Nicholson DE. Foot kinematics and kinetics during adolescent gait. Gait Posture 2003;17:214-24]. Their methods are generally well described, and in concept, lead us to new insights regarding foot biomechanics during gait, including kinetics of several joints within the foot itself. However, forces and moments (i.e., force systems) between mediolaterally adjacent segments were ignored in their inverse dynamics calculations. We show theoretically that these omitted force systems instead corrupt the calculated proximal force systems. We also show empirically that physiologically reasonable moment-arms (10-20 mm) and omitted forces (one to four bodyweights) could change both the shape and magnitude of the calculated proximal force systems. In this regard, we demonstrate that these kinetic data need to be viewed with caution. Finally, we extend the concept used in our analysis to general biomechanical modeling.


Testing of properties of digital modules used in gamma-ray spectrometry.
The properties of digital modules (analog-to-digital converters (ADC), digital signal processor (DSP)) in spectrometric chain are the decisive factors which affect the quality of spectrometric measurements. Several properties, integral and differential linearity, channel profiles and throughput, of various ADC and DSP models by CANBERRA were tested.


Effect of lactoferrin on enteric pathogens.
Much has been learned in recent years about the mechanisms by which breastfeeding improves child health and survival. However, there has been little progress in using these insights to improve pediatric care. Factors that are important for protecting the breast fed infant might be expected to decrease the adverse effects of weaning on diarrhea, growth, and development. Lactoferrin, an iron-binding protein with multiple physiological functions (anti-microbial, anti-inflammatory, and immunomodulatory), is one of the most important proteins present in mammalian milk. Protection against gastroenteritis is the most likely biologically relevant activity of lactoferrin. Multiple in vitro and animal studies have shown a protective effect of lactoferrin on infections with enteric microorganisms, including rotavirus, Giardia, Shigella, Salmonella and the diarrheagenic Escherichia coli. Lactoferrin has two major effects on enteric pathogens: it inhibits growth and it impairs function of surface expressed virulence factors thereby decreasing their ability to adhere or to invade mammalian cells. Thus, lactoferrin may protect infants from gastrointestinal infection by preventing the attachment by enteropathogens in the gut. Recently several clinical trials in children have started to address this issue. Whether lactoferrin can prevent a significant portion of diarrheal disease remains to be determined.


Assessment of physicochemical parameters and metal distribution in bog peat of the western segment of the North European part of Russia (Arkhangelsk region).
This article is devoted to the study of physicochemical parameters and the assessment of the accumulation and distribution of metals in peat deposits from the North European part of Russia (Arkhangelsk region). Peat profiles were selected both in the area with a high anthropogenic load and in a bog remote from industrial pollution. The determination of metals was carried out by using the methods X-ray fluorescence analysis and atomic absorption spectroscopy. It was determined that the studied bogs can be attributed to the low ash type, and the recorded pH and mineralisation values make it possible to attribute these deposits to the acid-oxidising facies of oligotrophic peatlands, characteristic of taiga landscapes. Assessment of metal accumulation showed a high content of titanium, chromium, lead, nickel, vanadium, cobalt, aluminium, silicon, and copper in peat, mainly caused by the burning of fossil fuels and industrial production, as well as the burning of urban and industrial waste. The peat profiles are characterised by significant fluctuations in the content of elements in different horizons. Studies have shown the need to monitor the content of metals in peatlands from the Arkhangelsk region to assess atmospheric pollution from industrial emissions, both at the moment and in the past.


Vimentin affects the mobility and invasiveness of prostate cancer cells.
A significant proportion of prostate cancer patients treated with curative intent go on to develop advanced disease. At a fundamental biological level, very little is known about what makes the disease aggressive and metastatic. Observational pathology reports and experimental data suggest that epithelial-mesenchymal transition is involved in prostate cancer invasiveness. Here, we investigated vimentin expression of prostate cancer cells, and explored the potential mechanism of vimentin promoting prostate cancer cells invasion. Vimentin expression was not detected in well differentiated tumors or in moderately differentiated tumors, but the majority of poorly differentiated cancers (5/11 with negative bone scan, 11/14 bone with positive scan) and bone metastases (8/8) had high vimentin expression in tumor cells. Downregulation of vimentin expression in PC-3 cells by transfection with antisense-vimentin led to a significant decrease in tumor cells motility and invasive activity. Furthermore, the expression of E-cadherin was inversely associated with expression of vimentin. Our results suggest that vimentin affects prostate cancer cells motility and invasiveness.


Effects of cis-diamminedichloroplatinum (CDDP) on HeLa cell non-histone nuclear proteins.
Two-dimensional isoelectric focusing and sodium dodecyl sulfate (SDS) gel electrophoretic analyses of successive salt extracts of purified HeLa cell nuclei were used to study the effects of cis-diamminedichloroplatinum (CDDP) (cisplatin) on the synthesis and extractability of nuclear non-histone proteins. Nuclei were extracted sequentially with 0.025 M NaCl-0.075 M EDTA, 0.01 M Tris, and 0.6 M NaCl. Each fraction contained 100-400 polypeptide spots, only a few of which were affected by a 3.5-h CDDP pretreatment of the cells. The biosynthesis and/or metabolism of four polypeptide spots was significantly affected by the CDDP treatment. These polypeptides included: (a) 36K/5.8 (designated by MW/PI) in the 0.025 M NaCl-0.075 M EDTA extract, which decreased in intensity with treatment at 10 micrograms CDDP/ml; (b) polypeptide spots 50K/6.0 and 45K/5.3 in the Tris extract, which increased in intensity over a range of CDDP concentrations of 0-5 microgram CDDP/ml; and (c) a polypeptide complex at 110K/7.7 in the 0.6 M Na Cl extract, which decreased in intensity at CDDP concentrations of 0-5 microgram CDDP/ml. Scanning densitometry of the protein spots of the 0.6 M NaCl extract demonstrated that the 110K/7.7 complex decreased to half its intensity compared with non-drug-treated controls at a CDDP concentration of 0.9 microgram CDDP/ml. We have found that high-resolution two-dimensional gel electrophoretic analysis of nuclear proteins is a valuable technique for studying the effects of cytotoxic agents on the synthesis and/or extractability of specific cellular proteins.


Add-on treatment with pregabalin for partial seizures with or without generalisation: pooled data analysis of four randomised placebo-controlled trials.
Pooled data analysis was performed on individual data from 807 pregabalin- and 367 placebo-treated patients with treatment-resistant partial seizures with or without generalization from four placebo-controlled studies evaluating the short-term efficacy, safety and tolerability of add-on pregabalin 150-600 mg/day. Short-term add-on treatment with pregabalin resulted in statistically significant reductions from baseline in seizure frequency and statistically significantly higher responder rates over placebo (OR 5.93 [95% CI 4.10, 8.57]). Its overall tolerability was good, with an OR of withdrawing from the study due to any reason of 1.71 (95% CIs 1.24, 2.35). The most commonly reported AEs were dizziness and somnolence, however, they were most pronounced during the first week of treatment, followed by a sharp fall in incidences across all dosing groups to <5% from Week 2 and onwards. Weight gain, reported by 5.4-17.1% of patients across pregabalin dosing groups, appeared to be dose-related, but it led to study withdrawal in only 0.74% (6 out of 810) pregabalin-treated subjects. Our analysis suggests that pregabalin has a robust efficacy and good tolerability demonstrated in a study population more treatment-refractory compared to the one enrolled into short-term studies of other new antiepileptic drugs.


Shear bond strength and quantitative microleakage of a multipurpose dental adhesive system resin bonded to dentin.
The shear bond strengths of a dental bonding system used in conjunction with a composite resin bonded to dentin were determined 1 minute after irradiation and after storage in saline at 37 degrees C for 24 hours, 1 week without and with temperature cycling, and 4 weeks without and with temperature cycling. The quantitative microleakage of class V preparations in cementum (dentin) restored with the system was determined by a spectrophotometric dye-recovery method. Excellent shear bond strengths ranging from 13.9 MPa (1 minute) to 19.5 MPa (1 week) were obtained. The shear bond strengths and quantitative microleakage of the multipurpose dental adhesive system compared favorably with the data obtained from other dental bonding systems under similar experimental conditions.


