Fatty acids as natural specific inhibitors of the proto-oncogenic protein Shp2.
Src homology-2 domain-containing protein tyrosine phosphatase (Shp2), a novel proto-oncogenic protein, is an important target in cancer therapy research. Approximately 2000 plant extracts were screened to find its natural specific inhibitors, with the ethyl acetate (EtOAc) active extract of the root of Angelica dahurica showing considerable inhibitory effects (IC(50)=21.6 mg/L). Bioguided isolation of EtOAc extract led to 13 compounds, including 10 fatty acids and derivatives. All these compounds were isolated from the plant for the first time. The inhibitory effects of these compounds on the enzyme activities of Shp2, VH1-related human protein (VHR), and hematopoietic protein tyrosine phosphatase (HePTP) were investigated. 8Z,11Z-Feptadecadienoic acid (4), 14Z,17Z-tricosadienoic acid (5), caffeic acid (9), and 2-hydroxy-3-[(1-oxododecyl) oxy]propyl-β-d-glucopyranoside (11) showed considerable selective inhibition of Shp2 activity. After treatment of HepG2 cells with the compounds, only compound 5, a polyunsaturated fatty acid, strongly induced poly (ADP-ribose) polymerase (PARP) cleavage in a dose- and time-dependent manner and increased the activities of caspase-3, caspase-8, and caspase-9 at 100 μM. Compound 5 also inhibited colony formation of HepG2 cells in a dose-dependent manner. Thus, this study reported fatty acids as specific Shp2 inhibitors and provided the molecular basis of one active compound as novel potential anticancer drug.


Missed and Delayed Preventive Health Care Visits Among US Children Due to the COVID-19 Pandemic.
The COVID-19 pandemic led to a substantial drop in US children's preventive care, which had not fully rebounded by the end of 2020. We sought to estimate the overall prevalence of missed, skipped, or delayed preventive checkups among households with children in the last 12 months because of the pandemic. We used data from the US Census Bureau's Household Pulse Survey, Phase 3.1 (collected April-May 2021). The analytic sample included 48 824 households with ≥1 child or adolescent aged <18 years. We estimated both national and state-level prevalences, examined associations with sociodemographic and household characteristics, and described reasons for missed or delayed preventive visits. Overall, 26.4% (95% CI, 25.5%-27.2%) of households reported that ≥1 child or adolescent had missed or delayed a preventive visit because of COVID-19; percentages varied by state, from 17.9% in Wyoming to 37.0% in Vermont. The prevalence of missed or delayed preventive visits was significantly higher among respondents who reported material hardships (ie, not caught up on rent/mortgage, difficulty paying usual household expenses, children not eating enough because of lack of affordability) than among respondents who did not report material hardships. The most common reasons for missing or delaying preventive visits were concern about visiting a health care provider, limited appointment availability, and the provider's location being closed. Programs and policies could reduce gaps in children's preventive care caused by the pandemic, with a particular focus on addressing social determinants of health.


Versatile strategy for the synthesis of biotin-labelled glycans, their immobilization to establish a bioactive surface and interaction studies with a lectin on a biochip.
The emerging role of glycans as versatile biochemical signals in diverse aspects of cellular sociology calls for establishment of sensitive methods to monitor carbohydrate recognition by receptors such as lectins. Most of these techniques involve the immobilization of one of the binding partners on a surface, e.g. atomic force microscopy, glycan array and Surface Plasmon Resonance (SPR), hereby simulating cell surface presentation. Here, we report the synthesis of fluorescent glycoconjugates, with a functionalization strategy which avoids the frequently occurring ring opening at the reducing end for further immobilization on a surface or derivatization with biotin. In order to improve the versatility of these derivatized glycans for biological studies, a new approach for the synthesis of biotinylated and fluorescent glycans has also been realized. Finally, to illustrate their usefulness the neoglycoconjugates were immobilized on different surfaces, and the interaction analysis with a model lectin, the toxin from mistletoe, proved them to act as potent ligands, underscoring the merit of the presented synthetic approach.


Metabolic mechanisms of acute proximal tubular injury.
Damage to the proximal tubule (PT) is the most frequent cause of acute kidney injury (AKI) in humans. Diagnostic and treatment options for AKI are currently limited, and a deeper understanding of pathogenic mechanisms at a cellular level is required to rectify this situation. Metabolism in the PT is complex and closely coupled to solute transport function. Recent studies have shown that major changes in PT metabolism occur during AKI and have highlighted some potential targets for intervention. However, translating these insights into effective new therapies still represents a substantial challenge. In this article, in addition to providing a brief overview of the current state of the field, we will highlight three emerging areas that we feel are worthy of greater attention. First, we will discuss the role of axial heterogeneity in cellular function along the PT in determining baseline susceptibility to different metabolic hits. Second, we will emphasize that elucidating insult specific pathogenic mechanisms will likely be critical in devising more personalized treatments for AKI. Finally, we will argue that uncovering links between tubular metabolism and whole-body homeostasis will identify new strategies to try to reduce the considerable morbidity and mortality associated with AKI. These concepts will be illustrated by examples of recent studies emanating from the authors' laboratories and performed under the auspices of the Swiss National Competence Center for Kidney Research (NCCR Kidney.ch).


Toward an evidence-based system for innovation support for implementing innovations with quality: tools, training, technical assistance, and quality assurance/quality improvement.
An individual or organization that sets out to implement an innovation (e.g., a new technology, program, or policy) generally requires support. In the Interactive Systems Framework for Dissemination and Implementation, a Support System should work with Delivery Systems (national, state and/or local entities such as health and human service organizations, community-based organizations, schools) to enhance their capacity for quality implementation of innovations. The literature on the Support System [corrected] has been underresearched and under-developedThis article begins to conceptualize theory, research, and action for an evidence-based system for innovation support (EBSIS). EBSIS describes key priorities for strengthening the science and practice of support. The major goal of EBSIS is to enhance the research and practice of support in order to build capacity in the Delivery System for implementing innovations with quality, and thereby, help the Delivery System achieve outcomes. EBSIS is guided by a logic model that includes four key support components: tools, training, technical assistance, and quality assurance/quality improvement. EBSIS uses the Getting To Outcomes approach to accountability to aid the identification and synthesis of concepts, tools, and evidence for support. We conclude with some discussion of the current status of EBSIS and possible next steps, including the development of collaborative researcher-practitioner-funder-consumer partnerships to accelerate accumulation of knowledge on the Support System.


Long Peritoneal Dialysis Dwells With Icodextrin: Kinetics of Transperitoneal Fluid and Polyglucose Transport.
Background and objective: During peritoneal dialysis (PD), the period of effective net peritoneal ultrafiltration during long dwells can be extended by using the colloidal osmotic agent icodextrin but there are few detailed studies on ultrafiltration with icodextrin solution exceeding 12 h. We analyzed kinetics of peritoneal ultrafiltration in relation to icodextrin and its metabolites for 16-h dwells with icodextrin. Design, setting, participants, and measurements: In 20 clinically stable patients (mean age 54 years; 8 women; mean preceding time on PD 26 months), intraperitoneal dialysate volume (VD) was estimated from dilution of 125I-human serum albumin during 16-h dwell studies with icodextrin 7.5% solution. Sodium was measured in dialysate and plasma. In 11 patients, fractional absorption of icodextrin from dialysate, dialysate, and plasma amylase and high and low (Mw <2 kDa) Mw icodextrin fractions were analyzed. Results: Average VD increased linearly with no difference between transport types. At 16 h, the cumulative net ultrafiltration was 729 ± 337 ml (range -18 to 1,360 ml) and negative in only one patient. Average transcapillary ultrafiltration rate was 1.40 ± 0.36 ml/min, and peritoneal fluid absorption rate was 0.68 ± 0.38 ml/min. During 16 h, 41% of the initial mass of icodextrin was absorbed. Plasma sodium decreased from 138.7 ± 2.4 to 136.5 ± 3.0 mmol/L (p < 0.05). Dialysate glucose G2-G7 oligomers increased due to increase of G2-G4 metabolites while G6-G7 metabolites and higher Mw icodextrin fractions decreased. In plasma maltose and maltotriose (G2-G3 metabolites) increased while higher Mw icodextrin oligomers were almost undetectable. Dialysate amylase increased while plasma amylase decreased. Conclusions: Icodextrin resulted in linear increase of VD with sustained net UF lasting 16 h and with no significant difference between peritoneal transport types. In plasma, sodium and amylase declined, G2-G3 increased whereas larger icodextrin fractions were not detectable. In dialysate, icodextrin mass declined due to decrease of high Mw icodextrin fractions while low Mw metabolites, especially G2-G3, increased. The ability of icodextrin to provide sustained UF during very long dwells - which is usually not possible with glucose-based solutions - is especially important in anuric patients and in patients with fast peritoneal transport.


Arthroscopic treatment of shoulder ochronotic arthropathy: a case report and review of literature.
Alcaptonuria is an inherited hereditary metabolic disorder, which is associated with various systemic abnormalities and related to the accumulation of homogentisic acid and a derived melanine-like pigment in the connective tissues; the latter is termed ochronosis. We present the arthroscopic findings in the shoulder of a 58-year-old female with ochronotic arthropathy and discuss the role of arthroscopy in the diagnosis and management of this rare metabolic disorder.


Cytogenetic toxicity of antitumor platinum compounds in Fanconi's anemia.
Peripheral blood lymphocytes of patients with Fanconi's anemia (FA) were tested for their susceptibility to chromosome breakage by cis-platinum(II)-diamminedichloride [cis-Pt(II)], cis-platinum(IV)diamminetetrachloride [cis-Pt(IV)], and trans-platinum(IV)diamminetetrachloride [trans-Pt(IV)]. Low doses (0.1 microgram/ml) of the DNA-DNA cross-linking agents cis-Pt(II) and cis-Pt(IV) dramatically increased the chromosome breakage level in FA cultures without affecting the controls. The predominantly DNA-protein cross-linking compound trans-Pt(IV), however, was much less effective in producing chromosomal damage in FA. The differential response of FA cells to cis-Pt(IV) and trans-Pt(IV) suggests that the high susceptibility of FA to bifunctional cross-linking agents is due to an impairment of the cells to tolerate DNA-DNA cross-links, rather than DNA-protein cross-links.


