ELITE-S2: the multifactorial movement analysis facility for the International Space Station.
Experimental observations of adaptation processes of the motor control system to altered gravity conditions can provide useful elements to the investigations on the mechanisms underlying motor control of human subject. The microgravity environment obtained on orbital flights represents a unique experimental condition for the monitoring of motor adaptation. The research in motor control exploits the changes caused by microgravity on the overall sensorimotor process, due to the impairment of the sensory systems whose function depends upon the presence of the gravity vector. Motor control in microgravity has been investigated during parabolic flights and short-term space missions, in particular for analysis of movement-posture co-ordination when equilibrium is no longer a constraint. Analysis of long-term adaptation would also be very interesting, calling for long-term body motion observations during the process of complete motor adaptation to the weightlessness environment. ELITE-S2 is an innovative facility for quantitative human movement analysis in weightless conditions onboard the International Space Station (ISS). ELITE-S2 is being developed by the Italian Space Agency, ASI is to be delivering the flight models to NASA to be included in an expressed rack in US Lab Module in February 2004. First mission is currently planned for summer 2004 (increment 10 ULF 2 ISS).


Auxin-responsive grape Aux/IAA9 regulates transgenic Arabidopsis plant growth.
We report the characterization of VvIAA9, an auxin/indole-3-acetic acid (Aux/IAA) protein, in grapevine (Vitis vinifera L.). VvIAA9 was expressed abundantly in leaves and berries. VvIAA9 transcription was drastically upregulated from anthesis to onset of ripening (termed véraison), in which berry diameter rapidly increased. Treatment with exogenous IAA induced VvIAA9 expression in grape leaves, suggesting that VvIAA9 is an auxin-responsive Aux/IAA protein. The overexpression of VvIAA9 in Arabidopsis thaliana promoted plant growth, including rapid floral transition. However, no morphological differences were observed between the control plant and the VvIAA9-overexpressing plant. The overexpression of VvIAA9 in Arabidopsis plants rendered the plants hyposensitive to exogenous IAA. The exogenous IAA treatment did not induce VvIAA9-overexpressing Arabidopsis plant growth and expression of IAA-responsive HAT2. Taken together, we conclude that grape Aux/IAA9 protein is likely to play a crucial role as a plant growth regulator.


Induction of DNA damage signaling by oxidative stress in relation to DNA replication as detected using "click chemistry".
Induction of DNA damage by oxidants such as H(2) O(2) activates the complex network of DNA damage response (DDR) pathways present in cells to initiate DNA repair, halt cell cycle progression, and prepare an apoptotic reaction. We have previously reported that activation of Ataxia Telangiectasia Mutated protein kinase (ATM) and induction of γH2AX are among the early events of the DDR induced by exposure of cells to H(2) O(2) , and in human pulmonary carcinoma A549 cells, both events were expressed predominantly during S-phase. This study was designed to further explore a correlation between these events and DNA replication. Toward this end, we utilized 5-ethynyl-2'deoxyuridine (EdU) and the "click chemistry" approach to label DNA during replication, followed by exposure of A549 cells to H(2) O(2) . Multiparameter laser scanning cytometric analysis of these cells made it possible to identify DNA replicating cells and directly correlate H(2) O(2) -induced ATM activation and induction of γH2AX with DNA replication on a cell by cell basis. After pulse-labeling with EdU and exposure to H(2) O(2) , confocal microscopy was also used to examine the localization of DNA replication sites ("replication factories") versus the H2AX phosphorylation sites (γH2AX foci) in nuclear chromatin in an attempt to observe the absence or presence of colocalization. The data indicate a close association between DNA replication and H2AX phosphorylation in A549 cells, suggesting that these DNA damage response events may be triggered by stalled replication forks and perhaps also by induction of DNA double-strand breaks at the primary DNA lesions induced by H(2) O(2) .


The relationship between external debt and ecological footprint in SANE countries: insights from Kónya panel causality approach.
There are many studies on the relationship between energy consumption and various environmental indicators in Africa, and SANE countries in particular. However, there is a dearth of studies that relate external debt to CO2 emissions, and even the ecological footprint, which is a more comprehensive environmental indicator. As such, this paper applies advanced estimation techniques to explore the role of external debt in the famous energy-growth-environmental nexus in SANE countries from 1970 to 2018. The findings from the Augmented Mean Group estimator indicate that economic growth and energy consumption increase environmental pressure in the SANE countries. On country-level results, the environmental Kuznets curve (EKC) hypothesis, monotonic increase, and monotonic decrease for ecological footprint holds in South Africa, Algeria, and Nigeria, respectively. Also, the results reveal that external debt increases the ecological footprint in South Africa and Algeria. Furthermore, the Kónya (2006) bootstrap country-level Granger causality test shows that ecological footprint is sensitive to economic growth and energy consumption in South Africa and Nigeria, while economic growth is sensitive to the ecological footprint in both Algeria and Nigeria. This study argues that stringent policy suggestions should be centred on reducing the overdependence on non-renewable energy sources since it underscores the major deteriorating state of environmental quality across SANE countries.


Hollow-fibre liquid-phase microextraction of phthalate esters from water.
A simple and efficient liquid-phase microextraction (LPME) technique using a hollow-fibre membrane, in conjunction with gas chromatography-mass spectrometry has been developed for the extraction and analysis of six phthalate esters in water samples. Parameters such as extraction solvent, agitation of the sample, salt addition and extraction time were controlled and optimised. The developed protocol was found to yield a linear calibration curve in the concentration range from 0.02 to 10 microg l(-1) for most target analytes and the limits of detection were in the low microg l(-1) level, ranging between 0.005 and 0.1 microg l(-1). The repeatability of the method varied between 4% and 11%. Under the present experimental conditions, the performance of the method was found comparable to that of solid-phase microextraction (SPME). The advantage of the proposed method over SPME was that it eliminated carry-over of analytes between runs. The applicability of the developed hollow-fibre LPME method and SPME was demonstrated for real water samples. The ability of both microextraction methods to concentrate many organic analytes was demonstrated as both methods allowed the confirmation of the presence of an extra contaminant (ethyl p-ethoxybenzoate) in bottled mineral water samples.


Infrared and Raman spectroscopic characterization of the arsenate mineral ceruleite Cu2Al7(AsO4)4(OH)13· 11.5(H2O).
The molecular structure of the arsenate mineral ceruleite has been assessed using a combination of Raman and infrared spectroscopy. The most intense band observed at 903 cm(-1) is assigned to the (AsO4)(3-) symmetric stretching vibrational mode. The infrared spectrum shows intense bands at 787, 827 and 886 cm(-1), ascribed to the triply degenerate ν3 antisymmetric stretching vibration. Raman bands observed at 373, 400, 417 and 430 cm(-1) are attributed to the ν2 vibrational mode. Three broad bands for ceruleite found at 3056, 3198 and 3384 cm(-1) are assigned to water OH stretching bands. By using a Libowitzky empirical equation, hydrogen bond distances of 2.65 and 2.75Å are calculated. Vibrational spectra enable the molecular structure of the ceruleite mineral to be determined and whilst similarities exist in the spectral patterns with the roselite mineral group, sufficient differences exist to be able to determine the identification of the minerals.


MCPIP1 Exogenous Overexpression Inhibits Pathways Regulating MYCN Oncoprotein Stability in Neuroblastoma.
The main physiological function of MCPIP1 (regnase-1) is negative regulation of inflammation. Moreover, roles of regnase-1 in apoptosis and differentiation have also been described, but its involvement in cancer is yet to be fully recognized. Earlier, we showed a lack of expression of MCPIP1 in both primary tumors and several neuroblastoma cell lines. Additionally, we reported that levels of MCPIP1 and the key neuroblastoma oncoprotein-MYCN were inversely correlated in BE(2)-C clones overexpressing the MCPIP1 gene. Here, we show that exogenous expression of the MCPIP1 protein decreases MYCN mRNA and protein levels without changing the MYCN mRNA half-life. Furthermore, it was shown that MCPIP1-wt exogenous expression affects levels and phosphorylation of MYCN partners such as Aurora A (Thr288), CDC2 (Tyr15 and Thr161), GSK3β (Ser9), and key cellular components of Akt/mTOR signaling, which regulate MYCN stability and activation. In accordance with the obtained results, we found increased phosphorylation of MYCN protein at Thr58 that causes destabilization of the oncoprotein. Moreover, it is shown that exogenous expression of MCPIP1 does not cause apoptosis. Our data extend knowledge on roles of MCPIP1 in our model and link the protein to regulation of expression and stability of MYCN through decrease of signaling via Akt/mTOR pathway. J. Cell. Biochem. 118: 1741-1755, 2017. © 2016 Wiley Periodicals, Inc.


Treating uncomplicated malaria in children: comparing artemisinin-based combination therapies.
In response to increased resistance to conventional drugs, the WHO is promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria. The objective of this report is to review the available evidence on the efficacy and effectiveness, acceptability, and deployment of ACT in resource-limited settings with a focus on sub-Saharan Africa. ACTs are very effective in the treatment of uncomplicated Plasmodium falciparum malaria in children. ACTs are relatively safe and tolerable with no reported resistance in sub-Saharan Africa despite indications of delayed clearance of infections in south-east Asia. The major challenges to the widespread use of ACT include its high cost, availability, and inefficient delivery due to, among other things, weak healthcare systems. ACTs are an essential tool in the fight to control and eliminate malaria. They are currently the most effective drugs against P. falciparum malaria. They should be deployed through programs that address availability, cost, adherence, and quality assurance. Initiatives including home-based management of malaria, improving public sector procurement and supply chains, and reducing private sector pricing should make ACTs more accessible for sub-Saharan African children who bear the brunt of the burden of malarial disease.


Correction: Using Natural Language Processing to Examine the Uptake, Content, and Readability of Media Coverage of a Pan-Canadian Drug Safety Research Project: Cross-Sectional Observational Study.
[This corrects the article DOI: 10.2196/13296.].


