A rapid GC method coupled with quadrupole or time of flight mass spectrometry for metabolomics analysis.
Gas chromatography-mass spectrometry (GC-MS) is an ideal tool for analyzing the intermediates of tricarboxylic acid cycle and glycolysis, sugars, organic acids and amino acids, etc. High-throughput metabolomics methods are required by large-scale clinical researches, and time of flight mass spectrometry (TOF MS) having fast scanning rate is preferable for rapid GC. Quadrupole MS (qMS) instruments have 95% market share, and their potential in rapid metabolomics is worth being studied. In this work, a within 15-min GC program was established and matched by qMS scanning for plasma metabolome analysis after N-methyl-N-(trimethylsilyl)-trifluoroacetamide derivatization. Compared to the longer-time program GC-qMS method, the rapid GC-qMS method had nearly no metabolome information loss, and it had excellent profile performance in repeatability, intra-day and inter-day precision, sampling range, linearity and extraction recovery. Compared to TOF MS, qMS achieved similar results in investigating lung cancer serum metabolic disruptions. Partial least squares-discriminant analysis revealed that the two datasets acquired by qMS and TOF MS had very similar model parameters, and most of top ranked differential metabolites were the same. This study provides a rapid and economical GC-qMS metabolomics method for researchers. Still, MS having faster scanning rate and higher sensitivity are recommended, if possible, to detect more small peaks and some co-eluted peaks.


Determining selectivity of phosphoinositide-binding domains.
The burgeoning of phosphoinositide-binding domains and proteins in cellular signaling and trafficking has drawn laboratories from a wide variety of fields into the study of lipid interactions with peripheral membrane proteins. Many different approaches have been developed to assess phosphoinositide binding, some of which are more problematic than others, and some of which can be quantitated more readily than others. With a focus on the methods used in our laboratory, we describe here the considerations that need to be taken into account when establishing-and quantitating-the specific binding of a protein or domain to phosphoinositides in membranes. We also discuss briefly a few examples in which no clear consensus has yet been reached as to the specificity of a given domain or protein because of discrepancies between different commonly used approaches.


Studies on the metabolism, mode of action, and development of insecticides acting on the GABA receptor.
γ-BHC and dieldrin are legacy insecticides that were extensively used after the second World War. When they were banned, their modes of action and metabolism were not known. This article aims at providing a picture of the metabolism of γ-BHC and the modes of action of γ -BHC and dieldrin. γ-BHC is metabolized via two independent metabolic pathways. One is a glutathione conjugation pathway resulting in the formation of dichlorophenyl mercapturic acid and the other is an oxidative metabolism catalyzed by microsomes to mainly 2,4,6-trichlorophenol (TCP) and (36/45)-1,2,3,4,5,6-hexachlorocyclohex-1-ene (HCCHE). Other metabolites of this pathway are 2,4,5-TCP, 2,3,4,6-tetrachlorophenol (TeCP), (36/45)- and (346/5)-1,3,4,5,6-pentachlorocyclohex-1-enes (PCCHE). Nowadays, γ-BHC and dieldrin are very important reagents which are used to study the GABA receptor in insects and mammals. They were found to be noncompetitive GABA antagonists blocking the chloride ion selective pores in the GABA-gated chloride channels and leading to inhibition of chloride ion conductance. [3H]EBOB binding data showed that γ-BHC, its analogs, dieldrin, and other cyclodiene insecticides interact with the same site on GABA receptor as picrotoxinin. Only γ-BHC, among other BHC isomers, exhibits this binding characteristic. Milbemycin, currently widely used as an insecticide, acaricide and nematicide, has been found to open the GABA-gated chloride channel.


