Ciprofloxacin pharmacokinetic profiles in paediatric sepsis: how much ciprofloxacin is enough?
To determine the pharmacokinetic profile of ciprofloxacin 20 mg/kg per day (10 mg/kg administered intravenously 12 hourly) in paediatric patients with severe sepsis. Open and prospective. Tertiary referral multi-disciplinary ICU. Twenty patients (two groups - group A: 3 months-1 year; group B 1-5 years). Timed blood samples were taken for pharmacokinetics after the first dose (D(0)), as well as day 2 (D(2)) and then between days 6-8. Ciprofloxacin serum levels were measured by high performance liquid chromatography. Demographic and clinical data and all adverse events were noted. Standard pharmacokinetic variables were calculated by non-compartmental methods. Peak concentrations (C(max)) for group A were D(0) 6.1+/-1.2 mg/l, D(2) 9.0+/-1.8 mg/l and D(7) 5.8+/-1.3 mg/l and, for group B, 7.4+/-1.3 mg/l, 7.8+/-1.6 mg/l and 6.4+/-1.3 mg/l, respectively, for the study periods. Concentration 12 h after the start of infusion (C(min)) for all periods were 0.2 mg/l or less. Areas under the curve (AUC, 12 h) were group A: 15.6+/-1.3, 19.2+/-1.63 and 14.1+/-1.4 mg/h per l, and group B: 15.9+/-1.3, 18.0+/-1.7 and 13.2+/-1.26 mg/h per l. One patient presenting with seizures, initially controlled, had another convulsion and a further patient developed seizures whilst on ciprofloxacin. C(max) in these patients were higher than the average C(max). The convulsions of both patients were easily controlled. No other drug-related serious adverse events occurred. No arthropathy was noted. Three patients died of their underlying disease. There was no accumulation of drug even after 7 days of administration. Our C(max) and AUC were lower than that achieved in a similar adult pharmacokinetic study. To achieve end points of area under the inhibitory curve (AUIC) of 100-150 mg/h per l, 10 mg/kg ciprofloxacin eight hourly would be required for some resistant ICU organisms.


Beta1 integrin deletion from the basal compartment of the mammary epithelium affects stem cells.
The mammary gland epithelium comprises two major cell types: basal and luminal. Basal cells interact directly with the extracellular matrix (ECM) and express higher levels of the ECM receptors, integrins, than luminal cells. We show that deletion of beta1 integrin from basal cells abolishes the regenerative potential of the mammary epithelium and affects mammary gland development. The mutant epithelium was characterized by an abnormal ductal branching pattern and aberrant morphogenesis in pregnancy, although at the end of gestation, the secretory alveoli developed from beta1 integrin-positive progenitors. Lack of beta1 integrin altered the orientation of the basal-cell division axis and in mutant epithelium, in contrast to control tissue, the progeny of beta1 integrin-null basal cells, identified by a genetic marker, was found in the luminal compartment. These results reveal, for the first time, the essential role of the basal mammary epithelial cell-ECM interactions mediated by beta1 integrins in the maintenance of a functional stem cell population, mammary morphogenesis and segregation of the two major mammary cell lineages.


[Transesophageal echocardiography for diagnosis of traumatic injuries to the major intrathoracic vessels in 150 patients: the effect of the learning curve].
To evaluate the role of transoesophageal echocardiography (TOE) in the management of patients with suspected traumatic lesions of the thoracic aorta (TLA) and its branches; to assess the influence of the learning curve on the diagnostic accuracy of TOE for the identification of TLA. Retrospective study. The study included 150 patients (age: 41 +/- 17; Injury Severity Scale score: 31 +/- 17) who were admitted during a 4-year period for severe blunt chest trauma and who underwent a TOE study. TOE were performed with either a monoplane (n = 54) or a multiplane probe (n = 96). In all cases, TLA were confirmed by angiography, computed tomography, surgery, or necropsy. Initially performed routinely, angiography was subsequently indicated when the TOE study was inconclusive or when a disruption of supraaortic arteries was suspected. Echocardiographic studies were reviewed by an experienced reader who was unaware of the medical history and initial conclusions. To evaluate the influence of the learning curve on the diagnostic accuracy of TOE, these conclusions were compared with the initial interpretations. A TLA was recognized in 25 patients out of 150 (17%), and evidenced using TOE in 22 of them. Three false negative and two false positive TOE results (needless thoracotomy) were recorded. After a learning period, the rate of inconclusive TOE studies decreased (18/150 vs 7/150: P < 0.05) and no false positive finding was recorded. The sensitivity and specificity of TOE for the diagnosis of TLA were 88 and 100%, and positive and negative predictive values were 100 and 97%, respectively. TOE is an accurate imaging technique for the diagnosis of TLA located at the aortic isthmus. However aortography becomes essential when injuries of the aorta branches are suspected. A learning period is required to improve the specificity of TOE for this indication.


Removal of Pb(II) and phosphorus in water by γ-Al2O3/biochar.
In this work, we synthesized activated alumina biochar composites (γ-Al2O3/BC) by sol-gel method, which improved the problem that the surface charge of γ-Al2O3 was not conducive to the removal of heavy metal cation in a neutral solution, and then explored the feasibility of removing Pb(II) by γ-Al2O3/BC as well as reusing Pb-laden waste sludge to remove phosphorus (P) and its micro-adsorption mechanisms. The results show that the maximum adsorption capacity of γ-Al2O3/BC for Pb(II) is 182.48 mg/g, and the removing capacity of recycled Pb-laden slag for P also reaches 87.13 mg/g. It was found that the presence of Pb in the slag makes P removal more effective. In addition, in the process of P removal, the Pb in the slag will not be released, which will not cause secondary pollution to the water. The micro-adsorption mechanism of Pb(II) and P on the composites was investigated by XPS, XRD, and FTIR. It demonstrates that special functional groups such as hydroxy-aluminum, hydroxyl, and carboxyl groups can remove Pb(II) through strong surface complexation and electrostatic attraction. Furthermore, the removal mechanism of P from Pb-laden sludge includes chemisorption and complexation, and the precipitation of P and Pb on the adsorbent surface is the main reason for the removal of P. Therefore, it is feasible to further effectively remove P by using the waste biochar containing Pb. The idea of this paper provides a potential method for the reuse of waste adsorbent.


Objectively measured physical activity, sedentary time and subclinical vascular disease: Cross-sectional study in older British men.
Low physical activity (PA) and high levels of sedentary time (ST) are associated with higher cardiovascular disease (CVD) risk among older people. However, their independent contribution and importance of duration of PA and ST bouts remain unclear. We investigated associations between objectively measured PA, ST and non-invasive vascular measures, markers of CVD risk. Cross-sectional study of 1216 men from the British Regional Heart Study, mean age 78.5years, measured in 2010-2012. Carotid intima thickness (CIMT), distensibility coefficient (DC) and plaque presence were measured using ultrasound; pulse wave velocity (cfPWV) and augmentation index (AIx) using a Vicorder. PA and ST were measured using hip-worn ActiGraph GT3X accelerometers. After adjusting for covariates, each additional 1000 steps per day was associated with a 0.038m/s lower cfPWV (95% CI=-0.076, 0.0003), 0.095 10(-3) kPa(-1) higher DC (95% CI=0.006, 0.185), 0.26% lower AIx (95% CI=-0.40, -0.12) and a 0.005mm lower CIMT (95% CI=-0.008, -0.001). Moderate and vigorous PA (MVPA) was associated with lower AIx and CIMT, light PA (LPA) with lower cfPWV and CIMT and ST with higher cfPWV, AIx and CIMT and lower DC. LPA and ST were highly correlated (r=-0.62). The independence of MVPA and ST or MVPA and LPA was inconsistent across vascular measures. Bout lengths for both PA and ST were not associated with vascular measures. In our cross-sectional study of older men, all PA regardless of intensity or bout duration was beneficially associated with vascular measures, as was lower ST. LPA was particularly relevant for cfPWV and CIMT.


"Ayurveda management of Palmoplantar Psoriasis (Vipadika) -a case report".
Palmo-plantar Psoriasis is a non-infectious chronic inflammatory disease of the skin bounded to the palm and soles in extent. In Ayurveda, all skin diseases are recounted under a single rubric i.e., Kushtha (skin diseases); PPP (Palmo-plantar Psoriasis) may be correspondent with Vipadika (one of the Kshudra Kushtha described in Ayurveda), based on its clinical sign & symptom. The role of Ayurvedic regimen in Palmo plantar psoriasis. Here we are presenting a case of 68-year-old man with a long 8-year history of pruritic rashes on his both palms and soles which was diagnosed as Palmo-Plantar Psoriasis (Vipadika) and successfully managed with simple Ayurveda medicines, external application of Jivantyadi Yamaka, external washing with Triphala decoction and 3 sitting of Jalaukavacharana (Leech Application). The patient reported a significant improvement in the complaints of itch and rash, on the scale and erythema of the palms and soles in a span of about 3 weeks. We, therefore, recommend the treatment of Palmo -plantar Psoriasis starting with leech application along with oral and external Ayurveda medication, and results can be seen.


Diagnostic test accuracy of adenosine deaminase for tuberculous meningitis: A systematic review and meta-analysis.
The measurement of adenosine deaminase (ADA) level in cerebrospinal fluid (CSF) has generated as a suitable test for tuberculous meningitis (TBM) diagnosis. The main objective in the present meta-analysis focused on analyzing the ADA test accuracy in order to diagnose TBM. We searched several databases including Medline, Embase and Cochrane databases to identify studies addressing the diagnosis of TBM. The quality of included reports were assessed by RevMan5 software (via QUADS2 checklist). Accuracy measures of ADA test (sensitivity, specificity and others) pooled with random effects models. In addition, the data was elicited by using midas and metan packages in stata (version 12). Twenty studies were eligible for inclusion within the meta-analysis. The pooled sensitivity and specificity for TBM diagnosis hallmarks were 89% (95% CI: 0.84-0.92) and 91% (95% CI: 0.87-0.93), respectively. The positive likelihood ratio was 9.4 (95% CI: 7-12.8), negative likelihood ratio was 0.12 (95% CI: 0.09-0.17), and diagnostic odds ratio was 77 (95% CI: 45-132). Indeed, the area under the summary receiver operating characteristic (SROC) was 0.96. It was magnificently attained that ADA test had a relatively high accuracy for TBM diagnosis.


Synthetic approaches to the 2011 new drugs.
New drugs are introduced to the market every year and each represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the synthesis of 26 NCEs that were launched in the world in 2011.