Matricellular proteins in development: perspectives from the Drosophila heart.
The Drosophila model represents an attractive system in which to study the functional contribution of specific genes to organ development. Within the embryo, the heart tube serves as an informative developmental paradigm to analyze functional aspects of matricellular proteins. Here, we describe two essential extracellular matricellular proteins, Multiplexin (Mp) and Lonely heart (Loh). Each of these proteins contributes to the development and morphogenesis of the heart tube by regulating the activity/localization of essential extracellular proteins. Mp, which is secreted by heart cardioblasts and is specifically distributed in the lumen of the heart tube, binds to the signaling protein Slit, and facilitates its local signaling at the heart's luminal domain. Loh is an ADAMTS-like protein, which serves as an adapter protein to Pericardin (a collagen-like protein), promoting its specific localization at the abluminal domain of the heart tube. We also introduce the Drosophila orthologues of matricellular proteins present in mammals, including Thrombospondin, and SPARC, and discuss a possible role for Teneurins (Ten-A and Ten-M) in the heart. Understanding the role of these proteins provides a novel developmental perspective into the functional contribution of matricellular proteins to organ development.


Characterization of human Fc alpha receptor transgenic mice: comparison of CD89 expression and antibody-dependent tumor killing between mouse strains.
Since mice do not express a homologue of the human Fc alpha receptor (FcαRI or CD89), a transgenic mouse model was generated in four different backgrounds (C57BL/6, BALB/c, SCID and NXG) expressing the FcαRI under the endogenous human promoter. In this study, we describe previously unknown characteristics of this model, such as the integration site of the FCAR gene, the CD89 expression pattern in healthy male and female mice and in tumor-bearing mice, expression of myeloid activation markers and FcγRs and IgA/CD89-mediated tumor killing capacity. In all mouse strains, CD89 expression is highest in neutrophils, intermediate on other myeloid cells such as eosinophils and DC subsets and inducible on, among others, monocytes, macrophages and Kupffer cells. CD89 expression levels are highest in BALB/c and SCID, lower in C57BL/6 and lowest in NXG mice. Additionally, CD89 expression on myeloid cells is increased in tumor-bearing mice across all mouse strains. Using Targeted Locus Amplification, we determined that the hCD89 transgene has integrated in chromosome 4. Furthermore, we established that wildtype and hCD89 transgenic mice have a similar composition and phenotype of immune cells. Finally, IgA-mediated killing of tumor cells is most potent with neutrophils from BALB/c and C57BL/6 and less with neutrophils from SCID and NXG mice. However, when effector cells from whole blood are used, SCID and BALB/c are most efficient, since these strains have a much higher number of neutrophils. Overall, hCD89 transgenic mice provide a very powerful model to test the efficacy of IgA immunotherapy against infectious diseases and cancer.


Lack of ethnic differences in the pharmacokinetics and pharmacodynamics of inclacumab in healthy Japanese and Caucasian subjects.
Inclacumab, a novel monoclonal antibody against P-selectin, is in development for the treatment and prevention of atherosclerotic cardiovascular diseases. This study was conducted to investigate potential differences in the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single intravenous doses of inclacumab between Japanese and Caucasian healthy volunteers. Sixty-two subjects (31 Japanese and 31 Caucasian) were enrolled in a single-center, open-label, parallel, three dose groups (0.3, 3.0, and 20 mg/kg), single-dose study in Japanese and Caucasian healthy volunteers. Inclacumab concentrations, platelet-leukocyte aggregates (PLA), free/total soluble P-selectin (sP-selectin) ratio, and antibody formation were measured along with routine safety monitoring during the conduct of the study. The PK profiles of inclacumab in Caucasian and Japanese subjects were similar following single-dose intravenous infusion. The statistical analysis of peak (C max) and total exposure (AUClast) indicated that bioavailability was similar for both races when corrected for body weight. The geometric mean ratios for AUClast and C max in the Japanese versus Caucasian cohort were 101 and 111%, respectively, in 0.3 mg/kg dose group, 108 and 107%, respectively, in 3.0 mg/kg dose group, and 97 and 96%, respectively, in 20 mg/kg dose group. No differences were observed in the level of PLA inhibition and mean free/total soluble P-selectin ratio between Japanese and Caucasian subjects. PK/PD relationship between the free/total sP-selectin ratio or PLA and plasma concentration of inclacumab appeared to be similar in both Japanese and Caucasian populations. The effect of race as a covariate was explored on both PK/PD models for PLA and free/total sP-selectin ratio and did not have a significant effect over the reduced model without race as a covariate. Ethnicity had no clinically relevant influence on inclacumab pharmacokinetics or pharmacodynamics. No dose adjustment of inclacumab is required for differences in race.


The relationship of serum triglycerides, serum HDL, and obesity to the risk of wheezing in 85,555 adults.
Asthma has been linked to obesity and the presence of the metabolic syndrome. To explore which components of the metabolic syndrome that were associated with wheezing, a main symptom of asthma. Further, to explore whether these associations were different in individuals with and without rhinitis symptoms. We used data from the Ibermutuamur Cardiovascular Risk Assessment Plan (ICARIA) including 85,555 Spanish workers (median age = 34, range = 16-75 years) with assessments of self reported wheezing and rhinitis symptoms. Fasting blood samples were analysed for serum triglyceride (s-TG), HDL (s-HDL) and glucose; blood pressure, waist circumference (WC) and body mass index (BMI) were measured. In mutually adjusted analyses including all components of the metabolic syndrome and possible confounders, elevated WC (or BMI), elevated s-TG and low s-HDL were significantly associated with wheezing. Odds ratio (OR) with confidence interval (CI) were: elevated WC = 1.54 (1.46-1.62), elevated s-TG = 1.24 (1.18-1.30), low s-HDL = 1.17 (1.12-1.22). These associations were stronger in individuals without than in those with rhinitis symptoms, OR's (CI's) were WC = without rhinitis 1.70 (1.57-1.85) vs. with rhinitis 1.47 (1.37-1.58). Elevated s-TG = without rhinitis 1.36 (1.26-1.46) vs. with rhinitis 1.21 (1.13-1.29). Low s-HDL = without rhinitis 1.24 (1.15-1.34) vs. with rhinitis 1.11 (1.04-1.18). High s-TG and low s-HDL were associated with wheezing after adjustment for adiposity. This may substantiate elevated s-TG and lowered s-HDL as markers or inducers of inflammation associated disease. The study supports the notion that these biochemical markers have differential effects on different types of wheezing.


[Epidemiology of strokes in pediatry].
Incidence of perinatal arterial stroke (ischemic stroke, intracerebral hemorrhage and subarachnoid hemorrhage) occurring between 20 weeks of gestation and postnatal day 28 ranges between 20 and 65 cases per 100,000 living births. In children aged 29 days to 18 years old, the total incidence is 1.3 to 4.3 for 100,000 per year. In France, almost 450 children are hospitalized for a stroke each year, among them approximately half have an intracerebral hemorrhage.


"Tandir": an old and well known cause of burn injury in the Middle East.
Analysis of an unusual cause of burn injury together with assessment of long-term end results was carried out. The 'tandir' is a kind of oven buried underground and resembles a big hole full of embers and surrounded with sheet iron. Most of the burn victims were children. 68 major burn cases have been admitted to our units in a 3 year period, 32 (47%) of them due to a 'tandir'. In most of the cases burn injuries included the head and both hands as a result of the specific characteristics of the 'tandir'.


Reduction of Distortion Artifacts in Brain MRI Using a Field Map-based Correction Technique in Diffusion-weighted Imaging : A Prospective Study.
The aim of this study was to evaluate the image quality and feasibility of a field map-based technique to correct for susceptibility-induced geometric distortions which are typical for diffusion EPI brain imaging. We prospectively included 52 patients during clinical routine in this single-center study. All scans were performed on a 3T MRI. Patients' indications for MRI mainly consisted of suspected stroke due to the clinical presentation. For the morphological comparison of the corrected and uncorrected EPI diffusion, three experienced radiologists assessed the image quality of the sequences in a blinded and randomized fashion using a Likert scale (1 being poor; 5 being excellent). To ensure comparability of the two methods, an additional quantitative analysis of the apparent diffusion coefficient (ADC) was performed. Corrected EPI diffusion was rated significantly superior in all the selected categories: overall level of artifacts (p < 0.001), degree of distortion at the frontal, temporal, occipital and brainstem levels (p < 0.001), conspicuousness of ischemic lesions (p < 0.001), image quality (p < 0.001), naturality (p < 0.001), contrast (p < 0.001), and diagnostic confidence (p < 0.001). Corrected EPI diffusion offers a significant reduction of geometric distortion in all evaluated brain regions and an improved conspicuousness of ischemic lesions. Image quality, overall artifacts, naturality, contrast and diagnostic confidence were also rated superior in comparison to uncorrected EPI diffusion.


Optimization of enzyme-assisted microwave extraction of Zanthoxylum limonella essential oil using response surface methodology.
Zanthoxylum limonella essential oil possesses potential antimicrobial activity and is of considerable interest as food flavouring and traditional herb. In this study, an enzymolysis-pretreatment-microwave-assisted extraction (EP-MAE) method was used to extract Z. limonella essential oil. The response surface methodology (RSM) with Plackett-Burman design (PBD) and Box-Behnken design (BBD) models were employed to optimize conditions in the EP-MAE method. Seven variables including water to plant ratio, enzyme amount, incubation temperature, incubation time, shaking speed, microwave time, and microwave power were selected to determine the optimal values for extracting Z. limonella essential oil. As the results, four variables including water to plant ratio, enzyme amount, microwave time and power were evaluated as significant variables affecting on yield and volatile compounds of Z. limonella essential oil from both PBD and BBD experiments. The optimum conditions of EP-MAE was obtained as follows: water to plant ratio (11.16 mL/g), enzyme amount (0.68%), microwave time (36.73 min), and power (1665 W). The Z. limonella essential oil composition and its yield from EP-MAE was compared to those extracted from MAE and hydrodistillation. The optimal extraction conditions in the EP-MAE method enhanced significantly higher essential oil yield (7.89 ± 0.08 mg/g) compared to those found by MAE (7.26 ± 0.04 mg/g) and hydrodistillation (7.04 ± 0.03 mg/g), respectively. Fifty-one volatile components were identified among these methods, with similar major compounds of limonene, β-pinene, and α-phellandrene, showing percentage ranging between 34.59-35.78%, 19.91-22.67%, 8.47-8.75%, respectively. However, an extremely higher content of compounds was detected using the EP-MAE method. This study demonstrates the significance of EP-MAE, which may be applied as a more potent extraction method for essential oils in aromatic plants compared to MAE and hydrodistillation.


