Phosphodiesterase activity of alkaline phosphatase in ATP-initiated Ca(2+) and phosphate deposition in isolated chicken matrix vesicles.
Inorganic pyrophosphate is a potent inhibitor of bone mineralization by preventing the seeding of calcium-phosphate complexes. Plasma cell membrane glycoprotein-1 and tissue nonspecific alkaline phosphatase were reported to be antagonistic regulators of mineralization toward inorganic pyrophosphate formation (by plasma cell membrane glycoprotein-1) and degradation (by tissue nonspecific alkaline phosphatase) under physiological conditions. In addition, they possess broad overlapping enzymatic functions. Therefore, we examined the roles of tissue nonspecific alkaline phosphatase within matrix vesicles isolated from femurs of 17-day-old chick embryos, under conditions where these both antagonistic and overlapping functions could be evidenced. Addition of 25 microM ATP significantly increased duration of mineralization process mediated by matrix vesicles, while supplementation of mineralization medium with levamisole, an alkaline phosphatase inhibitor, reduces the ATP-induced retardation of mineral formation. Phosphodiesterase activity of tissue nonspecific alkaline phosphatase for bis-p-nitrophenyl phosphate was confirmed, the rate of this phosphodiesterase activity is in the same range as that of phosphomonoesterase activity for p-nitrophenyl phosphate under physiological pH. In addition, tissue nonspecific alkaline phosphatase at pH 7.4 can hydrolyze ADPR. On the basis of these observations, it can be concluded that tissue nonspecific alkaline phosphatase, acting as a phosphomonoesterase, could hydrolyze free phosphate esters such as pyrophosphate and ATP, while as phosphodiesterase could contribute, together with plasma cell membrane glycoprotein-1, in the production of pyrophosphate from ATP.


Episodic future thinking: linking neuropsychological performance with episodic detail in young and old adults.
Episodic future thinking (EFT) has been linked with our ability to remember past events. However, its specific neurocognitive subprocesses have remained elusive. In Experiment 1, a study of healthy older adults was conducted to investigate the candidate subprocesses of EFT. Participants completed a standard EFT cue word task, two memory measures (Verbal Paired Associates I, Source Memory), and two measures of executive function (Trail Making Test, Tower Test). In Experiment 2, healthy young adults also completed an EFT task and neuropsychological measures. The link between neurocognitive measures and five characteristics of EFT was investigated. Specifically, it was found that Source Memory and Trail Making Test performance predicted the episodic specificity of future events in older but not younger adults. Replicating previous findings, older adults produced future events with greater semantic but fewer episodic details than did young adults. These results extend the data and emphasize the importance of the multiple subprocesses underlying EFT.


Suppression of MAPK and NF-κ B pathways by schisandrin B contributes to attenuation of DSS-induced mice model of inflammatory bowel disease.
Schisandrin B (Sch B), the most abundant dibenzocyclooctadiene lignan isolated from the traditional Chinese medicinal herb Schisandra chinensis (Turcz.) Baill, possesses various biological activities, such as hepatic protection, anti-tumor, anti-inflammatory and anti-cardiovascular properties. However, the effect of Sch B on inflammatory bowel disease (IBD) is not yet known. The aim of this study was to investigate whether Sch B has protective effect against dextran sulfate sodium (DSS)-induced colitis in a mouse model. The acute mouse model of IBD was induced by drinking 2.5% DSS water for 5 days. Sch B was administered orally in doses of 10, 40, and 100 mg/kg respectively. It significantly reduced concentration of TNF-α, IL-1β, INF-γ and IL-6 in colon tissue as well as the mRNA expression levels. In addition, we demonstrated that Sch B blocked the phosphorylation of IκBα, nuclear factor-κB (NF-κB) p65, p38 mitogen-activated protein kinase (MAPK), c-Jun NH2-terminal kinase, and extracellular signal regulated kinase in DSS-induced acute colitis. In conclusion, these results indicated that Sch B could exert beneficial effects on experimental IBD induced by DSS and may represent a novel treatment strategy for IBD.


Chemical speciation of chromium(III) and (VI) using phosphonium cation impregnated polyurethane foams prior to their spectrometric determination.
Fast and selective sorptions of Cr(VI) species from aqueous media onto tetraphenylphosphonium bromide (TPP(+) · Br(-)) physically immobilized polyurethane foams (PUFs) sorbent were achieved. Based on the Scatchard model of binding sites of the PUFs and Langmuir and Dubinin-Radushkevich (D-R) adsorption models of Cr(VI) retention onto TPP(+) · Br(-) immobilized PUFs, a dual retention mechanism involving absorption related to "weak-base anion ion exchange" and an added component for "surface adsorption" was proposed. Thus, the TPP(+) · Br(-) loaded PUFs were successfully packed in column mode for preconcentration of trace and ultra trace concentrations of Cr(VI) as halochromates [CrO(3)C](-)(aq) from aqueous HCl media. The retained [CrOCl(3)](-)(aq) species were recovered with NaOH (1.0 mol L(-1)) and analyzed by flame atomic absorption spectrometry. Cr(III) species after oxidation to Cr(VI) with H(2)O(2) in aqueous KOH (1.0 mol L(-1)) were also retained and could be recovered by the proposed method. The limits of detection (LOD) and quantification (LOQ) of Cr(VI) were 0.04 and 0.13 µg L(-1), respectively. The chemical speciation of Cr(III, VI) species in various water samples at trace and ultra trace levels were carried out by TPP(+) · Br(-) loaded PUFs packed column. The enhancement factor and sensitivity factor of [CrO(3)C](-)(aq) sorption were 80.0 and 30.0, respectively.


Hepatic and branchial thyroid hormone deiodinase activities associated with the parr-smolt transformation of coho salmon (Oncorhynchus kisutch).
Plasma 3,5,3'-triiodo-L-thyronine (T3) concentrations, liver and gill thyroid hormone deiodinase activities, growth parameters, and hypoosmoregulatory capacity were measured for an outdoor population of freshwater, hatchery-reared yearling coho salmon prior to, during, and after the parr-smolt transformation. The plasma Na+ response to a 24-hr seawater (30 ppt) challenge showed characteristic smolt hypoosmoregulatory capacity only from mid-May to mid-June. Increases in growth parameters (body weight and length) were curbed during this time. Two peaks in plasma T3 occurred in late April and early May. Both liver and gill T4 (L-thyroxine) outer-ring 5'-monodeiodinase (T4(5)'D) activities, converting T4 to T3, fell from March to June, with no biologically meaningful overall correlation with plasma T3. However, T4(5)'D activity of gill and liver did increase in presmolts in late May, coinciding with an elevation in plasma T3. Hepatic inner-ring T4(5)D activity, converting T4 to 3,3',5'-T3 (rT3 = reverse T3), was lower in smolts than in presmolts. Activity of hepatic outer-ring T3(5)'D, which converts T3 to 3,5-T2, was negligible, but activity of hepatic inner-ring T3(5)D, which produces 3,3'-T2 from T3, was higher in early smolts than in postsmolts. We conclude that hepatic deiodinase activities of smolting coho salmon may act to maintain hepatic and plasma T3 at modest levels and that the branchial production of T3 appears to parallel that of the liver.


Dissemination and Implementation of Evidence-Based Dementia Care Using Embedded Pragmatic Trials.
There are many nonpharmacologic interventions tested in randomized clinical trials that demonstrate significant benefits for people living with Alzheimer's disease (AD) and AD-related dementia, their care partners, or professional care providers. Nevertheless, with few exceptions, proven interventions have not been translated for delivery in real-world settings, such as home care, primary care, hospitals, community-based services, adult day services, assisted living, nursing homes, or other healthcare systems (HCSs). Using embedded pragmatic clinical trial (ePCT) methods is one approach that can facilitate dissemination and implementation (D&I) of dementia care interventions. The science of D&I can inform the integration of evidence-based dementia care in HCSs by offering theoretical frameworks that capture field complexities and guiding evaluation of implementation processes. Also, D&I science can suggest evidence-based strategies for implementing dementia care in HCSs. Although D&I considerations can inform each stage of dementia care intervention development, it is particularly critical when designing ePCTs. This article examines fundamental considerations for implementing dementia-specific interventions in HCSs and how best to prepare for successful dissemination upstream in the context of ePCTs, thereby illustrating the critical role of the D&I Core of the National Institute on Aging Imbedded Pragmatic Alzheimer's Disease and AD-Related Dementias Clinical Trials Collaboratory. The scientific premise of the D&I Core is that having the "end" in mind, upfront in the design and testing of dementia care programs, can lead to decision-making that optimizes the ultimate goal of wide-scale D&I of evidence-based dementia care programs in HCSs. J Am Geriatr Soc 68:S28-S36, 2020.


EGFR T790M Mutation Detection in Patients With Non-Small Cell Lung Cancer After First Line EGFR TKI Therapy: Summary of Results in a Three-Year Period and a Comparison of Commercially Available Detection Kits.
EGFR mutation in non-small cell lung cancer (NSCLC) offers a potential therapeutic target for tyrosine kinase inhibitor (TKI) therapy. The majority of these cases, however eventually develop therapy resistance, mainly by acquiring EGFR T790M mutation. Recently, third-generation TKIs have been introduced to overcome T790M mutation-related resistance. Cell free circulating tumor DNA (liquid biopsy) has emerged as a valuable alternative method for T790M mutation detection during patient follow up, when a tissue biopsy cannot be obtained for analysis. In this study, we summarized our experience with Super-ARMS EGFR Mutation Detection Kit (AmoyDx) on 401 samples of 242 NSCLC patients in a 3-year period in Hungary, comprising 364 plasma and 37 non-plasma samples. We also compared the performance of two commercially available detection kits, the cobas EGFR Mutation test v2 (Roche) and the Super-ARMS EGFR Mutation Detection Kit (AmoyDx). The same activating EGFR mutation was detected with the AmoyDx kit as in the primary tumor in 45.6% of the samples. T790M mutation was identified in 48.1% of the samples containing activating EGFR mutation. The detection rate of T790M mutation was not dependent on the DNA concentration of the plasma sample and there was no considerable improvement in mutation detection rate after a second, subsequent plasma sample. The concordance of EGFR activating mutation detection was 89% between the two methods, while this was 93% for T790M mutation detection. The AmoyDx kit, however showed an overall higher detection rate of T790M mutation compared to the cobas kit (p = 0.014). T790M mutation was detected at 29.8% of the patients if only plasma samples were available for analysis, while the detection rate was 70.2% in non-plasma samples. If the activating EGFR was detected in the plasma samples, the detection rate of T790M mutation was 42.4%. Although non-plasma samples provided a superior T790M mutation detection rate, we found that liquid biopsy can offer a valuable tool for T790M mutation detection, when a tissue biopsy is not available. Alternatively, a liquid biopsy can be used as a screening test, when re-biopsy should be considered in case of wild-type results.