The differential effects of the radioprotectant drugs amifostine and sodium selenite treatment in combination with radiation therapy on constituent bone cells, Ewing's sarcoma of bone tumor cells, and rhabdomyosarcoma tumor cells in vitro.
The purpose of this study was to determine the differential effects of therapeutic X-radiation on constituent bone cells relative to the pediatric tumor cells: Ewing's sarcoma of bone and rhabdomyosarcoma. In addition, the radioprotectant drugs amifostine and sodium selenite were administered to constituent bone cells and the two tumor cells to determine if the radioprotectants differentially protect bone cells while not benefiting the tumor cells. These studies are a necessary first step in determining the potential clinical benefit of radioprotective therapy. An established in vitro cell culture model employing both constituent bone cells (osteoblasts, primary bone marrow monocytes, osteoclasts chondrocytes, and endothelial cells) and the tumor cells lines (Ewing's sarcoma of bone and rhabdomyosarcoma) were exposed to irradiation, amifostine, and sodium selenite. Cells were then assayed for changes in cell number, cytotoxicity, mineralization, bone resorption, cell attachment, osteocalcin, caspase-3 expression, clonogenic survival, and alkaline phosphatase expression. Radiation therapy differentially decreased cell number; with osteoblasts being shown to be the least sensitive to irradiation, the tumor cells had an intermediate sensitivity and monocytes were the most sensitive. Both amifostine and sodium selenite protected chondrocytes and osteoblasts from the negative effects of irradiation, while not protecting the tumor cells. The pediatric tumor cell lines were generally more radiosensitive than the bone cells examined. The radioprotectant drugs amifostine and sodium selenite provided significant radioprotection to constituent bone cells while not protecting the tumor cells. Finally, amifostine and sodium selenite therapy provided an additional benefit beyond radioprotection by increasing cytotoxicity in nonirradiated and irradiated tumor cells.


Effect of long-term feeding of aluminium chloride on hexokinase and glucose-6-phosphate dehydrogenase in the brain.
Rats were fed 100 microM AlCl3 for 1 year in their drinking water, then killed and their brains homogenized in 0.1 M Tris (pH 7.4). The 800 g supernatants were assayed for Al3+ and the activities of acetylcholine esterase (ACE), hexokinase and glucose-6-phosphate dehydrogenase (G6PDH). The concentrations of Al in the homogenates, as computed on the original brain for the control and Al fed group were 40 ng and 80 ng/g wet wt, respectively. The activity of ACE was the same in both groups but that of hexokinase and G6PDH in the Al-fed group was about 73% and 80%, respectively, of the control. Dialysis restored the G6PDH but increased the hexokinase of the control group 2-fold and that of Al-fed group 2.7-fold. Thus at this elevated level it was same in both groups. The contribution of Al from the undialysed homogenates during assay was too low to account for the inhibition. It is therefore suggested that a dialyzable inhibitor for hexokinase is normally present in the brain and that Al feeding increases its concentration to further inhibit the utilization of glucose.


Capillary ion electrophoresis-capacitively coupled contactless conductivity detection of inorganic cations in human saliva on a polyvinyl alcohol-coated capillary.
Capillary ion electrophoresis-capacitively coupled contactless conductivity detection (CIE-C4D) with a polyvinyl alcohol chemically coated capillary (PVA capillary) was used to analyze inorganic cations (Na(+), K(+), NH(4)(+), Mg(2+), and Ca(2+)) commonly found in human saliva. The PVA capillary, which was made by our laboratory, minimized electro-osmotic flow in the wide pH range of the background electrolyte (BGE), and the PVA layer adsorbed to capillary wall did not affect the conductimetric background level. In this study, we determined an optimized BGE of 30 mM lactic acid/histidine plus 3 mM 18-crown-6 for the CIE-C4D system using the PVA capillary, which could simultaneously improve the separation of Mg(2+) and Ca(2+) from Na(+) and that of K(+) from NH(4)(+). This system obtained highly reproducible separation of cations in human saliva samples within 8 min at 20 kV without deprotonation. The quantifiability of cations in human saliva samples on the CIE-C4D system was demonstrated through identification by ion chromatography with satisfactory results.


Total synthesis of bisbibenzyl dibenzofuran asterelin A via intramolecular oxidative coupling.
Total synthesis of asterelin A was accomplished by applying intramolecular Suzuki-Miyaura and oxidative couplings to the formation of an 18-membered macrocyclic ring and a dibenzofuran, respectively.


CD8+ T cells in asthma: friend or foe?
While it is well established that CD4(+) T lymphocytes play a crucial role in the initiation, progression and persistence of asthma, the role of CD8(+) T cells is less understood. CD8(+) T cells form functionally similar subsets which exhibit similar cytokine profiles as Th1 and Th2 cells, known as Tc1 and Tc2. Evidence from animal studies suggest that CD8(+) T cells are capable of regulating IgE production through the induction of IL-12 and IL-18 production in dendritic cells, and that CD8(+) T cells may act to moderate Th2 polarisation within the localised lymph nodes during allergic sensitisation. Such findings have led to the suggestion that Th1 polarising, CD8(+) T cell-inducing vaccines would inhibit the development of airway hyperresponsiveness (AHR) and Th2 cell infiltration. Despite these positive findings, the role of CD8(+) T cells within the lung remains poorly understood. While CD8(+) T cells, particularly those expressing the Tc1 phenotype, are capable of moderating inflammation and suppressing AHR, it has been postulated that Tc2 CD8(+) T cells predominate within established asthma and may act to amplify the inappropriate immune response which defines the condition. Within the clinic, the association between CD8(+) T cells and asthma is almost universally defined as injurious, further suggesting a prejudicial role for these cells within the established disease. CD8(+) T cells may be a valuable potential target for therapeutic intervention, either by potentiating their regulatory effects prior to the development of sensitisation, or through suppressing their pro-inflammatory properties within established atopy.


Skin surface marking on the prickle cell layer.
We have shown that skin surface marking exists on the prickle cell layer after provocation of intra-epidermal vesiculation with a 50% solution of NH4OH.


Genetic polymorphisms of the sortase A gene and social-behavioural factors associated with caries in children: a case-control study.
Streptococcus mutans (S. mutans) is the primary etiological agent of dental caries. Sortase is a transpeptidase that anchors several surface proteins to the S. mutans cell wall and has been shown to play a major role in cariogenicity. The purpose of this study was to explore the genetic polymorphisms of the sortase gene (srtA) and the social-behavioural factors associated with dental caries in children with S. mutans. In this case-control study, 121 S. mutans strains were separately selected from caries-free children and high-severity caries children for sequencing of the srtA gene. Social and behavioural data were collected by self-administered questionnaires. Genomic DNA was extracted from S. mutans strains and amplified by PCR to obtain the srtA gene. The purified PCR products were sequenced and analysed for mutations with ABI Variant Reporter software. The distribution of missense mutations and the mean of social-behavioural factors were compared between the groups. A multiple logistic regression model was used to control for confounding factors. The mutation frequencies at loci 168 (P = 0.023) and 470 (P = 0.032) were significantly different between the groups. The best-fitting model showed that greater age, high frequencies of solid sugar consumption, prolonged breastfeeding, a high proportion of visible plaque, and S. mutans with a T at locus 168 of the srtA gene were associated with high-severity caries in children (P < 0.05). Children carrying a G at locus 168 of S. mutans had a decreased risk for high-severity caries (OR = 0.32, 95% CI = 0.12-0.86) compared with those carrying a T. The present study suggested that the locus 168 missense mutation of the srtA gene may correlate with caries susceptibility in children with S. mutans. In addition, age, duration of breastfeeding, solid sugar consumption, and poor oral hygiene contributed to this complex disease.


17alpha-methyl testosterone is a competitive inhibitor of aromatase activity in Jar choriocarcinoma cells and macrophage-like THP-1 cells in culture.
17alpha-methyl testosterone is a synthetic androgen with affinity for the androgen receptor. 17alpha-methyl testosterone is used widely as a component of hormone replacement therapy. Previous reports have indicated that contrary to testosterone, 17alpha-methyl testosterone is not aromatized. However, 17alpha-methyl testosterone still could affect local estrogen formation by regulating aromatase expression or by inhibiting aromatase action. Both possibilities have important clinical implications. To evaluate the effect of 17alpha-methyl testosterone on the expression and activity of aromatase, we tested the choriocarcinoma Jar cell line, a cell line that express high levels of P450 aromatase, and the macrophage-like THP-1 cells, which express aromatase only after undergoing differentiation. We found that in both cell lines, 17alpha-methyl testosterone inhibits aromatase activity in a dose-related manner. The curve of inhibition parallels that of letrozole and gives complete inhibition at 10(-4) M 17alpha-methyl testosterone, determined by the tritium release assay. 17alpha-methyl testosterone does not have detectable effects on aromatase RNA and protein expression by Jar cells. Undifferentiated THP-1 cells had no aromatase activity and showed no effect of 17alpha-methyl testosterone, but differentiated THP-1 (macrophage-like) cells had a similar inhibition of aromatase activity by 17alpha-methyl testosterone to that seen in Jar cells. The Lineweaver-Burke plot shows 17alpha-methyl testosterone to be a competitive aromatase inhibitor. Our results show for the first time that 17alpha-methyl testosterone acts as an aromatase inhibitor. These findings are relevant for understanding the effects of 17alpha-methyl testosterone as a component of hormone replacement therapy. 17alpha-methyl testosterone may, as a functional androgen and orally active steroidal inhibitor of endogenous estrogen production, also offer special possibilities for the prevention/treatment of hormone-sensitive cancers.


Cystine fluxes across the isolated jejunal epithelium in cystinuria: increased efflux permeability at the luminal membrane.
In cystinuria, renal clearance of cystine frequently exceeds creatinine clearance, suggesting net cystine secretion; and absorption of the (di)basic amino acid is impaired at the luminal membrane of the jejunal and probably also renal tubular epithelium. We studied cystine transport in vitro in jejunal biopsy specimens of eight subjects with homozygous cystinuria and in 12 controls. Cellular/medium cystine distribution ratio was reduced in cystinuria (1.36 +/- 0.36 versus 5.36 +/- 0.61, p less than 0.001). Cystine influx across the luminal membrane was normal (221 +/- 48 versus 261 +/- 79 pmol X h-1 cm-2). Measurement of transepithelial cystine fluxes showed net absorption in controls but secretion in cystinuria. Apparent permeability coefficients were close to normal in cystinuria except that the efflux permeability at the luminal membrane was significantly increased (0.839 +/- 0.22 versus 0.186 +/- 0.12 X h-1 cm-2), and, accordingly, at the luminal membrane, the influx over efflux permeability ratio was small (1.01 +/- 0.50 versus 4.95 +/- 0.80, p less than 0.001). The defect in cystine transport in cystinuria is apparently not caused by decreased influx but increased efflux of cystine (or cystine) from the cell to the lumen across the luminal membrane.