Suppressive effect of an orally active MEK1/2 inhibitor in two different animal models for rheumatoid arthritis: a comparison with leflunomide.
To examine the effects of a mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2-inhibitor, JTP-74057, on inflammatory arthritis development, and compare its anti-arthritic effect with leflunomide. Human, mouse, and rat peripheral blood mononuclear cells (PBMCs) were used. Lewis rats and DBA/1J mice were used for animal models. JTP-74057 was tested between 0.1-100 nM in in-vitro studies. JTP-74057 (0.01-0.3 mg/kg) and leflunomide (2-10 mg/kg) were administered orally in vivo. PBMCs were stimulated with lipopolysaccharide. Adjuvant-induced arthritis (AIA) and type II collagen-induced arthritis (CIA) was induced in Lewis rats or DBA1/J mice, respectively. JTP-74057 blocked tumor necrosis factor-α and interleukin-6 production from PBMCs. AIA and CIA development were suppressed almost completely by 0.1 mg/kg of JTP-74057 or 10 mg/kg of leflunomide. In the CIA, JTP-74057, but not leflunomide, suppressed collagen-reactive T-cell proliferation ex vivo, whereas leflunomide, but not JTP-74057, suppressed anti-collagen antibody production. JTP-74057 exerts potent anti-arthritic effects with a different profile from leflunomide, suggesting that JTP-74057 may be useful as a new therapeutic reagent in the treatment of rheumatoid arthritis.


Characterization of a variant of beta-hexosaminidase: "hexosaminidase Paris".
A family (father and daughter) was found with a deficiency of hexosaminidase (HEX A and HEX B). Residual HEX A activity was about 30% of usual heterozygotes with very little HEX B activity. Thermostability of HEX A was decreased. No immunological cross reacting material was found for HEX A or B. The mechanism seems to be the production of abnormal, unstable beta subunits, which are still capable of combining with alpha subunits to form functional HEX A.


VPAC1 and VPAC2 receptor deficiencies negatively influence pregnancy outcome through distinct and overlapping modulations of immune, trophoblast and vascular functions.
Pregnancy outcome relies on the maintenance of immune and metabolic homeostasis at the maternal fetal interface. Maternal and perinatal morbidity and mortality is associated with impaired placental development. Multiple regulatory effects of the endogenous-produced vasoactive intestinal peptide (VIP) on vascular, metabolic and immune functions at the maternal-fetal interface have been reported. Here we studied the involvement of the two primary high affinity receptors for VIP (VPAC1 and VPAC2) on maternal immune response, placental homeostasis and pregnancy outcome. Targeted disruption of each receptor gene led to altered placental structure, vascular and trophoblast functional markers and shaped the functional profiles of macrophages and neutrophils towards a proinflammatory state. Several changes in pregnant mice were receptor specific: ROS production elicited by VIP on neutrophils was selectively dependent on the presence of VPAC1 whereas apoptosis rate was associated with the VPAC2 deletion. In peritoneal macrophages from pregnant mice, levels of MHC-II, TLR2, and IL-10 were selectively altered in VPAC2 receptor-deficient mice, whereas IL-6 gene expression was reduced only in mice lacking VPAC1 receptors. Additionally, MMP9 mRNA in isolated TGCs was reduced in VPAC2 receptor deleted mice, while the percentage of IL-12 cells in post-phagocytosis macrophage cultures was selectively reduced in VPAC2 receptor deficient mice. The results indicate that manipulation of VPAC1 and VPAC2 receptor affects immune, vascular and metabolic environment at the maternal fetal interface. These mouse models offer new approaches to study pregnancy complications adding new perspectives to the development of VPAC receptor-selective drugs.


Optic disc drusen in children: morphologic features using EDI-OCT.
This study aimed to investigate morphologic features of optic disc drusen (ODD) and peripapillary hyperreflective ovoid mass-like structures (PHOMS) in children, using enhanced depth imaging optical coherence tomography (EDI-OCT). It also assessed if the presence of these features were associated with decreased peripapillary retinal nerve fibre layer (RNFL) thickness. Retrospective observational study of children with ODD. All subjects underwent complete ophthalmic examination and multimodal imaging. ODD were identified on EDI-OCT as circumscribed hyporeflective spheroidal elements located in front of lamina cribrosa, fully or partially surrounded by a hyperreflective border. PHOMS were identified as hyperreflective ovoid structures located in the peripapillary circumference. Both associations between ODD and RNFL loss and PHOMS and RNFL loss were tested using chi-squared test. In total, 38 eyes of 20 children were analysed. PHOMS were present in 90% of patients. ODD and PHOMS were predominantly found in the nasal, superonasal and inferonasal sectors. A significant positive association was found between ODD and decreased RNFL thickness in the nasal (p = 0.02), superonasal (p = 0.05) and inferotemporal (p = 0.04) sectors. There was no significant association found with the presence of PHOMS. EDI-OCT allowed morphological analysis of ODD and PHOMS in children. Drusen were found to be distinct from PHOMS both in their appearance and impact on the RNFL. ODD are hyporeflective and appear on the ONH above the lamina cribrosa and were associated with decreased thickness of the RNFL. On the contrary, PHOMS are hyperreflective structures located around the ONH and were not associated with RNFL loss.


Neural correlates of subliminal and supraliminal letter processing--an event-related fMRI study.
One problem of interpreting research on subconscious processing is the possibility that participants are weakly conscious of the stimuli. Here, we compared the fMRI BOLD response in healthy adults to clearly visible single letters (supraliminal presentation) with the response to letters presented in the absence of any behavioural evidence of visibility (subliminal presentation). No letter catch trials served as a control condition. Forced-choice responses did not differ from chance when letter-to-background contrast was low, whereas they were almost 100% correct when contrast was high. A comparison of fMRI BOLD signals for supraliminal and subliminal letters with the control trials revealed a signal increase in left BA 37 (fusiform gyrus). Comparison of supraliminal with subliminal letters showed a significant increase in the right inferior frontal gyrus (BA 44, partly extending to BA 9 and BA 45, as well as BA 46). Finally, a comparison of subliminal with supraliminal letters showed increases in the left middle temporal gyrus (BA 21) and the right extrastriate cortex (BA 19).


Objective assessment of surgical performance and its impact on a national selection programme of candidates for higher surgical training in plastic surgery.
The objective of this study was to develop and validate a transparent, fair and objective assessment programme for the selection of surgical trainees into higher surgical training (HST) in plastic surgery in the Republic of Ireland. Thirty-four individuals applied for HST in plastic surgery at the Royal College of Surgeons in Ireland (RCSI) in the academic years 2005-2006 and 2006-2007. Eighteen were short-listed for interview and further assessment. All applicants were required to report on their undergraduate educational performance and their postgraduate professional development. Short-listed applicants completed validated objective assessment simulations of surgical skills, an interview and assessment of their suitability for a career in surgery. When applicants' short-listing scores were combined with their interview scores and assessment of their suitability for a career in surgery, individuals who were selected for HST in plastic surgery performed significantly better than those who were not (P<0.002). However, when the assessment of technical skills scores were added the significance level of this difference increased further (P<0.0001) as did the statistical power of the difference to 99.9%, thus increasing the robustness of the selection package. The results from this study suggest that the assessment protocol we used to select individuals for HST in plastic surgery reliably and statistically significantly discriminated between the performances of candidates.


Local perceptions of dengue fever in northeast Thailand and their implications for adherence to prevention campaigns.
The government of Thailand has invested heavily in community-based dengue fever prevention campaigns, yet community participation has been inadequate to prevent transmission. This ethnographic study explored local understandings of dengue in rural northeast Thailand, and their implications for adherence to government-initiated prevention measures centred around mosquito control. While community members recognised the most severe manifestation of the disease - dengue haemorrhagic fever (DHF) - as life threatening, they were unaware of the existence of the milder form of dengue fever (DF) that makes up the majority of cases. Consequently, milder fevers were believed to be something other than dengue, such that dengue was perceived as a rare illness, hindering participation in prevention. Furthermore, a local illness category, khai mak mai ('fruit fever') complicated the diagnosis, treatment and prevention of dengue fever, as people viewed it as both difficult to distinguish from dengue, and untreatable by biomedicine.


Effects of long-term dumping of harbor-dredged material on macrozoobenthos at four disposal sites along the Emilia-Romagna coast (Northern Adriatic Sea, Italy).
Sediment from harbors of the Emilia-Romagna (Northern Adriatic Sea) were dredged and dumped in four disposal areas characterized by muddy bottoms. The long-term effects of the dumping on macrozoobenthic communities were investigated before and after 6 month, 8 month, 2 years and 4 years. The disposal of dredged material did not influence the granulometry and %TOC in the sediment, and no alterations in the structure of the macrobenthic communities were observed in the four areas. The lack of impact could be ascribed to the environmental characteristics and precautionary measures taken to minimize the effects of the dumping. It appears that: (1) the communities of the dumping areas are well adapted to unstable environments; (2) the sediments were disposed gradually and homogeneously over relatively large areas; Other factors that help to reduce the impact of sediment disposal are the low concentrations of contaminants in dredged materials and the similarity of sediment in the dredged and disposal areas. Off-shore discharge appears a sustainable strategy for the management of uncontaminated dredged sediments from the Northern Adriatic Sea harbors.