Desquamative interstitial pneumonia with clinical, radiological and histologic correlation.
Respiratory bronchiolitis-associated interstitial lung disease (ILD), desquamative interstitial pneumonia (DIP), and pulmonary Langerhans cell histiocytosis are entities of smoking-related ILD. While clinically regarded as 2 separate forms of idiopathic interstitial pneumonia, DIP, and respiratory bronchiolitis-associated ILD are thought to be representing ends of a continuous spectrum of disease that primarily affects tobacco smokers. This case report presents a 53-year-old female patient who has 58 pack-year smoking history who has been experiencing a dry cough and epigastric pains for 2 years. Open-lung biopsy is performed and histopathology indicated smoking-related interstitial fibrosis. The patient did not stop smoking, which after a year leads to significant clinical deterioration with a notable decrease in diffusion for carbon monoxide capacity. Upon smoking cessation and treatment with corticosteroids, a significant clinical improvement is achieved. In smokers complaining of cough and reduced exercise tolerance and in whom evidence of interstitial fibrosis is demonstrated radiologically, DIP should be considered as a differential diagnosis. Smoking is the exclusive etiologic factor of pathogenesis of DIP.


Impacts of poly(lactic acid) microplastics on organic compound leaching and heavy metal distribution during hydrothermal treatment of sludge.
This study provides an in-depth examination of the role of poly(lactic acid) microplastics (PLA-MPs) during sludge treatment, particularly in relation to organic compound leaching and heavy metal distribution. Through the application of advanced analytical techniques such as Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), thermal analysis, and gas chromatography-mass spectrometry (GC-MS), the release of degradation byproducts was quantified, and the effects on organic compound leaching and heavy metal distribution were assessed. Specifically, the results demonstrated that PLA-MPs significantly impacted the hydrolysis reaction, with the pH value descending in pure water as the hydrothermal temperature escalated. At 140 °C, the hydrolysate contained 20.66 % propylene ester and 16.57 % lactic acid. Furthermore, an increase in total organic carbon (TOC) was observed with increasing temperature, with TOC content at 140 °C in water almost doubling from that at 120 °C and 130 °C. With respect to heavy metals, the presence of PLA-MPs influenced the migration of Cr(VI) between solid and liquid phases in sludge. Notably, after 180 °C hydrothermal treatment, the content of Cr(VI) in the liquid phase of sludge with PLA-MPs was 9.72 %, which is higher than that of sludge without PLA-MPs at 5.80 %. These findings underline the need to consider PLA-MPs' influence on organic compound leaching and heavy metal distribution during sludge treatment.


Distance to faults as a proxy for radon gas concentration in dwellings.
This research was done to demonstrate the usefulness of the local structural geology characteristics to predict indoor radon concentrations. The presence of geologic faults near dwellings increases the vulnerability of the dwellings to elevated indoor radon by providing favorable pathways from the source uranium-rich bedrock units to the surface. Kruskal-Wallis one-way analyses of variance by ranks were used to determine the distance where faults have statistically significant influence on indoor radon concentrations. The great-circle distance between the 640 spatially referenced basement radon concentration measurements and the nearest fault was calculated using the Haversine formula and the spherical law of cosines. It was shown that dwellings located less than 150 m from a major fault had a higher radon potential. The 150 m threshold was determined using Kruskal-Wallis ANOVA on: (1) all the basement radon measurements dataset and; (2) the basement radon measurements located on uranium-rich bedrock units only. The results indicated that 22.8% of the dwellings located less than 150 m from a fault exceeded the Canadian radon guideline of 200 Bq/m(3) when using all the basement radon measurements dataset. This percentage fell to 15.2% for the dwellings located between 150 m and 700 m from a fault. When using only the basement radon measurements located on uranium-rich bedrock units, these percentages were 30.7% (0-150 m) and 17.5% (150 m-700 m). The assessment and management of risk can be improved where structural geology characteristics base maps are available by using this proxy indicator.


A nucleoside transporter is functionally linked to ectonucleotidases in rat liver canalicular membrane.
Prevention of nucleoside loss in bile is physiologically desirable because hepatocytes are the main source of nucleosides for animal cells which lack de novo nucleoside biosynthesis. We have demonstrated a Na+ gradient-energized, concentrative nucleoside transport system in canalicular membrane vesicles (CMV) from rat liver by studying [3H]adenosine uptake using a rapid filtration technique. The Na(+)-dependent nucleoside transporter accepts purine, analogues of purine nucleosides and uridine; exhibits high affinity for adenosine (apparent Km, 14 microM); is not inhibited by nitrobenzylthioinosine or dipyridamole, and is present in CMV but not in rat liver sinusoidal membrane vesicles. Adenosine transport in right side-out CMV was substantially greater than with inside-out CMV. CMV also contain abundant ecto-ATPase and ecto-AMPase (5'-nucleotidase). These ectoenzymes were shown to degrade nucleotides into nucleosides which were conserved by the Na(+)-dependent nucleoside transport system.


Applying a test system for discriminating fetal from maternal cells.
The objectives of this study were to enhance and apply a simple system capable of testing the capacity of putative, gender-independent fetal cell markers, individually and in combination, to discriminate between fetal and maternal cells. Chorionic villi tissue obtained from 25 male pregnancies at 10 to 12 weeks' gestation served as the experimental group. Following removal of villi pieces for clinical use, unattached cells were collected by centrifugation of the CVS fluid, fixed in the tube, and used as a source of mixed fetal and maternal cells. Blood obtained from a fetus at 13 weeks' gestation served as a positive control. Peripheral blood from two adult males served as negative controls. Antibodies to three possible fetal markers were tested using immunohistochemical techniques: anti-Flk-1, anti-epsilon globin, and anti-CD71. Each antibody was used alone and in combination in conjunction with fluorescent in situ hybridization (FISH) of X and Y chromosomes to confirm that positively stained cells were in fact fetal in origin. On CVS samples, the average predictive value for anti-Flk-1 was 35.8%, 76.2% for anti-CD71, and 90.5% for anti-epsilon. The combination of anti-epsilon and anti-CD71 antibodies identifying a fetal cell was 87.2% and the combined use of single and double antibodies gave a value of 82.7%. The combination of anti-epsilon globin and anti-CD71 increased the sensitivity of identifying pure fetal blood cells from 63%, for anti-epsilon alone, and 67%, for anti-CD71 alone, to 86%. Although anti-Flk-1 has been reported to be a successful marker of fetal cells, the results in this test system did not support this finding. This work supports the use of CVS washings containing both fetal and maternal cells as a viable test system for assessing antigenic markers. The combination of anti-CD71 and anti-epsilon as fetal identifiers may increase the chances of identifying a fetal cell without compromising the predictive value.


Atorvastatin-induced hemorrhagic cystitis: a case report.
The first case of hemorrhagic cystitis due to atorvastatin for treatment of hyperlipidemia is reported. Hematuria resolved spontaneously with discontinuation of the drug.


Are torso asymmetry and torso displacements in a computer brace model associated with initial in-brace correction in adolescent idiopathic scoliosis?
Lack of initial in-brace correction is strongly predictive for brace treatment failure in adolescent idiopathic scoliosis (AIS) patients. Computer-aided design (CAD) technology could be useful in quantifying the trunk in 3D and brace characteristics in order to further investigate the effect of brace modifications on initial in-brace correction and subsequently long-term brace treatment success. The purpose of this pilot study was to identify parameters obtained from 3D surface scans which influence the initial in-brace correction (IBC) in a Boston brace in patients with AIS. Twenty-five AIS patients receiving a CAD-based Boston brace were included in this pilot study consisting of 11 patients with Lenke classification type 1 and 14 with type 5 curves. The degree of torso asymmetry and segmental peak positive and negative torso displacements were analyzed with the use of patients' 3D surface scans and brace models for potential correlations with IBC. The mean IBC of the major curve on AP view was 15.9% (SD = 9.1%) for the Lenke type 1 curves, and 20.1% (SD = 13.9%) for the type 5 curves. The degree of torso asymmetry was weakly correlated with patient's pre-brace major curve Cobb angle and negligible correlated with major curve IBC. Mostly weak or negligible correlations were observed between IBC and the twelve segmental peak displacements for both Lenke type 1 and 5 curves. Based on the results of this pilot study, the degree of torso asymmetry and segmental peak torso displacements in the brace model alone are not clearly associated with IBC.


Lipomatous ependymoma: report of a rare differentiation pattern with a comprehensive review of literature.
We report the case of a 13-year-old girl presenting with left-sided hemiparesis, altered sensorium and episodic headache with bouts of projectile vomiting. Imaging revealed a large heterodense intraventricular mass lesion displaying focal calcification and hyperintensity on T1- and T2- weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance images suggesting the presence of intratumoral fat. Histologically, the tumour showed sheets of glial cells, focal perithelial rosettes and individual cells showing fat vacuoles. The morphological impression was of an ependymoma with lipomatous differentiation. Glial fibrillary acid protein (GFAP) immunohistochemistry revealed positivity in the cytoplasmic processes of the tumour cells as well as in the cytoplasmic rim of the cells having an adipocytic appearance. S100 and vimentin were also immunoreactive. Ultrastructural studies confirmed the ependymal differentiation of the tumour and the presence of an osmiophilic fat component confirming the diagnosis. After 1 year of follow-up, the patient presented with similar complaints and MRI evidence of recurrence of the tumour. A comprehensive literature review revealed that half of the reported cases of this pattern recurred suggesting a possibly tenacious clinical course.


Relationship Between Explosive Strength Capacity of the Knee Muscles and Deceleration Performance in Female Professional Soccer Players.
The present study aimed to investigate the relationship between linear deceleration performance and explosive strength capacity of the knee muscles. Fourteen female professional soccer players completed the maximal sprint deceleration tests and knee flexor (KF) and knee extensor (KE) isokinetic concentric (240° and 60°.s-1) and eccentric contractions (30°.s-1). Linear deceleration performance was evaluated from horizontal breaking force (F H), power (P H), and impulse (I H) during a maximal linear deceleration. The peak torque (PT) of KF and KE, PT ratio between KF and KE (conventional and functional H/Q ratio), rate of torque development (RTD) for each muscle group, and RTD between KF and KE (RTD H/Q) were extracted from the isokinetic contractions. Pearson's correlation coefficients revealed that the eccentric (30°.s-1) and concentric (60°.s-1, 240°.s-1) KE peak torque, and the concentric KF peak torque (240°.s-1) were significantly correlated with FH, PH , and IH (-0.75<r<-0.54). Moreover, a significant correlation was found between KE RTD during eccentric contraction and FH , PH , and IH (-0.63<r<-0.54). Besides, a significant correlation was observed between RTD H/Q at 60°.s-1 and PH , IH (-0.61<r<-0.57). No significant relationship was observed between the H/Q ratio, KF RTD and deceleration performance. These main findings indicated the importance of the ability to quickly produce high KE eccentric torque, contributing to braking force production. Meanwhile, RTD H/Q should be assessed for its essential role in knee joint dynamic stability and can be a relevant index to determine deceleration performance.