Design of active and stable Co-Mo-Sx chalcogels as pH-universal catalysts for the hydrogen evolution reaction.
Three of the fundamental catalytic limitations that have plagued the electrochemical production of hydrogen for decades still remain: low efficiency, short lifetime of catalysts and a lack of low-cost materials. Here, we address these three challenges by establishing and exploring an intimate functional link between the reactivity and stability of crystalline (CoS2 and MoS2) and amorphous (CoSx and MoSx) hydrogen evolution catalysts. We propose that Co(2+) and Mo(4+) centres promote the initial discharge of water (alkaline solutions) or hydronium ions (acid solutions). We establish that although CoSx materials are more active than MoSx they are also less stable, suggesting that the active sites are defects formed after dissolution of Co and Mo cations. By combining the higher activity of CoSx building blocks with the higher stability of MoSx units into a compact and robust CoMoSx chalcogel structure, we are able to design a low-cost alternative to noble metal catalysts for efficient electrocatalytic production of hydrogen in both alkaline and acidic environments.


Increased risks between Interleukin-10 gene polymorphisms and haplotype and head and neck cancer: a meta-analysis.
Molecular epidemiological research suggests that interleukin-10 (IL-10) polymorphisms may be associated with an increased risk of head and neck cancer (HNC), but results remain controversial. To derive a more precise evaluation, we performed a meta-analysis focused on genetic polymorphisms of IL-10. PubMed, Embase, CNKI and Wanfang databases were searched for studies that examined the relationship between IL-10 polymorphisms or haplotypes and HNC risk. The odds ratio (OR) and 95% confidence interval (CI) were applied to assess the relationship strength. Publication bias, sensitivity and cumulative analyses were conducted to measure the robustness of our findings. Overall, nine related studies involving 2,258 patients and 2,887 control samples were analyzed. Significant associations between the IL-10-1082A > G polymorphism and HNC risk were observed (G vs. A: OR = 1.56, 95% CI = 1.27-1.92, P < 0.01, I(2) = 69.4%; AG vs. AA: OR = 1.64, 95% CI = 1.32-2.05, P < 0.01, I(2) = 55.6%; GG vs. AA: OR = 2.24, 95% CI = 1.69-2.97, P < 0.01, I(2) = 38.5%; AG + GG vs. AA: OR = 1.70, 95% CI = 1.36-2.14, P = 0.02, I(2) = 61.8%; GG vs. AA + AG: OR = 1.89, 95% CI = 1.23-2.90, P = 0.01, I(2) = 46.3%) in the total population, as well as in subgroup analysis. Moreover, increased HNC risks were also associated with the IL-10 -819T > C polymorphism and the GCC haplotype. In conclusion, our meta-analyses suggest that IL-10 polymorphisms, specifically the -1082A > G polymorphism, may be associated with increased risk of HNC development.


Cerebrospinal fluid glutamine levels and EEG findings in patients with hepatic encephalopathy.
The cerebrospinal fluid glutamine level was determined and an electro-encephalogram was made at roughly the same time in 41 patients on 55 occasions. A modified electro-encephalographic grading for practical use was introduced, because the classical electroencephalographic grading described by PARSONS-SMITH et al. (1957) does not apply to patients in deep coma. A significant correlation was found between the natural logarithms of cerebrospinal fluid glutamine levels and the electro-encephalic grade. In combination, these parameters provide valuable diagnostic and prognostic information in hepatic encephalopathy, and each can serve separately for follow-up purposes.


Assessment of endoscopic aspiration cytology and endoscopic retrograde cholangi-pancreatography (ERCP) in patients with cancer of the pancreas. Part I.
This report is concerned with studies on duodenofiberscopic examinations with aspiration cytology endoscopic retrograde cholangio-pancreatography (ERCP) in 44 patients with cancer of the pancreas. Aspiration cytology alone was diagnostic in 91% of cancer of the head of the pancreas, 55% of cancer the body and tail of the pancreas and 100% of cancer of the whole pancreas. ERCP alone was diagnostic in 59% of cancer of the head of the pancreas, 75% of cancer of the body and tail of the pancreas and 100% of cancer of the whole pancreas. By combining these two approach a diagnostic result was obtained in 95% of cancer of the head of the pancreas and 90% of cancer of body and tail of the pancreas. It is concluded that the combined diagnostic approach has enhanced diagnostic accuracy of malignant lesions of the pancreas and that it has not yet led to an improvement resectability and mortality.


Diversification and trends in biliary tree cancer among the three major ethnic groups in the state of New Mexico.
New Mexico's population is composed of 45% non-Hispanic whites, 42% Hispanics, 10% American Indians, and 3% other minorities. The purpose of this study was to compare the trends of biliary tract cancer among these groups over the past 3 decades. The state's tumor registry was used to ascertain the incidence of gallbladder cancer, extrahepatic bile duct cancer, and intrahepatic bile duct cancer. A total of 1,449 new biliary cancers were diagnosed between 1981 and 2008. The contemporary incidence of gallbladder cancer remains several times higher among American Indians than in other ethnicities: for men, 4.1%, 1.1%, and .8% for American Indians, Hispanics, and non-Hispanic whites, respectively, and for women, 8.1%, 2.1%, and 1.0%, respectively. Biliary malignancies are more prevalent among American Indians. Despite a decline in the incidence of gallbladder cancer among American Indians and Hispanics, it remains higher compared with the state's non-Hispanic white population.


Seasonality of meal patterns and hormonal correlates in red deer.
Two groups of six adult, castrated, male red deer were housed under natural daylength conditions and at ambient temperature at 57 degrees N and fed ad lib. (AL) or at a fixed rate of 50 g/kg0.75 initial liveweight per day throughout the study (restricted, R). Mean daily intakes of AL animals were higher during periods of long daylength than during short daylength (p < 0.001). The higher rates of food intake during periods of long daylength were a function of greater meal durations (p < 0.001), shorter inter-meal intervals (p < 0.001) and higher (p < 0.001) mean rates of ingestion (g/min). In both groups mean plasma concentrations of prolactin, T3, T4, and insulin-like growth factor 1 (IGF-1) were higher (p < 0.001) during long daylength than short daylength although changes in thyroid hormone profiles were much less marked in AL animals. Insulin and growth hormone (GH) profiles exhibited no consistent seasonal trend. Mean plasma concentrations of T3 were higher in AL than in R animals. Mean plasma IGF-1 concentrations during long days were consistently greater in the AL than R animals. It is concluded that the effects of seasonal changes in daylength on appetite and food intake are expressed through changes in both the duration of daylight periods per se and in underlying seasonal changes in physiology and associated meal patterns and eating rates. It is concluded that the roles of T3, IGF-1, and prolactin in the expression of seasonal changes in appetite should be investigated further and, particularly, their effects on other hormone profiles and liver and gut function.


Influence of catabolite repression and inducer exclusion on the bistable behavior of the lac operon.
A mathematical model of the lac operon which includes all of the known regulatory mechanisms, including external-glucose-dependent catabolite repression and inducer exclusion, as well as the time delays inherent to transcription and translation, is presented. With this model we investigate the influence of external glucose, by means of catabolite repression and the regulation of lactose uptake, on the bistable behavior of this system.


The Effect of Ultrafine Process on the Dissolution, Antibacterial Activity, and Cytotoxicity of Coptidis rhizoma.
The dosage of herb ultrafine particle (UFP) depended on the increased level of its dissolution, toxicity, and efficacy. The dissolution, antibacterial activity, and cytotoxicity of Coptidis rhizoma (CR) UFP were compared with those of traditional decoction (TD). The dissolution of berberine (BBR) of CR TD and UFP was determined by high-performance liquid chromatography. The antibacterial activity of CR extract was assayed by plate-hole diffusion and broth dilution method; the inhibitory effect of rat serums against bacteria growth was evaluated after orally given CR UFP or TD extract. The cytotoxicity of CR extract was evaluated by 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide assay. The dissolution amount of BBR from CR UFP increased 6-8-folds in comparison to TD at 2 min, the accumulative amount of BBR in both UFP and TD group increased in a time-dependent manner. The minimal inhibitory concentrations and minimal bactericidal concentrations of CR UFP extract decreased to 1/2~1/4 of those of TD extract. The inhibitory effect of rat serums against bacteria growth decreased time-dependently, and no statistical difference was observed between two groups at each time point. The 50% cytotoxic concentrations of UFP extract increased 1.66~1.97 fold than those of TD. The antibacterial activity and cytotoxicity of CR UFP increased in a dissolution-effect manner in vitro, the increased level of cytotoxicity was lower than that of antibacterial activity, and the inhibitory effect of rat serums containing drugs of UFP group did not improve. Ultrafine grinding process caused a rapid increase of BBR dissolution from CR.The antibacterial activity and cytotoxicity of UFP extract in vitro increased in a dissolution-effect manner, but the cytotoxicity increased lower than the antibacterial activity.The antibacterial activity of rat serums of UFP group did not improve in comparison to that of TD group.


Long-gap esophageal atresia: reconstruction preserving all portions of the esophagus by Schärli's technique.
For distances of over 4-5 cm, esophageal replacement is almost always necessary in esophageal atresias. We present the technical details and describe our experience with esophageal reconstruction by elongation of the lesser curvature (Schärli's technique) in four cases of very long atresias. A retrosternal transposition was made without a thoracotomy in two children, and an orthotopic mediastinal route through a right thoracotomy was done in two others. There were two main complications: anastomotic leaks in three patients that closed spontaneously, and too-rapid gastric emptying, resulting in dumping symptoms that improved with time and diet. One patient developed an anastomotic stricture that responded to bouginage, while another had temporary feeding problems. Esophageal reconstruction by elongation of the lesser curvature provides a relatively simple method of esophageal replacement in children in that all portions of the esophagus are preserved. We propose this technique for early establishment of esophageal continuity in neonates.


Development of cortical circuits: lessons from ocular dominance columns.
The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected. These observations indicate that the initial establishment of cortical functional architecture, and its subsequent plasticity during the critical period, are distinct developmental phases that might reflect distinct mechanisms.