Getting key players to work together and defending against diversion--Massachusetts.
In this report, the authors trace the development of an effective statewide tobacco control program following victory at the Massachusetts polls in 1992. They examine the pitfalls standing in the way of coalition building and present important lessons for states in similar positions.


Results of early cranial decompression as an initial approach for damage control therapy in severe traumatic brain injury in a hospital with limited resources.
Severe traumatic brain injury (sTBI) is a disease that generates significant mortality and disability in Latin America, and specifically in Colombia. The purpose of this study was to evaluate the 12-month clinical outcome in patients with sTBI managed with an early cranial decompression (ECD) as the main procedure for damage control (DC) therapy, performed in a University Hospital in Colombia over a 4-year period. A database of 106 patients who received the ECD procedure, and were managed according to the strategy for DC in neurotrauma, was analyzed. Variables were evaluated, and the patient outcome was determined according to the Glasgow Outcome Score (GOS) at 12 months postinjury. This was used to generate a dichotomous variable with "favorable" (GOS of 4 or 5) or "unfavorable" (GOS of 1-3) outcomes; analysis of variance was performed with the Chi-square, Wilcoxon-Mann-Whitney and Fisher tests. An overall survival rate of 74.6% was observed for the procedure, At 12 months postsurgery, a favorable clinical outcome (GOS 4-5) was found in 70 patients (66.1%), Unfavorable outcomes in patients were associated with the following factors: Closed trauma, an Injury Severity Score >16, obliterated basal cisterns, subdural hematoma as the main injury seen on the admission computed tomography, and nonreactive pupils observed in the emergency department. Twelve months outcome of patients with sTBI managed with ECD in a neuromonitoring limited resource University Hospital in Colombia shows an important survival rate with favorable clinical outcome measure with GOS.


Growth-controlling molluscan neurons produce the precursor of an insulin-related peptide.
Insulin and related peptides are key hormonal integrators of growth and metabolism in vertebrates. There is little biochemical evidence for insulin-related peptides in invertebrates, apart from insects for which definitive structural information on these peptides (prothoracicotropic hormone, PTTH) has recently been obtained. We report here the first complete complementary DNA-derived primary structure of a preproinsulin-related protein from identified neurons in an invertebrate, the mollusc Lymnaea stagnalis. We have demonstrated by in situ hybridization that transcription of the gene for this molluscan insulin-related peptide (MIP) occurs in the cerebral light-green cells, giant neuroendocrine cells involved in the control of growth, as well as in a pair of neuroendocrine cells called the canopy cells. The insulin-related peptide precursor has the same overall structure as its vertebrate counterparts. The discovery of insulin-related peptides in invertebrates substantiates the evidence for a widespread and early evolutionary origin of the insulin superfamily.


Profiling ocular surface responses to preserved and non-preserved topical glaucoma medications: A 2-year randomized evaluation study.
Use of topical glaucoma medications has been reported to cause ocular surface (OS) discomfort and inflammation. This study explores the profile of inflammatory cytokines and OS symptoms induced in response to preserved and non-preserved drops. Prospective, randomized evaluation on 36 treatment-naïve patients over 24 months of three differently preserved glaucoma drop preparations: Preservative-free (PF), polyquad (PQ) and benzalkonium chloride (BAK). Study participants were evaluated at baseline and then at 1, 3, 6, 12 and 24 months while on medication. At each visit, participants completed the OS disease index (OSDI) questionnaire, had basal tear sampling and impression cytology (IC) of the conjunctival epithelium. Quantitative polymerase chain reaction was performed to measure the gene expression of inflammatory cytokines [interleukin (IL)-6, IL-8, IL-10, IL-12A, IL-12B, IL-17A, IL-1β and tumour necrosis factor-α] in the IC samples. Corresponding protein expression of cytokines in tear samples was assessed by the Becton-Dickinson cytometric bead arrays. Compared to PF and PQ groups, mRNA and protein expression of IL-6, IL-8 and IL-1β increased in samples from the BAK group in a time-dependent fashion, whereas all other cytokines showed a non-significant increase. In the BAK group, there was a strong correlation between OSDI and the levels of IC/IL-1β (r = .832, R2 = .692 and P = .040); IC/IL-10 (r = .925, R2 = .856 and P = .008) and tear/IL-1β (r = .899, R2 = .808 and P = .014). BAK-preserved topical drops stimulate a sterile inflammatory response on the OS within 3 months which is maintained thereafter, whereas PF-drops and PQ-preserved drops showed no significant OS inflammation.


Perception of the touch-induced visual double-flash illusion correlates with changes of rhythmic neuronal activity in human visual and somatosensory areas.
A single brief visual stimulus accompanied by two brief tactile stimuli is frequently perceived incorrectly as two flashes, a phenomenon called double-flash illusion (DFI). We investigated whether the DFI is accompanied by changes in rhythmic neuronal activity, using magnetoencephalography in human subjects. Twenty-two subjects received visuo-tactile stimulation and reported the number of perceived visual stimuli. We sorted trials with identical physical stimulation according to the reported subjective percept and assessed differences in spectral power in somatosensory and occipital sensors. In DFI trials, occipital sensors displayed a contralateral enhancement of gamma-band (80-140 Hz) activity in response to stimulation. In somatosensory sensors, the DFI was associated with an increase of spectral power for low frequencies (5-17.5 Hz) around stimulation and a decrease of spectral power in the 22.5-30 Hz range between 450 and 750 ms post-stimulation. In summary, several components of rhythmic activity predicted variable subjective experience for constant physical stimulation. Notably, the enhanced occipital gamma-band activity during DFI was similar in time and frequency extent to the somatosensory gamma-band response to tactile stimulation. We speculate that the DFI might therefore occur when the somatosensory gamma-response is transmitted to visual cortex. This transmission might be supported by the observed modulations in low-frequency activity.


Aerosol release fraction by concrete scarifying operations and its implications on the dismantling of nuclear facilities.
The sanitation of concrete structures through dismantling of nuclear buildings is complicated by the radiological threat associated with the airborne release of fine dust. This is the reason why the aerosol release fraction (ARF) associated with mechanical removal of concrete structure containing radioactivity needs to be accurately evaluated to implement efficient radiological survey and containment techniques. We characterize experimentally the ARF resulting from milling operations on a standard non-radioactive concrete slab in a confined experimental chamber using an industrial scarifying machine. Our results reveal a significant production of fine aerosol particles with a mass median aerodynamic diameter close to 4 μm and which mineralogical composition is dominated by calcium and silica compounds. The ARF measured when a vacuum suction device is used to confine the dust production close to the source is on the order of 5 × 10-4; the maximum ARF estimated when no suction device is used is on the order of 0.5. As the study is focused on non-radioactive concrete, transposition of aerosol characteristics investigated in this study to assess radioactive airborne release is only relevant for in-depth neutron activation on elemental compounds of concrete.


Graphene-based nanomaterials in the electroplating industry: A suitable choice for heavy metal removal from wastewater.
The presence of various heavy metal ions in the industrial waste waters has recently been a challenging issue for human health. Since heavy metals are highly soluble in the aquatic environments and they can be absorbed easily by living organisms, their removal is essential from the environmental point of view. Many studies have been devoted to investigating the environmental behaviour of graphene-based nanomaterials as sorbent agents to remove metals from wastewaters arising by galvanic industries. Among the graphene derivates, especially graphene oxide (GO), due to its abundant oxygen functional groups, high specific area and hydrophilicity, is a high-efficient adsorbent for the removal of heavy and precious metals in aquatic environment. This paper reviews the main graphene, GO, functionalized GO and their composites and its applications in the metals removal process. The influencing factors, adsorption capacities and reuse capability are highlighted for the most extensively used heavy metals, including copper, zinc, nickel, chromium, cobalt and precious metals (i.e., gold, silver, platinum, palladium, rhodium, and ruthenium) in the electroplating process.