Comparison of transcranial radiograph and magnetic resonance imaging in the evaluation of mandibular condyle position.
Several image modalities have been used to assess the condylar position in the glenoid fossa. However, despite the development of more advanced techniques for imaging the temporomandibular joint (TMJ), the transcranial projection remains widely used in dentistry. The purpose of this study was to compare the condylar position in transcranial radiography (TRANS) with MRI. 70 matched pairs of TMJs (35 patients) who had undergone TRANS and MRI were evaluated. The TRANS scans were compared with the lateral, central and medial MRI scans, and the condylar position was assessed in the closed and open mouth position according to subjective and objective methods. The sensitivity, specificity and accuracy values were calculated for each group and Bowker's test was used to analyse the data. There was no statistical significance between TRANS and MRI (P > 0.05). However, even though there were similar mean values between them, the comparison with the lateral image showed higher values, which might be due to TRANS representing the lateral one-third of the condyle. It can be concluded that TRANS seems to be an acceptable method and its applicability as an adjunctive method in the condylar position should not be rejected.


Neospora caninum DNA in Coyote Fecal Samples Collected in an Urban Environment.
Definitive hosts of Neospora caninum are species of canids, such as domestic dogs ( Canis lupus familiaris), coyotes ( Canis latrans) and foxes ( Vulpes vulpes), whereas ruminants, such as cattle ( Bos taurus), sheep ( Ovis aries), and deer (Cervidae) serve as intermediate hosts. We investigated the presence of N. caninum in feces of coyotes in Calgary, Alberta, Canada. One hundred coyote fecal samples were collected from five city parks. Following DNA extraction, the presence of N. caninum DNA was determined by using real-time PCR analysis with a primer and probe pair targeting the Nc5 gene. Ten of the 100 samples contained detectable amounts of N. caninum DNA. White-tailed deer ( Odocoileus virginianus) and mule deer ( Odocoileus hemionus) are common in Calgary's city parks, and although we did not examine them for the presence of N. caninum bradyzoites, the presence of N. caninum DNA in coyote fecal samples is indicative that a sylvatic host of N. caninum exists within this urban environment.


Measurement and simulation of the morphological development of filamentous microorganisms.
Growth of Streptomyces tendae was investigated in submerged culture. Images of several mycelia were analyzed by means of an image-processing system. The studies revealed that tip growth angles and branching outgrowth angles could be regarded as normally distributed. Based on these results, a random model for directional growth of hyphal tips as well as directional growth of branches is proposed. This model shows curved elongation of hyphal tips, so that the morphological development of a mycelium up to the formation of a pellet is predicted, similar to that observed in nature.


Long Noncoding RNA uc001pwg.1 Is Downregulated in Neointima in Arteriovenous Fistulas and Mediates the Function of Endothelial Cells Derived from Pluripotent Stem Cells.
Recent studies indicate important roles for long noncoding RNAs (lncRNAs) as essential regulators of gene expression. However, the specific roles of lncRNAs in stenotic lesions of arteriovenous fistula (AVF) failure are still largely unknown. We first analyzed the expression profiles of lncRNAs in human stenosed and nonstenotic uremic veins using RNA-sequencing methodology. A total of 19 lncRNAs were found to be differentially expressed in stenotic lesions. Among these, uc001pwg.1 was one of the most significantly downregulated lncRNAs and enriched in both control vein segments and human umbilical vein endothelial cells (HUVECs). Further studies revealed that uc001pwg.1 overexpression could increase nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) production in endothelial cells (ECs) derived from human-induced pluripotent stem cells (HiPSCs). Mechanistically, uc001pwg.1 improves endothelial function via mediating MCAM expression. This study represents the first effort of identifying a novel candidate lncRNA for modulating the function of iPSC-ECs, which may facilitate the improvement of stem cell-based therapies for AVF failure.


Influence of different computational approaches for stent deployment on cerebral aneurysm haemodynamics.
Cerebral aneurysms are abnormal focal dilatations of artery walls. The interest in virtual tools to help clinicians to value the effectiveness of different procedures for cerebral aneurysm treatment is constantly growing. This study is focused on the analysis of the influence of different stent deployment approaches on intra-aneurysmal haemodynamics using computational fluid dynamics (CFD). A self-expanding stent was deployed in an idealized aneurysmatic cerebral vessel in two initial positions. Different cases characterized by a progression of simplifications on stent modelling (geometry and material) and vessel material properties were set up, using finite element and fast virtual stenting methods. Then, CFD analysis was performed for untreated and stented vessels. Haemodynamic parameters were analysed qualitatively and quantitatively, comparing the cases and the two initial positions. All the cases predicted a reduction of average wall shear stress and average velocity of almost 50 per cent after stent deployment for both initial positions. Results highlighted that, although some differences in calculated parameters existed across the cases based on the modelling simplifications, all the approaches described the most important effects on intra-aneurysmal haemodynamics. Hence, simpler and faster modelling approaches could be included in clinical workflow and, despite the adopted simplifications, support clinicians in the treatment planning.


Testicular interstitial cells, and steroidogenic detection in the protogynous fish, Synbranchus marmoratus (Teleostei, Synbranchidae).
The swamp eel, Synbranchus marmoratus, is a freshwater protogynic diandric species. Primary males develop directly as males while secondary males arise from the sex reversal of females. Fishes from Argentine and Brazil inland waters were collected, examined and compared for this study. In order to characterize the interstitial testicular compartment, light and electron microscopy techniques and an enzyme histochemical examination for steroidogenic cells detection were used. The interstitial compartment of S. marmoratus is composed of Leydig and myoid cells, collagen fibers, blood cells, macrophages,and amyelinic nerves. At the ultrastructural level, no differences were observed in the interstitial tissue, either between specimens from the different sampling sites or between primary and secondary males. Leydig cells are present in all testes examined throughout the year. A cytoplasmatic reaction of 3beta-HSD was detected only in Leydig cells during sex reversal and in both type of males, mainly during the regressed and early maturation classes (autumn and winter). Leydig cells possess the typical fine structural characteristics associated with steroidogenesis. Furthermore, in both type of males, during sex reversal and after the spawning period, the number of granulocytes and macrophages present in the testes increased, suggesting that they could be involved in phagocytosis and resorption of damaged cells.


Regioselective C8-metalation of N-phosphine tethered adenine derivatives via C8-H activation.
Two new adenine derivatives bearing a N-methylene (1) or N-ethylene (2) tethered diphenylphosphine group have been reacted with [MIIICl2Cp*]2 (M = Ir, Rh) or [RuIIClCp*]4. The formation of Werner-type phosphine complexes [3]-[6] and upon heating their subsequent rearrangement into complexes bearing an NH,NR-NHC^PRPh2 chelate ligand in [7]Cl (M = Ir) and [8] (M = Ru) have been observed.


Epidemiology of influenza B/Yamagata and B/Victoria lineages in South Africa, 2005-2014.
Studies describing the epidemiology of influenza B lineages in South Africa are lacking. We conducted a prospective study to describe the circulation of influenza B/Victoria and B/Yamagata lineages among patients of all ages enrolled in South Africa through three respiratory illness surveillance systems between 2005 and 2014: (i) the Viral Watch (VW) program enrolled outpatients with influenza-like illness (ILI) from private healthcare facilities during 2005-2014; (ii) the influenza-like illnesses program enrolled outpatients in public healthcare clinics (ILI/PHC) during 2012-2014; and (iii) the severe acute respiratory illnesses (SARI) program enrolled inpatients from public hospitals during 2009-2014. Influenza B viruses were detected by virus isolation during 2005 to 2009 and by real-time reverse transcription polymerase chain reaction from 2009-2014. Clinical and epidemiological characteristics of patients hospitalized with SARI and infected with different influenza B lineages were also compared using unconditional logistic regression. Influenza viruses were detected in 22% (8,706/39,804) of specimens from patients with ILI or SARI during 2005-2014, of which 24% (2,087) were positive for influenza B. Influenza B viruses predominated in all three surveillance systems in 2010. B/Victoria predominated prior to 2011 (except 2008) whereas B/Yamagata predominated thereafter (except 2012). B lineages co-circulated in all seasons, except in 2013 and 2014 for SARI and ILI/PHC surveillance. Among influenza B-positive SARI cases, the detection of influenza B/Yamagata compared to influenza B/Victoria was significantly higher in individuals aged 45-64 years (adjusted odds ratio [aOR]: 4.2; 95% confidence interval [CI]: 1.1-16.5) and ≥65 years (aOR: 12.2; 95% CI: 2.3-64.4) compared to children aged 0-4 years, but was significantly lower in HIV-infected patients (aOR: 0.4; 95% CI: 0.2-0.9). B lineages co-circulated in most seasons except in 2013 and 2014. Hospitalized SARI cases display differential susceptibility for the two influenza B lineages, with B/Victoria being more prevalent among children and HIV-infected persons.


Entering the ninth decade is not a contraindication for carotid endarterectomy.
The role of carotid endarterectomy (CEA) in stroke prevention is now better defined. However, its role in patients older than 79 years of age is controversial. This group of patients has been excluded in most clinical trials. In this study the authors reviewed their experience with CEA patients >79 years old. The records of all patients older than 79 years of age who underwent a CEA in a recent time period from January 1988 to December 1996 were retrospectively reviewed. Forty-one patients (31 men, 10 women) were identified by computer search. The indication for operation included transient ischemic attack in 12 (29.3%), amaurosis fugax in nine (22%), stroke in two (4.9%), and nonhemispheric symptoms in three (7.3%). Fifteen patients (36.6%) were asymptomatic. Medical risk factors included coronary artery disease in 26 (63.4%), hypertension in 22 (53.7%), and smoking in 12 (29.3%). The procedure was performed under EEG monitoring in all patients. General anesthesia was administered in 37 (90%) and regional anesthesia in four (10%). Shunts were used in four (10%) patients. The internal carotid artery was patched in 16 patients (39%). One patient (2.4%) developed a perioperative stroke and only one patient developed perioperative myocardial infarction (MI). None of the patients died within 30 days of surgery. In addition to the one MI case, five patients developed minor complications. The average length of time for stay after CEA was 3.4 days. Patients were followed up for an average of 20.7 months. Six patients died during follow-up. Four of those died from an MI and two from a stroke. The authors conclude that with proper selection of patients, CEA is safe in the octogenarian. Age alone should not be a contraindication for CEA.


