Functional impairment in older liver transplantation candidates: From the functional assessment in liver transplantation study.
The emerging epidemic of older patients with cirrhosis has led to a sharp increase in the number of ≥65 year olds considering liver transplantation (LT). However, clinicians lack objective measures to risk stratify older patients. We aimed to determine whether the short physical performance battery (SPPB), a well-validated geriatric measure of physical function, has greater prognostic value in older versus younger LT candidates. Adult outpatients listed for LT with laboratory Model for End-Stage Liver Disease score ≥ 12 underwent physical function testing using the SPPB, consisting of gait speed, chair stands, and balance. Patients were categorized by age ("younger," < 65 years; "older," ≥ 65 years) and SPPB ("impaired," ≤ 9; "robust," > 9). Competing risks models associated age and SPPB with wait-list death/delisting. Of 463 LT candidates, 21% were ≥ 65 years and 18% died or were delisted. Older patients had slower gait (1.1 versus 1.3 m/seconds; P < 0.001), a trend of slower chair stands (12.8 versus 11.8 seconds; P = 0.06), and a smaller proportion able to complete all balance tests (65% versus 78%; P = 0.01); SPPB was lower in older versus younger patients (10 versus 11; P = 0.01). When compared to younger robust patients as a reference group, younger impaired patients (hazard ratio [HR], 1.77; P = 0.03) and older impaired patients (HR, 2.70; P = 0.003) had significantly higher risk of wait-list mortality, but there was no difference in risk for older robust patients (HR 1.38; P = 0.35) [test of equality, P = 0.01]. After adjustment for Model for End-Stage Liver Disease-sodium (MELD-Na) score, only older impaired patients had an increased risk of wait-list mortality compared to younger robust patients (HR, 2.36; P = 0.01; test of equality P = 0.05). In conclusion, functional impairment, as assessed by the SPPB, predicts death/delisting for LT candidates ≥65 years independent of MELD-Na. Further research into activity-based interventions to reduce adverse transplant outcomes in this population is warranted.


Detecting Malaria Hotspots: A Comparison of Rapid Diagnostic Test, Microscopy, and Polymerase Chain Reaction.
Malaria control strategies need to respond to geographical hotspots of transmission. Detection of hotspots depends on the sensitivity of the diagnostic tool used. We conducted cross-sectional surveys in 3 sites within Kilifi County, Kenya, that had variable transmission intensities. Rapid diagnostic test (RDT), microscopy, and polymerase chain reaction (PCR) were used to detect asymptomatic parasitemia, and hotspots were detected using the spatial scan statistic. Eight thousand five hundred eighty-one study participants were surveyed in 3 sites. There were statistically significant malaria hotspots by RDT, microscopy, and PCR for all sites except by microscopy in 1 low transmission site. Pooled data analysis of hotspots by PCR overlapped with hotspots by microscopy at a moderate setting but not at 2 lower transmission settings. However, variations in degree of overlap were noted when data were analyzed by year. Hotspots by RDT were predictive of PCR/microscopy at the moderate setting, but not at the 2 low transmission settings. We observed long-term stability of hotspots by PCR and microscopy but not RDT. Malaria control programs may consider PCR testing to guide asymptomatic malaria hotspot detection once the prevalence of infection falls.


Isolation of apolipoprotein-B-48 from chylomicrons by high-performance liquid chromatography.
Apolipoprotein-B-48 (B-48) is a component of chylomicrons and chylomicron remnants and originates in the human gut wall. Its molecular weight represents 48% of the hepatic apolipoprotein-B-100 (B-100). So far, immunochemical assays are only available for B-100 and do not permit the specific determination of B-48. As a convenient immunochemical method is necessary for clinical and biochemical investigations of chylomicron remnants, we isolated B-48 in amounts sufficient to permit the production of monoclonal antibodies. After delipidation of the chylomicron fraction from 3 1 of human chylous ascites, size-exclusion chromatography was performed by using two serially connected TSK columns. B-48 was eluted as a second peak at about 35% of the total volume, well separated from B-100 (eluted as a first peak). After detection by UV absorption at 280 nm, the fractions collected from 25 automated runs were combined, ultrafiltered and examined for their protein composition by sodium dodecyl sulphate polyacrylamide gel electrophoresis. This indicated that we were able to isolate rapidly 3.4 mg of B-48 in a purity sufficient to perform immunization.


Which subgroup of patients with pathologic N2 non-small cell lung cancer benefit from surgery?
Patients with pathologic N2 non-small cell lung cancer comprise a heterogeneous group. The objective of this study was to evaluate which subgroup of patients with pathologic N2 benefit from surgery in terms of survival probability. This retrospective study included 141 patients who had undergone major resection with pathologically proven N2 from 1990 to 2006 (103 with adenocarcinoma, 38 with squamous cell carcinoma). Patients undergoing preoperative induction therapy were excluded. Records were examined for age, gender, tumor size, surgical procedure, surgical side, clinical N status, primary tumor lobe, curative resection, and metastatic N2 stations. In patients with adenocarcinoma, surgical procedure, clinical N status, curative resection, and metastatic N2 stations were significant prognostic factors in univariate analysis. Age and curative resection were significant factors in patients with squamous cell carcinoma. In multivariate analysis, clinical N2 (P = 0.003), incomplete resection (P = 0.04), and multi-station N2 (P = 0.004) were significant adverse prognostic factors in patients with adenocarcinoma, whereas only incomplete resection (P = 0.002) was significant in patients with squamous cell carcinoma. For adenocarcinoma patients with pathologic N2, the 5-year survival rates were 58.8% for clinical N0-1 and single-station N2, 50% for clinical N2 and single-station N2, 23.9% for clinical N0-1 and multi-station N2, and 0% for clinical N2 and multi-station N2. Prognosis of patients with pathologic N2 can be grouped according to clinical N status and metastatic N2 stations in adenocarcinoma, but not in squamous cell carcinoma. Only adenocarcinoma patients with pathologic N2 appear to have heterogeneous subgroups with different prognoses.


Assessing diagnostic radiology knowledge among Syrian medical undergraduates.
The role of radiology in medicine and healthcare is rapidly expanding worldwide, but awareness about this field among medical students is poor. This is the first study to assess Syrian medical students' knowledge and attitude regarding radiology. This is a cross-sectional study conducted at the Syrian Private University, on November 8, 2019, on the International Day of Radiology during the war crisis. Data were collected through self-administered surveys and analyzed using the Statistical Package for Social Sciences version 25.0 (SPSS Inc., Chicago, IL, USA). The questionnaire was completed by 269 students whose ages ranged between 17 and 30 years old. Males constituted 63.6% of the respondents. The results revealed adequate knowledge about the basics of radiology. 73.6% of the students had previously heard about interventional radiology. There were slight misconceptions with certain points in each section, especially those pertaining to the radiation exposure of each imaging method. Finally, the students expressed low interest in radiology as a future career (24.5%). The level of awareness can affect a student's decision in considering radiology as a future career. Further evaluation of the methods of teaching, input from medical boards, curriculum advisors, and guidance from radiologists is required.


A studyforrest extension, MEG recordings while watching the audio-visual movie "Forrest Gump".
Naturalistic stimuli, such as movies, are being increasingly used to map brain function because of their high ecological validity. The pioneering studyforrest and other naturalistic neuroimaging projects have provided free access to multiple movie-watching functional magnetic resonance imaging (fMRI) datasets to prompt the community for naturalistic experimental paradigms. However, sluggish blood-oxygenation-level-dependent fMRI signals are incapable of resolving neuronal activity with the temporal resolution at which it unfolds. Instead, magnetoencephalography (MEG) measures changes in the magnetic field produced by neuronal activity and is able to capture rich dynamics of the brain at the millisecond level while watching naturalistic movies. Herein, we present the first public prolonged MEG dataset collected from 11 participants while watching the 2 h long audio-visual movie "Forrest Gump". Minimally preprocessed data was also provided to facilitate the use of the dataset. As a studyforrest extension, we envision that this dataset, together with fMRI data from the studyforrest project, will serve as a foundation for exploring the neural dynamics of various cognitive functions in real-world contexts.


Adolescent Health Implications of New Age Technology.
This article examines the health implications of new age technology use among adolescents. As Internet prevalence has increased, researchers have found evidence of potential negative health consequences on adolescents. Internet addiction has become a serious issue. Pornography is now easily accessible to youth and studies have related pornography with several negative health effects. Cyberbullying has become a large problem as new age technologies have created a new and easy outlet for adolescents to bully one another. These technologies are related to increased morbidity and mortality, such as suicides due to cyberbullying and motor vehicle deaths due to texting while driving.


Particle-induced oxidative damage is ameliorated by pulmonary antioxidants.
This investigation focuses on the application of an in vitro assay in elucidating the role of lung lining fluid antioxidants in the protection against inhaled particles, and to investigate the source of bioreactivity in urban PM10 collections from South Wales. The Plasmid Assay is an in vitro method of assessing and comparing the oxidative bioreactivity of inhalable particles. This method has provided the basis of limited toxicological studies into various inhaled xenobiotics including asbestos, and more recently PM10. Carbon Black M120 and Diesel Exhaust Particles (DEP) were tested as PM10 surrogates, DEP displaying the greatest oxidative bioreactivity. Both urban PM2.5 (fine fraction) and PM2.5-10 (coarse fraction) (Cardiff, S. Wales, UK) caused significant damage, the coarse fraction displaying higher oxidative capacity. The soluble components were found to be responsible for most of the bioreactivity in both PM sizes. Low molecular components of fresh lung lavage were found to offer most antioxidant protection, and surrogate Epithelial Lining Fluid (sELF) showed significant amelioration of DNA damage by the coarse fraction but less effect against the fine. Overall, the coarse, soluble fraction of PM10 is a great source of oxidative bioreactivity, but natural pulmonary low molecular weight antioxidants can significantly ameliorate its effects.


Information needs for the rapid response team electronic clinical tool.
Information overload in healthcare is dangerous. It can lead to critical errors and delays. During Rapid Response Team (RRT) activations providers must make decisions quickly to rescue patients from physiological deterioration. In order to understand the clinical data required and how best to present that information in electronic systems we aimed to better assess the data needs of providers on the RRT when they respond to an event. A web based survey to evaluate clinical data requirements was created and distributed to all RRT providers at our institution. Participants were asked to rate the importance of each data item in guiding clinical decisions during a RRT event response. There were 96 surveys completed (24.5% response rate) with fairly even distribution throughout all clinical roles on the RRT. Physiological data including heart rate, respiratory rate, and blood pressure were ranked by more than 80% of responders as being critical information. Resuscitation status was also considered critically useful by more than 85% of providers. There is a limited dataset that is considered important during an RRT. The data is widely available in EMR. The findings from this study could be used to improve user-centered EMR interfaces.