Prevalence, treatment, and outcomes of the hepatic artery stenosis after liver transplantation.
Hepatic artery stenosis (HAS) after liver transplantation can lead to altered hepatic function and/or thrombosis, there by increasing morbidity and mortality. The prevalence of HAS in the literatures varies from 4% to 11%. We sought to describe the prevalence and treatment of hepatic artery stenosis. We performed a descriptive retrospective analysis of 253 liver transplantations from March 1998 to May 2007, including patients with suspected HAS owing to increased hepatic enzymes, altered Doppler ultrasound (us) and hepatic biopsy. The confirmation of HAS was achieved through areriography. Nine patients were identified to have HAS, a 3.5% prevalence. Among the HAS patients, seven were male and two female. Their average age was 35.5 years (range, 65 to 53). The average time between the diagnosis and transplantation was 14.2 months (range, 9 to 68). The increase in hepatic enzymes among this group averaged: aspartate aminotransferase 131 U/L (range, 26 to 412) and alanine aminotransferase 192 U/L (range, 35 to 511). Doppler US showed alteration in the resistance level index. All patients underwent areriography; only one could not be treated owing to severe hepatic artery spasm, which also occurred during another attempt weeks after the first one. Among the eight patients, six were treated with stents and two with angioplastis. All treated patients displayed improvements in parameters. Four patients treated with stents required retreatment: two underwent angioplasty and two, a thrombolytic. One graft rethrombosed but evolved in compensated fashion with recanalization by collaterals. There has been no graft loss or mortality in this population. The average time of posttreatment follow-up was 31.28 (range, 9 to 68) months. The prevalence of HAS in our unit was within that reported in the literature. Treatment with a stent or angioplasty proved to be efficient to control this complication, considering that hepatic function recovered and that there was neither graft nor patient loss.


The presence of gestational diabetes is associated with increased detection of anti-HLA-class II antibodies in the maternal circulation.
Gestational diabetes (GD) may be associated with temporarily reduced immune tolerance toward alloantigens for the time of pregnancy. The aim of this study was to assess anti-HLA-class I and -II antibodies as markers for an aberrant immunostimulation in women with GD. The percentage of anti-HLA-class I and -II antibodies was estimated in women with GD, normal term delivery and fetal distress, which was confirmed by demonstrating low cord blood pH for this patient group. These antibodies may cross the placental barrier and cause interleukin-6 (IL-6) release from fetal monocytes by cross-linking monocytes with antibody-loaded cells. Therefore we estimated the percentage of IL-6-positive monocytes in the fetal circulation of these three patient groups. We found a significantly increased percentage of anti-HLA-class II in the circulation of women with GD. In comparison with women with normal term delivery, a significantly increased percentage of IL-6-positive monocytes was detected for women with GD and for women with fetal distress. Significantly decreased cord blood pH were detected for neonates born in the presence of fetal distress but not for neonates born in the presence of GD. Our results suggest that GD is associated with an increased humoral immune response against HLA-class II antigens.


Cerumen impaction was composed of abnormal exfoliation of keratinocytes that was correlated with infection.
This study investigated the exact composition and tried to be helpful in explaining the etiologic mechanism of cerumen impaction in the external auditory canal (EAC). A hundred impacted cerumen samples and 15 normal cerumen samples were collected by manual removal and divided into 2 groups. All samples were examined via microbial culture, hematoxylin-eosin staining, periodic acid-Schiff staining, and fungal fluorescent staining. Eighty-eight patients in group 1 were in the habit of using cotton buds. Forty-seven impacted cerumen samples tested positive for microbes, while only 1 sample of normal cerumen tested positive for microbes (p < .05). The most commonly isolated bacterium and fungus was Staphylococcus aureus and Aspergillus terreus respectively. All cerumen samples were composed of exfoliated keratinocytes and microorganisms assessed via pathologic examination. However, unlike normal cerumen, impacted cerumen contained nucleated keratinocytes and infiltrated neutrophils. Recurrent impaction was found only among patients who tested mold culture-positive. Impacted cerumen is composed of abnormal exfoliated keratinocytes that was correlated with microbial-induced neutrophil-mediated inflammation. Mold infection is highly correlated with recurrent cerumen impaction. Microbial culture of removed impacted cerumen is strongly recommended. Ear cleaning with cotton buds, particularly when the EAC is wet might be one of the important causes of cerumen impaction which is need further studied. 2b.


Modeling effective transmission pathways and control of the world's most successful parasite.
Toxoplasma gondii(T. gondii) is a single-celled, intracellular protozoan responsible for the disease toxoplasmosis. The parasite is prevalent worldwide, and it infects all warm-blooded vertebrates. Consumption of meats in which this parasite has encysted confers risk of infection to people and other animals, as does ingestion of water or foods contaminated with environmentally resistant oocysts excreted by cats. Vertical transmission (from mother to offspring) is also possible, leading to disease risk and contributing additional means of ensuring perpetuation of transmission. In this work, we adopt a differential equation model to investigate the effective transmission pathways of T. gondii, as well as potential control mechanisms. Detailed analyses are carried out to examine the significance of transmission routes, virulence, vertical transmission, parasite-induced changes in host behavior, and controls based on vaccination and harvesting. Modeling and analysis efforts may shed insights into understanding the complex life cycle of T. gondii.


Secondary angle-closure glaucoma in cicatricial retrolental fibroplasia.
Five patients had cicatricial retrolental fibroplasia with a complication of secondary angle-closure glaucoma. In all the patients, the glaucoma occurred after age 2 years. All were treated with a pars plana lensectomy and anterior vitrectomy, which alleviated the glaucoma. They all achieved normal intraocular pressure and a pain-free eye. However, visual acuity was poor, in the range of light perception to hand motions. All patients have been followed up for one year and in only one patient has the fellow eye developed secondary angle-closure glaucoma.


Hype or opportunity? Using microbial symbionts in novel strategies for insect pest control.
All insects, including pest species, are colonized by microorganisms, variously located in the gut and within insect tissues. Manipulation of these microbial partners can reduce the pest status of insects, either by modifying insect traits (e.g. altering the host range or tolerance of abiotic conditions, reducing insect competence to vector disease agents) or by reducing fitness. Strategies utilizing heterologous microorganisms (i.e. derived from different insect species) and genetically-modified microbial symbionts are under development, particularly in relation to insect vectors of human disease agents. There is also the potential to target microorganisms absolutely required by the insect, resulting in insect mortality or suppression of insect growth or fecundity. This latter approach is particularly valuable for insect pests that depend on nutrients from symbiotic microorganisms to supplement their nutritionally-inadequate diet, e.g. insects feeding through the life cycle on vertebrate blood (cimicid bugs, anopluran lice, tsetse flies), plant sap (whiteflies, aphids, psyllids, planthoppers, leafhoppers/sharpshooters) and sound wood (various xylophagous beetles and some termites). Further research will facilitate implementation of these novel insect pest control strategies, particularly to ensure specificity of control agents to the pest insect without dissemination of bio-active compounds, novel microorganisms or their genes into the wider environment.


Dengue hepatitis with acute liver failure: Clinical, biochemical, histopathological characteristics and predictors of outcome.
Hepatitis infection from non-hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV-related ALF. We aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV-related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively. Thirty-six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty-one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non-survivors. Lactate levels, pH at admission, and model for end-stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non-survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non-survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively. Dengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome.


uSIMPK. An Excel for Windows-based simulation program for instruction of basic pharmacokinetics principles to pharmacy students.
Pharmacokinetics can be a challenging topic to teach due to the complex relationships inherent between physiological parameters, mathematical descriptors and equations, and their combined impact on shaping the blood fluid concentration vs. time curves of drugs. A computer program was developed within Microsoft Excel for Windows, designed to assist in the instruction of basic pharmacokinetics within an entry-to-practice pharmacy class environment. The program is composed of a series of spreadsheets (modules) linked by Visual Basic for Applications, intended to illustrate the relationships between pharmacokinetic and in some cases physiological parameters, doses and dose rates and the drug blood fluid concentration vs. time curves. Each module is accompanied by a simulation user's guide, prompting the user to change specific independent parameters and then observe the impact of the change(s) on the drug concentration vs. time curve and on other dependent parameters. "Slider" (or "scroll") bars can be selected to readily see the effects of repeated changes on the dependencies. Topics covered include one compartment single dose administration (iv bolus, oral, short infusion), intravenous infusion, repeated doses, renal and hepatic clearance, nonlinear elimination, two compartment model, plasma protein binding and the relationship between pharmacokinetics and drug effect. The program has been used in various forms in the classroom over a number of years, with positive ratings generally being received from students for its use in the classroom.


Sequential UV-biological degradation of chlorophenols.
The sequential UV-biological degradation of a mixture of 4-chlorophenol (CP), 2,4-dichlorophenol (DCP), 2,4,6-trichlorophenol (TCP), and pentachlorophenol (PCP) was first tested with each pollutant supplied at an initial concentration of 50 mg l(-1). Under these conditions, the chlorophenols were photodegraded in the following order of removal rate: PCP>TCP>DCP>CP with only CP and DCP remaining after 40 h of irradiation. The remaining CP (41 mg l(-1)) and DCP (13 mg l(-1)) were then completely removed by biological treatment with an activated sludge mixed culture. Biodegradation did not occur in similar tests conducted with a non-irradiated mixture due to the high microbial toxicity of the solution. UV treatment lead to a significant reduction of the phytotoxicity to Lipedium sativum but no further reduction of phytotoxicity was observed after biological treatment. Evidence was found that the pollutants were partially photodegraded into toxic and non-biodegradable products. When the pollutants were tested individually (initial concentration of 50 mg l(-1)), PCP, TCP, DCP, 4-CP were photodegraded according to first order kinetic model (r2>99) with half-lives of 2.2, 3.3, 5.7, and 54 h, respectively. The photoproducts were subsequently biodegraded. This study illustrates the potential of UV as pre-treatment for biological treatment in order to remove toxicity and enhance the biodegradability of organic contaminants. However, it also shows that UV treatment must be carefully optimized to avoid the formation of toxic and/or recalcitrant photoproducts and results from studies conducted on single contaminants cannot be extrapolated to mixtures.