Complex folding and misfolding effects of deer-specific amino acid substitutions in the β2-α2 loop of murine prion protein.
The β2-α2 loop of PrP(C) is a key modulator of disease-associated prion protein misfolding. Amino acids that differentiate mouse (Ser169, Asn173) and deer (Asn169, Thr173) PrP(C) appear to confer dramatically different structural properties in this region and it has been suggested that amino acid sequences associated with structural rigidity of the loop also confer susceptibility to prion disease. Using mouse recombinant PrP, we show that mutating residue 173 from Asn to Thr alters protein stability and misfolding only subtly, whilst changing Ser to Asn at codon 169 causes instability in the protein, promotes oligomer formation and dramatically potentiates fibril formation. The doubly mutated protein exhibits more complex folding and misfolding behaviour than either single mutant, suggestive of differential effects of the β2-α2 loop sequence on both protein stability and on specific misfolding pathways. Molecular dynamics simulation of protein structure suggests a key role for the solvent accessibility of Tyr168 in promoting molecular interactions that may lead to prion protein misfolding. Thus, we conclude that 'rigidity' in the β2-α2 loop region of the normal conformer of PrP has less effect on misfolding than other sequence-related effects in this region.


[Sex role and identity of childless andrology patients].
By means of the Bem Sex-Role Inventory (BSRI) 1000 childless married patients of andrology have been examined in order to determine their masculinity, femininity, androgynity and social desire scores. The results have been compared with a control group of 111 students of medicine and dentistry and with data of a study on 444 students at Stanford University. Significant differences have been shown in social desire only, but in no other respect. Thus, the results do not indicate differences of sex role and self image between andrological patients and control groups in Hamburg as well as in Stanford.


Factors Associated With Voluntary Refusal of Emergency Medical System Transport for Emergency Care in Detroit During the Early Phase of the COVID-19 Pandemic.
Emergency department (ED) and emergency medical services (EMS) volumes decreased during the COVID-19 pandemic, but the amount attributable to voluntary refusal vs effects of the pandemic and public health restrictions is unknown. To examine the factors associated with EMS refusal in relation to COVID-19 cases, public health interventions, EMS responses, and prehospital deaths. A retrospective cohort study was conducted in Detroit, Michigan, from March 1 to June 30, 2020. Emergency medical services responses geocoded to Census tracts were analyzed by individuals' age, sex, date, and community resilience using the Centers for Disease Control and Prevention Social Vulnerability Index. Response counts were adjusted with Poisson regression, and odds of refusals and deaths were adjusted by logistic regression. A COVID-19 outbreak characterized by a peak in local COVID-19 incidence and the strictest stay-at-home orders to date, followed by a nadir in incidence and broadly lifted restrictions. Multivariable-adjusted difference in 2020 vs 2019 responses by incidence rate and refusals or deaths by odds. The Social Vulnerability Index was used to capture community social determinants of health as a risk factor for death or refusal. The index contains 4 domain subscores; possible overall score is 0 to 15, with higher scores indicating greater vulnerability. A total of 80 487 EMS responses with intended ED transport, 2059 prehospital deaths, and 16 064 refusals (62 636 completed EMS to ED transports) from 334 Census tracts were noted during the study period. Of the cohort analyzed, 38 621 were women (48%); mean (SD) age was 49.0 (21.4) years, and mean (SD) Social Vulnerability Index score was 9.6 (1.6). Tracts with the highest per-population EMS transport refusal rates were characterized by higher unemployment, minority race/ethnicity, single-parent households, poverty, disability, lack of vehicle access, and overall Social Vulnerability Index score (9.6 vs 9.0, P = .002). At peak COVID-19 incidence and maximal stay-at-home orders, there were higher total responses (adjusted incident rate ratio [aIRR], 1.07; 1.03-1.12), odds of deaths (adjusted odds ratio [aOR], 1.60; 95% CI, 1.20-2.12), and refusals (aOR, 2.33; 95% CI, 2.09-2.60) but fewer completed ED transports (aIRR, 0.82; 95% CI, 0.78-0.86). With public health restrictions lifted and the nadir of COVID-19 cases, responses (aIRR, 1.01; 0.97-1.05) and deaths (aOR, 1.07; 95% CI, 0.81-1.41) returned to 2019 baselines, but differences in refusals (aOR, 1.27; 95% CI, 1.14-1.41) and completed transports (aIRR, 0.95; 95% CI, 0.90-0.99) remained. Multivariable-adjusted 2020 refusal was associated with female sex (aOR, 2.71; 95% CI, 2.43-3.03 in 2020 at the peak; aOR 1.47; 95% CI, 1.32-1.64 at the nadir). In this cohort study, EMS transport refusals increased with the COVID-19 outbreak's peak and remained elevated despite receding public health restrictions, COVID-19 incidence, total EMS responses, and prehospital deaths. Voluntary refusal was associated with decreased EMS transports to EDs, disproportionately so among women and vulnerable communities.


The allergic nasal mucosa following vidian neurectomy. Electron microsopic study.
The fine structure of the allergic nasal mucosufollowing vidian neurectomy was studied in 15 patients. The structure of the mucous glands, venules, arterioles and tunical cellular elements returned to normal 1 month after the operation, while that of the epithelium and of the capillaries only 3 months post-operatively. The effect of interrupting the hyperactive cholinergic nerve impulses on the various constituents of the nasal mucosa is described.


The relationship between food insecurity and binge and night eating symptoms in prebariatric surgery patients is mediated by depressive symptoms.
Eleven percent of households in the United States experience food insecurity, which is a lack of access to adequate, desirable food for a healthy lifestyle. Although food insecurity is associated with increased risk of obesity and nonadherence to dietary management of chronic diseases such as diabetes, the correlates of food insecurity have not yet been studied in a bariatric surgery population. To replicate, in a bariatric sample, previous findings that food insecurity is related to eating pathology and to test the hypothesis that this relationship is mediated by depressive symptoms. University hospital, United States. Two hundred forty bariatric surgery candidates responded to self-report measures of food insecurity and mood, night-eating, and binge-eating symptoms. The sample was 74% female and 71% white, with a mean age of 41.09 (11.84) years. Based on responses to the United States Department of Agriculture Adult Food Security Survey Model, 15.8% were categorized as food insecure and 25.8% as marginally food secure. Multiple regression models with bootstrapping for confidence interval estimates were used to explore mediation hypotheses. Food insecurity was positively associated with symptoms of night eating and binge eating, and these relationships were cross-sectionally mediated by depressive symptoms. Food insecure bariatric candidates may be at increased risk of poorer postoperative outcomes because of lack of access to needed food and the detrimental mental health impact of this lack of access.


Hepatitis B virus core protein sensitizes hepatocytes to tumor necrosis factor-induced apoptosis by suppression of the phosphorylation of mitogen-activated protein kinase kinase 7.
Hepatitis B, which caused by hepatitis B virus (HBV) infection, remains a major health threat worldwide. Hepatic injury and regeneration from chronic inflammation are the main driving factors of liver fibrosis and cirrhosis in chronic hepatitis B. Proinflammatory tumor necrosis factor alpha (TNF-α) has been implicated as a major inducer of liver cell death during viral hepatitis. Here, we report that in hepatoma cell lines and in primary mouse and human hepatocytes, expression of hepatitis B virus core (HBc) protein made cells susceptible to TNF-α-induced apoptosis. We found by tandem affinity purification and mass spectrometry that receptor of activated protein kinase C 1 (RACK1) interacted with HBc. RACK1 was recently reported as a scaffold protein that facilitates the phosphorylation of mitogen-activated protein kinase kinase 7 (MKK7) by its upstream activators. Our study showed that HBc abrogated the interaction between MKK7 and RACK1 by competitively binding to RACK1, thereby downregulating TNF-α-induced phosphorylation of MKK7 and the activation of c-Jun N-terminal kinase (JNK). In line with this finding, specific knockdown of MKK7 increased the sensitivity of hepatocytes to TNF-α-induced apoptosis, while overexpression of RACK1 counteracted the proapoptotic activity of HBc. Capsid particle formation was not obligatory for HBc proapoptotic activity, as analyzed using an assembly-defective HBc mutant. In conclusion, the expression of HBc sensitized hepatocytes to TNF-α-induced apoptosis by disrupting the interaction between MKK7 and RACK1. Our study is thus the first indication of the pathogenic effects of HBc in liver injury during hepatitis B. Our study revealed a previously unappreciated role of HBc in TNF-α-mediated apoptosis. The proapoptotic activity of HBc is important for understanding hepatitis B pathogenesis. In particular, HBV variants associated with severe hepatitis may upregulate apoptosis of hepatocytes through enhanced HBc expression. Our study also found that MKK7 is centrally involved in TNF-α-induced hepatocyte apoptosis and revealed a multifaceted role for JNK signaling in this process.


A Fast Algorithm for Intra-Frame Versatile Video Coding Based on Edge Features.
Versatile Video Coding (VVC) introduces many new coding technologies, such as quadtree with nested multi-type tree (QTMT), which greatly improves the efficiency of VVC coding. However, its computational complexity is higher, which affects the application of VVC in real-time scenarios. Aiming to solve the problem of the high complexity of VVC intra coding, we propose a low-complexity partition algorithm based on edge features. Firstly, the Laplacian of Gaussian (LOG) operator was used to extract the edges in the coding frame, and the edges were divided into vertical and horizontal edges. Then, the coding unit (CU) was equally divided into four sub-blocks in the horizontal and vertical directions to calculate the feature values of the horizontal and vertical edges, respectively. Based on the feature values, we skipped unnecessary partition patterns in advance. Finally, for the CUs without edges, we decided to terminate the partition process according to the depth information of neighboring CUs. The experimental results show that compared with VTM-13.0, the proposed algorithm can save 54.08% of the encoding time on average, and the BDBR (Bjøntegaard delta bit rate) only increases by 1.61%.


Optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers.
The optical and redox properties of a series of 3,4-ethylenedioxythiophene oligomers (EDOTn, n=1-4) and their beta,beta'-unsubstituted analogues (Tn, n=1-4) are described. Both series are end capped with phenyl groups to prevent irreversible alpha-coupling reactions during oxidative doping. Absorption and fluorescence spectra of both series reveal a significantly higher degree of intrachain conformational order in the EDOTn oligomers. Oxidation potentials (E(PA1) and E(PA2)) determined by cyclic voltammetry reveal that those of EDOTn are significantly lower than the corresponding Tn oligomers as a consequence of the electron-donating 3,4-ethylenedioxy substitution. Linear fits of E(PA1) and E(PA2) versus the reciprocal number of double bonds reveal significantly steeper slopes for the EDOTn than for the Tn oligomers. This could indicate a more effective conjugation for the EDOTn series, confirmed by the fact that coalescence of E(PA1) and E(PA2) is reached already at relatively short chain lengths ( approximately 5 EDOT units) in contrast to the Tn series (>10 thiophene units). The stepwise chemical oxidation of the EDOTn and Tn oligomers in solution was carried out to obtain radical cations and dications. The energies of the optical transitions of the radical cations and dications as determined by UV/Vis/NIR spectroscopy were similar for the two series. These spectroscopic observations are consistent with quantum-chemical calculations performed on the singly charged molecules. Cooling solutions containing T2.+, T3.+, EDOT2.+, and EDOT3.+ revealed the reversible formation of dimers, albeit with a somewhat different tendency, expressed in the values for the dimerization enthalpy.


Somatic correction of junctional epidermolysis bullosa by a highly recombinogenic AAV variant.
Definitive correction of disease causing mutations in somatic cells by homologous recombination (HR) is an attractive therapeutic approach for the treatment of genetic diseases. However, HR-based somatic gene therapy is limited by the low efficiency of gene targeting in mammalian cells and replicative senescence of primary cells ex vivo, forcing investigators to explore alternative strategies such as retro- and lentiviral gene transfer, or genome editing in induced pluripotent stem cells. Here, we report correction of mutations at the LAMA3 locus in primary keratinocytes derived from a patient affected by recessive inherited Herlitz junctional epidermolysis bullosa (H-JEB) disorder using recombinant adenoassociated virus (rAAV)-mediated HR. We identified a highly recombinogenic AAV serotype, AAV-DJ, that mediates efficient gene targeting in keratinocytes at clinically relevant frequencies with a low rate of random integration. Targeted H-JEB patient cells were selected based on restoration of adhesion phenotype, which eliminated the need for foreign sequences in repaired cells, enhancing the clinical use and safety profile of our approach. Corrected pools of primary cells assembled functional laminin-332 heterotrimer and fully reversed the blistering phenotype both in vitro and in skin grafts. The efficient targeting of the LAMA3 locus by AAV-DJ using phenotypic selection, together with the observed low frequency of off-target events, makes AAV-DJ based somatic cell targeting a promising strategy for ex vivo therapy for this severe and often lethal epithelial disorder.


Transient depletion of T cells with high LFA-1 expression from peripheral circulation during acute Plasmodium falciparum malaria.
Acute P. falciparum malaria is associated with loss of in vitro T cell responsiveness to antigenic stimulation, and with high plasma levels of soluble interleukin 2 receptor (IL 2R). In the present study peripheral T cells from acute P. falciparum malaria patients from a malaria-endemic area of Sudan were analyzed for expression of cell surface antigens associated with T lymphocyte adhesion, activation and maturation. The results were compared to results from T cells obtained from the same donors either before the attack, or during convalescence. Most donors showed a remarkable loss of T cells with high expression of the surface marker LFA-1 (CD11a/CD18) during the clinical episode, in addition to the functional changes described above. Two donors that did not show phenotypic changes were furthermore characterized by having an unabated proliferative response and normal plasma IL 2R levels. All peripheral CD3+ T lymphocytes expressed LFA-1, which had a clearly bimodal distribution on these cells. The T cell subpopulation having high LFA-1 expression (LFA-1++) was composed of both memory and unprimed T cells, according to their expression of CD45RA and CD45R0. Analysis of expression of membrane-bound IL 2R (CD25) and ICAM-1 (CD54) did not reveal in vivo activated T cells in the peripheral blood of the patients. Taken together, these data suggest that circulating T cells recognizing parasite antigens are temporarily withdrawn from peripheral circulation during P. falciparum malaria.


Effect of orlistat on fecal fat, fecal biliary acids, and colonic cell proliferation in obese subjects.
Orlistat is a weight management agent that selectively inhibits gastrointestinal lipase activity. Because of orlistat's mode of action, increased fecal fat is presented to the colonic mucosa, and fecal bile acid and free fatty acid composition may be altered during treatment. Our aim was to assess the effect of treatment of obese subjects with orlistat 120 mg 3 times a day for 6 weeks on fecal lipid and bile acid parameters and colonic mucosal cell proliferation. Twenty-four obese (body mass index, 30-40 kg/m2) but otherwise healthy male and female subjects were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group study. Participants were hospitalized during days 1-3 and 33-42 of treatment and were treated as outpatients for the remaining days. Treatment with orlistat for 6 weeks resulted in significantly greater increases in fecal weight, total fecal fat, and fecal free fatty acids than placebo. Total fecal bile acid amounts decreased slightly with orlistat, and increased significantly with placebo treatment (P < .05 between-group difference). Orlistat did not alter colonic cell proliferation as assessed by the 3 proliferative indices (5-bromo-2-deoxyuridine, whole crypt mitotic count, and proliferating cell nuclear antigen). Biochemical changes in fecal composition related to the pharmacodynamic mode of action of orlistat are not accompanied by altered colonic cell proliferation, a putative biomarker of colon cancer risk.


Drug-induced lesions of the oesophageal mucosa.
Lesions of the oesophageal mucosa are observed in various situations: most often with gastrooesophageal reflux disease, but also with infections, cancer, contact with a toxic substance, etc. When they are symptomatic, these lesions provoke burning sensations, dysphagia, regurgitation and sometimes dorsal pain. The changes to the oesophageal mucosa may take various forms: inflammation, erosion, ulceration or necrosis. Serious or even fatal complications can develop but are rare; they include oesophageal perforation, stricture and haemorrhage. Some oral drugs damage the oesophageal mucosa through direct contact. The symptoms often develop several hours after ingestion. The pain is of sudden onset. The resulting lesions are solitary or multiple ulcers that vary in depth and usually occur in the upper portion of the oesophagus. Various factors prolong contact between a drug and the oesophageal mucosa, in particular: swallowing the drug with insufficient liquid or just before lying down; capsule forms; and oesophageal abnormalities. The drugs most frequently implicated are tetracyclines, particularly doxycycline, bisphosphonates and various nonsteroidal anti-inflammatory drugs (NSAIDs). Many drugs, used in various situations, provoke gastro-oesophageal reflux disease, sometimes causing mucosal lesions in the lower oesophagus: calcium-channel blockers, nitrates, exenatide and liraglutide, drugs with antimuscarinic effects, theophylline, etc. Some drugs affect all mucous membranes in the body, including the oesophageal mucosa, irrespective of their route of administration: cancer drugs, isotretinoin, and nicorandil.


Antiproliferative properties of polyamine analogues: a structure-activity study.
A basis set of polyamine analogues was designed and synthesized. These compounds were used to initiate a systematic investigation of the role of chain length, terminal nitrogen alkyl group size, and symmetry of the methylene backbone in the antineoplastic properties of polyamine analogues. New synthetic methods predicated on our earlier polyamine fragment synthesis are described for accessing the tetraamines of interest. An unsymmetrically substituted diamine reagent, N-(tert-butoxycarbonyl)-N,N'-bis(mesitylenesulfonyl)-1,4-diaminobu tane, was developed for entry into unsymmetrical tetraamines. All of the tetraamines synthesized were first evaluated in a murine leukemia L1210 cell IC50 assay at 48 and 96 h. In an attempt to correlate this behavior with some aspect of polyamine metabolism, each compound was tested for its ability to compete with spermidine for the polyamine uptake apparatus, its impact on the polyamine biosynthetic enzymes ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC), and its effect on the polyamine-catabolizing enzyme spermidine/spermine N1-acetyltransferase (SSAT) and on polyamine pools. While there was no obvious correlation between the 48 and 96 h IC50's and the impact of the analogues on polyamine metabolism, there were other structure-activity relationships. Correlations were observed to exist between chain length and IC50's and between terminal alkyl substituents and impact on Ki, ODC, and AdoMetDC. Also, preliminary studies suggest a relationship may exist between the 48 and 96 h IC50 activities and the analogue's chronic toxicity in vivo. Finally, when the overall length of the polyamine backbone was held constant, the symmetry of the methylene chains of the polyamine fragments was shown to be unimportant to the compound's activity.


No prognostic significance of antimitochondrial antibody profile testing in primary biliary cirrhosis.
The rate of disease progression varies considerably between individuals with primary biliary cirrhosis (PBC). On the basis of serological subtyping 4 antimitochondrial antibody (AMA) profiles (A, B, C and D) can be defined. The finding of previous studies that profile C/D is associated with a progressive course, in contrast to profile A/B, is a question of debate. The aim of the study was to investigate whether AMA profiles predicted the course for a cohort of Dutch PBC patients. Patients with an established diagnosis of AMA-positive PBC, AMA-negative PBC patients, non-PBC decompensated cirrhotics and healthy volunteers. Serum samples from 38 AMA-positive progressive patients, 31 AMA-positive patients without evidence of progression for at least 6 years, 5 AMA-negative PBC patients, 5 non-PBC decompensated cirrhotics and 5 healthy volunteers were assessed. AMA profiles were determined without knowledge of the clinical data. In the progressive AMA-positive group, 13% had profile A/B and 84% had profile C/D. In the non-progressive group, 13% had profile A/B, 77% profile C/D; 10% had no profile. During follow-up, a change from profile A/B to profile C/D or vice versa was not observed. This study found that not only PBC patients with AMA profile C/D but also patients with profile A/B may run a progressive course and therefore does not support the suggestion that AMA profiles can be used as independent prognostic indicator. The divergent results of this and previous studies may be explained by the selection of different patient populations.


Genetic diversity and structure of an estuarine fish (Fundulus heteroclitus) indigenous to sites associated with a highly contaminated urban harbor.
Intense selection on isolated populations can cause loss of genetic diversity, which if persistent, reduces adaptive potential and increases extinction probability. Phenotypic evidence of inherited tolerance suggests that polychlorinated biphenyls (PCBs), have acted as strong selective agents on populations of a non-migratory fish, Fundulus heteroclitus, indigenous to heavily contaminated sites. To evaluate population genetic structure and test for effects of intense, multi-generational PCB contamination on genetic diversity, we used AFLP analysis on fish collected from six sites along the east coast of North America that varied widely in PCB contamination. The sites included a heavily contaminated urban harbor (New Bedford, MA), an adjacent moderately contaminated sub-estuary (Buzzards Bay, MA), and an uncontaminated estuary 60 km away (Narragansett, RI). AFLP markers distinguished populations at moderate and small scales, suggesting genetic differentiation at distances of 2 km or less. Genetic diversity did not differ across the study sites. Genome-wide diversity may have been preserved because of large effective population sizes and/or because the mechanism for genetic adaptation to these contaminants affected only a small number of loci. Alternatively, loss in diversity may have been restored with moderate levels of migration and relatively short generation time for this species.


