Prioritizing Outcome Measures for Value-Based Healthcare: Physicians' Perspectives in Saudi Arabia.
To inform the stepwise transformation to value-based healthcare in Saudi Arabia, we assess physicians' priorities for measuring general patient outcomes. This is done as an initial step toward the implementation of disease-specific outcome sets. A cross-sectional, electronic self-administered questionnaire-based study among physicians in 6 hospitals in Saudi Arabia was conducted between March 2022 and May 2022. Purposive sampling was used to select hospitals and physicians. The questionnaire included 30 health outcomes taken from about 60 disease-specific outcome sets. These were classified into 6 domains per the Outcome Measures Hierarchy Framework of Michael Porter. The physicians were asked to prioritize outcomes in each domain by their order of importance. The Relative Importance Index (RII) and multivariate binary logistic regression were used to analyze the priorities and to relate them to physicians' characteristics. A total of 204 physicians completed the questionnaire accounting for 40% response rate. The top priority outcomes per domain were overall survival (RII 89.4%); quality of life (RII 92.4%); time to treatment (RII 90.8%); incidence of adverse effects (RII 72.9%); need for retreatment (RII 80.5%); and incidence of hospital-acquired infections (RII 89.3%). Regression analysis revealed that physician seniority is a characteristic associated with physicians' perceptions of the importance of measuring health outcomes (highest odds ratio 2.693; 95% CI 1.501-4.833; P = .001). Establishing a general set of the most important outcomes that applies to all patients, including survival and mortality, quality of life, adverse events, and complications, need to be considered in the early stages of hospitals' transformation to value-based healthcare.


Reductive capabilities of different cyanobacterial strains towards acetophenone as a model substrate - Prospect of applications for chiral building blocks synthesis.
Bioreductive capabilities of four morphologically different strains of cyanobacteria have been assessed in this work. Arthrospira maxima, Leptolyngbya foveolarum, Nodularia sphaerocarpa and Synechococcus bigranulatus were applied as catalysts for the reduction of acetophenone to the corresponding chiral phenylethyl alcohol. The process was modified regarding substrate concentration, duration of pre-cultivation period, duration of biotransformation, light regime and glucose addition to the culture media. Obtained results clearly showed that cyanobacteria were active towards acetophenone what resulted in the substrate reduction to (S)-1-phenylethanol with high enantiomeric excess. The reaction efficiency increased with the biotransformation time, but the higher concentration of substrate limited the process yield. Also, all tested strains performed reaction with the highest efficacy under continuous light regime. The most active strains - N. sphaerocarpa and S. bigranulatus carried out the conversion of 1 mM acetophenone with high efficiency of respectively 97.6% and 96.2% after 13 days of biotransformation. A. maxima reached 45.8% of conversion after 13 days of biotransformation whereas L. foveolarum did not exceed 20%. The enantiomeric excesses were respectively 98.8%- A. maxima, 91.7%- L. foveolarum, 72.6%- S. bigranulatus and N. sphaerocarpa 16.2%.


A fluorescence-based assay for measuring the viable cell concentration of mixed microbial communities in soil.
Microbial cell concentration is a particularly important bioindicator of soil health and a yardstick for determining biological quotients which are likely to gain in ecological significance if they are calculated in relation to the viable, rather than total, microbial density. A dual-staining technique with fluorescent dyes was used for the spectrofluorimetric quantitative determination of the concentration of viable microbial cells present in three different soil types. This is a novel and substantially modified application of the dual-staining procedure implemented in the LIVE/DEAD BacLight viability kit which has never been successfully applied to the quantification of naturally occurring soil microbial communities. Indigenous microbial cell concentrations were quantified using an internal standard, i.e. spiking environmental samples with suspensions containing different concentrations of live E. coli cells, and external calibration, by comparing fluorescence emission by indigenous bacteria and known concentrations of E. coli in nutrient saline. Two types of environmental samples were tested: bacterial preparations obtained by density gradient centrifugation and soil suspensions. In both cases, prior dilution of the sample was necessary to minimise fluorescence quenching by soil particulate matter. Spectrofluorimetric measurements of indigenous cell concentration in bacterial preparations were in close agreement with those found using epifluorescence microscopy. Limits of detection of 5x10(6) for the soil bacterial preparations and 8x10(7) for the soil suspensions were estimated. Deviations observed when soil suspensions are dealt with are likely due to the selection of a unique bacterial strain for standardisation and calibration. Thorough testing of a variety of reference bacteria and fungi is suggested to determine a more accurate average fluorescence enhancement per microbial cell or mass unit.


Utilisation of an enzyme-linked immunosorbent assay (ELISA) for determination of alkylphenols in various environmental matrices. Comparison with LC-MS/MS method.
Among the wide range of substances discharged continuously in the environment, alkylphenols became a major focus of environmental research in the last decades, as it was found that they possess endocrine disrupting properties. Knowledge about the occurrence and levels of alkylphenols in environment is critical for the risk assessment of these compounds on both ecosystem and human health. However, the analysis of traces of alkylphenols in environmental matrices is a very difficult task, and the suitable methods involve generally an extraction followed by an extensive sample clean-up before detection, steps often time-consuming and costly. In order to reduce the analysis time, obtain a high throughput of analysis and thus improve work efficiency, the objective of the present study is to investigate the use of immunochemical technique (ELISA) for the determination of nonylphenol and octylphenol in soils and various kinds of water. To our knowledge, this is the first time that the determination of alkylphenols in soil using immunoassay technique is described. A methodology is developed, based on the combination of a single preparation step and the use of a simply ELISA kit. The performances of the method are compared with LC-MS/MS, considered as reference. The developed procedure offers the sensitivity and selectivity necessary for the detection of the target alkylphenols in the ng/g or ng/L range, and is successfully applied to the analysis of several samples. Results indicate that alkylphenols are quantified with concentrations in the same order than LC-MS/MS, meaning that ELISA may be useful not only in screening the samples and get a positive/negative response, but also it allows a good approximation of the concentrations.


INTRAOPERATIVE OPTICAL COHERENCE TOMOGRAPHY FOR REAL-TIME VISUALIZATION OF THE POSITIONAL RELATIONSHIP BETWEEN BUCKLING MATERIAL AND RETINAL BREAKS DURING SCLERAL BUCKLING FOR RHEGMATOGENOUS RETINAL DETACHMENT.
To report the usefulness of a new surgical method using intraoperative optical coherence tomography that can more accurately place the buckling material for scleral buckling using a noncontact wide-angle viewing system with a cannula-based chandelier endoilluminator for the treatment of rhegmatogenous retinal detachment. The medical records of 12 eyes of 11 patients with rhegmatogenous retinal detachment treated with scleral buckling combined with real-time intraoperative optical coherence tomography observation were retrospectively reviewed. Real-time observations of the positional relationship between the protrusion of buckling material and retinal breaks with intraoperative optical coherence tomography revealed that retinal breaks were not properly placed on the protrusion of the buckling material in five eyes, requiring the intraoperative repositioning of the buckling material. Eventually, the scleral buckling combined with real-time intraoperative optical coherence tomography observation yielded the initial anatomical success rates of 100% without noteworthy intraoperative or postoperative complications. This procedure is a novel approach that enables safer and more accurate placement of the buckling material and may contribute to improving the outcomes of scleral buckling in the future.


Solvent effect on phenolics and antioxidant activity of Huangshan Gongju (Dendranthema morifolium (Ramat) Tzvel. cv. Gongju) extract.
Huangshan Gongju was extracted with organic solvents (ethanol, methanol and acetone) of different concentrations (0-90%), and the extracts' phenolic content and antioxidant activity, as well as the correlations between them were examined. With the increasing concentration of organic solvent, the total phenolic compound (TPC) increased continuously and met its maximum at 70% acetone, whereas the total flavonoid compound (TFC) and most individual phenolics met their maximums at 70% ethanol. Similar changes occurred to the antioxidant activity, including DPPH and ABTS scavenging activities, and their maximums were respectively found at 50% acetone and 70% ethanol. The antioxidant activity correlated strongly with TPC/TFC (r > 0.954, p < 0.01) and individual phenolics (r > 0.886, p < 0.05), and the strongest correlations between them were mainly given by luteolin-7-O-glucoside (r > 0.975, p < 0.001). These results suggested that high content organic solvent (50-70%) was beneficial to obtain Huangshan Gongju extracts of higher phenolic content and antioxidant activity, and 70% ethanol may be the promising solvent. Besides, phenolics were found to be the main antioxidants of Huangshan Gongju extracts, and flavonoids especially luteolin-7-O-glucoside may play more important roles in the antioxidant activity.


Laboratory-acquired brucellosis in Turkey.
Laboratory healthcare workers (HCWs) are at risk of laboratory-acquired brucellosis (LAB). To describe the risk factors of LAB among HCWs. A multicentre survey study was conducted by face-to-face interview in 38 hospitals from 17 provinces of Turkey. A structured survey was administered to the HCWs, working in infectious diseases clinics and microbiology departments, who were at risk of brucella infection. The survey response rate was 100%. Of the 667 laboratory workers, 38 (5.8%) had a history of LAB. In multivariate analysis, factors independently associated with an increased risk of LAB included working with the brucella bacteria (odds ratio: 5.12; 95% confidence interval: 2.28-11.52; P < 0.001) and male gender (2.14; 1.02-4.45; P = 0.042). Using a biosafety cabinet level 2 (0.13; 0.03-0.60; P = 0.009), full adherence to glove use (0.27; 0.11-0.65; P = 0.004) and longer duration of professional life (0.86; 0.80-0.92; P < 0.001) were found to be protective. Working with the brucella bacteria, being male, a lack of compliance with personal protective equipment and biosafety cabinets were the independent risk factors for the development of LAB in our series. Increased adherence to personal protective equipment and use of biosafety cabinets should be priority targets to prevent LAB.


Intrinsic forces alone are sufficient to cause closure of the neural tube in the chick.
An isolated neural plate or a postnodal piece of early chick embryos, when cultured under appropriate experimental conditions, can undergo morphogenetic movements and form tubular structures closely resembling neural tubes of early chick embryos.