Inhibition of calcium release from skeletal muscle sarcoplasmic reticulum by calmodulin.
The effect of calmodulin on calcium release from heavy sarcoplasmic reticulum isolated from rabbit skeletal muscle was investigated with actively and passively calcium loaded sarcoplasmic reticulum vesicles and measured either spectrophotometrically with arsenazo III or by Millipore filtration technique. The transient calcium-, caffeine- and AMP-induced calcium release from actively loaded sarcoplasmic reticulum vesicles was reduced to 29%, 51% and 59% of the respective control value by 1 microM exogenous calmodulin. Stopped-flow measurements demonstrate that calmodulin reduces the apparent rate of caffeine-induced calcium release from actively loaded sarcoplasmic reticulum. The rate of calcium uptake measured in the presence of ruthenium red, which blocks the calcium release channel, was not affected by calmodulin or calmodulin-dependent phosphorylation of sarcoplasmic reticulum vesicles with ATP[S]. The rate of the calcium-, caffeine- and AMP-induced calcium release from passively loaded sarcoplasmic reticulum vesicles was reduced 1.4-2.0-fold by 1 microM exogenous calmodulin, i.e. the half-time of release was maximally increased by a factor of two, whilst calmodulin-dependent phosphorylation of a 57 kDa protein with ATP[S] had no effect. The data indicate that calmodulin itself regulates the calcium release channel of sarcoplasmic reticulum.


Biomarkers of endothelial cell activation: candidate markers for drug-induced vasculitis in patients or drug-induced vascular injury in animals.
There is a pressing need for vascular biomarkers for studies of drug-induced vasculitis in patients and drug-induced vascular injury (DIVI) in animals. We previously reviewed a variety of candidate biomarkers of endothelial cell (EC) activation (Zhang et al., 2010). Now we update information on EC activation biomarkers from animal data on DIVI and clinical data of vasculitic patients, particularly patients with primary antineutrophil cytoplasmic autoantibody (ANCA)-associated small vessel vasculitis (primary AAVs), including Wegener's granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and necrotizing crescentic glomerulonephritis. Drug-associated ANCA-positive small vessel vasculitis (drug-AAVs) can closely resemble primary AAVs, suggesting the large overlap between primary idiopathic systemic vasculitis and drug-induced vasculitis. AAVs in patients and DIVI in animals vary considerably; however, there is close resemblance between AAVs and DIVI in some respects: (1) the immunopathogenetic mechanisms (activation of primed neutrophils, ECs and T cells by ANCA in patients and activation of ECs, mast cells, and macrophages by drugs in animals); (2) the morphologic changes (fibrinoid necrosis of the vessel wall and neutrophilic infiltration); (3) the preferable sites (small arteries, arterioles, capillaries and venules); and (4) elevation of vascular biomarkers suggestive of an endothelial origin. The present review discusses soluble and cell component biomarkers and provides a rationale for the potential utility of EC activation biomarkers in nonclinical and clinical studies during new drug development. Further investigation, however, is needed to assess their potential utility.


Genetic association of OPR genes with resistance to Hessian fly in hexaploid wheat.
Hessian fly (Mayetiola destructor) is one of the most destructive pests of wheat. The genes encoding 12-oxo-phytodienoic acid reductase (OPR) and lipoxygenase (LOX) play critical roles in insect resistance pathways in higher plants, but little is known about genes controlling resistance to Hessian fly in wheat. In this study, 154 F6:8 recombinant inbred lines (RILs) generated from a cross between two cultivars, 'Jagger' and '2174' of hexaploid wheat (2n = 6 × =42; AABBDD), were used to map genes associated with resistance to Hessian fly. Two QTLs were identified. The first one was a major QTL on chromosome 1A (QHf.osu-1A), which explained 70% of the total phenotypic variation. The resistant allele at this locus in cultivar 2174 could be orthologous to one or more of the previously mapped resistance genes (H9, H10, H11, H16, and H17) in tetraploid wheat. The second QTL was a minor QTL on chromosome 2A (QHf.osu-2A), which accounted for 18% of the total phenotypic variation. The resistant allele at this locus in 2174 is collinear to an Yr17-containing-fragment translocated from chromosome 2N of Triticum ventricosum (2n = 4 × =28; DDNN) in Jagger. Genetic mapping results showed that two OPR genes, TaOPR1-A and TaOPR2-A, were tightly associated with QHf.osu-1A and QHf.osu-2A, respectively. Another OPR gene and three LOX genes were mapped but not associated with Hessian fly resistance in the segregating population. This study has located two major QTLs/genes in bread wheat that can be directly used in wheat breeding programs and has also provided insights for the genetic association and disassociation of Hessian fly resistance with OPR and LOX genes in wheat.


Cone beam computed tomography (CBCT) guidance is helpful in reducing dose exposure to pediatric patients undergoing radiofrequency ablation of osteoid osteoma.
To assess efficacy and safety of cone beam computed tomography (CBCT) in the radiofrequency ablation (RFA) of osteoid osteoma (OO) in children and adolescents, and to compare technical success, clinical success, radiation dose and procedure duration time of CBCT guidance to conventional computed tomography (CT) guidance. Between 2015 and 2019, 53 consecutive percutaneous RFA were performed on pediatric patients with CBCT or conventional CT guidance, respectively, in 24 and 29 children and adolescents with 24-month follow-up. Dose area product (DAP) and dose length product (DLP) were recorded, respectively, for CBCT and conventional CT and converted to effective doses (ED). CBCT and conventional CT groups were similar in terms of patient age and weight, tumor size and tumor location. Technical success was achieved in all cases. Primary clinical success was 91.67% (22/24) for the CBCT group and 89.66% (26/29) for the conventional CT group. Mean DAP was 64.75Gycm2 (range 6.0-266.7). Mean DLP was 972.62mGycm (range 337-2344). ED was significantly lower in the CBCT group compared to the conventional CT group (0.34 mSv vs. 5.53 mSv, p = 0.0119). Procedure duration time was not significantly longer in the CBCT group (102.25 min vs. 92.34 min, p = 0.065). No major complication was registered. Minor complications were observed in 4 patients (2 in CBCT; 2 in conventional CT). Compared to conventional CT guidance, CBCT guidance for percutaneous OO ablation shows similar technical and clinical success rates, with reduced radiation dose and equivalent procedure duration time. This technique helps sparing dose exposure to pediatric patients.


Phylogenetic analysis of Newcastle disease viruses isolated from commercial poultry in Mozambique (2011-2016).
The complete sequence of the fusion (F) protein gene from 11 Newcastle disease viruses (NDVs) isolated from commercial poultry in Mozambique between 2011 and 2016 has been generated. The F gene cleavage site motif for all 11 isolates was (112)RRRKRF(117) indicating that the viruses are virulent. A phylogenetic analysis using the full F gene sequence revealed that the viruses clustered within genotype VIIh and showed a higher similarity to NDVs from South Africa, China and Southeast Asia than to viruses previously described in Mozambique in 1994, 1995 and 2005. The identification of these new NDVs has important implications for Newcastle disease management and control in Mozambique.


Comparison of three methods used for the measurement of the avidity of antibody to DNA.
Three methods for determining the avidity of antibodies to single-stranded DNA (ssDNA) have been compared. None of the 3 methods was totally satisfactory but for theoretical and practical reasons the measurement of avidity by determination of dissociation rate is considered the most appropriate.


Design, development, and evaluation of a virtual reality game-based application to support computational thinking.
Computational thinking (CT) has become an essential skill nowadays. For young students, CT competency is required to prepare them for future jobs. This competency can facilitate students' understanding of programming knowledge which has been a challenge for many novices pursuing a computer science degree. This study focuses on designing and implementing a virtual reality (VR) game-based application (iThinkSmart) to support CT knowledge. The study followed the design science research methodology to design, implement, and evaluate the first prototype of the VR application. An initial evaluation of the prototype was conducted with 47 computer science students from a Nigerian university who voluntarily participated in an experimental process. To determine what works and what needs to be improved in the iThinkSmart VR game-based application, two groups were randomly formed, consisting of the experimental (n = 21) and the control (n = 26) groups respectively. Our findings suggest that VR increases motivation and therefore increase students' CT skills, which contribute to knowledge regarding the affordances of VR in education and particularly provide evidence on the use of visualization of CT concepts to facilitate programming education. Furthermore, the study revealed that immersion, interaction, and engagement in a VR educational application can promote students' CT competency in higher education institutions (HEI). In addition, it was shown that students who played the iThinkSmart VR game-based application gained higher cognitive benefits, increased interest and attitude to learning CT concepts. Although further investigation is required in order to gain more insights into students learning process, this study made significant contributions in positioning CT in the HEI context and provides empirical evidence regarding the use of educational VR mini games to support students learning achievements.


Isolation of myosin light chain kinase inhibitors from microorganisms: dehydroaltenusin, altenusin, atrovenetinone, and cyclooctasulfur.
Dehydroaltenusin, cyclooctasulfur, atrovenetinone, and altenusin were isolated from the culture broths of Penicillium verruculosum IAM-13756, Streptomyces verticillus subsp. tskushiensis ATCC-21633, Penicillium sp. SPC-16375, and Penicillium sp. SPC-16524, respectively, as new myosin light chain kinase (MLCK) inhibitors. These compounds inhibited the calmodulin-dependent activity of MLCK with IC50 values of 0.69, 0.86, 3.7, and 350 microM, respectively. Among them, dehydroaltenusin was the best MLCK inhibitor in terms of potency and selectivity examined in the purified enzyme systems.


Marketing authorization of COVID-19 vaccines across UK, EU, and the US: fact-checking and the implications for future research.
While having access to safe and efficient vaccines is essential for eradicating the COVID-19 pandemic, gaining marketing authorisation is a critical step in enabling and speeding this process. On December 2, 2020, the United Kingdom became the first country to approve the first COVID-19 vaccine. This commentary aims to provide a quick overview of the UK's COVID-19 vaccine authorization process and compare it to that of the EU and the US. While the UK, EU, and US expedited the COVID-19 vaccine approval process, regulatory authorities did not appear to cut corners in their approval of the Pfizer COVID-19 vaccine, as evidenced by their decisions to switch emergency use authorization to full authorization in the US and to renew conditional/temporary use authorization in the EU and UK, respectively. There is an opportunity to conduct a thorough investigation into and comparison of the filed dossiers, as well as the robustness of the evaluation process for the approval of COVID-19 vaccines.