Intrabiliary metastasis of colorectal adenocarcinoma: the SPY perspective.
We report a case of a 54-year-old female that underwent sigmoidectomy for stage IIA adenocarcinoma. After 5 years of follow-up, despite normal colonoscopy and CEA and CA-19.9 levels, abdominal CT revealed a 3 cm perianastomotic peritoneal lesion and suspected liver metastasis. Although liver biopsy was negative for malignancy, the perianastomotic lesion was confirmed to be metastasis of colonic adenocarcinoma. After chemotherapy, a mild elevation of alkaline phosphatase and γ-GT was evident. MRCP revealed dilation of intrahepatic bile ducts in segment VIII due to an intraluminal lesion in the right hepatic duct, suggestive of intraductal cholangiocarcinoma.


[Efficacy of adjuvant endocrine therapy in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy].
Objective: To evaluate the efficacy of adjuvant endocrine therapy (AET) in breast cancer patients with a positive-to-negative switch of hormone receptor status after neoadjuvant chemotherapy (NAC). Methods: One hundred and six patients who presented with hormone receptor (HR)-positive breast cancer at diagnosis and turned to HR-negative after NAC during December 2000 and December 2013 in Jiaxing Maternity and Child Health Care Hospital were retrospectively identified. Kaplan-Meier analysis and log-rank test were used for univariate analyses of factors related to disease free survival (DFS) and overall survival (OS). Multivariate analysis was carried out using the Cox proportional hazards model in patients with DFS and OS. Results: All the patients were categorized into two groups on the basis of the administration of AET:61 AET-administered patients (57.5%) and 45 AET-naïve patients (42.5%). After a median follow-up of 68 months (range 14-103 months), human epidermal growth factor receptor 2 (HER-2) status, initial clinical stage, pathological axillary lymph node status and the use of AET were identified as the variables affecting DFS and OS (all P<0.05). Patients treated with AET had a significantly improved 5-year DFS rate when compared with that without AET (77.1% vs 53.5%,P<0.05). The 5-year OS of AET-administered patients was also better than that of AET-naïve patients (80.9% vs 71.0%,P<0.05). Cox regression analysis showed that AET-administered or not was the independent predictor for 5-year DFS (HR=2.096, 95% CI:1.081-4.065, P<0.05). Conclusion: Patients with HR altered from positive to negative after NAC may still gain benefit from AET.


Broken selection rule in the quantum Rabi model.
Understanding the interaction between light and matter is very relevant for fundamental studies of quantum electrodynamics and for the development of quantum technologies. The quantum Rabi model captures the physics of a single atom interacting with a single photon at all regimes of coupling strength. We report the spectroscopic observation of a resonant transition that breaks a selection rule in the quantum Rabi model, implemented using an LC resonator and an artificial atom, a superconducting qubit. The eigenstates of the system consist of a superposition of bare qubit-resonator states with a relative sign. When the qubit-resonator coupling strength is negligible compared to their own frequencies, the matrix element between excited eigenstates of different sign is very small in presence of a resonator drive, establishing a sign-preserving selection rule. Here, our qubit-resonator system operates in the ultrastrong coupling regime, where the coupling strength is 10% of the resonator frequency, allowing sign-changing transitions to be activated and, therefore, detected. This work shows that sign-changing transitions are an unambiguous, distinctive signature of systems operating in the ultrastrong coupling regime of the quantum Rabi model. These results pave the way to further studies of sign-preserving selection rules in multiqubit and multiphoton models.


End-of-life decisions of physicians in the city of Hasselt (Flanders, Belgium)
The objective of this study is to estimate the proportion of different types of end-of-life decisions (ELDs) of physicians in the city of Hasselt (Flanders, Belgium). The question is addressed to what degree these ELD meet legal constraints and the ethical requirements for prudent practice. All physicians of the city of Hasselt who signed at least one death certificate in 1996 (N=166) received an anonymous self-administered mail questionnaire per death case (max. 5/doctor). The response rate was 55% (N=269). In 37.3% of all cases at least one ELD was made (16.5% non-treatment decisions; 16% potential life-shortening by intensifying the treatment of pain and symptoms; 4.8% administration, supply or prescription of lethal drugs). In 59.5% of the cases where an ELD was made that decision was legally questionnable. Patient characteristics were clearly related to the type of ELD. There was no influence of physician characteristics, except for commitment to life-stance. In 71.3% of the cases the ELD was in no way discussed with the patient. 8.1% of the ELD-cases were in response to a direct request from the patient. The incidences of ELDs in Hasselt are consistent with earlier findings. The study shows that religious commitment influences the behaviour of physicians at the end of their patients' life. The patient's and her family's entitlements to participation in the decision making process were rather poorly respected.


Genetic polymorphisms in oxidative stress-related genes are associated with clinical outcome in patients with advanced non-small cell lung cancer receiving tyrosine kinase inhibitors.
Many types of cancer have high antioxidant capacity that effectively scavenges reactive oxygen species and thus protect cancer cells against oxidative damage. The aim of this study was to examine the effect of 20 single nucleotide polymorphisms (SNPs) in 20 oxidative stress-related genes on clinical outcome in 219 patients with advanced non-small cell lung cancer (NSCLC) who were treated with EGFR tyrosine kinase inhibitors (TKIs). We assessed the associations of SNPs with prognosis in all patients as well as stratified by clinical characteristics. Three SNP (rs1695, rs2333227 and rs699512) were significantly associated with overall survival (OS). In a multivariate analysis, rs1695 AA and rs2333227 AG/GG genotypes were identified as independent prognostic factors for poor OS. Stratification analyses revealed that these 3 SNPs remained significantly associated with OS. Furthermore, there was a strong gene-dosage effect of these 3 SNPs on OS that patients with increasing number of unfavorable genotypes had significantly increased death risk. In conclusion, our findings provide the first evidence that genetic variants in oxidative stress-related genes may influence treatment outcome in advanced NSCLC patients receiving EGFR TKIs.


Cyclosporine in psoriatic arthropathy.
Psoriatic arthropathy (PsA) is an inflammatory arthropathy associated with skin or nail psoriasis with heterogeneous clinical manifestations. A pragmatic therapeutic approach to PsA is to stratify the disease manifestations according to their response to synthetic and biological agents. It is now reasonably well established that peripheral arthritis is amenable to treatment with synthetic disease-modifying anti-rheumatic drugs, while psoriatic pelvispondylitis and inflammatory tendon lesions appear to require the use of biological agents. Cyclosporine is a calcineurin inhibitor belonging to the synthetic disease-modifying anti-rheumatic drugs group. It has been shown to be effective in treating both arthritis and psoriasis. In this paper, we will briefly summarise the current knowledge about the efficacy of cyclosporine, both as a monotherapy and as an adjunctive treatment for PsA.


Intensity-modulated radiotherapy.
Intensity-modulated radiotherapy represents a recent advancement in conformal radiotherapy. It employs specialized computer-driven technology to generate dose distributions that conform to tumor targets with extremely high precision. Treatment planning is based on inverse planning algorithms and iterative computer-driven optimization to generate treatment fields with varying intensities across the beam section. Combinations of intensity-modulated fields produce custom-tailored conformal dose distributions around the tumor, with steep dose gradients at the transition to adjacent normal tissues. Thus far, data have demonstrated improved precision of tumor targeting in carcinomas of the prostate, head and neck, thyroid, breast, and lung, as well as in gynecologic, brain, and paraspinal tumors and soft tissue sarcomas. In prostate cancer, intensity-modulated radiotherapy has resulted in reduced rectal toxicity and has permitted tumor dose escalation to previously unattainable levels. This experience indicates that intensity-modulated radiotherapy represents a significant advancement in the ability to deliver the high radiation doses that appear to be required to improve the local cure of several types of tumors. The integration of new methods of biologically based imaging into treatment planning is being explored to identify tumor foci with phenotypic expressions of radiation resistance, which would likely require high-dose treatments. Intensity-modulated radiotherapy provides an approach for differential dose painting to selectively increase the dose to specific tumor-bearing regions. The implementation of biologic evaluation of tumor sensitivity, in addition to methods that improve target delineation and dose delivery, represents a new dimension in intensity-modulated radiotherapy research.


Interrelated and interdependent.
The possibilities for building and nourishing connections among the social, cultural, neuroscientific, biological, and cognitive sciences in the service of understanding children and their development are tremendously exciting. Crossing, and integrating across, disciplinary boundaries, especially those disciplines relating to biology/neuroscience, society/culture, cognition, emotion, perception, and motor function has greatly increased over the last decade and hopefully will increase exponentially in the future. All of these aspects of being human are multiply-interrelated and we need to make far more progress in understanding those interrelations.


DNA-protein immunization using Leishmania peroxidoxin-1 induces a strong CD4+ T cell response and partially protects mice from cutaneous leishmaniasis: role of fusion murine granulocyte-macrophage colony-stimulating factor DNA adjuvant.
To date, no universally effective and safe vaccine has been developed for general human use. Leishmania donovani Peroxidoxin-1 (LdPxn-1) is a member of the antioxidant family of proteins and is predominantly expressed in the amastigote stage of the parasite. The aim of this study was to evaluate the immunogenicity and protective efficacy of LdPxn-1 in BALB/c mice in heterologous DNA-Protein immunization regimen in the presence of fusion murine granulocyte-macrophage colony-stimulating factor (mGMCSF) DNA adjuvant. A fusion DNA of LdPxn1 and mGMCSF was cloned into a modified pcDNA vector. To confirm the expression in mammalian system, Chinese hamster ovary cells were transfected with the plasmid vector containing LdPxn1 gene. BALB/c mice were immunized twice with pcDNA-mGMCSF-LdPxn-1 or pcDNA-LdPxn1 DNA and boosted once with recombinant LdPxn-1 protein. Three weeks after the last immunization, mice were infected with Leishmania major promastigotes. The result showed that immunization with pcDNA-mGMCSF-LdPxn1 elicited a mixed Th-1/Th-2 immune response with significantly higher production of IFN-γ than controls. Intracellular cytokine staining of antigen-stimulated spleen cells showed that immunization with this antigen elicited significantly higher proportion of CD4+ T cells that express IFN-γ, TNF-α, or IL-2. The antigen also induced significantly higher proportion of multipotent CD4+ cells that simultaneously express the three Th-1 cytokines. Moreover, a significant reduction in the footpad swelling was seen in mice immunized with pcDNA-mGMCSF-LdPxn1 antigen. Expression study in CHO cells demonstrated that pcDNA-mGMCSF-LdPxn-1 was expressed in mammalian system. The result demonstrates that immunization of BALB/c mice with a plasmid expressing LdPxn1 in the presence of mGMCSF adjuvant elicits a strong specific immune response with high level induction of multipotent CD4+ cells that mediate protection of the mice from Leishmania major infection. To our knowledge, this is the first study showing the vaccine potential of Leishmania peroxidoxin -1.