Comparison of axial vibration membrane and submerged aeration membrane in microalgae harvesting.
The submerged aeration membrane (SAM) system and axial vibration membrane (AVM) system can mitigate membrane fouling. In this study, both systems were investigated to compare the performance of filtration and the membrane fouling in algae filtration. In 5-h filtration, the transmembrane pressure (TMP) of SAM reached to 70.0 kPa, while there was almost no increase in TMP for AVM. After continuous filtration, it could be found that there was hardly any algae cells on the membrane of AVM (0.11 g/m(2)), which was about 32.4 times less than that of SAM (3.56 g/m(2)). Compared with the SAM system, AVM had a lesser membrane fouling, regardless of the reversible fouling or irreversible fouling. By SEM, FTIR and EEM, it could be found there was less irreversible extracellular organic matter (EOM) on the membrane of AVM. By MW distribution, it could be observed that less EOM with high-MW adhered to membrane of AVM.


Prescription Opioid Misuse Among Adolescents.
Although recent spikes in overdose deaths are largely attributable to heroin and fentanyl, prescription opioids still account for a significant percentage of overdose deaths. Additionally, overdose deaths are not a problem solely for adults; roughly 8% of all overdose deaths occur in persons aged 15 to 24. In addition to identifying factors that increase risk for misuse and negative outcomes among adolescents, research must examine the causal mechanisms that link these factors to increased risk. Finally, the extant research must serve as the foundation for prevention/intervention strategies and identify treatments that are effective among adolescents with opioid use disorders.


Effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on purine release from the rat cerebral cortex.
The effects of two nucleoside transport inhibitors, dipyridamole and soluflazine, on adenosine, inosine and oxypurine release from the normoxic and hypoxic/ischemic rat cerebral cortex have been studied. Dipyridamole (500 micrograms/kg) enhanced adenosine release during hypoxic/ischemic challenges in comparison with saline-injected controls. It decreased the hypoxia/ischemia-elicited releases of inosine, hypoxanthine and xanthine. Both basal and hypoxia/ischemia-elicited releases of uric acid were elevated. Soluflazine, administered topically or systemically, failed to enhance adenosine release and did not consistently alter the hypoxia/ischemia-evoked releases of inosine, hypoxanthine and xanthine. Basal release of uric acid was elevated. The failure of either drug to elevate the basal or hypoxia/ischemia-evoked releases of adenosine above predrug levels illustrates one of the problems which may be inherent in the use of bidirectional nucleoside transport inhibitors for the manipulation of adenosine levels in the cerebral interstitial fluid.


Preoperative CT diagnosis of right nonrecurrent inferior laryngeal nerve.
The nonrecurrent inferior laryngeal nerve is an anomaly associated with the absence of the brachiocephalic artery (BCA) and the presence of arteria lusoria. The preoperative CT scans from 290 patients (9 nonrecurrent, 281 recurrent) were retrospectively reviewed. We identified the BCA or the arteria lusoria, and classified the relationship between the right subclavian artery (SCA) and the tracheoesophagus into 2 subtypes. The arteria lusoria was identified in 6 nonrecurrent cases. The BCA was identified in 143 recurrent cases. The right SCA was detected on the ventral side of the membranous wall of the trachea in 273 recurrent cases, whereas it was detected on the dorsal side in 8 recurrent cases with enlarged thyroid, and it was detected on the dorsal side in 9 nonrecurrent cases without pressure sign. It is possible to predict a nonrecurrent inferior laryngeal nerve by identifying the arteria lusoria or other features on the preoperative CT.


[The relationship between early neo-maternal exposure, and maternal attachment, maternal self-esteem and postpartum depression in the mothers of NICU infants].
This study was performed to investigate the quantities of three neo-maternal exposures; visiting frequency, auditory contact and physical contact, and to examine the relationship between the quantities of each exposure and maternal attachment, maternal self-esteem and postpartum depression in 40 mothers of NICU babies during the first week in the NICU. Each neo-maternal exposure was counted at every mother's visit to the newborn and maternal attachment, maternal self-esteem and postpartum depression were measured using the maternal attachment inventory, the maternal self-report inventory and Edinburgh Postpartum Depression Scale (EPDS) on the first and seventh day in the NICU. The Mean of each neo-maternal exposure was 8.77(2.81) for the visiting frequency, 5.82(3.66) for the auditory contact and 5.60(2.89) for the physical contact during 7 days in the NICU. No significant changes were found in the scores of maternal attachment, maternal self-esteem and postpartum depression between the first and the seventh day in the NICU. The quantities of neo-maternal exposures were positively related to the scores of maternal attachment and maternal self-esteem but not related to postpartum depression. The results of the study suggest the lack of early neo-maternal exposure in cases of NICU hospitalization negate its beneficial effects on maternal psychological well-being in increasing maternal attachment and self-esteem. More efforts are needed for the neo-maternal interaction and the reevaluation of NICU visitation hours in order to promote maternal-infant interaction.


Role of platelets and thrombosis in coronary atherosclerotic disease and sudden death.
During the last decade, significant advances have been made in the understanding of the pathogenesis of coronary atherosclerotic disease. Two facts are important: 1) the early and some of the advanced coronary atherosclerotic lesions progress very slowly, probably by means of a complex stepwise biologic process with one of the steps being an interaction between platelets and the arterial wall; the process can be favored by the so-called risk factors of atherosclerotic disease, and 2) some of the advanced coronary atherosclerotic lesions progress very rapidly, probably by means of complicating anatomic events, one of which is related to a thrombogenic process. From a clinical point of view, technologic improvements, such as serial coronary arteriography, reperfusion during the acute coronary artery syndromes, postmortem coronary arteriography, and methods for serial histopathologic and histochemical studies, have brought to light the clinical importance of the processes of plaque rupture, dissecting hemorrhage and, most important, thrombosis. These complicated processes appear to be of paramount importance in the pathogenesis of some of the acute coronary syndromes including unstable angina, myocardial infarction and sudden coronary death. Antithrombotic and platelet inhibitor therapy is under investigation and appears promising in some of these patient subsets.


Chlordiazepoxide, go-nogo successive discrimination and brain biogenic amines in cats.
Chlordiazepoxide (CDP; 0.4 mg/kg/day, per os) was administered to cats during either the acquisition (CDP 21-22 days) of a go-nogo successive discrimination task (SD) or the performance (CDP 10 days) of the previously learned SD task. Endogenous levels of serotonin, 5-hydroxyindoleacetic acid, noradrenaline and dopamine were assayed in 12 brain areas, in trained as well as in untrained cats. This study has shown that (1) CDP strongly impaired the acquisition but not performance of the SD task, revealing a dissociation of the effects of CDP on these two stages of training; (2) the CDP administration, as well as the SD training, produced regional changes in brain levels of biogenic amines, suggesting the involvement of particular monoaminergic neurons in the behavioral effects of CDP and in operant behavior; and (3) in particular brain areas, interactions were observed between the effects of the SD training and those of the CDP administration on monoamines, indicating that the behavioral state may interfere with the neurochemical effects of CDP.


[Acquired von Willebrand's disease in the course of severe primary hypothyroidism in a patient with autoimmune polyglandular syndrome type 3].
The case of a 20-year old female, who had been followed because of von Willebrand disease (vWD) was presented in this paper . She had a past history of menorrhagia and bleeding after dental procedures and the activity of von Willebrand factor (vWF) was decreased. Because of suggestive clinical features, the workup for hypothyroidism was performed and the patient was found to have severe hypothyroidism due to Hashimoto thyroiditis. After the institution of replacement therapy with levothyroxine, von Willebrand factor activity returned to normal range and symptoms of von Willebrand disease disappeared. Based on these findings, the diagnosis of acquired von Willebrand syndrome (AvWS) due to hypothyroidism was made. The development of myasthenia led to the final diagnosis of autoimmune polyglandular syndrome type 3 (APS) with myasthenia gravis and vitiligo.


MARDER--multi-axes rotation device for experimental research. A new concept for investigations of the vestibular, oculomotor, and visual systems of humans in three-dimensional space.
A hydraulically driven, digitally servo-controlled multi-axes rotary chair is described. This device generates motion profiles with the subjects head in the center of rotation mainly in order to adequately stimulate the semicircular canals which are sensitive sensors for angular accelerations. This newly developed apparatus allows for motion stimuli which are below the vestibular threshold up to accelerations of 12 rad/s2 (688 degrees/s2) and is thus suitable for a variety of experiments in the field of vestibular, oculomotor, and intersensory research in 3-dimensional space.


Analyses of the terminal sequences of West Nile virus structural proteins and of the in vitro translation of these proteins allow the proposal of a complete scheme of the proteolytic cleavages involved in their synthesis.
The proteolytic processes involved in the synthesis of the structural proteins of the West Nile (WN) flavivirus were analyzed: The carboxy-terminal sequences of the structural proteins were determined and the proteins translated in vitro in the presence of membranes from a mRNA coding for the structural polyprotein were analyzed. The results obtained indicate that the following proteolytic activities are involved in the synthesis and assembly of WN virus structural proteins: The growing peptide chain which contains the sequences of the structural proteins in the order C-pre-M-E is cleaved at three places by cellular signalase(s). This cleavage generates the primary amino acid sequence of the mature structural proteins pre-M and E (and the amino-terminus of the ensuing nonstructural protein NS 1). The amino-terminal part of the polyprotein containing the amino acid residues 1 to 123 is released as a molecule which migrates slightly slower than the mature viral core protein and which presumably is associated to the RER membranes via its carboxy-terminal sequence. This protein is called the anchored C virus particles the anchored C protein is converted into mature C protein by removal of the carboxy-terminal hydrophobic segment containing the amino acid residues 106 to 123. Presumably a virus-coded protease which can cleave the polyprotein after two basic amino acid residues is responsible for this cleavage. The cell-associated WN virus particles are constructed from the proteins C, pre-M, and E which contain the amino residues 1-105, 124-290, and 291-787 of the polyprotein, respectively. Cleavage of the pre-M protein between amino acid residues 215 and 216, presumably by a cellular enzyme located in the Golgi vesicles, and loss of the amino-terminal fragment of this protein are associated with the release of virus from the cells.