Effect of compression stockings on post thrombotic syndrome in patients with deep vein thrombosis: a meta-analysis of randomised controlled trials.
Whether compression stockings are effective in the prevention of post thrombotic syndrome in patients with deep vein thrombosis remains unknown. Since the recently published SOX trial, no meta-analysis has been done to re-evaluate the available literature on whether compression stockings are beneficial in these patients. We aimed to determine the effectiveness of elastic compression stockings on preventing post thrombotic syndrome in patients with deep vein thrombosis. For this meta-analysis, we searched PubMed, the Cochrane Library, and Embase databases from inception to July 29, 2015, with no language restrictions, for randomised controlled trials comparing compression therapy with placebo (either none or placebo stockings) in patients with deep vein thrombosis. We did a meta-analysis with primary outcome as incidence of post thrombotic syndrome. Secondary outcomes analysed were mortality and recurrence of deep vein thrombosis. Sensitivity analysis was done for heterogeneity, study quality, diagnosis by Villalta scoring, and non-delayed randomisation. We identified 674 reports, of which six were randomised controlled trials including 1462 patients. Use of elastic compression stockings was not associated with prevention of post thrombotic syndrome compared with controls (OR 0·56 [95% CI 0·27-1·16]; 36% [269/739] vs 45% [322/723]; p=0·12). Subgroup sensitivity analysis showed that elastic compression stockings were not associated with prevention of post thrombotic syndrome despite trying to account for heterogeneity (OR 0·63 [95% CI 0·29-1·33]; 27% [63/234] vs 37% [85/231]; p=0·23), diagnosis by Villalta scoring (0·81 [0·36-1·84]; 43% [228/535] vs 45% [235/517]; p=0·62), nor those that patients randomised within 1 month of diagnosis (0·57 [0·22-1·45]; 41% [258/631] vs 49% [304/615]; p=0·24). Secondary outcomes such as mortality (OR 0·98 [95% CI 0·68-1·41]; 10% [68/703] vs 10% [67/690]; p=0·92) or recurrence of deep vein thrombosis (OR 0·93 [95% CI 0·66-1·31]; 6·4% [70/1094] vs 6·8% [73/1066]; p=0·69) did not differ significantly between the treatment and control groups. In patients with deep venous thrombosis, use of elastic compression stockings does not significantly reduce the development of post thrombotic syndrome, however the current body of evidence is limited and we believe at present there is equipoise and further conclusive studies are needed to establish the role of this therapy. None.


[Post-radiotherapy care and monitoring of head and neck cancers].
Radiotherapy performed to treat head and neck cancer results in considerable side effects and the patient must be provided with all the necessary information and regular monitoring. From the announcement of the diagnosis, during and after the radiotherapy, the nurse coordinator identifies and assesses the needs, expectations and concerns of the patients. Their role helps to simplify and personalise the care pathway, providing a liaison between the different professionals and offering support for the patient.


The Effects of an Educational Intervention on Exercise Advice Behaviors of Thai Oncology Nurses.
To evaluate an educational intervention based on the Theory of Planned Behavior to increase oncology nurses' exercise advice behaviors. A single-group, quasi-experimental repeated measures design study was used with 124 oncology nurses in a Thai cancer institute. The educational intervention included preeducation self-directed activities for 1 hour, a 2-hour group education session, and posteducation outreach contact 1 week later. The outcome measures, including the Theory of Planned Behavior constructs, exercise knowledge, and self-reported exercise prescription behaviors, were collected at three time points: Time 1 (2 weeks preintervention), Time 2 (immediately preintervention), and Time 3 (2 weeks after the intervention). Results indicated a statistically significant increase in scores after the intervention for all outcomes, including the Theory of Planned Behavior constructs (overall P value <.001), exercise knowledge (β = 2.99, P < .001), and exercise prescription behaviors: asking (odds ratio [OR] = 12.98, P < .001), assessing (OR = 6.20, P < .001), referring (OR = 4.10, P < .001), and writing exercise advice (OR = 11.52, P < .001). Additionally, verbal counseling behavior was performed by all participants, and therefore, the odds for verbal counseling were not reported. Structural equation modeling analysis demonstrated that attitudes and perceived behavioral control explained 41% of the variance in exercise advice intention. Perceived behavioral control and intention also explained 20% of the variance in self-reported exercise advice behaviors. Attitudinal and perceived behavioral control constructs should be a focus of attention to improve health care professionals' exercise advice behaviors. More focused research is required to examine whether patients engage in and follow the exercise advice provided by oncology nurses.


X-ray-Induced Cherenkov Optical Triggering of Caged Doxorubicin Released to the Nucleus for Chemoradiation Activation.
Concurrent chemoradiotherapy is used for advanced cancers, but the chemotherapy is dose limited by normal tissue toxicity. Localized X-ray activation of chemotherapy could overcome this, as studied here, with release from self-assembled nanomicelles (NMs) created from copolymers loaded with doxorubicin (DOX) having a photocleavable o-nitrobenzyl ester (o-Ne) group. The micelles demonstrated release of DOX from X-ray-induced Cherenkov light and conversion from a caged hydrophobic form to hydrophilic DOX, which achieves nuclear localization. Folate on the exterior of the NMs directed them for effective intracellular uptake prior to irradiation. Irradiation with 8 Gy released the DOX, which then entered the cell nucleus, providing near-complete in vivo tumor eradication and negligible off-target organ damage. Micelles were assembled from molecular component materials that are commonly in human use. This study realizes triple targeting in chemoradiation with potential for cell-receptor-mediated uptake, localized radiotherapy activation, and nuclear relocalization, all leading to limited off-target toxicity.


Antimicrobial activity of essential oils against Staphylococcus aureus and Staphylococcus chromogenes isolated from bovine mastitis.
Staphylococcus aureus and Staphylococcus chromogenes are pathogens frequently detected in bovine mastitis. Treatment and prevention of this disease have been usually carried on with antimicrobials. However, the emergence of bacterial isolates with antimicrobial resistance has aroused interest in new therapeutic alternatives. Plant essential oils (EOs) have been largely studied as antibacterial treatments. In the present study, EOs from five plants were evaluated for their antibacterial activities against S. aureus and S. chromogenes. Bacterial isolates were obtained in a previous study of clinical cases of bovine mastitis. EOs from lemongrass, eucalyptus, lavender, peppermint, and thyme were obtained by hydrodistillation and their chemical compositions were evaluated by gas chromatography (GC). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated for all EOs. The results demonstrated that citral (40.9%), myrcene (24.7%), and geraniol (1.9%) were detected in lemongrass EO; 1,8-cineole (76.9%), α-pinene (8.2%), and ledene (5.1%) in eucalyptus EO; 1,8-cineole (45.2%), camphor (18.2%), and fenchone (14.6%) in lavender EO; L-menthol (38.5%), menthofuran (16.3%), and citronellal (10.6%) in peppermint EO; and thymol (44.2%), p-cymene (24.6%) and 1,8-cineole (9.9%) in thyme EO. More effective antibacterial activities were observed only with the use of lemongrass (MIC and MBC ranging from 0.39 to 3.12 mg/mL and 0.39 to 6.35 mg/mL, respectively) and thyme (MIC and MBC ranging from 0.39 to 1.56 mg/mL and 0.39 to 3.12 mg/mL, respectively). Peppermint, lavender and eucalyptus EOs did not show bactericidal activities. In conclusion, lemongrass and thyme EOs are promising antibacterial alternatives against Staphylococcus species associated with bovine mastitis.


Clinical significance of umbilicoportal manometry.
Ninety-six adult patients had measurements of portal pressur over 1 to 5 days via indwelling extraperitoneal umbilicoportal catheters. Liver biopsy specimens obtained during catheterization showed 50 patients to have a normal liver; the remainder had liver disease. Portal pressure averaged 16.08 +/- 2.87 (SED) cm of saline in normal patients. Ten patients, 6 with cirrhotic and 4 with normal livers, were recatheterized 1.5 days to 7 months later when they came to laparotomy. In all but one, portal pressures were decreased during anesthesia and laparotomy. Twenty additional patients undergoing cholecystectomy had portal pressures measured before and after laparotomy, and after recovery from anesthesia for 1 to 3 postoperative days. Laparotomy caused a decrease in portal pressure of 2.7 +/- 1.3 (SED) cm of saline; after recovery from anesthesia portal pressure was higher by 2.5 +/- 1.7 (SED) cm of saline. Umbilicoportal catheterization is a safe and accurate technique for studying the portal system. In the intact unanesthetized state, we consider 22 cm of saline to be the upper limit of normal for portal pressure.


A new very-small-bore Simmons guiding sheath for transradial neurointervention: Technical note and initial experience.
Transradial access during neurointerventions has increased in popularity because of reduced complications and patient preference. Nevertheless, transradial cannulation into the left common carotid artery can be difficult technically because of the lack of catheter support in the aortic arch. Furthermore, the use of large sheaths can increase the risk of complications at the access site. Here, we developed a new very-small-bore transradial system using a 3F Simmons guiding sheath, to increase the procedural success rate and minimize access-site complications. This system can represent a valuable treatment option for neurointerventions and has the potential to expand the indications for transradial access.


Is ureteral stenting necessary after uncomplicated ureteroscopic lithotripsy? A prospective, randomized controlled trial.
We conducted a prospective, randomized controlled study to investigate the advantages and disadvantages of ureteral stenting after ureteroscopic lithotripsy. A total of 60 patients who underwent ureteroscopic lithotripsy were equally randomized into a stented or a nonstented group. The inclusion criteria were stone 6 to 10 mm., absence of polyp or stricture in the ureter and no mucosal injury during ureteroscopy. The operation was performed with a 6Fr rigid ureteroscope without ureteral dilation and stones were fragmented with a 1.9Fr electrohydraulic lithotriptor without extraction. A 7Fr double pigtail stent was placed in the stented group for 3 days after ureteroscopy. Urinalysis, plain x-ray and renosonography were performed before and after lithotripsy in each patient. Subjective symptoms and pain score were recorded on admission to the hospital and 3 days postoperatively. The stone-free rate was 100% in each group and preoperative hydronephrosis equally resolved in both groups. Mean pain score plus or minus standard deviation improved significantly in the nonstented (6.33 +/- 1.81 preoperatively to 2.30 +/- 1.93 postoperatively, paired Student's t test p <0.0001) and stented (7.10 +/- 1.03 to 2.30 +/- 2.22, p < 0.0001) group. There was no statistical difference in pain reduction between the 2 groups (p = 0.18). The amount of extra parenteral analgesic used was similar in both groups. One patient in the nonstented group visited the emergency room for postoperative renal colic, 25 (83.3%) patients in the stented group complained of at least 1 irritative bladder symptom and only 4 (13.3%) in the nonstented group experienced bladder discomfort. After uncomplicated ureteroscopic electrohydraulic lithotripsy patients without ureteral stenting tend to have similar renal function recovery and satisfactory pain reduction with less irritative symptoms compared to those treated with a ureteral stent. We suggest that it is not necessary to place a ureteral stent routinely after uncomplicated ureteroscopic electrohydraulic lithotripsy for stones smaller than 1 cm.