Role of membrane bound calcium in histamine secretion from rat peritoneal mast cells.
Calcium loosely bound to the mast cell membrane may be utilized for histamine release induced by antigen, concanavalin A, compound 48/80 and the calcium ionophore A23187. Cells incubated in the presence of calcium and diluted into a medium free of divalent cations give a maximal release of histamine which decays with time, consistent with dissociation of the ion from the membrane. Anti-rat IgE and suboptimal concentrations of the ionophore show an immediate decrease in response followed by a further progressive decay. These results are consistent with the slower progress decay. These results are consistent with the slower time-course of secretion shown by these agonists, thus permitting dissociation of calcium from the membrane, before exocytosis is induced. In accord with this hypothesis, the initial suppression of response to the ionophore is reversed by preincubation of the cells with adenosine which enhances the rate of histamine release. The response of dextran is totally abolished by the described treatment, supporting suggesting that free extracellular calcium may be required for the polysaccharide to express its activity.


An artificial cell system for biocompatible gene delivery in cancer therapy.
The gene therapy of cancer is generally recognized as a promising approach for the reversal of neoplastic progress of cancer cells. However, the lack of biocompatibility as well as highly available carriers is the bottleneck in gene therapy. In recent years, with the advances of understanding in cell signaling and cell based functions, the development of cell mimic carriers is showing great potential in evaluating the anticancer efficacy of drugs. Here in our study, an artificial cell (AC) system was fabricated to mimic the gene protection and transfection functions of cancer cells using cancer cell derived histone and membranes. As expected, the AC showed high biocompatibility as well as preferable gene transfection capability both in vitro and in vivo, and might be a promising tool for the flexible assembly of cell mimic systems in cancer therapy.


Development of the functional assessment of migraine scale using a patient guided approach.
A better understanding of the multi-dimensional burden and impact of migraine has grown over recent years, yet the tools used to measure these concepts have not been updated to reflect such findings. Additionally, due to the increase in the number of both prophylactic and acute therapeutic options for migraine, a comprehensive assessment of treatment response is necessary. The goal of this project was to develop a patient guided outcome measure which evaluates patient identified efficacy factors when appraising migraine treatment response. A group of patients with migraine (N = 10) were given an in-person semi-structured interview collecting information regarding a patient's perspective on meaningful response to headache and migraine treatment. Using the patient information collected during these interviews, a set of questions aimed at evaluating meaningful response were developed. Two additional groups (N = 100, 200) of patients with migraine then provided feedback on the drafted questions in an online setting. Interviews indicated thematic areas of interest to patients with migraine are not commonly assessed on popular measures. Over two hundred items were developed to assess thematic areas indicated by patients. Factor analysis used on the focus groups' results led to the development of an 18-item scale (Functional Assessment of Migraine Scale-Research: FAMS-R) that assesses the impact of migraine on a patient and shows the potential to measure treatment response. The FAMS portrays promising results at measuring a multi-faceted migraine treatment response and disease impact.


Effects of moisture content and additives on the ensiling quality and vitamins changes of alfalfa silage with or without rain damage.
We investigated the effects of moisture, rain damage, and additives on fermentation quality and vitamins change in alfalfa (Medicago sativa L.) silage. Two moisture content alfalfa (53 and 72% moisture content) were received artificial rain damage. Then, the formic acid and L. plantarum (LP) + sucrose were added. After 30 days, silos were opened. The significant interaction between rain damage and moisture content were found for nutrients and fermentation characteristics in alfalfa silage, which showed more rain damage effects occurred in 53% moisture content rather than in 72% moisture content material. Treatment with LP + sucrose had lower pH value, ammonia-N/total N, and higher lactic acid content compared to the other additives. The concentrations of α-tocopherol and phylloquinone increased, but thiamine, riboflavin, and ascorbic acid decreased in alfalfa silage treated with LP + sucrose, especially when the alfalfa was subjected to rain damage. The highly significant correlations were found between pantothenic acid (VB5) and pH, and between VB5 and lactic acid. The improvements in fermentation quality by adding of LP + sucrose was observed after rain damage for either 53% or 72% moisture alfalfa, which can be a guideline for forage processor who ensiles alfalfa after rain damage.


[Pharmacological action of mazindol on behaviors and metabolism].
To elucidate the mechanism of the action of mazindol, an anorectic drug, mazindol effects on behaviors of rats such as feeding, drinking and activities were examined. Mazindol (40 mg/100 g of diet) addition to the diet elicited the transient decrease in food and water intakes, and increases in Animex and running wheel activities compared to those behaviors seen before the mazindol addition. The mazindol addition essentially did not affect the circadian rhythms of the above behaviors. Continuous infusion of mazindol (1-10 ng/h) into the brain reduced the total food intake and increased the light period food intake. The strongest effect of mazindol on food intake was observed when it was infused into a site of median eminence which was 2 mm posterior to the suprachiasmatic nucleus of the hypothalamus. This fact suggests that the site of the anorectic action of mazindol might be located in this area. Since food efficiency (= body weight increase per day/food intake per day) reduced during the period of mazindol addition to the diet in the above experiment, metabolic alterations due to mazindol were examined in rats. The results suggest that mazindol administration enhances degradations of proteins and amino acids and increases gluconeogenesis in the liver.


Technical note: Evaluation of a real-time wireless pH measurement system relative to intraruminal differences of digesta in dairy cattle.
The aim of this study was to evaluate the accuracy and precision of indwelled wireless sensors relative to intrareticuloruminal differences in dairy cows transitioned from a forage to a high-concentrate diet. A feeding trial was performed with 8 rumen-cannulated Holstein cows. The cows were stepwise switched from 0 to 60% concentrate in the diet and fed 5 wk. Samples from the free ruminal liquid (FRL) from the ventral rumen and from the particle-associated ruminal liquid (PARL) in the rumen mat were manually taken at 0, 4, and 8 h after the morning feeding on d 0, 7, 14, and 34 of the experiment through the ruminal cannula to measure pH in FRL and PARL using a pH electrode. Additionally indwelling reticular wireless pH sensors were used to measure reticular pH every 10 min throughout the experiment. Precision and accuracy properties as a measure of reproducibility of the methods were statistically evaluated. Data showed significant differences among pH readings of indwelling sensors and pH measurements taken by means of a conventional electrode in both FRL and PARL (P<0.05). These differences became more evident when 60% concentrate diet was fed. Across all experimental days, the pH of the FRL was greatest and the pH reported by indwelling sensors intermediate, whereas the pH of PARL was lowest. The concordance correlation coefficient (CCC) analysis revealed a high agreement between indwelling sensors and FRL (CCC=0.709) but a low agreement with the pH of PARL (CCC=0.495). In conclusion, the study indicated that wireless sensors can satisfactorily reflect the pH of FRL but poorly reflect that of PARL.


Sweat Gland Carcinoma With Lymphadenopathy.
Sweat gland carcinoma is a rare tumour, being almost 1% of primary skin lesions. The tumour has tendency to spread to regional lymph nodes and distant metastases has also been reported. Their exact incidence in Pakistan is not known. Treatment options are also not clearly defined though surgery is the initial treatment approach as adjuvant treatment has not been properly explored. We report a case of sweat gland carcinoma with lymphadenopathy.


Whipple's operation without an operative mortality in 37 consecutive patients: Thai surgeons' experiences.
Pancreaticoduodenectomy (Whipple's operation) represents a considerable surgical challenge. The operative mortality rate after Whipple's operation is still less than 5%. Recent studies show pancreaticojejunostomy (PJ) anastomosis is the "Achilles heel" of the procedure. The authors present the results of Whipple's operation without mortality which were performed in the Division of General Surgery, Department of Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. From January 1991 to December 2003, thirty-seven consecutive patients who underwent Whipple's operation were enrolled in the present study. The ages ranged from 33 to 79 years (mean 57.13). There were 19 male and 18 female patients. Twenty-nine of them underwent a pylorus preserving pancreaticoduodenctomy (PPPD). Construction of the PJ anastomosis was mostly performed by a dunking technique, that is, the invagination of the pancreatic resected end into the jejunum. There was no postoperative mortality from anastomotic leakage. Surgical wound infections occurred in 7 patients, gastric atony in 2 patients, and PJ anastomosis leakage which created a fistula in 1 patient. All 37 patients were discharged in an improved condition following surgery. The median follow-up was 2 years (range: 4 month-11 years). Eighteen patients died from liver failure. Until now 19 patients are doing well. The authors demonstrated that the dunking technique used for PJ anastomosis in Whipple's operation provided a good result without any mortality rate.


Envisioning nursing in 2050 through the eyes of nurse theorists: Leininger and Watson.
Madeleine Leininger and Jean Watson envision how their theoretical ideas will be expressed in the world in 2050. Leininger explains how her theory and ethnoresearch methodology have given rise to transcultural nursing and the culture care nursing paradigm and predicts that they will continue to contribute to culturally congruent care practices that promote health, healing, quality of life, and even world peace. Watson provides a vision based on an emergent perspective that emphasizes subjective dimensions related to self-knowledge, self-control, self-caring, and self-healing potential; spirit and wholeness of being/becoming; natural healing approaches; and caring, healing relationships with self and others.