Temporal dynamics of bacteria-plasmid coevolution under antibiotic selection.
Horizontally acquired genes can be costly to express even if they encode useful traits, such as antibiotic resistance. We previously showed that when selected with tetracycline, Escherichia coli carrying the tetracycline-resistance plasmid RK2 evolved mutations on both replicons that together provided increased tetracycline resistance at reduced cost. Here we investigate the temporal dynamics of this intragenomic coevolution. Using genome sequencing we show that the order of adaptive mutations was highly repeatable across three independently evolving populations. Each population first gained a chromosomal mutation in ompF which shortened lag phase and increased tetracycline resistance. This was followed by mutations impairing the plasmid-encoded tetracycline efflux pump, and finally, additional resistance-associated chromosomal mutations. Thus, reducing the cost of the horizontally acquired tetracycline resistance was contingent on first evolving a degree of chromosomally encoded resistance. We conclude therefore that the trajectory of bacteria-plasmid coevolution was constrained to a single repeatable path.


Infected total hip arthroplasty revision: one- or two-stage procedure?
Better outcomes have been reported for two-stage total hip arthroplasty (THA) revision for infection. However, one-stage revision arthroplasty remains an attractive alternative option since it requires only one operation. A decision tree has been developed by the authors in order to determine which type of surgical procedure can be performed safely. The goal of this study was to assess this decision tree for THA replacement in the case of a peri-prosthetic infection. A one-stage procedure may be as successful as a two-stage procedure provided some criteria are fulfilled. A prospective study included 84 patients, all diagnosed with infected THA who had prosthesis replacement. A one-stage exchange was performed in 38 cases and a two-stage procedure in 46 cases. A two-stage procedure was decided in the case of important bone loss or unidentified germ. Postoperatively, patients received intravenous antibiotics (six weeks), then oral antibiotics (six weeks). The main evaluation criterion was the rate of infection eradication at 2 years minimal follow-up since surgery. If new infection was suspected, a hip aspiration was performed to determine whether it was non-eradication (same germ) or a new re-infection (other germ), which was not considered as a failure. The initial infection was cured in 83 out of 84 patients (98.8%), 38 (100%) for the one-stage group and 45 (97.8%) for the two-stage group. Three patients were re-infected with different germs in the two-stage group. Eighty out of 84 (95.2%) patients were infection free, all patients (100%) of the one-stage group and 42 patients (91.3%) of two-stage group. If some selection criteria were respected, a high success rate in THA replacement for infection may be achieved with a one-stage procedure. It permits to reduce the costs with no loss of chance for the patients. The decision tree was validated. Level III; prospective case control study.


Data Mining Models for Automatic Problem Identification in Intensive Medicine.
This paper aims to support medical decision making on predicting the diagnosis of COVID-19. Thus, a set of Data Mining (DM) models was developed using prediction techniques and classification models. These models try to understand whether the vital signs of patients have a correlation with a diagnosis. To achieve the objective of the paper, initially, the data was acquired and collected from several data sources such as bedside monitors and electronic nursing records from the Intensive Care Unit of the Santo António Hospital. Secondly, the data was transformed so that it could be used in DM models. The models were induced using the following algorithms: Decision Trees, Random Forest, Naive Bayes, and Support Vector Machine. The analysis of the sensitivity, specificity, and accuracy were the metrics used to identify the most relevant measures to predict COVID-19 diagnosis. This work demonstrates that the models created had promising results.


Capillary zone electrophoresis method for the simultaneous determination of cations in honey.
A capillary electrophoresis system for the simultaneous determination of cations in honey samples has been developed. The complete separation and quantification of K+, Ca2+, Na+, Mg2+, Mn2+, Ni2+ and Li+, which represent more than 99% of the total content of cations in honey, can be achieved in 4 min with only a dilution and filtration of the honey sample. Electrolyte solution was composed by 10 mM imidazole as the carrier buffer and background absorbance provider and acetic acid as the complexing agent (pH 3.60). The running voltage was + 25 kV at 25 degree C. Indirect UV detection was achieved at 185 nm. Under the optimum conditions the detection limits ranged from 0.02 to 48.2 mg/kg and the quantification limits have ranged from 0.41 to 48.7 mg/kg. Precision data in honey samples analysed have shown repeatability and reproducibility RSD (%) lower than 2.84 and 6.62%, respectively. Recoveries of cations in honey samples analysed have ranged from 88.5 to 101.8%. These cations were identified by their relative migration times with regard to Ba2+ migration time used as reference standard and they were quantified by using an external standard calibration. Twenty-five honey samples were analysed to test the proposed method. Mean contents of 1.22 x 10(3), 93, 85, 54, 11, 1.9 and 2.3 mg/kg were found, respectively, for K+, Ca2+, Na+, Mg2+, Mn2+, Ni2+ and Li+ cations in analysed honeys. These results were similar than the obtained by other authors.


Hirschsprung's disease in the laparoscopic transanal pull-through era: implications of age at surgery and technical aspects.
Detailed implications of age at laparoscopic transanal pull-through (LTAPT) on postoperative bowel function (POBF) in Hirschsprung's disease (HD) are somewhat obscure because of a spectrum of factors. Age at surgery was used to categorize 106 consecutive postoperative HD cases treated by our modified LTAPT (JLTPAT) between 1997 and 2015; group A: < 3 months old (n = 31); group B: 3-11 months old (n = 44); group C: 1-3 years old (n = 19); and group D: ≥ 4 years old (n = 12). POBF was assessed by reviewing outpatient records 1, 3, 5, 7, and 10 years after JLTAPT prospectively and scoring each of 5 criteria on a scale of 0-2; best score = 10. Only operative time was statistically longer in group D versus groups A, B, and C. Differences in gender ratios, blood loss, duration of follow-up, and POBF scores were not statistically significant. Mean POBF scores over time were: group A: 6.8, 7.6, 8.4, 8.6, and 8.4; group B: 7.1, 7.8, 8.3, 8.5, and 9.0; group C: 6.9, 7.9, 8.1, 8.3, and 8.6; group D: 7.0, 7.4, 8.2, 8.1, and 8.5, respectively. Age at JLTAPT was not correlated with POBF in HD.


Effects of soda-lime-silica waste glass on mullite formation kinetics and micro-structures development in vitreous ceramics.
The effects of soda-lime waste glass, from the recovery of bottle glass cullet, in partial replacement of Na-feldspar for sanitary-ware ceramic production are discussed. Attention is paid to the mullite growth kinetics and to the macroscopic properties of the final output, the latter ones depending on the developed micro-structures and vitrification grade. Measurements have been performed by in situ high temperature X-ray powder diffraction, scanning electron microscopy, thermal dilatometry, water absorption and mechanical testing. Glass substituting feldspar from 30 to 50 wt% allows one (i) to accelerate the mullite growth reaction kinetics, and (ii) to achieve macroscopic features of the ceramic output that comply with the latest technical requirements. The introduction of waste glass leads to (i) a general saving of fuel and reduction of the CO2-emissions during the firing stage, (ii) a preservation of mineral resources in terms of feldspars, and (iii) an efficient management of the bottle glass refuse by readdressing a part of it in the sanitary-ware manufacturing.


Preparation and characterization of nano chitosan for treatment wastewaters.
Chitosan nanorod with minimum particle size of <100 nm was prepared by crosslinking low molecular weight chitosan with polyanion sodium tripolyphosphate and physicochemically characterized (FT-IR, XRD, SEM, AFM, TGA and DSC) for waste water treatment. Its sorption capacity and sorption isotherms for chromium (Cr) were studied. The effect of initial concentration of Cr ions, sorbent amount, agitation period and pH of solution that influence sorption capacity were also investigated. It was found that nanochitosan in the solid state was rod shaped which could sorb Cr (VI) to Cr (III) ions effectively. Based on the Langmuir, the Freundlich and the Temkin sorption isotherms, the sorption capacity of chitosan nanoparticles is very high and the adsorbent favors multilayer adsorption. The kinetics studies show that the adsorption follows the pseudo-second-order kinetics, which infers the transformation of Cr (VI) to Cr (III). From the results it was concluded that nanochitosan is an excellent material as a biosorbent for Cr removal from water.


Preparation and Electrocapacitive Properties of Hierarchical Porous Carbons Based on Loofah Sponge.
Four porous carbon samples denoted as LSC-1, LSC-2, LCS-3, and LSC-4 were prepared by carbonization of loofah sponge pretreated by ZnCl₂ activation, immersion in N,N-dimethylformamide (DMF), DMF-assisted solvothermal and melamine-assisted hydrothermal processes, and the specific surface areas were 1007, 799, 773, and 538 m²·g-1 with mainly micropores, respectively. Electrocapacitive properties of four porous carbon-based electrodes were investigated with cyclic voltammetry, galvanostatic charge-discharge, and electrochemical impedance spectroscopy in symmetric supercapacitors. All the cyclic voltammetries of four types of supercapacitors showed a rectangular shape, even under a high scan rate of 500 mV·s-1. The capacitances of LSC-1, LSC-2, LSC-3, and LSC-4 were 107.4, 92.5, 60.3, and 82.3 F·g-1 at the current density of 0.1 A·g-1, respectively, and LSC-1 displayed the excellent capacitance retention of about 81.3% with a current density up to 5 A·g-1. All supercapacitors showed excellent electrochemical stability, and the LSC-1-based supercapacitor showed a cycle stability with 92.6% capacitance retention after 5000 cycles at 1 A·g-1. The structure-property relationship of LSC samples is discussed and analyzed on the basis of the experimental data.


