Empirical Bayesian analysis of paired high-throughput sequencing data with a beta-binomial distribution.
Pairing of samples arises naturally in many genomic experiments; for example, gene expression in tumour and normal tissue from the same patients. Methods for analysing high-throughput sequencing data from such experiments are required to identify differential expression, both within paired samples and between pairs under different experimental conditions. We develop an empirical Bayesian method based on the beta-binomial distribution to model paired data from high-throughput sequencing experiments. We examine the performance of this method on simulated and real data in a variety of scenarios. Our methods are implemented as part of the RbaySeq package (versions 1.11.6 and greater) available from Bioconductor (http://www.bioconductor.org). We compare our approach to alternatives based on generalised linear modelling approaches and show that our method offers significant gains in performance on simulated data. In testing on real data from oral squamous cell carcinoma patients, we discover greater enrichment of previously identified head and neck squamous cell carcinoma associated gene sets than has previously been achieved through a generalised linear modelling approach, suggesting that similar gains in performance may be found in real data. Our methods thus show real and substantial improvements in analyses of high-throughput sequencing data from paired samples.


Correction to: Perioperative antibiotic prescribing in surgery departments of two private sector hospitals in Madhya Pradesh, India.
[This corrects the article DOI: 10.1186/s13741-019-0121-3.].


Economic evaluation of facility-based HIV self-testing among adult outpatients in Malawi.
HIV self-testing (HIVST) in outpatient departments (OPD) is a promising strategy for HIV testing in Malawi, given high OPD patient volumes and substantial wait times. To evaluate the relative cost and expected impact of facility-based HIVST (FB-HIVST) at OPDs in Malawi for increasing HIV status awareness, we conducted an economic evaluation of an HIVST cluster-randomized controlled trial. A cluster-randomized trial was conducted at 15 sites in Malawi from September 2017 to February 2018 with three arms: 1) Standard provider-initiated-testing-and-counselling (PITC); 2) Optimized PITC (additional provider training and job-aids) and 3) FB-HIVST (HIVST demonstration, distribution and kit use in OPD, private kit interpretation and optional HIV counselling). The total production cost per newly identified positive and per person newly initiated on ART were calculated by study arm. These were calculated as the total cost of testing everyone divided by the number of newly identified positives; and the total cost of testing everyone divided by the number of those initiated on ART. Cost-outcomes were calculated under three cost scenarios: (1) full study costs, (2) routine implementation costs and (3) routine implementation + reduced cost for HIVST kits. The average cost per person newly diagnosed in the full study cost scenario was $101, $156 and $189, and cost per person initiated on ART was $121, $156 and $279 for Standard PITC, Optimized PITC and FB-HIVST respectively. In the routine implementation cost scenario, the average cost per person newly diagnosed was reduced to $83, and $93, and cost per person initiated on ART to $83, and $137 for Optimized PITC and FB-HIVST respectively. In the negotiated HIVST cost scenario, the average cost per person newly diagnosed was reduced to $55 and cost per person newly initiated on ART reduced to $81 in the FB-HIVST arm. While the cost per new ART initiation through FB-HIVST was higher than Standard PITC, FB-HIVST could become cost-saving compared to PITC if the cost of kits is reduced or if treatment linkage rate were increased in the FB-HIVST arm. For high volume OPDs, HIVST may increase facility capacity and increase the number of newly diagnosed positives.


Monoclonal antibodies against Fel d I and other clinically relevant cat allergens.
Several mouse monoclonal antibodies (MAbs) were obtained which specifically recognized allergen molecules from cat dander extract. Two of them (C5.8 and C5.24) were specific for the main cat allergen, Fel d I. One (C5.25) recognized an important allergen with approximate molecular weight of 30000 Da and a pI between 3.9 and 4.3. A third group of MAbs comprised several hybridomas which were specific either for cat albumin or cat immunoglobulin. The immunochemical characterization and the clinical significance of the cat dander components recognized by these MAbs is presented and discussed.


Effects of the COVID-19 Pandemic on Anxiety Symptoms in Long-Term Care Residents: A Multilevel Growth Curve Analysis.
The coronavirus disease 2019 (COVID-19) pandemic has negatively impacted the mental health functioning of older adults residing in long-term care (LTC) settings. This study examines the impact of the lockdown on anxiety symptoms over time in LTC residents. Secondary data analysis was conducted on clinical data obtained with permission from a large behavioral health company that provides behavioral health services in long-term care (LTC) and assisted living (AL) facilities. Data were obtained from 1149 adults (mean age 72.37, 70% female) in LTC and AL facilities across the United States who were receiving psychological services 1 year prior, and 1 year after, the COVID-19 pandemic lockdown. Changes in anxiety (measured using a clinician rating scale) over time before and after the pandemic were assessed using latent growth curve modeling with psychiatric diagnosis, psychiatric medication, and demographic factors included as covariates. Anxiety severity decreased over time before and after the onset of the COVID-19 pandemic. Although pandemic-level factors such as facility closure and telehealth availability did not affect anxiety over time, individual treatment factors such as obsessive compulsive disorder diagnosis, initial anxiety severity, bipolar disorder diagnosis, and prescriptions for anxiolytic and antipsychotic medications affected the trajectory of anxiety during the pandemic. These results demonstrate that individual covariates such as diagnosis, symptom severity, and medication use impacted the trajectory of anxiety symptoms before and during the COVID-19 pandemic more strongly than pandemic-related circumstances (facility closure, telehealth availability). The impact of the COVID-19 pandemic may be better observed through treatment-relevant variables, rather than pure symptom severity. In preparation for future pandemics or other large-scale disasters potentially impacting service delivery, facilities should continue to prioritize continuity of care or a timely resumption of services attending to individual treatment factors.


Responses to ammonium and nitrate additions by boreal plants and their natural enemies.
Separate effects of ammonium (NH4+) and nitrate (NO3-) on boreal forest understorey vegetation were investigated in an experiment where 12.5 and 50.0 kg nitrogen (N) ha(-1) year(-1) was added to 2 m2 sized plots during 4 years. The dwarf-shrubs dominating the plant community, Vaccinium myrtillus and V. vitis-idaea, took up little of the added N independent of the chemical form, and their growth did not respond to the N treatments. The grass Deschampsia flexuosa increased from the N additions and most so in response to NO3-. Bryophytes took up predominately NH4+ and there was a negative correlation between moss N concentration and abundance. Plant pathogenic fungi increased from the N additions, but showed no differences in response to the two N forms. Because the relative contribution of NH4+ and NO3- to the total N deposition on a regional scale can vary substantially, the N load a habitat can sustain without substantial changes in the biota should be set considering specific vegetation responses to the predominant N form in deposition.


Hydrogen peroxide burst triggers accumulation of jasmonates and salicylic acid inducing sesquiterpene biosynthesis in wounded Aquilaria sinesis.
Agarwood, a non-timber fragrant wood, is produced in wounded Aquilaria trees and widely used in perfume, incense, and medicine. Sesquiterpene is one of its main active compounds. It has been demonstrated that hydrogen peroxide (H2O2) plays a role in promoting agarwood sesquiterpene biosynthesis, but little is known about its signaling pathway. In this study, the pruning of actively growing saplings of A. sinensis resulted in an H2O2 burst and the accumulation of jasmonic acid (JA), salicylic acid (SA), and ethylene (ET), which was followed by the up-regulation of sesquiterpene synthase and the production of sesquiterpene in the pruned stems. This process could be enhanced by absorbed H2O2 and inhibited by an H2O2 scavenger (ascorbate, AsA) in pruned stems, although the concentration of ET and transcription of ET-related synthase genes remained unaffected. These results confirmed that the H2O2 burst in wounded stems triggered JA and SA accumulation to promote agarwood sesquiterpene biosynthesis. ET was also activated by injury that was independent with H2O2. All results excavated a full-scale signaling transduction nets among multiple stress signals during wound-induced agarwood production in A. sinensis and provide a new insight into improving the artificial technology of agarwood production.


Isolation and characterization of urethanase from Penicillium variabile and its application to reduce ethyl carbamate contamination in Chinese rice wine.
A strain with urethanase activity was isolated from mouse gastrointestine. By combination of morphological characterization of the colony, hyphae, and spore and the sequence analysis of its rDNA ITS, the strain was determined as Penicillium variabile and named as P. variabile JN-A525. The enzymatic properties of urethanase from P. variabile JN-A525 were further studied. The optimum temperature and pH value of urethanase are of 50 °C and 6.0, respectively. The enzyme maintains stability when the temperature is below 50 °C and the pH is in the range of 7.0-10.0. The enzyme also exhibits ethanol tolerance. It can remove ethyl carbamate from Chinese rice wine without the change of flavor substances in the wine.


Shipboard determination of radiocesium in seawater after the Fukushima accident: results from the 2011-2012 Russian expeditions to the Sea of Japan and western North Pacific Ocean.
A total of 88 seawater samples were collected during two Russian research expeditions (April-May 2011 and August-September 2012) to the Sea of Japan, the Oyashio Current region near Kuril Islands and the Kuroshio-Oyashio transition area in the western North Pacific Ocean. The observations were made aboard the R/V Pavel Gordienko and Akademik Shokalsky in order to study the impact of the Fukushima accident on radioactive contamination of the marine environment. On the board of a ship, the water samples were passed through filters to retain particles with the size of >1 micron. Cesium was extracted from the large volumes (100-3000 L) of the filtrated water using a selective fiber chemisorbent impregnated with copper ferrocyanide. Measurements of (134)Cs and (137)Cs activities in 83 samples of sorbents and 21 samples of filters were performed in the ship-based laboratory with a semiconductor HP-Ge detector. The quantified activity concentrations of dissolved radiocesium ranged from 1 Bq m(-3) to 34 Bq m(-3) for (137)Cs and from 0.2 Bq m(-3) to 29 Bq m(-3) for (134)Cs. Activity concentrations of (137)Cs and (134)Cs were strongly correlated with each other (r = 0.993, n = 59). The (137)Cs/(134)Cs activities ratio in the Fukushima-derived radiocesium inventory for the study areas was deduced to be 0.99 ± 0.03 (on 15 March 2011) and the pre-Fukushima background level of (137)Cs in seawater was estimated as 1.3 ± 0.3 Bq m(-3). The lowest activities of both isotopes were determined in the western part of the Sea of Japan near the Russian coast, while the maximal levels were observed in the open Pacific Ocean, some 500-800 km offshore the Fukushima Dai-ichi Nuclear Power Plant. Contamination with (134)Cs at a level of 0.3-2.6 Bq m(-3) was registered in seawater samples collected in 2011 near the Kuril Islands and Kamchatka in the Oyashio Current region. During the period from April-May 2011 to August-September 2012, activity concentrations of (137)Cs and (134)Cs in surface waters had decreased for all seven stations repeatedly sampled in the study. A detailed observation of radiocesium distribution within the water column down to the depth of 200 m at nine stations from the Kuroshio-Oyashio Interfrontal Zone and Kuroshio Extension in 2012 revealed maximal activity concentrations of both cesium radionuclides in the 100-200 m depth layer. The average inventory of Fukushima-derived (137)Cs in the top 200 m of the water column for the nine stations was estimated as 1.19 kBq m(-2) (decay corrected to 15 March 2011) which is 4.6 times higher than the background value of 0.26 kBq m(-2) expected for this depth. The monitoring results obtained in the study and relevant data published by others show that following the Fukushima accident, the Oyashio current acts as a provider of low-contaminated subarctic waters to the heavily contaminated Kuroshio-Oyashio mixed water region.