Quality of life of women with urinary incontinence: cross-cultural performance of 15 language versions of the I-QOL.
Urinary incontinence (UI) has substantial and important impacts on health-related quality of life. The purpose of this research is to report the psychometric performance of 15 different language versions of the Incontinence-specific Quality of Life (I-QOL)measure, a patient-reported outcome measure specific to stress, urge and mixed urinary incontinence. The multi-national dataset consisted of data from four clinical trials for stress incontinent females and from two additional population studies, enrolling women with stress, urge and mixed UI. All enrolled patients completed the I-QOL and comparative measures at baseline. The clinical trial populations had multiple administrations up to 12 weeks, and the two population studies included a shorter retest. Country-specific psychometric testing for validity, reliability, and responsiveness followed standardized procedures. Confirmatory factor analyses were performed to assess the I-QOL subscales. The I-QOL measurement model was confirmed as three subscales. Summary and subscale scores for the 15 versions were internally consistent (alpha values = 0.91-0.96) and reproducible (ICC = 0.72-0.97). Using changes in the independent measures of incontinence episode frequency standardized response means were predominantly strong (ranged 0.71-1.05) across 13 versions (out of 15) in association with these measures and effect sizes. These additional language versions of the I-QOL instrument demonstrate psychometric properties similar to the original version. The I-QOL has shown good results in both community studies and clinical trials with varying types and severity of urinary incontinence. It is a reliable and valid measure of HRQOL, suitable for use in a variety of international settings.


ADP-ribosylation of nuclear proteins in rat ventral prostate during ageing.
Poly(ADPR)polymerase activity and poly(ADP-ribosyl)ation of nuclear proteins have been investigated in ventral prostate nuclei of different aged rats (14, 28, 60, 180, 360 day old animals), by reverse-phase HPLC and acetic acid-urea polyacrylamide gel electrophoresis. The major ADP-ribose acceptor proteins were identified as histone H1 and H2b. It is concluded that concomitant with major changes to chromatin organization, poly(ADP-ribosyl)ation reaction is progressively inhibited during aging of rat ventral prostate. These results support the hypothesis that prostatic dysfunction in senescent animals is related to a failure of DNA repair mechanisms and deregulated template activity.


Compound connection mechanism of Al2O3 ceramic and TC4 Ti alloy with different joining modes.
In this paper, laser welding-brazing of TC4 Titanium (Ti) alloy and Al2O3 ceramic dissimilar material was carried. The results showed that the Ti alloy and Al2O3 were joined by melting filler metal when the laser was concentrated in the Ti alloy side of the joint. The joint with one fusion weld and one brazed weld separated by remaining unmelted Ti alloy. Laser beam offset the Ti alloy 1.5 mm, Ti alloy would not be completely melted in joint. Through heat conduction, the filler metal melted occurred at the Ti-ceramic interface. A brazed weld was formed at the Ti-ceramic interface with the main microstructure of β-CuZn + Ti2Zn3, β-CuZn and Al2Cu + β-CuZn. The joint fractured at the brazed weld with the maximum tensile strength of 169 MPa.


Pulmonary artery banding.
Two hundred nine children with congenital heart defects characterized by excessive pulmonary blood flow underwent pulmonary artery banding at The Hospital for Sick Children from January, 1972, through December, 1982. The indications for banding, rather than complete repair, varied with the type of cardiac defect as well as with the year of presentation to our hospital. A simplified method of estimating required band circumference has been developed for infants with ventricular septal defect, with or without major intracardiac mixing disorders. Infants with simple defects without intracardiac bidirectional mixing disorders receive a band at a circumference of 20 mm + 1 mm for each kilogram of body weight, whereas infants with bidirectional mixing disorders receive a band at a circumference of 24 mm + 1 mm for each kilogram of body weight. The overall operative mortality varies with the underlying cardiac defect and with associated medical conditions but is relatively low in the less-complicated cases. The use of a formula to predict a starting band circumference, with loosening only as required by cyanosis or bradycardia, allows predictable control of congestive symptoms and pulmonary hypertension in the majority of infants. The cumbersome measurement of pulmonary artery pressure and the unpredictable changes in pressure during anesthesia are avoided. Pulmonary artery banding remains an effective means of achieving satisfactory palliation in infants with congenital heart disease and excessive pulmonary blood flow.


Applications of immunohistochemistry in rodent tumor pathology.
Immunohistochemistry can serve as a valuable adjunct to rodent tumor pathology. Specific antigens may be localized to cells and tissues in normal organs, preneoplastic lesions, and benign and malignant tumors. The immunoreactivity of polyclonal and monoclonal antibodies to these antigens provide a more accurate basis for tumor diagnosis and aid in understanding pathogenesis. Ultimately, the application of more precise understanding of tumor histogenesis and diagnosis will lead to more accurate interpretations of tumor incidence data for safety assessment in toxicology.