Characterization of candidate class A, B and E floral homeotic genes from the perianthless basal angiosperm Chloranthus spicatus (Chloranthaceae).
The classic ABC model explains the activities of each class of floral homeotic genes in specifying the identity of floral organs. Thus, changes in these genes may underlay the origin of floral diversity during evolution. In this study, three MADS-box genes were isolated from the perianthless basal angiosperm Chloranthus spicatus. Sequence and phylogenetic analyses revealed that they are AP1-like, AP3-like and SEP3-like genes, and hence these genes were termed CsAP1, CsAP3 and CsSEP3, respectively. Due to these assignments, they represent candidate class A, class B and class E genes, respectively. Expression patterns suggest that the CsAP1, CsAP3 and CsSEP3 genes function during flower development of C. spicatus. CsAP1 is expressed broadly in the flower, which may reflect the ancestral function of SQUA-like genes in the specification of inflorescence and floral meristems rather than in patterning of the flower. CsAP3 is exclusively expressed in male floral organs, providing the evidence that AP3-like genes have ancestral function in differentiation between male and female reproductive organs. CsSEP3 expression is not detectable in spike meristems, but its mRNA accumulates throughout the flower, supporting the view that SEP-like genes have conserved expression pattern and function throughout angiosperm. Studies of synonymous vs nonsynonymous nucleotide substitutions indicate that these genes have not evolved under changes in evolutionary forces. All the data above suggest that the genes may have maintained at least some ancestral functions despite the lack of perianth in the flowers of C. spicatus.


Tissue engineering: a promising therapeutic approach to necrotizing enterocolitis.
Tissue engineering is a promising potential candidate for treating intestinal failure resulting from necrotizing enterocolitis. This requires the acquisition, preparation and implantation of autologous organoid units. This may be affected by the complexities of periods of storage of viable donor tissue and delayed implantation. This chapter addresses the development, methodology, and application of tissue-engineered intestine in the experimental and clinical setting. Tissue engineering has the potential of avoiding the inherent toxicities of intestinal transplantation and prolonged immunosuppression.


The Geometric and Ergonomic Appeal of Uniportal Video-Assisted Thoracic Surgery.
The geometric characteristics of uniportal video-assisted thoracic surgery (VATS) are known: one small incision without further dissection of the intercostal space with the simultaneous introduction of instruments to the thoracoscope through an ideal circular truncated cone, as wide as a surgeon's fingerbreadth. The perspective of the uniportal VATS approach realizes projective planes that preserves the depth of intraoperative visualization. The instruments, moving along this planes, enable the surgeon to bring the operative fulcrum inside the chest. Also, the uniportal VATS approach generate an ergonomic advantage during surgery.


A Novel Prediction Model of Acute Kidney Injury Based on Combined Blood Variables in STEMI.
Development of acute kidney injury (AKI) is associated with poor prognosis in patients with ST-segment elevation myocardial infarction (STEMI). This study sought to investigate whether a combination of pre-procedural blood tests could predict the incidence of AKI in patients with STEMI. A total of 908 consecutive Japanese patients with STEMI who underwent primary percutaneous coronary intervention within 48 hours of symptom onset were recruited and divided into derivation (n = 617) and validation (n = 291) cohorts. A risk score model was created based on a combination of parameters assessed on routine blood tests on admission. In the derivation cohort, multivariate analysis showed that the following 4 variables were significantly associated with AKI: blood sugar ≥200 mg/dL (odds ratio [OR]: 2.07), high-sensitivity troponin I >1.6 ng/mL (upper limit of normal ×50) (OR: 2.43), albumin ≤3.5 mg/dL (OR: 2.85), and estimated glomerular filtration rate <45 mL/min/1.73 m2 (OR: 2.64). Zero to 4 points were given according to the number of those factors. Incremental risk scores were significantly associated with a higher incidence of AKI in both cohorts (P < 0.001). Receiver-operating characteristic curve analysis of risk models showed adequate discrimination between patients with and without AKI (derivation cohort, area under the curve: 0.754; 95% confidence interval: 0.733-0.846; validation cohort, area under the curve: 0.754; 95% confidence interval: 0.644-0.839). Our novel laboratory-based model might be useful for early prediction of the post-procedural risk of AKI in patients with STEMI.


Manganese dipyridoxal diphosphate-enhanced magnetic resonance imaging in the evaluation of hepatocyte function.
To determine whether contrast-enhanced magnetic resonance imaging can detect ethanol hepatotoxicity in rats. Rats were treated with a single high dose of ethanol (acute) intraperitoneally or with a 36% ethanol diet (chronic) for up to 5.5 months. Magnetic resonance imaging was performed before and after intravenous administration of manganese dipyridoxal diphosphate (Mn-DPDP). Enhancement (acute group) was significantly lower in ethanol treated animals on T1-weighted scans (P < .02). Precontrast, a significant difference in intensity was seen on T2-weighted scans (P < .01). Electron microscopy revealed severe hepatocyte damage. In the chronic groups, there was no significant difference in intensity precontrast. Postcontrast, enhancement (ethanol group) was significantly lower on T1-weighted scans only at 2 weeks (P < .05). Electron microscopy demonstrated progressive ethanol hepatotoxicity. Magnetic resonance imaging can distinguish between normal and certain types of ethanol damaged livers on T1-weighted scans. Enhancement, however, does not correlate with progressive microscopic liver damage.


Interconnections between Inflammageing and Immunosenescence during Ageing.
Acute inflammation is a physiological response to injury or infection, with a cascade of steps that ultimately lead to the recruitment of immune cells to clear invading pathogens and heal wounds. However, chronic inflammation arising from the continued presence of the initial trigger, or the dysfunction of signalling and/or effector pathways, is harmful to health. While successful ageing in older adults, including centenarians, is associated with low levels of inflammation, elevated inflammation increases the risk of poor health and death. Hence inflammation has been described as one of seven pillars of ageing. Age-associated sterile, chronic, and low-grade inflammation is commonly termed inflammageing-it is not simply a consequence of increasing chronological age, but is also a marker of biological ageing, multimorbidity, and mortality risk. While inflammageing was initially thought to be caused by "continuous antigenic load and stress", reports from the last two decades describe a much more complex phenomenon also involving cellular senescence and the ageing of the immune system. In this review, we explore some of the main sources and consequences of inflammageing in the context of immunosenescence and highlight potential interventions. In particular, we assess the contribution of cellular senescence to age-associated inflammation, identify patterns of pro- and anti-inflammatory markers characteristic of inflammageing, describe alterations in the ageing immune system that lead to elevated inflammation, and finally assess the ways that diet, exercise, and pharmacological interventions can reduce inflammageing and thus, improve later life health.


Adaptive radiotherapy planning on decreasing gross tumor volumes as seen on megavoltage computed tomography images.
To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV. Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages of replanning for patients with differing GTV regression characteristics. Average GTV change observed over 30 fractions was -38%, ranging from -12 to -87%. No significant correlation was observed between GTV change and patient's physical or tumor features. Patterns of GTV changes in the 17 patients could be divided broadly into three groups with distinctive potential for benefit from adaptive planning. Changes in GTV are difficult to predict quantitatively based on patient or tumor characteristics. If changes occur, there are points in time during the treatment course when it may be appropriate to adapt the plan to improve sparing of normal tissues. If GTV decreases by greater than 30% at any point in the first 20 fractions of treatment, adaptive planning is appropriate to further improve the therapeutic ratio.


Heat and ZnCl2 chemical carbonization of date stone as an adsorbent: optimization of material fabrication parameters and adsorption studies.
In the present study, the optimization of factors for the fabrication of highly adsorptive activated carbon from agricultural waste (date stone) was investigated by using ZnCl2 as a chemical agent during the heat treatment. ZnCl2 acts as a dehydration agent during the heat treatment, allowing a better porosity. In addition, it boosts the fragmentation of the lignocellulosic structure and the condensation of carbon rings. The findings of this investigation showed that the synthesis conditions for better ZnCl2 chemical/heat carbonization to fabricate an adsorbent from date stone are 700 °C, 120 min, and 2.0 g/g. The characterization analysis showed that the as-prepared activated carbon exhibits a surface area of 1036 m2/g, an iodine number of 928.5 mg/g, and phenol number of 2.1 mmol/g, which are comparable to commercial activated carbons. Batch sorption tests to remove methylene blue (MB) from water showed a maximum adsorption capacity of 384.6 mg/g using the prepared activated carbon. Equilibrium data was best fitted by the Langmuir isotherm model. It was found also that the kinetic adsorption data obeyed the pseudo-first order, and both external diffusion and intra-particle diffusion control the adsorption. Based on the obtained results, the optimization of synthesis conditions may help the transfer of technology in terms of agriculture-based material valorization towards the environmental remediation.


Absorption from the jejunum is increased by forward and backward pacing.
In 4 dogs a 75-cm segment of jejunum was isolated from the intestinal stream. Stimulating electrodes were implanted at each end of the segment and recording electrodes at intervals between. The two ends of the segment were fashioned as stomas on the anterior abdominal wall. After recovery, the electrical activity of the segment was continuously recorded, whilst a solution of 100 mmol/l glucose and 90 mmol/l NaCl was infused into the proximal stoma at 2.9 ml/min. Effluent from the distal stoma was collected in 5-min aliquots for three consecutive 30-min periods. In the second period electrical stimuli were given via either the proximal or the distal bipolar electrodes to entrain pacesetter potentials. Both forward and backward electrical pacing decreased the output of water, glucose and sodium from the jejunal segment, but the decrease was significantly greater with backward pacing. We conclude that pacing a segment of jejunum backwards with electrical stimuli produces a greater increase in absorption from the segment than pacing it forwards, a finding which has therapeutic implications in patients with the short bowel syndrome.


Small burns among out-patient children and adolescents with attention deficit hyperactivity disorder.
There is a controversy about the association of attention deficit hyperactivity disorder (ADHD) with burns among children. Whereas some studies of children with burns have suggested ADHD as a risk factor for thermal injury, others have reported it as protective against such injury. This case-control study was designed to assess the association of ADHD with burns. The case group consisted of 123 children with ADHD diagnosed by the standardised diagnostic criteria of DSM-IV. The comparison group comprised of 100 children without ADHD. Children and their carers were asked about the frequency of burns during the past year. A significant association was found between frequency of burn and group, but no such association was found with sibling number, rank of birth of the child or mother's occupation. The incidence of burns among children with ADHD was higher than among the control group.