A cost-effectiveness analysis of remote monitoring after pacemaker implantation for bradycardia in Japan.
Although remote monitoring (RM) after pacemaker implantation is common, its cost-effectiveness has not been fully investigated. Therefore, we assessed the cost-effectiveness of RM compared with conventional follow-up (CFU) in Japanese patients with pacemakers. A Markov model was constructed to analyze costs and quality-adjusted life years after pacemaker implantation. The target population was Japanese patients implanted with a dual-chamber pacemaker for bradycardia. Transition probabilities (e.g. atrial fibrillation, stroke, and device trouble) were obtained from literature and expert sources. Additionally, stroke risk was determined according to anticoagulation and CHADS2 scores. We used a 10-year horizon with sensitivity analyses for significant variables. Compared to CFU, RM was more effective; however, it was also more expensive. When the range of the Japanese willingness-to-pay threshold was considered to be ¥5,000,000, RM was at least cost-neutral relative to the CFU in all elderly patients with pacemakers for bradycardia. The cost-effectiveness of RM relative to CFU could be higher for patients with high CHADS2 scores, especially in patients with a CHADS2 score ≥ 3. Scenario analyses changing the interval between visits to an in-office evaluation in the CFU also demonstrated the same conclusions. In particular, when the interval between office visits was 1 year for the CFU, the RM could be more cost-effective. This study demonstrated that RM can be a cost-effective option for Japanese patients, especially those with high CHADS2 scores and long-term intervals between office visits.


Guidelines for determining probability of causation under the Energy Employees Occupational Illness Compensation Program Act of 2000; revision of guidelines on non-radiogenic cancers. Final rule.
In a notice of proposed rulemaking published in the Federal Register on March 21, 2011, the Department of Health and Human Services (HHS) proposed to treat chronic lymphocytic leukemia (CLL) as a radiogenic cancer under the Energy Employees Occupational Illness Compensation Program Act of 2000 (EEOICPA) (76 FR 15268). Under this final rule, CLL will be treated as being potentially caused by radiation and hence as potentially compensable under EEOICPA. HHS reverses its decision to exclude CLL from such treatment.


A comparison of the effects of isoflurane and ketamine anesthesia on auditory brainstem response (ABR) thresholds in rats.
The auditory brainstem response (ABR) is an acoustically evoked potential commonly used to determine hearing sensitivity in laboratory animals. Both isoflurane and ketamine/xylazine anesthesia are commonly used to immobilize animals during ABR procedures. Hearing threshold determination is often the primary interest. Although a number of studies have examined the effect of different anesthetics on evoked potential waveforms and growth functions, none have directly compared their effect on ABR hearing threshold estimates. The present study used a within-subject comparison and typical threshold criteria, to examine the effect of isoflurane and ketamine/xylazine on ABR thresholds for clicks and pure-tone stimuli extending from 8 to 32 kHz. At comparable physiological doses, hearing thresholds obtained with isoflurane (1.7% in O(2)) were on average elevated across a broad frequency range by greater than 27 dB compared to ketamine/xylazine (ketamine HCl, 50mg/kg; xylazine, 9 mg/kg). This highly significant threshold effect (F(1,6) = 158.3403, p = 3.51 × 10(-22)) demonstrates a substantial difference between general anesthetics on auditory brainstem sensitivity. Potential mechanisms and implications for ABR threshold determination under anesthesia are discussed.


Tocilizumab for severe cytokine-release syndrome after haploidentical donor transplantation in a patient with refractory Epstein-Barr virus-positive diffuse large B-cell lymphoma.
It has been well documented that patients may develop cytokine-release syndrome (CRS) following the administration of monoclonal antibodies, such as chimeric antigen receptor-modified T cell. Cytokine-release syndrome is a common complication in patients who have received haploidentical donor allogeneic haematopoietic cell transplantation (haplo-HCT). Although severe CRS after haplo-HCT is a potentially life-threatening toxicity, a standard treatment has not been established. Cytokine blockade with tocilizumab, an anti-IL-6 receptor antibody, has been effective for the treatment of patients with CRS after chimeric antigen receptor-modified T-cell treatment and has also improved CRS after haplo-HCT. A 46-year-old man was diagnosed with haemophagocytic syndrome associated with Epstein-Barr virus-positive diffuse large B-cell lymphoma. Salvage chemotherapy was unsuccessful; consequently, he received haplo-HCT. On day +4, he developed grade 3 CRS, subsequently high-dose corticosteroid initiated. Nevertheless, on day +6, he developed grade 4 CRS, resulting in requirement for ventilator support and multiple vasopressors. Corticosteroid could not improve severe CRS; therefore, tocilizumab was administered on day +14. Serum C-reactive protein level transiently decreased and weaned multiple vasopressors. Although CRS improved, he developed candidaemia; consequently, he died on day +34. Tocilizumab could transiently improve severe CRS after haplo-HCT. Although tocilizumab may have led to the improvement of CRS, a remaining concern is whether it inhibited the patient's ability to mount antifungal immunity, leading to their demise.


The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous polyposis: a prospective randomized placebo-control trial.
Duodenal adenomas occur in about 90% of patients with familial adenomatous polyposis (FAP) and are the second cause of death of patients who have had a prophylactic proctocolectomy. Studies suggest that biliary acids have a role in the development of duodenal adenomas. The aim of this study was to evaluate the impact of ursodesoxycholic acid (UDCA) on duodenal adenoma formation in patients with FAP. A randomized, double-blinded, placebo-controlled study was carried out of 71 patients (20-65 years) who already had a restorative proctocolectomy. Subjects received either 10 mg/kg of UDCA orally per day or a placebo tablet for 24 months. The Spigelman severity score was determined after duodenal axial and lateral view endoscopy at 12 and 24 months. At 2 years 55 patients had completed the entire period of treatment. At the end of the follow-up period, nine (25%) patients in the UDCA group and seven (20%) in the placebo group had a decrease in the Spigelman score (P = 0.6142). Patients receiving UDCA had no side-effects (0%) compared with four (14%) in the placebo group (P = 0.0392). UDCA had no effect on the development of duodenal adenomas in FAP patients (NCT: 00134758).


Angelchik antireflux device: computed tomography appearance.
The Angelchik antireflux prosthesis is a silicon gel-filled, doughnut-shaped device with a tantalum tie strap that wraps around the gastroesophageal junction after reduction of a hiatal hernia. If dislodged, this prosthesis may produce a confusing picture on computed tomography, as it is of soft tissue density and may mimic a mass lesion. The computed tomography appearance of a normally placed prosthesis is demonstrated, and a case of prosthesis dislodgment diagnosed by computed tomography is reported.


Can virtual reality exposure therapy gains be generalized to real-life? A meta-analysis of studies applying behavioral assessments.
In virtual reality exposure therapy (VRET), patients are exposed to virtual environments that resemble feared real-life situations. The aim of the current study was to assess the extent to which VRET gains can be observed in real-life situations. We conducted a meta-analysis of clinical trials applying VRET to specific phobias and measuring treatment outcome by means of behavioral laboratory tests or recordings of behavioral activities in real-life. Data sources were searches of databases (Medline, PsycInfo, and Cochrane). We included in total 14 clinical trials on specific phobias. Results revealed that patients undergoing VRET did significantly better on behavioral assessments following treatment than before treatment, with an aggregated uncontrolled effect size of g = 1.23. Furthermore, patients undergoing VRET performed better on behavioral assessments at post-treatment than patients on wait-list (g = 1.41). Additionally, results of behavioral assessment at post-treatment and at follow-up revealed no significant differences between VRET and exposure in vivo (g = -0.09 and 0.53, respectively). Finally, behavioral measurement effect sizes were similar to those calculated from self-report measures. The findings demonstrate that VRET can produce significant behavior change in real-life situations and support its application in treating specific phobias.


SARS-CoV-2 infected children form early immune memory responses dominated by nucleocapsid-specific CD8+ T cells and antibodies.
This is the third year of the SARS-CoV-2 pandemic, and yet most children remain unvaccinated. COVID-19 in children manifests as mostly mild or asymptomatic, however high viral titers and strong cellular and humoral responses are observed upon acute infection. It is still unclear how long these responses persist, and if they can protect from re-infection and/or disease severity. Here, we analyzed immune memory responses in a cohort of children and adults with COVID-19. Important differences between children and adults are evident in kinetics and profile of memory responses. Children develop early N-specific cytotoxic T cell responses, that rapidly expand and dominate their immune memory to the virus. Children's anti-N, but not anti-S, antibody titers increase over time. Neutralization titers correlate with N-specific antibodies and CD8+T cells. However, antibodies generated by infection do not efficiently cross-neutralize variants Gamma or Delta. Our results indicate that mechanisms that protect from disease severity are possibly different from those that protect from reinfection, bringing novel insights for pediatric vaccine design. They also underline the importance of vaccination in children, who remain at risk for COVID-19 despite having been previously infected.


A donor splice site mutation in intron 1 of CYBA, leading to chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a rare congenital disorder in which the patients' phagocytes fail to kill ingested microbes due to an inability to generate superoxide and other microbicidal oxygen derivatives. This inability is caused by mutations in one of the four components of the phagocyte-specific NADPH oxidase. A small subgroup of CGD patients has mutations in the CYBA gene that encodes the p22-phox subunit of the NADPH oxidase. This subunit forms, together with gp91-phox, a flavocytochrome b(558) heterodimer in the phagocyte plasma membrane. Expression of both subunits is required for normal expression of this heterodimer. Here, we report an autosomal recessive CGD patient with neutrophils that did not express flavocytochrome b(558) and did not generate superoxide upon activation. Analysis of genomic DNA revealed a 4-bp deletion at the exon-1/intron-1 boundary in CYBA (IVS1+4_7delAGTG). In the patient's cDNA, we found a low expression of an abnormal product, containing exon 1 extended by 79 nucleotides from intron 1, joined to exon 2. This extension is apparently caused by the activation of a cryptic donor splice site with a GT sequence at position 84-85 in intron 1. Both parents of the patient had the same mutation in their genomic DNA, in heterozygous form, but their cDNA contained exclusively the wild-type p22-phox cDNA sequence, indicating that the mutant mRNA was labile. This is, as far as we know, the first description of the molecular and clinical consequences of a donor splice site mutation in intron 1 of any gene reported so far.