Studies on the Onchocerca (nematoda: Filarioidea) found in cattle in the United States. I. Systematics of O. gutturosa and O. lienalis with a description of O. stilesi sp. n.
Onchocerca gutturosa and O. lienalis are redescribed and comparative morphological descriptions provided. In addition, a third species of Onchocerca is described from cattle in the United States. This third species, Onchocerca stilesi sp. n., localizes in the connective tissues around the stifle joint, and can be distinguished morphologically from O. gutterosa and O. lienalis. Onchocerca gutturosa and O. lienalis apparently have widespread distribution in the eastern United States; however O. stilesi has been reported only from Minnesota.


Differences in collagen types in the semitendinosus, quadriceps, and patellar tendons: A report using samples from an 11-year-old patient.
This study aimed to determine the differences in the proportions of types I and type III collagen in the semitendinosus tendon (ST), quadriceps tendon (QT), and patellar tendon (PT), which are frequently used as autografts for anterior cruciate ligament (ACL) reconstruction. Orthopedic surgeons diagnosed habitual dislocation of the left patella and surgically treated an 11-year-old boy. Medial patellofemoral ligament reconstruction, medial patellar tibial ligament reconstruction, and arthroscopic lateral release were performed simultaneously. Tissue samples obtained during treatment that were no longer necessary were used as samples for this study. The samples were fixed, paraffin-embedded, and immunostained for type I and type III collagen. Stained samples were observed under a confocal microscope and evaluated visually and quantitatively to determine the percentages of type I and type III collagen. Visually, the ST had a higher percentage of type III collagen than the PT and QT. The QT and PT were similar in appearance; both consisted mostly of collagen type I. Quantitative evaluation using images showed that the PT comprised 100% type I collagen. The QT comprised 1% type III collagen. The ST comprised 34% type III collagen. In this patient, the QT and PT had higher percentages of type I collagen, which is considered physically strong. Type III collagen, which is considered physically weak, was most common in the ST. These factors may be associated with the high re-injury rates after ACL reconstruction using the ST for physically immature patients.


Improved recovery of a fusion protein containing the antigenic domain 1 of the human cytomegalovirus glycoprotein B.
Heterologous expression in Escherichia coli often leads to production of the expressed proteins as insoluble and inactive inclusion bodies. The general strategy for protein recovery includes isolation and washing of inclusion bodies, solubilization of aggregated protein and refolding of solubilized protein. The process of refolding, as well as the other steps involved in inclusion body recovery, must be optimized according to the characteristics of each protein. For the development of reliable and inexpensive serodiagnostic tests, the antigenic domain 1 (AD-1) of human cytomegalovirus glycoprotein B was expressed in E. coli and a process was developed to increase recovery of the fusion protein containing AD-1. A comparison of disruption methods and different conditions involved in recovery of this fusion protein from inclusion bodies is presented. The developed method gives a high yield of the fusion protein with a purity sufficient for use in diagnostic tests.


PET/CT Imaging Characteristics After Radioembolization of Hepatic Metastasis from Breast Cancer.
To define positron emission tomography/computed tomography (PET/CT) imaging characteristics during follow-up of patients with metastatic breast cancer (MBC) treated with yttrium-90 (Y90) radioembolization (RE). From January 2011 to October 2017, 30 MBC patients underwent 38 Y90 glass or resin RE treatments. Pre-RE PET/CT was performed on average 51 days before RE. There were 68 PET/CTs performed after treatment. Response was assessed using modified PERCIST criteria focusing on the hepatic territory treated with RE, normalizing SUVpeak to the mean SUV of liver uninvolved by tumor. An objective response (OR) was defined as a decrease in SUVpeak by at least 30%. Of the 68 post-RE scans, 6 were performed at 0-30 days, 15 at 31-60 days, 9 at 61-90 days, 13 at 91-120 days, 14 scans at 121-180 days, and 11 scans at > 180 days after RE. Of the 30 patients, 25 (83%) achieved OR on at least one follow-up. Median survival was 15 months after the first RE administration. Highest response rates occurred at 30-90 days, with over 75% of cases demonstrating OR at that time. After 180 days, OR was seen in only 25%. There was a median TTP of 169 days among responders. In MBC, follow-up PET/CT after RE demonstrates optimal response rates at 30-90 days, with progression noted after 180 days. These results help to guide the timing of imaging and also to inform patients of expected outcomes after RE.