Plasma clearances of branched-chain amino acids in control subjects and in patients with cirrhosis.
In an attempt to clarify the pathogenesis of the decreased branched-chain amino acid (BCAA) plasma concentrations in cirrhosis, the plasma clearances were measured in 7 patients with cirrhosis and in 7 age- and sex-matched control subjects. BCAA were given as prime-continuous infusions. The plasma clearances of valine, isoleucine, and leucine, calculated as infusion rate divided by steady state concentration, were low normal in cirrhotics despite hyperinsulinaemia, but different BCAA had different clearances (P less than 0.01). The endogenous basal appearance rates of BCAA, estimated by the basal concentrations multiplied by the plasma clearances, were lower in cirrhotics (P less than 0.025). The apparent theoretical volumes of distribution of BCAA, assessed by the ratio between the clearance and the concentration decay constant after infusion stop, were on average 67% of the total body weight, and were neither different among the three BCAA, nor between the two groups. The urea nitrogen synthesis rate did not increase significantly, suggesting that most of the infused BCAA nitrogen was taken up in peripheral tissues. The decreased concentration of BCAA in cirrhotics (394 +/- 81 mumol/l (mean +/- SD) in the present series vs 510 +/- 68 in controls; P less than 0.025) is not attributable to changes in plasma clearance. The most likely explanation is decreased afflux of BCAA into plasma.


Lottery incentives did not improve response rate to a mailed survey: a randomized controlled trial.
Our study aimed to examine the effect of an instant lottery ticket incentive on the response rate to a mailed questionnaire in a population of trauma patients. A randomized controlled trial at a major trauma center with 728 patients randomized into 2 groups prior to mailing of a questionnaire. One group of patients (Group A) had a sentence inserted into the cover letter stating that they would receive a $4 instant lottery ticket upon receipt of a completed questionnaire; Group B did not have an incentive. The response rate for both groups was measured after the initial mailing and at the end of the study. The results were analyzed using the X2 test to compare 2 proportions and a P value of .05 was considered significant. The early response rate in Group A was lower than in Group B, and the response rates for both groups were similar at final follow-up. The differences at both time periods were not statistically significant. The use of an instant lottery ticket incentive did not improve the response rate to a mailed questionnaire.


Plasma membrane association and preliminary characterization of Drosophila sperm surface glycosidases.
Previous studies have identified beta-N-acetylglucosaminidase (GlcNAc'ase) and (alpha-mannosidase activities on the Drosophila melanogaster sperm surface which may have a role in fertilization. The aim of this study was to investigate their linkage to the sperm plasma membrane. We verified that glycosidases are not peripherally adsorbed to the cell surface by evaluating their resistance to release by KI, by buffered salt solutions of high ionic strength or alkaline buffers. Glycosidases were released from the sperm surface by detergents and, only to a minor extent, by mild proteolysis. Differential detergent solubilization pointed out that Triton X-114 was the most effective releasing agent for GlcNAc'ase and CHAPS for mannosidase. No activity was released from the membrane by a phosphatidylinositol-specific phospholipase C (PI-PLC). The released forms were quite hydrophilic in phase separation experiments with Triton X-114. This finding indicates the presence of a hydrophobic domain limited to a single transmembrane helix or/and the presence of an extensive glycosylation. The use of a Con-A binding assay demonstrated that both the enzymes are glycosylated. The molecular weight of the released glycosidases estimated by gel filtration was 158 kDa for GlcNAc'ase and 317 kDa for mannosidase. These results suggest that Drosophila melanogaster GlcNAc'ase and mannosidase are mannosylated integral membrane proteins that would function as exoenzymes with their active sites accessible in the extracellular space.


Competency-based integrated practical examinations: Bringing relevance to basic science laboratory examinations.
The practical examinations in subject-based curriculum have been criticized for lack of relevance and clinical application. We developed competency-based integrated practical examinations (IPEs) for first two years incorporating basic science principles with clinical relevance in our integrated curriculum. To bring relevance to basic science laboratory practical examinations by conducting competency-based IPEs. IPEs were developed according to competency-based blueprinting for each integrated module. Clinical scenarios were used as triggers followed by tasks pertaining to laboratory tests, relevant physical diagnosis and ethics/professional aspects utilizing standardized patients. Checklists were developed for standardized marking. A feedback questionnaire and two focus group discussions were administered to a random group of students from both first and second year students. Faculty members' feedback was also recorded on a questionnaire. Almost all the students agreed that IPE was a useful experience. Eighty-nine percent agreed that it was a fair examination and elicited a lesser degree of psychological stress. Eighty-two percent agreed that IPE encouraged critical thinking and application of knowledge. However, students suggested better organization and longer duration of stations. Faculty members also liked the experience. In conclusion, IPEs were well-received and valued both by students and faculty members.


A comparison of malaria prevention behaviours, care-seeking practices and barriers between malaria at-risk worksite migrant workers and villagers in Northern Shan State, Myanmar-a mixed method study.
Migrant populations are at an increased risk of exposure to malaria due to their nature of work and seasonal migration. This study aimed to compare malaria prevention behaviours and care-seeking practices among worksite migrant workers and villagers in the malaria-at-risk areas of Eastern Myanmar close to the China border. A mixed method study was conducted in March 2019. The malaria-at-risk worksites in the four targeted townships, and villages located the nearest to these worksites were approached. Key stakeholders, such as worksite managers and village leaders, were interviewed. A total of 23 worksites, which employed 880 migrants and 447 locals, and 20 villages, which were homes for 621 migrants and 9731 locals, were successfully interviewed. Regarding malaria prevention behaviours, sleeping under a bed net was common among both worksites (74%) and villages (85%). In contrast, insecticide-treated nets/long-lasting insecticidal nets (ITN/LLIN) usage was much lower in the worksites than in the villages (39% vs 80%). Regarding care-seeking practices for febrile illness, self-medication was a popular choice for both worksite workers and villagers owing to the easy availability of western medicine. Moreover, local-belief-driven traditional practices were more common among villagers. For occasions in which fever was not relieved, both would seek health care from rural health centres, private clinics, or public hospitals. As for barriers, villagers mostly cited language barriers, which often lead to misunderstanding between health providers and them. In contrast, most of the worksites cited logistics issues as they were in remote areas with devastated road conditions and the routes to formal health facilities were not secure due to frequent armed conflicts. This study demonstrated that site-workers and villagers had different malaria prevention behaviours and care-seeking practices even though they resided in the same geographic area. Hence, it is important to recognize such differences for more effective intervention approaches.


Substitution at the indole 3 position yields highly potent indolecombretastatins against human tumor cells.
Resistance to combretastatin A-4 is mediated by metabolic modification of the phenolic hydroxyl and ether groups of the 3-hydroxy-4-methoxyphenyl (B ring). Replacement of the B ring of combretastatin A-4 by a N-methyl-5-indolyl reduces tubulin polymerization inhibition (TPI) and cytotoxicity against human cancer cell lines but cyano, methoxycarbonyl, formyl, and hydroxyiminomethyl substitutions at the indole 3-position restores potent TPI and cytotoxicity against sensitive human cancer cell lines. These highly potent substituted derivatives displayed low nanomolar cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies, and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was suggested by molecular modeling studies. Substituted combretastatins displayed higher potencies than the isomeric isocombretastatins and the highest potencies were achieved for the hydroxyiminomethyl (21) and cyano (23) groups, with TPI values in the submicromolar range and cytotoxicities in the nanomolar and subnanomolar range. Dose-response and time-course studies showed that drug concentrations as low as 1 nM (23) or 10 nM (21) led to a complete G2/M cell cycle arrest after 15 h treatment followed by a high apoptosis-like cell response after 48-72 h treatment. The P-glycoprotein antagonist verapamil increased 21 and 23 cytotoxicity to IC50 values of 10-10 M, and highly potentiated the cytotoxic activity in 100-fold of the CHO derivative (17), in A-549 human non-small cell lung cancer cells. The cyano substituted indolecombretastatin 23 is by itself highly potent against rather resistant HT-29 and A-549 cell lines. A 3,4,5-trimethoxyphenyl ring always afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.


Induction of sister-chromatid exchanges in human lymphocytes and Chinese hamster cells exposed to aflatoxin B1 and N-methyl-N-nitrosourea.
The effect of a 1-h exposure to aflatoxin B1 (AFB1) in inducing sister-chromatid exchange in Chinese hamster ovary (CHO) cells and human lymphocytes in the presence or absence of mixed function oxidase ("S9 mix") was compared. CHO cells were also exposed to a graded series of doses of N-methyl-N-nitrosourea, a powerful inducer of SCE whose action was independent of the presence or absence of S9 mix. CHO and human cells showed a close correlation in response to SCE induction by AFB1 and in both cell systems the additon of mixed function oxidases in the S9 mix resulted in a marked enhancement of action of AFB1.


Network topology metrics explaining enrichment of hybrid epithelial/mesenchymal phenotypes in metastasis.
Epithelial to Mesenchymal Transition (EMT) and its reverse-Mesenchymal to Epithelial Transition (MET) are hallmarks of metastasis. Cancer cells use this reversible cellular programming to switch among Epithelial (E), Mesenchymal (M), and hybrid Epithelial/Mesenchymal (hybrid E/M) state(s) and seed tumors at distant sites. Hybrid E/M cells are often more aggressive and metastatic than the "pure" E and M cells. Thus, identifying mechanisms to inhibit hybrid E/M cells can be promising in curtailing metastasis. While multiple gene regulatory networks (GRNs) based mathematical models for EMT/MET have been developed recently, identifying topological signatures enriching hybrid E/M phenotypes remains to be done. Here, we investigate the dynamics of 13 different GRNs and report an interesting association between "hybridness" and the number of negative/positive feedback loops across the networks. While networks having more negative feedback loops favor hybrid phenotype(s), networks having more positive feedback loops (PFLs) or many HiLoops-specific combinations of PFLs, support terminal (E and M) phenotypes. We also establish a connection between "hybridness" and network-frustration by showing that hybrid phenotypes likely result from non-reinforcing interactions among network nodes (genes) and therefore tend to be more frustrated (less stable). Our analysis, thus, identifies network topology-based signatures that can give rise to, as well as prevent, the emergence of hybrid E/M phenotype in GRNs underlying EMP. Our results can have implications in terms of targeting specific interactions in GRNs as a potent way to restrict switching to the hybrid E/M phenotype(s) to curtail metastasis.