Predictive saccade behavior is enhanced in schizophrenia.
In this study, we investigated the ability of schizophrenic patients to produce predictive saccades in response to a visual target moving with predictable timing and location. The performance of visually guided saccades and predictive saccades (gain and latency) were analyzed in a group of 12 schizophrenic patients as compared with a group of ten control subjects. Our main finding was an enhancement of the predictive tracking ability in schizophrenics. In particular, the predictive tracking built-up and became installed as a steady pattern of highly anticipatory saccades (in terms of percentage of negative latency saccades) much faster in the schizophrenic group than in the control group. These data are discussed in terms of an involvement of the fronto-striatal system in this specific enhancement of predictive saccade behavior in schizophrenia.


Supporting Children and Families at a Child's End of Life: Pediatric Palliative Care Pearls of Anticipatory Guidance for Families.
Mental health professionals can play a key role in helping pediatric patients and their families prepare for and endure the death of a child. Impactful interventions include assisting a family's transition toward acceptance of a child's pending death, using prognostication as a tool in emotional preparedness, and education on expectant symptoms to optimize management and sense of caregiver efficacy.


COVID-19, Personal Data Protection and Privacy in India.
The corona pandemic altered many traditional and historical norms of society and law. COVID-19 created a humanitarian crisis in some parts of globe, while pandemic privacy and civil liberties were under threat all over world. To combat the deadly virus, individual liberty and equality were compromised. This paper focuses on how India's health problem has compromised people's right to privacy. It will highlight how strict executive policies led to the creation of a massive surveillance system in the name of combating the COVID-19 pandemic, as well as how the absence of any policy or legal framework led to the exclusion of individuals and their families who were suspected of having the virus or caring for those who were infected with the deadly virus. The paper uses case studies and data collected from primary as well as secondary sources. The authors will also point out how the absence of privacy regulation puts millions of citizens' private information at risk of being compromised or exploited against their will.


The effect of registration surrogate and patient factors on the interobserver variability of electronic portal image guidance during prostate radiotherapy.
Intraprostatic fiducial markers (IPM) and electronic portal imaging (EPI) are commonly used to identify and correct for prostate motion during radiotherapy. However, little data is available on the precision of this image-guidance technique. This study quantified impact of different registration surrogates and patient factors on the interobserver variability of manual EPI alignment during prostate radiotherapy. For 50 prostate radiotherapy patients previously implanted with 3 IPM, five observers manually aligned 150 pairs of orthogonal EPI to the reference digital reconstructed radiograph using Varian Vision EPI analysis software. Images were aligned using: Bony anatomy (BA), single mid-prostate IPM (SM); and 2 strategies using 3 IPM: center of mass (COM) and rotate & translate (R&T). Intraclass correlation coefficients (ICCs) were calculated to quantify interobserver variability. The absolute displacements measured using SM and R&T were compared with those using COM. The impact of patients' pelvic diameter and adjuvant hormone therapy on interobserver variability were also evaluated. Twelve thousand displacement values were collected for analysis. The maximum discrepancy between the 5 observers was >2 mm in 47% of measurements using BA, 5% using SM, 4% using R&T, and 3% using COM. Both of the 3 IPM alignment strategies demonstrated lower interobserver variability than the single IPM strategy (ICC 0.94-0.97 vs. 0.82-0.94). BA had the highest interobserver variability (ICC = 0.43-0.90). Pelvic diameter and hormone therapy had no discernible impact on interobserver variability. Compared with COM, the absolute displacements measured using the other IPM strategies were statistically different (p < 0.001), but 95% of the absolute magnitude of differences between the strategies were ≤1 mm. The high reproducibility among the observers demonstrated the precision of prostate localization using multiple IPM and EPI, which was not influenced by the patient factors studied. Bony anatomy displayed the highest interobserver variability of the 4 alignment, likely because of the limited EPI field-of-view. Alignment using more than one IPM is recommended to minimize interobserver variability.


MCP-1 gene regulatory region polymorphism in Chinese children with mild, moderate and near-fatal asthma.
A polymorphism in the monocyte chemoattractant protein 1 (MCP-1) gene regulatory region has been associated with asthma in Caucasians. This polymorphism is possibly endemic to the Asian region, but its impact on Asian populations is unclear. In addition, the relationship of this marker with life-threatening asthma has not been clarified. The aim of this study was to test the genetic association between the MCP-1 -2518A/G polymorphism and asthma/atopy in a cohort of Chinese children, with particular emphasis on those patients who had experienced life-threatening asthma attacks. Forty-eight children with near-fatal asthma, 134 mild-to-moderate asthmatics, 69 allergic-disorder cases without asthma, and 107 nonasthmatic, nonatopic control children were genotyped by a polymerase chain reaction-based assay. Comparison of the four groups of children (n = 358) revealed no detectable differences in genotype or allele frequencies of the MCP-1 -2518A/G polymorphism. There was no evidence of association between the polymorphism and any of the outcomes of interest including clinical severity, blood eosinophil count, atopy, total serum IgE levels, and degree of bronchial hyper-responsiveness. These results suggest that the MCP-1 -2518A/G polymorphism is not a risk factor for near-fatal asthma. Furthermore, this polymorphism seems to play no role in the development of asthma or atopy in Chinese subjects, possibly as a result of the genetic heterogeneity between Asian and Caucasian populations with respect to regulation of MCP-1 expression. Our results underscore the necessity of accounting for ethnic background in the investigation of asthma-predisposition genes.


Nomogram for prediction of severe community-acquired pneumonia development in diabetic patients: a multicenter study.
Diabetic patients with community-acquired pneumonia (CAP) have an increased risk of progressing to severe CAP. It is essential to develop predictive tools at the onset of the disease for early identification and intervention. This study aimed to develop and validate a clinical feature-based nomogram to identify diabetic patients with CAP at risk of developing severe CAP. A retrospective cohort study was conducted between January 2019 to December 2020. 1026 patients with CAP admitted in 48 hospitals in Shanghai were enrolled. All included patients were randomly divided into the training and validation samples with a ratio of 7:3. The nomogram for the prediction of severe CAP development was established based on the results of the multivariate logistic regression analysis and other predictors with clinical relevance. The nomogram was then assessed using receiver operating characteristic curves (ROC), calibration curve, and decision curve analysis (DCA). Multivariate analysis showed that chronic kidney dysfunction, malignant tumor, abnormal neutrophil count, abnormal lymphocyte count, decreased serum albumin level, and increased HbA1c level at admission was independently associated with progression to severe CAP in diabetic patients. A nomogram was established based on these above risk factors and other predictors with clinical relevance. The area under the curve (AUC) of the nomogram was 0.87 (95% CI 0.83-0.90) in the training set and 0.84 (95% CI 0.78-0.90). The calibration curve showed excellent agreement between the predicted possibility by the nomogram and the actual observation. The decision curve analysis indicated that the nomogram was applicable with a wide range of threshold probabilities due to the net benefit. Our nomogram can be applied to estimate early the probabilities of severe CAP development in diabetic patients with CAP, which has good prediction accuracy and discrimination abilities. Since included biomarkers are common, our findings may be performed well in clinical practice and improve the early management of diabetic patients with CAP.


Effects of soil amendments on lead uptake by two vegetable crops from a lead-contaminated soil from Anhui, China.
Previous studies have documented that phosphate compounds of lead (Pb) [e.g., pyromorphite Pb5(PO4)3-(X), where X=OH, F or Cl] are comparatively insoluble, and their formation in Pb-contaminated soil may be a means of reducing the bioavailability and chemical lability of Pb in soil. In this study, the effect of phosphate compound amendments on the bioavailability of Pb in a polluted alkaline soil was examined. A Pb-contaminated soil was treated with hydroxyapatite (HA), phosphate rock (PR), water-soluble P fertilizer (single superphosphate, SSP) and the combination of HA with SSP. The bioavailability of Pb was determined in plant uptake studies with vegetables (Brassica campetris L. var. communis, BC) and Brassica oleracea L. var. acephala, BO) and sequential extraction. The results indicated that the Pb concentrations in both shoots and roots of two vegetable plants decreased with increasing quantities of added P compound, and the HA treatment had the best effect at the level of 5000 mg of P kg(-1)as compared with other treatments in which the Pb concentrations in shoots of BO and BC decreased 51.9% and 65.5%, respectively, and the Pb concentrations in roots of BO and BC decreased 67.3% and 57.2%, respectively, as compared with the control treatment. The SSP treatment had little effect on the Pb concentrations in plant tissues. Sequential extraction results indicated that the addition of soil amendments transform soil Pb from nonresidual fractions to residual fraction substantially. The effect of treatments followed this order at the equivalent P addition: HA>PR>HA+SSP>SSP. The results suggested that HA amendments can lower the bioavailability and increase the geochemical stability of soil Pb, so it has the potential for in situ remediation in Pb-contaminated soils.


Gastrin-releasing peptide, a bombesin-like neuropeptide, promotes cutaneous wound healing.
Little is known about the effects of neuropeptides on wound healing. To investigate the effect of gastrin-releasing peptide (GRP), one of the bombesin-like neuropeptides, on wound healing. The effects of GRP on cultured keratinocyte proliferation and migration were measured by BrdU uptake and in vitro scratch assay, respectively. Various concentrations of GRP ointments (0, 10(-9), 10(-8), 10(-7), 10(-6) M) were topically applied to 1.0 mm wounds on porcine flanks. GRP stimulated keratinocyte growth and locomotion in a dose-dependent manner. Topical administration of GRP accelerated macroscopic epidermal regeneration in a dose-dependent manner, as measured by planimetry. Histologic studies also showed that GRP promoted reepithelialization, including epidermal thickness as well as superficial skin coverage. Topical use of GRP may clinically accelerate wound healing of burns, injuries, chronic ulcers, and skin graft donor sites through the enhancement of keratinocyte growth and spreading.


Implementing Evidence-Based Treatments for Youth in Acute and Intensive Treatment Settings.
Evidence-based treatments (EBTs) have been well studied in outpatient and research settings to address a myriad of mental health concerns. Research studies have found benefits and challenges when implementing these interventions. However, less is known about the implementation of EBTs in acute and intensive treatment settings such as inpatient psychiatric hospitalization (IPH) units, partial hospitalization programs (PHPs), or intensive outpatient programs (IOPs). As a result, the specific benefits and challenges of providing EBTs in these settings are less clear. For example, challenges of implementing EBTs in IPHs, PHPs, and IOPs can include working within a multi-disciplinary team setting and sustaining trained staff. The current article provides an overview of implementing EBTs in IPHs PHPs, and IOPs. Current PHP, IOP, and IPH models of implementing evidence-based interventions along with strategies for engaging stakeholders, program development and implementation, and measurement are reviewed. Further considerations for sustainability and practice consideration are also provided.


Shielding properties of fibre cement wallboard.
Transmission data for a fibre cement wallboard (villaboard) are determined for use in diagnostic shielding designs. Villaboard is found to be more attenuating than plasterboard e.g. 9 mm of villaboard is equivalent to 16 mm of plasterboard.