Maternal Malnutrition During Pregnancy Among Women with Metabolic and Bariatric Surgery.
As the utilization of metabolic and bariatric surgery (MBS) continues to rise, it is important to address the nutritional needs of women who had MBS who become pregnant. Not meeting those nutritional needs could lead to complications associated with malnutrition. To better understand the relationship between MBS, pregnancy, and malnutrition, this study sought to determine whether differences exist in the presence of malnutrition during pregnancy in women with a history of MBS compared to women without a history of MBS. This cross-sectional study used the National Inpatient Sample (NIS) from 2012 to 2017, which samples 20% of hospital discharges in the USA. Multivariate logistic regression models were fitted, and odds rations and 95% confidence intervals were calculated with obesity and MBS as the independent variables and malnutrition during pregnancy as the dependent variable. Covariates included in the multivariate model were age, primary payer, hypertension, hyperlipidemia, and depression. Compared to women who did not have MBS, women who had MBS had higher odds of malnutrition during pregnancy (aOR = 8.33, 95% CI 7.30-9.50), this result was moderated by racial category (aORBlack = 6.35, 95% CI 4.97-8.13; aORwhite = 8.25, 95% CI 7.00-9.73; aORLatina = 10.93, 95% CI 8.38-14.25). Women with obesity also had higher odds of malnutrition during pregnancy. The increased odds of malnutrition among women with MBS suggests that it is important to consider tailoring nutrition recommendations to address the different nutritional needs of pregnant women who had MBS and may be at risk for malnutrition.


Novel Variant of OCT4, Named OCT4B5, is Highly Expressed in Human Pluripotent Cells.
Alternative promoter and alternative splicing are two important mechanisms of gene regulation and protein diversity in different physiological contexts of eukaryotes, especially in stem cells and developmental stages. Pou5f1 gene which codes the stemness marker OCT4, utilizes alternative splicing and promoter mechanisms, which result in generation of multiple spliced variants and subsequently multiple protein isoforms. By far, nine variants of OCT4 (OCT4A, OCT4B, OCT4B1, OCT4B2, OCT4B3, OCT4B4, OCT4C, OCT4C1, and OCT4D) have been introduced. It has been well established that OCT4A plays essential roles in early developmental stages as well as maintenance of stemness in embryonic stem cells (ESCs). However, the roles and functions of other variants and isoforms of OCT4 in biological systems are less appreciated. In this study, we report a new OCT4 variant, designated as OCT4B5. RT-PCR assay on different human cell lines including pluripotent, normal and cancer cells showed that OCT4B5 is expressed at variable level in different cell lines. By semi-quantifying of OCT4B5 expression in pluripotent and differentiated states of NT2 cell lines, we reveal that this variant of OCT4 is highly expressed in undifferentiated state and its expression is down-regulated upon differentiation. Compared to OCT4A which is sharply down-regulated in retinoic acid induced differentiation of NT2 cell line, the expression of OCT4B5 remains at low level in differentiated state. Overall, this study emphasizes the complexity of OCT4 gene expression and regulation in different states of stem cells and physiological contexts. Graphical Abstract.


Six-Minute Walk as a Measure of Walking Capacity and Endurance in Patients With Pediatric-Onset Multiple Sclerosis.
Despite low levels of disability, youth with pediatric-onset MS (POMS) engage in less physical activity compared to peers. The contribution of walking capacity, endurance, behavior, and MS co-morbidities remain relatively undefined and may provide valuable insights into the limitations toward physical activity in youth with MS. Investigate differences in walking capacity, endurance and real-world behaviors of daily activity between youth with POMS and controls. DESIGN/METHODS: Youth diagnosed with MS prior to 18 years and aged ≤21 years were recruited in addition to healthy controls. Subjects completed questionnaires to quantify fatigue, depression, and physical activity levels and the timed 2- and 6-minute walk (2MW, 6MW) as an assessment of walk capacity and endurance. Subjects were sent home with a waist-worn accelerometer to assess real-world walking behavior. Forty-five POMS and 85 control subjects were enrolled. The POMS cohort had a mean age of 16.9±2.7 years with a mean disease duration of 2.8±2.6 years. A greater proportion of the POMS cohort was overweight/obese compared to controls (60% versus 33%). Subjects with MS walked a significantly shorter distance in 6 minutes compared to controls (1848 feet vs 2134 feet, p<0.0001) and, unlike controls, were unable to accelerate to their peak speed at the end of the 6MW. BMI category and MS disease significantly impacted 6MW performance. Using continuous accelerometry, subjects with MS spent less time in moderate-to-vigorous physical activity compared to controls (20.4 minutes/day vs 35.4 minutes/day, p=0.0003). The POMS cohort reported significantly higher levels of depression and fatigue, but self-reported similar levels of daily physical activity as controls. Youth with POMS exhibit slower 6MW performance and less daily engagement in moderate-to-vigorous physical activity, suggesting limitations in functional walking capacity, endurance, and daily activity behavior. Limitations in walking endurance and capacity are most prominent in those youth who are overweight/obese and living with MS. This study provides Class III evidence that, compared to healthy controls, patients with pediatric-onset MS walk shorter distances on the 6 minute walk test, are less able to accelerate to peak speed at the end of the test, and are less physically active.