Using chief complaints for syndromic surveillance: a review of chief complaint based classifiers in North America.
A major goal of Natural Language Processing in the public health informatics domain is the automatic extraction and encoding of data stored in free text patient records. This extracted data can then be utilized by computerized systems to perform syndromic surveillance. In particular, the chief complaint--a short string that describes a patient's symptoms--has come to be a vital resource for syndromic surveillance in the North American context due to its near ubiquity. This paper reviews fifteen systems in North America--at the city, county, state and federal level--that use chief complaints for syndromic surveillance.


Sample size determination based on Fisher's Exact Test for use in 2 x 2 comparative trials with low event rates.
A collection of sample size tables are presented for designing comparative trials when the event rates p1 and p2 are low. The tables are based on exact power calculations for Fisher's Exact Test. Both one-sided and two-sided alternative hypotheses are considered. A comparison is made between these sample sizes and those obtained by using popular asymptotic approximations.


Gonadotropin-releasing hormone from brains of reptiles: turtles (Pseudemys scripta) and snakes (Thamnophis sirtalis parietalis).
Gonadotropin-releasing hormone (GnRH)-like peptides were present in whole brain extracts of turtle (Pseudemys scripta) and snake (Thamnophis sirtalis parietalis) with higher content and concentration in the turtle brain. The peptides were identified by cross-reactivity profiles with four GnRH antisera and by retention times on reverse-phase high-pressure liquid chromatography (HPLC) compared with synthetic GnRH standards. Turtle brain extracts contained two HPLC peaks that cross-reacted with GnRH antisera; these peaks eluted from the HPLC in the same positions as chicken I and II GnRH. Snake brain extracts contained only one major HPLC peak (and two minor peaks in some brains) that cross-reacted with anti-GnRH sera; the major peak eluted with the same retention time as chicken I GnRH. Mammalian, salmon, and lamprey GnRH-like peptides were not detected. In extracts from both turtle and snake brains, the cross-reactivity profile of the HPLC peaks compared with those of synthetic chicken I and II GnRH showed a similar order of sensitivity with four antisera. It is likely that chicken I and II GnRH-like peptides were present in ancestral reptiles prior to the evolution of the three living reptilian subclasses of Anapsida (turtle), Lepidosauria (snake and lizard), and Archosauria (alligator). This assertion is based on the present demonstration and work by others showing that chicken I and II GnRH-like peptides are in turtle and alligator, chicken I is in snake, and chicken II is in lizard.


The mission is remission: health economic consequences of achieving full remission with antidepressant treatment for depression.
The aim of the present study was to determine the magnitude of the impact of treating depression to full remission on cost and health-related quality of life. In a naturalistic longitudinal survey recordings of resource use and quality of life were carried out among depressed patients treated with antidepressant therapy in 56 Swedish primary care clinics. We found that a total of 52% of the patients achieved full remission during the study period. Remitting patients had, on average, three outpatient visits less than non-remitting patients (p < 0.01), 22 fewer sick leave days (p = 0.01), which translated into a significantly lower total cost (Euro 2700) compared with non-remitting patients (p < 0.01). Health-related quality-of-life scores improved by 40% for remitting patients when compared with non-remitting ones (p < 0.01). We conclude that remission has a substantial health economic impact on patients treated for depression, which further strengthens the importance of aiming for full remission in the treatment of depression.


Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor.
This case report highlights the risk of nutritional supplements and misinformation obtained from the internet particularly for those on monamine oxdiase inhibitors (MAOIs). Despite sophisticated medical knowledge, this patient, who was taking an MOAI and complying with a tyramine-free diet, used a supplement of hydroxytryptophan that along with the MAOI appears to have precipitated mania, despite no personal or familial history of bipolar disorder.


Graphene-ophicalcite heterogeneous composite sponge for rapid hemostasis.
Synergistic functionalization of interface coagulation stimulation and liquid absorption capacity is the key to improve the hemostatic efficiency of hemostats. Herein, we prepared a graphene-ophicalcite (OPH) heterogeneous composite sponge (GOCS) by using the heterogeneous gradient composite strategy. The sponge took cross-linked graphene sponge (CGS) as the main skeleton, allowing the OPH to be controllably positioned on the surface of GOCS. The heterogeneous strategy gave full play to the advantages of the material. On the one hand, GOCS had excellent liquid absorption ability, which enriched blood cells and other coagulation components at the wound interface after contacting blood. On the other hand, the OPH at the interface obviously activated platelets and rapidly triggered coagulation cascade reactions, exhibiting fast response and feedback characteristics for coagulation signals. Under the synergistic effects, the blood clotting index value of GOCS was reduced to 33.87 ± 9.97%, which was significantly lower than those of OPH (46.33 ± 16.85%) and CGS (67.53 ± 5.35%). Importantly, GOCS rapidly stopped bleeding within 51 s in the rat femoral artery model, suggesting its great potential in the field of hemostasis. Therefore, this study provides a new idea for the design and preparation of hemostatic materials via heterogeneous strategy.


Structural homology between hard alpha-keratin and the intermediate filament proteins desmin and vimentin.
Although it has been assumed that the microfibrils in hard -keratin are members of the class of structures known as intermediate filaments (IF), no firm chemical evidence relating the low-sulfur proteins in hard -keratin to other IF proteins has yet been published. We now present primary sequence data for two components from wool keratin which show striking similarities with two IF proteins, desmin and vimentin. The sequences show marked homology, a heptad repeat and a 9.5-residue periodicity in the linear disposition of the acidic and the basic residues. These data thus provide the first evidence that the low-sulfur proteins in hard -keratin and the other IF proteins do indeed have both a similar structure and a common evolutionary origin.


Megacolon complicating pregnancy. A case report.
Megacolon is a rare complication of pregnancy. Its presence during pregnancy may require genetic counseling, anticipation of dystocia and a search for an underlying serious medical disease, the presenting symptom of which may be chronic constipation. Pharmacologic treatment is not usually successful, and the colon can best be kept clean with enemas and disimpaction.


Farm-Level Agricultural Biodiversity in the Peruvian Andes Is Associated with Greater Odds of Women Achieving a Minimally Diverse and Micronutrient Adequate Diet.
The extent to and mechanisms by which agricultural biodiversity may influence diet diversity and quality among women are not well understood. We aimed to 1) determine the association of farm-level agricultural biodiversity with diet diversity and quality among women of reproductive age in Peru and 2) determine the extent to which farm market orientation mediates or moderates this association. We surveyed 600 households with the use of stratified random sampling across 3 study landscapes in the Peruvian Andes with diverse agroecological and market conditions. Diet diversity and quality among women were assessed by using quantitative 24-h dietary recalls with repeat recalls among 100 randomly selected women. We calculated a 10-food group diet diversity score (DDS), the Minimum Dietary Diversity for Women (MDD-W) indicator, probability of adequacy (PA) of 9 micronutrients by using a measurement-error model approach, and mean PA (MPA; mean of PAs for all nutrients). Agricultural biodiversity was defined as a count of crop species cultivated by the household during the 2016-2017 agricultural season. In regression analyses adjusting for sociodemographic and agricultural characteristics, farm-level agricultural biodiversity was associated with a higher DDS (incidence rate ratio from Poisson regression: 1.03; P < 0.05) and MPA (ordinary least-squares β-coefficient: 0.65; P < 0.1) and higher odds of achieving a minimally diverse diet (MDD-W: OR from logistic regression: 1.17; 95% CI: 1.11, 1.23) and a diet that met a minimum threshold for micronutrient adequacy (MPA >60%: OR: 1.21; 95% CI: 1.10, 1.35). Farm market orientation did not consistently moderate these associations, and in path analyses we observed no consistent evidence of mediation of these associations by farm market orientation. Farm-level agricultural biodiversity was associated with moderately more diverse and more micronutrient-adequate diets among Peruvian women. This association was consistent across farms with varying levels of market orientation, although agricultural biodiversity likely contributed to diets principally through subsistence consumption.


Changes in labor patterns over 50 years.
The objective of the study was to examine differences in labor patterns in a modern cohort compared with the 1960s in the United States. Data from pregnancies at term, in spontaneous labor, with cephalic, singleton fetuses were compared between the Collaborative Perinatal Project (CPP, n = 39,491 delivering 1959-1966) and the Consortium on Safe Labor (CSL; n = 98,359 delivering 2002-2008). Compared with the CPP, women in the CSL were older (26.8 ± 6.0 vs 24.1 ± 6.0 years), heavier (body mass index 29.9 ± 5.0 vs 26.3 ± 4.1 kg/m(2)), had higher epidural (55% vs 4%) and oxytocin use (31% vs 12%), and cesarean delivery (12% vs 3%). First stage of labor in the CSL was longer by a median of 2.6 hours in nulliparas and 2.0 hours in multiparas, even after adjusting for maternal and pregnancy characteristics, suggesting that the prolonged labor is mostly due to changes in practice patterns. Labor is longer in the modern obstetrical cohort. The benefit of extensive interventions needs further evaluation.


Carbapenemase-producing Enterobacterales in solid organ transplantation: Tip of the iceberg?
A liver transplant recipient developed a urinary tract infection with Citrobacter freundii complex and Klebsiella aerogenes, both producing dual carbapenemases (KPC-3/NDM-1). Whole-genome sequencing suggested plasmid transfer between organisms. Silent plasmid transmission highlights emergent threats to infection prevention, with implications for screening and antimicrobial stewardship.


The effect of hyperthermia on ornithine decarboxylase activity in different rat tissues.
Hyperthermia produced a decrease of ornithine decarboxylase activity in different tissues of adult rats. The fall in ornithine decarboxylase was dependent on time of exposure and temperature. The decay of ornithine decarboxylase activity in liver, brain, kidney, heart, spleen and testes was rather similar. The t1/2 for liver ornithine decarboxylase determined by the hyperthermic treatment (40 degrees ambient temperature) was 20 min. Ornithine decarboxylase activity was recovered in all tissues exposed to the hyperthermic shock after a period of 4 hours, although the degree of recovery was dependent on the type of tissue. The effect that hyperthermia produces on ornithine decarboxylase activity in rats could be related to an inhibition in the synthesis of active enzyme rather than to a specific degradation or inactivation of ornithine decarboxylase molecule.


Targetoid hemosiderotic hemangioma.
A case of targetoid hemosiderotic hemangioma on the buttock of a 20-year-old pregnant woman is presented. Eight cases of this newly-described entity were initially reported by Santa Cruz and Aronberg in 1988. It is important to distinguish these vascular lesions from Kaposi's sarcoma, epithelioid hemangioma, and progressive lymphangioma.