Cyclotorsion: a possible cause of residual astigmatism in refractive surgery.
To determine whether cyclotorsion occurs when a subject changes from binocular to monocular fixation and to assess positionally induced cyclotorsion. Clinics of the Rotterdam Eye Hospital, Rotterdam, The Netherlands. The axis of astigmatism was measured with the Nidek handheld keratometer in 15 normal subjects under monocular and binocular fixation and in seated and supine positions. The limits of agreement for the repeatability of measurements with the Nidek keratometer were used to identify subjects with statistically significant cyclotorsion. Two subjects (13%) showed statistically significant excyclotorsion when changing from binocular to monocular fixation in a seated position. In a supine position, 3 subjects (20%) showed excyclotorsion when the fixation changed. Body position itself had no influence on ocular torsion. Significant cyclotorsion may occur under monocular viewing conditions. If monocular photorefractive keratectomy procedures are based on binocular keratometry readings, an undercorrection of myopic astigmatism may result. Individuals at risk should be identified before refractive keratectomy is performed.


Effects of reduced contaminant loading on downgradient water quality in an idealized two-layer granular porous media.
The following explores the issue of how reductions in contaminant loading to plumes will effect downgradient water quality. An idealized scenario of two adjacent layers of uniform geologic media, one transmissive and the other low permeability, is considered. A high concentration source, similar to a thin DNAPL pool, is introduced in the transmissive layer immediately above the low permeability layer. While the source is active, dissolved constituents are driven along the contact by advection and into the low permeability layer by transverse diffusion. Removing the source reverses the concentration gradient between the layers, driving back diffusion of contaminants from the low permeability layer. Laboratory studies involving four contaminants demonstrate that 15 to 44% of the introduced contaminant moves into the low permeability zone (along a distance of 87 cm in a sand tank) over a period of 25 days. The greatest movement of contaminants into the low permeability zone is seen with the contaminants with the greatest sorption coefficients. A unique two-dimensional analytical solution is developed for the two-layer scenario. Processes addressed include advection; transverse dispersion; adsorption and degradation in the transmissive zones; and diffusion, adsorption, and degradation in the low permeability layer. Laboratory data agree favorably with the analytical solutions. Collectively, the laboratory results and analytical solutions provide a basis for testing other modeling approaches that can be applied to more complex problems. A set of field-scale scenarios are considered using the analytical solutions. Results indicate that improvement in water quality associated with source removal diminish with distance downgradient of the source. Furthermore, contaminant degradation and contaminant adsorption in the stagnant zone are shown to be critical factors governing the timing and magnitude of downgradient improvements in water quality. For five of six scenarios considered, observed improvements in water quality 100 m downgradient of the source fall in the range of 1 to 2 orders of magnitude 15 years after complete source removal. The sixth scenario, involving a contaminant half-life of three years and no adsorption, shows greater than three order of magnitude improvements in downgradient water quality within one year of source removal.


Crossing anastomosis of nerve bundles near innervated organs to treat irreparable nerve injuries.
To study the therapeutical effects of crossing anastomosis of nerve on the peripheral and central nerve injuries. Twelve kinds of central and peripheral nerve disorders and their complications were treated with 11 kinds of crossing anastomosis of nerve bundles near the innervated organs. After nerve injury and repair, somatosensory evoked potentials (SEPs) and horseradish peroxidase (HRP) retrograde tracing studies were used to investigate the rabbit's nerve function and morphology. The ulcers of all patients healed. Sensation, voluntary movement, and joint function recovered. Four weeks after the anastomosis of distal stump of radialis superficialis nerve and median nerve, pain sensation regained and SEPs appeared. HRP retrograde tracing studies demonstrated sensory nerve ending of medial nerve formed new connection with the body of neuron. Crossing anastomosis of nerve is an effective method to treat peripheral and central nerve injuries.


Protein structure prediction in CASP6 using CHIMERA and FAMS.
In CASP6, the CHIMERA-group predicted full-atom models of all targets using SKE-CHIMERA, a Web-user interface system for protein structure prediction that allows human intervention at necessary stages; we used a lot of information from our own data and from publicly available data. Using SKE-CHIMERA, we iterated manual step (template selection and alignment by the in-house program CHIMERA) and automatic step (three-dimensional model building by the in-house program FAMS). The official CASP6 assessment showed that CHIMERA-group was one of the most successful predictors in homology modeling, especially for FR/H (Fold Recognition/Homologous). In this article, we introduce the method of CHIMERA-group and discuss its successes and failures in CASP6.


Active site labeling of the RNA polymerases A, B, and C from yeast.
RNA polymerases A, B, and C from yeast were modified by reaction with 4-formylphenyl-gamma-ester of ATP as priming nucleotide followed by reduction with NaBH4. Upon phosphodiester bond formation with [alpha-32P]UTP, only the second largest subunit, A135, B150, or C128, was labeled in a template-dependent reaction. This indicates that these polypeptide chains are functionally homologous. The product covalently bound to B150 subunit was found to consist of a mixture of ApU and a trinucleotide. Enzyme labeling exhibited the characteristic alpha-amanitin sensitivity reported for A and B RNA polymerases. Labeling of both large subunits of enzyme A and B but not of any of the smaller subunits was observed when the reduction step stabilizing the binding of the priming nucleotide was carried out after limited chain elongation. These results illustrate the conservative evolution of the active site of eukaryotic RNA polymerases.


Geometrical characteristics of the symptomatic and non-symptomatic ossa trigona.
Posterior ankle impingement is strongly associated with the presence of an os trigonum, however, most patients with an os trigonum will never develop symptoms. It is hypothesized that the os trigonum is larger in the symptomatic ankle than in the non-symptomatic ankle, the distance between os trigonum and tibia is smaller and there are more degenerative changes in ankles with symptoms of posterior impingement. In this study the geometrical characteristics of the ipsilateral and contralateral os trigonum are compared in patients with a bilateral os trigonum and unilateral posterior impingement symptoms. Patients with a bilateral os trigonum and unilateral posterior impingement complaints were included. Comparison between the symptomatic and asymptomatic ankles was done within each patient. From the CT-scan of each ankle, the tibia, fibula, calcaneus, talus and os trigonum were segmented and a geometric model was created. Based on these bone models, the volume of the os trigonum and talus, the size of the os trigonum, the distance between os trigonum and surrounding bones (talus, calcaneus, fibula and tibia) were calculated. In addition, the CT images were assessed for the type of os trigonum, the presence of cysts, irregular synchondrosis, calcifications and whether the os trigonum consisted of more than one fragment. A total of 22 patients were included in this study. In seventeen of the 22 patients, the symptomatic os trigonum was larger in comparison with the non-symptomatic side in terms of length (median Δ 2.4 mm, 8.9 versus 10.6 mm) and relative volume (median Δ 0.09%, 0.30 versus 0.45% of talar volume). Distances between the ossa trigona and surrounding bones were not statistically significantly different between both sides. Calcifications were more frequently found around the os trigonum in the symptomatic side (10 versus 3/22). The findings in this study support the hypothesis that symptomatic ossa trigona are larger in comparison with asymptomatic ossa trigona. Calcifications around the os trigonum were found more frequently in symptomatic than in non-symptomatic ossa trigona. III.


Impact of a mass media campaign on participation rates in a National Bowel Cancer Screening Program: a field experiment.
This field experiment aimed to compare bowel cancer screening participation rates prior to, during and after a mass media campaign promoting screening, and the extent to which a higher intensity campaign in one state led to higher screening rates compared with another state that received lower intensity campaign exposure. An 8-week television-led mass media campaign was launched in selected regions of Australia in mid-2014 to promote Australia's National Bowel Cancer Screening Program (NBCSP) that posts out immunochemical faecal occult blood test (iFOBT) kits to the homes of age-eligible people. The campaign used paid 30-second television advertising in the entire state of Queensland but not at all in Western Australia. Other supportive campaign elements had national exposure, including print, 4-minute television advertorials, digital and online advertising. Monthly kit return and invite data from NBCSP (January 2012 to December 2014). Return rates were determined as completed kits returned for analysis out of the number of people invited to do the iFOBT test in the current and past 3 months in each state. Analyses adjusted for seasonality and the influence of other national campaigns. The number of kits returned for analysis increased in Queensland (adjusted rate ratio 20%, 95% CI 1.06% to 1.35%, p<0.01) during the months of the campaign and up to 2 months after broadcast, but only showed a tendency to increase in Western Australia (adjusted rate ratio 11%, 95% CI 0.99% to 1.24%, p=0.087). The higher intensity 8-week television-led campaign in Queensland increased the rate of kits returned for analysis in Queensland, whereas there were marginal effects for the low intensity campaign elements in Western Australia. The low levels of participation in Australia's NBCSP could be increased by national mass media campaigns, especially those led by higher intensity paid television advertising.


Persistence and calcium-dependent ATPase staining of denervated fungiform taste buds in the hamster.
Some fungiform taste buds in the hamster have been previously shown to persist for indefinite periods when deprived of their gustatory, chorda tympani (CT), innervation or both their CT and their trigeminal, lingual nerve, innervation (CT-L). The properties and numbers of persisting fungiform taste buds were examined 1 or 3 weeks after permanent CT or combined CT-L nerve cuts. The purpose was to reveal the status of taste buds at a time (3 weeks) when regenerating nerve fibres would normally be expected to reinnervate the epithelium. Denervated taste buds retain many normal characteristics including the pattern of histochemical staining for ectocalcium-dependent ATPase (Ca-ATPase). Taste-bud cells (including basal cells) have an intensely Ca-ATPase stained core surrounded by lightly stained peripheral cells. The Ca-ATPase stain was used to help identify and to define the size of the taste-bud core in denervated taste buds. Following CT-L or CT denervation most taste buds persisted; however the size of the taste-bud core was dramatically reduced. Fungiform taste buds differed in size based on their location in one of three tongue regions. The percentage decrease in size after denervation was also region specific and about the same for CT-L or CT cuts, suggesting that trigeminal fibres have no trophic effect on taste buds. However, trigeminal denervation caused a reduction in the number of persisting taste buds relative to CT denervation alone, which may be due to damage because of the loss of somatosensation.


Specificity and reversibility of the transpeptidation reaction catalyzed by the Streptomyces R61 D-Ala-D-Ala peptidase.
The specificity of the Streptomyces R61 penicillin-sensitive D-Ala-D-Ala peptidase has been re-examined with the help of synthetic substrates. The products of the transpeptidation reactions obtained with Gly-L-Xaa dipeptides as acceptor substrates are themselves poor substrates of the enzyme. This is in apparent contradiction with the classically accepted specificity rules for D-Ala-D-Ala peptidases. The Gly-L-Xaa dipeptide is regenerated by both the hydrolysis and transpeptidation reactions. The latter reaction is observed when another Gly-L-Xaa peptide or D-Alanine are supplied as acceptors. Utilization of substrates in which the terminal -COO(-) group has been esterified or amidated shows that a free carboxylate is not an absolute prerequisite for activity. The results are discussed in the context of the expected reversibility of the transpeptidation reaction.