The efficient removal of methylene blue from water samples using three-dimensional poly (vinyl alcohol)/starch nanofiber membrane as a green nanosorbent.
In the present study, a simple, fast, and economical method was introduced to eliminate methylene blue from dye wastewater water using a non-toxic, inexpensive, stable, and efficient adsorbent. The poly (vinyl alcohol) (PVA)/starch hydrogel nanofiber membrane with high surface area and the three-dimensional structure was fabricated in water via electrospinning strategy, and the cross-linking reaction was done by thermal treatment. The characterization of the nanofibers was carried out using Fourier-transform infrared spectrometer (FT-IR) and field-emission scanning electron microscopy (FE-SEM), and the cross-linked PVA/starch nanofiber was applied as a membrane for the removal of methylene blue (MB). The recovery of MB was performed by methanol solution containing 5% (v/v) HCl. Langmuir isotherm model successfully described the adsorption of MB on nanosorbent, and the maximum adsorption capacity (qm) was 400 mg g-1. Also, the kinetic of adsorption was well fitted by the pseudo-second-order model. In this study, because of the high stability of fabricated membrane (based on the tensile testing), it can be used as a filter for the fast separation of MB (cationic dye) and methyl orange (MO, anionic dye). Graphical abstract.


Rhamnazin suppresses melanosome transport by promoting the ubiquitin-mediated proteasomal degradation of melanophilin.
Melanosomes are intracellularly transported from the perinuclear region to the cell periphery and then to neighboring keratinocytes. We recently reported that the flavonoid rhamnazin suppresses melanosomal transport within pigment cells, yet the action mechanism remained unclear. Our aim was to elucidate how rhamnazin influences the intracellular transport of melanosomes. A melanosome distribution assay and immunostaining were performed using B16F10 mouse melanoma cells and normal human epidermal melanocytes, respectively. Expression levels of melanosome transport-related proteins, including melanophilin (MLPH), RAB27A, and myosin VA (MYO5A), were analyzed by immunoblotting. Ubiquitinated MLPH was detected using a commercial ubiquitin detection kit. To investigate the interaction between rhamnazin and MLPH, we prepared rhamnazin conjugated with magnetic FG beads. Immunoblotting analysis revealed that rhamnazin specifically reduces the expression of MLPH but not RAB27A or MYO5A proteins. The ubiquitin detection assay, which made use of a proteasome inhibitor, showed that MLPH accumulated as a polyubiquitinated protein after treatment with rhamnazin. We speculated that the affinity of rhamnazin for the components of the melanosome transport-related tripartite complex may alter the stability of the formation of the tripartite assembly. By using affinity-based techniques with B16F10 whole cell lysates or recombinant MLPH and RAB27A proteins, we revealed the interaction of rhamnazin with the components of the tripartite complex. We found that rhamnazin inhibits intracellular transport of melanosomes through proteasomal degradation of MLPH. Our results suggest that topical application of rhamnazin may provide a new approach for treating skin pigmentation disorders.


A procedure to validate and correct the 13C chemical shift calibration of RNA datasets.
Chemical shifts reflect the structural environment of a certain nucleus and can be used to extract structural and dynamic information. Proper calibration is indispensable to extract such information from chemical shifts. Whereas a variety of procedures exist to verify the chemical shift calibration for proteins, no such procedure is available for RNAs to date. We present here a procedure to analyze and correct the calibration of (13)C NMR data of RNAs. Our procedure uses five (13)C chemical shifts as a reference, each of them found in a narrow shift range in most datasets deposited in the Biological Magnetic Resonance Bank. In 49 datasets we could evaluate the (13)C calibration and detect errors or inconsistencies in RNA (13)C chemical shifts based on these chemical shift reference values. More than half of the datasets (27 out of those 49) were found to be improperly referenced or contained inconsistencies. This large inconsistency rate possibly explains that no clear structure-(13)C chemical shift relationship has emerged for RNA so far. We were able to recalibrate or correct 17 datasets resulting in 39 usable (13)C datasets. 6 new datasets from our lab were used to verify our method increasing the database to 45 usable datasets. We can now search for structure-chemical shift relationships with this improved list of (13)C chemical shift data. This is demonstrated by a clear relationship between ribose (13)C shifts and the sugar pucker, which can be used to predict a C2'- or C3'-endo conformation of the ribose with high accuracy. The improved quality of the chemical shift data allows statistical analysis with the potential to facilitate assignment procedures, and the extraction of restraints for structure calculations of RNA.


Investigating the factors affecting health care workers' intention to remain in villages.
Settlement in a village and being native is one of the special conditions for choosing to be a health care worker as they must be accessible day and night and provide people with health services when needed. The aim of this study was to investigate the factors affecting health care workers' intention to remain in villages covered by Jundishapur University, Ahvaz, Iran. This is a cross-sectional study in 2019. The total number of health workers working at Ahvaz Jundishapur University of Medical Sciences and Health Services, Iran was 1034, amongst whom 280 individuals participated in this study. The data collection tool was a questionnaire consisted of two parts, in the first part of which there were 11 questions on personal information of the participants. In the second part, a total of six measures (physical, social, educational and cultural, occupational, welfare, personal and family) were used to examine the factors affecting the health workers' intention to remain in rural areas. The results of this study showed that the current residence of 55% of the health workers was villages while 45% of them lived in urban areas. The results indicated that there was a significant relationship between physical, social, educational and cultural, occupational, welfare, personal and family factors and the health workers' intention to remain in rural areas. Besides, female HCWs were more affected by personal and family factors compared to the male participants. Increasing the quality and paying more attention to physical, social, educational and cultural, occupational, welfare, personal and family factors can cause health workers to remain longer in rural areas.


People with Williams syndrome process faces holistically.
This study compared the performance of 47 adolescents and adults with Williams syndrome to 39 age-matched controls on a face recognition task. Using the whole-part paradigm developed by Tanaka and his colleagues, we found that although performance overall was lower in the participants with Williams syndrome, both groups showed similar patterns of performance across the different conditions. Both groups performed significantly better in the whole-face than in the isolated-part test condition for upright faces, but not for inverted faces. The whole-face advantage only in the upright condition provides strong evidence that people with Williams syndrome encode and recognize faces holistically in the same way as normal controls, suggesting the use of similar underlying neurocognitive mechanisms. These findings contradict earlier reports in the literature that people with Williams syndrome process faces abnormally.


Betaine analogues alter homocysteine metabolism in rats.
Glycine betaine supplementation lowers homocysteine levels in homocystinuria and in chronic renal failure patients through methylation catalysed by betaine-homocysteine methyltransferase (BHMT). The aim of this study was to determine the effect of glycine betaine analogues on homocysteine metabolism in Lewis rats. Glycine betaine, proline betaine, trigonelline, dimethylsulfoniopropionate (DMSP) or dimethylthetin (1.5 mmoles) was subcutaneously administered to rats fed a low betaine diet. The effect of each betaine on total plasma homocysteine and urinary and plasma betaine concentrations was monitored for 24h following administration. Baseline plasma homocysteine was 8.5 +/- micromol/l (S.E.M., n=44) and compared to controls concentrations decreased following glycine betaine (0.8+/-0.4 micromol/l, P = 0.064), DMSP (1.0+/-0.5 micromol/l, P = 0.041) and dimethylthetin (1.5 +/- 0.7micromol/l, P = 0.033) treatment, while concentrations increased following proline betaine (2.24 +/-0.7micromol/l, P = 0.002) and trigonelline (1.6 +/-0.3 micromol/l, P < 0.001) treatment. The effect of glycine betaine, DMSP and dimethylthetin on circulating homocysteine concentrations was thought to be mediated by BHMT in vivo. This hypothesis was supported by the finding that circulating glycine betaine concentrations increased following DMSP and dimethylthetin treatment. Proline betaine and trigonelline appeared to be poor BHMT substrates, being largely excreted in the urine unchanged, yet increased circulating homocysteine levels. This suggests they are inhibitors of BHMT. Urinary excretion of glycine betaine increased following treatment with all betaines, suggesting that the resorption of glycine betaine in the kidney was inhibited. The study shows that glycine betaine analogues have multiple effects on homocysteine metabolism (250).


Color and conventional image-directed Doppler ultrasonography: accuracy and sources of error in quantitative blood flow measurements.
Accuracy of two systems--conventional (DRF 400, Diasonics) and color-coded (Angiodynograph, Quantum/Phillips) image-directed Doppler ultrasonography--was investigated using an in vitro model that generated both monophasic and triphasic pulsatile flow patterns. Estimated and actual blood volume flow rates showed good correlations, but the sampling with a hand-held transducer led to wide variations in measurement error for the conventional (-69.2% to 50%) and the color-coded (-79.3% to 265.7%) systems. By performing multiple measurements, one could improve accuracy considering only the maximal values of a series instead of the mean values. Accuracy was impaired by interposed muscular or fatty tissue due to false low time-average velocity measurements caused by a loss of Doppler signal. Comparison of both systems revealed significant differences between pulsatility index values (p less than 0.001), blood flow velocities (p less than 0.001), and blood volume flow rates (p less than 0.05 for program flow, p less than 0.001 for manual and automatic flow program of the color-coded system).