AMPK activation induced by promethazine increases NOXA expression and Beclin-1 phosphorylation and drives autophagy-associated apoptosis in chronic myeloid leukemia.
Relapse and drug resistance is still major challenges in the treatment of leukemia. Promethazine, an antihistaminic phenothiazine derivative, has been used to prevent chemotherapy-induced emesis, although there is no report about its antitumor potential. Thus, we evaluated the promethazine cytotoxicity against several leukemia cells and the underlying mechanisms were investigated. Promethazine exhibited potent and selective cytotoxicity against all leukemia cell types in vitro at clinically relevant concentrations. Philadelphia positive chronic myeloid leukemia (CML) K562 cells were the most sensitive cell line. The cytotoxicity of promethazine in these cells was triggered by the activation of AMPK and inhibition of PI3K/AKT/mTOR pathway. The subsequent downstream effects were NOXA increase, MCL-1 decrease, and Beclin-1 activation, resulting in autophagy-associated apoptosis. These data highlight targeting autophagy may represent an interesting strategy in CML therapy, and also the antitumor potential of promethazine by acting in AMPK and PI3K/AKT/mTOR signaling pathways. Since this drug is currently used with relative low side effects, its repurposing may represent a new therapeutic opportunity for leukemia treatment.


Effectiveness of corticosteroids for post-extubation stridor and extubation failure in pediatric patients: a systematic review and meta-analysis.
While the results of previous meta-analyses have shown beneficial effects of corticosteroid therapy on post-extubation stridor and extubation failure in adults, these results might not be generalizable to children because of the differences in anatomy and structure. We aimed to determine the benefits of corticosteroids on those outcomes in pediatric populations. We searched PubMed, EMBASE, and reference lists of articles from inception until February 2019. Randomized controlled trials and observational studies on the efficacy of systemic corticosteroid administration given prior to elective extubation in mechanically ventilated pediatrics were eligible. Outcomes included post-extubation stridor indicating laryngeal edema and extubation failures. A total of ten randomized controlled trials with 591 pediatric patients were included: seven of the ten studies for post-extubation stridor/suspected upper airway obstruction and nine of the ten studies for extubation failure. The estimate of pooled odds ratios (ORs) for post-extubation stridor/suspected upper airway obstruction was 0.40 (95% CI: 0.21-0.79). When analysis was restricted to trials that had explicit data for infants and explicit data for pediatric patients under 5 years old excluding infants, the estimates of pooled ORs were 0.53 (95% CI: 0.20-1.40) and 0.68 (95% CI: 0.38-1.22), respectively. For pediatric patients who received corticosteroids, there was a 0.37-fold lower odds of extubation failure than that in pediatric patients who did not receive corticosteroids (OR, 0.37; 95% CI, 0.22-0.61). While three observational studies were included in this review, their estimates have a potential for bias and we did not perform a meta-analysis. Despite a relatively small sample size in each randomized controlled trial and wide ranges of ages and steroid administration regimens, our results suggest that the use of corticosteroids for prevention of post-extubation stridor and extubation failure could be considered to be acceptable in pediatric patients.


Potential role of microbiome in oncogenesis, outcome prediction and therapeutic targeting for head and neck cancer.
In the last decade, human microbiome research is rapidly growing involving several fields of clinical medicine and population health. Although the microbiome seems to be linked to all sorts of diseases, cancer has the biggest potential to be investigated. Following the publication of the National Institute of Health - Human Microbiome Project (NIH-HMP), the link between Head and Neck Cancer (HNC) and microbiome seems to be a fast-moving field in research area. However, robust evidence-based literature is still quite scarce. Nevertheless the relationship between oral microbiome and HNC could have important consequences for prevention and early detection of this type of tumors. The aims of the present review are: (i) to discuss current pre-clinical evidence of a role of oral microbiome in HNC; (ii) to report recent developments in understanding the human microbiome's relationship with HNC oncogenesis; (iii) to explore the issue of treatment response and treatment toxicity; (iv) to describe the role of microbiota as potentially modifiable factor suitable for targeting by therapeutics. Further studies are needed to better establish the causal relationship between oral microbiome and HNC oncogenesis. Future trials should continue to explore oral microbiome in order to build the scientific and clinical rationale of HNC preventative and ameliorate treatment outcome.


Prognostic value of programmed cell death ligand 1 expression in patients with intrahepatic cholangiocarcinoma: a meta-analysis.
Programmed cell death ligand 1 (PD-L1) is highly expressed in intrahepatic cholangiocarcinoma (ICC) tissues. But there is still a dispute over the prognostic value of PD-L1 in patients with ICC. This study aimed to evaluate the prognostic value of PD-L1 expression in patients with ICC. We performed a meta-analysis based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines. We searched the literature from PubMed, Embase, Web of Science, and the Cochrane Library up to December 5, 2022. Hazard ratios (HR) and their 95% confidence intervals (95% CI) were calculated to analyze the overall survival (OS), recurrence-free survival (RFS), and time to relapse. The quality of the studies was assessed using the Newcastle-Ottawa scale. Publication bias was assessed using a funnel plot and Egger's test. Ten trials with 1944 cases were included in this meta-analysis. The results showed that the low-PD-L1 group had a statistically significant advantage in OS (HR, 1.57; 95% CI, 1.38-1.79, P <0.00001), RFS (HR, 1.62; 95% CI, 1.34-1.97, P <0.00001), and time to relapse (HR, 1.60; 95% CI, 1.25-2.05, P = 0.0002) compared with the high-PD-L1 group. High programmed cell death (PD1)levels, on the other hand, were correlated with poorer OS (HR, 1.96; 95% CI, 1.43-2.70; P <0.0001) and RFS (HR, 1.87; 95% CI, 1.21-2.91; P = 0.005). Multivariate analysis showed that PD-L1 could act as an independent predictor for OS (HR, 1.48; 95% CI, 1.14-1.91; P = 0.003) and RFS (HR, 1.74; 95% CI, 1.22-2.47; P = 0.002), and PD1 acted as an independent predictor for OS (HR, 1.66; 95% CI, 1.15-2.38; P = 0.006). This meta-analysis demonstrated that high PD-L1/PD1 expression is associated with poor survival in ICC. PD-L1/PD1 may be a valuable prognostic and predictive biomarker and potential therapeutic target in ICC. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022380093.


Interleukin-2 production in head and neck cancer patients.
Interleukin-2, a lymphocyte-produced hormone or lymphokine, is required to support proliferation of antigen-triggered T lymphocytes and cytotoxic T cells that are considered essential elements for host tumor control. We have addressed the question of whether interleukin-2 production is altered in head and neck cancer patients, a group that is frequently immunosuppressed. Interleukin-2 production was measured by the tritium-labeled thymidine CT6 assay on the supernatants of peripheral blood lymphocytes of head and neck cancer patients and controls after 24 hour stimulation with phytohemagglutinin. The mean levels of interleukin-2 produced were 127 units (range 3 to 336 units) in the head and neck cancer patients versus 125 units (range 26 to 307 units) in the control group (not statistically significant). There were no significant differences in mean interleukin-2 values between cancer patients with stages I and II or III and IV disease compared with the control subjects. Twenty-seven percent of the cancer patients had interleukin-2 levels below the 10th percentile cutoff point (p = 0.015). The lymphocyte proliferative response to phytohemagglutinin was significantly depressed in the head and neck cancer patients compared with the control subjects. This did not correlate with interleukin-2 production abnormalities, except in patients with advanced disease, in whom there was a borderline correlation between phytohemagglutinin response and interleukin-2 production (correlation coefficient 0.23, p = 0.05). We conclude that the commonly observed depressed T-cell proliferative response to phytohemagglutinin in head and neck cancer patients is not explained by impaired interleukin-2 production.


Isolated rib fractures in elderly patients: mortality and morbidity.
To describe the management, morbidity and mortality seen with isolated rib fractures in elderly patients and assess the need for hospitalization. A case series. A tertiary care centre in Tel Aviv. Hospital records of 77 elderly patients (age 65 yr and older) admitted with isolated rib fractures were reviewed over a 9-year period. Demographic, medical and hospitalization data, blood hemoglobin and oxygen saturation levels. The number of fractured ribs was found to correlate with the morbidity (p = 0.027) and mortality (p = 0.006). There were no significant differences in these rates with respect to comorbidity except for diabetes (higher morbidity) and congestive heart failure (higher mortality). Twenty-eight patients (36%) had pulmonary complications and 1 had cardiac complications. Pulmonary complications were fatal in 6 patients (7.8%). Multivariate analysis of the factors related to morbidity demonstrated that only oxygen saturation (p = 0.0009) and diabetes (p = 0.03) correlated significantly. In spite of significant morbidity and mortality in elderly patients with isolated rib fractures, prediction of the prognosis for these patients is presently not possible. Admission for observation and treatment is therefore justified and beneficial.


Challenge Based Learning nurtures creative thinking: An evaluative study.
The demand for more creative and innovative nurses and together with the rapid expansion of nurse education in Mainland China have called for new approaches to student learning. Challenge Based Learning, an active student-directed approach was incorporated into an elective course in an undergraduate nursing programme. Initially, the students were given some big ideas about the real world. They worked together in small groups to identify the most challenging problems from these ideas, develop some innovative solutions, formulate an action plan for a selected solution, carry out the actions and evaluate the outcome. To evaluate the effectiveness of Challenge Based Learning on students' creativity and innovativeness. Quasi-experimental. A medical university in Guangzhou, China. A convenience sample of 48 undergraduate nursing students from the bilingual class, who enrolled in the elective course, Innovation and Creative Thinking was invited to participate in the evaluative study. They completed the Creativity and Innovation Effectiveness Profile before and after the course. Apart from descriptive statistics, the mean scores of the Creativity and Innovation Effectiveness Profile between the pretest and posttest assessments were analyzed using the Wilcoxon signed ranks test. The results showed that the mean scores of all 7 domains (i.e. creative consciousness, levels of curiosity, pattern breaking skills, idea nurturing ability, willingness to experiment and take risks, courage and resilience and energetic persistence) of Creativity and Innovation Effectiveness were significantly higher in the posttest. Students can enhance their ability to innovate and create through learning. The successful practical experience of using CBL in the study provides a good reference for nurse teachers who want their students to be self-directed, creative and innovative.


Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial.
To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964.