Protection of DNA and membrane from gamma radiation induced damage by gallic acid.
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a naturally occurring plant phenol. In vitro and in vivo studies have shown that this phytochemical protected DNA and membranes against ionizing radiation. Rat liver microsomes and plasmid pBR322 DNA were exposed to various doses of gamma radiation in presence and absence of GA. Exposure of the microsomes to gamma radiation resulted in the formation of peroxides of membrane lipids measured as thiobarbituric acid reactive substances and presence of GA during irradiation prevented the formation of lipid peroxidation. Gamma irradiation of plasmid DNA resulted in induction of strand breaks in DNA resulting in disappearance of the supercoiled (ccc) form. Presence of GA during irradiation protected the DNA from undergoing the strand breaks. In in vivo studies it was found that whole body exposure of mice to gamma radiation (4 Gy) increased the formation of lipid peroxides in various tissues and damage to cellular DNA (as measured by alkaline comet assay) in peripheral blood leucocytes. Administration of GA to mice prior to whole body radiation exposure reduced the peroxidation of lipids and the damage to the cellular DNA indicating in vivo radiation protection of membranes and DNA by GA.


Management for Benign Ureteral Stricture: Comparison of Robot-Assisted Laparoscopy, Conventional Laparoscopy, and Balloon Dilation.
Purpose: Robot-assisted laparoscopy (RALP), conventional laparoscopy (LP), and balloon dilation (BD) have all been identified as common treatments for benign ureteral stricture (BUS). The purpose of the research would be to compare the safety and efficacy differences in the three groups. Patients and Methods: Patients who received RALP, LP, or BD for BUS were studied retrospectively from January 2016 through December 2020. Professional and experienced surgeons performed all operations. We collect and analyze baseline characteristics, stricture details, and perioperative and follow-up information. Results: The results showed no statistically significant difference between the three groups for baseline characteristics and stricture details. No statistical difference was also found between RALP and LP in specific surgical techniques. The average operative time was longer in the LP group than RALP and BD groups (178 minutes vs 150 minutes vs 67 minutes, respectively, p < 0.001). BD had lower estimated blood loss than RALP and LP (14 mL vs 40 mL vs 32 mL, p < 0.001) and similar between the RALP and LP groups (p = 0.238). The BD group had the shortest postoperative hospital stay compared with the RALP and LP groups (2.95 days vs 5.25 days vs 6.52 days, p < 0.001), and no statistically significant difference existed between the RALP and LP groups (p = 0.098). RALP had considerably greater hospitalization expenses than both LP (p < 0.001) and BD (p < 0.001). Complications and short-term success rates (6 months) were similar. The BD group had poorer long-term success (12 and 24 months) than the RALP and LP groups, whereas there was no statistically significant difference between the RALP and LP groups. Conclusions: For the management of BUS, RALP, LP, and BD are all safe and effective, with equivalent complication rates and short-term success. In long-term success rates, BD is low than RALP and LP.


The P. furiosus mre11/rad50 complex promotes 5' strand resection at a DNA double-strand break.
The Mre11/Rad50 complex has been implicated in the early steps of DNA double-strand break (DSB) repair through homologous recombination in several organisms. However, the enzymatic properties of this complex are incompatible with the generation of 3' single-stranded DNA for recombinase loading and strand exchange. In thermophilic archaea, the Mre11 and Rad50 genes cluster in an operon with genes encoding a helicase, HerA, and a 5' to 3' exonuclease, NurA, suggesting a common function. Here we show that purified Mre11 and Rad50 from Pyrococcus furiosus act cooperatively with HerA and NurA to resect the 5' strand at a DNA end under physiological conditions in vitro. The 3' single-stranded DNA generated by these enzymes can be utilized by the archaeal RecA homolog RadA to catalyze strand exchange. This work elucidates how the conserved Mre11/Rad50 complex promotes DNA end resection in archaea and may serve as a model for DSB processing in eukaryotes.


Elevated serum soluble E-selectin levels in Korean children with measles.
Measles is a highly infectious, acute viral illness characterized by high fever and generalized skin rash of which pathogenesis is uncertain. E-selectin, a ligand of the cutaneous lymphocyte-associated antigen (CLA)+ T lymphocytes is highly expressed on vascular endothelium in atopic dermatitis and psoriasis, but in the past there has been a lack of statistical data on its impact on patients with measles. The aim of the present study was to investigate whether the serum soluble E-selectin (sE-selectin) levels are elevated in children with measles. Twenty-five children with measles, 33 children with atopic dermatitis, 20 with atopic asthma and 20 healthy controls were enrolled. Serum sE-selectin and tumor necrosis factor (TNF)-alpha levels were measured using sandwich enzyme-linked immunosorbent assay. Serum levels of sE-selectin were found to be significantly higher in children with measles than in children with atopic dermatitis, atopic asthma and healthy controls. But it was not significantly correlated with the duration of rash or with the presence of a complication in children with measles. Serum TNF-alpha levels were higher in children with measles than in children with atopic dermatitis. There was no correlation between sE-selectin and TNF-alpha levels. sE-selectin levels are elevated in children with measles, which may imply that CLA+ T lymphocytes are associated with the development of measles rash.


An ortho-activation strategy to develop NIR fluorescent probe for rapid imaging of biothiols in vivo.
Biothiols are the main antioxidants in regulating the redox balance and resisting oxidative stress in various biological processes, but the long detection time of current fluorescent probes hinders their rapid imaging in vitro and in vivo. To reveal the influx of biothiols, we rationally develop an ortho-activation approach to accelerate the reaction between the probe and biothiols, by introducing electron-withdrawing fluorine atom into the ortho-site of the phenolic hydroxyl group in the NIR probe to generate an ortho-inductive effect. The ortho-fluorine helps to increase the chemical reactivity of the molecular structure, resulting in a significantly shorter detection time (within 5 min) as compared to previous reports (> 20 min for acrylates-based probes in aqueous solution). Based on this approach, our near-infrared probe 2F-RBX can sensitively and efficiently detect endogenous biothiols in living HepG2 cells and in vivo. These data suggest that ortho-activation is a simple and flexible approach to construct sensitive fluorescent probes for rapid imaging of biothiols, and perhaps other molecules in future, under biological circumstances.


Extended operation of a pressurized 75-L bioreactor for shLkn-1 production by Pichia pastoris using dissolved oxygen profile control.
In this study, a dissolved oxygen (DO)-stat fed-batch process was conducted in a pressurized 75-L bioreactor, resulting in the production of the short version of human leukotactin-1 (shLkn-1) using Pichia pastoris as the host, with control of the DO-stat profile and an extension of the recombinant shLkn-1 production phase. By regulation of the exhaust-gas valve, we were able to maintain the vessel pressure at up to 120 kPa, in order to overcome DO limitations associated with the use of the DO-stat. The lowest DO value was adjusted by varying the feed pump speed, allowing us to control the DO-stat profile. This principle was successfully applied to both glycerol feeding during the growth phase and methanol feeding for the induction of shLkn-1. The extension of the methanol induction phase to a total of 192 h of culture time resulted in a shLkn-1 concentration of 2.5 g/L, and a total of 102 g of cumulative production. During this extended induction period, the C-terminal residue of shLkn-1 was truncated and this was confirmed by both reverse-phase HPLC and mass spectrometry.


Occurrence of polybrominated diphenyl ethers and benzotriazole UV stabilizers in the hadal amphipod Hirondellea gigas.
The accumulation of polybrominated diphenyl ethers (PBDEs) and benzotriazole UV stabilizers (BZT-UVs) were examined in the hadal amphipod Hirondellea gigas caught from a near-land trench off the Japan island (9200 m). H. gigas were collected from two distinct sites: one is located at the outlet of submarine canyons directly connected to land and the other is apart from the outlet and geographically isolated from the first site. The level of the PBDEs in H. gigas at the canyon outlet (mean 219 ng/g lipid weight (l.w.)) was significantly higher than that in the isolated site (mean 42 ng/g l.w.) and BZT-UVs were only detected within the first site (mean 1.5 ng/g wet weight). In addition to vertical transport from the surface water, near-land trenches associated with submarine canyons and troughs may have more complex influx of contaminants through horizontal transportation from the land, resulting in more severe contamination.


KRASG12R-Independent Macropinocytosis in Pancreatic Cancer.
Macropinocytosis is a critical route of nutrient acquisition in pancreatic cancer cells. Constitutive macropinocytosis is promoted by mutant KRAS, which activates the PI3Kα lipid kinase and RAC1, to drive membrane ruffling, macropinosome uptake and processing. However, our recent study on the KRASG12R mutant indicated the presence of a KRAS-independent mode of macropinocytosis in pancreatic cancer cell lines, thereby increasing the complexity of this process. We found that KRASG12R-mutant cell lines promote macropinocytosis independent of KRAS activity using PI3Kγ and RAC1, highlighting the convergence of regulation on RAC signaling. While macropinocytosis has been proposed to be a therapeutic target for the treatment of pancreatic cancer, our studies have underscored how little we understand about the activation and regulation of this metabolic process. Therefore, this review seeks to highlight the differences in macropinocytosis regulation in the two cellular subtypes while also highlighting the features that make the KRASG12R mutant atypical.


Neural dynamics of the production of newly acquired words relative to well-known words.
An adult continues acquiring new lexical entries in everyday life. Brain networks and processes at play when producing newly learnt words might be similar to well-known words, yet some processes are bound to be slower. Here, we compared the neural dynamics of producing newly acquired words with those of well-known frequent words, both qualitatively and quantitatively, using event-related potentials (ERPs) associated to high-density microstate analyses. ERPs revealed several temporal windows with differences in waveform amplitudes, which correspond to enhanced duration of similar microstates for newly acquired words compared to well-known words. The time-periods of these ERP modulations converged to suggest that both lexical processes and word form encoding are slowed down for words that have been learned recently, but that the same brain processes are implemented as for well-known words.


Life History Theory and economic modernity.
Baumard's new explanation of the Industrial Revolution shows that Life History Theory holds great potential. Here, I suggest two related hypotheses for examination. One is that there are long-term roots of slow life traits and preferences. The other is that Life History Theory can explain other aspects of economic modernity such as the Scientific Revolution and bureaucratic states. If so, then Life History Theory offers a way to reconcile several bodies of evidence and lines of explanation into a coherent general account of economic modernity.