Comparison of imaging using 11C-ITMM and 18F-FDG for the detection of cerebellar ataxia.
Objective Newly developed methods for imaging type 1 metabotropic glutamate receptor (mGluR1) have the potential use for estimating cerebellar function. We aimed to compare mGluR1 imaging using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-11C-methoxy-N-methylbenzamide (11C-ITMM) with the existing marker, fluorine-18-labeled fluorodeoxyglucose (18F-FDG) imaging, in the cerebellum. Fourteen subjects consisting of 12 patients with cerebellar ataxia and two healthy subjects underwent 11C-ITMM and 18F-FDG positron emission tomography. The degree of ataxia was scored with the Scale for the Assessment and Rating of Ataxia (SARA). Volumes-of-interest were placed on the anterior and posterior lobes and vermis. The binding potential (BPND) was calculated to estimate mGluR1 availability using the white matter as a reference region. 18F-FDG uptake was normalized using the white matter (FUwm). There were significant positive correlations between the BPND and FUwm values in the anterior lobe (r=0.83, P<0.001), posterior lobe (r=0.69, P=0.009), and vermis (r=0.58, P=0.042). Regarding the relationship of SARA scores with the BPND and FUwm values, a significant negative correlation was found only in the anterior lobe between the SARA scores and BPND values (r=-0.64, P=0.029). This study showed that mGluR1 imaging was comparable to 18F-FDG imaging in the cerebellum. However, mGluR1 imaging was more strongly associated with the SARA scores than 18F-FDG imaging was, suggesting that mGluR1 imaging can be a more specific technique than 18F-FDG imaging for evaluating cerebellar ataxia.


Prevalence of natural infection by Trypanosoma evansi in Crioula LAGEANA cattle.
Cattle trypanosomiasis negatively impacts animal husbandry due to high morbidity, productivity losses, and mortality rates. Knowledge regarding Trypanosoma evansi infections in locally adapted breeds remains limited. Some cattle breeds exhibit trypanotolerance, requiring the determination of prevalence, as well as related tolerance and resistance characteristics, for disease control programs. This study aimed to determine T. evansi prevalence in Crioula Lageana cattle and associate clinical, hematological, and biochemical aspects with the infection to further research on tolerance in this population. Blood samples from 310 Crioula Lageana cattle were tested using Polymerase Chain Reaction (PCR) and Indirect Immunofluorescence Reaction (IIFR). T. evansi prevalence was 8% (24/310) using PCR and 4% (11/310) using IIFR. Positive animals showed increased ruminal movements, elevated eosinophil counts, and reduced monocyte numbers, but both latter within the reference range for the species. Albumin concentrations were low in positive cases and remained below the reference range limit for both groups. However, triglycerides exceeded the physiological range for the species in both positive and negative groups. Increased gamma-glutamyltransferase (GGT) activity was observed in positive animals. In conclusion, Crioula Lageana cattle exhibited enzootic instability with a low T. evansi infection prevalence when assessed using PCR and IIFR techniques. Furthermore, the animals did not display clinical, hematological, or biochemical alterations attributable to the presence of hemoparasites.


The significance of APACHE II as a predictor of mortality in paraquat poisoning: A systematic review and meta-analysis.
The Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system is utilised as a prognostic method in paraquat poisoning; however, current evidence shows ambiguity. Although some studies have shown APACHE II to be a superior tool, others have reported it inferior to other prognostic markers, such as lactate, severity index of paraquat poisoning and urine paraquat concentration. Hence, to address this ambiguity, we conducted a systematic review and meta-analysis to analyse prognostic accuracy of APACHE II score in predicting mortality in paraquat poisoning. We included twenty studies with 2524 paraquat poisoned patients in the systematic review, after a comprehensive literature search in databases PubMed, Embase, Web of Science, Scopus and Cochrane Library, from which 16 studies were included in the meta-analysis. The survivors of paraquat poisoning were found to have significantly lower APACHE II scores (Mean Difference (MD): -5.76; 95% CI: -7.93 to -3.60 p < 0.0001; n = 16 studies) compared to non-survivors. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for APACHE II score <9 was found to be 74%, 68%, 2.58, 0.38 and 7.10, respectively (n = 5 studies). The area under the curve (AUC) of the bivariate summary receiver operating characteristic (SROC) curve was found to be 0.80. The pooled sensitivity, specificity, PLR, NLR and DOR for APACHE II score ≥9 was found to be 73%, 86%, 4.69, 0.33 and 16.42, respectively (n = 9 studies). The AUC of the SROC curve was found to be 0.89. Pairwise AUC comparison of APACHE II with other prognostic markers showed serum presepsin to have a significantly better discriminatory ability than APACHE II. Through the findings of this study, we conclude that APACHE II was found to be a good indicator of death in paraquat poisoning patients. However, higher APACHE II scores (≥9) depicted greater specificity in predicting mortality in paraquat poisoning. Thus, APACHE II can be used as a practical tool in the hand of physicians to prognose patients with paraquat poisoning to aid clinical decisions.


Use of propofol for prevention of post-delivery nausea during cesarean section: a double-blind, randomized, placebo-controlled trial.
Nausea and vomiting are common, undesirable symptoms during cesarean section. We conducted this study to assess the antiemetic properties of propofol for the prevention and immediate treatment of post-delivery nausea and vomiting during cesarean section under combined spinal-epidural anesthesia. Eighty women undergoing elective cesarean delivery under combined spinal-epidural anesthesia were randomized to receive either propofol at a plasma concentration of 1000 ng/mL or normal saline immediately after clamping of the umbilical cord. The incidence of post-delivery nausea and vomiting, patients requiring rescue antiemetic, bispectral index, sedation score, and the incidence of hypotension were assessed intraoperatively. Satisfaction and neonatal behavioral neurological assessments were evaluated postoperatively. The incidence of nausea was significantly lower in the propofol group compared to the placebo group (25% versus 60%, P < 0.001). The incidence of retching and vomiting showed no significant difference between the two groups. Propofol 20 mg as a rescue antiemetic was significantly effective in both the groups. Satisfaction level of patients and obstetricians in the propofol group was higher than in the placebo group. There was no statistical difference in the incidence of hypotension between the two groups both pre- and post-delivery. There was no difference in postoperative neonatal behavioral neurological assessment between groups. Propofol at a plasma concentration of 1000 ng/mL significantly reduced the incidence of post-delivery nausea compared to placebo, but had no effect on reducing retching or vomiting episodes during cesarean section.


Effects of timing, location and definition of reinfarction on mortality in patients with totally occluded infarct related arteries late after myocardial infarction.
The Occluded Artery Trial (OAT) randomized stable patients (n=2201)>24 h (calendar days 3-28) after myocardial infarction (MI) with totally occluded infarct-related arteries (IRA), to percutaneous coronary intervention (PCI) with optimal medical therapy, or optimal medical therapy alone (MED). PCI had no impact on the composite of death, reinfarction, or class IV heart failure over extended follow-up of up to 9 years. We evaluated the impact of early and late reinfarction and definition of MI on subsequent mortality. Reinfarction was adjudicated according to an adaptation of the 2007 universal definition of MI and the OAT definition (≥2 of the following--symptoms, EKG and biomarkers). Cox regression models were used to analyze the effect of post-randomization reinfarction and baseline variables on time to death. After adjustment for baseline characteristics the 169 (PCI: n=95; MED: n=74) patients who developed reinfarction by the universal definition had a 4.15-fold (95% CI 3.03-5.69, p<0.001) increased risk of death compared to patients without reinfarction. This risk was similar for both treatment groups (interaction p=0.26) and when MI was defined by the stricter OAT criteria. Reinfarctions occurring within 6 months of randomization had similar impact on mortality as reinfarctions occurring later, and the impact of reinfarction due to the same IRA and a different epicardial vessel was similar. For stable post-MI patients with totally occluded infarct arteries, reinfarction significantly independently increased the risk of death regardless of the initial management strategy (PCI vs. MED), reinfarction definition, location and early or late occurrence.