Can family or replacement blood donors become regular volunteer donors?
In sub-Saharan Africa (SSA) confirmed viral marker prevalence between family donors (FDs) and first-time volunteer nonremunerated donors (VNRDs) is similar. In a blood service collecting 10 units/1000 inhabitants, a questionnaire examined FD donation conditions and willingness of becoming repeat VNRDs. Four areas were explored: circumstances of visit to hospital, external pressure, experience of donating, and potential repeat donation. After donation and consent, research assistants administered 25 questions and, according to literacy, helped with translation and completion. Of 513 FDs, three-fourths were males (median age, 27 years). Only 1.3% were unemployed and more than 50% were students or teachers. Ties with hospitalized patient were family (76%), friends (13%), colleagues, or sharing place of worship (10%). Donating blood was the reason for visiting in 16.8% and 20.9% had previously donated blood probably as FDs. In one-third of FDs, the family asked for donation of which 10% was pressured by the unjustified reason that not donating was endangering the patient's life. For two-thirds of FDs, donation was given "because individuals were asked." Donation was a positive experience for 77% of donors, 62% being interested in predonation testing. Repeating donation was acceptable for 99% of 79% FDs answering. FDs are active in the population, are willing to donate blood if asked, are submitted to little pressure, do not receive incentives, and accept repeat donation. Except for circumstances of donation, FDs are not different from VNRDs and more directly motivated. They constitute a legitimate and important source to improve the blood supply in SSA.


Comparison of apically extruded debris associated with several nickel-titanium systems after determining working length by apex locator.
To compare apically extruded debris using ProTaper Universal (PTU), ProTaper Next (PTN), WaveOne (WO), Twisted File (TF), M-Two (MT), and Revo-S (RS) after determining the working length (WL) with root ZX. Seventy-two teeth were selected. The WL determination was performed with root ZX. The teeth were divided into six experimental groups, randomly. In groups, root canals were prepared with PTU to size F4/0.06, with PTN to size X4/0.06, with WO to size 40/0.08, with TF to size 40/0.04, with MT to size 40/0.06, and with RS to size AS40/0.06. After preparations were completed, final irrigation was performed with 2 mL distilled water, and a total of 10 mL of distilled water was used in each tooth. Tubes were stored in an incubator at 68°C for 5 days to evaporate the distilled water before weighing the dry debris. Data were analyzed by the Mann-Whitney U-test. The RS group led to the highest amount of extruded debris, however, WO led to the least amount of extruded debris. There was no statistically difference among the groups (P > 0.05). The authors conclude that the results obtained might depend on the apex locator used to determine the WL.


Efficacy of pre-supplementary motor area transcranial direct current stimulation for treatment resistant obsessive compulsive disorder: A randomized, double blinded, sham controlled trial.
A significant proportion of obsessive compulsive disorder (OCD) patients do not respond to specific serotonin reuptake inhibitors (SSRIs). There is a need to evaluate novel treatment options for OCD. In this double blinded, randomized, sham controlled study, we investigated the efficacy of add-on transcranial direct current stimulation (tDCS) in reducing the symptoms in SSRI-resistant OCD patients by employing anodal pre-supplementary motor area (pre-SMA) stimulation. Twenty-five patients with DSM-IV OCD having persistent symptoms despite adequate and stable treatment with at least one SSRI were randomly allocated to receive 20 min of verum (active) 2-mA tDCS or sham stimulation twice daily on 5 consecutive days [anode over Pre-SMA; cathode over right supra-orbital area]. Response to treatment was defined as at least 35% reduction in the Yale-Brown Obsessive-Compulsive Scale (YBOCS) total score along with a Clinical Global Impression - Improvement (CGI-I) score of 1 (very much improved) or 2 (much improved). The response rate was significantly greater in the verum tDCS(4 out of 12) compared to sham-tDCS (0 out of 13) [Fisher's exact test, p = 0.04]. Repeated measures analysis of variance with tDCS type (verum vs. sham) as between subjects factor showed that there was a significant tDCS-type X time-point interaction with significantly greater reduction of YBOCS total score [F (1,22) = 4.95,p = 0.04,partial-η2 = 0.18] in verum-tDCS group. The results of this RCT suggest that tDCS may be effective in treating SSRI-resistant OCD. Future studies should examine the efficacy in larger samples of OCD and explore other potential target regions using randomized sham-controlled designs, in addition to examining the sustainability of the beneficial effects. Clinical Trials Registry India (http://ctri.nic.in/Clinicaltrials/login.php): Registration Number- CTRI/2016/04/006837).


Rapid detection of Haemophilus influenzae by hel gene polymerase chain reaction.
To evaluate the efficiency of hel gene polymerase chain reaction (PCR) to detect Haemophilus influenzae in various clinical/non-clinical samples. Seventy-four clinical samples (cerebrospinal fluid, blood, sputum, throat and nasal swabs) and throat swabs of 17 asymptomatic carriers were collected. Primers were used to amplify the hel gene of H. influenzae encoding P4 outer membrane protein directly from the processed samples. The samples were also examined by conventional culture methods and the results were compared with those of PCR. The culture methods showed positive results in 60 (65.9%) of 91 samples in contrast to 62 (68.12%) samples tested positive by PCR. None of the culture-positive samples were PCR-negative while two of the culture-negative samples were PCR-positive. The specificity of the products was confirmed by Southern hybridization and failure of various other organisms to amplify the hel gene product. The sensitivity of the PCR assay was found to be 50 pg of DNA. These findings suggest that the hel gene PCR is a rapid, sensitive and a specific new method for direct identification of H. influenzae. Thus, this PCR test can improve the detection rate of H. influenzae in suspected clinical samples as compared with that of conventional culture methods.


Favorable cytogenetic abnormalities in secondary leukemia.
The authors report on five patients with secondary leukemia (SL) and one of the "specific" chromosomal rearrangements usually encountered in de novo acute nonlymphoblastic leukemia: inv(16), t(15;17), t(8;21), and t(9;11). They were characterized by solid tumor as the primary malignancy in four of five cases, absence of preleukemic phase in all cases, and myelodysplastic features in one of five cases only. All patients achieved complete remission (CR) with aggressive chemotherapy. Only two relapsed, but follow-up is still limited in the three remaining cases. Cytogenetic analysis is important in all younger patients with SL, especially if unusual features (such as absence of preleukemic phase or myelodysplastic features) are found. Aggressive chemotherapy appears to be indicated in those patients if a "specific" rearrangement is found.


Model of competence: a conceptual framework for understanding the person-environment interaction for persons with motor disabilities.
The "Model of Competence" has been recently elaborated to help expand our understanding relating to a person's interaction with the environment. Specifically, it seeks to deal with the issues related to the home adaptation (the home layout and equipment) for a person living with motor disabilities. This theoretical model takes into account various characteristics of the person as well as of the environment, by re-grouping six concepts: person, environment, activity, role, competence and handicap situation. The "Model of Competence" is distinct because it includes: (1) both the human and the nonhuman dimension of the environment; (2) personal characteristics other than the strictly physical ones; (3) a clear identification of the interaction between the person and the environment; and (4) a means of operationalizing it via an assessment instrument. This model proposes an innovative approach to the person-environment relation in terms of personalizing accessibility, and thereby offers a new approach to understanding the concept of universal access. It has been developed for research and application, and addresses several disciplines.


Effect of insulin and 20-hydroxyecdysone in the fat body of the yellow fever mosquito, Aedes aegypti.
In mosquitoes, yolk protein precursor (YPP) gene expression is activated after a blood meal through the synergistic action of a steroid hormone and the amino acid/target of rapamycin (TOR) signaling pathway in the fat body. We investigated the role of insulin signaling in the regulation of YPP gene expression. The presence of mosquito insulin receptor (InR) and the Protein kinase B (PKB/Akt) in the adult fat body of female mosquitoes was confirmed by means of the RNA interference (RNAi). Fat bodies stimulated with insulin were able to promote the phosphorylation of ribosomal S6 Kinase, a key protein of the TOR signaling pathway. Importantly, insulin in combination with 20-hydroxyecdysone activated transcription of the YPP gene vitellogenin (Vg), and this process was sensitive to the phosphoinositide-3 kinase (PI-3k) inhibitor LY294002 as well as the TOR inhibitor rapamycin. RNAi-mediated knockdown of the mosquito InR, Akt, and TOR inhibited insulin-induced Vg gene expression as well as S6 Kinase phosphorylation in in vitro fat body culture assays.


Patient Safety in Anesthesia: Hand Hygiene and Perioperative Infection Control.
This review highlights the importance of the anesthesia team in minimizing perioperative infection risks and prevention of surgical site infection. Due to the immense financial and patient care burden that results from perioperative infection, a foundational knowledge in preventive measures is essential. Perioperative infection control, the role of the anesthesia team in reducing infection risk, and more specifically the outsized importance of hand hygiene in this space have become increasingly apparent. Maintenance of workspace cleanliness along with hand hygiene forms the cornerstone of preventing microbial transmission. Unfortunately, improvements around perioperative infection control are lacking. The importance of the anesthesia team in maintaining proper hand hygiene, a clean work environment, and appropriate patient conditions to minimize risk of perioperative infection cannot be overstated. Poor clinical outcomes, economic burden, and external pressure from payers highlight the need for anesthesia providers to have an up-to-date knowledge of best practices in this area. In this article, we will review the current recommendations for hand hygiene practices and perioperative infection prevention.


Electrocatalytic assay of mercury(II) ions using a bifunctional oligonucleotide signal probe.
Engineered nucleic acid probes containing recognition and signaling functions find growing interest in biosensor design. In this paper, we developed a novel electrochemical biosensor for sensitive and selective detecting of Hg(2+) based on a bifunctional oligonucleotide signal probe combining a mercury-specific sequence and a G-quadruplex (G4) sequence. For constructing the electrochemical Hg(2+) biosensor, a thiolated, mercury-specific oligonucleotide capture probe was first immobilized on gold electrode surface. In the presence of Hg(2+), a bifunctional oligonucleotide signal probe was hybridized with the immobilized capture probe through thymine-mercury(II)-thymine interaction-mediated surface hybridization. The further interaction between G4 sequence of the signal probe and hemin generated a G4-hemin complex, which catalyzed the electrochemical reduction of hydrogen peroxide, producing amplified readout signals for Hg(2+) interaction events. This electrochemical Hg(2+) biosensor was highly sensitive and selective to Hg(2+) in the concentration of 1.0 nM to 1 μM with a detection limit of 0.5 nM. The new design of bifunctional oligonucleotide signal probes also provides a potential alternative for developing simple and effective electrochemical biosensors capable of detecting other metal ions specific to natural or artificial bases.


Clinical assessment of visual acuity in human infants.
Electrophysiological and fixation preference techniques have been used in the laboratory to assess numerous visual functions in infants. However, the laboratory situation is considerably different from the clinical setting. A modification of the procedures developed in the laboratory is required before they may be applied to the routine clinical examination of infants. This paper reviews these issues.