Implementation of therapeutic hypothermia guidelines for post-cardiac arrest syndrome at a glacial pace: seeking guidance from the knowledge translation literature.
The 2005 International Liaison Committee on Resuscitation (ILCOR) Consensus on Science and Treatment Recommendations document represents the most extensive and rigorous systematic review of the resuscitation literature to date and included evidence-based recommendations for post-resuscitation care. A new recommendation for the induction of mild therapeutic hypothermia for comatose cardiac arrest survivors was included in this document. Accordingly, constituent national member associations of ILCOR, including the American Heart Association, incorporated the recommendation for therapeutic hypothermia into their respective guidelines. Despite these endorsements there is a concern that therapeutic hypothermia is not being used in practice. Data from a number of surveys in Europe and the United States suggest that rates of use among physicians may be as low as 30-40%. Despite the cost and effort associated with the production of these guidelines and the potential impact on patient care, current efforts in implementing the guideline have not achieved widespread success. This commentary explores the issue of underutilization of the American Heart Association guidelines for therapeutic hypothermia and looks to the knowledge translation literature to inform a new approach to implementation. We will review the underlying phenomenon of research implementation into practice, specific barriers to guideline implementation and interventions that may improve therapeutic hypothermia uptake.


Enhanced photocatalytic and SERS performance of Ag nanoparticles functionalized MoS2 nanoflakes.
We report the preparation of Ag nanoparticles functionalized MoS2 nanoflakes by using the chemical reduction method followed by the hydrothermal method. Field emission scanning electron microscopy and elemental mapping reveals the uniform functionalization of Ag nanoparticles with MoS2 nanoflakes. High density of Ag plasmonic nanoparticles onto MoS2 nanoflakes demonstrates tremendously improved charge separation behavior in Ag-MoS2 nanohybrids. Photodecomposition capability of plasmonic Ag-MoS2 nanohybrids was explored by the decomposition of industrial pollutant molecules, showing a direct correlation between the Ag content over the MoS2 surface with their photodecomposition ability. The SERS-based detection profiles of the plasmonic were investigated by the ultra-low detection of MB molecules. The Ag-MoS2 nanohybrids SERS substrate manifests the detection of MB molecules solution up to a concentration of 10-9 M with an enhancement factor of 107. In the current study, we proposed and elucidated the probable efficient charge transfer mechanism for improved photocatalytic behavior and SERS-based sensing performance.


Early clinical experience of a new heparinoid, Org 10172, in prevention of deep venous thrombosis.
The potential antithrombotic effect of a new low molecular weight heparinoid, Org 10172, was examined in a randomized, double-blind, placebo-controlled, dose-ranging pilot study of the prevention of deep venous thrombosis (DVT) in 45 high-risk patients having major thoracic or abdominal surgery for cancer. Org 10172 was given in doses of 500, 750 or 1000 U bd subcutaneously. DVT occurred in 9 of 14 patients given placebo and in 4 of 11 patients given 500 U bd but in none of the 20 patients given 750 or 1000 U bd. Operative blood loss and post-operative bleeding were not significantly different between the groups but one patient given 1000 U bd had major post-operative bleeding. Average mid-interval and trough plasma anti-Xa levels reached 0.26 and 0.20 U/ml respectively following the highest dose. It is concluded that Org 10172 is a potentially useful antithrombotic agent and that the effective and safe dose appears to be between 500 and 1000 U bd for prevention of DVT in high-risk patients.


[Genetics and arrhythmias].
In the last 50 years we have been very successful at prolonging survival and improving the quality of life of patients with cardiac disease. The innovations in technology and pharmacology, better preventive and diagnostic tools have provided tremendous breakthroughs. However, despite our best efforts, the majority of cardiac diseases are structural in origin and will progress to their ultimate outcome. Curative therapies are not available due in part to our poor understanding of the basic mechanisms responsible for these diseases. The new developments in molecular genetics and biology are likely to change the way we approach a cardiac patient in the future. The diseases are presently being deciphered at the most basic level, and the information obtained opens new possibilities not only for better therapeutic and diagnostic measures but also for prevention of the disease.


End-of-life care for the dying child: what matters most to parents.
To identify and define the dimensions of pediatric end-of-life (EOL) care that are important to parents. Parents of children who died as a result of an illness, chronic condition, or birth defect while receiving EOL care in hospital or at home in 2004 and 2005. Qualitative data derived from semi-structured and focus group interviews were analyzed using content analysis. A large pediatric hospital located in the Midwestern United States. Seven dimensions of pediatric EOL care were identified--respect for the family's role, comfort, spiritual care, access to care and resources, communication, support for parental decision making, and caring/ humanism. There are clear dimensions of pediatric EOL care that are important to parents; these can be defined in terms of health care provider behaviours, some of which require balancing seemingly conflicting objectives. Developing a measurement tool based on these dimensions would help to improve the quality of pediatric EOL care.


Study of soil to plant transfer factors of 226Ra, 232Th, 40K and 137Cs in Vietnamese crops.
The study of staple food products is crucial to assure public safety and provides input for predictive dose assessment models. To further this goal, the activity concentrations, transfer factors, and radiological hazards of 226Ra, 232Th, 40K, and 137Cs were studied for ten pairs of selected vegetables and soils in Tien Le near Hanoi in Vietnam. This is the first study in this area for Vietnamese vegetable samples. The ten most popular vegetables in Vietnamese diet were selected, namely choy sum, crown daisy, lettuce, cabbage, Malabar spinach, beans, sweet potato, potato, kohlrabi and carrot. The research results showed that the activity concentrations observed in vegetable crops did not present the previously reported strong correlation to those in soil. The ranges of TFs of 226Ra, 232Th, and 40K were 4 × 10-2 - 6.9 × 10-1, 8 × 10-2 - 9.7 × 10-1; and 1.0 × 100-1.6 × 101, respectively. Values for leafy vegetables and tubers exceed previous world range figures for Th and K. The soil has been evaluated for radiological hazard indices, which predict almost no risk to human health in the study area.


Sociodemographic factors and use of pain medication are associated with health-related quality of life: results from an adult community mental health service in Norway.
Health-related quality of life (HRQoL) is an important aspect of mental health outcomes. There are few studies on HRQoL in heterogeneous patient populations seeking help at community mental health services. The aims of the study were to compare how HRQoL, measured by the EuroQol five dimensions with five levels (EQ-5D-5L), was distributed compared to other samples from national and international studies, and to explore what factors are associated with HRQoL. In a cross-sectional study, 1379 Norwegian outpatients reported their HRQoL before starting treatment. Associations with demographic variables, job status, socio-economic status, and use of pain medication were examined using multiple regression analysis. Most of the sample, 70% to 90%, reported problems with usual activities, pain/discomfort, and anxiety/depression; 30% to 65% reported that these problems were of a moderate to extreme degree. Forty percent reported problems with mobility, and about 20% reported problems with self-care. The sample's HRQoL was considerably lower than the general population, and comparable to patient-groups from specialist mental health services. Originating from a developing country, lower level of education, lower yearly household income, being on sick leave or unemployed, and using pain medication were associated with lower HRQoL. Age, gender, and relationship status were not associated with HRQoL. This is the first study to simultaneously examine the unique contribution of these variables in one study. The most impacted domains of HRQoL were pain/discomfort, anxiety/depression, and usual activities. Lower HRQoL was associated with several socio-demographic factors and use of pain medication. These findings might have clinical implications and suggest that mental health professionals should routinely measure HRQoL in addition to symptom severity, to identify areas that should be targeted to improve HRQoL.


Modeling and countering the effects of cosmic radiation using bioengineered human tissues.
Cosmic radiation is the most serious risk that will be encountered during the planned missions to the Moon and Mars. There is a compelling need to understand the effects, safety thresholds, and mechanisms of radiation damage in human tissues, in order to develop measures for radiation protection during extended space travel. As animal models fail to recapitulate the molecular changes in astronauts, engineered human tissues and "organs-on-chips" are valuable tools for studying effects of radiation in vitro. We have developed a bioengineered tissue platform for studying radiation damage in individualized settings. To demonstrate its utility, we determined the effects of radiation using engineered models of two human tissues known to be radiosensitive: engineered cardiac tissues (eCT, a target of chronic radiation damage) and engineered bone marrow (eBM, a target of acute radiation damage). We report the effects of high-dose neutrons, a proxy for simulated galactic cosmic rays, on the expression of key genes implicated in tissue responses to ionizing radiation, phenotypic and functional changes in both tissues, and proof-of-principle application of radioprotective agents. We further determined the extent of inflammatory, oxidative stress, and matrix remodeling gene expression changes, and found that these changes were associated with an early hypertrophic phenotype in eCT and myeloid skewing in eBM. We propose that individualized models of human tissues have potential to provide insights into the effects and mechanisms of radiation during deep-space missions and allow testing of radioprotective measures.


Anaesthesia for isolated lung transplantation.
The anaesthetic management of a patient undergoing successful, left-sided orthotopic single lung transplantation is presented. Problems, specific to the operation, are featured and discussed.


Changes of tissue factor activity on inflammatory stimulus and aging in rat.
Tissue factor (TF), a principal initiator of the vertebrate coagulation cascade, is expressed in organ tissues, cells and blood. TF is known to be induced in endothelial cells, monocytes and macrophages by inflammatory stimuli and in many pathologic conditions. By using the modified method for in vivo TF activity assay, we found that turpentine oil injection as an inflammatory stimulus also induced the TF activity in lung and brain tissues of rats. And the age-related increase in TF activity was observed in healthy rat brain tissue.


High Tumor Mutation Burden and Other Immunotherapy Response Predictors in Breast Cancers: Associations and Therapeutic Opportunities.
The recent development of effective immunotherapies with immune checkpoint inhibitors for the treatment of cancer has rekindled the interest for the immune system and its activation for an anti-cancer response. At the same time, it has become evident that not all types of cancers respond equally to these treatments, and even within the same tumor type only a subset of patients derive clinical benefit. Biomarkers predictive of response to immunotherapy have been sought and in certain occasions incorporated in the indication for treatment. These include expression of PD-L1 and defects in DNA mismatch repair (MMR). Tumor mutation burden (TMB) has been associated with response to immune checkpoint inhibitors. The current investigation examines TMB as a biomarker of response to immunotherapy in breast cancer. Publicly available data from the breast cancer study of The Cancer Genome Atlas (TCGA) and the METABRIC study were analyzed. Parameters examined included the TMB and specific mutations that may impact on TMB. In addition, correlations with breast cancer sub-types were investigated. The percentage of breast cancers with high TMB (more than 192 mutations per sample) was low (3.5-4.6%) in luminal and triple-negative cancers and higher (14.1%) in the HER2-positive subset. Almost all cancers with high TMB had defects in MMR proteins or the replicative polymerases POLE and POLD1. Small sub-sets of breast cancers with high TMB exist and may present an opportunity for effective immunotherapeutic targeting.