Gambling problems, risk factors, community knowledge, and impact in a US Lao immigrant and refugee community sample.
The objectives of this study were to examine gambling-related problems, risk factors, help-seeking attitudes, community perceptions, and correlates of problem gambling in a Lao sample of Southeast Asian refugees and immigrants and to discuss cultural implications for the treatment and prevention of gambling problems in Southeast Asian refugee and immigrant populations. This was a cross-sectional, community-based interview study. Participants (N = 200, males = 51%, females = 49%) were recruited from a Lao community center in a major US metropolitan area (convenience sample; community center recruitment and peer nomination). Structured interviews on gambling and substance use were conducted by Lao center staff members in both English and Lao languages. Gambling-related problems were measured using the South Oaks Gambling Screen (SOGS), gambling frequency, and quantity measures. In a previous study, we reported a substantial number of participants from the sample endorsed gambling-related harms and problems (SOGS score of five or more = 24%) and common methods of play were slots, house betting, cards at a casino, and sports betting. Among those endorsing five or more gambling problems, reasons for gambling included making money (68%), social life (31.3%), entertainment (58.3%), and reducing boredom (35.4%). Less commonly endorsed reasons were depression or stress (14.6%) and escape (10.4%). Many participants reported a family history of gambling problems. Those with problem gambling had twice the level of sibling problem gambling histories relative to those without problem gambling (35.4% vs. 11.1%). There were substantially more participants in the problem gambling group who had started gambling before the age of 13 years than in non-problem gamblers (P < .05). Many recognized gambling as a significant issue in the community and reported knowing several individuals affected by gambling-related problems. Many participants recognized gambling as a significant issue in the Lao community. We include insights gleaned from a research partnership with a community organization. Although data cannot be generalized to the Lao community because of limitations in sampling methodology, participants viewed gambling as a culturally common social practice. Cultural norms affected where community members gamble, types of games, and betting practices. In this context, community members may view gambling-related harms as both a community-level and individual-level concern. These data suggest a significant need for rigorous research to inform policies and a culturally sensitive approach to public health prevention, intervention, and education. We discuss the challenges and cultural barriers to research and community engagement and offer suggestions for prevention and intervention ideas efforts.


An Ixodes scapularis glutathione S-transferase plays a role in cell survival and viability during Langat virus infection of a tick cell line.
Ticks are important vectors of diseases affecting both humans and animals. To be an efficient vector, ticks have to survive infection by pathogens such as the Langat virus (LGTV). One method utilized by ticks is their complex antioxidant mechanism. Included in the vast antioxidant processes are several enzymes involved in redox homeostasis. The ubiquitous glutathione S-transferases (GSTs) belong to the antioxidant family of enzymes. In this study, we evaluated the role of a GST during LGTV infection. ISE6 cells were infected with LGTV with a multiplicity of infection (MOI) of 0.01 and observed daily. The infection success was monitored via indirect immunofluorescent antibody test (IFAT) for LGTV for up to 4 days. The gene expression of IsGST1 was determined by real-time polymerase chain reaction (PCR) using IsGST1 gene-specific primers. Knockdown of the IsGST1 gene with subsequent LGTV infection was also performed. Afterward, ISE6 cell mortality and viability were checked daily until the fourth day. The virus titer from supernatants of IsGST1-knockdown cells was quantified using a focus-formation assay. IFAT data showed that LGTV infects ISE6 cells in a time-dependent manner with increasing infection from day 0 to day 4. The IsGST1 genes showed an increasing expression until day 2 of infection, while decreased expression was observed from day 3 to day 4 post-infection. Knockdown of the IsGST1 resulted in increased mortality on the third day of infection, while the cell viability was also negatively affected by the knockdown of the IsGST1 genes from day 0 to day 4 post-infection. Knockdown of the IsGST1 genes also resulted in a decreased viral titer from the supernatants of the ISE6 cells infected with LGTV. Based on the results, GSTs are possibly utilized both by cells and the virus for mutual survival and proliferation.


Significance of anomalous thermoregulation in the pre-diabetic spiny mouse (Acomys cahirinus): oxygen consumption and temperature regulation.
In keeping with studies of other desert rodents, the potentially diabetic spiny mouse has been demonstrated to have a very low basal metabolic rate, disproportionate to its body weight. The maintenance of a lower body temperature in response to high environmental temperatures and a lack of increase in metabolic rate in response to cooling have also been demonstrated. Assessments of "mechanical efficiency" have shown that spiny mice carry a potential selective advantage under fasting conditions. The findings, some of which are similar to those noted in other desert rodents, and in other species showing either spontaneous or induced hyperglycaemia, suggest that the low metabolic rate is at least partly based on ineffective glucose utilization. This phenomenon may be the common denominator of the survival advantage which has allowed both the successful evolution of species inhabiting warm, arid climes, and the persistence of the diabetic genotype in animal and human populations.


Recombinant activated Factor VII as a hemostatic agent in very low birth weight preterms with gastrointestinal hemorrhage and disseminated intravascular coagulation.
Acute hemorrhage in preterm infants leads immediately to a life-threatening event because of the small circulating blood volume. The beneficial use of recombinant activated Factor VII (rFVIIa; NovoSeven, NovoNordisk, Gentofte, Denmark) as hemostatic treatment in neonates with hemorrhagic shock has been described. Necrotizing enterocolitis is a challenge in neonatology as the disease represents one of the leading causes of mortality in preterm infants. We report on the use of rFVIIa in very low birth weight (<1500 g), preterms with intestinal hemorrhage, and disseminated intravascular coagulation (DIC). Retrospective analysis of 5 cases. Five preterm infants <or=28 weeks gestational age with DIC and hemorrhagic shock due to severe diffuse gastrointestinal bleeding. Intravenous bolus administration of 100 to 180-microg/kg rFVIIa (total of 9 doses) as rescue procedure after other interventions (substitution of platelets, fresh frozen plasma, red packed cells, surgery) failed to achieve hemostasis. Two patients with severe acidosis, hypothermia, and thrombopenia died in hemorrhagic shock, treatment with rFVIIa was unsuccessful. In 3 patients, rFVIIa was effective and gastrointestinal bleeding could be stopped. No acute adverse event, increasing bowel necrosis, increasing platelet consumption, or thromboembolic complications were observed. In this small group of preterms with DIC, intestinal hemorrhage, and persistent hemorrhagic shock, rFVIIa was effective as a rescue therapy but failed in patients with severe acidosis, hypothermia, and thrombopenia.


[Habitual shoplifting in multi-infarct syndrome].
The authors report on a 59-year-old male who repeatedly had been apprehended for shoplifting. The behavior only started after he had suffered multiple ischemic strokes. The deviant behavior is explained as a consequence of frontal lobe lesions leading to behavioral disinhibition. Criminal responsibility had to be denied.


Acute urinary retention.
Acute urinary retention is a common emergency genitourinary symptom. The etiology of acute retention includes obstructive, neurogenic, pharmacologic, and psychogenic causes. The emergency management of acute urinary retention is bladder decompression, which is usually accomplished with a Foley catheter.


Physiological and functional characteristics of Propionibacterium strains of the poultry microbiota and relevance for the development of probiotic products.
The prevention and control of pathogens colonization through probiotics administration in poultry feeding is of increasing interest. The genus Propionibacterium is an attractive candidate for the development of probiotic cultures as they produce short chain fatty acids (SCFA) by carbohydrates fermentation. The presence of strains of this genus in hens of conventional production systems and backyard hens was investigated. Propionibacteria were isolated from the intestine and identified by physiological and biochemical tests. PCR amplification of the 16S rRNA gene of the isolates was performed and products were compared with sequences from databases. The presence of the genus Propionibacterium was demonstrated in 26% of hens and Propionibacterium acidipropionici and Propionibacterium avidum were the identified species. A comparative study of their physiological and functional characteristics was performed. P. acidipropionici strains were the most resistant to in vitro gastrointestinal digestion, but the adhesion to intestinal tissue was strain dependent. Some differences were found between both species with respect to their growth and SCFA production in an in vitro cecal water model, but all the strains were metabolically active. The production of SCFA in cecal slurries inoculated with the strain P. acidipropionici LET 105 was 30% higher than in non-inoculated samples. SCFA concentrations obtained were high enough to inhibit Salmonella enterica serovar Enteritidis when assayed in a cecal water model. P. acidipropionici LET 105 was also able to compete with Salmonella for adhesion sites on the intestinal mucosa in ex vivo assays. Results contribute to the knowledge of the species diversity of the genus Propionibacterium in the intestine of poultry and provide evidence of their potential for probiotics products development.