Induction and immunolocalization of manganese superoxide dismutase in acute acetic acid-induced colitis in the rat.
Oxygen radicals and reactive oxygen species play an important role in inflammatory episodes in the bowel. Nonetheless, little is known about the regulation of colonic superoxide dismutases and key antioxidant enzymes with cytoprotective and radical detoxifying properties. The aim of this study was to examine the regulation of manganese superoxide dismutase (SOD) in acute acetic acid-induced colitis. Colitis was induced in adult rats by the rectal administration of 5% acetic acid. Total RNA and protein were isolated from the inflamed colon from 1 to 24 hours after the induction of colitis. MnSOD messenger RNA and protein levels were evaluated by Northern and Western analyses, respectively. MnSOD protein was localized in cross sections of the colon by immunocytochemistry. MnSOD messenger RNA levels showed a rapid 14-96-fold induction in response to acetic acid administration. Western analysis showed a 22-49-fold induction in MnSOD protein levels. Immunocytochemistry showed induction of MnSOD protein, specifically in smooth muscle cells, epithelial cells at the base of the glands, and myenteric plexus neurons. MnSOD messenger RNA and protein levels are rapidly induced following the inflammatory insult, implicating a role for MnSOD in the acute phase of colonic inflammation. We suggest that induction of MnSOD in specific cell types may have a cytoprotective function.


Lithium ions and the release of transmitter at the frog neuromuscular junction.
1. Transmitter release has been examined at the frog neuromuscular junction when all or part of the Na of the Ringer is replaced by Li ions. 2. No immediate change occurs in either the mean quantal content of the end-plate potential or the miniature end-plate potential frequency on changing to Li Ringer but over the following hour both these quantities increase by more than two orders of magnitude. 3. During thefirst 30-40 min of an exposure to Li-Ringer the m.e.p.p. frequency rises exponentially with a time constant of 10 min, and the mean quantal content of the e.p.p. grows by addition of extra evoked quanta, the increment rising exponentially with a time constant the same as that of the m.e.p.p. frequency. 4. Following this initial period in Li-Ringer the m. e.p.p. frequency accelerates to a peak of several hundred quanta per second and then declines slowly over the next few hours. Just before the m.e.p.p.frequency peak the conduction velocity of the presynaptic action potential declines and shortly afterwards synaptic transmission fails as the action potential no longer conducts into the terminals. 5. The rise in the m.e.p.p. frequency during the first 30-40 min is independent of the [Ca-2+]o. At subsequent times before the peak external Cabecomes progressively more effective in accelerating the m.e.p.p. frequency and in the presence of 1mM-EGTA spontaneous release stabilizes at 60-80 quanta/sec. 6. The [Li-+]o strongly influences the rate of increases in both evoked and spontaneous release but not their extent; replacing only half the Na of the Ringer by Li increases the time constants of the increases to about 30 min. 7. Rises in the m.e.p.p. frequency can be irreversibly accelerated by tetanizing the nerve in a Li-Ringer in which the Ca has been chelated by EGTA. The extent of the increases in the m.e.p.p. frequency is dependent on the number of pulses in the tetanus and is little affected by the frequency of stimulation. Accumulation of Li ions inside the presynaptic terminals probably underlies the changes in spontaneous release. 8. When only 10 percent of the Na of the Ringer is replaced by Li-+ ions the magnitude of post-tetanic potentiation of the e.p.p. and of the post-tetanic rise in the m.e.p.p. frequency is increased. Under these conditions changes in facilitation of the e.p.p. are small. 9. Various mechanisms by which Li could alter transmitter release are discussed and it is suggested that intracellular Ca sequestering mechanisms of the presynaptic terminals are affected when an end-plate is exposed to Li-Ringer.


Jitter of the stimulated motor axon.
Electrical microstimulation of motor axons in conjunction with single fiber EMG (SFEMG) is increasingly used to measure the jitter of the motor endplates. This study examines the jitter of the stimulation site on the axon when stimulus strength is at threshold. In the absence of spurious blocking, this was found to be 5 microseconds on the average. With intermittent blocking, however, a mean additional jitter of 40 microseconds was obtained. The latter is considered to result from changing propagation velocity in the muscle fiber due to irregularity of activation rate. In clinical jitter studies, inadvertent threshold stimulation can result in significant error when associated with intermittent blocking.


Annual cycle of pituitary and plasma gonadotropins and plasma sex steroids in a wild population of the toad, Bufo japonicus.
Pituitary and plasma gonadotropins and plasma sex steroids of free-living toads, Bufo japonicus, were measured monthly from March 1981 to February 1982 and examined in relation to gonadal cycles. Toads were captured at Mizuno, Saitama Prefecture. Individual blood samples were collected by cardiac puncture within 3 min of capture in the field. In males, testicular weight was maximal in August. Plasma follicle-stimulating hormone (FSH) levels changed in association with testicular weight. Plasma androgen levels showed a small peak in November and a large peak in March just prior to breeding. Plasma luteinizing hormone (LH) levels changed in parallel with plasma androgen levels. In females, neither plasma FSH nor LH alone were correlated significantly with ovarian weight. However, ovarian and oviductal weights both correlated significantly with plasma steroid levels. Plasma estradiol levels showed a sharp peak in March, followed by a rapid decrease to the minimum in April. A gradual increase of estradiol occurred from July to November in parallel with an increase in ovarian weight. Changes in plasma progesterone and androgen levels in females resembled those for estradiol. However, the changes in progesterone were not so marked as in estradiol. Plasma androgen levels in females were especially high between January and March. In both sexes, the pituitary gonadotropin contents changed in parallel with plasma levels of both FSH and LH. The pituitary almost always contained more LH than FSH, while the reverse was true in the plasma in both sexes. In addition, plasma FSH levels increased markedly in early summer when plasma LH remained unchanged (males) or increased only slightly (females). These results indicate that the toad may serve as excellent material for the study of differential control of FSH and LH secretion.


Diet, exercise, and pharmacotherapy for sarcopenia in people with diabetes.
Diabetes prevalence is increasing rapidly in older people, and sarcopenia is prevalent as a novel complication, particularly in patients with type 2 diabetes mellitus (T2DM). Therefore, sarcopenia prevention and treatment in these people is necessary. Diabetes accelerates sarcopenia through several mechanisms, such as hyperglycemia, chronic inflammation and oxidative stress. The effects of diet, exercise, and pharmacotherapy on sarcopenia in patients with T2DM need to be considered. In diet, low intake of energy, protein, vitamin D, and ω-3 fatty acid are associated with sarcopenia risk. In exercises, although intervention studies in people, especially older and non-obese patients with diabetes, are few, accumulating evidence shows the usefulness of exercise, particularly resistance exercise for muscle mass and strength, and aerobic exercise for physical performance in sarcopenia. In pharmacotherapy, certain classes of anti-diabetes compounds have possibility of preventing sarcopenia. However, much data on diet, exercise, and pharmacotherapy were obtained in obese and non-elderly patients with T2DM, demanding actual clinical data on non-obese and older patients with diabetes.


Comparative evaluation of the diagnostic performance of autofluorescence and diffuse reflectance in oral cancer detection: a clinical study.
Autofluorescence (AF) and diffuse reflectance (DR) spectroscopic techniques have shown good diagnostic accuracies for noninvasive detection of oral cavity cancer. In the present study, AF and DR spectra recorded in vivo from the same set of sites in 65 patients were analyzed using Principal component analysis (PCA) and linear discriminant analysis (LDA). The effectiveness of these two techniques was assessed by comparison with gold standard and their discrimination efficiency was determined from the area under the receiver operator characteristic (AUC-ROC) curve. Analysis using a DR technique shows a higher AUC-ROC of 0.991 as against 0.987 for AF spectral data.


HIF-1α immunohistochemical expression in decidual cells, villous and extravillous trophoblast in placentas from pregnancies complicated with preeclampsia.
Etiology of preeclampsia (PE) remains unknown despite it being the leading cause of maternal and neonatal morbidity and mortality worldwide. PE placentas show signs of chronic oxidative stress, therefore we set to investigate the HIF-1α immunohistochemical expression in PE placentas. For the first time presented study reported on significantly higher HIF-1α immunohistochemical expression in all of the placental segments; villous trophoblast (VTB), decidual cells (DC) and extravillous trophoblast (EVTB) in the PE placentas compared to placentas from normal pregnancies. The further studies on the subject are necessary in order to understand the mechanisms behind elevated HIF-1α immunohistochemical levels in PE.


Diffusion tensor imaging of the median nerve in recurrent carpal tunnel syndrome - initial experience.
To investigate median nerve structure in patients with recurrent carpal tunnel syndrome (CTS) using diffusion tensor imaging (DTI) and to relate DTI changes to anatomical MRI and to measures of median nerve function. Median nerve structure was quantified according to DTI in patients with recurrent CTS and in healthy controls of similar age. Anatomical MRI was used to identify the presence of nerve compression and fibrosis. Median nerve function was measured using electromyography, a force-tracking task (accuracy of precision grip control) and clinical measures. Patients showed reduced apparent diffusion coefficient (ADC), reduced axial diffusivity (AD) and radial diffusivity (RD) along the median nerve compared with controls (P < 0.001). Patients with endoneural fibrosis had the greatest reductions in ADC and in RD. ADC and AD correlated positively with nerve conduction velocity (R = 0.54 and R = 0.68, respectively) and fractional anisotropy correlated negatively with error during force-tracking (R = -0.58). A specific pattern of DTI changes in the median nerve was identified in patients with recurrent CTS. Fibrosis may be underlying these structural changes. The correlations with nerve conduction velocity and accuracy of force control suggest that DTI is a promising technique in the study of median nerve structure in recurrent CTS. • Diffusion tensor imaging (DTI) offers further possibilities in musculoskeletal magnetic resonance imaging. • DTI reveals median nerve changes in recurrent carpal tunnel syndrome. • DTI changes were greater with signs of median nerve fibrosis. • DTI parameters correlated with nerve conduction and force control measures. • DTI is a promising technique in recurrent carpal tunnel syndrome.


Downregulation of PIK3IP1 in retinal microglia promotes retinal pathological neovascularization via PI3K-AKT pathway activation.
Retinal pathological neovascularization involves endothelial cells, pericytes, photoreceptor cells, ganglion cells, and glial cells, whose roles remain unclear. Using the Scissor algorithm, we found that microglia are associated with formation of fibrovascular membranes and can promote pathological neovascularization. GO and KEGG results showed that PI3K-AKT pathway activation in retinal microglia was associated with pathological neovascularization, and PIK3IP1 was associated with retinal microglia activation. Then we used PCR, Western blot and Elisa techniques to confirm that the expression of VEGFA, FGF2, HGFα and MMP9 was increased in microglia after Lipopolysaccharide (LPS) induction. We also used cell flow cytometry and OIR models to verify the role of PI3K-AKT pathway and PIK3IP1 in microglia. Targeting of PIK3IP1 regulated the activation of the PI3K-AKT pathway in microglia, microglia function activation, and pro-angiogenic effects. These findings reveal the role of M1-type microglia in pathological neovascularization and suggests that targeting the PI3K-AKT pathway in microglia may be a new strategy for treating retinal pathological neovascularization.