REM sleep behavior disorder, as assessed by questionnaire, in G2019S LRRK2 mutation PD and carriers.
Rapid eye movement sleep behavior disorder occurs with idiopathic Parkinson's disease (PD) and often precedes PD. Its frequency in LRRK2-PD and utility as a preclinical marker has not been established. One hundred forty-four idiopathic PD, 142 LRRK2 G2019S mutation PD, 117 non-manifesting carriers, 93 related noncarriers, and 40 healthy controls completed the Rapid eye movement sleep Behavior Disorder Screening Questionnaire. Cut scores were met by 30.6% idiopathic PD, 19.7% LRRK2-PD, 6% nonmanifesting carriers, 20.4% related noncarriers, and 15% controls. The likelihood of abnormal scores was decreased in LRRK2-PD versus idiopathic PD (odds ratio = 0.55, P = 0.03), nonmanifesting carriers versus related noncarriers (OR = 0.25, P < 0.01), and PD of less than 3 years' duration, 1 of 19 LRRK2-PD versus 14 of 41 idiopathic PD (P < 0.05). A lower frequency of abnormal questionnaire scores is seen in LRRK2-PD, especially in early LRRK2-PD, and in nonmanifesting carriers. Therefore, the Rapid eye movement sleep Behavior Disorder Questionnaire is unlikely to serve as a preclinical marker for phenoconversion to PD.


The use of Zickel supracondylar nails in the presence of a cemented hip prosthesis.
Zickel supracondylar nails are a useful method of treating fractures of the distal third of the femur. A case is reported to show their use is not precluded by the presence of a cemented hip prosthesis.


Generation of green fluorescent protein-expressing monkey embryonic stem cells.
Monkey embryonic stem (ES) cells are a useful tool for studying early human development and evaluating the efficacy of stem cell therapy. Monkey ES cells show closer similarity to human ES cells than their mouse counterparts regarding morphology, cell surface markers, and the maintenance of pluripotency, including the leukemia inhibitory factor requirement. The generation of genetically modified monkey ES cells with a biomarker such as green fluorescent protein, which allows noninvasive monitoring of progeny ES cells, is invaluable for the development of cell transplantation therapy and the study of differentiation mechanisms in primates. Here, we describe the generation of green fluorescent protein-expressing monkey ES cells using a conventional electroporation method.


Predicting a rapid response to adalimumab treatment and favorable short-term outcomes through the high platelet count in patients with ulcerative colitis: A multicenter retrospective cohort study.
This study aimed to investigate the short-term effectiveness of adalimumab therapy in patients with ulcerative colitis (UC), especially its rapid response.This retrospective, multicenter, cohort study involved 7 institutes in Japan, compiling data from patients with UC who had received at least 1 induction dose of 160 mg of adalimumab between June 2013 and May 2017. Patients should have a Lichtiger clinical activity index score of ≥5 at the initial adalimumab administration. Remission was defined as clinical activity index score of ≤4, whereas response was defined as a reduction of ≥50% from the baseline value. Rapid responders are defined as patients who achieved response at 2 weeks.A total of 91 patients were included in this study: 37.4% and 45.1% achieved clinical response at 2 and 8 weeks, respectively, whereas clinical remission rates 12 weeks were 45.1%. Among the rapid responders, 82.4% achieved clinical remission at 12 weeks. Multivariate logistic regression analysis identified a higher platelet count as an independent prognostic factor for a higher rate of rapid response. Receiver operating characteristic curve showed that a platelet counts cutoff value of ≥312 × 10/L was associated with a rapid response.Approximately 40% of patients with UC showed a rapid response to adalimumab therapy after 2 weeks. Up to 80% of the rapid responders also achieved remission at 12 weeks. A higher platelet count was identified as an independent prognostic factor for a higher rapid response rate.


Where Women Access Contraception in 36 Low- and Middle-Income Countries and Why It Matters.
We examined where women access modern contraceptives, using recent Demographic and Health Survey data from 36 low- and middle-income countries and disaggregating results by contraceptive method, age, marital status, residence, socioeconomic status, and country income. We used bivariate and multivariate regression analysis to assess how demographic factors are associated with contraceptive source. In pooled analysis across countries analyzed, we found that 34% of users rely on private sources, 63% use public sources, and 3% use other sources. Among private sector users, 41% use pharmacies or drug shops, 11% general shops or markets, 36% private hospitals and clinics, and 12% nongovernmental or faith-based organizations. This analysis demonstrates the importance of the private sector for specific population segments including women in the wealthiest population quintile (odds ratio [OR]: 4.09, P<.001 compared with women in the poorest quintile), adolescents (OR: 2.03, P<.001 compared with women ages 40-49), never married women (OR 1.55, P<.001 compared with ever-married women), and urban women (OR: 1.42, P<.001 compared with rural women). The private sector does not only serve these populations, however. On average across countries analyzed, 22% of the poorest contraceptive users and 27% of rural users use private sources. Leveraging both sectors is key to meeting the reproductive needs of women across all sociodemographic groups in low- and middle-income countries.


Fabrication of fenofibrate nanocrystals by probe sonication method for enhancement of dissolution rate and oral bioavailability.
Fenofibrate (FBT) is lipophillic drug used in hypercholesterolemia and hypertriglyceridemia having logP 5.375, low solubility (practically insoluble in water) and low oral bioavailability (36%). The purpose of work was to develop FBT nanocrystals for the enhancement of solubility and oral bioavailability. Fenofibrate nanosuspension was prepared using probe sonicator and transformed into dry powder using freeze drying and characterized by DSC, FTIR, XRPD, SEM, particle size, polydispersity index (PDI), zeta potential, solubility, in vitro dissolution, in vivo bioavailability and stability studies. Formulation FNS3 and pure drug exhibited the in vitro dissolution about 73.89% and 8.53% in 1% sodium lauryl sulfate (SLS) media, respectively. When the particle size reduced from 80,000±923nm to 460±20nm, saturation solubility was significantly increased. The saturation solubility of formulation FNS3 in 0.5% and 1% of SLS media found to be 67.51±1.5μg/mL and 107±1.9μg/mL, respectively. While, the saturation solubility of pure drug in 0.5% and 1% of SLS was found to be 6.02±1.51μg/ml and 23.54±1.54μg/ml, respectively. The pharmacokinetic study of optimized nanocrystals (FNS3) conducted in New Zealand white rabbits showed 4.73-fold increase in relative bioavailability than that of pure drug. Long term stability studies showed that there was no significant change in the mean particle size and PDI at 5°C±3°C after 180 days. This enhanced dissolution and bioavailability of fenofibrate nanocrystals could be the promising approach for oral delivery.


Serum progesterone level above 0.85 ng/mL and progesterone/estradiol ratio may be useful predictors for replacing cleavage-stage with blastocyst-stage embryo transfer in fresh IVF/ICSI cycles without premature progesterone elevation.
To assess the impact of serum progesterone level and the progesterone/estradiol ratio on determining the appropriate day of embryo transfer in fresh IVF/ICSI cycles without premature progesterone elevation. This was a retrospective cohort study in a university teaching hospital. Only fresh embryo transfer cycles in the GnRH-antagonist protocol without elevated trigger-day progesterone levels (n = 508) were analyzed after taking into consideration the exclusion criteria. The main outcome measure was to determine the association between below and above of the cut-off values of serum progesterone level and P/E2 ratio regarding clinical pregnancy, ongoing pregnancy and live birth rates. These rates were assessed with the use of percentile and logistic regression analyses according to the threshold levels of serum progesterone levels < 0.85 ng/mL versus ≥ 0.85 ng/mL on the day of hCG administration. The clinical pregnancy rates were significantly lower in fresh cycles with P levels ≥ 0.85 ng/mL on the day of hCG administration than in cycles with P levels < 0.85 ng/mL for the cleavage-stage embryo transfers (26.7% vs. 47.5%, p = 0.001). Blastocyst-stage embryo transfer improved pregnancy results although the P levels were ≥ 0.85 ng/mL (53.8% vs. 51.4%, p > 0.05). The adjusted odds ratio of P levels < 0.85 ng/mL revealed significant differences in only cleavage-stage embryo transfer cycles (aOR = 0.424, p = 0.016). Although serum progesterone levels are below the accepted cut-off level of 1.5 ng/mL, there may be reduced pregnancy outcomes in fresh embryo transfer cycles. A threshold level such as 0.85 ng/mL may ensure the decision to replace the cleavage stage with the blastocyst-stage embryo transfer in fresh cycles without premature progesterone elevation.


Rudolf Virchow, not just a pathologist: a re-examination of the report on the typhus epidemic in Upper Silesia.
Rudolf Virchow (1821-1902) is mainly remembered as the "father" of cellular pathology; however, he was not just a pathologist. His contributions to anthropology, archeology, ethnography, and history, as well as his involvement in epidemiology, public health, and politics, portray a man with multiple interests, deeply engaged in the controversies of his time. In his Report on the Typhus Epidemics of Upper Silesia of 1848, the young Virchow reveals himself to be a self-assured pathologist, although his postmortem examinations failed to shed much light on typhus. Despite of his shortcomings and biases, Virchow's genius is revealed in his deep appreciation of the importance of the total physical, socio-cultural, economic, and political background of epidemic diseases. One can discern in the Report the making of Virchow, the politician and statesman who will contribute to the modernization of Germany's public health, and of the physician-scholar and physician-citizen who, despite of his shortcomings and militancy, continues to inspire and challenge us today.