Decapentaplegic-responsive silencers contain overlapping mad-binding sites.
Smad proteins regulate transcription in response to transforming growth factor-beta signaling pathways by binding to two distinct types of DNA sites. The sequence GTCT is recognized by all receptor-activated Smads and by Smad4. The subset of Smads that responds to bone morphogenetic protein signaling recognizes a distinct class of GC-rich sites in addition to GTCT. Recent work has shown that Drosophila Mad protein, the homologue of bone morphogenetic protein rSmads, binds to GRCGNC sites through the same MH1 domain beta-hairpin interface used to contact GTCT sites. However, binding to GRCGNC requires base-specific contact by two Mad proteins, and here we provide evidence that this is achieved by contact of the two Mad subunits that overlap across the two central base pairs of the site. This topology is supported by results indicating that His-93, which is located at the tip of the Mad beta-hairpin, is in close proximity to base pairs 2 and 5. Also consistent with the model is disruption of binding by mutation of Glu-39 and Glu-40, which are predicted to lie at the interface of the two overlapping Mad MH1 domains. As predicted from the overlapping model, binding is disrupted by insertion of 1 bp in the middle of the site, whereas insertion of 2 bp creates abutting sites that can be bound by the Mad-Medea heterotrimer without requiring Glu-39 and Glu-40. Overlapping Mad sites predominate in decapentaplegic response elements, consistent with a high degree of specificity in response to signaling.


Stepwise estrogen suppression manipulating the estrostat.
Estrogen suppression is an effective endocrine treatment option in pre- as well as postmenopausal breast cancer patients. The fact that it produces clinical benefits not only in these two groups of patients that differ significantly with respect to plasma estrogen levels but also among patients with very low plasma estrogen levels due to previous hypophysectomy, adrenalectomy or treatment with first/second generation aromatase inhibitors, suggests estrogen deprivation to work independent of pretreatment plasma estrogen levels. Interestingly, in vitro studies have revealed MCF-7 cells to respond to estrogen deprivation by sensitization, causing maximum estradiol stimulation at a concentration 10(-5) to 10(-4) the concentration needed in wild-type cells. While results from recent phase III studies comparing novel aromatase inhibitors and inactivators to conventional therapy have suggested that a more effective hormone ablation may be translated into an improved clinical efficacy, the biochemical rationale for lack of complete cross-resistance between aromatase inhibitors and inactivators or aromatase inhibitors and megestrol acetate remains to be explained. Interestingly, patients becoming resistant to estrogen deprivation may still respond to estrogens administered in pharmacological doses. Future studies are warranted to explore alterations in gene expression and signaling mechanisms in response to different therapies in tumor tissue in vivo.