A retrospective cohort study of dermatological problems observed in paediatric intensive care unit.
Dermatological manifestations are often encountered in paediatric intensive care units (PICU). Spectrum of dermatological problems that may arise in critically ill children in intensive care unit remains unknown. The aim of this study was to find out the burden of dermatological problems and to describe the proportional distribution of paediatric dermatoses in ICU set-up. In a retrospective cohort study, we analysed all types of paediatric dermatological conditions manifesting in children admitted to a tertiary level ICU in South India. During the study period of 25 months, 1180 new cases were admitted to PICU. A total of 318 children with 361 skin manifestations were observed. Majority of the skin lesions were minor and were secondary to systemic disease. Infection was the leading cause of dermatoses in ICU. Dengue infection was detected in 64% of total cases included in the study. Stevens-Johnson syndrome was the only primary dermatological condition leading to PICU admission in the present cohort. The spectrum and proportional distribution of skin conditions in children differ from adult ICU-data. Further large-scale investigations are needed to define the characteristics and distribution of infections along with other disease conditions leading to ICU-admissions and mortality among critically ill paediatric patients.


Implementation of Peer Messengers to Deliver Feedback: An Observational Study to Promote Professionalism in Nursing.
The Co-Worker Observation System (CORS) is a tool and a process to address disrespectful behavior through feedback from trained peer messengers. First used by physicians and advanced practice providers (APPs), CORS has been shown to decrease instances of unprofessional behaviors among physicians and APPs. The research team assessed the feasibility and fidelity of implementing CORS for staff nurses. CORS was implemented at three academic medical centers using a project bundle with 10 essential implementation elements. Reports of unprofessional behavior among staff nurses that were submitted through the institution's electronic reporting system were screened through natural language processing software, coded by trained CORS coders using the Martinez taxonomy, and referred to a trained peer messenger to share the observations with the nurse. A mixed methods, observational design assessed feasibility and fidelity. A total of 590 reports from three sites were identified by the Center for Patient and Professional Advocacy from September 1, 2019, through August 31, 2021. Most reports included more than one problematic behavior, each of which was coded. Of the peer messages, 76.5% were successfully documented using the debriefing survey as complete, 2.2% as awaiting messenger feedback, and 0.2% as awaiting messenger assignments (total of 78.9 % considered delivered). A total of 21.1% were not shared; 4.7% of reports were intentionally not shared because the issue stemmed from a new system or policy implementation (4.0%) or because of known factors affecting the nurse (0.7%). CORS can be implemented with staff nurses efficiently when nursing infrastructure is adequate.


Sixteen-Year-Old Boy From Nigeria With a Rash.
DATE: Thursday, October 20, 2011. Pediatric Fellows' Day Workshop Hosting Organization: Infectious Diseases Society of America. 49th Annual Meeting of the Infectious Diseases Society of America. Boston, Massachusetts.


Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass.
Mitochondrial DNA (mtDNA) was reported as a pro-inflammatory agent. In our previous study, elevation of plasma mtDNA was revealed after cardiac surgery with cardiopulmonary bypass (CPB). Platelets were activated during the cardiac surgery and recent study revealed its ability to release mtDNA. Our present study postulated that the elevated plasma mtDNA comes from activated platelets, which plays a critical role in post-CPB inflammatory responses. Sixty-eight patients who underwent coronary artery bypass graft (CABG) with CPB were enrolled in our study. Blood samples were collected before induction of anaesthesia (T1), at the end of CPB (T2), 12 h post-CPB (T3), 24 h post-CPB (T4), 48 h post-CPB (T5) and 72 h post-CPB (T6). Blood samples were analyzed for the routine blood test and prepared for plasma isolation. MtDNA concentration was measured by rt-PCR, and TNF-α and IL-6 were examined by specific ELISA kits. Subgroup study was analyzed by activation levels of platelet. Basic information, mtDNA level, TNF-α level and IL-6 level were all carefully studied in each quartile. Activation level of platelets increased and peaked at T2, which decreased gradually from T3 to T6 (P < 0.05). MtDNA increased after CPB, peaked at T3, and then backed from T4 to T6 (P < 0.05). Bivariate correlation between peak activation level of platelets and peak plasma mtDNA level showed a positive correlation between these two parameters (r = 0.683, P < 0.0001). Both TNF-α and IL-6 showed similar patterns as mtDNA, with an increase from T1 to T3 and a decrease from T4 to T6 (P < 0.05). Subgroup analysis further demonstrated that patients with higher activation levels of PLT had higher plasma mtDNA levels and inflammatory level (P < 0.05). Our study revealed the dynamic changes of activation level of platelets and identified the interesting association between platelets activation and plasma mtDNA, suggesting a novel potential mechanism of activated platelets-induced post-CPB inflammatory responses.


Disulfide reductase systems in liver.
Intermediary metabolism and detoxification place high demands on the disulfide reductase systems in most hepatocyte subcellular compartments. Biosynthetic, metabolic, cytoprotective and signalling activities in the cytosol; regulation of transcription in nuclei; respiration in mitochondria; and protein folding in endoplasmic reticulum all require resident disulfide reductase activities. In the cytosol, two NADPH-dependent enzymes, glutathione reductase and thioredoxin reductase, as well as a recently identified NADPH-independent system that uses catabolism of methionine to maintain pools of reduced glutathione, supply disulfide reducing power. However the necessary discontinuity between the cytosol and the interior of organelles restricts the ability of the cytosolic systems to support needs in other compartments. Maintenance of molecular- and charge-gradients across the inner-mitochondrial membrane, which is needed for oxidative phosphorylation, mandates that the matrix maintain an autonomous set of NADPH-dependent disulfide reductase systems. Elsewhere, complex mechanisms mediate the transfer of cytosolic reducing power into specific compartments. The redox needs in each compartment also differ, with the lumen of the endoplasmic reticulum, the mitochondrial inter-membrane space and some signalling proteins in the cytosol each requiring different levels of protein oxidation. Here, we present an overview of the current understanding of the disulfide reductase systems in major subcellular compartments of hepatocytes, integrating knowledge obtained from direct analyses on liver with inferences from other model systems. Additionally, we discuss relevant advances in the expanding field of redox signalling. LINKED ARTICLES: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc.


[Investigations of basic feed quality: Mycotoxins on maize for silage 1997-2003].
Maize for silage purposes is investigated on Zeralenone (ZEA) and Deoxynivalenol (DON) in Saxony since 1997. About 45 samples from various regions of Saxony are analyzed every year. The occurrence of DON and ZEA was proved for 20 to 90% of all samples. Most of the samples showed both of these toxins. The quantity of the detected toxins was generally very low, even in so called "Fusarium years" only 20% of samples exceeded the lowest border of orientation values for critical dietary concentrations in cattle feed. We observed a higher contamination with DON in samples from the region "Erzgebirge" and clear higher contents of ZEA in the region "Sächsisches Heideland". Correlation between toxin content and other parameters like cultivation, pre-fruit etc. were not observed, probably because of masking these effects by variety and location.


Use of the blood transfusion service in total knee replacement arthroplasty. The cost implications.
In view of the rising costs of blood transfusion and reports of inappropriate transfusions an audit of the local practice was organised. The aim was to investigate whether blood transfusion in primary unilateral Total Knee replacement Arthroplasty (TKA) operations was being used inappropriately locally, the resultant cost implications and suggest ways of reducing these. A 1-year retrospective survey of blood transfusion practice was conducted for all consecutive elective, primary, unilateral TKA operations at a District-General Hospital. 169 operations were performed and 58 (34%) patients were transfused. A retrospective Haemoglobin concentration (Hb) analysis was performed for all the transfused patients to identify the number of transfusions that satisfied the suggested transfusion criteria of a threshold Hb of 8 g/dl and when indicated, a minimum transfusion of 2 units. Complete transfusion data was available on 49/58 (84%) patients transfused. When applying the above criteria to this sample, the potential annual saving for the department was estimated at approximately 8000 pounds Sterling; only 9 of these patients were deemed to be appropriately transfused.


Pseudoaneurysm: Cause of Unusual Postoperative Bleed in Head and Neck.
Although, instances of postoperative bleeding in ENT surgery are infrequent, sometimes they can be dreadful for both patient & surgeon. Here we are reporting 2 cases of postoperative bleeding that we encountered recently. (1) Superficial temporal artery aneurysmal bleed- post parotidectomy (2) Left superior thyroid artery aneurysmal bleed- post tracheostomy.


Effects of copper exposure on hatching success and early larval survival in marbled salamanders, Ambystoma opacum.
The creation of wetlands, such as urban and industrial ponds, has increased in recent decades, and these wetlands often become enriched in pollutants over time. One metal contaminant trapped in created wetlands is copper (Cu(2+)). Copper concentrations in sediments and overlying water may affect amphibian species that breed in created wetlands. The authors analyzed the Cu concentration in dried sediments from a contaminated wetland and the levels of aqueous Cu released after flooding the sediments with different volumes of water, mimicking low, medium, and high pond-filling events. Eggs and larvae of Ambystoma opacum Gravenhorst, a salamander that lays eggs on the sediments in dry pond beds that hatch on pond-filling, were exposed to a range of Cu concentrations that bracketed potential aqueous Cu levels in created wetlands. Embryo survival varied among clutches, but increased Cu levels did not affect embryo survival. At Cu concentrations of 500 µg/L or greater, however, embryos hatched earlier, and the aquatic larvae died shortly after hatching. Because Cu concentrations in sediments increase over time in created wetlands, even relatively tolerant species such as A. opacum may be affected by Cu levels in the posthatching environment.


Calcium-induced membrane microdomains trigger plant phospholipase D activity.
Plant alpha-type phospholipase D proteins are calcium-dependent, lipolytic enzymes. The morphology of the aggregates of their phospholipid substrate fundamentally defines the interaction between the enzyme and the surface. Here we demonstrate that the Ca(2+)-induced generation of membrane microdomains dramatically activates alpha-type phospholipase D from white cabbage. 500-fold stimulation was observed upon incorporation of 10 mol % 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphate (POPA) into 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) vesicles in the presence of Ca(2+) ions. Enhanced association of PLDalpha2 with phospholipid surfaces containing anionic components was indicated by lag phase analysis and film balance measurements. Differential scanning calorimetry showed that the POPA-specific activation correlates with the phase behavior of the POPC/POPA vesicles in the presence of Ca(2+) ions. We conclude from the results that the Ca(2+)-induced formation of POPA microdomains is the crucial parameter that facilitates the binding of PLD to the phospholipid surface and suggest that this effect serves as a cellular switch for controlling PLD activity.