Adjuvant Whole Breast Radiotherapy Improve Survival in Women with Heart Failure with Reduced Ejection Fraction Receiving Breast-Conserving Surgery.
to date, no data on the effect of adjuvant whole breast radiotherapy (WBRT) on oncologic outcomes, such as all-cause death, locoregional recurrence (LRR), and distant metastasis (DM), are available in women with left-side breast invasive ductal carcinoma (IDC) and heart failure with reduced ejection fraction (HFrEF). we included 294 women with left-breast IDC at clinical stages IA-IIIC and HFrEF receiving breast-conserving surgery (BCS) followed by adjuvant WBRT or non-adjuvant WBRT. We categorized them into two groups based on their adjuvant WBRT status and compared their overall survival (OS), LRR, and DM outcomes. We calculated the propensity score and applied inverse probability of treatment weighting (IPTW) to create a pseudo-study cohort. Furthermore, we performed a multivariate analysis of the propensity score-weighted population to obtain hazard ratios (HRs). in the IPTW-adjusted model, adjuvant WBRT (adjusted HR [aHR]: 0.60; 95% confidence interval [CI]: 0.44-0.94) was a significant independent prognostic factor for all-cause death (p = 0.0424), and the aHR (95% CI) of LRR and DM for adjuvant WBRT was 0.33 (0.24-0.71; p = 0.0017) and 0.37 (0.22-0.63; p = 0.0004), respectively, compared with the non-adjuvant WBRT group. Adjuvant WBRT was associated with a decrease in all-cause death, LRR, and DM in women with left IDC and HFrEF compared with non-adjuvant WBRT.


Cationic detergents enable the separation of membrane proteins of Plasmodium falciparum-infected erythrocytes by 2D gel electrophoresis.
The intraerythrocytic stage of Plasmodium falciparum alters the characteristics of its host cell by exporting selected plasmodial proteins. Although it is clear that the physicochemical and immunobiological properties of the host cell are modulated during parasite development, the involved plasmodial proteins and their mode of action are not completely known. Using cetyltrimethylammonium bromide (CTAB) or benzyldimethyl-n-hexadecylammonium chloride (16-BAC) for the first dimension and SDS for the second dimension, we separated proteins from membranes of human erythrocytes and of erythrocytes infected with the malaria parasite P. falciparum. Protein spots were analyzed by MALDI-TOF/TOF MS and annotated in respective 2D master gels. By using the alternative 2D approach, characteristic host cell membrane proteins and, more importantly, membrane-associated and exported plasmodial proteins were identified that might play a role in parasite-induced host cell modulation.


Low-dose ranibizumab as primary treatment of posterior type I retinopathy of prematurity.
The aim of this study was to evaluate the visual and structural outcomes of eyes that received ranibizumab as treatment for retinopathy of prematurity (ROP). This was a retrospective case series of infants who received a 0.2 mg (0.02 mL) intravitreal injection of ranibizumab as the primary treatment for type 1 ROP. Outcome measures included regression or recurrence of ROP, complications of treatment, and assessment of visual acuity and refractive error. Forty-two eyes of 21 infants (13 male) were included. Mean gestational age and birth weight were 24.6 ± 1.3 weeks and 613 ± 91 g, respectively. Mean age at injection was 37.4 ± 2.2 weeks postmenstrual age, and mean follow-up period was 10.1 ± 7 months. Active neovascularization regressed rapidly, and anatomical outcomes were favourable in all eyes. Twelve eyes of 6 infants received supplemental laser photocoagulation at a mean post-menstrual age (PMA) of 72.0 ± 27.3 weeks when vascularization had not advanced beyond zone II. Visual acuity was measurable in 28 of 42 eyes. Mean visual acuity was 0.94 ± 0.36 logMAR. Mean spherical equivalent was +1.00. There were no ocular or systemic complications in these patients and no cicatricial complications were observed with no progression to stage 4 or 5 disease. A single intravitreal dose of 0.2 mg (0.02 mL) ranibizumab showed favourable anatomical and functional outcomes in eyes with type 1 ROP.


Generation Y in healthcare: leading millennials in an era of reform.
The healthcare workforce has grown with the addition of a new group of physicians, nurses, allied health professionals, administrators, and support staff who belong to America's youngest generation now in the workforce-generation Y, or the millennials. This generation consists of more than 70 million people, the oldest of whom are now in their late 20s and early 30s. With traits and workplace expectations that differ from those observed in other generations, and with a size that threatens to overtake the total number of baby boomers, generation Yers are positioned to influence (if not drastically change) current leadership approaches. The common traits that define or are associated with generation Y workers are often regarded as barriers yet provide healthcare leaders with a clear guide to understanding these employees and drawing out their best qualities and performance. For the organization to fulfill its social contract to provide high-quality, cost-effective, and safe healthcare, it must satisfy the needs and manage the expectations of those who directly deliver these services. This is especially important in today's environment, which is marked by the still-fluid stipulations of the Affordable Care Act (ACA), changed consumer expectations, and public demands for transparency and accountability.


Correction: Comparison Between Levothyroxine and Lifestyle Intervention on Subclinical Hypothyroidism in Women: A Review.
[This corrects the article DOI: 10.7759/cureus.38309.].


Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.
Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.


Role of PFC during retrieval of recognition memory in rodents.
One of the challenges for memory researches is the study of the neurobiology of episodic memory which is defined by the integration of all the different components of experiences that support the conscious recollection of events. The features of episodic memory includes a particular object or person ("what"), the context in which the experience took place ("where") and the particular time at which the event occurred ("when"). Although episodic memory has been mainly studied in humans, there are many studies that demonstrate these features in non-human animals. Here, we summarize a set of studies that employ different versions of recognition memory tasks in animals to study the role of the medial prefrontal cortex in episodic memory.


Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression.
Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found that infectious virus production was reduced in cells transfected with chimeric virus RNA that had Gln at aa 70 (aa70Q) compared with RNA with Arg at aa 70 (aa70R). Using flow cytometry analysis, we confirmed that HCV core protein accumulated in aa70Q clone transfected cells, and it caused a reduction in cell-surface expression of major histocompatibility complex (MHC) class I molecules induced by IFN treatment through enhanced protein kinase R phosphorylation. We could not detect any effects due to the polymorphism at aa 91. In conclusion, the polymorphism at aa 70 was associated with efficiency of infectious virus production, and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV.


Abnormal sexual development and psychosexual issues.
Animal models of gonadal hormone influences on the sexual differentiation of brain and behaviour are reviewed and discussed as a basis for predicting hormonal influences on human neurobehavioural development. Behavioural outcomes in clinical intersex cases, including congenital adrenal hyperplasia, androgen insensitivity syndrome, enzymatic deficiencies and situations in which hormones have been prescribed during pregnancy are reviewed. It is concluded that the prenatal or neonatal hormone environment contributes to the development of human behaviours that show sex differences, particularly childhood play behaviour, sexual orientation and core gender identity. There also is some evidence for influences on aggression and cognition. It is also concluded that additional research is needed to determine why some intersex patients assigned and reared as girls are not successful in this identity and role.


Introducing antisense oligodeoxynucleotides into Paramecium via electroporation.
A method utilizing electroporation to deliver antisense oligodeoxynucleotides into Paramecium tetraurelia has been developed. For these studies antisense oligonucleotides directed to different regions of the calmodulin mRNA were used. It was found that a pulse delivered at 150-250 V (375-625 V/cm field strength) for 3.9-4.2 ms using a 275 microF capacitor with resistance set at 13 Ohms was sufficient to achieve measurable incorporation of fluorescently-labeled oligodeoxynucleotides in up to 95% of the cells treated. Optimal parameters included using oligodeoxynucleotides of at least 12 bases in length with a 3' blocking group at a dose of around 10 microM. In addition, multiple oligodeoxynucleotides directed to the same target mRNA resulted in at least a 10-fold reduction in the dose of oligodeoxynucleotide required to achieve the desired effects. Taken together, these results indicate that the use of antisense oligodeoxynucleotides can be an easy and useful method for linking genes to specific functions in Paramecium tetraurelia. Finally, this report discusses how different 3' blocking groups and the use of combinations of oligodeoxynucleotides directed to different regions of the same target mRNA can help address concerns about specificity.


Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis.
Coronavirus Disease 2019 (COVID-19) is characterized by an unpredictable disease course, ranging from asymptomatic to severe, life-threatening infections. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation forms. We searched PubMed® and Google® (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) scans. Pooled incidence rates of clinical characteristics were analyzed using random-effect models. In total, 506 patients from 34 studies (68 single cases and 438 from case-series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 ± 17.17 years) than patients with abnormal radiology (39.14 ± 26.70 years) (p-value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases; ground-glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). More than half of the patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.


Disentangling the effects of race/ethnicity and socioeconomic status of neighborhood in cancer stage distribution in New York City.
Stage at diagnosis is an important prognostic factor for the majority of cancers; it may be an indicator for quality of access to health care and is usually correlated with socioeconomic status (SES) and ethnicity/race. We aimed to investigate the association between stage of cancer at diagnosis with neighborhood of residence (as proxy for SES) and ethnicity/race, while controlling for each other, in selected areas of New York City (NYC). The cancer summary data (1999-2008) were provided by the New York State Cancer Registry. Multinomial logistic regression models were applied to calculate risk estimates for being diagnosed with late- or unknown-stage (versus early-stage) cancers in two low-SES and two high-SES neighborhoods of NYC and among several ethnic/racial groups for all cancers combined and cancers of the female breast, lung, colorectum, and prostate, with additional adjustments for sex (for all cancers combined), age, and year of diagnosis. A total of 34,981 cancer cases were included in this study. There were significant and independent ethnic/racial and neighborhood disparities in stage of cancer at diagnosis of most of the cancers studied. The effect of ethnicity/race on the disparity appeared stronger than the effect of neighborhood. There was an overall decreasing trend in the proportion of late-stage cancers, particularly for colorectal cancer, and to a greater extent in the proportion of cancers without staging information. In this population, ethnicity/race seems to be a stronger predictor for late stage at diagnosis than SES, stressing the need for ethnicity/race-oriented programs for cancer screening and improved access to care.