The essential role of charge-shift bonding in hypervalent prototype XeF₂.
Hypervalency in XeF₂ and isoelectronic complexes is generally understood in terms of the Rundle-Pimentel model (which invokes a three-centre/four-electron molecular system) or its valence bond version as proposed by Coulson, which replaced the old expanded octet model of Pauling. However, the Rundle-Pimentel model is not always successful in describing such complexes and has been shown to be oversimplified. Here using ab initio valence bond theory coupled to quantum Monte Carlo methods, we show that the Rundle-Pimentel model is insufficient by itself in accounting for the great stability of XeF₂, and that charge-shift bonding, wherein the large covalent-ionic interaction energy has the dominant role, is a major stabilizing factor. The energetic contribution of the old expanded octet model is also quantified and shown to be marginal. Generalizing to isoelectronic systems such as ClF₃, SF₄, PCl₅ and others, it is suggested that charge-shift bonding is necessary, in association with the Rundle-Pimentel model, for hypervalent analogues of XeF₂ to be strongly bonded.


Effects of ATP, vanadate, and molybdate on cathepsin D-catalyzed proteolysis.
The effects of ATP, vanadate, and molybdate on cathepsin D-catalyzed hydrolysis of proteins and peptides were examined. Hydrolysis of bovine serum albumin, hemoglobin, parathyroid hormone, and a synthetic octapeptide was activated by ATP. Degradation of the protein substrates all had similar ATP concentration dependence, but the magnitude of the activation varied. Kinetic constants for ATP activation were obtained with a synthetic substrate. ATP increased kcat from 0.4 to 2 s-1 but did not change KM. Kact for ATP was 800 microM. Studies with pepstatin-Sepharose confirm that ATP does not alter the substrate binding site on cathepsin D. Pepsin, a homologous aspartate protease, was not activated by ATP. It was also found that vanadate and molybdate inhibit cathepsin D-catalyzed proteolysis. However, this inhibition was dramatically dependent on substrate concentration and was eliminated at high substrate. Hydrolysis of the synthetic peptide was not inhibited at concentrations of molybdate below 50 microM, and above this concentration the peptide precipitated. Protein substrates were also found to precipitate in the presence of molybdate. The ATP dependence of the enzyme was not altered by molybdate or vanadate. These results suggest that inhibition by vanadate and molybdate is related to interactions with the substrate rather than with cathepsin D. It is concluded that ATP activation of cathepsin D may play a physiological role in regulation of proteolysis in lysosomes, but that vanadate and molybdate inhibition of lysosomal proteolysis does not establish ATP dependence.


Fertility preservation in adolescent males: experience over 22 years at Rouen University Hospital.
Sperm banking is a suitable procedure to prevent infertility after cancer therapy in male adolescents. We evaluated the feasibility of semen preservation in 156 adolescents aged between 13 and 20 years and then we assessed fertility outcome after treatment. Age, urogenital history, indications for cryopreservation, histological diagnosis and semen parameters were recorded. Fertility status after treatment was assessed by a questionnaire addressed to those patients who had utilized sperm storage. Post-treatment semen analysis was performed for 22 patients. Cryopreservation was possible in 88.5% of cases. Azoospermia was detected in 2.6% of the patients at the time of diagnosis. Malignant disease accounted for 84% of our male adolescents. In this type of disease, semen parameters were significantly altered only among patients with metastatic malignant bone tumour. After treatment, nine patients presented azoospermia, five patients achieved pregnancy spontaneously, two achieved it after assisted reproductive technique using fresh ejaculated spermatozoa and one following sperm donation. Three failed with cryopreserved sperm. Semen cryopreservation is possible for most adolescents and, regardless of disease type, may be a means of preserving fertility prior to gonadotoxic treatment that might impair the spermatogenesis process.


Biliary tract tuberculosis--a diagnostic dilemma.
Most western patients who have not had a previous operation and present with biliary obstruction are thought to have a malignant lesion. However in our country where the disease is common, we found that some of these patients had a tuberculous cause which considerably altered their management as well as their prognosis. We herein present our experience of these patients whom we had operated with a preoperative diagnosis of biliary tract malignancy and discuss, retrospectively, how they might have been detected before operation to have tuberculosis. Between August 1996 and June 2010, we operated on 209 patients with a preoperative diagnosis of carcinoma of the gallbladder and common bile duct. Seven out of these 209 patients had biliary tuberculosis. We retrospectively analyzed the clinical features of these patients from our prospectively maintained database. There were four males and three females who had a mean age of 54 (32-65) years. The bile duct was involved in four and gallbladder in three patients. In contrast to those with malignancy, patients with tuberculosis had a longer history (122 vs 44 days), an abdominal mass was present less frequently (28% vs 57%), the serum bilirubin was lower (1.6 vs 6 mg/dl), and they also had evidence of tuberculosis elsewhere in the body (28.5%). There was no operative mortality in biliary tract tuberculosis in contrast to 7.5% in biliary tract malignancy. Though tuberculosis of the biliary tract is rare, it needs to be considered in the differential diagnosis of patients with biliary obstruction especially in countries where the disease is endemic.


Is there a ceiling lamotrigine serum level in epileptic children in remission?
Seizure control, in patients with epilepsy, is proportionally associated with health-related quality of life. Antiepileptic therapy leads to seizure remission in most cases. However, some patients are resistant to treatment despite achieving high doses which can be explained by interindividual variability of antiepileptic drugs' metabolism. A ceiling exposure, in epilepsy, helps to adapt the therapeutic strategy in a faster way and to prevent unnecessary exposure to adverse drug reactions. Due to the increasing use of new generations of antiepileptic drugs, we aimed to explore the distribution of lamotrigine (LMT) trough serum levels in epileptic children, stratified between remission and ongoing seizures, in order to determine whether there is a ceiling effect associated with remission. We conducted a retrospective study (2012-2021) including children, with generalized epilepsy (2-18 years), addressed for a therapeutic drug monitoring of LMT trough serum levels. Patients in remission, should have as lasting three times the longest pre-treatment seizure-free interval and more than one year. The population of 114 children with generalized epilepsy was divided in to groups: epileptic children in remission (36) and epileptic children with ongoing seizures (78). There was no significant difference in age and sex in the two groups. Median LMT daily dose and trough serum levels were significantly higher in group 2. The highest LMT serum trough level was 11μg/mL in group 1 and 23.1μg/mL in group 2. Valproate was associated in 29%. There was no significant difference of the distribution of valproate in the two groups (P=0.08). Children in remission had a LMT trough serum levels under 11μg/mL and a daily dose of 3.36mg/kg/day or less. These results suggest that this LMT serum level and daily dose might be associated with a ceiling effect in epileptic children.


Ca2+ signalling in exocrine acinar cells: the diffusional properties of cellular inositol 1,4,5-trisphosphate and its role in the release of Ca2+.
The correlation between acetylcholine induced changes in the intracellular free, Ca2+ concentration ([Ca2+]i), and the inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) content in isolated acini from the rat parotid and lacrimal glands was investigated. Applying digital image processing on Fura-2 loaded acini, we observed that Ca2+ increases either simultaneously throughout the acinar configurations or that occasionally, the rise near the lumen can precede the rise near the basal part by 50-100 ms. Measurements on cell suspensions revealed a correlation between changes in [Ca2+]i and changes in the cellular Ins(1,4,5)P3 content, and it is concluded that in the individual cells Ins(1,4,5)P3 is released to the cytosol within the first second after stimulation. Applying a diffusion coefficient for cytoplasmic Ins(1,4,5)P3 of 2.83 x 10(-6) cm2/s (Allbritton et al., 1992, Science, 258, 1812-1815), we have calculated the concentration profile for this messenger in a sphere with a radius of 10 microns where Ins(1,4,5)P3 is released in the center following a monoexponential function with a rate constant of 4 s-1. Assuming that Ins(1,4,5)P3 concentrations of 1 or 5% of the maximum value is able to release Ca2+, we calculated that Ca2+ waves can appear at a rate of 100 or 40 microns/s. The present data are consistent with Ins(1,4,5)P3 being a cellular messenger, that by diffusion, initiates the Ca2+ release from the cellular pools within the first fraction of a second.


The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy.
The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy. This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien-Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival. Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029). In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.


A study of glycogen storage disease with 99Tcm-MIBI gated myocardial perfusion imaging.
Gated myocardial perfusion imaging (G-MPI) is regularly performed using single-photon emission computed tomography. The objective of this study was to evaluate the clinical value of 99Tcm-methoxyisobutylisonitrile (MIBI) myocardial imaging in glycogen storage disease (GSD). 99Tcm-MIBI G-MPI was performed in nine patients with clinically proven GSD. QGS quantitative software was used for processing and interpretation. Left ventricular ejection fraction (LVEF), end-diastolic volume (EDV) and end-systolic volume (ESV) were automatically generated. The myocardium was divided into seven segments, 20 sub-segments and a five-point scoring system was used. Seven out of nine cases were abnormal and the positive rate of G-MPI was 77.8 %. Sixty-two sub-segments of injured myocardium were detected in 140 sub-segments of seven abnormal patients. One injured segment was observed in one patient (14.3 %), two segments were detected in two patients (28.6 %) and three or more abnormal segments were observed in four patients (57.1 %). 99Tcm-MIBI G-MPI can detect myocardial damage in GSD as a non-invasive method. It plays an important role in the clinic.