Correlation Between Surgical Extent and Prognosis in Node-Negative, Early-Stage Papillary Thyroid Carcinoma Originating in the Isthmus.
The association between surgical extent and prognosis in papillary thyroid carcinoma originating in the isthmus is unclear. We included 233 patients with early-stage, node-negative papillary thyroid cancer originating in the isthmus; 126 were treated by lobectomy plus isthmusectomy with ipsilateral central neck dissection and 97 were treated by total thyroidectomy with bilateral central neck dissection. Subgroup analysis was performed according to tumor size (≤ 1 vs. >1 cm) to evaluate whether tumor size had a significant impact on determining the optimal extent of surgery in our cohort. Total thyroidectomy patients had longer recurrence-free survival (RFS) than those treated by lobectomy plus isthmusectomy. Subgroup analysis showed that this was true only for tumors >1 cm. In multivariate analysis, total thyroidectomy was an independent risk factor for RFS only for tumors >1 cm. Lobectomy plus isthmusectomy may be optimal for early-stage, node-negative papillary thyroid carcinoma originating in the isthmus for tumors ≤ 1 cm; total thyroidectomy might be better for tumors >1 cm.


Reactivity of monoclonal antibodies to oncoproteins with normal rat liver, carcinogen-induced tumours, and premalignant liver lesions.
Monoclonal antibodies to proteins encoded by the ras, myb, myc, erb-B, src and PDGF-2 genes were tested for reactivity with normal rat liver, livers from rats fed with 0.06% 2-acetylaminofluorene (AAF), and premalignant lesions and primary liver tumours from rats given AAF alone or a combined treatment with diethylnitrosamine and AAF. Radioimmunoassays were performed with plasma membrane fractions and total soluble subcellular extracts of the tissues, and immunoperoxidase staining was carried out on frozen tissue sections. All of the antibodies were positive in radioimmunoassays, some more strongly than others, and each antibody bound equally to extracts of different kinds of tissue. Immunohistology revealed significant staining of normal liver by 5 of the 6 antibodies, and only minor qualitative differences of the staining pattern in some tumours and hyperplastic nodules. It was concluded that these antibodies were not able to discriminate sufficiently well between normal, premalignant and malignant rat liver to be of value in identifying the precursor cells of malignant tumours.


Interobserver variability: comparison between liquid-based and conventional preparations in gynecologic cytology.
Studies have shown that the ThinPrep Papanicolaou test (TP) increases the detection of epithelial cell abnormalities compared with the conventional preparation. Little is known about the interobserver variability of reporting gynecologic cytology results using the TP preparation and its comparison with results obtained using the conventional method. To compare the interobserver variability between the TP method and the conventional method for reporting the diagnoses of gynecologic cytology, 20 pairs of conventional and TP slides (total, 40 slides) that were prepared from split samples were evaluated blindly by 19 cytotechnologists from three different laboratories. Each reviewer was asked to categorize each slide into the following five categories: within normal limits, benign cellular changes, atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion (LSIL), and high-grade squamous intraepithelial lesion (HSIL). For both conventional and TP preparations, interobserver variability was analyzed using Spearman rank correlation coefficients. The mean correlation coefficients (weak, 0.0-0.4; fair, 0.4-0.7; and strong, 0.7-1.0) between the TP method and the conventional method were then compared. The overall interobserver agreement as well as interobserver agreement within each laboratory was good for both TP and conventional preparations. Based on the set of conventional cervical smears, only one slide that was diagnosed as HSIL had unanimous agreement; whereas, based on the set of TP slides, three slides, including two diagnosed as HSIL and one diagnosed as LSIL, had a unanimous diagnosis. The difference in the interobserver agreement between TP and conventional methods, based on comparing their mean +/- standard deviation correlation coefficients (TP method, 0.84 +/- 0.081; conventional method, 0.82 +/- 0.105; P < 0.001), was statistically significant. Interobserver agreement in reporting gynecologic cytology using the TP method is good, particularly for squamous intraepithelial lesions, and appears to be superior to the conventional method.


Harder, better, faster, stronger: biochemistry and biophysics in the immunosurveillance concert.
Antitumor immunosurveillance is triggered by immune cell recognition of characteristic biochemical signals on the surfaces of cancer cells. Recent data suggest that the mechanical properties of cancer cells influence the strength of these signals, with physically harder target cells (more rigid) eliciting better, faster, and stronger cytotoxic responses against metastasis. Using analogies to a certain electronic music duo, we argue that the biophysical properties of cancer cells and their environment can adjust the volume and tone of the antitumor immune response. We also consider the potential influence of biomechanics-based immunosurveillance in disease progression and posit that targeting the biophysical properties of cancer cells in concert with their biochemical features could increase the efficacy of immunotherapy.


[Experience with medico-genetic counseling of the families of patients with Duchenne muscular dystrophy].
The article presents the experience with the use of comprehensive clinico-genealogic and biochemical methods of examination for the purpose of detecting heterozygotic carriership and preventing the birth of children with Duchenne's progressive myodystrophy in the practice of genetic counselling of families in Leningrad.


Laparoscopic surgery for rectal cancer, specimen extraction: transanal or transabdominal?
Comparison of natural orifice specimen extraction (NOSE) and transabdominal specimen extraction (TASE) in colorectal surgery remains controversial. Herein, we aimed to perform a retrospective analysis on surgical outcomes of NOSE and TASE at three hospitals in east of Iran. Consecutive locally advanced rectal adenocarcinoma patients who underwent laparoscopic surgery using either NOSE or TASE from 2011 to 2017 were recruited. These patients were followed-up till 2020. Data, including postoperative complications, long-term overall and recurrence-free survival were analyzed retrospectively. 239 eligible patients were included in this study. 169 (70.71%) patients underwent NOSE, and 70 (29.29%) patients underwent TASE. Although this study has achieved similar outcomes in terms of overall and recurrence-free survival, metastasis, circumferential margin involvement as well as complications of intra-operative bleeding, obstruction, anastomosis-fail, rectovaginal-fistula in women and pelvic collection/abscess in both groups, we observed higher rates of locoregional recurrence, incontinency, stenosis and the close distal margins involvement in NOSE group and also obstructed defecation syndrome in TASE cases. According to our findings, NOSE laparoscopic surgery showed significantly higher incontinency, impotency, stenosis and involvement of the close distal margins rates. Nevertheless, considering the similarity of long-term overall and recurrence-free survival, metastasis, circumferential margin involvement, NOSE procedure is still could be considered as a second choice for lower rectal adenocarcinoma patients.


Intravenous regional anaesthesia in upper limb trauma.
Practical experience in the use of Bier block anaesthesia of the upper limb is described. The revival of this well-tested technique is particularly relevant in circumstances where, for a variety of reasons, the administration of a general anaesthetic is impracticable. The quality of surgery, the safety of anaesthesia and the patient's comfort can be well maintained by following a few simple rules. We have satisfied these criteria in this series by using low doses which are safe and sufficient in a busy accident department.


Retrospective analysis of the Beijing family of Mycobacterium tuberculosis in preserved lung tissues.
Direct repeat spoligotyping of 85 paraffin-embedded lung biopsies was used to investigated the occurrence around Beijing of the Beijing family of Mycobacterium tuberculosis. Samples ranged in time from 1956 to 1990. Hybridization patterns were found with 49 (58%) samples, and 45 (92%) produced typical Beijing family patterns extending over the 34-year period.


Recent update of the various sources originating ghost peaks in gas chromatography: A review.
Gas chromatography (GC) is a versatile tool for separating various volatile, semi-volatile, and thermally stable compounds. However, the ghost peaks in the GC are now a major concern for chromatographic analysts. Ghost peaks may interfere with the analyte, leading to inaccurate results, so identifying the sources generating these peaks is essential for the validated analysis of the compounds of interest. This review compiles various sources responsible for generating ghost peaks in the GC and their possible troubleshooting methods for the smooth and consistent running of the ghost peak-free gas chromatography system, which will be very helpful for rapid and validated analysis.


Glucocorticoid receptor signaling in health and disease.
Glucocorticoids are steroid hormones regulated in a circadian and stress-associated manner to maintain various metabolic and homeostatic functions that are necessary for life. Synthetic glucocorticoids are widely prescribed drugs for many conditions including asthma, chronic obstructive pulmonary disease (COPD), and inflammatory disorders of the eye. Research in the past few years has begun to unravel the profound complexity of glucocorticoid signaling and has contributed remarkably to improved therapeutic strategies. Glucocorticoids signal through the glucocorticoid receptor (GR), a member of the superfamily of nuclear receptors, in both genomic and non-genomic ways in almost every tissue in the human body. In this review, we provide an update on glucocorticoid receptor signaling and highlight the role of GR signaling in physiological and pathophysiological conditions in the major organ systems in the human body.


Plasma and milk kinetics of eprinomectin following topical or oral administration to lactating Chinese Holstein cows.
Chinese Holstein, bred by mating the Holstein-Friesian to Chinese Yellow Cattle, is a major dairy cattle breed in China. Eprinomectin is widely used in the treatment of nematode and ectoparasite infections in lactating cattle. The pharmacokinetics of eprinomectin in the plasma and milk were determined in Chinese Holstein cows following topical (at 0.5 mg kg(-1)) or oral (at 0.2 mg kg(-1)) administration. For topical administration, the concentrations of eprinomectin in plasma reached peak values (C(max)) of 16.16 ± 6.02 ng ml(-1) at 3.20 ± 1.30 days (T(max)). In milk, the C(max) values of 2.28 ± 0.85 ng ml(-1) were obtained at 3.48 ± 0.65 days. The MRT values were 5.00 ± 0.96 days for plasma and 4.65 ± 0.60 days for milk. The AUC values were 91.00 ± 25.32 ng d ml(-1) for plasma and 10.53 ± 1.55 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.124 ± 0.041. Significant differences were found in C(max) and AUC of eprinomectin in plasma between Chinese Holstein and Prim Holstein following topical administration. It was probably due to the lower storage of body fat in Chinese Holstein than in Prim Holstein. For oral administration, the concentrations of eprinomectin reach peak values of 30.02 ± 5.73 ng ml(-1) at 1.60 ± 0.55 days in plasma and 3.14 ± 0.88 ng ml(-1) at 1.40 ± 0.27 days in milk. The MRT values for plasma and milk were 3.00 ± 0.46 and 3.18 ± 0.55 days, respectively. The AUC values were 98.46 ± 24.75 ng d ml(-1) for plasma and 10.42 ± 4.22 ng d ml(-1) for milk. The ratio of AUC milk/plasma was 0.104 ± 0.022. Compared with the topical administration, a significantly shorter MRT of eprinomectin in plasma was obtained following oral administration, which would shorten residue time of this compound in faeces and reduce its ecotoxicological effect. The low exposure of eprinomectin in milk would favor the use of eprinomectin in lactating Chinese Holstein for topical or oral administration.