Doppelgänger spotting in biomedical gene expression data.
Doppelgänger effects (DEs) occur when samples exhibit chance similarities such that, when split across training and validation sets, inflates the trained machine learning (ML) model performance. This inflationary effect causes misleading confidence on the deployability of the model. Thus, so far, there are no tools for doppelgänger identification or standard practices to manage their confounding implications. We present doppelgangerIdentifier, a software suite for doppelgänger identification and verification. Applying doppelgangerIdentifier across a multitude of diseases and data types, we show the pervasive nature of DEs in biomedical gene expression data. We also provide guidelines toward proper doppelgänger identification by exploring the ramifications of lingering batch effects from batch imbalances on the sensitivity of our doppelgänger identification algorithm. We suggest doppelgänger verification as a useful procedure to establish baselines for model evaluation that may inform on whether feature selection and ML on the data set may yield meaningful insights.


Evaluation of methods of administering tyramine to raise systolic blood pressure.
To compare the relative merits of two different administration regimens, tyramine was administered intravenously in ascending doses to 12 healthy subjects to raise systolic blood pressure slightly more than 30 mm Hg. Six subjects received tyramine by bolus injection and six other subjects received tyramine by infusion. The bolus dose of tyramine needed was 4.34 +/- 1.51 mg (X +/- SD) and the infusion rate needed was 1.11 +/- 0.33 mg/min. Four blood pressure response patterns to continuous tyramine infusion were observed. Because different units were measured for the quantity of tyramine administered, the between-subject variance estimate to within-subject variance estimate ratios were calculated. The two techniques had equivalent consistency. With the bolus method, in contrast to the infusion procedure, the dose-response relationship was obvious in most subjects. Therefore the bolus method was judged to be more useful than the infusion method.


Radon concentrations in the community groundwater system of South Korea.
Groundwater samples were collected from 3818 wells used for the community groundwater system (CGS) in the remote rural areas of South Korea and analyzed to determine radon concentrations. Radon concentrations varied with rock type, ranging from 0.1 to 2393.5 Bq/L with an average of 86.6 Bq/L and a median of 46.4 Bq/L. Among 10 geological units, the median CGS radon concentration was highest (59.6-103.0 Bq/L) in granite, and lower in sedimentary rocks (16.9-21.1 Bq/L) and porous volcanic rocks (17.6 Bq/L), respectively. Of the 3818 samples, 26.1% exceeded the World Health Organization (WHO) radon level limit of 100 Bq/L. The application of the natural radon reduction rate (26.5%) recently suggested by Yun et al. Applied Radiation and Isotopes, 126(1), 23-25 (2017) to the CGS water tank appeared to decrease exceedance of the WHO radon level limit to 20.2%. Because of the high radon concentrations in CGS groundwater in South Korea, the establishment of a radon level limit for drinking water is strongly recommended to ensure the health and safety of the people using CGS water.


Formation of one-way-structured cultured neuronal networks in microfluidic devices combining with micropatterning techniques.
We present a simple method to regulate the direction of axon development in cultured neurons using microfabrication and microfluidics techniques. We fabricate a PDMS-based device and place it onto a chemically micropatterned glass substrate. We confirm that cultured neurons extend neurites along the medium flow direction and the micropatterned regions.


Confocal laser-scanning microscopical image of the distribution of intracellular organelles in cochlear outer hair cells.
Confocal laser-scanning microscopy was used to observe cytosolic Ca2+, organelles and cytoskeleton in the cochlear outer hair cell. The characteristic distribution of the subsurface cistern was observed in coincidence of the infracuticular network of F-actin and membrane-bound calcium, suggesting the source of Ca2+ for the actin-mediated process.


The roles of polycarboxylates in Cr(VI)/sulfite reaction system: Involvement of reactive oxygen species and intramolecular electron transfer.
In this study, the effects of polycarboxylates on both Cr(VI) reduction and S(IV) consumption in Cr(VI)/S(IV) system was investigated in acidic solution. Under aerobic condition, the productions of reactive oxygen species (ROS), i.e., SO4(-) and OH, have been confirmed in S(IV) reducing Cr(VI) process by using electron spin resonance and fluorescence spectrum techniques, leading to the excess consumption of S(IV). However, when polycarboxylates (oxalic, citric, malic and tartaric acid) were present in Cr(VI)/S(IV) system, the affinity of polycarboxylates to CrSO6(2-) can greatly promote the reduction of Cr(VI) via expanding the coordination of Cr(VI) species from tetrahedron to hexahedron. Besides, as alternatives to S(IV), these polycarboxylates can also act as electron donors for Cr(VI) reduction via intramolecular electron transfer reaction, which is dependent on the energies of the highest occupied molecular orbital of these polycarboxylates. Notably, the variant electron donating capacity of these polycarboxylates resulted in different yield of ROS and therefore the oxidation efficiencies of other pollutants, e.g., rhodamine B and As(III). Generally, this study does not only shed light on the mechanism of S(IV) reducing Cr(VI) process mediated by polycarboxylates, but also provides an escalated, cost-effective and green strategy for the remediation of Cr(VI) using sulfite as a reductant.


Tubulins in Aspergillus nidulans.
The discovery and characterization of the tubulin superfamily in Aspergillus nidulans is described. Remarkably, the genes that encode alpha-, beta-, and gamma-tubulins were all identified first in A. nidulans. There are two alpha-tubulin genes, tubA and tubB, two beta-tubulin genes, benA and tubC, and one gamma-tubulin gene, mipA. Hyphal tubulin is encoded mainly by the essential genes tubA and benA. TubC is expressed during conidiation and tubB is required for the sexual cycle. Promoter swapping experiments indicate that the alpha-tubulins encoded by tubA and tubB are functionally interchangeable as are the beta-tubulins encoded by benA and tubC. BenA mutations that alter resistance to benzimidazole antimicrotubule agents are clustered and define a putative binding region for these compounds. gamma-Tubulin localizes to the spindle pole body and is essential for mitotic spindle formation. The phenotypes of mipA mutants suggest, moreover, that gamma-tubulin has essential functions in addition to microtubule nucleation.


Purification to homogeneity and some properties of L-phenylalanine ammonia-lyase of irradiated mustard (Sinapis alba L.) cotyledons.
1. Lyase (L-Phenylalanine ammonia-lyase, EC 220.127.116.11) from far-red light-irradiated mustard cotyledons was purified to a single protein using ammonium sulphate fractionation, column chromatography on L-phenylalanyl-Sepharose 4B and on Sephadex G-200, isoelectric focusing and polyacryalmide gel electrophoresis. 2. The enzyme constituted 0.01% of total cellular protein, did not catalyse the deamination of L-tyrosine, had a pH optimum of pH 8.6 and an isoelectric point of pH 5.6. 3. The sedimentation coefficient was estimated as 11.3 S, the Stokes' radius 4.25 nm, and the molecular weight 240 000 +/- 9000 (S.E.). 4. Electrophoresis on denaturing polyacrylamide gels gave a single stained protein band corresponding to a subunit molecular weight of 55 000 indicating a tetrameric structure of equal (or near-equal) size subunits. 5. Maximum velocity (V) for the purified lyase at 25 degrees C was 3.83--4.10 nkat. 1(-1) enzyme and Km value 0.151--0.154 mM. Negative cooperativity (Hill coefficient, n = 1.08) was not detected over the substrate concentration range tested. 6. A putative non-diffusible inhibitor isolated from dark-grown gherkin hypocotyls inhibited the homogeneously purified mustard lyase.


Retracted: Research on Application Experience Design of Ice and Snow Sports Equipment Based on Bee Colony Model.
[This retracts the article DOI: 10.1155/2022/8760053.].


Complotype genetic loci segregate more frequently with HLA-DR than with HLA-B.
The loci for BF, C2, C4A, and C4B are very closely linked to each other so that alleles of these plasma protein markers occur in populations in linkage disequilibrium and are inherited as single genetic units called complotypes. These complotypes are coded by a DNA region of the short arm of chromosome 6 embracing approximately 100 kilobases, which serve as a marker of the major histocompatibility complex. We have studied the complotypes of nine families with known HLA-B/DR crossovers. In seven families, the complotypes were inherited with HLA-DR, including in one family with a double recombination. The haplotype HLA-A28, Cw1, B27, FC3, 20, DR4 of JTr resulted from two recombinations between HLA-A2, Cw1, B27, SC42, DR7 and HLA-A28, Cwx or Cw1, B37, FC3, 20, DR4. In the remaining two families (Ro and Lo) the complotypes were inherited with HLA-B. The haplotype A2, Cw5, Bw44, SC30, DR3 of StLo resulted from paternal recombination between the haplotypes A2, Cw5, Bw44, SC30, DR4 and A24, B8, SC01, DR3, and the haplotype A24, Cw4, Bw35, SC31, DR3 of NaRo resulted from maternal recombination between A24, Cw4, Bw35, SC31, DR4 and A26, Bw41, FC31, DR3. Our data suggest that the complotype region maps closer to HLA-D than to HLA-B.


Optimism bias and its relation to scenario valence, gender, sociality, and insecure attachment.
Optimism bias refers to the tendency to display unjustified high/low expectations of future positive/negative events. This study asked 202 participants to estimate the likelihood of 96 different events. We investigated optimism biases for both oneself and the general population, and how these biases are influenced by gender, valence of the event, sociality of the event, as well as attachment anxiety and attachment avoidance. We found that sociality interacted with gender, with the difference in optimism bias for social vs. alone events being larger among women than among men. Attachment anxiety mainly reduced the optimism bias among men deliberating over future alone situations, while attachment avoidance primarily reduced optimism bias among female respondents deliberating over future social interactions. These results may have implications for the well-being and motivation of differently attached men and women and ultimately inspire psychotherapy interventions.


Vaccines in older age: moving from current practice to optimal coverage-a multidisciplinary consensus conference.
Vaccines are a key strategy to promote healthy aging, but vaccine coverage remains below target levels in at-risk adults and older individuals. We present here the results of a multidisciplinary consensus conference convened to perform a multidimensional assessment of vaccination in geriatric medicine, with a view to developing a well-defined strategy for the promotion of vaccines in older people. We discuss recommended vaccines in older individuals, and describe the wide regional heterogeneity between regions in the Italian context. The main obstacles to implementation of vaccines in practice are reviewed, as well as potential strategies to remove these barriers. Finally, the importance of including vaccines and vaccination in undergraduate and postgraduate medical education is underlined. The information summarized in this document is expected to help develop educational and promotional initiatives to achieve greater uptake of vaccines among older individuals, as a key means to promote healthy aging.