Oral Alitretinoin in the Treatment of Severe Refractory Chronic Hand Eczema in the Spanish National Health System: Description and Analysis of Current Clinical Practice.
Hand eczema affects nearly 10% of the population. The condition becomes severe and chronic in 5% to 7% of cases and is refractory to topical corticosteroids in 2% to 4%. This study aimed to describe the current use of oral alitretinoin in treating Spanish national health system patients with hand eczema that is refractory to potent topical corticosteroids. Observational, descriptive, exploratory, cross-sectional study based on the retrospective analysis of records for patients with hand eczema treated with alitretinoin in the Spanish national health system. We reviewed the records for 62 patients in 13 hospitals in 5 different administrative areas (autonomous communities) of Spain. Alitretinoin was usually used at a dosage of 30mg/d. In most cases the physician judged the clinical response to be satisfactory after a single cycle. The recorded adverse effects were foreseeable and of the type reported for systemic retinoids. The dermatologists agreed that the clinical benefits achieved with alitretinoin favored adherence to treatment and an early return to work. The results show that oral alitretinoin is being used according to established recommendations and that response is good, with few adverse effects. The dermatologists agreed that the benefits favored adherence and improved the patients' health related quality of life.


Effects of lime on nickel uptake and toxicity in celery grown on muck soil contaminated by a nickel refinery.
A study was conducted to investigate the effects of soil lime application as a means of conteracting nickel phytotoxicity in muck soil. Metal-contaminated muck soil (5700 micrograms g-1 Ni, 650 micrograms g-1 Cu and 90 micrograms g-1 Co) was obtained from a farm adjacent to a nickel refinery in southern Ontario and was placed on a field test plot at Brampton, Ontario, during the summer of 1984. The treatments were: (a) control soil (uncontaminated), (b) unlimed metal soil and (c) limed metal soil. Calcium hydroxide was used at the rate of 10 t ha-1 to raise the pH of the metal-rich soil from approximately 5.7 to 6.9. The amount of Ni extracted by ammonium acetate was reduced by 36% in the limed metal soil compared with the unlimed metal soil. Distinct Ni-toxicity foliar symptoms appeared only on celery grown on the unlimed metal soil. The unlimed metal treatment resulted in an average celery shoot weight 28% less than the control (significant at P = 0.05). Liming the metal soil increased average celery shoot height by 36.5% (significant at P = 0.05), but slight increases in shoot and root weight of 13 and 8%, respectively, were not significant.


Neonatal overnutrition programming impairs cholecystokinin effects in adultmale rats.
Overfeeding and rapid weight gain during early life are risk factors for the development of obesity in adulthood. This metabolic malprogramming may be mediated by endocrine disturbances during critical periods of development. Cholecystokinin (CCK) acts on the central nervous system by elevating thermogenesis and the activity of anorectic neurons, modulating overall energy balance. Therefore, we tested the hypothesis that postnatal overfeeding impaired CCK effects. Pups were raised in either a litter of three (neonatal overnutrition/small litter group) or 12 (controls/normal litter group) pups per dam to study the effects of postnatal overfeeding on the central and peripheral CCK systems in adulthood. Rats raised in small litters became overweight during lactation and remained overweight as adults, with increased adiposity and plasma levels of lipids, glucose, insulin, and leptin. Neonatally over-nourished rats showed attenuation of gastric emptying and anorexigenic response to CCK, suggesting that offspring from the SL group may present CCK resistance as adult male rats. Consistent with this idea, overweight rats displayed impaired central response in c-Fos immunoreactivity on the nucleus tractus solitarius, area postrema, paraventricular nucleus, central amygdala, arcuate nucleus, and dorsomedial hypothalamus in response to peripheral CCK at adulthood. The small litter group of adult male rats also exhibited reduced norepinephrine- and CCK-stimulated thermogenesis. Unresponsiveness to the effects of CCK may contribute to overweight and metabolic dysfunctions observed in postnatally over-nourished adult rats. Thus, the involvement of an impaired CCK system, among other neurohormonal failures, may contribute to the development of obesity.


Colo-colic intussusception in Henoch-Schönlein purpura.
Intussusception is the commonest surgical complication of Henoch-Sch onlein purpura (HSP), occurring in 1.3%-13.6% of affected children. Colo-colic intussusception is a rare occurrence in HSP, with only three other reported cases. Intussusception in HSP almost always originates in the ileum (90%) or jejunum (7%), and more than one-half of cases (58.4%) are confined to the small bowel. This is in contrast to idiopathic intussusception, where the majority (80%-90%) are ileo-colic and can be diagnosed and reduced by contrast enema.


Personal and professional quality of life among French health care workers during the first COVID-19 wave: a cross-sectional study.
We aimed to assess the personal and professional quality of life changes among health care workers of different professions during the COVID-19 pandemic in a large French university hospital. Other published data originated from countries with different health care systems and outbreak dynamics. All health care workers from our hospital were invited to fill-in an anonymous e-questionnaire of 71 questions regarding perceived personal, professional and overall quality of life before and during the first COVID-19 wave, general profile, occupation and job characteristics, change of assignment, COVID-care features if relevant, general perception during the first wave, and personal experience of being encouraged or stigmatised. There were 794 participants, with a majority of nursing professionals (n = 416, 56%), including 57 nurse managers, 243 nurses, and 116 nurse assistants. Other participants were physicians (n = 188) and other health care staff (n = 140). Before the crisis, professional quality of life was low (6.5 on a 10-point scale) overall. The personal quality of life was higher (8.1) particularly for physicians and nurse managers. The COVID crisis saw a marked decrease in the personal quality of life (- 1.7), more pronounced in younger health care workers. Professional quality of life was less affected (- 0.4) and stayed almost constant for physicians. Staff in COVID units had a more positive perception of the crisis but experienced more fatigue, which resulted in similar quality of life levels in COVID and non-COVID units. Encouragements originated more often from relatives or colleagues than hospital managers and were exceptionally common: 63.4% of all participants, from 50.5% for other staff to 71.3% for physicians (p = 0.0005). Stigmatisation was reported by 19.3% of participants, with a higher proportion (p = 0.0001) among nurses (26.3%) and assistant nurses (23.3%) than among physicians (8.5%). From multivariate analysis, higher age, working as a physician and receiving encouragements were independently associated with lower loss of overall quality of life. The resilience of health care workers was high overall during the first COVID wave although the quality of life decreased more among nursing staff. Social support in the form of encouragements is a key part of management, particularly in times of crisis.


Vascular complications of vascularized composite tissue transfer: outcome and salvage techniques.
Two hundred fifty-two vascularized composite tissue transfers were performed from 1985 to 1992 at Nara Medical University Hospital. Free tissue transfers were performed in 185 patients and island tissue transfers in 67 patients. Of these, 39 flaps were reexplored because of vascular complications. On initial reexploration, vascular obstruction was found at the site of anastomosis or in the main vascular pedicle in 36 patients and in the perforating vessels to the monitor flap in three patients. Arterial thrombus occurred in 11 patients, venous thrombosis in 12, and both in nine. Twenty-five reexplored flaps were salvaged. Initially, heparin was administered systemically when vascular compromise was suspected intraoperatively or postoperatively. Recently, we have used a "continuous local heparinization" technique to minimize blood loss. This method has been used in 12 patients who underwent reexploration and in nine patients in whom vascular compromise was suspected. Nineteen flaps survived completely, and two flaps failed.


The major histocompatibility complex, MnLA, of pigtailed macaques: definition of fifteen specificities.
The major histocompatibility complex (MHC) of pigtailed macaques (Macaca nemestrina, Mn) is defined and designated as MnLA. Twenty-nine alloantisera were generated by fullsib alloimmunization and tested against a panel of 220 unrelated animals. The reactivities of different alloantisera were analyzed statistically in pairwise comparisons. Using 2 X 2 contingency tables, we calculated chi 2 independence, chi 2 allelism, and correlation coefficient values. Initially, specificities were defined by significant associations of certain sera, but some sera defined specificities individually. In all, 15 specificities were defined, and by family studies and negative correlation coefficients, a two-locus model was evident. Genetic analyses, together with statistical applications, revealed that the behavior of these specificities is consistent with the nature of MHC in other primate species, including man.


Highlights of the EANM Congress 2011: Birmingham, UK.
The EANM Congress 2011 took place in Birmingham between the 15th and 19th October 2011 under the presidency of Professor Werner Langsteger. The attendance was reassuringly high, in line with other EANM congresses, despite the current 'Eurozone Crisis'. Participants from 87 countries came along, met old friends and made new ones. They were presented with a massive programme of 1,480 abstracts, symposia, and CME, scientific, plenary and featured sessions. The industry made a substantial contribution to the success of the congress with 109 hardware, software and radiopharmaceutical companies demonstrating the latest technology and innovations in the field. A feature in this year's congress was the emphasis on the role of the young generation. The highlight lecture was presented and this article was compiled by three young EANM members chosen from the young investigator project of the EANM. They review the most highly rated presentations in clinical and preclinical imaging in oncology, neuroendocrine tumours, cardiology, paediatrics and neurology, and provide an update on radionuclide therapy, physics, instrumentation, innovative tracers and techniques.


Allogeneic lymphocytes immunotherapy in female infertility: Lessons learned and the road ahead.
The endometrium is an essential tissue in the normal immunologic dialogue between the mother and the conceptus, which is necessary for the proper establishment and maintenance of a successful pregnancy. It's become evident that the maternal immune system plays a key role in the normal pregnancy's initiation, maintenance, and termination. In this perspective, the immune system contributes to regulating all stages of pregnancy, thus immunological dysregulation is thought to be one of the major etiologies of implantation failures. Many researchers believe that immune therapies are useful tactics for improving the live births rate in certain situations. Lymphocyte immunotherapy (LIT) is an active form of immunotherapy that, when used on the relevant subgroups of patients, has been shown in multiple trials to dramatically enhance maternal immunological balance and pregnancy outcome. The primary goal of LIT is to regulate the immune system in order to create a favorable tolerogenic immune milieu and tolerance for embryo implantation. However, there are a plethora of influential factors influencing its therapeutic benefits that merit to be addressed. The objective of our study is to discuss the mechanisms and challenges of allogeneic LIT.