Two novel techniques to screen Abies seedlings for resistance to the balsam woolly adelgid, Adelges piceae.
Since its introduction into the Southern Appalachians in the 1950s, the balsam woolly adelgid, Adelges piceae Ratzeburg (Hemiptera: Adelgidae), has devastated native populations of Fraser fir, Abies fraseri (Pursh) Poir. (Pinales: Pinaceae), and has become a major pest in Christmas tree plantations requiring expensive chemical treatments. Adelges piceae-resistant Fraser fir trees would lessen costs for the Christmas tree industry and assist in the restoration of native stands. Resistance screening is an important step in this process. Here, four studies directed toward the development of time- and cost-efficient techniques for screening are reported. In the first study, three methods to artificially infest seedlings of different ages were evaluated in a shade-covered greenhouse. Two-year-old seedlings had much lower infestation levels than 7 year-old seedlings. Placing infested bark at the base of the seedling was less effective than tying infested bark to the seedling or suspending infested bolts above the seedling. Although the two latter techniques resulted in similar densities on the seedlings, they each have positive and negative considerations. Attaching bark to uninfested trees is effective, but very time consuming. The suspended bolt method mimics natural infestation and is more economical than attaching bark, but care must be taken to ensure an even distribution of crawlers falling onto the seedlings. The second study focused on the density and distribution of crawlers falling from suspended bolts onto paper gridded into 7.6 × 7.6 cm cells. Crawler density in a 30 cm band under and to each side of the suspended bolt ranged from 400 to over 3000 crawlers per cell (1 to 55 crawlers per cm²). In the third study, excised branches from 4 year-old A. fraseri and A. vetchii seedlings were artificially infested with A. piceae to determine whether this technique may be useful for early resistance screening. The excised A. fraseri branches supported complete adelgid development (crawler to egg-laying adult), and very little adelgid development occurred on A. vetchii branches. The fourth study compared infestation levels and gouting response on excised versus intact branches of 4 year-old A. fraseri seedlings from three different seed sources, and excised branches from 4 year-old and 25 year-old trees. There were no differences in infestation levels between excised versus intact branches nor in very young versus mature trees; gouting response was observed only on intact branches.


Spanish Heart Transplantation Registry. 26th Official Report of the Spanish Society of Cardiology Working Group on Heart Failure and Heart Transplantation (1984-2014).
We present the characteristics and outcomes of heart transplantation in Spain since it was first performed in 1984. A descriptive analysis of the characteristics of recipients, donors, the surgical procedure, and the outcomes of heart transplantations performed in Spain until 31 December 2014. In 2014, 266 procedures were performed, making a time series of 7289 transplantations. The temporal analysis confirmed a significant worsening of the clinical profile of recipients (higher percentage of older patients, patients with severe renal failure, insulin-dependent diabetes, previous cardiac surgery, and previous mechanical ventilation), of donors (higher percentage of older donors and greater weight mismatch), and of the procedure (higher percentage of emergency transplantations, reaching 41.4% in 2014, and ischemia time>240min). Mechanical assist devices were used less than in 2013; in 2014 they were used in 18.8% of all transplant recipients. Survival at 1, 5, 10, and 15 years was 76%, 65%, 52%, and 38%, respectively, and has remained stable since 1995. Cardiac transplantation activity in Spain has remained stable in recent years, at around 250 procedures per year. Despite a clear deterioration in donor and recipient characteristics and surgical times, the mortality outcomes have remained comparable to those of previous periods in our environment. The growing use of circulatory assist devices before transplantation is also confirmed.


Tegument changes of Schistosoma japonicum and Schistosoma mansoni in mice treated with artemether.
To study the effect of artemether (Art) on the tegument of schistosomes. Mice infected with S japonicum cercariae for 7 and 35 d, or with S mansoni cercariae for 49 d were treated intragastrically with Art 200-300 mg.kg-1.d-1 for 2 d. Schistosomes were collected in groups of 2 mice at various intervals after medication for scanning electron microscopic observation. The tegumental changes induced by Art appeared to be similar in S japonicum and S mansoni: swelling and fusion of tegumental surfaces, vesicle formation and collapse of discoid-like sensory structures. In S japonicum the emergence of tegumental alterations was earlier in 7-d-old schistosomulae than that in 35-d-old adult worms. Art injured the teguments of S japonicum and S mansoni.


Does self-rated health predict death in older adults with depressive symptoms?
We analysed a prospective cohort study to determine (1) if self-rated health (SRH) predicts mortality in older adults with and without depressive symptoms, and (2) to determine if there is an interaction between SRH and depressive symptoms on mortality. We followed 1,751 community-dwelling adults aged 65 and older over five years. Measurements included age, gender, education, the Center for Epidemiological Studies-Depression (CES-D), SRH, the Modified Mini-Mental State Examination (3MS), and the Older Americans Resource Survey (OARS). Our outcome measure was time to death. Analyses were conducted in those with, and those without, depressive symptoms. We constructed Cox regression models with an interaction term for the CES-D and SRH. The hazard ratio (HR) for mortality was 1.63 for those with depressive symptoms; it was 1.68 for those without. No significant interaction was found between depressive symptoms and SRH for mortality.


Effects of salinity on gills' chloride cells, stress indices, and gene expression of Asian seabass (Lates calcarifer, Bloch, 1790).
A 2-week research was carried out to assess water salinity (WS) effects including 0, 15, 35, and 50‰ on osmoregulatory mechanisms and stress indices in Asian sea bass (34.4 g) juveniles. Except for fish reared at 50‰, in the other treatments, it gradually decreased to the prescribed WS during a 10-day period (- 5‰ a day). After a 10-day acclimation period, fish were reared at the prescribed WS for 2 weeks. Fish reared at 15 and 35‰ had higher chloride cell (CC) counts in the interlamellar region. The number of CC in the interlamellar region elevated with increment of WS up to 35‰, but they were pronouncedly reduced in 50‰ group. The diameter of CC in the interlamellar region was not affected by WS. The smallest nucleus diameter of CC in the interlamellar region was observed in fish reared at 15‰ (P < 0.05). The largest and the smallest amounts of serum aspartate aminotransferase were observed in fish reared at freshwater and 15‰, respectively. Fish reared at 35‰ had the highest serum sodium and potassium contents. Serum chloride content and total osmolality increased with increment of WS (P < 0.05). Serum cortisol and glucose contents gradually increased with elevation of WS up to 35‰; then, their contents remarkably decreased. The relative expression of insulin like growth factor-1 in the liver of fish reared at 35‰ was strikingly higher than that in the other groups. The relative expression of HSP70 gene in fresh water group was pronouncedly elevated compared to other treatments. The relative expression of interleukin-1β in 15 and 35‰ groups was higher than that in the other groups; however, the relative expression of lysozyme gene in the liver of fish reared at fresh water was pronouncedly lower than that in the other treatments. The results of this study suggested rearing L. calcarifer at 15‰ closer to the isosmotic point and better provide its welfare.


Endothelial biomarkers and platelet reactivity on ticagrelor versus clopidogrel in patients after acute coronary syndrome with and without concomitant type 2 diabetes: a preliminary observational study.
Pleiotropic effects have been implicated in clinical benefits of ticagrelor compared to thienopyridine P2Y12 antagonists. There are conflicting data regarding effects of ticagrelor vs. thienopyridine P2Y12 blockers on endothelial function. Our aim was to compare endothelial biomarkers and their relations with platelet reactivity in real-world patients after acute coronary syndrome (ACS) on maintenance dual antiplatelet therapy (DAPT) with ticagrelor or clopidogrel stratified by diabetes status. Biochemical indices of endothelial dysfunction/activation and platelet reactivity by multiple electrode aggregometry were compared in 126 stable post-ACS subjects (mean age: 65 ± 10 years, 92 men and 34 women), including patients with (n = 61) or without (n = 65) coexistent type 2 diabetes (T2DM) on uneventful maintenance DAPT with either ticagrelor (90 mg b.d.) or clopidogrel (75 mg o.d.) in addition to low-dose aspirin. Exclusion criteria included a complicated in-hospital course, symptomatic heart failure, left ventricular ejection fraction < 40% and relevant coexistent diseases except for well-controlled diabetes, mild renal insufficiency or hypertension. Clinical characteristics were similar in patients on ticagrelor (n = 62) and clopidogrel (n = 64). The adenosine diphosphate-induced platelet aggregation and circulating soluble P-selectin (sP-selectin) were decreased in ticagrelor users irrespective of T2DM status (p < 0.001 and p < 0.01 for platelet reactivity and sP-selectin, respectively). Plasma levels of soluble vascular cell adhesion molecule-1 (sVCAM-1) were lower in T2DM subjects on ticagrelor vs. clopidogrel (758 ± 162 vs. 913 ± 217 µg/L, p < 0.01). In contrast, plasma sVCAM-1 was similar in non-diabetic patients on ticagrelor and clopidogrel (872 ± 203 vs. 821 ± 210 µg/L, p > 0.7). The concentrations of sE-selectin, monocyte chemoattractant protein-1 and asymmetric dimethylarginine did not differ according to the type of P2Y12 antagonist regardless of T2DM status. Platelet reactivity was unrelated to any endothelial biomarker in subjects with or without T2DM. Our preliminary findings may suggest an association of ticagrelor-based maintenance DAPT with favorable endothelial effects compared to clopidogrel users in stable post-ACS patients with T2DM. If proven, this could contribute to more pronounced clinical benefits of ticagrelor in diabetic subjects.


Characterization of a novel variant allele, HLA-B*56:04:05, identified in a Chinese Han individual.
The novel HLA-B *56:04:05 allele differs from its most closely related allele B*56:04:01:01 in exon 4.