The presence in bovine trachealis muscle of cytosol receptors with high affinity for glucocorticoids.
Whereas receptors with high affinity for glucocorticoids have been reported present in both fetal and adult lungs, there has been no attempt to identify such receptors in airways smooth muscle. We have examined the binding characteristics of glucocorticoids for a cytosol fraction prepared from bovine trachealis muscle. The cytosol fraction, which was prepared in 10 mM Tris, 1.5 mM Na2 EDTA and 2 mM dithiothreitol, contained macromolecular high affinity receptors for 3H-dexamethasone (Kd = 5.6 nM) at a concentration of 0.20 pmol/mg protein. The comparative affinities of other steroids in descending order were: beclomethasone-17, 21-dipropionate, dexamethasone, beta-methasone, triamcinolone and triamcinolone acetonide. Progesterone and deoxycorticosterone only bound to a limited extent, whereas the binding with 5 alpha-dihydrotesterone and pregnenolone was negligible. We conclude that airways smooth muscle is a target tissue for glucocorticoids and postulate that the binding of glucocorticoids to these receptors may receptors may represent the initial step in the anti-asthmatic action of these drugs.


[The quality of dental care: characteristics and criteria].
The paper discusses features and criteria of dental care according to legislative acts in Russian Federation. The study contains detailed assessment of safety, cost/effectiveness ratio and adequate timing as features and adhesion to standards, absence of complications and patients satisfaction as criteria for dental care quality.


Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation.
Chk2 is a kinase critical for DNA damage-induced apoptosis and is considered a tumor suppressor. Chk2 is essential for p53 transcriptional and apoptotic activities. Although mutations of p53 are present in more than half of all tumors, mutations of Chk2 in cancers are rare, suggesting that Chk2 may be inactivated by unknown alternative mechanisms. Here we elucidate one such alternative mechanism regulated by PML (promyelocytic leukemia) that is involved in acute promyelocytic leukemia (APL). Although p53-inactivating mutations are extremely rare in APL, t(15;17) chromosomal translocation which fuses retinoic acid receptor (RARalpha) to PML is almost always present in APL, while the other PML allele is intact. We demonstrate that PML interacts with Chk2 and activates Chk2 by mediating its autophosphorylation step, an essential step for Chk2 activity that occurs after phosphorylation by the upstream kinase ATM (ataxia telangiectasia-mutated). PML/RARalpha in APL suppresses Chk2 by dominantly inhibiting the auto-phosphorylation step, but inactivation of PML/RARalpha with alltrans retinoic acid (ATRA) restores Chk2 autophosphorylation and activity. Thus, by fusing PML with RARalpha, the APL cells appear to have achieved functional suppression of Chk2 compromising the Chk2-p53 apoptotic pathway.


Clinical performance evaluation of a SARS-CoV-2 Rapid Antibody Test for determining past exposure to SARS-CoV-2.
Due to the number of asymptomatic infections and limited access to high-performance antibody tests, the true prevalence and seropositivity of SARS-CoV-2 infection remains unknown. To fill this gap, the clinical performance of a point-of-care SARS-CoV-2 Rapid Antibody Assay, a chromatographic immunoassay for detecting IgM/IgG antibodies, in near patient settings was assessed. Forty-two anti-SARS-Cov-2 positive (CoV+) and 92 anti-SARS-Cov-2 negative (CoV-) leftover samples from before December 2019 were assessed; the Elecsys® Anti-SARS-CoV-2 was used as the reference assay. Analytical specificity was tested using leftover samples collected before December 2019 from patients with common cold symptoms. The SARS-CoV-2 Rapid Antibody Test was 100.0% (95% CI 91.59-100.0) sensitive and 96.74% (95% CI 90.77-99.32) specific, with 0.00% assay failure rate. No cross-reactivity was observed against the common cold panel. Method comparison was additionally conducted by two external laboratories, using 100 CoV+ and 275 CoV- samples, also comparing whole blood versus plasma matrix. The comparison demonstrated 96.00% positive and 96.36% negative percent agreement for plasma with the Elecsys Anti-SARS-CoV-2 and 99.20% percent overall agreement between whole blood and EDTA plasma. The SARS-CoV-2 Rapid Antibody Test demonstrated similar performance to the manufacturer's data and a centralised automated immunoassay, with no cross-reactivity with common cold panels.


Multiple instance learning for lung pathophysiological findings detection using CT scans.
Lung diseases affect the lives of billions of people worldwide, and 4 million people, each year, die prematurely due to this condition. These pathologies are characterized by specific imagiological findings in CT scans. The traditional Computer-Aided Diagnosis (CAD) approaches have been showing promising results to help clinicians; however, CADs normally consider a small part of the medical image for analysis, excluding possible relevant information for clinical evaluation. Multiple Instance Learning (MIL) approach takes into consideration different small pieces that are relevant for the final classification and creates a comprehensive analysis of pathophysiological changes. This study uses MIL-based approaches to identify the presence of lung pathophysiological findings in CT scans for the characterization of lung disease development. This work was focus on the detection of the following: Fibrosis, Emphysema, Satellite Nodules in Primary Lesion Lobe, Nodules in Contralateral Lung and Ground Glass, being Fibrosis and Emphysema the ones with more outstanding results, reaching an Area Under the Curve (AUC) of 0.89 and 0.72, respectively. Additionally, the MIL-based approach was used for EGFR mutation status prediction - the most relevant oncogene on lung cancer, with an AUC of 0.69. The results showed that this comprehensive approach can be a useful tool for lung pathophysiological characterization.


Notch and melanocytes: diverse outcomes from a single signal.
Notch signaling is an evolutionally conserved pathway that serves as a critical regulator of cell fate. From a series of studies, including a report in this issue, researchers have begun to elucidate the critical functions of Notch signaling in the regulation of melanocyte lineage development. With evidence of a recently identified role for Notch signaling in melanomagenesis, characterization of downstream molecular events may offer potential avenues for the development of novel therapeutic strategies.


ChemNet: A Deep Neural Network for Advanced Composites Manufacturing.
Among advanced manufacturing techniques for fiber-reinforced polymer-matrix composites (FRPCs) which are critical for aerospace, marine, automotive, and energy industries, frontal polymerization (FP) has been recently proposed to save orders of magnitude of time and energy. However, the cure kinetics of the matrix phase, usually a thermosetting polymer, brings difficulty to the design and control of the process. Here, we develop a deep learning model, ChemNet, to solve an inverse problem for predicting and optimizing the cure kinetics parameters of the thermosetting FRPCs for a desired fabrication strategy. ChemNet consists of a fully connected FeedForward 9 layer deep neural network trained on one million examples, and predicts activation energy and reaction enthalpy given the front characteristics such as speed and maximum temperature. ChemNet provides highly accurate predictions measured by the mean squared error (MSE) and by the maximum absolute error (MAE) metrics. ChemNet's performance on the "hidden" test data set had an MSE of 5.58 × 10-6 and a MAE of 1 × 10-3.


Non-enzymatic electrochemical determination of cholesterol in dairy products on boron-doped diamond electrode.
Determination of cholesterol in food matrices is essential for quality control concerning the health of consumers. Herein, a simple electrochemical approach for cholesterol quantitation in dairy products is evaluated. The newly developed differential pulse voltammetric method using acetonitrile-perchloric acid mixture as a supporting electrolyte is statistically compared to GC-MS and HPLC-UV. Oxidation signals of cholesterol at +1.5 V and +1.4 V (vs. Ag/AgNO3 in acetonitrile) provide detection limits of 4.9 µM and 6.1 µM on boron-doped diamond and glassy carbon electrodes, respectively. A simple liquid-liquid extraction procedure from dairy products into hexane resulted in a recovery rate of (74.8 ± 3.8)%. The method provides results in close agreement (at a 95% confidence level) with GC-MS, while HPLC-UV resulted in a significant difference in estimated cholesterol concentrations for all samples. This newly developed method is a simpler, faster and cheaper alternative to instrumentally demanding MS-based methods and clearly outperforms HPLC-UV.


Giant Intrahepatic Portal Vein Aneurysm: Leave it or Treat it?
Portal vein aneurysm (PVA) is a rare vascular dilatation of the portal vein. It is a rare vascular anomaly representing less than 3% of all visceral aneurysms and is not well understood. Usually, PVA are incidental findings, are asymptomatic, and clinical symptoms are proportionally related to size. Patients present with nonspecific epigastric pain or gastrointestinal bleeding with underlying portal hypertension. PVA may be associated with various complications such as biliary tract compression, portal vein thrombosis/rupture, duodenal compression, gastrointestinal bleeding, and inferior vena cava obstruction. Differential diagnoses of portal vein aneurysms are solid, cystic, and hypervascular abdominal masses, and it is important that the radiologists be aware of their multi-modality appearance; hence, the aim of this article was to provide an overview of the available literature to better simplify various aspects of this rare entity and diagnostic appearance on different modality with available treatment options. In our case, a 55-year-old male patient came to the gastroenterology OPD for further management of pancreatitis with portal hypertension and biliary obstruction with plastic stents in CBD and PD for the same. In this article, we have reported a case of largest intrahepatic portal vein aneurysm and its management by endovascular technique. As per our knowledge, this is the largest intrahepatic portal vein aneurysm and first case where the endovascular technique was used for the treatment of the same.


Intramolecular hetero-Diels-Alder reactions of imine and iminium dienophiles: quantum mechanical exploration of mechanisms and stereoselectivities.
A series of intramolecular hetero-Diels-Alder reactions of iminium and imine dienophiles has been explored with density functional theory using the B3LYP functional and 6-31+G* basis set. Aqueous solvation energies were calculated with the CPCM method. DFT predicts that these reactions are concerted but involve highly asynchronous transition states. Stereochemical preferences of imine cycloaddition transition states arise from electron repulsion of the nitrogen lone pair with electron density from the butadiene moiety. Protonation of the nitrogen leads to a highly asynchronous transition state. The iminium dienophiles are predicted to have a 17 kcal/mol lower barrier than the corresponding imines, even in aqueous solution.