Rehabilitation following knee injury.
Over the past decade, there has been a resurgence of interest in techniques of rehabilitation of the injured knee. Technologic advances have provided instruments that yield objective measurements so that appropriate staging can be done as part of the rehabilitation plan. Research in multidisciplinary fields has provided data that currently allow a rational physiologic approach to progressive care of the injured lower extremity. No longer is the adage "work it out and let's see how it goes" appropriate care for the injured knee. Starting with the proper diagnosis, rehabilitation begins at the time of injury and is specific for both the patient and the injury. A time frame is established for the rehabilitation, with progressive monitoring to allow gradual return to activity and the goals of both the patient and the surgeon taken into consideration. The management of knee injuries, whether from an overuse stress syndrome or following severe trauma with major ligament disruption, deal with the management of the inflammatory response. Since we do not know the exact time period for full mechanical competence following ligament healing, gradual assessment of objective data is necessary before return to full vigorous activity. Improved methods of rehabilitation allow patients to feel a sense of an active, dynamic process during which they are made to realize that much of their total improvement is up to them, under the guidance of the physician and therapist. The maintenance of function and fitness in uninjured extremities also allows for a feeling of well-being. Techniques now available make this often-forgotten phase of treatment a more pleasurable one and one that must be considered as much a part of knee injury management as is the knee immobilizer or the surgeon's scalpel.


Transmural care. A new approach in the care for terminal cancer patients: its effects on re-hospitalization and quality of life.
Despite their wishes, terminal cancer patients are frequently readmitted to hospitals. This appears in part to be due to poor communication amongst professional caregivers and/or the overburdening of their (informal) caregivers. This quasi-experimental study investigated the effects of a transmural home care programme on re-hospitalization, quality of life and place of death for terminal cancer patients. The programme intended to optimize communication, cooperation and coordination between intra- and extra-mural health care organizations (transmural care). Initial patient characteristics of the intervention group (n = 79) matched those of the control group (n = 37) well. When compared to the control group, which received the standard community care, patients in the intervention group underwent significantly less re-hospitalization during the terminal phase of their illness (5.8 versus 11.5 days; P < 0.01) while the intervention contributed significantly positive to the patients' "physical" quality of life 1 month after the start of the intervention. A higher, but not significant (P = 0.06) percentage of patients in the intervention group also died at home (81 versus 65%). The introduction of measures to enhance coordination and cooperation of intra- and extramural care, seems to be an improvement compared to standard community care.


An Electronic Disease Early Warning System in Sana'a Governorate, Yemen: Evaluation Study.
Electronic Disease Early Warning System (eDEWS) is one of the effective programs in epidemiological surveillance. This study aimed to identify the strengths and weaknesses of eDEWS in Sana'a governorate, determine its usefulness, and assess its performance in terms of the system attributes, including simplicity, flexibility, data quality, acceptability, representativeness, timeliness, and stability. Updated guidelines on the evaluation of public health surveillance from the Center for Disease Control and Prevention (CDC) were used to evaluate the eDEWS in Sana'a governorate. Stakeholders from different levels were interviewed about the performance of the eDEWS. The overall score for the usefulness of the eDEWS was good (mean=83%). The overall system performance was good (86%). The highest attribute score was 100% for representativeness and the lowest score was 70% for stability. The system simplicity and acceptability were good. Although the system representativeness and flexibility were excellent, the stability was average. System completeness and timeliness were 100%. In conclusion, eDEWS in Yemen is useful and met its main objective. The overall level of system performance was good.


Feasibility of a short term severely restricted sodium diet with counselling support.
For the purpose of short term clinical trials previous studies have made use of metabolic kitchens to provide severely restricted sodium diets. We evaluated the feasibility of administering a 5-day severely restricted (22 mmol) sodium diet on an outpatient basis with counselling support, outside a metabolic unit. In 13 highly-motivated volunteers, 24-h urinary sodium excretion fell from 128.5 +/- 11.9 on a normal diet to 19.2 +/- 2.88 mmol per day and plasma sodium dropped from normal diet to 19.2 +/- 2.88 mmol per day and plasma sodium dropped from 140 +/- 0.41 to 137 +/- 0.78 mmol/L, showing that such an approach is effective.


Characterization of the innate immune response in goats after intrauterine infusion of E. coli using histopathological, cytologic and molecular analyses.
The objective was to characterize the innate immune response in dairy goats after intrauterine infusion of E. coli. A suspension of Escherichia coli (E. coli; 4 × 10(9) cfu (cfu)/mL; experimental group, n = 6) or 5 mL PBS (control group, n = 6) were infused once into each uterine horn in goats at 25 days postpartum. Blood and endometrial biopsy samples were collected preinoculation (0 h) and at 3, 6, 12, 24, 72, 120, and 168 h post inoculation (pi). Relative gene expression analyses of Toll-like receptor4 (TLR4), tumor necrosis factorα (TNF-α), β-defensin2, and interleukins (IL-1β, IL-6, IL-8) were performed on RNA extracted from endometrial tissue and peripheral white blood cells (WBCs) using quantitative real-time PCR. Endometrial tissue was also used for histopathology and cytology. In experimental goats, the mRNA expression of TLR4 and proinflammatory cytokines were increased within 24 h pi (P < 0.01) in endometrium and WBCs. Similarly, expression of β-defensin2 was higher at 72 h pi in endometrium (P < 0.001), and at 120 h pi in WBCs (P < 0.05). The %PMNs in the experimental group increased up to 92.16 ± 3.95% at 3 h pi (P < 0.001). Endometrial histopathology revealed a severe inflammatory response at 3 to 12 h pi, whereas no changes were detected in the control group. In conclusion, intrauterine infusion of E. coli in goats resulted in a rapid activation of the local innate immune response, characterized by infiltration of PMNs into the endometrium and up-regulation of gene expression for TLR4, cytokines and β-defensin2.


Psoas abscess rarely requires surgical intervention.
Surgeons are increasingly encountering psoas abscesses. We performed a review of 41 adults diagnosed and treated for psoas abscess at a county hospital. Treatment modalities and outcomes were evaluated to develop a contemporary algorithm. Eighteen patients had a primary psoas abscess, and 23 had a secondary psoas abscess. Patient characteristics were similar in both groups. Intravenous drug abuse was the leading cause of primary abscesses. Secondary abscesses developed most commonly after abdominal surgery. Treatment was via open drainage (3%), computed tomography-guided percutaneous drainage (63%), or antibiotics alone (34%). Four recurrences occurred in the percutaneous group. Statistical analysis showed that the median size of psoas abscesses in the percutaneous group was significantly larger than in the antibiotics group (6 vs 2 cm; P < .001). The mortality rate was 3%. Initial management of psoas abscesses should be nonsurgical (90% success). Small abscesses may be treated with antibiotics alone, and surgery can be reserved for occasional complicated recurrences.


[Clinical aspects and pathology of mycobacterial infections in AIDS. Pulmonary and extrapulmonary manifestations].
Infections with M. tuberculosis and other mycobacteria (atypical mycobacteria) are frequently found in patients with AIDS. They are almost always disseminated, and are associated with a spectrum of findings that is often unhelpful for the diagnosis. In the case of tuberculosis, typical granulomas are a major finding. The histological correlate of mycobacteriosis is histiocytosis; granulomas are rarely observed, and when they do present, are incompletely developed.


The structure of negative self-statements in children and adolescents: a confirmatory factor-analytic approach.
The aim of this study was to examine the nature and organization of a range of negative self-statements in children and adolescents, using a structural equations/confirmatory factor-analytic approach. A community sample of 978 children aged 7-16 years completed a questionnaire about the frequency with which they experienced a broad range of negative automatic thoughts. The outcome of comparative modeling provided strongest support for a model in which 4 distinct cognitive factors were all related to a single higher order factor. The 4 lower order factors related to cognitions on social threat, physical threat, personal failure, and hostility. The pattern of results was consistent across age and gender. Results were consistent with assumptions of cognitive specificity models of psychopathology, on the latent structure of automatic thoughts in children and adolescents.


Thromboxane and prostacyclin in maternal and fetal circulation in pre-eclampsia.
A major pathophysiologic change of pre-eclampsia has been attributed to the overproduction of thromboxane A2 (TXA2) mainly from activated platelets. On the other hand, increased biosynthesis of TXA2 has also been reported from preeclamptic placentas. The systemic role of these different sources of TXA2 has not been clarified. The purpose of this study is to define the changes of TXA2 and the antagonizing prostacyclin (PC) in maternal and fetal circulations. The stable metabolites of TXA2 and PC [Thromboxine B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha), respectively] in the cord and maternal blood of nine patients with pre-eclampsia and nine normal parturients were measured by radioimmunoassay. In normal pregnancy, the cord blood contained much higher TXB2 (1697+/-898 vs. 267+/-128 ng/ml, P < 0.01) and 6-keto-PGF1alpha (266+/-263 vs. 12.5+/-3.9 ng/ml, P < 0.05) levels than the maternal blood. In the preeclamptic state, a marked increase of TXB2 was noted in both maternal and cord blood, reaching levels which were significantly higher than during normal pregnancy (2995+/-1103 vs. 267+/-128 ng/ml in maternal blood, P < 0.0001, and 3197+/-1288 vs. 1697+/-898 ng/ml in cord blood, P < 0.005). A less significant increase in 6-keto-PGF1alpha (134+/-10.8 vs. 12.5+/-3.9 ng/ml, P < 0.05) was also noted in the maternal blood. Moreover, the level of TXB2 correlated with the diastolic blood pressure of preeclamptic patients before and after delivery. The results suggest an abundant source of eicosanoids in the feto-placental circulation, which does not readily cross the placental barrier. In pregnancy complicated with pre-eclampsia, thromboxane level of both fetal and maternal circulations are markedly increased, which may be responsible for the pathophysiologic changes. The lack of adverse systemic effects on the fetus highlights a placental source of TXA2 of transient bioactivity which is rapidly hydrolyzed to non-active TXB2. Federation of Gynecology and Obstetrics


52-year-old man • hematemesis • history of cirrhosis • persistent fevers • Dx?
► Hematemesis ► History of cirrhosis ► Persistent fevers.