Exploring the mechanism of andrographolide in the treatment of gastric cancer through network pharmacology and molecular docking.
Gastric cancer has emerged as a key challenge in oncology research as a malignant tumour with advanced stage detection. Apart from surgical management, a pharmacotherapeutic approach to stomach cancer treatment is an appealing option to consider. Andrographolide has been shown to have anticancer and chemosensitizer properties in a variety of solid tumors, including stomach cancer but the exact molecular mechanism is skeptical. In this study, we identified and validated pharmacological mechanism involved in the treatment of GC with integrated approach of network pharmacology and molecular docking. The targets of andrographolide and GC were obtained from databases. The intersected targets between andrographolide and GC-related genes were used to construct protein-protein interaction (PPI) network. Furthermore, mechanism of action of the targets was predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Finally, these results were validated by molecular docking experiments, mRNA and protein expression level. A total of 197 targets were obtained for andrographolide treating GC. Functional enrichment analysis revealed that the target genes were exerted promising therapeutic effects on GC by HIF-1 and PI3K-Akt signaling pathway. The possible mechanism of action is by inactivation of HIF-1 signaling pathway which is dependent on the inhibition of upstream PI3K-AKT pathway. The PPI network identified SRC, AKT1, TP53, STAT3, PIK3CA, MAPK1, MAPK3, VEGFA, JUN and HSP90AA1 as potential hub targets. In addition, these results were further validated with molecular docking experiments. Survival analysis indicated that the expression levels of the hub genes were significantly associated with the clinical prognosis of GC. This study provided a novel approach to reveal the therapeutic mechanisms of andrographolide on GC, making future clinical application of andrographolide in the treatment of GC.


Spontaneous intracranial hypotension presenting with coma: a case report and literature review.
Spontaneous intracranial hypotension is characterized by orthostatic headache in the absence of a history of head trauma or lumbar puncture, and diagnosis is confirmed by a specific cerebrospinal fluid pressure and neuroimaging findings. It rarely presents with coma. A 62-year-old man presented with progressive cognitive decline of 2 to 4 weeks' duration. He was diagnosed with spontaneous intracranial hypotension according to cerebrospinal fluid pressure and neuroimaging findings, and treated conservatively.


Memory disorders in children.
Memory disorders are a frequent consequence of a variety of childhood neurological conditions. We will review the characteristics of memory disorders as a function of the main four memory systems: short-term memory, episodic memory, semantic memory, and procedural memory. For each system, we will identify the most typical cerebral and/or genetic correlates, and we will discuss the impact of impairment of each memory system on everyday life functioning.


Metabolic Syndrome Sinkholes: What to Do When Occam's Razor Gets Blunted.
The real promise of the metabolic syndrome concept was the opportunity to elucidate a singular common mechanism for its component abnormalities and consequently a singular therapy. That promise has not produced. This relates to the following considerations: (1) metabolic syndrome remains a syndrome not a disease, (2) its diagnosis offers little more than what can be determined by measuring waist circumference, (3) risk assessment is not improved by the diagnosis of metabolic syndrome, (4) the diagnosis of metabolic syndrome does not impact the treatment of each component of the syndrome, and (5) there is no effective therapy for metabolic syndrome in its entirety.


Functions of microRNAs in plant stress responses.
The discovery of microRNAs (miRNAs) as gene regulators has led to a paradigm shift in the understanding of post-transcriptional gene regulation in plants and animals. miRNAs have emerged as master regulators of plant growth and development. Evidence suggesting that miRNAs play a role in plant stress responses arises from the discovery that miR398 targets genes with known roles in stress tolerance. In addition, the expression profiles of most miRNAs that are implicated in plant growth and development are significantly altered during stress. These later findings imply that attenuated plant growth and development under stress may be under the control of stress-responsive miRNAs. Here we review recent progress in the understanding of miRNA-mediated plant stress tolerance.


Health related quality of life and perceived social support in French and Lebanese MS patients: A comparative study.
The perception of diagnosis announcement, the social support and the coping strategies seem to be determining factors for the quality of life of multiple sclerosis (MS) patients, with possible transcultural variations. This study explores these psychosocial dimensions in Lebanese and French MS patients. For this cross-sectional multi-center study, 8 questionnaires were used to assess quality of life, family support, coping strategies, mood, fatigue, stress, and hopelessness in MS patients. 7 were translated into Arabic and then back translated into French. These were administered to a group of Lebanese MS patients and compared to an MS sample from France. The data was collected for both populations and analyzed. A total of 107 patients were included, 46 Lebanese and 61 French. The majority of MS patients were young females with a high level of education, relapsing remitting form of MS and a low level of disability. Both populations exhibited comparable quality of life and answers on the questionnaires regarding mood disorders, hopelessness, and perceived stress. However, the French patients had significantly more fatigue. Perceived social support given by family was considered greater in the French group compared to the Lebanese one. Also, maladaptive coping strategies (such as self-distraction, denial, behavioral disengagement, substance use, self-blame, venting) were used more frequently by the French population compared to the Lebanese, and this correlated with higher anxiety scores. Diagnosis communication was overall brief, informative, and satisfying in both populations. This study highlighted transcultural differences between French and Lebanese MS patients mainly in social support and coping strategies.