Thiols-Induced Rapid Photoluminescent Enhancement of Glutathione-Capped Gold Nanoparticles for Intracellular Thiols Imaging Applications.
The rapid detection and imaging of intracellular thiols is of great importance during the occurrence and development of some chronic diseases. Here we demonstrate the rapid thiols-induced photoluminescence (PL) enhancement of the low luminescent glutathione (GSH) stabilized Au nanoparticles, AuGSH (low). The dynamic PL investigation reveals that the PL enhancement fits a first-order reaction model. The X-ray photoelectron spectroscopic and mass spectroscopic results indicate that AuGSH (low) are mainly comprised of "thiols-insufficient" Au species and the additional thiols can efficiently attach to the "unsaturated" surface of Au nanoparticles, accompanied by significant PL enhancement. The noncytotoxic AuGSH (low) probe can be successfully applied for imaging of intracellular thiols. Generally, this work illustrates the great prospects of facile-prepared AuGSH (low) as a candidate for thiols labeling and imaging.


Gemcitabine plus conventional-dose epirubicin versus gemcitabine plus cisplatin as first-line chemotherapy for stage IIIB/IV non-small cell lung carcinoma--a randomized phase II trial.
Epirubicin was effective for the treatment of non-small cell lung carcinoma (NSCLC). This study compared the efficacy and safety of gemcitabine plus conventional-dose epirubicin (GE) with gemcitabine-cisplatin (GC) as first-line chemotherapy for stage IIIB/IV NSCLC and evaluated the predictive value of nuclear expression of excision repair cross-complementing group 1 (ERCC1) and topoisomerase IIalpha (TopoIIalpha) on treatment outcome. Patients were randomized to GE (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and epirubicin, 70mg/m(2) on day 15) or GC (gemcitabine, 1000mg/m(2) on days 1, 8, and 15 and cisplatin, 80mg/m(2) on day 15). Treatment cycles were repeated every 4 weeks. Immunohistochemical study of ERCC1 and TopoIIalpha was done for patients with available tumor specimens. The response rate was 31.0% (95% CI 16.4-45.5%) for GC (n=41) and 37.2.0% (95% CI 22.2-52.3%) for GE (n=39). No significant differences in median time-to-treatment-failure (TTF) (GC, 6.1 months; GE, 6.2 months) or overall survival (GC, 13.2 months; GE, 21.5 months) were found between the two arms. Grade 3/4 neutropenia and febrile neutropenia were more common in GE. However, delay of protocol treatment due to leukopenia was similar between the two arms. Patients with expression of both ERCC1 and TopoIIalpha had a significantly shorter TTF (median 2.4 months, 95% CI 0.7-4.1 months) than other patients (median 8.8 months, 95% CI 5.8-11.8 months) (p=0.04). GE regimen is effective and well-tolerated for NSCLC patients. Expression of both ERCC1 and TopoIIalpha may be associated with poor response to chemotherapy.


The role of epithelial P2Y2 and P2Y4 receptors in the regulation of intestinal chloride secretion.
UTP-induced chloride secretion by the intestinal mucosa mounted in Ussing chambers was assessed by measurement of the short-circuit current (I(sc)) in the presence of phloridzin in the case of jejunum or amiloride in the case of colon to eliminate any contribution of electrogenic Na(+) movement to the net ionic transport. Since we have previously demonstrated the absence of chloride-secretory response to apical UTP in the jejunum from P2Y(4)-null mice, in the present study we studied the response to basolateral UTP in the jejunum and to either apical or basolateral UTP in the colon, in both P2Y(2)- and P2Y(4)-deficient mice. In the jejunum, the chloride-secretory response to basolateral UTP was partially reduced in both P2Y(2)- (40%) and P2Y(4)- (60%) null mice. In the colon, both apical or basolateral UTP increased the I(sc). That response was abolished in a chloride-free medium. The colonic chloride-secretory response to either basolateral or apical UTP was abolished in P2Y(4)-deficient mice, but not significantly affected in P2Y(2)-deficient mice. The chloride-secretory response to forskolin was potentiated by prior basolateral addition of UTP and this potentiation was abolished in P2Y(4)-null mice. The jejunum of mice homozygous for the DeltaF508 mutation of cystic fibrosis transmembrane conductance regulator was responsive to UTP, but the magnitude of that response was smaller than in the wild-type littermates. In conclusion, the P2Y(4) receptor fully mediates the chloride-secretory response to UTP in both small and large intestines, except at the basolateral side of the jejunum, where both P2Y(2) and P2Y(4) receptors are involved.


Therapeutic potential of graphitic carbon nitride as a drug delivery system for cisplatin (anticancer drug): A DFT approach.
In the current study, for the first time; the drug loading efficacy of graphitic‑carbon nitride (g-C3N4) for an anticancer drug, cisplatin was evaluated. To explore the effectiveness of g-C3N4 as a drug-delivery system, some important properties of cisplatin drug, g-C3N4 carrier, and g-C3N4-cisplatin complex were calculated at ground state and excited state. The cisplatin drug prefers to interact via H atoms to the N atoms of g-C3N4 carrier with an adsorption energy of about -1.25 eV. The type of interactions between g-C3N4 carrier molecule and cisplatin drug are visualized with the help of non-covalent interaction (NCI) analysis which demonstrated the presence of weak non-covalent interactions. These weak interactions between cisplatin drug and g-C3N4 carrier play a key role in drug-offloading at the target site. The charge-transfer process was studied with the help of HOMO-LUMO analysis and further supported by charge-decomposition analysis (CDA). Furthermore, excited-state calculations for g-C3N4-cisplatin complex revealed that λmax is red-shifted by 154 nm in the gaseous phase, and the inclusion of water results in the blue shift of λmax. Interestingly, by comparing theoretical and experimental spectra, it was found that our theoretical spectra in the solvent phase are in close agreement with experimental results. The photoinduced electron-transfer (PET) process and its effect on fluorescence phenomena, was investigated for different excited-states of g-C3N4-cisplatin complex with the help of electron-hole theory. Moreover, g-C3N4 with +1 and - 1 charge state shows negligible structural distortion and it also gives stable complexes with cisplatin drug. Overall the findings suggest that g-C3N4 could be used as an efficient drug-delivery system for the cisplatin drug to treat various types of cancer.


Radial portal tendon harvest and interposition in arthroscopic treatment of thumb basilar joint osteoarthritis.
This study describes an arthroscopic technique that uses the same radial arthroscopic access portal to harvest and to interpose tendon material into the trapeziometacarpal joint in the treatment of Eaton-Littler stage 2 and 3 osteoarthritis of the trapeziometacarpal joint. Clinical application of this technique has resolved pain and preserved motion at the trapeziometacarpal joint in this study experience.


Changes in the regulation by endothelium of norepinephrine response in isolated, perfused mesenteric vascular bed of rats at different ages.
Age-related changes of norepinephrine response were studied in isolated perfused mesenteric arteries and veins of rats at 4, 32 and 75 weeks of age. Norepinephrine (0.1-100 nmole) significantly and dose-dependently increased perfusion pressure of the arteries, whereas it only slightly changed that of the veins. The arterial response increased, but the venous response decreased with age. Indomethacin at 5 x 10(-6) M did not change the arterial response at any of the ages. The combination of indomethacin and NG-nitro-L-arginine methyl ester (L-NAME) at 5 x 10(-6) M, and endothelium denudation similarly augmented the response in 4-week-old rats, but neither of these affected the responses in 32- and 75-week-old rats. At raised tone by 100 mM potassium chloride, acetylcholine-induced decrease in perfusion pressure and inhibition of the response by L-NAME were attenuated gradually with age. The raised tone in 75-week-old rats was higher than that in either 4- or 32-week-old rats, but the difference disappeared in the presence of L-NAME. These results demonstrate that the arterial portion is predominant in norepinephrine response and the arterial and venous responses change oppositely with age. It is also suggested that neither prostanoids nor endothelial nitric oxide regulate the arterial response in mature animals, while only in 4-week-old rats, nitric oxide may counteractively regulate the response. Additionally, the roles of nitric oxide in the regulation of transient norepinephrine response, in the regulation of the potassium-induced tonic contracture, and in the vasodilation through muscarinic receptor stimulation seem to change somewhat differently with age.


Comparison of the early-term clinical results of capitate forage procedure and radial shortening osteotomy in Stage 3A Kienböck's disease.
This study aims to evaluate the efficacy of an alternative method by comparing an old established method with a new less invasive method in the surgical treatment of Stage 3A Kienböck's disease. Between January 2014 and July 2018, a total of 35 patients (28 males, 7 females; mean age: 22.8±3.3 years; range, 17 to 29 years) who underwent surgery due to Kienböck's disease were retrospectively analyzed. The patients were divided into two groups according to the procedure applied as the capitate forage procedure (CFP) group (Group 1, n=16) and the radial shortening osteotomy (RSO) group (Group 2, n=19). Patients with a minimum follow-up period of 18 months were examined according to the MAYO wrist scores pre- and postoperatively. The postoperative MAYO scores were statistically significantly higher in both groups (CFP, p=0.001; RSO, p=0.000). However, the osteotomy group showed statistically significantly higher results than the forage group in terms of not only postoperative scores, but also pre- and postoperative score difference (p=0.004). Our study results confirm that both CFP and RSO are effective in the treatment of Stage 3A Kienböck's disease. However, RSO should be the first choice in Stage 3A patients with high success rates. Supported by long-term follow-up results, CFP may be considered a minimally invasive alternative only in selected patients who avoid major surgery or expect a rapid return to work.