Training and certification in first responder care among mountaineering practitioners in east Africa.
Mountaineering activities have potential risks for injuries and illnesses. Extreme weather conditions, high altitude, limited resources and accessibility to transport and definitive medical services calls for mountaineering practitioners to be well prepared through training and certification in first responder care. This is useful in cases when they have an injured climber and need to offer support in the tier-one emergency system care before accessing further care in a medical facility. The study sought to establish the first responder care training status of mountaineering practitioners and the associations of mountaineering practitioners' first responder care training levels and gender, age, years of work experience, and designation. The study used cross-sectional analytical research design with a purposive sample of one hundred and thirty six (136) mountaineering practitioners in East Africa. Snowball sampling procedure was used to identify the respondents since there were no records indicating the population size or specific location of these mountaineering practitioners. A self-administrated questionnaire was used to collect data on whether they were trained or not; status of their up-to-date certification; institutions where they did their training and recertification; and their training levels in first responder care, which would cover the aim of the study. Majority of mountaineering practitioners (91.2%) had received some form of training. However, 47.1% had received training in basic first aid, which did not involve mountain related components. Outdoor practitioners' up-to-date training was dependent on their age (p = 0.005), and years of work experience (p= 0.014). There is need for mountaineering practitioners to have standardized minimum training in wilderness specific first responder care. The study recommends that the training and recertification should be undertaken on a regular basis by the mountaineering practitioners in East Africa.


Looking on the horizon; potential and unique approaches to developing radiation countermeasures for deep space travel.
Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human health and performance on future missions beyond low Earth orbit. This paper will describe three funded and complementary avenues for reducing the risk to humans from radiation exposure experienced in deep space. The first focus is on identifying new therapeutic targets to reduce the damaging effects of radiation by focusing on high throughput genetic screens in accessible, sometimes called lower, organism models. The second focus is to design innovative approaches for countermeasure development with special attention to nucleotide-based methodologies that may constitute a more agile way to design therapeutics. The final focus is to develop new and innovative ways to test radiation countermeasures in a human model system. While animal studies continue to be beneficial in the study of space radiation, they can have imperfect translation to humans. The use of three-dimensional (3D) complex in vitro models is a promising approach to aid the development of new countermeasures and personalized assessments of radiation risks. These three distinct and unique approaches complement traditional space radiation efforts and should provide future space explorers with more options to safeguard their short and long-term health.


Effect of Exposure to Cats and Dogs on the Risk of Asthma and Allergic Rhinitis: A Systematic Review and Meta-analysis.
Controversies persist regarding whether exposure to cat or dog increases the risk of asthma and allergic rhinitis. This meta-analysis aimed to assess the associations between exposure to cats or dogs and the development of asthma and allergic rhinitis. A systematic review was performed to identify case-control and cohort studies before May 2019, evaluating the association between exposure to cats and dogs and the risk of asthma and rhinitis. The risk of bias was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) and risk ratios (RRs) were pooled for case-control and cohort studies, respectively. Subgroup analyses were performed on prespecified study-level characteristics. The meta-analysis of 34 cohort studies showed a protective role of exposure to cats [RR: 0.88, 95% confidence interval (CI): 0.77-0.99] or dogs (RR: 0.85, 95% CI: 0.73-0.97) in the development of asthma. The subgroup analysis of birth cohort (RR: 0.74, 95% CI: 0.56-0.93) and children population (RR: 0.83, 95% CI: 0.70-0.96) also suggested a favorable role of exposure to dogs in the development of asthma. Pooled evidence from 13 case-control studies indicated no significant impact of cats (OR: 1.66, 95% CI: 0.39-2.94) and dogs (OR: 1.22, 95% CI: 0.92-1.52) on the development of asthma. A pooled analysis of five cohort studies showed a favorable effect of exposure to cats (RR: 0.60, 95% CI: 0.33-0.86) or dogs (RR: 0.68, 95% CI 0.44-0.90) on the development of allergic rhinitis. The findings indicated a protective effect of exposure to cats and dogs, especially ownership, on the development of asthma and allergic rhinitis.


N-doped graphene aerogel cathode with internal aeration for enhanced degradation of p-nitrophenol by electro-Fenton process.
A columnar N-doped graphene aerogel (NGA) was successfully fabricated by one-step hydrothermal synthesis using L-hydroxyproline as reductant, N-doping, and swelling agent, and it was used as the cathode with internal aeration mode for the electro-Fenton degradation of p-nitrophenol. Owing to the stable solid-liquid-gas three-phase interface, more active defects, and modulated nitrogen dopants, the NGA cathode exhibited enhanced electrocatalytic activity. H2O2 could be continuously electro-generated via a two-electron oxygen reduction, and the yield of H2O2 was 153.3 mg·L-1·h-1 with the low electric energy consumption of 15.3 kWh kg-1. Simultaneously, the NGA cathode had better charge transfer capability with N-doping, which was conducive to the conversion of Fe3+/Fe2+. Under the optimal condition, nearly 100% removal of p-nitrophenol and 84% removal of TOC were obtained within 60 and 120 min, respectively. The NGA cathode also presented good stability and versatile applicability in different water matrices. Therefore, the NGA is a cost-effective cathode material in electro-Fenton system with adequate activity and reuse stabilization.


Localization and identification of gamma-endorphin and beta-endorphin-like peptides in the hypothalamus and ventral forebrain of the rat.
Gamma-endorphin (gamma E) and related peptides were localized in the brain of the rat, and compared to the distribution of beta-endorphin related peptides. gamma E-like immunoreactivity (gamma E-LI) was shown to exist only in brain regions known to receive innervation from POMC neurons but not in their pericaria in the arcuate nucleus. Nuclei of the hypothalamus and ventral forebrain contained the major concentration of gamma E-LI and extracts from these regions were purified and subjected to HPLC in order to identify gamma E-related peptides. gamma E, des-tyrosine1 gamma E, des-enkephalin-gamma E, and alpha-N acetyl gamma E co-elutable peptides as well as various unidentified forms were evident. This study provides evidence of the endogenous presence of pharmacologically active gamma E-related peptides in brain regions where they have been postulated to modulate dopaminergic transmission.


Behavioral correlates of hippocampal type 2 theta in the rat.
Previous research has indicated that there are two types of theta activity which can be recorded from the hippocampus in most rodents. One type (type 1) of theta is correlated with voluntary movements while the second (type 2) occurs during immobility. A third waveform termed LIA (Large Amplitude Irregular Activity) occurs during more automatic behaviors, e.g., grooming, shivering or immobility. In the rabbit and guinea pig type 2 theta can readily be elicited in unrestrained animals. However, type 2 theta is rarely seen in the unrestrained rat. The purpose of the present study was to determine the stimulus conditions that are necessary for the elicitation of type 2 theta in the rat. In the present study 20 unrestrained rats were observed in the presence of a cat or a ferret. Movements by the cat or ferret produced theta in immobile rats. Sensory stimuli which did not ordinarily produce type 2 theta would reliably do so in the presence of the cat or ferret. It is hypothesized that type 2 theta in the unrestrained immobile rat occurs during sensory processing but only when the animal is in a high state of "arousal."


β-adrenergic agonist infusion during extracorporeal lung perfusion: effects on glucose concentration in the perfusion fluid and on lung function.
We recently showed in a pig model of ex vivo lung perfusion (EVLP) that lung edema correlates with glucose consumption. We investigated whether salbutamol, a β-adrenergic receptor agonist known to upregulate fluid transport in the lung, modulates glucose concentration in the perfusate during EVLP. Lungs from domestic pigs underwent normothermic EVLP. At the end of controlled reperfusion, lungs were ventilated and perfused for 60 minutes, then randomized to salbutamol (β-Agonist) infusion or placebo (Control) for 180 minutes. Functional parameters were assessed. In the β-Agonist group, glucose concentration decreased over time more than corresponding Control values (analysis of variance [ANOVA], p = 0.05). Mean pulmonary artery pressure (mPAP) was 16 ± 1 mm Hg in the β-Agonist group vs 21 ± 1 mm Hg in the Controls (ANOVA p < 0.05). Baseline mPAP was correlated with the drop of mPAP after the β-agonist infusion (R(2) = 0.856, p < 0.05). Dynamic compliance dropped from 51 ± 10 to 31 ± 6 ml/cm H(2)O in the β-Agonist group and from 60 ± 4 to 21 ± 3 ml/cm H(2)O in the Control group (ANOVA, p < 0.05 β-agonist vs Control). The Δ partial pressure of oxygen/fraction of inspired oxygen was 418 ± 15 and 393 ± 12 mm Hg in the β-Agonist and Control groups, respectively (t-test p = 0.106). Glucose concentration in the perfusate was affected by salbutamol. Salbutamol was associated with lower pulmonary pressures and better lung mechanics. These data suggest a possible role for salbutamol as a pharmacologic adjunct during EVLP before transplantation.


CCAAT/enhancer-binding proteins (C/EBPs) regulate the basal and cAMP-induced transcription of the human 11beta-hydroxysteroid dehydrogenase encoding gene in adipose cells.
Android obesity is often associated with a metabolic syndrome characterized, in particular, by a type 2 diabetes and cardiovascular problems. This could be induced by an excess of local production of glucocorticoids (GC) by adipose tissue (or other tissues). This production of GC by its target tissues depends on the 11beta-hydroxysteroid dehydrogenase type 1 (11betaHSD1) enzyme. Our aim was to characterize some mechanisms which control the expression of the human 11betaHSD1 gene (hHSD11B1) in preadipocytes. By using different luciferase constructs containing fragments of the hHSD11B1 promoter, we demonstrate that two members of the CCAAT/enhancer-binding protein family, C/EBPalpha and C/EBPbeta, are required for the basal transcriptional activity of HSD11B1 in 3T3-L1 preadipocyte cells. This effect depends on the binding of each isoform to specific binding sites. Mutation of either one of these sites induced a 40-50% decrease of the constitutive activity of the hHSD11B1 promoter. A forskolin treatment of 3T3-L1 preadipocyte cells induced an increased endogenous expression of HSD11B1. By transfection studies using the hHSD11B1 luciferase constructs, it appears that C/EBPbeta was strongly involved in this induction, as the forskolin stimulation was suppressed after mutation of the C/EBPbeta binding site. Part of the mechanism involved the increase of nuclear C/EBPbeta protein levels induced by forskolin and a phosphorylation step associated with an enhanced binding of the transcription factor to its site. These data indicate that members of the C/EBP family control intracellular levels of GC in preadipocytes via the regulation of the constitutive and cAMP-dependent expressions of HSD11B1.