Early and midterm outcomes of a modified single-patch technique for repairing complete atrioventricular septal defect in children and adults.
The "modified single-patch" technique (Nunn's technique) has become more widely adopted, especially in small infants with common atrioventricular septal defect (CAVSD). In this study, we retrospectively reviewed our surgical experiences of the "modified single-patch" technique with CAVSD patients, including newborns and adults, to reveal the early and midterm clinical results. There were 233 cases diagnosed with CAVSD undergoing biventricular repair in our hospital from June 2009 to 2016. A total of 197 cases (84.5%) with the "modified single-patch" technique were enrolled in the final analysis, including type A in 106 cases (53.8%), type B in 13 cases (6.6%), type C in 15 cases (7.6%), and intermediate type in 63 cases (32%). Major associated cardiovascular malformations included five cases of unroofed coronary sinus syndrome with LSVC (UCS), five cases of coarctation of the aorta and one case of translocation of the great artery. The median age at operation of the studied 197 cases was 44.3 ± 103.3 months (ranging from 18 days to 58 years old), including two newborns. Detailed information on the "modified single-patch" procedure was described previously, and the other cardiac malformations were repaired simultaneously with surgical repair. There were 14 (7.1%) early deaths and 3 (1.5%) late deaths at 3 months and 1 year after the initial operation, respectively. The total mortality rate was 8.1%, and there was no significant difference in mortality among the different age groups (P = .291). Five patients (2.5%) underwent reoperation because of severe mitral insufficiency (MI), and another patient was reoperated for left ventricular outflow tract obstruction 3 years after the initial surgery. Long-term survival in the <3 months group was significantly lower than that in the group of older children (1-18 years old). Of the 180 survivors who were followed up for at least 1 year, the proportion of severe MI began to drop from 26.2% before the operation to 13.8% just 1-week postoperation and continued to decline to the lowest level, 3.4%, at 3 months postoperation. However, MI began to rebound at 3 months and reached 20.8% at 1-year postoperation. The rebound of MI was evident in the (3 months, 6 months) age group and the >18 years age group. However, compared to the preoperation situation, the proportion of severe tricuspid insufficiencies decreased each month from 24.8% to 0.0% until 3 months after the operation and remained at a relatively low level within 1 year after surgery. In our experience, age is not a limitation of the modified single-patch technique, and patients even in adults with surgical indications can apply this technique. In older children and adults, we should pay more attention to atrioventricular valve annuloplasty. Infants may suffer from severe residual left atrioventricular valve regurgitation, especially in the <3 months age group, so we should improve postoperative follow-up work during infancy.


Structural, inorganic, and adsorptive properties of hydrochars obtained by hydrothermal carbonization of coffee waste.
The hydrothermal carbonization process is a suitable process for the conversion of potentially harmful lignocellulosic waste into hydrochars. Defective coffee beans were the precursor raw material for hydrochar synthesis. Reactions were performed in a high-pressure reactor at 150, 200, and 250 °C, in autogenous pressure, for 40 min. Hydrochars were recovered by filtration and characterized by energy dispersive X-ray fluorescence spectroscopy, UV-Vis spectrophotometry, attenuated total reflection Fourier-transform infrared spectroscopy, differential thermal analysis, and scanning electron microscopy. Methylene blue adsorption tests were performed and analyzed by Langmuir and Freundlich adsorption isotherms. Adsorption mechanisms were investigated by computational calculations at DFT level. Results suggest that hydrochars from defective coffee beans can be applied as technological resources in the agronomic and environmental fields due to their inorganic composition, mainly to high magnesium content, the structural characteristics of porosity, biodegradation control, soil carbon-fixation and adsorption capacity. Important adsorption processes are caused by the development of oxygenated functional groups on the hydrochar surface.