Fixed coronal malalignment (CM) in the lumbar spine independently impacts disability in adult spinal deformity (ASD) patients when considering the obeid-CM (O-CM) classification.
Postoperative flatback has been described in detail for sagittal plane considerations over the past 2 decades, and its correlations with disability are now accepted. Fixed Coronal Malalignment (CM) has been less described, and some authors report no significant association with the clinical outcome. The O-CM classification analyses CM and incorporates specific modifiers for each curve type. This study evaluates the O-CM classification modifiers according to age, sagittal alignment, and patient-reported outcome measures (PROMs). Our hypothesis is that fixed CM correlates with PROMs independently from sagittal alignment and age. Retrospective analysis of a large adult spinal deformity (ASD) database prospectively collected. We included 747 patients from the database with long lumbar fusion (more than 3 levels), with at least two years of follow-up. Three categories of patients met the inclusion criteria (prior surgery at baseline and no revision surgery afterward, prior surgery at baseline and revision afterward, no prior surgery at baseline but fusion>3 levels and 2 years follow-up). All patients completed the Oswestry Disability Index (ODI), Short Form 36 (SF36), and Scoliosis Research Society 22 scores. The patients were classified according to the six modifiers of the O-CM classification. Central Sacral Vertical Line (CSVL) above 2, 3, and 4 cm's impact on PROMs was analyzed. Multivariate analysis was performed on the relationship between PROMS and age, global tilt (GT), and CM modifiers. After multivariate analysis using age and GT as confounding factors, we found that CM independently affects PROMs starting at 2 cm offset. Disability increases linearly with CSVL. Patients classified with 2B modifiers have the worst SRS-22 total score, social life, and self-image. In a fused spine, CM independently affects disability in ASD patients. Disability increases linearly with CSVL. Despite previous reports that failed to find correlations of CM with PROMs, our study showed that fixed postoperative CM, according to O-CM classification, correlates independently from sagittal malalignment with worse PROMs. III.


Improved Hand Function, Self-Rated Health, and Decreased Activity Limitations: Results After a Two-Month Hand Osteoarthritis Group Intervention.
To evaluate the effects on hand function, activity limitations, and self-rated health of a primary care hand osteoarthritis (OA) group intervention. Hand OA causes pain, impaired mobility, and reduced grip force, which cause activity limitations. OA group interventions in primary care settings are sparsely reported. Sixty-four individuals with hand OA agreed to participate; 15 were excluded due to not fulfilling the inclusion criteria. The 49 remaining (90% female) participated in an OA group intervention at a primary care unit with education, paraffin wax bath, and hand exercise over a 6-week period. Data were collected at baseline, end of intervention, and after 1 year. Instruments used were the Grip Ability Test (GAT), the Signals of Functional Impairment (SOFI), dynamometry (grip force), hand pain at rest using a visual analog scale (VAS), the Patient-Specific Functional Scale (PSFS), the Quick Disabilities of the Arm, Shoulder, and Hand (Quick-DASH), and the EuroQol VAS (EQ VAS). Data were analyzed using nonparametric statistics. Hand function, activity limitation, and self-rated health significantly improved from baseline to end of intervention, grip force (right hand: P < 0.001; left hand: P = 0.008), SOFI (P = 0.011), GAT (P < 0.001), hand pain at rest (P < 0.001), PSFS (1: P = 0.008, 2: P < 0.001, and 3: P = 0.004), Quick-DASH (P = 0.001), and EQ VAS (P = 0.039), and the effects were sustained after 1 year. The hand OA group intervention in primary care improves hand function, activity limitation, and self-rated health. The benefits are sustained 1 year after completion of the intervention.


Tailoring a novel ovalbumin emulsion gel for stability improvement and functional properties enhancement: Effect of oil phase structure changes by beeswax.
This study aimed to form a novel emulsion gel (EG) through structured oil phase of natural component beeswax (BW), together with ovalbumin (OVA), and to investigate the mechanism of its formation and stabilization in terms of microstructure and processing properties. Confocal laser scanning microscopy (CLSM) demonstrated that the EG formed a continuous double network structure since the superior crystallinity of the oil phase was given by BW. Fourier transform infrared spectroscopy (FT-IR) illustrated that the acylation of the phenolic hydroxyl group in BW with an amide bond in OVA, increased the hydrogen bonding of EG. Furthermore, the immobilization of the oil phase results in better thermal and freeze-thaw stability of EG. Finally, EG was used as a curcumin delivery system, and the presence of BW significantly improved its adaptability to multiple environmental factors. In summary, our study would provide valuable ideas for developing the design of finely structured functional food.


Effect of Antimicrobial Exposure on AcrAB Expression in Salmonella enterica Subspecies enterica Serovar Choleraesuis.
Understanding the impact of antimicrobial use on the emergence of resistant bacteria is imperative to prevent its emergence. For instance, activation of the AcrAB efflux pumps is responsible for the emergence of antimicrobial-resistant Salmonella strains. Here, we examined the expression levels of acrB and its multiple regulator genes (RamA, SoxS, MarA, and Rob) in 17 field isolates of S. Choleraesuis by using quantitative PCR methods. The expression of acrB increased in eight of the field isolates (P < 0.05). The expression of acrB was associated with that of ramA in one isolate, soxS in one isolate, and both these genes in six isolates. Thereafter, to examine the effect of selected antimicrobials (enrofloxacin, ampicillin, oxytetracycline, kanamycin, and spectinomycin) on the expression of acrB and its regulator genes, mutants derived from five isolates of S. Choleraesuis were selected by culture on antimicrobial-containing plates. The expression of acrB and ramA was higher in the mutants selected using enrofloxacin (3.3-6.3- and 24.5-37.7-fold, respectively), ampicillin (1.8-7.7- and 16.1-55.9-fold, respectively), oxytetracycline (1.7-3.3- and 3.2-31.1-fold, respectively), and kanamycin (1.6-2.2- and 5.6-26.4-fold, respectively), which are AcrAB substrates, than in each of the parental strains (P < 0.05). In contrast, in AcrAB substrate-selected mutants, the expression of soxS, marA, and rob remained similar to that in parental strains. Of the four antimicrobials, the level of ramA expression was significantly higher in the enrofloxacin- and ampicillin-selected mutants than in the oxytetracycline- and kanamycin-selected mutants (P < 0.05), whereas the expression levels of acrB and multiple regulator genes in spectinomycin-selected mutants were similar to those in each parental strain. These data suggest that exposure to antimicrobials that are AcrAB substrates enhance the activation of the AcrAB efflux pump via RamA, but not via SoxS, MarA, or Rob in S. Choleraesuis.


Pareto-like sequential sampling heuristic for global optimisation.
In this paper, we propose a simple global optimisation algorithm inspired by Pareto's principle. This algorithm samples most of its solutions within prominent search domains and is equipped with a self-adaptive mechanism to control the dynamic tightening of the prominent domains while the greediness of the algorithm increases over time (iterations). Unlike traditional metaheuristics, the proposed method has no direct mutation- or crossover-like operations. It depends solely on the sequential random sampling that can be used in diversification and intensification processes while keeping the information-flow between generations and the structural bias at a minimum. By using a simple topology, the algorithm avoids premature convergence by sampling new solutions every generation. A simple theoretical derivation revealed that the exploration of this approach is unbiased and the rate of the diversification is constant during the runtime. The trade-off balance between the diversification and the intensification is explained theoretically and experimentally. This proposed approach has been benchmarked against standard optimisation problems as well as a selected set of simple and complex engineering applications. We used 26 standard benchmarks with different properties that cover most of the optimisation problems' nature, three traditional engineering problems, and one real complex engineering problem from the state-of-the-art literature. The algorithm performs well in finding global minima for nonconvex and multimodal functions, especially with high dimensional problems and it was found very competitive in comparison with the recent algorithmic proposals. Moreover, the algorithm outperforms and scales better than recent algorithms when it is benchmarked under a limited number of iterations for the composite CEC2017 problems. The design of this algorithm is kept simple so it can be easily coupled or hybridised with other search paradigms. The code of the algorithm is provided in C++14, Python3.7, and Octave (Matlab).


Discovery of DS42450411 as a potent orally active hepcidin production inhibitor: Design and optimization of novel 4-aminopyrimidine derivatives.
Hepcidin has emerged as the central regulatory molecule in systemic iron homeostasis. The inhibition of hepcidin may be a favorable strategy for the treatment of anemia of chronic disease. Here, we have reported the design, synthesis, and structure-activity relationships (SAR) of a series of 4-aminopyrimidine compounds as inhibitors of hepcidin production. The optimization study of 1 led to the design of a potent and bioavailable inhibitor of hepcidin production, 34 (DS42450411), which showed serum hepcidin-lowering effects in a mouse model of interleukin-6-induced acute inflammation.


Evaluating the completeness of the reporting of abstracts since the publication of the CONSORT extension for abstracts: an evaluation of randomized controlled trial in ten nursing journals.
As a practice-oriented discipline, strict adherence to reporting guidelines is particularly important in randomized controlled trial (RCT) abstracts of the nursing area. However, whether abstract reports after 2010 have complied with the Consolidated Standards of Reporting Trials for Abstracts (CONSORT-A) guideline is unclear. This study aimed to evaluate whether the publication of CONSORT-A has improved abstract reporting in nursing and explores the factors associated with better adherence to the guidelines. We searched the Web of Science for 200 RCTs randomly selected from ten nursing journals. We used a data extraction form based on CONSORT-A, including 16 items, to analyze the reporting adherence to the guidelines, and the reporting rate of each item and the total score for each abstract were used to indicate adherence and overall quality score (OQS, range 0-16). A comparison of the total mean score between the two periods was made, and affecting factors were analyzed. In the studies we included, 48 abstracts were published pre-CONSORT-A whereas 152 post-CONSORT-A. The overall mean score for reporting adherence to 16 items was 7.41 ± 2.78 and 9.16 ± 2.76 for pre- and post-CONSORT-A, respectively (total score: 16). The most poorly reported items are "harms (0%)," "outcomes in method (8.5%)," "randomization (25%)," and "blinding (6.5%)." Items including the year of publication, impact factor, multiple center trial, word count, and structured abstract are significantly associated with higher adherence. The adherence to abstract reporting in nursing literature has improved since the CONSORT-A era, but the overall completeness of RCT abstracts remained low. A joint effort by authors, editors, and journals is necessary to improve reporting quality of RCT abstracts.


White versus blue: Does the wild 'albino' bilberry (Vaccinium myrtillus L.) differ in fruit quality compared to the blue one?
Wild albino and blue bilberry fruit were analyzed to compare different fruit characteristics linked to the composition of primary and secondary metabolites. Compounds were identified using HPLC-MS and standard quality parameters were determined. Albino berries were significantly smaller, accumulated less water and were characterized by 23% higher dry weight. Soluble solids content and pH value were higher in albino bilberry and their surface was lighter and characterized by a yellow hue. Both bilberry forms accumulated identical individual sugars and organic acids; however, the albino form had 33% higher content of total sugars and 9% higher content of total organic acids compared to the blue type. Fifteen anthocyanins were identified in both forms, but in albino bilberries, individual anthocyanins were only detected in traces. Blue bilberry contained 1.6-fold higher levels of flavanols, 2.1-fold higher levels of flavonols, 2.5-fold higher levels of hydroxycinnamic acid derivatives and consequently, 4.6-fold higher total phenolic content.