Evaluation of a positively charged submicron emulsion of piroxicam on the rabbit corneum healing process following alkali burn.
The effect of piroxicam in three different formulations was tested on rabbits for 28 days in an alkali burn model. The ulceration healing process was determined by evaluating the severity of the burn (scored from 0 to 5), and the re-epithelization healing process was measured by the area of the defects. The results indicated that the piroxicam positively charged submicron emulsion was the most effective formulation in lowering the ulcerative cornea score while the piroxicam positively charged emulsion and the blank emulsion were more effective in promoting the re-epithelization healing process. The piroxicam solution elicited the slowest healing re-epithelization rate after 28 days and was unable to complete the entire healing process. The new positively charged submicron emulsion formulation of piroxicam had a pronounced effect on both the ulceration rate and epithelial defects in the management of corneal alkali-burning.


The adjuvanted recombinant zoster vaccine co-administered with the 13-valent pneumococcal conjugate vaccine in adults aged ≥50 years: A randomized trial.
Herpes zoster (HZ) results from reactivation of latent varicella-zoster virus. Adults at increased risk of HZ (due to immunocompromising conditions or older age) are also at risk of pneumococcal disease, both of which are preventable by vaccination. We evaluated simultaneous versus sequential administration of the adjuvanted recombinant zoster vaccine (RZV) and the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. In this phase IIIB multinational trial (NCT03439657), participants were randomized 1:1 to receive either the first RZV dose and PCV13 simultaneously followed by the second RZV dose two months later (Co-Ad, N = 449), or at two-month intervals, PCV13, the first RZV dose, and the second RZV dose sequentially (Control, N = 463). Objectives were to demonstrate that immune responses to both vaccines are non-inferior when co-administered compared to sequential administration and to evaluate the safety of their co-administration. The RZV vaccine response rate (VRR) in the Co-Ad group was 99.1% (95% confidence interval [CI]: 97.6-99.7), meeting the VRR success criterion. Non-inferiority criteria for the Co-Ad versus Control group were also met for anti-glycoprotein E antibodies (adjusted geometric mean concentration Control/Co-Ad ratio 1.07 [95%CI: 0.99-1.16]) and all PCV13 serotypes (adjusted antibody geometric mean titer Control/Co-Ad ratios 1.02 [95%CI: 0.86-1.22] to 1.36 [95%CI: 1.07-1.73]). Upon co-administration, the frequency of solicited local adverse events was consistent with the known safety profile of each individual vaccine, whereas solicited general adverse events were within the same range as for RZV alone. RZV co-administered with PCV13 had an acceptable safety profile. Humoral immune responses to both vaccines were non-inferior when co-administered compared to sequential administration. These results suggest that adults may benefit from receiving RZV and a PCV at the same healthcare visit.


The carotenoids of Flavobacterium strain R1560.
The main carotenoid of Flavobacterium strain R1560 has been identified as (3R,3'R)-zeaxanthin. Also present were small amounts of 15-cis-phytoene, phytofluene, "zeta-carotene" (7,8,7',8'-tetrahydro-psi, psi-carotene plus 7,8,11,12-tetrahydro-psi, psi-carotene), neurosporene, lycopene, beta-zeacarotene, gamma-carotene, beta-carotene, beta-cryptoxanthin, rubixanthin, 3-hydroxy-beta-zeacarotene and several apo-carotenals. Zeaxanthin production was inhibited by nicotine (10 mM), and lycopene and rubixanthin accumulated. The biosynthesis of zeaxanthin is discussed in terms of pathways and also of "half-molecule" reaction sequences. The presence of zeaxanthin may be a characteristic of a group of Flavobacterium species, and may thus be useful in the taxonomic classification of these organisms.


Characterising differences in red blood cell usage patterns between healthcare sectors in South Africa: 2014-2019.
South Africa aims to transition from a two-tiered healthcare system (public and private) to universal health coverage. Data on red blood cell (RBC) product usage reveal disparities between the sectors. Blood transfusion services further need to understand differing disease profiles and transfusion prescribing practices between the sectors to ensure blood security should the transition to a two-tiered health system come to fruition. Operational data for public and private healthcare RBC requests between 1 January 2014 and 31 March 2019, obtained from the South African National Blood Service (SANBS), were retrospectively analysed. Sector-specific demographic and utilisation trends were compared for the dominant clinical disciplines. Pre-transfusion haemoglobin (Hb) patterns were also delineated for 2018. Between 2014 and 2019, 2,356,411 public and private sector RBC transfusion events resulted in the issue of 4,020,094 RBC units (1,553,159 transfusion events and 2,495,054 units within the public sector versus 803,282 transfusion events and 1,525,040 units in private). The dominant clinical disciplines within the public sector were Medical (32.9%), Gynaecology/Obstetrics (27.3%), General Surgery (13.6%), and Paediatrics (including Paediatric Surgery) (6.5%), compared to Intensive Care Units (33.2%), Medical (28.3%), General Surgery (10.4%), and Haematology/Oncology (8.3%) in the private sector. Median pre-transfusion Hb values for 2018 were lower in the public than in the private sector: 6.9 g/dL public sector versus 8 g/dL private sector. Clinical drivers of RBC usage within the public and private healthcare sectors in South Africa differ significantly. Disparate pre-transfusion Hb between the sectors are likely due to differing disease profiles and severity, as well as differences in practice in prescribing transfusions. Implementation of a nationally co-ordinated Patient Blood Management programme may help to address these disparities and help ensure a sustainable blood transfusion system.


[Cost-effectiveness analysis high flow oxygen therapy in the treatment of SARS-CoV-2 pneumonia].
high-oxygen nasal cannulas in patients with respiratory failure secondary to SARS-CoV-2 pneumonia have not been studied from a cost-effectiveness point of view. Retrospective analysis of patients who had entered the COVID-area of an intensive medicine service in a third reference hospital, between March-December 2020. An effectiveness cost analysis was carried out comparing 2therapeutic decisions: the experimental strategy was defined as a mixed strategy consisting of the initial application of high flow nasal oxygen (HFNO) and application of VMI only to HFNO failures. The optimal rational decision was defined as maximizing expected profit, and economic efficiency was assessed by calculating the Incremental Cost-Effectiveness Ratio (ICER) for years of life gained. Of the 185 patients tested, 101 (55%) received invasive mechanical ventilation immediately and 84 (45%) were treated with HFNO at the outset. In the cost-effectiveness analysis, comparing both therapeutic strategies, the probability that the experimental strategy would be more effective was 0.974, reaching statistical significance: Difference in average proportions -0.113; 95% CI:-0.018 to -0.208. This corresponds to an NNT of 9 patients. The optimal decision was HFNO's strategy followed by VMI in HFNO failures. This option had an RCEI of 5582 euros per year of life gained. It is important to establish in the future reliable markers in the use of HFNO so that this therapy improves its cost-effective benefits.


Predicting the complex phase behavior of self-assembling drug delivery nanoparticles.
Amphiphilic lyotropic liquid crystalline self-assembled nanomaterials have important applications in the delivery of therapeutic and imaging agents. However, little is known about the effect of the incorporated drug on the structure of nanoparticles. Predicting these properties is widely considered intractable. We present computational models for three drug delivery carriers, loaded with 10 drugs at six concentrations and two temperatures. These models predicted phase behavior for 11 new drugs. Subsequent synchrotron small-angle X-ray scattering experiments validated the predictions.


Preparation of amyloid-like fibrils containing magnetic iron oxide nanoparticles: effect of protein aggregation on proton relaxivity.
A method to prepare amyloid-like fibrils functionalized with magnetic nanoparticles has been developed. The amyloid-like fibrils are prepared in a two step procedure, where insulin and magnetic nanoparticles are mixed simply by grinding in the solid state, resulting in a water soluble hybrid material. When the hybrid material is heated in aqueous acid, the insulin/nanoparticle hybrid material self assembles to form amyloid-like fibrils incorporating the magnetic nanoparticles. This results in magnetically labeled amyloid-like fibrils which has been characterized by Transmission Electron Microscopy (TEM) and electron tomography. The influence of the aggregation process on proton relaxivity is investigated. The prepared materials have potential uses in a range of bio-imaging applications.


Near-infrared and orange-red emission from a continuous-wave, second-Stokes self-Raman Nd:GdVO4 laser.
We report the first cw intracavity crystalline Raman laser operating at the second-Stokes wavelength. Approximately 950 mW emission is obtained at 1308 nm from a Nd:GdVO(4) self-Raman laser, with an overall (diode to 1308 nm) conversion efficiency of 6.8%. By intracavity sum-frequency mixing the first- and second-Stokes lines, 1027 mW emission at 620 nm is demonstrated with an overall (diode-to-visible) conversion efficiency of 4.9%.


Distributional shape of nutrition data.
Nutrition data from 111 undergraduate college students (51 males and 60 females, ranging in age from 17 to 24) were studied with respect to the shape of the underlying probability distributions. Three-day averages for total energy, percent protein, percent saturated fat, percent unsaturated fat, percent complex carbohydrates, percent refined carbohydrates, cholesterol, sodium, vitamin C, and iron (measured in milligrams) were computed, and their distributions were compared with the normal (Gaussian) distribution. The distribution of values of sodium for females and, to a lesser extent, cholesterol for females and of cholesterol and vitamin C for males, differed from the normal distribution. The remaining distributions appeared to be reasonably close to normal in shape. It is recommended that nutrition researchers verify the normal distribution assumptions prior to applying parametric techniques to their data and that they use nonparametric (distribution-free) techniques to analyze their data whenever those assumptions are not valid.


Effect of intravenous lipid on human pancreatic secretion.
Parenteral alimentation, including intravenous fat, is sometimes used in the treatment of patients with pancreatitis, although the effect of intravenous fat on human pancreatic secretion has not been systematically studied. Intravenous fat, however, has been shown to stimulate pancreatic protein secretion in the dog. The purpose of these studies was to clarify the effect of intravenous fat on human pancreatic secretion. Pancreatic secretion was assessed by measurement of enzymes and bicarbonate in duodenal aspirate collected via a double-lumen tube from 6 healthy volunteers. Four studies were randomly conducted on different days. On day 1, graded concentrations of Intralipid (5%, 10%, and 20%) were given intravenously for 1 h each, while secretin (8.2 pmol . kg-1 . h-1) was given as a background. On day 2, the same doses of Intralipid were infused intravenously without secretin. On day 3, the same doses of Intralipid were perfused into the intestine, and, finally, on day 4, 20% Intralipid was given by intestinal infusion for 2 h while 10% Intralipid was infused intravenously during the second hour. Significant stimulation of enzyme secretion was observed only during the infusion of fat into the intestine, not after intravenous infusion at any concentration. Pancreatic enzyme secretion, stimulated by intraintestinal fat, was not significantly modified by simultaneous intravenous lipid infusion. We conclude that since intravenous fat does not stimulate pancreatic secretion, its use in conditions where pancreatic stimulation is undesirable appears safe.