Calciuria and preeclampsia: a case-control study.
Calciuria has been reported to decrease in preeclampsia. We compared calciuria among groups of normal, hypertensive and preeclamptic pregnant women, and assessed its correlation with the severity of the disease. We conducted a case-control study of mild and severe preeclampsia, chronic hypertension, and normal pregnancy, with 14 patients in each group. The groups were analyzed by one-way anova (variance analysis) for symmetrical distribution and Kruskal-Wallis test for asymmetrical distribution when comparing quantitative variables, and by crossed tables when comparing qualitative variables. There were statistically significant differences between the groups when comparing severe preeclampsia with chronic hypertension, and severe preeclampsia with the control group (P < 0.0001). The calciuria medians were 81.5 mg/24 h for severe preeclampsia, 118 mg/24 h for mild preeclampsia, 226 mg/24 h for chronic hypertension, and 272 mg/24 h for the control group. In a ROC (receiver operating characteristic) curve analysis, the best cutoff point for preeclampsia diagnosis was 167 mg/24 h, with a sensitivity of 75% and a specificity of 85%. The outcomes were more severe as the level of calciuria dropped. Measurement of calciuria can differentiate between severe preeclampsia and chronic hypertension, and hypocalciuria is also a marker for disease severity.


Anti-TNFα drug levels in patients with rheumatoid arthritis and spondyloarthritis.
Knowledge of the levels of anti-TNFa drugs can modify treatment in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). To compare the levels of anti-TNFa in patients with RA vs SpA, in different clinical situations. A retrospective, observational study was conducted. Levels of anti-TNFa and the presence of anti-drug antibodies were measured in consecutively selected patients, using the ELISA technique. Fifty-three, 73 and 78 patients treated with infliximab, adalimumab and etanercept were studied, respectively. The median drug levels in patients using standard doses were infliximab 2.2 µg/mL (1.4-5.2), adalimumab 4.9 µg/mL (0.8-8.9) and etanercept 3.1 µg/mL (2.3-4.4). There were no differences in drug levels according to disease activity but we found differences in etanercept and infliximab levels according to DMARD use. Levels of anti-TNFa drugs will change with DMARD treatment.


Unique synergistic antiviral effects of Shufeng Jiedu Capsule and oseltamivir in influenza A viral-induced acute exacerbation of chronic obstructive pulmonary disease.
The aim of the present study was to investigate the synergistic effects and interactive mechanisms of Shufeng Jiedu Capsule (SFJDC) combined with oseltamivir in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) induced by the influenza A virus (IAV). The extraction of SFJDC was analyzed by UHPLC/ESI Q-Orbitrap Mass Spectrometry. Human bronchial epithelial cells were isolated from COPD (DHBE) bronchial tissues, co-cultured with IAV for 24 h, and were subsequently treated with SFJDC and/or oseltamivir. Cell viability was detected by MTT assay. A rat model of COPD with IAV infection was established and treated with SFJDC and/or oseltamivir. Interleukin (IL)-1β and IL-18 in serum and bronchoalveolar lavage fluid (BALF) were measured by ELISA. Additionally, mRNA and protein levels of NLRP3 inflammasome pathway were measured by quantitative real-time PCR and Western blotting, respectively. SFJDC and/or oseltamivir, at their optimal concentrations, had no significant cytotoxicity against DHBEs. The levels of NLRP3-inflammasome-associated components were significantly elevated after cells were inoculated with IAV, whereas the mRNA and protein levels of these components were significantly decreased after treatment with SFJDC and/or oseltamivir in vitro. Moreover, in vivo, the combination of SFJDC and oseltamivir improved survival rates, attenuated clinical symptoms, induced weight gain, alleviated lung damage, and significantly reduced IL-1β and IL-18 levels in serum and BALF, as well as reduced the expression levels of NLRP3-associated components and viral titers in lung homogenates. SFJDC combined with oseltamivir treatment significantly attenuated IAV-induced airway inflammation and lung viral titers. Hence, our findings may provide a novel therapeutic strategy for IAV-induced respiratory infection.


An independence of induced amnesia and emotional response.
A photograph of a nude was interpolated midway through a 30-item list. Recognition memory of items at various serial positions was measured by presenting 12 old and 12 new pictures on a test trial. Palmar conductance was also measured. Significantly decreased recognition memory and increased palmar conductance accompanied presentation of the picture of the nude. When the two measures were compared for individual subjects, however, no correlation was found. These data suggest that both responses are likely to occur to the presentation of the critical item but that the responses are independent.


GABAB receptors increase intracellular calcium concentrations in chromaffin cells through two different pathways: their role in catecholamine secretion.
The activation of GABAB receptors of adrenal chomaffin cells produces an increase of [Ca2+]i measured by fura-2 AM techniques. GABAB agonists 3-aminopropylphosphinic acid or (-)baclofen, at concentrations of 0.5 mM, increased basal Ca2+ values 332 +/- 60.9 and 306 +/- 40.5 nM, respectively, in cells suspended in a 2.5 mM Ca2+ buffer. The GABAB-induced increase of [Ca2+]i seemed to have two different components. The first was due to an entry from the extracellular medium mainly through L-type voltage-dependent Ca2+ channels as the dihydropiridine nifedipine 50 microM was able to decrease it more than 60%, while omega-conotoxin, which blocks N-type channels, did not produce any change in the GABAB-evoked Ca2+ increment. The second component was due to a release of Ca2+ from intracellular pools and was about one-third of the total GABAB-induced increase of [Ca2+]i. GABAB receptors stimulated inositol 1,4,5-trisphosphate-sensitive and not the caffeine-sensitive Ca2+ store. In a low-Ca2+ buffer after treatment with 2 microM angiotensin II, neither 0.5 mM 3-APPA nor baclofen were able to produce an additional increase of [Ca2+]i, whereas 4 mM caffeine had no effect on GABAB response. This intracellular Ca2+ mobilization could be due to inositol 1,4,5-trisphosphate accumulation produced by the activation of GABAB receptors. In fact, the specific agonists after 10 minutes incubation produced a dose-dependent increase of inositol 1,4,5-trisphosphate. The maximal effect was obtained at 100 microM baclofen and 3-APPA, and it was 3.63 +/- 0.75 and 3.2 +/- 1.5 times the basal levels (7.3 +/- 0.3 pmol/10(6) cells), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Why tandem mass spectrometry for trace analysis: Concepts of tandem analytical techniques.
The triple quadrupole mass spectrometer, typically in combination with a gas or liquid chromatograph (GC/MS/MS and LC/MS/MS), is perhaps the most iconic example today of a tandem analytical instrument. Here I present the concepts of tandem or hyphenated techniques for trace analysis (that is, the detection and/or quantitation of one or more analytes present in a mixture at low levels). This tutorial presents the principles of tandem trace analytical techniques such as GC/MS/MS and LC/MS/MS, including the capabilities and requirements for such tandem techniques, the role of sensitivity and selectivity in tandem techniques, ways to assess the "informing power" of these techniques, and a comparison of tandem techniques with individual techniques at high resolution. These points are illustrated with several examples of trace analysis using tandem analytical techniques. Several characteristics of the triple quadrupole have made it the "laboratory workhorse" for trace analysis, including the remarkable efficiency of the low-energy collision-induced dissociation (CID) process in a radiofrequency (RF)-only multipole collision cell, the ease of computer control, and the capability for rapid scanning, rapid switching from mass to mass, and high transmission efficiency, enabling a wide variety of MS/MS scans. The efficiency of selected reaction monitoring means that triple quadrupoles dominate MS/MS for detection and quantitation of targeted compounds. This special issue addresses the intriguing question of how the triple quadrupole mass spectrometer progressed from "bleeding edge" to "the laboratory workhorse" over the last 40 years. This tutorial on the principles of tandem trace analytical techniques provides perspectives and insights into answering that question and should help educate the novice and stimulate the sophisticate.


Emerging Organometallic Methods for the Synthesis of C-Branched (Hetero)aryl, Alkenyl, and Alkyl Glycosides: C-H Functionalization and Dual Photoredox Approaches.
Transition-metal-catalyzed C-H functionalization and photoredox nickel dual catalysis have emerged as innovative and powerful avenues for the synthesis of C-branched glycosides. These two concepts have been recently established and provide efficient and mild methods for accessing a series of valuable complex C-branched glycosides of great interest. Herein, recent developments in the synthesis of C-branched aryl/alkenyl/alkyl glycosides through these two approaches are highlighted.


SOLiD SAGE sequencing shows differential gene expression in jejunal lymph node samples of resistant and susceptible red deer (Cervus elaphus) challenged with Mycobacterium avium subsp. paratuberculosis.
This study compared in vivo lymph node gene expression levels between six young red deer that were either relatively resistant (R) or susceptible (S) to paratuberculosis following experimental challenge with Mycobacterium avium subsp. paratuberculosis. Intestinal lymph nodes were biopsied at 4, 12 and 50 weeks post challenge (pc) and parallel changes in histopathology, immunology and bacterial load monitored. SOLiD SAGE (serial analysis of gene expression) next generation sequencing of biopsied lymph node samples generated a total of 373 million transcript tags 26-28bp in length after filtering. A total of 36,632 unique transcripts were identified and 14,325 of these were able to be annotated. The copy number of each transcript was counted, averaged and compared for R and S animals (R-S). P values and False Discovery Rates (FDR) were calculated for each transcript. Genes differentially upregulated ≥2 fold (FDR<0.5) totalled 9, 40 and 32 in R animals (+ values) and 23, 164 and 47 in S animals (- values) at weeks 4, 12, and 50pc, respectively. Transcripts displaying greatest differential expression between R and S animals at each time point were IFIT2 (189 fold) and S100A8 (-32.7 fold) at week 4, LRR1 (52.7 fold), SERPINF2 (-214.6 fold) at week 12 and CEACAM8 (84.6 fold), and STK31 (-129.5 fold) at week 50, respectively. All 9 genes significantly upregulated at week 4 in R animals relate specifically to host defence and all involve Type I interferon stimulated genes. By contrast genes upregulated in S animals at week 4, relate predominantly to inflammation, but also involve adaptive immune responses, mitochondrial function and apoptosis regulation. At week 12, the genes differentially upregulated in R animals are linked predominantly to regulation of adaptive immunity and mucosal immunity, while many of the genes in S animals are associated with pro-inflammatory interleukins involved with innate and adaptive immunity. These correlated with greater lesion severity and higher MAP numbers in lymph nodes of S animals. By week 50 the number of upregulated genes declined in both groups. A number of genes upregulated in R animals appear to be associated with host resistance and regulation of adaptive immunity, especially CEACAM8. Genes upregulated in S animals involve antigen presentation (ENDOD1) and gut associated immune pathology (HSH2D). In conclusion, gene expression in jejunal lymph nodes of resistant and susceptible deer infer that the resistant phenotype is associated with pathways of adaptive immunity, while susceptibility is linked with upregulated non-protective pro-inflammatory responses, following experimental MAP infection.