Targeting of Streptococcus mutans Biofilms by a Novel Small Molecule Prevents Dental Caries and Preserves the Oral Microbiome.
Dental caries is a costly and prevalent disease characterized by the demineralization of the tooth's enamel. Disease outcome is influenced by host factors, dietary intake, cariogenic bacteria, and other microbes. The cariogenic bacterial species Streptococcus mutans metabolizes sucrose to initiate biofilm formation on the tooth surface and consequently produces lactic acid to degrade the tooth's enamel. Persistence of S. mutans biofilms in the oral cavity can lead to tooth decay. To date, no anticaries therapies that specifically target S. mutans biofilms but do not disturb the overall oral microbiome are available. We screened a library of 2-aminoimidazole antibiofilm compounds with a biofilm dispersion assay and identified a small molecule that specifically targets S. mutans biofilms. At 5 µM, the small molecule annotated 3F1 dispersed 50% of the established S. mutans biofilm but did not disperse biofilms formed by the commensal species Streptococcus sanguinis or Streptococcus gordonii. 3F1 dispersed S. mutans biofilms independently of biofilm-related factors such as antigen I/II and glucosyltransferases. 3F1 treatment effectively prevented dental caries by controlling S. mutans in a rat caries model without perturbing the oral microbiota. Our study demonstrates that selective targeting of S. mutans biofilms by 3F1 was able to effectively reduce dental caries in vivo without affecting the overall oral microbiota shaped by the intake of dietary sugars, suggesting that the pathogenic biofilm-specific treatment is a viable strategy for disease prevention.


The effects of bovine myelin basic protein on the phase transition properties of sphingomyelin.
The basic protein of myelin can spontaneously associate with the synthetic phospholipid N-palmitoyl-sphingosinephosphatidylcholine. The protein alters the phase transition properties of the lipid from a single transition at 41.5 degrees C to two overlapping transitions, one being slightly above and the other slightly below the transition temperature of the pure lipid. The effect was not seen upon the addition of poly(L-lysine) to this lipid nor does the myelin basic protein alter the phase transition properties of dimyristoylphosphatidylcholine. The results thus demonstrate that the myelin basic protein can interact with a major zwitterionic lipid component of myelin in addition to acidic phospholipids.


Devonian gametophytes with anatomically preserved gametangia.
The oldest anatomically preserved and physiologically apparently independent gametophytes are described from the Lower Devonian of Scotland. These gametophytes have upright, leafless axes with terminally borne, bowl-shaped game-tangiophores. The antheridia are stalked and their walls are multicellular. The archegonia are clustered in groups on common bases.


Development of a method for quantification of acrolein-deoxyguanosine adducts in DNA using isotope dilution-capillary LC/MS/MS and its application to human brain tissue.
Acrolein is a highly reactive alpha,beta-unsaturated aldehyde and is known to react with DNA forming exocyclic acrolein-deoxyguanosine adducts (Acro-dG). These aldehyde-DNA lesions may play a role in mutagenesis, carcinogenesis, and neurodegenerative diseases. In the present work, we described the development and evaluation of a highly sensitive and selective capillary liquid chromatography nanoelectrospray isotope dilution tandem mass spectrometry method for quantitatively analyzing Acro-dG in DNA hydrolysates. This was achieved by applying a stable isotope-labeled analogue Acro-dG-13C10,15N5 as an internal standard to the DNA to be analyzed and then hydrolyzing the DNA enzymatically to nucleosides. The acrolein-modified nucleosides were separated from normal nucleosides by capillary liquid chromatography and quantified by a high-capacity ion trap mass spectrometer in the MS/MS mode. The developed method achieved attomole-level sensitivity (limit of detection was 10 fg, 31 amol on column) for detection of pure Acro-dG adduct standards. The limit of quantification of Acro-dG adducts obtained in 10 mug of DNA hydrolysates was 1.5 fmol, which corresponded to 50 adducts/10(9) normal nucleosides. Application of this method to the analysis of Acro-dG adducts in acrolein (10-fold)-treated calf thymus DNA showed approximately 830 lesion/10(6) DNA nucleosides using as low as 50 ng of DNA. Application of this method to DNA samples (1-2 mug) isolated from brain tissues from Alzheimer's disease subjects and age-matched controls demonstrated 2800-5100 Acro-dG adducts/10(9) DNA nucleosides. Statistically significant differences (P < 0.05) in levels of Acro-dG between AD subjects and controls were observed in DNA isolated from the hippocampus/parahippocampal gyrus.


A Study on the Data Compression Technology-Based Intelligent Data Acquisition (IDAQ) System for Structural Health Monitoring of Civil Structures.
In this paper, a data compression technology-based intelligent data acquisition (IDAQ) system was developed for structural health monitoring of civil structures, and its validity was tested using random signals (El-Centro seismic waveform). The IDAQ system was structured to include a high-performance CPU with large dynamic memory for multi-input and output in a radio frequency (RF) manner. In addition, the embedded software technology (EST) has been applied to it to implement diverse logics needed in the process of acquiring, processing and transmitting data. In order to utilize IDAQ system for the structural health monitoring of civil structures, this study developed an artificial filter bank by which structural dynamic responses (acceleration) were efficiently acquired, and also optimized it on the random El-Centro seismic waveform. All techniques developed in this study have been embedded to our system. The data compression technology-based IDAQ system was proven valid in acquiring valid signals in a compressed size.


Weight management strategies for those with chronic kidney disease: A consensus report from the Asia Pacific Society of Nephrology and Australia and New Zealand Society of Nephrology 2016 renal dietitians meeting.
The aim of the present study was to develop a consensus report to guide dietetic management of overweight or obese individuals with chronic kidney disease (CKD). Six statements relating to weight management in CKD guided a comprehensive review of the literature. A summary of the evidence was then presented at the renal nutrition meeting of the 2016 Asia Pacific Society of Nephrology and Australia and New Zealand Society of Nephrology. Majority agreement was defined as group agreement on a statement of between 50-74%, and consensus was considered ≥75% agreement. The recommendations were developed via a mini Delphi process. Two statements achieved group consensus: the current guidelines used by dietitians to estimate energy requirements for overweight and obese people with CKD are not relevant and weight loss medications may be unsafe or ineffective in isolation for those with CKD. One statement achieved group agreement: Meal replacement formulas are safe and efficacious in those with CKD. No agreement was achieved on the statements of whether there is strong evidence of benefit for weight loss prior to kidney transplantation; whether traditional weight loss strategies can be used in those with CKD and if bariatric surgery in those with end stage kidney disease is feasible and effective. There is a limited evidence base to guide the dietetic management of overweight and obese individuals with CKD. Medical or surgical strategies to facilitate weight loss are not recommended in isolation and require a multidisciplinary approach with the involvement of a skilled renal dietitian.


Effects of the Fe-Co interaction on the growth of multiwall carbon nanotubes.
The influences of active species Fe-Co composition on the growth of carbon nanotubes (CNTs) were systemically investigated. CNTs were grown from the pyrolytic decomposition of C(2)H(2) over Fe-Co/CaCO(3) catalysts by radio frequency chemical vapor deposition (CVD). The catalyst stoichiometry was found to strongly influence the carbon deposition rate as well as the nanotube crystallinity characteristics. Compared to the CNTs synthesized over the Co/CaCO(3) catalyst, those produced by Fe-containing catalysts have less amorphous carbon. The maximum yield of high-quality CNTs was achieved at the Fe/Co atomic ratio of 2:1 due to a suitable concentration of benzene generated from acetylene CVD on such catalytic system. Fe and Co can form alloy and therefore the d-electron interaction between Fe and Co was believed to play an important role in the CNT growth.


Comparison of Cardiac Auscultation Features on Four Different Simulation Mannequins Performed by Pediatric Residents.
Cardiac murmurs are a common problem in pediatric clinical practice. Studies demonstrated low accuracy in detecting and diagnosing various cardiac murmurs at all levels of medical training. So, supplementary training methods started to evolve, including simulation for auscultation skills training. Over the years, mannequins have evolved with different types of technology. Therefore, we decided to compare cardiac auscultation accuracy among high-fidelity mannequins as the primary objective and compare the performance of various postgraduate-level residents as a secondary objective. Pediatric residents at King Abdulaziz University Hospital were given a lecture on the basics of cardiac auscultation and then requested to auscultate four mannequins, namely SimJumior® (Laerdal Medical, Stavanger, Norway), SimBaby™ (Laerdal Medical), Pediatric HAL® (Gaumard Scientific, Miami, FL, USA), and Cardiac Patient Simulator K-Plus (Kyoto Kagaku Co. Ltd., Kyoto, Japan). The accuracies of murmur type, diagnosis, and auscultation time were compared. Results: A total of 56 pediatric residents were enrolled. Median murmur accuracy ranged from 50% to 53% (p-value 0.79), and median diagnosis accuracy ranged from 33% to 36% (p-value 0.77), with a nonsignificant difference between mannequins. Comparing resident levels in all mannequins, median murmur accuracy ranged from 49% to 56% (p-value 0.70), and median diagnosis accuracy ranged from 29% to 41% (p-value 0.09). While the median average auscultation time was between 41 and 50 seconds (p-value 0.34). Auscultation skills can be taught through simulation on any mannequin used in this comparison, not necessarily the cardiac one. For better accuracy, future comparisons might include more advanced cardiac mannequins based on cardiac auscultation expertise (i.e., consultant level). The introduction of an auscultation program from the undergraduate level throughout the training process and monitoring of these skills are mandated.


Mechanism of morphology transformation during annealing of nanostructured gold films on glass.
Nanostructured, just-percolated gold films were prepared by evaporation on bare glass. Annealing of the films at temperatures close to or higher than the softening temperature of the glass substrate induces morphological transformation to discrete Au islands and gradual embedding of the formed islands in the glass. The mechanism and kinetics of these processes are studied here using a combination of in situ high-temperature optical spectroscopy; ex situ characterization of the island shape by high-resolution scanning electron microscopy (HRSEM), atomic force microcopy (AFM) and cross-sectional transmission electron microscopy (TEM); and numerical simulations of transmission spectra using the Multiple Multipole Program (MMP) approach. It is shown that the morphological transformation of just-percolated, 10 nm (nominal thickness) Au films evaporated on glass and annealed at 600 °C, i.e., in the vicinity of the substrate glass transition temperature (Tg = 557 °C), proceeds via three processes exhibiting different time scales: (i) fast recrystallization and dewetting, leading to formation of single-crystalline islands (minutes); the initial spectrum characteristic of a continuous Au film is transformed to that of an island film, displaying a surface plasmon (SP) absorption band. (ii) Reshaping and faceting of the single-crystalline islands accompanied by formation of circumferential glass rims around them (first few hours); the overall optical response shows a blue shift of the SP band. (iii) Gradual island embedding in the glass substrate (tens of hours), seen as a characteristic red shift of the SP band. The influence of the annealing atmosphere (air, vacuum) on the embedding process is found to be minor. Numerical modeling of the extinction cross-section corresponding to the morphological transformations during island recrystallization and embedding is in qualitative agreement with the experimental data.