Autoantibody Profile of a Cohort of 78 Italian Patients with Mucous Membrane Pemphigoid: Correlation Between Reactivity Profile and Clinical Involvement.
Direct diagnosis of mucous membrane pemphigoid (MMP) is not easy. Circulating autoantibodies targeting bullous pemphigoid antigens of 180 kDa and 230 kDa (BP180 and BP230), α6β4 integrin, laminin 332 and type VII collagen (Col VII) are not always present. The aims of this study were to characterize the humoral immune response of a cohort of Italian patients with MMP, its association with clinical involvement and severity, and to design an algorithm for efficient serological diagnosis. Seventy-eight MMP sera were studied retrospectively by indirect immunofluorescence on salt-split skin, enzyme-linked immunosorbent assay (ELISA) and immunoblotting. Indirect immunofluorescence on salt-split skin resulted in the most sensitive approach for diagnosis of MMP. BP180 was the major autoantigen in MMP patients with oral and cutaneous involvement. Significant associations were found between BP180 reactivity and oral and cutaneous localization of the lesions (p = 0.006), and between Col VII positivity and Setterfield severity score (p = 0.020).


Keap1 Cystenine 151 as a Potential Target for Artemisitene-Induced Nrf2 Activation.
Artemisitene (ATT) activates the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) by increasing its stabilization and reducing ubiquitination. The cysteine (Cys) residues of the cytosolic Nrf2 repressor Kelch-like ECH-associated protein-1 (Keap1) function as redox sensors and may be crucial in activating Nrf2. To determine whether ATT-induced Nrf2 activation is dependent on the modification of Keap1 and to elucidate the underlying mechanism, we transfected cell lines with six different Keap1 mutant constructs, each with a Cys (-77, -151, -257, -273, -288, and -297) to Ser substitution. Only the Cys151Ser mutant prevented ATT-mediated activation of Nrf2, indicating that the Cys151 residue of Keap1 likely interacts with ATT and is essential for Nrf2 stabilization and transcription of downstream genes. Our finding provides a pharmacological basis for using artemisitene against oxidative stress-related diseases.


Apparent diffusion coefficients in oligodendroglial tumors characterized by genotype.
To investigate whether oligodendroglial tumors with or without 1p/19q loss differ in their diffusion-weighted imaging characteristics. Oligodendroglial tumors with or without 1p/19q loss differ in their therapeutic responsiveness and prognosis, and recent reports also suggest that these tumors may differ in their magnetic resonance characteristics and blood volume. Apparent diffusion coefficients (ADCs) were assessed in three grade II oligodendrogliomas, nine grade II and five grade III oligoastrocytomas with known 1p/19q status. Regions of interest (ROIs) were placed on ADC maps: 1) around tumor margins to generate pixel histograms; 2) over minimum and maximum tumor ADC; 3) on areas comparable to the highest choline (Cho)/creatine (Cr) ratio determined from chemical shift imaging (CSI); and 4) across tumor margins to measure the ADC transition coefficient (ATC). Tumor ADC was significantly different from normal brain (P < 0.001). ADC in regions of highest Cho/Cr was greater than minimum ADC and did not correlate with the Cho/Cr ratio. ADC and ATC were not significantly different between oligodendroglial subtypes or grades. Tumors with intact 1p/19q had higher maximum (P = 0.021) and histogram ADC (P = 0.015), and greater ATC (P = 0.001) compared to those with 1p/19q loss, which may reflect differences in edema and cellularity. This preliminary study identified differences in ADC and ATC between oligodendroglial tumor genotypes that may reflect underlying biology. Confirmation in a larger series is warranted.


Effects of mercaptoacetate on feeding, circulating glucose and lipids, and gastric emptying in rats fed a carbohydrate-free high-fat diet.
In the present study we investigated whether glucose deprivation contributes to feeding induced by mercaptoacetate (MA), an inhibitor of fatty acid oxidation, in Sprague-Dawley rats fed a carbohydrate-free, high-fat diet (HF-rats). The results show that inhibition of fatty acid oxidation by MA, reflected by a decrease in plasma beta-hydroxybutyrate, elicited eating in the HF-rats and that the eating response was not associated with a decrease in circulating glucose. The effect of MA on food intake was tested in two different substrains (Zur:SD and Ico:OFA SD) of Sprague-Dawley rats. The threshold dose of MA for eliciting eating was much higher in Zur:SD (between 800 and 1,600 micromol/kg) in comparison to Ico:OFA SD rats (between 200 and 400 micromol/kg). At a high dose of MA (1,200 micromol/kg), but not at a low dose (400 micromol/kg) the feeding response in the Ico:OFA SD rats was associated with hyperglycemia due to an increase in glycogenolysis. Unlike in Zur:SD, in Ico:OFA SD rats the higher doses of MA (800 and 1,200 micromol/kg but not 400 micromol/kg) produced a long-term suppression of feeding, which partly might be causally related to the observed inhibitory effect of MA on gastric emptying. The present results indicate that glucose deprivation does not contribute to feeding elicited by MA-induced inhibition of fatty acid oxidation in rats fed a carbohydrate-free, high-fat diet.


Neisseria flavescens Infection in Atypical Multiple Vallecular Cysts.
A 53 year-old female patient presented with symptoms of intermittent odynophagia and halitosis persisting for 2 months. Physical examination revealed bilateral lingual tonsillar cysts and multiple vallecular cysts with clear fluid. Laboratory studies were unremarkable. The patient underwent surgery, during which uncapping of the multiple vallecular cysts was performed, and multiple microbiological samples and biopsies were taken. After surgery, the patient had complete resolution of all her symptoms. Pathological results demonstrated lymphoepithelial cysts. Microbiological tests demonstrated an infection by Neisseria flavescens, which is a non-pathogenic commensal of the oropharynx, and has never been described as causing agent of infected vallecular cysts.


Theoretical modeling of prion disease incubation.
We apply a theoretical aggregation model to laboratory and epidemiological prion disease incubation time data. In our model, slow growth of misfolded protein aggregates from small initial seeds controls the latent or lag phase; aggregate fissioning and subsequent spreading leads to an exponential growth phase. Our model accounts for the striking reproducibility of incubation times for high dose inoculation of lab animals. In particular, low dose yields broad incubation time distributions, and increasing dose narrows distributions and yields sharply defined onset times. We also explore how incubation time statistics depend upon aggregate morphology. We apply our model to fit the experimental dose-incubation curves for distinct strains of scrapie, and explain logarithmic variation at high dose and deviations from logarithmic behavior at low dose. We use this to make testable predictions for infectivity time-course experiments.


Lower-Limb Factors Associated with Balance and Falls in Older Adults: A Systematic Review and Clinical Synthesis.
Despite sufficient evidence to suggest that lower-limb-related factors may contribute to fall risk in older adults, lower-limb and footwear influences on fall risk have not been systematically summarized for readers and clinicians. The purpose of this study was to systematically review and synethesize the literature related to lower-limb, foot, and footwear factors that may increase the risk of falling among community-dwelling older adults. We searched PubMed, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Library, and AgeLine. To describe the trajectory toward increasing risk of falls, we examined those articles that linked age-related changes in the lower limb or footwear to prospective falls or linked them to evidenced-based fall risk factors, such as gait and balance impairment. This systematic review consisted of 81 articles that met the review criteria, and the results reflect a narrative review of the appraised literature for eight pathways of lower-limb-related influences on fall risk in older adults. Six of the eight pathways support a direct link to fall risk. Two other pathways link to the intermediate factors but lack studies that provide evidence of a direct link. This review provides strong guidance to advance understanding and assist with managing the link between lower-limb factors and falls in older adults. Due to the lack of literature in specific areas, some recommendations were based on observational studies and should be applied with caution until further research can be completed.


Au Gratings Fabricated by Interference Lithography for Experimental Study of Localized and Propagating Surface Plasmons.
Optical properties of high-frequency Au gratings with a fixed period (296.6 ± 0.5 nm) and a variable modulation depth are studied using measurements of spectral and angular dependence of transmission and reflection of polarized light in order to build the dispersion curves of excited optical modes and to identify their types. It was shown that in gratings with small modulation depth only propagating surface plasmon-polaritons (SPP) modes were observed. With increasing of modulation depth, the intensity of SPP decreases and localized plasmon (LP) resonance appears, which is more intense at small incident angles, and overlaps with the SPP modes. For grating with isolated grooves (nanowires), mostly LP resonance is observed. After additional deposition of gold onto grating with isolated grooves, the intensity of the SPP mode increases again, and the LP band maximum shifts to longer wavelengths.


Immunofluorescent localization of histone H10 in the nuclei of proliferating and differentiating Friend cells.
By using affinity-purified antibodies to H10 and to H1AB the localization of these histones was studied by indirect immunofluorescence in the nuclei of proliferating (EAT and uninduced Friend cells) and of differentiating (induced Friend cells) cell populations. While with H1AB antibodies a bright fluorescence all over the chromatin was obtained, the localization of H10 varied depending on the state of the cell population. In the proliferating EAT cells it was localized strictly in the nucleoli. The Friend cell population revealed a heterogeneous picture with two types of H10 localization-nucleolar predominating in uninduced cell populations and peripheral predominating in induced cells. A comparison with literature data suggests that H10 seems to be associated with chromatin regions containing active genes.


The natural history of human papillomavirus infection.
Human papillomavirus (HPV) is a small double-stranded DNA virus that commonly infects humans. The oncogenic characteristics of HPV derive from the oncoproteins E6 and E7 that act inhibiting p53 and pRB tumor suppressors. About 5% of all cancers worldwide are attributable mainly to those known as high-risk, including HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Infection with HPV is common after sexual initiation, but the majority of HPV infections do not cause symptoms or disease and are cleared within 12-24 months post-infection. Only a small fraction of those infections that persist or progress to a preneoplastic lesion result in cancer. Persistence of HPV infection is needed to start the oncogenic process. Clearance of infection is common in young adults. Viral load and viral type are the main cofactors for progression from infection to cervical intraepithelial lesions and cancer. Smoking, hormonal exposure, and HIV are additional exposures that increase the risk of progression to cancer. The adverse health effects of HPV infections can be largely controlled through vaccination and screening.