Discriminative stimulus effects of ethanol: neuropharmacological characterization.
Generally, compounds discriminated by animals possess psychotropic effects in animals and humans. As with many other drugs of abuse, strength of the ethanol discriminative stimulus is dose related. The majority of studies show that doses close to 1.0 g/kg are close to the minimum at which the discrimination can be learned easily. Substitution studies suggest that anxiolytic, sedative, atactic, and myorelaxant effects of ethanol all play an important role in the formation of its intercoeptive stimulus. Low doses of ethanol produce more excitatory cues, similar to amphetamine-like subjective stimuli, whereas higher doses produce rather sedative/hypnotic stimuli similar to those elicited by barbiturates. Substitution studies have shown that the complete substitution for ethanol may be exerted by certain GABA-mimetic drugs acting through different sites within the GABA(A)-benzodiazepine receptor complex (e.g., diazepam, pentobarbital, certain neurosteroids), gamma-hydroxybutyrate, and antagonists of the glutamate NMDA receptor. Among the NMDA receptor antagonists both noncompetitive (e.g., dizocilpine) and competitive antagonists (e.g., CGP 40116) are capable of substituting for ethanol. Further, some antagonists of strychnine-insensitive glycine modulatory sites among the NMDA receptor complex (e.g., L-701,324) dose-dependently substitute for the ethanol discriminative stimulus. On the other hand, neither GABA-benzodiazepine antagonists nor NMDA receptor agonists produce contradictory effects (i.e., reduce the ethanol discriminative stimulus). There is influence of a particular training dose of ethanol on the substitution pattern of different compounds. For example, 5-HT(1B/2C) agonists substitute for intermediate (1.0 g/kg) but not higher (2.0 g/kg) ethanol training doses. Discrimination studies with ethanol and drugs acting on NMDA and GABA receptors consistently indicate asymmetrical generalization. For example, ethanol is able to generalize to barbiturates and benzodiazepines, but neither the benzodiazepine nor barbiturate response generalizes to ethanol. Only a few drugs are able to antagonize, at least to some extent, the discriminative stimulus of ethanol (e.g., partial inverse GABA-benzodiazepine receptor antagonist Ro 15-4513 and the opioid antagonist naloxone). The ethanol stimulus effect may be increased (i.e., stronger recognition) by N-cholinergic drugs (nicotine), dopaminergic drugs (apomorphine), and 5-HT3 receptor agonists (m-chlorophenylbiguanide). Thus, the ethanol stimulus is composed of the several components, with the NMDA receptor and GABA(A) receptor complex being of particular importance. This suggests that a drug mixture may be more capable of substituting for ethanol (or block its stimulus) than a single compound. The ability of drugs to substitute for the ethanol discriminative stimulus is frequently, although not preclusively, associated with the reduction of voluntary ethanol consumption. The examples of positive correlation are gamma-hydroxybutyrate, possibly memantine and certain serotonergic drugs such as fluoxetine. However, it remains uncertain to what extent the discriminative stimulus of ethanol can be seen as relevant in the understanding of the complex mechanisms of dependence.


Purification of Tannerella forsythia Surface-Layer (S-Layer) Proteins.
The objective of this chapter is to provide a detailed purification protocol for the surface-layer (S-layer) glycoproteins of the periodontal pathogen Tannerella forsythia. The procedure involves detergent based solubilization of the bacterial S-layer followed by cesium chloride gradient centrifugation and gel permeation chromatography. The protocol is suitable for the isolation of S-layer glycoproteins from T. forsythia strains with diverse O-glycan structures, and aid in understanding the biochemical basis and the role of protein O-glycosylation in bacterial pathogenesis.


Acoustic Response to Playback of Pile-Driving Sounds by Snapping Shrimp.
There is concern about the effects of noise from impact pile driving as this constructional technique becomes increasingly widespread in coastal areas. The habitats of most marine invertebrate species are likely to overlap with the areas of human activities along the coast and be affected by the increased levels of noise produced. This paper investigates the acoustic response of chorusing snapping shrimp to different sound pressure levels. A significant increase in the snap number and snap amplitude was recorded during the playback of piling noise, suggesting that noise exposure affected the acoustic behavior of these animals.


Regulation of immunity by Taeniids: lessons from animal models and in vitro studies.
Taeniidae is the largest family of the Cyclophyllidea order of parasites despite being composed of just two genera: Taenia spp and Echinococcus spp. These parasites are flatworms with a terrestrial life cycle, having an immature or larval stage called metacestode, which develops into the mature form within the intestine of the primary host after being consumed in raw or poorly cooked meat. Consumed eggs hatch into oncospheres, penetrate the intestinal walls and are transported via the bloodstream to later develop into metacestodes within the muscles and internal organs of secondary and sometimes primary hosts, thereby initiating the cycle again. Larval stages of both Taenia spp and Echinococcus spp are well known to produce tissue-dwelling, long-lasting infections; in this stage, these parasites can reach centimetres (macroparasites) and both genera may cause life-threatening diseases in humans. Establishing such long-term infections requires an exceptional ability to modulate host immunity for long periods of time. In this review, we analyse the immunoregulatory mechanisms induced by these tapeworms and their products, mainly discussing the importance of taeniid strategies to successfully colonize their hosts, such as antigen-presenting cell phenotype manipulation and the consequent induction of T-cell anergy, among others.


Some factors related to sum-DDT levels in Ugandan mothers' breast milk.
A total of 143 samples of Ugandan mothers' breast milk were analysed by gas chromatography for the presence and levels of DDT residues. The relationship between the level of DDT in the milk and the mother's age, parity, dietary habits, and place of usual residence were studied. DDT levels in the milk were not significantly related to the mother's age. Mothers nursing their first child had a significantly higher mean DDT level in their milk than those nursing their second child. Furthermore, mothers who resided in the urban area had a significantly higher mean-DDT level in their milk than those who resided in the rural area. No statistically significant differences were observed in the mean levels of DDT in the milk samples of vegetarian and non-vegetarian mothers. From the present findings, it could be concluded that milk from mothers nursing the first child and residing in an urban area is a good bioindicator for assessing exposure of lactacting mothers to DDT in Uganda.


HBx M130K and V131I (T-A) mutations in HBV genotype F during a follow-up study in chronic carriers.
Around 400 million people worldwide are chronically infected with Hepatitis B virus (HBV). An estimated 10% of these chronic patients develop progressive liver damage including cirrhosis and Hepatocellular Carcinoma (HCC). The HBx gene encodes a protein of 154 amino acids which is a transactivator and has been associated with HBV pathogenesis. A change in the amino acid sequences at positions 130 and 131 in the HBV-X protein (M130K and V131I) produced by T-A point mutations at the nucleic acids level has been associated with severe liver damage and HCC in patients from China and Africa. Further, such changes have been proposed as a prognostic marker for progressive liver damage and HCC. The purpose of this study was to determine if T-A mutations are present in HBV chronic carriers with genotype F (the major genotype in Costa Rica) and further, if these mutations are associated with HBV disease progression in Costa Rica HBV patients from 1972 to 1985. Serum samples from 50 HBV positive individuals were amplified and directly sequenced, 48 belonged to genotype F, 1 from genotype D and another was classified as D or E. T-A mutations were absent in 17 acute patients who recovered, but was present in 12 of 29 chronic carrier samples (42.8%), in one sample the T-A mutations were detected as early as 29 days after clinical onset of disease. In 17 carriers with available liver biopsies, T-A mutations were found in 8 sera of 13 (61.5%) classified as moderate or severe, and none in 4 biopsies with mild liver damage. However, it was not possible to demonstrate a statistical association between the presence of T-A mutations and moderate/severe liver damage, using a Fischer exact test, 1 tail, p = 0.05. In 4 patients HCC was diagnosed, and 2 of them presented the T-A mutations in their sera. T-A mutations were found in HBV genotype F in chronic carriers but not in patients who recovered from acute infection. These mutations could be developing early during infection although the possibility of infection with the mutant virus could not be excluded. More studies are necessary to establish if the T-A mutation can be used as a prognostic marker for severity of liver disease in patients infected with HBV.


Indomethacin and renal function in premature infants with persistent patent ductus arteriosus.
Renal function during indomethacin treatment was studied in 12 premature infants with patent ductus arteriosus. Decreases in urinary flow rate, GFR, and CH2O by 56, 27, and 66%, respectively, occurred during Indo therapy. Urinary excretion rates of ions were also reduced: Na by 70%, Cl by 79%, K by 40%. These changes were accompanied by slight decreases in plasma sodium concentration and osmolality. Except for GFR and urinary Na and osmolality, all these functions returned to pretreatment values one to two weeks after stopping the drug.


Cross-presentation of oral antigens by liver sinusoidal endothelial cells leads to CD8 T cell tolerance.
After ingestion, oral antigens distribute systemically and provoke T cell stimulation outside the gastrointestinal tract. Within the liver, scavenger liver sinusoidal endothelial cells (LSEC) eliminate blood-borne antigens and induce T cell tolerance. Here we investigated whether LSEC contribute to oral tolerance. Oral antigens were efficiently cross-presented on H-2K(b) by LSEC to naive CD8 T cells. Cross-presentation efficiency in LSEC but not dendritic cells was increased by antigen-exposure to heat or low pH. Mechanistically, cross-presentation in LSEC requires endosomal maturation, involves hsc73 and proteasomal degradation. H-2K(b)-restricted cross-presentation of oral antigens by LSEC in vivo induced CD8 T cell priming and led to development of CD8 T cell tolerance in two independent experimental systems. Adoptive transfer of LSEC from mice fed with antigen (ovalbumin) into RAG2-/- knockout mice, previously reconstituted with naive ovalbumin-specific CD8 T cells, prevented development of specific cytotoxicity and expression of IFN-gamma in CD8 T cells. Using a new transgenic mouse line expressing H-2K(b) only on endothelial cells, we have demonstrated that oral antigen administration leads to tolerance in H-2K(b)-restricted CD8 T cells. Collectively, our data demonstrate a participation of the liver, in particular scavenger LSEC, in development of CD8 T cell tolerance towards oral antigens.


Determination of trenbolone residual in bovine liver by liquid chromatography-mass spectrometry.
A sensitive method was developed and validated for the quantitation of trenbolone residues in bovine liver. Target analytes were extracted from liver homogenate using solid phase cartridges, separated on a Phenyl column and detected using an electrospray ionization mass spectrometer operating in positive ion mode. The mean recovery of the analytes was between 62% and 69%. The method provided detection capabilities of 1 microg/kg for trenbolone. The method is suitable for application in veterinary drug residue in surveillance programme.


Impact of the COVID-19 Pandemic on Patients with Gastrointestinal Cancer Undergoing Active Cancer Treatment in an Ambulatory Therapy Center: The Patients' Perspective.
The mortality risk increases greatly in patients with cancer if they are infected with severe acute respiratory syndrome coronavirus 2. The new American Society of Clinical Oncology (ASCO) and the European Society of Medical Oncology (ESMO) guidelines for the COVID-19 pandemic suggested modifications to the standards of care to reduce harm from treatment. However, it is unclear whether these changes suit the wishes of patients. We conducted a survey of patients with gastrointestinal cancer who were undergoing active chemotherapy in our ambulatory therapy center between 17 August and 11 September 2020. The survey comprised 18 questions on five topics: patient characteristics, lifestyle changes, disturbance in their psychological health, thoughts on the cancer treatment, and infection control in the hospital. Among the 63 patients who received the questionnaire, 61 participated in the study. The COVID-19 pandemic has led to changes in their lifestyles and substantially impacted their psychological wellbeing. The incidence of anxiety and insomnia has considerably increased during the pandemic. However, female patients and patients aged 70 years or older reported no notable differences. There was no significant difference in the responses to the questions regarding thoughts on the cancer treatment. Our study revealed that the COVID-19 pandemic has substantially impacted patients' lifestyles and psychological wellbeing. However, most patients preferred to continue their usual treatment without any change to their treatment plan. It is important to involve the patient in the decision-making process when formulating treatment goals.