Serum BPI as a novel biomarker in asthma.
Neutrophils, eosinophils and inflammatory cells contribute to asthmatic inflammation. The anti-bactericidal/permeability-increasing protein (BPI), produced by neutrophils, peripheral blood monocytes or epithelial cells, can neutralize lipopolysaccharide activity and enhance phagocytosis regulation function. This study aimed to assess the clinical significance of BPI in asthmatic patients. We recruited 18 controlled asthma, 39 uncontrolled asthma and 35 healthy controls individuals. Clinical characteristics (age, gender, allergy history, body mass index (BMI) and smoking history), clinical indicators [whole blood count, forced expiratory volume in one second as percentage of predicted volume (FEV1% predicted), IgE level, high sensitivity C-reactive protein (hs-CRP) and fractional expiratory nitric oxide (FeNO)] and serum BPI levels were measured to compare among each group. We then evaluated the correlation between BPI, clinical characteristics and clinical indicators. Finally, linear regression analysis was performed to exclude the influence of other factors and to find the independent influencing factors of BPI. Our results showed that the serum BPI levels increased by twofold in the controlled asthma group (12.83 ± 6.04 ng/mL) and threefold in the uncontrolled asthma group (18.10 ± 13.48 ng/mL), compared to the healthy control group (6.00 ± 2.58 ng/mL) (p < 0.001). We further found that serum BPI levels were positively correlated with the hs-CRP (p = 0.002). There was no significant association among BPI, age, gender, BMI, allergy, blood eosinophils, blood neutrophils, IgE, FeNO or FEV1% predicted. BPI levels were increased in asthma and positively correlated with hs-CRP. BPI as a potential asthma biomarker that still needs further research.


Role of WUSCHEL in regulating stem cell fate in the Arabidopsis shoot meristem.
The shoot meristem gives rise to the aerial parts of higher plants by continuously initiating new organs. The basis of this activity is its ability to maintain a pool of pluripotent stem cells, which are the ultimate source of all tissues of the shoot. In Arabidopsis plants mutant for the WUSCHEL (WUS) gene, the stem cells are misspecified and appear to undergo differentiation. Here, we show that WUS encodes a novel homeodomain protein which presumably acts as a transcriptional regulator. The pattern of WUS expression suggests that stem cells in the shoot meristem are specified by an underlying cell group which is established in the 16-cell embryo and becomes localized to its prospective domain of function by asymmetric cell divisions.


Inherited pericentric inversion of chromosome 16 in chronic phase of chronic myeloid leukaemia.
The simultaneous occurrence of two specific acquired chromosomal abnormalities in chronic or acute leukaemias is rare. Inherited chromosomal abnormalities are also rare events in the general population. In chronic myeloid leukaemia (CML), characterised by the t(9;22)(q34;q11), the inv(16)(p13q22) has been described associated with the acceleration of disease or onset of blast crisis. We report on a patient with chronic phase of CML and both acquired t(9;22)(q34;q11) and inherited inv(16)(p13q22), who obtained a complete remission of the disease after bone marrow transplant. Therefore, it is worth to comment that an additional chromosomal abnormality in disease does not obligatory mean transformation of the disease to a more aggressive form, since chromosomal abnormalities are also seen in normal individuals.


Whole genome annotation and comparative genomic analyses of bio-control fungus Purpureocillium lilacinum.
The fungus Purpureocillium lilacinum is widely known as a biological control agent against plant parasitic nematodes. This research article consists of genomic annotation of the first draft of whole genome sequence of P. lilacinum. The study aims to decipher the putative genetic components of the fungus involved in nematode pathogenesis by performing comparative genomic analysis with nine closely related fungal species in Hypocreales. de novo genomic assembly was done and a total of 301 scaffolds were constructed for P. lilacinum genomic DNA. By employing structural genome prediction models, 13, 266 genes coding for proteins were predicted in the genome. Approximately 73% of the predicted genes were functionally annotated using Blastp, InterProScan and Gene Ontology. A 14.7% fraction of the predicted genes shared significant homology with genes in the Pathogen Host Interactions (PHI) database. The phylogenomic analysis carried out using maximum likelihood RAxML algorithm provided insight into the evolutionary relationship of P. lilacinum. In congruence with other closely related species in the Hypocreales namely, Metarhizium spp., Pochonia chlamydosporia, Cordyceps militaris, Trichoderma reesei and Fusarium spp., P. lilacinum has large gene sets coding for G-protein coupled receptors (GPCRs), proteases, glycoside hydrolases and carbohydrate esterases that are required for degradation of nematode-egg shell components. Screening of the genome by Antibiotics & Secondary Metabolite Analysis Shell (AntiSMASH) pipeline indicated that the genome potentially codes for a variety of secondary metabolites, possibly required for adaptation to heterogeneous lifestyles reported for P. lilacinum. Significant up-regulation of subtilisin-like serine protease genes in presence of nematode eggs in quantitative real-time analyses suggested potential role of serine proteases in nematode pathogenesis. The data offer a better understanding of Purpureocillium lilacinum genome and will enhance our understanding on the molecular mechanism involved in nematophagy.


The UPR Transducer IRE1 Promotes Breast Cancer Malignancy by Degrading Tumor Suppressor microRNAs.
Dysregulation of inositol-requiring enzyme 1 (IRE1), the primary transducer of Unfolded Protein Response (UPR), has been observed in tumor initiation and progression, but the underlying mechanism remains to be further elucidated. In this study, we identified that the IRE1 gene is frequently amplified and over-expressed in aggressive luminal B breast cancer cells and that IRE1 upregulation is significantly associated with worse overall survival of patients with breast cancer. IRE1 processes and mediates degradation of a subset of tumor suppressor microRNAs (miRNAs), including miR-3607, miR-374a, and miR-96, via a mechanism called Regulated IRE1-Dependent Decay (RIDD). IRE1-dependent degradation of tumor suppressor miR-3607 leads to elevation of RAS oncogene GTPase RAB3B in breast cancer cells. Inhibition of IRE1 endoribonuclease activity with the pharmacological compound 4μ8C or genetic approaches effectively suppresses luminal breast cancer cell proliferation and aggressive cancer phenotypes. Our work revealed the IRE1-RIDD-miRNAs pathway that promotes malignancy of luminal breast cancer.


Discriminative imaging of maternal and fetal blood flow within the placenta using ultrafast ultrasound.
Being able to map accurately placental blood flow in clinics could have major implications in the diagnosis and follow-up of pregnancy complications such as intrauterine growth restriction (IUGR). Moreover, the impact of such an imaging modality for a better diagnosis of placental dysfunction would require to solve the unsolved problem of discriminating the strongly intricated maternal and fetal vascular networks. However, no current imaging modality allows both to achieve sufficient sensitivity and selectivity to tell these entangled flows apart. Although ultrasound imaging would be the clinical modality of choice for such a problem, conventional Doppler echography both lacks of sensibility to detect and map the placenta microvascularization and a concept to discriminate both entangled flows. In this work, we propose to use an ultrafast Doppler imaging approach both to map with an enhanced sensitivity the small vessels of the placenta (~100 μm) and to assess the variation of the Doppler frequency simultaneously in all pixels of the image within a cardiac cycle. This approach is evaluated in vivo in the placenta of pregnant rabbits: By studying the local flow pulsatility pixel per pixel, it becomes possible to separate maternal and fetal blood in 2D from their pulsatile behavior. Significance Statement: The in vivo ability to image and discriminate maternal and fetal blood flow within the placenta is an unsolved problem which could improve the diagnosis of pregnancy complications such as intrauterine growth restriction or preeclampsia. To date, no imaging modality has both sufficient sensitivity and selectivity to discriminate these intimately entangled flows. We demonstrate that Ultrafast Doppler ultrasound method with a frame rate 100x faster than conventional imaging solves this issue. It permits the mapping of small vessels of the placenta (~100 μm) in 2D with an enhanced sensitivity. By assessing pixel-per-pixel pulsatility within single cardiac cycles, it achieves maternal and fetal blood flow discrimination.


[Role of helical computed tomography in petrous bone trauma: about 12 cases at the University Hospital Ibn Rochd of Casablanca].
Temporal bone injuries occur in 14-22% of skull fractures occurring due to head trauma. The purpose of this study is to understand the role of helical computed tomography in petrous bone trauma and to show the different types of fractures and the associated lesions. We conducted a retrospective study of 12 patients with petrous bone trauma (including 10 men and 2 women) over a period of 14 months. The average age of patients was 30, ranging from 18 to 42 years. High-resolution multi-slice computed tomography of petrous bone without contrast agent injection, with infra-millimeter slices thickness of 0.6mm every 0.3mm, allowed to detect the following fractures: 8 extralabyrinthine transverse fractures; 1 extralabyrinthine longitudinal fracture; 2 translabyrinthine fractures and 1 oblique fracture. The associated lesions were dominated by: 5 ossicular lesions; 4 cases of temporal bone involvement and 2 cases of geniculate ganglion involvement. High-resolution computed tomography can confirm the presence of a fracture, show the orientation of the fracture line and specify the different structures affected. It can be performed for emergency assessment or after a period of observation.


Enhancements on volatile organic compounds (VOCs) adsorption and desorption performance of ZSM-5 by fabricating hierarchical MCM-41.
ZSM-5 zeolite has been considered a promising adsorbent for capturing VOCs. However, its hydrophilicity and narrow micropore structure limit their practical application especially under humid atmospheres. In this study, the pure silica mesoporous molecular sieve MCM-41 was assembled on ZSM-5 zeolite with different SiO2/Al2O3 ratios (SARs) via a surfactant-mediated recrystallization method. Then, its adsorption-desorption behaviors were investigated using n-hexane, toluene, and ethyl acetate as VOC model molecules. The results showed that the hydrophobicity of ZSM-5/MCM-41 composites and their VOC diffusion behaviors were significantly improved. Furthermore, the SARs of the ZSM-5 precursors had a remarkable influence on the adsorption performance of ZSM-5/MCM-41 composites. ZSM-5/MCM-41(130) was the optimum option, and its dynamic adsorption capacity for ethyl acetate (111.30 mg·g-1) was higher than that of the corresponding ZSM-5 zeolites even under statured humidity. Meanwhile, the ratios of dynamic adsorption capacities at humid and dry atmospheres (qs,wet/qs,dry) of ZSM-5/MCM-41(130) for n-hexane, toluene, and ethyl acetate were 84.89%, 61.46%, and 73.81% respectively. The results will provide guidelines for the preparation of hydrophobic adsorbents.