Myasthenia gravis. Identification of skeletal and heart muscle antigens not related to the acetylcholine receptor.
Myasthenia gravis (MG) is a neuromuscular disease thought to have an autoimmune etiology. The acetylcholine receptor has been considered the primary site of antibody binding; however, other muscle components may be involved in the pathogenesis of myasthenia gravis. This study describes a hypertonic sucrose extract of skeletal muscle (Muscle-HSE) that reacts with antibodies in myasthenic sera. The active component in Muscle-HSE is not the acetylcholine receptor as demonstrated by the inability of this extract to bind [125I]alpha-bungarotoxin. Muscle-HSE does, however, contain two distinct antigenic components reactive with MG sera. One antigen reacted with 70% (14/20) of myasthenic sera in the passive hemagglutination assay. This antigen was detected in the HSE of both skeletal muscle and heart, and was unaffected by treatment with Triton X-100. The second antigen reacted with 10% (2/20) of MG sera in the complement fixation assay, was unique to skeletal muscle, and was inactivated by Triton X-100.


Defecographic study of rectal evacuation in constipated patients and control subjects.
To validate a computer-based area calculation method of quantification of rectal evacuation by using defecography videotapes and to use that method to compare evacuation in constipated patients with that in control subjects. For validation of the method, simultaneous defecography and weight measurements were compared in 36 patients with constipation or incontinence. Evacuation was calculated as the rate of change of the contrast medium-covered rectal area (percentage per second) or of the evacuated amount of contrast medium (percentage per second [relative] and grams per second [absolute]). After method validation, from a series of 215 consecutive constipated patients, individuals with an isolated radiologic diagnosis of intussusception greater than 0.6 cm (n = 27), rectocele greater than 2 cm (n = 19), enterocele (n = 12), or paradoxic puborectal muscle contraction (n = 12) were selected. Rectal evacuation in these groups was compared with that in 30 control subjects. Rectal evacuation rates measured at defecography correlated well with weighed amounts of evacuated contrast medium during the initial and total evacuation periods in 21 patients without contrast medium leak (r = 0.92, P < .001). Constipation overall, a rectocele greater than 2 cm, or paradoxic puborectal muscle contraction were associated with impaired evacuation (P < .001). Area calculations of rectal evacuation reflect rectal emptying. A rectocele greater than 2 cm or a paradoxic puborectal muscle contraction may be associated with obstructed defecation.


Age-related changes in cerebral congenital toxoplasmosis: Histopathological and immunohistochemical evaluation.
Congenital toxoplasmosis is a widespread worldwide disease producing varying degrees of damage to the fetus including ocular and neurological impairment. However, the underlying mechanisms are not yet clear. Therefore, the current study aimed to investigate the progress of congenital cerebral toxoplasmosis in experimentally infected offspring animal model at different age groups till become adults. To fulfill this aim, the offspring of Me49 T. gondii infected pregnant mice were divided into groups; embryo, infant, young and adult phases. Blood and brain samples were collected for further hormonal and histopathological studies and immunohistochemical staining of glial fibrillary acidic protein (GFAP) and synaptophysin (SYN). Our results showed several encephalitic changes in the infected groups ranging from gliosis to reduced cortical cell number and fibrinoid degeneration of the brain. We showed increased expression of GFAP and SYN indicating activation of astrocytes and modification of the synaptic function, respectively. These changes started intrauterine following congenital infection and increased progressively afterward. Moreover, infected mice had elevated corticosterone levels. In conclusion, the current study provided new evidences for the cellular changes especially in the infected embryo and highlighted the role of GFAP and SYN that may be used as indicators for T. gondii-related neuropathy.


Agreement between Fourier-domain and swept-source optical coherence tomography used for optic nerve head measurements.
To assess the correlation between optic nerve head measurements generated by Fourier-domain (FD) and swept-source (SS) optical coherence tomography (OCT) both in healthy Caucasian subjects and patients with primary open angle glaucoma (POAG). This was a cross-sectional study of the right eyes of 118 subjects. In each participant, the measurements of disc area, cup to disc ratio (CDR), vertical cup to disc ratio (VCDR), rim area and rim volume were performed consecutively by FD-OCT and then SS-OCT. Participant age, gender and spherical equivalent were also recorded. Agreement between the two devices was assessed through intraclass correlation coefficients (ICC) and Bland-Altman plots. The study sample consisted of 95 healthy eyes and 23 eyes with glaucoma. Mean participant age was 48.6±20.0 years, 54.2% were female, and mean spherical equivalent was -1.6±3.0 diopters. FD-OCT and SS-OCT measurements were respectively: mean disc area 1.79±0.3 vs 1.83±0.3 mm2 (ICC=0.71), mean CDR 0.38±0.2 vs 0.33±0.2 (ICC=0.91), mean VCDR 0.58±0.2 vs 0.52±0.2 (ICC=0.92), mean rim area 1.05±0.4mm2 vs 1.03±0.5mm2 (ICC=0.29), and mean rim volume 0.14±0.11 vs 0.21±0.17mm3 (ICC=0.53). Good agreement between the devices was noted for rim area and rim volume in glaucoma subjects (ICC=0.76 and 0.68 respectively), while weak agreement was observed for these variables in healthy subjects (ICC≤0.50). The CDR and VCDR measurements provided by FD and SS OCT showed excellent agreement for the overall sample. When the devices were used for rim measurements, agreement was excellent only in the POAG patients.


Metabolism of dietary ODAP in humans may be responsible for the low incidence of neurolathyrism.
The reasons for the very low incidence of the disease neurolathyrism in humans even after excessive consumption of the pulse, Lathyrus sativus, under severe drought and famine conditions, and its continued consumption by large populations during normal periods without any deleterious effects have been examined in the context of a possible metabolism or detoxification of beta-N-oxalyl-L-alpha, beta-diaminopropionic acid (ODAP), the major neurotoxic amino acid of L. sativus. ODAP in urine samples from 54 subjects habitually consuming the pulse and in three volunteers on an L. sativus diet was determined by the OPT method following clean up of the samples on an alumina column. Urinary oxalate was also determined in these individuals. Twenty-five subjects showed no excretion of ODAP and it was only less than 0.7% of the dietary intake in the remaining 29 subjects. Urinary excretion of ODAP in three volunteers was also less than 1% with a peak excretion in the 4-h sample. The 4-h blood sample from one volunteer had a maximum ODAP concentration of 177 microM. The urinary oxalate content in the volunteers was nearly 3-fold higher compared to controls. The low excretion of dietary ingested ODAP in humans is in sharp contrast to that seen in animals and indicates a metabolism or detoxification of ODAP which may be unique to humans and may explain the low incidence of neurolathyrism.


Identification of Genes Related to Squab Muscle Growth and Lipid Metabolism from Transcriptome Profiles of Breast Muscle and Liver in Domestic Pigeon (Columba livia).
The improvements in muscle growth rate and meat quality are the major breeding aims in pigeon industry. Liver and muscle are recognized as important sites for fatty acid metabolism; understanding the role of specific transcripts in the breast muscle and liver might lead to the elucidation of interrelated biological processes. In this study, RNA-Sequencing (RNA-Seq) was applied to compare the transcriptomes of breast muscle and liver tissues among pigeons at five developmental periods (0, 1, 2, 3, 4 weeks post-hatching) to identify candidate genes related to muscle growth and lipid metabolism. There were 3142 differentially expressed genes (DEGs) identified in the breast muscle libraries; 1794 genes were up-regulated while 1531 genes were down-regulated. A total of 1323 DEGs were acquired from the liver libraries, with 791 up-regulated genes and 591 down-regulated genes. By pathway enrichment analysis, a set of significantly enriched pathways were identified for the DEGs, which are potentially involved in cell proliferation and differentiation, lipid metabolism and energy metabolism in pigeon breast muscle and liver. Our results are consistent with previous partial reports from domestic animals and poultry and provide some unidentified genes involved in muscle growth and lipid metabolism. The reliability of the sequencing data was verified through qPCR analysis of 16 genes from eight comparison groups (two genes per group). The findings from this study could contribute to future investigations of muscle growth and lipid metabolism mechanisms and establish molecular approaches to improve muscle growth rate and meat quality in domestic pigeon breeding.