Suppression of macrophages- Induced inflammation via targeting RAS and PAR-4 signaling in breast cancer cell lines.
Tumor associated macrophages (TAMs) have a crucial role in cancer progression, metastasis and drug response. Piroxicam and sulindac sulfide are non-steroidal anti-inflammatory drugs (NSAID) that decrease the incidence and progression of several types of cancer. However, their role in suppressing the interactions between TAMs and cancer cells remain unclear. Herein, we studied the impact of human monocytes conditioned media (CM) on cellular proliferation of ER-dependent MCF-7 and ER-independent MDA-MB-231 cells, and the effects of piroxicam and sulindac sulfide on the expression levels of RAS, COX-2, IL-6, IL-1β and PAR-4 (qRT-PCR), BCL-2 and BAX (western blot), Caspase-3, VEGF-a and PGE2 (ELISA), MMP-2 and -9 (zymography) in the stimulated cells. Our results showed that CM caused a significant increase in cells survival through significant increase in RAS expression which resulted in upregulation of COX-2, PGE2, BCL-2, IL-6, IL-1β, VEGF-A and MMP-9 and down regulation of PAR-4. Treatment with one of the NSAIDs used in this study produced a time and concentration dependent growth inhibition of stimulated cells by inhibiting RAS expression. Suppression of RAS was accompanied by downregulation of its downstream signaling of IL-1β, IL-6, COX-2 and PGE2, activation of apoptotic machinery through upregulation of PAR-4 and caspase-3, as well as, inhibition of BCL-2, VEGF-A, MMP-2 and MMP-9. In conclusion, our data support the role of piroxicam and sulindac sulfide in suppressing inflammation-driven breast cancer progression and identifies promising novel target in RAS and PAR-4 signaling.


Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin.
An elevated plasma concentration of serotonin ([5-HT]) is a common feature of cardiovascular disease often associated with enhanced platelet activation and thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent risk factor for platelet hyperreactivity or only is an epiphenomenon of cardiovascular disease is poorly understood. We examined in vitro and in vivo platelet function following a 24h elevation of plasma [5-HT] in mice. In vivo administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated mice compared to control mice instrumented with saline loaded pumps. 5-HT infusion did not increase systolic blood pressure, but markers of platelet activation including P-selectin and (PE)Jon/A staining were increased and these findings coincided with the enhanced aggregation of isolated platelets in response to type I fibrillar collagen. Tail bleeding times and the time to occlusion following chemical damage to the carotid artery were shortened in 5-HT-infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and attenuated platelet activation and aggregation. These results and our biochemical indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused mice reveal a mechanistic link between elevated plasma [5-HT], abnormal intracellular 5-HT signaling and accentuated platelet aggregation. Although a down-regulation of the serotonin transporter (SERT) on the platelet surface may counteract the pro-thrombotic influence of elevated plasma [5HT], this compensatory mechanism may fail to prevent the increased thrombotic risk caused by elevated plasma [5-HT].


Activity responses of two species of Peromyscus (Rodentia, Muridae) to varying light cycles.
Activity of Peromyscus floridanus and P. gossypinus was studied through a sequence of light-dark regimes including 12-hr light, 12-hr dark; 18-hr light, 6-hr dark; continuous light; and 12-hr light, 12-hr dark. Two populations of each species and both wild caught ("field") and first generation laboratory conceived and reared ("lab") mice of each stock were tested. All mice were strongly nocturnal during the initial 12-hr and 18-hr photoperiods, although gossypinus was relatively more active during the light phase than floridanus. Both species tended to become aperiodic in constant light, but floridanus showed a greater tendency to adhere to the nocturnal cycle of the preceding 18-hr photoperiod. Although the two species were relatively more active in light during the second 12-hr photoperiod than during the first 12-hr light, 12-hr dark regime, floridanus reestablished a stronger nocturnal cycle than gossypinus. Lab groups exhibited essentially the same trends between species and populations as the field animals, thus indicating some genetic basis for the observed differences. P. gossypinus had a higher over-all absolute activity level than floridanus. There was also less difference between the performance of field and lab groups of gossypinus than of floridanus. Both species showed a decline in activity with increased photoperiod, the effect being more pronounced in floridanus.The difference in the activity responses of the two species appears to be correlated with the characteristics of their habitats and nest sites. The stricter nocturnality of floridanus is associated with relatively xeric, open habitat in which daytime activity would seem to involve higher risk of predation and greater heat strss and water loss than in the case of the more humid denser forest environments typical of gossypinus. P. floridanus also nests in burrows, whereas nests of gossypinus are typically located in more accessible places where a lower threshold for activity in light might increase a mouse's chances of escaping from a predator when surprised in the nest during the day. The floridanus populations tended to differ more in percentage of activity in light and level of absolute activity than the corresponding gossypinus stocks. The difference in the activity patterns of the two floridanus populations was correlated with the density of vegetation in their respective habitats. Relative eye size was not clearly associated with species and population differences in activity responses to light.


Caseous Calcification of Mitral Annulus: A Rare Monster Leading to Cerebrovascular Accident.
Caseous calcification of the mitral annulus (CCMA) is a rare variant of mitral annular calcification that maybe easily misdiagnosed or confused with an abscess, a tumor, or infective vegetation. The main pathophysiological mechanism leading to CCMA involves degeneration and calcium deposition on the mitral valve. We present a case of CCMA to help understand this clinical entity.


Base-Dependent Divergent Annulation of 4-Chloro-3-formylcoumarin and Tetrahydroisoquinoline: Application to the Synthesis of Isolamellarins and Hydroxypyrrolones.
A series of pyrrolo[2,1- a]isoquinoline and coumarin-fused pentacyclic derivatives were synthesized via base-mediated divergent annulation of 4-chloro-3-formylcoumarin and tetrahydroisoquinoline as a key step. This method was then extended to the preparation of isolamellarins A and B (isolamellarin G trimethyl ether). When exposed to UV light, the pyrrolo[2,1- a]isoquinoline- and coumarin-fused pentacycles B were found to undergo aerobic oxidation to give the corresponding hydroxypyrrolones.


Outcomes of duct stenting and modified Blalock-Taussig shunt in cyanotic congenital heart disease with duct-dependent pulmonary circulation.
Transcatheter ductus arteriosus stenting (DS) is emerging as an alternative method to modified Blalock-Taussig shunt (MBTS) in providing pulmonary blood flow in cyanotic congenital heart disease (CCHD) with duct-dependent pulmonary circulation. To evaluate post-procedural outcomes and survival between patients undergoing DS and MBTS. All infants ≤ 60 days of age having CCHD with diminished pulmonary blood flow who underwent palliative procedure either with MBTS or DS at King Chulalongkorn Memorial Hospital during January 1st, 2013 and December 31th, 2017 were retrospectively reviewed. 98 patients were included; 34 patients underwent a transcatheter DS and 64 patients underwent MBTS. There was no significant difference in post-procedural outcomes and overall mortality rate between two groups (17.6% in MBTS group and 6.1% in DS group, p = 0.09). Single ventricle morphology was the major risk factor associated with increased mortality compared with biventricular morphology (aHR 3.9, 95% CI 1.49-10.2, p = 0.01). There was similar number of early and pre-repair additional interventions focusing on MBTS/DS patency between two groups. The MBTS group had a greater number of early interventions on PA branch stenosis related to baseline diagnosis. Risk factors associated with additional intervention were pre-existing pulmonary branch stenosis (aHR 2.54, 95% CI 1.3-4.97, p = 0.006) and body weight less than 2.5 kg (aHR 3.33, 95% CI 1.57-7.08, p = 0.003). Having pulmonic valve perforation or balloon pulmonary valvuloplasty to promote antegrade pulmonary blood flow could result in a lower number of additional interventions required before definitive repair. Duct stenting is a feasible and safe alternative to MBTS in cyanotic infants with duct-dependent pulmonary circulation. However, mortality rate was significantly higher in patients with single ventricle that required careful follow-up after procedure.


Vitamin A and arachidonic acid altered the skeletal mineralization in Atlantic cod (Gadus morhua) larvae without any interactions on the transcriptional level.
The main object of this study was to evaluate the impact of different levels of vitamin A (VA) and arachidonic acid (ARA) in relation to eicosapentaenoic acid (EPA) on mineralization and gene expression in Atlantic cod larvae (Gadus morhua). First-feeding larvae were fed enriched rotifers from start-feeding until 29 days post hatch (dph). Larvae in four tanks were fed one of the following diets: control (EPA/ARA ratio: 15.8, 0.9μg VA g(-1)), control+VA (EPA/ARA ratio: 15.8, 7.8μg VA g(-1)), High ARA (EPA/ARA ratio: 0.9, 1.5μg VA g(-1)) or High ARA+VA (EPA/ARA ratio: 0.9, 12.0μg VA g(-1)). Larvae fed High ARA+VA were shorter at 29dph compared to the other groups and had significantly less mineralized bones when comparing larvae of similar size, showing interaction effects between VA and ARA. Although transcriptomic analysis did not reveal any interaction effects, a higher number of genes were differentially expressed in the high ARA fed larvae compared to control+VA fed larvae. Furthermore, bglap1, bglap2 and col10a1 were all down-regulated in larvae fed High ARA-diets and to a greater extent than larvae fed VA supplemented diet, indicating an additive effect on mineralization. In conclusion, this study showed that the dietary increase in ARA and VA altered the skeletal metabolism during larval development, most likely through signaling pathways specific for each nutrient rather than an interaction. The present study also demonstrates that VA could affect the larval response to ARA, even within the accepted non-toxic/non-deficient range.