EFFECTS OF MATERNAL EPILEPSY AND ANTIEPILEPTIC THERAPY IN WOMEN DURING PREGNANCY.
The aim of this study was to analyse the effects of epilepsy and antiepileptic drug (AED) treatment on pregnancy and the perinatal outcome, retrospectively. We examined the obstetric and fetal outcomes among women with epilepsy (WWE), who were followed-up at the Department of Neurology, and who delivered at the Department of Obstetrics and Gynaecology (n=91) between 31th December 2000 and 31th March 2014. Statistical comparisons of different obstetric and fetal parameters on a sample of 91 WWE and 182 non-WWE were assessed by the chi-square-test, the independent sample t-test. The rate of major congenital malformations (MCMS) among the newborns of all AEDs exposed mothers was 7.69%. There were three peaks of seizures: during the third trimester, during delivery and in the puerperium. The prevalence of miscarriages, post-term birth and the rate of caesarean section were significantly higher among the WWE than among the non-WWE (p=0.001; p<0.001; p=0.02). Parameters of neonates (birth weight, birth length, head-, and chest circumference) were significantly different between the WWE group and the non-WWE group (p=0.003, p<0.001, p<0.001, p<0.001) CONCLUSIONS: In contrast with recent publications, there were significant differences in the parameters of neonates between the two groups. Our results are in accordance with those of previous studies from the aspect of AED-related MCM, the elevated risk of miscarriages and pre-existing hypertension.


Effect of flow rate and lead/copper pipe sequence on lead release from service lines.
A pilot experiment examined lead leaching from four representative configurations of service lines including: (1) 100% lead (Pb), (2) 100% copper (Cu), (3) 50% Pb upstream of 50% Cu, and (4) 50% Pb-downstream of 50% Cu using a range of flow rates. The cumulative mass of lead release indicated that a typical partial replacement configuration (50% lead downstream of copper) did not provide a net reduction in lead when compared to 100% lead pipe (85 mg for 50% Pb-downstream versus 83 mg for 100%-Pb) due to galvanic and deposition corrosion. The partially replaced service line configuration also had a much greater likelihood of producing water with "spikes" of lead particulates at higher flow rates, while tending to produce lower levels of lead at very low flow rates. After the first 214 days the galvanic current between copper and lead was only reduced by 34%, proving that galvanic impacts can be highly persistent even in water with optimized corrosion control by dosing of zinc orthophosphate. Finally, this experiment raises concern about the low flow rates used during some prior home sampling events, which may underestimate exposure to lead during normal water use, especially when galvanic Pb:Cu connections are present.


Changes in Oral Health-Related Quality of Life in Elderly Edentulous Patients after Complete Denture Therapy and Possible Role of their Initial Expectation: A Follow-Up Study.
An edentulous patient's psychosocial attributes that may have influence on the oral health-related quality of life (OHRQoL) are given little consideration in therapeutic care. The aim of this study was to assess the impact of complete denture therapy on overall OHRQoL in elderly edentulous patients. The possible role of the patient's initial expectation toward OHRQoL was also evaluated. OHRQoL was assessed using the OHIP-EDENT psychometric instrument, and 56 patients participated in the study. The assessment was done at three time points including pretreatment, after 1 month, and after 6 months. Significant differences in the OHIP-EDENT scores between pretreatment to after 1 month and pretreatment to after 6 months were calculated using Wilcoxon Signed Rank test (p < 0.05). Mann-Whitney test was used to analyze the association of patient expectations with OHIP-EDENT scores. Statistically significant improvement in OHRQoL after complete denture therapy at both 1 and 6 months postinsertion was evident. Statistically significant difference in the mean scores between the genders was observed after 6 months. There was no statistically significant difference in the levels of dysfunction, discomfort, and disability associated with oral problems between moderate and high expectation group at any time point. Elderly edentulous patients had an improved overall OHRQoL after complete denture therapy, and female patients had appreciably better OHRQoL than their male counterparts. A patient's initial expectation did not have significant influence on overall OHRQoL.


Do atypical antipsychotics improve cognition?
One of the major symptoms of schizophrenia is cognitive deficits. Despite this, these impairments still lack an effective treatment. It was hoped that atypical antipsychotics would treat these symptoms better than their first generation counterparts, but unfortunately the likes of quetiapine and clozapine did not do so. Asenapine and lurasidone, two newer atypicals, have shown promise, as have agents that interact with the glutamate system. Another approach has been to add agents such as modafinil. More research is needed to consolidate the findings of these studies.


Respiratory Tract Viral Infections and Coinfections Identified by Anyplex™ II RV16 Detection Kit in Pediatric Patients at a Riyadh Tertiary Care Hospital.
Respiratory infections are caused by an array of viruses, and limited information is available about viral coexistence, comparative symptoms, and the burden of illness. This retrospective cohort study aimed to determine the etiological agents responsible for respiratory tract infections by Anyplex II RV16 detection kit (RV16, Seegene), involving 2266 pediatric patients with respiratory infections admitted to the Department of Pediatrics at King Abdul-Aziz Medical City, Ministry of National Guard, Riyadh, from July 2014 to June 2015. The most frequent respiratory infections were recorded in the 1 to 5 year age group (44.7%). Rhinovirus (32.5%), Adenovirus (16.9%), and Respiratory syncytial virus (RSV) B (10.4%) were most common. In single viral infections, Rhinovirus (41.2%), Metapneumovirus (15.3%), and Bocavirus (13.7%) were most frequent. In multiple viral infections, Rhinovirus (36.7%), Adenovirus (35.2%), Bocavirus (11.2), RSV B (7.8%), and RSV A (6.7%) were most frequent. No significant difference was observed in clinical presentations; however, rhinorrhea and hypodynamia were significantly associated with viral respiratory infections. Most respiratory viral pathogens peaked during December, January, March, and April. Rhinovirus, Adenovirus, and Bocavirus circulations were detected throughout the year. Winter peaks were recorded for Rhinovirus, RSV B, Adenovirus, and RSV A, whereas the Metapneumovirus, and the Bocavirus peaked in March and April. These findings enhance understanding of viral etiology and distribution to improve respiratory infection management and treatment.


AIDS, combination therapy and survival.
New antiretroviral drugs have changed the natural history of HIV illness in relation to morbidity and mortality. People who were expecting to die and have since responded well to therapy report experiencing mixed emotions. This research study identified the impact of this shift in health on: hope and future outlook, changes in their quality of life and the need for social identity and support.


The messenger RNA sequences in human fibroblast cells induced with poly rI.rC to produce interferon.
Induction of human fibroblast cells with poly rI.rC induces interferon mRNA which can be translated into interferon precursor in wheat germ cell free system or in Xenopus oocytes into biologically active interferon. The extent of gene expression in the poly rI.rC induced cells was compared to that of the uninduced cells by hybridization of the mRNA to complementary DNA. Homologous template driven hybridization of cDNA revealed the presence of two clearly defined transitions in the total poly A RNA from the induced cells; abundant class and a scarce class comprising approximately 37,000 diverse species of RNA. Heterologus hybridization of the cDNA with total uninduced mRNA showed that the majority of the mRNA sequences are the same in both the induced and uninduced cells. The results of the hybridization using cDNA prepared to the fraction enriched for interferon mRNA, however, showed that about 4% of the sequences present in the interferon enriched fraction are not present in the uninduced cells. These differences may result from the poly rI.rC induced alterations in gene expression.


[Antibiotic sensitivity of Streptococcus group B].
The minimal inhibitory and bactericidal concentration of 18 antibiotics for 412 isolates of group B streptococci from newborns, mothers or pregnant women were determined. 3.2% of these strains were less susceptible to penicillin G, 1% failed to be inhibited by erythromycin and 1% by chloramphenicol. Antibiotic-killing kinetics was studied with beta-lactams, aminoglycosides, and in combination for 20 isolates. Killing was accelerated by the combination. For these reasons, at least at the beginning of the treatment, the association of ampicillin and an aminoglycoside can be recommended.


Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model.
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson's disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila. Elav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC). Exogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration. The protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.


Antibacterial and biodegradable tissue nano-adhesives for rapid wound closure.
Although various organic tissue adhesives designed to facilitate would healing are gaining popularity in diverse clinical applications, they present significant inherent limitations, such as rejection, infections, toxicity and/or excessive swelling. It is highly desirable to develop efficient, biocompatible and anti-bacterial tissue adhesives for skin wound healing. Inspired by the fact that inorganic nanoparticles can directly glue tissues through the "nanobridging effect", herein disulfide bond-bridged nanosilver-decorated mesoporous silica nanoparticles (Ag-MSNs) was constructed as an effective and safe tissue adhesive with antibacterial and degradable properties for wound closure and healing. Ag-MSNs was fabricated by controlled reduce of ultrasmall nanosilvers onto the both surface and large pore of biodegradable MSNs. The obtained MSNs were characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, energy-dispersive X-ray spectroscopy, and measurement of size distribution, zeta potential, and mesopore properties. Furthermore, adhesion strength test, anti-bacterial assessment, mouse skin wound model, and MTT assays were used to investigate the tissue adhesive property, antibacterial effect, biodegradability and biocompatibility of the Ag-MSNs. Ag-MSNs exhibited not only strong adhesive properties but also excellent antibacterial activities than that of MSNs. Importantly, this antibacterial nano-adhesive achieved rapid and efficient closure and healing of wounds in comparison to sutures or MSNs in a mouse skin wound model. Furthermore, Ag-MSNs with fast degradable behavior caused little cellular toxicity and even less systemic toxicity during wound healing. Our findings suggest that biodegradable Ag-MSNs can be employed as the next generation of nano-adhesives for rapid wound closure and aesthetic wound healing.


Identity consolidation in early adulthood: relations with ego-resiliency, the context of marriage, and personality change.
Identity consolidation during early adulthood was conceptualized as a process of investing oneself in new adult roles, responsibilities, and contexts and evaluating one's ongoing experience in order to construct a coherent, grounded, and positive identity. The current study longitudinally examined (age 21 to age 27) the roles of ego-resiliency, an important personality resource, and marriage, an important identity context, in the process of identity consolidation as it unfolded in a cohort of women who experienced early adulthood during the early 1960s. Prototypes of identity in marriage were developed to reflect the different ways these women invested and evaluated their identities in the context of marriage. Results showed that ego-resiliency at age 21 and the experience of identity in marriage at age 27 were both related to identity consolidation at age 27, and findings also suggested that the relation of age 21 ego-resiliency to age 27 identity consolidation was mediated by identity in marriage. Finally, successful identity consolidation was associated with increasing ego-resiliency from age 21 to age 27. Discussion focuses on the interaction between personality and social context in the process of identity consolidation and the role of identity consolidation in personality change.