A simple and rapid optical biosensor for detection of aflatoxin B1 based on competitive dispersion of gold nanorods.
This report illustrates a promising one-step and label-free optical biosensor for determination of aflatoxin B1 (AFB1) that is most commonly found in foods and highly dangerous even at very low concentrations. In this research, gold nanorods (GNRs) were employed as a sensing platform, which showed high stability under high ionic strength conditions without addition of any stabilizing agent. GNR-AFB1-BSA (bovine serum albumin) conjugates aggregated after mixing with free antibodies, resulting in significant changes in absorption intensity. At the same time the existence of AFB1 molecules in samples caused dispersion of nanorods, as a result of competitive immune-reaction with antibodies. By taking advantages of the competitive dispersion of GNRs, the developed method could effectively reduce false results caused by undesirable aggregation, which is a big problem for spherical gold nanoparticles. Absorption intensity of UV-vis spectra served as the sensing indicator, with dynamic light scattering (DLS) measurement as another sensing tool. The designed biosensing system could detect AFB1 in a linear range from 0.5 to 20ngmL(-1), with a good correlation coefficient of 0.99. And the limit of detection (LOD) was 0.16ngmL(-1), indicating an excellent sensitivity with absorbance result. The recoveries of the spiked AFB1 in real peanut samples ranged from 94.2% to 117.3%. Therefore the proposed nano-biosensor was demonstrated to be sensitive, selective, and simple, providing a viable alternative for rapid screening of toxins in agriculture products and foods.


Decrease in nickel sensitization in a Danish schoolgirl population with ears pierced after implementation of a nickel-exposure regulation.
To reduce the skin nickel exposure of the population, the Danish Ministry of Environment issued a regulation that was implemented in 1992, and the European Union countries have recently adopted an expanded regulation. The aim of our combined patch testing and questionnaire investigation of girls in public schools and high schools/production schools was to evaluate whether the regulation has had an impact on the prevalence of nickel sensitization. To find a group of girls with ears pierced mainly after implementation of the nickel-exposure regulation in Denmark, girls were recruited from the fifth and sixth grade in 12 public schools (the public school group). After the public school level almost all girls from a public school population continue their education in high schools or other schools such as production schools or technical schools. Therefore, to find girls demographically similar to the public school girls but older, and with ears pierced before implementation of the regulation, girls from seven high schools and two production schools were recruited (the high school group). Four hundred and twenty-seven girls in the public school group (mean age 12.4 years, range 10-14) and 534 in the high school group (mean age 18.8 years, range 17-22) participated. All participants filled out a questionnaire concerning ear piercing, use of oral braces and former patch testing for nickel sensitivity. Three hundred and five girls (71.4%) in the public school group and 275 (51.5%) in the high school group were patch tested or had been tested previously and the results of these tests were included in the study. The relation between the frequency of nickel sensitization and the various factors that might influence the prevalence of nickel sensitization was evaluated by multivariate logistic regression analysis. The investigation was conducted from March 1999 to March 2000. The study showed that both increasing age and having ears pierced before 1992 enhanced the prevalence of nickel sensitization. We found that 17.1% of the girls in the high school group demonstrated a positive patch test reaction to nickel. In contrast, the prevalence of nickel sensitization in the public school group was only 3.9%. Comparing girls with and without pierced ears, the prevalence of nickel sensitization was significantly higher in girls with ears pierced before, but not after, 1992 (odds ratio 3.34 and 1.20, respectively). Only in the high school group was there a tendency that wearing oral braces before ear piercing had a protective effect on nickel sensitization, but this did not reach statistical significance. As we found an effect of ear piercing before but not after 1992, this study strongly suggests that implementation of the nickel-exposure regulation in 1992 in Denmark has had the intended effect of protecting the female population from becoming allergic to nickel.


Cancer and orofacial pain.
Orofacial pain is commonly associated with cancer and may motivate patients to seek care from an oral and maxillofacial surgeon. Pain may be a presenting symptom of primary tumors, metastatic disease, systemic cancer, or distant non-metastasized cancer. Patients with head and neck cancer undergoing therapy may suffer treatment-induced complications, which are often associated with acute pain. Following cancer therapy, permanent changes to tissues may cause late effects of treatment that may result in chronic orofacial pains. Oral and maxillofacial surgeons should be knowledgeable regarding these orofacial pain presentations.


Schedule-induced drinking and thirst: a pharmacological analysis.
Similar levels of water consumption were induced in two groups of rats by means either of prior fluid deprivation or a schedule of food pellet delivery. Injections of d-amphetamine (0.25, 0.5, 1.0 and 2.0 mg/kg) had similar attenuating effects of drinking induced by both procedures. Chlordiazepoxide (2.5, 5.0, 10 and 20 mg/kg), however, exerted differential actions on schedule-induced and deprivation-induced drinking. Drinking induced by deprivation was facilitated by all doses of this drug while the higher doses decreased levels of schedule-induced drinking. This result emphasises the difficulties involved in using the concept of thirst in explanations of behavior and of drug action.


Physician Identification Badges: A Multispecialty Quality Improvement Study to Address Professional Misidentification and Bias.
To evaluate whether providing resident physicians with "DOCTOR" role identification badges would impact perceptions of bias in the workforce and alter misidentification rates. Between October 2019 and December 2019, we surveyed 341 resident physicians in the anesthesiology, dermatology, internal medicine, neurologic surgery, otorhinolaryngology, and urology departments at Mayo Clinic in Rochester, Minnesota, before and after an 8-week intervention of providing "DOCTOR" role identification badges. Differences between paired preintervention and postintervention survey answers were measured, with a focus on the frequency of experiencing perceived bias and role misidentification (significance level, α=.01). Free-text comments were also compared. Of the 159 residents who returned both the before and after surveys (survey response rate, 46.6% [159 of 341]), 128 (80.5%) wore the "DOCTOR" badge. After the intervention, residents who wore the badges were statistically significantly less likely to report role misidentification at least once a week from patients, nonphysician team members, and other physicians (50.8% [65] preintervention vs 10.2% [13] postintervention; 35.9% [46] vs 8.6% [11]; 18.0% [23] vs 3.9% [5], respectively; all P<.001). The 66 female residents reported statistically significantly fewer episodes of gender bias (65.2% [43] vs 31.8% [21]; P<.001). The 13 residents who identified as underrepresented in medicine reported statistically significantly less misidentification from patients (84.6% [11] vs 23.1% [3]; P=.008); although not a statistically significant difference, the 13 residents identifying as underrepresented in medicine also reported less misidentification with nonphysician team members (46.2% [6] vs 15.4% [2]; P=.13). Residents reported decreased role misidentification after use of a role identification badge, most prominently improved among women. Decreasing workplace bias is essential in efforts to improve both diversity and inclusion efforts in training programs.


Role models for pregnancy, birth, and breastfeeding.
In this column, the editor of The Journal of Perinatal Education discusses how the media provide role models-good and bad-for pregnancy, birth, and breastfeeding. There is a critical need for more positive role models that promote natural, safe, and healthy pregnancy and birth. The editor also describes the contents of this issue, which offer a broad range of resources, research, and inspiration for childbirth educators in their efforts to promote natural, safe, and healthy birth.


Chronic cough and eosinophilic esophagitis: an uncommon association.
An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow's milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients.


The anatomy of the inferolateral trunk (ILT) of the internal carotid artery.
The authors of the paper present the results of 20 anatomical dissections of the cavernous sinus area, correlated to 90 angiographies and to basic embryological knowledge; they emphasize the role played by the inferolateral trunk in the arterial blood supply of the cavernous area and its complex and the value of the internal maxillary angiogram for its visualization.


How do low doses of desferrioxamine B and EDTA affect the phytoextraction of metals in sunflower?
The aim of this study was to compare the efficiency of siderophore desferrioxamine B (DFOB) and EDTA in increasing the phytoextraction of metals in sunflower. A 28-day pot experiment was conducted in a metal-contaminated soil supplied with 200μmolkg-1 of DFOB or EDTA. Pore water was collected and pseudo-polarographic analyses were conducted to assess the impact of the two chelators on the mobility and speciation of metals in the liquid phase. Our results showed that DFOB is not an efficient mobilizing agent of divalent metals in soil. Adding DFOB selectively increased the mobility of trivalent metals while the supply of EDTA simultaneously increased the mobility of both trivalent and divalent metals. EDTA significantly reduced the labile fractions of Cd, Cu, (Pb) and Zn measured in the porewater. The labile concentration of Cd and Zn measured in presence of EDTA was even less than that measured in the control. As expected from the pore water analysis, the addition of DFOB did not affect the phytoextraction of any divalent metals. In contrast, the addition of EDTA enhanced Cu and Ni phytoextraction in sunflower 2.0 to 2.8 fold for Cu and 1.3 to 2.3 fold for Ni, depending on the cultivar. This result supports different hypotheses regarding the forms and the related pathways in which metals are taken up in presence of EDTA. Based on the results obtained for Ni, whose uptake is rate limited by its internalization across the cell membrane, the direct uptake of metal-EDTA complexes via the non-selective apoplastic pathway is hypothesized to contribute the most to the overall uptake of metals in presence of EDTA, even added at "low" concentrations.


Possible impacts of a future grand solar minimum on climate: Stratospheric and global circulation changes.
A future decline in solar activity would not offset projected global warmingA future decline in solar activity could have larger regional effects in winterTop-down mechanism contributes to Northern Hemisphere regional response.