[Status of the capillary endothelium of the lung in normovolemic perfusion of the organ through the system of the pulmonary artery].
Pulmonary perfusion for 30 min to the dog under conditions of normovolemia is not accompanied with any essential changes in parameters of alveolar capillaries endothelium. Just the opposite, transformation of endothelial lining of the peribronchial capillaries demonstrates possible disturbances of the liquor transport across the walls of these vessels. The volumetric part of the interstitial space near these capillaries increases, while in the alveolar septa it does not change. In lymph formation, flowing out of the lung, together with bronchial capillaries, blood capillaries of the alveoli must take part.


First-principles studies of HF and HCl adsorption over graphene.
In this paper, the adsorption characteristics of HF and HCl over graphene were studied by the first-principles method. The results showed that the adsorption of HCl over graphene was a weak chemical adsorption, while HF was a weak physical adsorption. The density of states showed that HCl and graphene at - 4.3 eV are relative to the Fermi level. At the same time, there is no obvious change and hybridization between HF-graphene system near the Fermi level. Furthermore, when HCl and HF molecules adsorbed over the graphene simultaneously, two optimal adsorption structures would be chosen to investigate how HCl and HF molecules jointly affected adsorption properties. The result showed that two gas molecules adsorbed over graphene could enhance the adsorption effect and influenced electronic distribution. Graphical abstract HF and HCl over graphene belong to weak physical and chemical adsorption separately. Two gases on graphene surface can be enhanced.


The PRINTEMPS study: protocol of a cluster-randomized controlled trial of the local promotion of a smartphone application and associated website for the prevention of suicidal behaviors in the adult general population in France.
Suicide constitutes a cause of death which could be prevented by e-health programs accessible to the general population. Effective promotion has the potential to maximize the uptake of such programs. However, few e-health programs have been combined with promotion campaigns. The primary objective of this trial is to assess the effectiveness of a tailored promotion, at a local level, of a mobile application and website offering evidence-based content for suicide prevention (the StopBlues program), and to compare the effectiveness of two types of local promotion in terms of their impact on suicidal acts. Secondary objectives focus on the effectiveness of the promotion in terms of the intensity of utilization of the StopBlues program, help-seeking behaviors and the level of psychological impairment of program users. This is a three-arm, parallel-group, cluster-randomized controlled trial, with before-and-after observation. Thirty-four clusters, corresponding to geographical areas sharing a common local authority in France, will be included. They will be randomly assigned to one of the following arms with a ratio of 1:1:1: a control group; a basic promotion group in which promotion of the StopBlues program will be done by local authorities; and an intensified promotion group in which basic promotion will be supplemented by an additional one in a general practitioner's waiting room. The primary outcome measure will be the number of suicidal acts within each cluster over a 12-month period following the launch of the intervention. Baseline data will be collected for each cluster over the 12-month period prior to the trial. Secondary outcomes will include length of use of the StopBlues program, measures of help-seeking behaviors and level of psychological distress among users of the program, as well as the cost-effectiveness and budgetary impact of its promotion. A more sustained promotion by local authorities will also be implemented after 12 months in the control group and assessed using the same outcome measures. This research should contribute to the sparse evidence base regarding the promotion of e-health programs and will support the wider delivery of the intervention evaluated if proven effective. ClinicalTrials.gov, ID: NCT03565562. Registered on 11 June 2018.


Formation of carbonated hydroxyapatite films on metallic surfaces using dihexadecyl phosphate-LB film as template.
Hydroxyapatite serves as a bioactive material for biomedical purposes, because it shares similarities with the inorganic part of the bone. However, how this material deposits on metallic surfaces using biomimetic matrices remains unclear. In this study, we deposited dihexadecyl phosphate, a phospholipid that bears a simple chemical structure, on stainless steel and titanium surfaces using the Langmuir-Blodgett (LB) technique; we employed the resulting matrix to grow carbonated hydroxyapatite. We obtained the calcium phosphate coating via a two-step process: we immersed the surfaces modified with the LB films into phosphate buffer, and then, we exposed the metal to a solution that simulated the concentration of ions in the human plasma. The latter step generated carbonated hydroxyapatite, the same mineral existing in the bone. The free energy related to the surface roughness and composition increased after we modified the supports. We investigated the film morphology by scanning electron and atomic force microscopies and determined surface composition by infrared spectroscopy and energy dispersive X-ray. We also studied the role of the surface roughness and the surface chemistry on cell viability. The surface-modified Ti significantly increased osteoblastic cells proliferation, supporting the potential use of these surfaces as osteogenic materials.


A cost effective SiO2-CaO-Na2O bio-glass derived from bio-waste resources for biomedical applications.
The present paper describes the in vitro bioactivity, cytocompatibility and degradation performance of SiO2-CaO-Na2O bio-glass synthesized using bio-waste. Egg shells and rice husk ash (RHA) bio-wastes were used as sources of calcium oxide (CaO) and silica (SiO2), respectively. Glass samples were obtained by melt-quenching technique. Bioactivity was studied using in vitro experiments in simulated body fluid (SBF), degradation behaviour was evaluated in Tris-HCl buffer solutions recommended by ISO 10993-14 standards and cytocompatibility was estimated using MTT assay. The formation of hydroxyapatite was characterized by XRD, FTIR and SEM-EDS after soaking the glass samples in SBF solution. XRD confirmed the phase of hydroxyapatite with its standard JCPDS data. FTIR analyses revealed the occurrence of distinctive functional groups related to hydroxyapatite. Surface micrographs showed the agglomerated globular shape morphology of hydroxyapatite, while EDS analysis confirmed the existence of biological elements of apatite such as Ca, P and O. Degradation study results showed that the glass thus prepared has considerable controlled degradation rate. MTT assay revealed the cytocompatibility nature for different dosages (1000-50 μg/mL) of the prepared glass with MG-63 cells. These results perfectly established that egg shells and RHA are potentially beneficial resources for the production of bio-glasses.


Limb Salvage Does Not Predict Functional Limb Outcome after Revascularization for Traumatic Acute Limb Ischemia.
Traumatic vascular injury leading to acute limb ischemia (ALI) is an uncommon problem with a potential for high morbidity. We describe a contemporary series of patients with traumatic ALI managed primarily by vascular surgeons at a tertiary referral center and review factors associated with limb salvage and functional limb outcomes. We conducted a single institution, retrospective review of all patients requiring revascularization for upper extremity (UE) and lower extremity (LE) ALI secondary to trauma from 2013 to 2016. Demographic data, transfer timing, injury severity score (ISS), Rutherford classification (RC), preoperative imaging, level of occlusion, procedural information, fasciotomy characteristics, and discharge disposition were reviewed. Outcome measures included limb salvage and functional limb outcomes. We identified 68 patients with traumatic ALI requiring revascularization. The majority of patients had moderate ISS scores, were RC 2a or 2b on presentation (65%), were transferred from another institution (53%), and underwent preoperative imaging (62%) with expeditious time to operation (median 4.5 hr). The most common location of vascular injury for UE was axillary-brachial (88%) and for LE was femoral-popliteal (69%). Open vascular procedures dominated the treatment strategy, and the median number of operations was 3. Fasciotomy was performed in 25% of UE and 58% of LE injuries. Shunts were utilized in only 2 patients. Overall LS was 94% for UE and 78% for LE. The median length of stay (LOS) was 11 days, with 25% of patients discharged to a skilled nursing facility. Follow-up was obtained for 59% of patients. For UE injuries, 57% of patients had no or minimal functional deficits, while 33% had major functional deficits and 10% underwent amputation. For LE injuries, 68% of patients had no or minimal functional deficits, while 6% had major functional deficits, and 26% had undergone amputation. Rutherford class and the number of operations performed were independent predictors of amputation and functional limb at follow-up in our logistic regression model (P < 0.05). Revascularization for traumatic ALI yields high limb salvage rates in patients with RC 1 and 2 ischemia and patients with UE injuries. However, limb salvage does not necessarily equate to good functional outcomes. This signifies the complex nature of injuries in this patient population, especially when multiple operations are required.


Chronic variable stress prevents amphetamine-elicited 50-kHz calls in rats with low positive affectivity.
The relationship between stress response and positive affective states is thought to be bidirectional: whilst stress can lead to a blunted hedonic response, positive affect reduces the negative effects of stress. We have previously shown that persistently high positive affectivity as measured by 50-kHz ultrasonic vocalizations (USVs) is protective against chronic variable stress (CVS). The present study examined the effect of CVS on 50-kHz USVs elicited by amphetamine administration, simultaneously considering the stable inter-individual differences in positive affectivity. Forty juvenile male Wistar rats were categorised as of high (HC) or low (LC) positive affectivity based on their 50-kHz USV response to imitation of rough-and-tumble play ('tickling'). As adults, the rats were subjected to four weeks of CVS, after which D-amphetamine was administered in five daily doses followed by a challenge dose (all 1mg/kg IP) nine days later. CVS reduced sucrose preference in LC-rats only. After CVS, amphetamine-elicited 50-kHz USVs were significantly reduced in LC-rats, the effect of stress in HC-rats being smaller and less consistent. In previously stressed and amphetamine-treated LC-rats, locomotor response to amphetamine was attenuated. In stressed LC-rats, DOPAC levels and dopamine turnover were increased in striatum after amphetamine treatment, and dopamine D1 receptor levels were upregulated in nucleus accumbens. LC-rats had lower isoleucine levels in frontal cortex. These results show that stress-related changes in response to amphetamine are dependent on inter-individual differences in positive affectivity both at neurochemical and behavioural levels, and further support the notion of higher vulnerability of animals with low positive affect.


Ultrastructural diagnosis of pleural tumors.
The significant association of two kind of mesothelial cells, differentiated and fibroblastoid, caracterises the ultrastructure of malignant pleural mesotheliomas. The differentiated mesothelial cancer cells (MCC's), whether they are observed in fluids or in biopsies, are not caracteristic enough to assert the diagnosis of mesothelioma. They can easily be mistaken for metastatic cells. Therefore, the diagnosis of mesothelioma relies on the identification of fibroblastoid MCC's, whether they are in association with the preceeding form in epithelial-like tumors, or the main component in sarcomatous-like tumors. Since the absence of fibroblastoid MCC's would eliminate the diagnosis of mesothelioma, patient and careful search for these cells must be done in all pleural tumors with a unique differentiation (epithelial-like or sarcomatouslike). This justifies the need for electron microscopy in the diagnosis of these pleural tumors: for this reason, pleural biopsies should routinely be embedded for possible future ultrastructural examination.


Strategies to enhance effectiveness of individual based nutrition communications.
Lifestyle modifications, including dietary and physical activity, are treatments for many chronic health conditions. Therefore, there is continued interest in improving the quantity and quality of nutrition information provided to the patient by the physician. This paper reviews the evidence to support motivational interviewing and other similar strategies for nutrition communications. Limited but positive data were found.