Filipino help-seeking for mental health problems and associated barriers and facilitators: a systematic review.
This systematic review aims to synthesise the evidence on behavioural and attitudinal patterns as well as barriers and enablers in Filipino formal help-seeking. Using PRISMA framework, 15 studies conducted in 7 countries on Filipino help-seeking were appraised through narrative synthesis. Filipinos across the world have general reluctance and unfavourable attitude towards formal help-seeking despite high rates of psychological distress. They prefer seeking help from close family and friends. Barriers cited by Filipinos living in the Philippines include financial constraints and inaccessibility of services, whereas overseas Filipinos were hampered by immigration status, lack of health insurance, language difficulty, experience of discrimination and lack of acculturation to host culture. Both groups were hindered by self and social stigma attached to mental disorder, and by concern for loss of face, sense of shame, and adherence to Asian values of conformity to norms where mental illness is considered unacceptable. Filipinos are also prevented from seeking help by their sense of resilience and self-reliance, but this is explored only in qualitative studies. They utilize special mental health care only as the last resort or when problems become severe. Other prominent facilitators include perception of distress, influence of social support, financial capacity and previous positive experience in formal help. We confirmed the low utilization of mental health services among Filipinos regardless of their locations, with mental health stigma as primary barrier, while resilience and self-reliance as coping strategies were cited in qualitative studies. Social support and problem severity were cited as prominent facilitators.


Effects of apigenin pretreatment against renal ischemia/reperfusion injury via activation of the JAK2/STAT3 pathway.
The aim of our study is to investigate the protective effect of apigenin and the role of the JAK2/STAT3 signaling pathway in renal ischemia/reperfusion injury (IRI) in rats. For in vivo experiments, rat kidneys were subjected to 45min of ischemia, followed by 24h of reperfusion. The kidneys were pretreated for 24h with apigenin (4mg/kg) intraperitoneally in the absence or presence of the JAK2 kinase-specific inhibitor AZD1480 (30mg/kg). The serum creatinine and urea nitrogen levels were analyzed. Histologic examinations were evaluated. Expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 was detected by immunohistochemistry or western blot. For In vitro experiments, NRK-52E cells were exposed to I/R in the absence or presence of apigenin and JAK2 siRNA was used to explore JAK2/STAT3 activity. Cell viability, cell apoptosis and expression of p-JAK2, p-STAT3, Bcl-2, Bax and Caspase-3 were examined in NRK-52E culture after I/R. Consequently, apigenin conferred a renoprotective effect on the kidneys against IRI, as evidenced by decreased serum creatinine and urea nitrogen, mitigated renal histologic damage, improved NRK-52E cell viability and a decreased apoptotic index, including up-regulation of the anti-apoptotic protein Bcl-2 and down-regulation of the pro-apoptotic proteins Bax and Caspase3. However, AZD1480 and JAK2 siRNA blocked the apigenin-mediated renoprotective effects by attenuating the JAK2/STAT3 signaling pathway as well as abolished the effect of anti-oxidative stress and anti-apoptosis of apigenin. Our study demonstrates that apigenin pretreatment can protect against renal IRI via the activation of the JAK2/STAT3 signaling pathway.


Risk factors for experiencing psychosis during cocaine use: a preliminary report.
Cocaine induced psychosis (CIP) is a common, but not universal side effect of cocaine abuse. Factors underlying the development and severity of CIP remain poorly understood. This study tests the hypothesis that earlier age of initiation of regular use may increase the likelihood of developing CIP, or the severity of CIP symptoms. Cocaine use history and severity of CIP (if any) were assessed with the Cocaine Experience Questionnaire in 51 abstinent (3 weeks-1 year) cocaine dependent individuals. Subjects were divided into those with high and low CIP severity, and into those with early age of initiation of regular cocaine use, and later age of initiation. Various cutoffs between early and late age of initiation were used, ranging from 15 to 22 years. From ages 17 through 20, controlling for cumulative duration of use, severity scores were significantly higher for the early initiation group than for the later initiation group (p values ranged from 0.031 to 0.036). Cumulative duration of use, but not age of initiation, significantly predicted initial development of CIP (p=0.044). The data suggest that early age of initiation of regular cocaine use occurring during vulnerable periods of brain development, may lead to increased severity of CIP.


Thiamethoxam-mediated alteration in multi-biomarkers of a model organism, Galleria mellonella L. (Lepidoptera: Pyralidae).
Thiamethoxam (TMX), a second-generation neonicotinoid, is extensively used to control numerous pests that infest crops. We investigated the effects of TMX (10, 20, 30, 40, and 50 μg/mL for 24, 48, 72, and 96 h) on biomarkers such as antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)); malondialdehyde (MDA), protein, lipid, and carbohydrate levels; micronucleus formation; and total hemocyte count in a model organism, Galleria mellonella L. SOD and CAT activities significantly decreased after 72 and 96 h of treatment at all TMX concentrations compared with control. MDA level increased following treatment with all TMX doses, with the exception of that following treatment with the lowest dose (10 μg/mL) at all tested treatment durations. Lipid and carbohydrate levels significantly decreased following treatment with high doses of TMX (40 and 50 μg/mL) after 48, 72, and 96 h. Micronucleated cell number significantly increased following treatment with all TMX doses at all tested treatment durations, except with 10 μg/mL of TMX for 24 h, when compared with control. During the first 72 h, total hemocyte count significantly decreased following treatment with 20-, 30-, 40-, and 50-μg/mL TMX; however, it was significantly reduced at all doses of TMX after 96 h. These results suggest that TMX can induce immunotoxicity, oxidative stress, and genotoxicity in a potential target and also in the model organism, G. mellonella. In addition, our study provides additional information regarding the prospective toxic effects of TMX.


A role for fibroblast growth factor signaling in the lobuloalveolar development of the mammary gland.
The inappropriate expression of growth factors, or activating mutations of their receptors, have been implicated as causative factors in mouse and human mammary cancer. For example, it has been known for some time that three members of the fibroblast growth factor (FGF) family behave like oncogenes in virally induced mammary cancer of mice. In normal circumstances, signaling via FGF receptors is known to mediate growth, differentiation, and patterning, during embryogenesis and fetal development. A powerful approach to dissecting the roles for these signaling pathways is to determine the developmental consequences of abrogating their function in transgenic mice. In this review, we describe the use of dominant negative FGF receptors to evaluate the contribution of specific FGF signals in normal mammary gland development. These studies have revealed that normal lobuloalveolar development requires FGF signaling to the mammary epithelium, a function that is presumably usurped by MMTV in mouse mammary tumorigenesis.


Novel Approaches to Access Arylfluorosulfates and Sulfamoyl Fluorides Based on Sulfur (VI) Fluoride Exchange.
Sulfur (VI) fluoride exchange (SuFEx) is a new family of click chemistry reactions that relies on readily available sulfuryl fluoride (SO2 F2 ) and ethenesulfonyl fluoride to build diverse chemical structures bearing the SVI -F motif, such as fluorosulfate (-OSO2 F) and sulfonyl fluoride (-SO2 F). These motifs could be useful functional groups and connective linkers in organic synthesis. This unit describes two protocols for performing SuFEx. The first protocol describes an in situ method for rapid generation of arylfluorosulfates in 96-well plates for high-throughput screening. The second protocol outlines use of a shelf-stable fluorosulfuryl imidazolium salt for generating arylfluorosulfates and sulfamoyl fluorides. © 2019 by John Wiley & Sons, Inc.


Partition and location of nimesulide in EPC liposomes: a spectrophotometric and fluorescence study.
Study of the mechanism of action of anti-inflammatory drugs (NSAIDs) and their side-effects may fall in the domain of membranology. In this work the extent of the interaction between an NSAID (nimesulide) and membrane phospholipids was quantified by the partition coefficient, K(p ), using egg phosphatidylcholine (EPC) liposomes as cell membrane models. The liposome/aqueous phase partition coefficients were determined under physiological conditions, by derivative spectrophotometry and fluorescence quenching. Derivative spectrophotometry allows elimination of background signal effects (light scattering) due to the presence of liposomes. Theoretical models, accounting for simple partition of the NSAID between two different media, were used to fit the experimental data, allowing the determination of K(p)in multilamellar vesicles (MLVs) and large unilamellar vesicles (LUVs). The location of nimesulide in MLVs and LUVs was evaluated by fluorescence quenching using spectroscopic probes located at different sites on the membrane. All n-AS probes were quenched and the relative quenching efficiencies were ordered as 2-AS<6-AS approximately 9-AS<12-AS; this suggests the drug is deeply buried in the membrane. Fluorescence quenching using the 12-AS probe was also used to determine the partition coefficient of the drug in MLVs and LUVs. The two techniques yield similar results. Finally, measurement of zeta-potential in the presence of different concentrations of nimesulide was performed to investigate possible changes in the zwitterionic phosphatidylcholine membranes. The membrane surface potential was not altered, which seems to be an indication that nimesulide binds to lipid bilayer mostly by hydrophobic interactions.


GEM, a member of the GRAM domain family of proteins, is part of the ABA signaling pathway.
Abscisic acid (ABA) is fundamental for plant development. Multiple factors have been identified that participate in the ABA signaling network, although a role of many proteins still await to be demonstrated. Here we have investigated the role of GEM (GL2 EXPRESSION MODULATOR), originally annotated as an ABA-responsive protein. GEM contains a GRAM domain, a feature shared with other eight Arabidopsis proteins for which we propose the name of GRE (GEM-RELATED) proteins. We found that (i) GEM expression responds to ABA, (ii) its promoter contains ABRE sites required for ABA response, and (iii) GEM expression depends on members of the ABA signaling pathway. This is consistent with the expression pattern of GEM during development in plant locations were ABA is known to play a direct role. We also found that GEM binds various phospholipids, e.g. mono and diphosphates and phosphatidic acid, suggesting a potential link of GEM with membrane-associated processes. Consistent with this, we found that the phosphoinositol-4-phosphate kinase PIP5K9 binds GEM in vivo. Finally, we demonstrated a role of GEM in seed dormancy. Together, our data led us to propose that GEM is an ABA-responsive protein that may function downstream of ABI5 as part of the ABA signaling pathway.


Integrated control of vector-borne diseases of livestock--pyrethroids: panacea or poison?
Tick- and tsetse-borne diseases cost Africa approximately US$4-5 billion per year in livestock production-associated losses. The use of pyrethroid-treated cattle to control ticks and tsetse promises to be an increasingly important tool to counter this loss. However, uncontrolled use of this technology might lead to environmental damage, acaricide resistance in tick populations and a possible exacerbation of tick-borne diseases. Recent research to identify, quantify and to develop strategies to avoid these effects are highlighted.