Drugs of anesthesia acting on central cholinergic system may cause post-operative cognitive dysfunction and delirium.
Given the progressive and constant increase of average life expectancy, an increasing number of elderly patients undergo surgery. After surgery, elderly patients often exhibit a transient reversible state of cerebral cognitive alterations. Among these cognitive dysfunctions, a state of delirium may develop. Delirium is an aetiologically non-specific syndrome characterised by concurrent disturbances of consciousness and attention, perception, thinking, memory, psychomotor behaviour and the sleep-wake cycle. Delirium appears to occur in 10-26% of general medical patients over 65, and is frequently associated with a significant increase in morbidity and mortality. During hospitalization, mortality rates have been estimated to be 10-26% of patients who developed post-operative delirium, and 22-76% during the following months. Over the last few decades, post-operative delirium has been associated with several pre-operative predictor factors, as well as age (50 years and older), alcohol abuse, poor cognitive and functional status, electrolyses or glucose abnormalities, and type of surgery. The uncertain pathogenesis of post-operative cognitive dysfunctions and delirium has not permitted a causal approach to developing an effective treatment. General anesthesia affects brain function at all levels, including neuronal membranes, receptors, ion channels, neurotransmitters, cerebral blood flow and metabolism. The functional equivalents of these impairments involve mood, memory, and motor function behavioural changes. These dysfunctions are much more evident in the occurrence of stress-regulating transmission and in the alteration of intra-cellular signal transduction systems. In addition, more essential cellular processes, that play an important role in neurotransmitter synthesis and release, such as intra-neuronal signal transduction and second messenger system, may be altered. Keeping in mind the functions of the central muscarinic cholinergic system and its multiple interactions with drugs of anesthesia, it seems possible to hypothesize that the inhibition of muscarinic cholinergic receptors could have a pivotal role in the pathogenesis not only of post-operative delirium but also the more complex phenomena of post-operative cognitive dysfunction.


Effect of phospholipase A on the structure and functions of membrane vesicles from Mycobacterium phlei.
The phospholipid composition of the electron transport particles and coupling factor-depleted electron transport particles of Mycobacterium phlei are the same, but they differ in contents. The accessibility of partially purified phospholipase A to these membrane phospholipids was found to be different. Treatment of membranes of Mycobacterium phlei with phospholipase A impairs the rate of oxidation as well as phosphorylation. The inhibition of phosphorylation can be reversed by washing the membranes with defatted bovine serum albumin. The reconstitution of membrane-bound coupling factor-latent ATPase activity to phospholipase A-treated depleted electron transport particles and their capacity to couple phosphorylation to oxidation of substrates remained unaffected after phospholipase A treatment. However, the pH gradient as measured by bromthymol blue was not restored after reconstitution of phospholipase A-treated depleted electron transport particles with membrane-bound coupling factor-latent ATPase. These findings show that the phosphorylation coupled to the oxidation of substrates can take place without a pronounced pH gradient in these membrane vesicles. The dye 1-anilino-8-naphthalene sulfonic acid (ANS) exhibited low levels of energized and nonenergized fluorescence in phospholipase A-treated membranes. This decrease in the level of ANS fluorescence in phospholipase A-treated membranes was found to be directly related to the amount of phospholipids cleaved. The decrease in the energy-dependent ANS response in phospholipase A-treated electron transport particles, as compared with untreated electron transport particles, was shown to be a result of a change in the apparent K-d of the dye-membrane complex, and of a decrease in the number of irreversible or slowly reversible binding sites, with no change in the relative quantum efficiency of the dye. The decrease in ANS fluorescence in phospholipase A-treated particles appears to be due to a decrease in the hydrophobicity of the membranes.


A new technique for continent urinary diversion.
Canine experimental surgery was used to investigate the feasibility of creating a new continent urinary reservoir. Remodelled ileum was used to fashion this reservoir like the Kock pouch, but without either of the intussuscepted nipple valves which it uses. Ureters were implanted directly into the wall of the reservoir using a nonrefluxing technique. Continence was obtained by plication of a short limb of intact ileum exiting from the reservoir through which intermittent catheterization was performed. Three of four animals which remained infection-free had good to excellent results. Reservoir infection in four additional animals was associated with failure due to ureteral obstruction. The advantages of this reservoir include the use of ileum to achieve a low-pressure reservoir, the absence of the complex nipple valves of the Kock pouch, and the absence of foreign bodies such as staples and artificial sphincters. While the followup in this study is recognized as relatively short-term, the successes seen in this difficult-to-use animal model suggest that further evaluation of this simplified procedure is warranted.


Alpha-1-antitrypsin for the improvement of autoimmunity and allograft rejection in beta cell transplantation.
Islet transplantation offers hope for patients with type 1 diabetes, which is an autoimmune disease. However, islet transplant recipients must overcome two obstacles in both allograft rejection and autoimmune reaction. Alpha-1-antitrypsin (a1-proteinase inhibitor, AAT) possesses anti-inflammatory properties, reduces cytokine-mediated islet damage, and induces specific immune tolerance. In this study, an insulinoma cell line, NIT-1, was transfected with human AAT (hAAT), named NIT-hAAT, and was transplanted to the left renal subcapsular spaces of 7-week-old female non-obese diabetic (NOD) mice (n=22). Cyclophosphamide(CY) was administered to synchronize and accelerate the development of diabetes. Thus, the immunosuppressive and cytoprotective activity of hAAT in β-cell transplantation was investigated. NIT-hAAT has immunomodulatory properties, which delay the onset of autoimmune diabetes, reduce diabetes incidence, inhibit insulitis and β-cell apoptosis, and dampen transplant site inflammation. We propose that NIT-hAAT has a dual function by improving islet autoimmunity and protecting transplanted β-cells from allograft rejection. However, the low expression of hAAT in vivo results in the inability of NIT-hAAT to induce long-term specific immune tolerance and to completely block allograft rejection.


Exposure of gnotobiotic Artemia franciscana larvae to abiotic stress promotes heat shock protein 70 synthesis and enhances resistance to pathogenic Vibrio campbellii.
Larvae of the brine shrimp Artemia franciscana serve as important feed in fish and shellfish larviculture; however, they are subject to bacterial diseases that devastate entire populations and consequently hinder their use in aquaculture. Exposure to abiotic stress was shown previously to shield Artemia larvae against infection by pathogenic Vibrio, with the results suggesting a mechanistic role for heat shock protein 70. In the current report, combined hypothermic/hyperthermic shock followed by recovery at ambient temperature induced Hsp70 synthesis in Artemia larvae. Thermotolerance was also increased as was protection against infection by Vibrio campbellii, the latter indicated by reduced mortality and lower bacterial load in challenge tests. Resistance to Vibrio improved in the face of declining body mass as demonstrated by measurement of ash-free dry weight. Hypothermic stress only and acute osmotic insult did not promote Hsp70 expression and thermotolerance in Artemia larvae nor was resistance to Vibrio challenge augmented. The data support a causal link between Hsp70 accumulation induced by abiotic stress and enhanced resistance to infection by V. campbellii, perhaps via stimulation of the Artemia immune system. This possibility is now under investigation, and the work may reveal fundamental properties of crustacean immunity. Additionally, the findings are important in aquaculture where development of procedures to prevent bacterial infection of feed stock such as Artemia larvae is a priority.


COVID-19 Vaccination Status and Capsular Contracture Following Prosthetic Breast Reconstruction: A Retrospective, Multicenter Nested Case-Control Study.
Capsular contracture (CC) is a common long-term complication following prosthetic-based breast reconstruction (PBBR). Seven cases of CC following mRNA vaccination for coronavirus 2019 (COVID-19) are reported in the literature. The aim of this study was to determine whether receiving the COVID-19 vaccine was associated with CC development following PBBR. A retrospective, multicenter nested case-control study was performed from January 2014 to July 2022 of adult female patients who underwent PBBR with acellular dermal matrix placement. Cases of CC were selected if no adjuvant radiation was received and they presented for follow-up between December 2020 and July 2022. Controls included patients who met inclusion criteria but who did not experience CC in either breast. Patient demographics, breast cancer characteristics, reconstructive surgery details, postoperative complications, and COVID-19 exposure details were analyzed and correlated with CC development. Of a total of 230 patients (393 breasts) who received PBBR, 85 patients (135 breasts) met inclusion criteria, of whom 12 patients (19 breasts) developed CC and 73 patients (116 breasts) did not. At the time of median follow-up of 18.1 months (n = 85; interquartile range, 12.2-33.6 months), no statistically significant differences were observed between the short- or long-term complications in cases or controls. There were no significant differences in COVID-19 vaccination status, number of vaccine doses, or vaccination type between cases and controls. Vaccination status was not associated with greater odds of CC development (odds ratio, 1.44; 95% CI, 0.42-5.37; P > .05). Direct association between CC and COVID-19 vaccination is difficult to prove. Given the known risk of severe COVID-19 infection among immunocompromised patients, those with breast cancer who undergo PBBR should be properly counseled on the benefits and risks of vaccination.


Apo E polymorphism and the removal of remnants of triglyceride-rich lipoproteins in normolipidemic subjects during a carbohydrate-rich diet.
The role of the apo E polymorphism in the removal of remnants of very low density lipoproteins and chylomicrons was studied after a carbohydrate-rich diet in 10 healthy normolipidemic volunteers with different apo E phenotypes during 7 days. The cholesterol concentration in the heparin-sepharose bound part of the VLDL + IDL fraction (d < 1.019 g/ml) was taken as an estimate of the remnant concentration. Before and after carbohydrate-rich diet retinyl palmitate, mixed with cream, was consumed by each subject the evening before the fasting venepuncture to quantify the removal of chylomicron remnants. After the diet there was a comparable mean rise in the three groups in serum and in very low density lipoprotein triglycerides of about 30% and 50%, respectively. The concentration of remnants of very low density lipoproteins increased slightly in all subjects. The concentration of retinyl palmitate in the d < 1.019 g/ml fraction was 20% lower than before this diet in the E-2 homozygous subjects. In the other two groups, however, 25 to 80% higher retinyl palmitate levels were found. It is concluded, that after a carbohydrate-rich diet there is only a slight increase of very low density lipoprotein remnants, independent of the apo E polymorphism. The removal of chylomicron remnants, however, seems to be facilitated in E-2 homozygous subjects, in contrast to a slower removal in the groups with other apo E phenotypes.


Personality and emotional intelligence in teacher burnout.
This paper aims to investigate the relationship between teacher's personality types, emotional intelligence and burnout and to predict the burnout levels of 147 teachers in the city of Mashhad (Iran). To this end, we have used three inventories: Maslach Burnout Inventory (MBI), NEO Five Factor Inventory (NEO-FFI), and Emotional Quotient Inventory (EQ-I). We used Homogeneity Analysis and Multiple Linear Regression to analyze the data. The results exhibited a significant relationship between personality types and emotional intelligence and the three dimensions of burnout. It was indicated that the best predictors for emotional exhaustion were neuroticism and extroversion, for depersonalization were intrapersonal scale of emotional intelligence and agreeableness, and for personal accomplishment were interpersonal scale and conscientiousness. Finally, the results were discussed in the context of teacher burnout.