Proteases of enhanced stability: characterization of a thermostable variant of subtilisin.
A procedure has been developed for the isolation and identification of mutants in the bacterial serine protease subtilisin that exhibit enhanced thermal stability. The cloned subtilisin BPN' gene from Bacillus amyloliquefaciens was treated with bisulfite, a chemical mutagen that deaminates cytosine to uracil in single-stranded DNA. Strains containing the cloned, mutagenized subtilisin gene which produced subtilisin with enhanced thermal stability were selected by a simple plate assay procedure which screens for esterase activity on nitrocellulose filters after preincubation at elevated temperatures. One thermostable subtilisin variant, designated 7150, has been fully characterized and found to differ from wild-type subtilisin by a single substitution of Ser for Asn at position 218. The 7150 enzyme was found to undergo thermal inactivation at one-fourth the rate of the wild-type enzyme when incubated at elevated temperatures. Moreover, the mid-point in the thermally induced transition from the folded to unfolded state was found to be 2.4-3.9 degrees C higher for 7150 as determined by differential scanning calorimetry under a variety of conditions. The refined, 1.8-A crystal structures of the wild-type and 7150 subtilisin have been compared in detail, leading to the conclusion that slight improvements in hydrogen bond parameters in the vicinity of position 218 result in the enhanced thermal stability of 7150.


Direct Evaluation of Treatment Response in Brain Metastatic Disease with Deep Neuroevolution.
Cancer centers have an urgent and unmet clinical and research need for AI that can guide patient management. A core component of advancing cancer treatment research is assessing response to therapy. Doing so by hand, for example, as per RECIST or RANO criteria, is tedious and time-consuming, and can miss important tumor response information. Most notably, the prevalent response criteria often exclude lesions, the non-target lesions, altogether. We wish to assess change in a holistic fashion that includes all lesions, obtaining simple, informative, and automated assessments of tumor progression or regression. Because genetic sub-types of cancer can be fairly specific and patient enrollment in therapy trials is often limited in number and accrual rate, we wish to make response assessments with small training sets. Deep neuroevolution (DNE) is a novel radiology artificial intelligence (AI) optimization approach that performs well on small training sets. Here, we use a DNE parameter search to optimize a convolutional neural network (CNN) that predicts progression versus regression of metastatic brain disease. We analyzed 50 pairs of MRI contrast-enhanced images as our training set. Half of these pairs, separated in time, qualified as disease progression, while the other 25 image pairs constituted regression. We trained the parameters of a CNN via "mutations" that consisted of random CNN weight adjustments and evaluated mutation "fitness" as summed training set accuracy. We then incorporated the best mutations into the next generation's CNN, repeating this process for approximately 50,000 generations. We applied the CNNs to our training set, as well as a separate testing set with the same class balance of 25 progression and 25 regression cases. DNE achieved monotonic convergence to 100% training set accuracy. DNE also converged monotonically to 100% testing set accuracy. We have thus shown that DNE can accurately classify brain metastatic disease progression versus regression. Future work will extend the input from 2D image slices to full 3D volumes, and include the category of "no change." We believe that an approach such as ours can ultimately provide a useful and informative complement to RANO/RECIST assessment and volumetric AI analysis.


[Interventional study on Dolutegravir and other antiretrovirals in patients with subclinical atherosclerosis in the Kinshasa Hospital].
After 2016, the World Health Organization (WHO) proposed Dolutegravir (DTG) as an alternative first-line treatment for adults. Thus, the purpose of this study was to identify biomarkers of cardiometabolic risk capable of demonstrating the beneficial effect of Dolutegravir (DTG) compared to other antiretrovirals in predicting atherosclerosis in people living with HIV (PLHIV) and hospitalized in Kinshasa Hospital. we conducted an interventional study of people living with HIV who had received antiretroviral therapy (ART) for at least 6 months and were treated in the structures of the network coordinated by the Catholic Church (BDOM-Bureau Diocésain des Oeuvres Médicales) and of the University Clinics of Kinshasa (CUK) between January 2017 and December 2021. Subclinical atherosclerosis was defined as Pulsed Pressure (PP) ≥60 mm Hg; Carotid Intima-Media Thickness (CIMT) > 0.8 mm; and Systolic Pressure Index (SPI) < 0.9. Logistic regression was used in the statistical analysis of associations. a total of 334 PLHIV were recruited, of whom 96.1% (n=321) were on ART and 13.9% (n=13) were ART naïve patients. The mean age of PLHIV was 51±12 years with a female predominance (70.4%; n=235); the independent determinants of subclinical atherosclerosis were marital status (aOR: 4. 95% CI 1.5-10.5; p<0.006), low socioeconomic level (aOR: 10.7, 95% CI 2.3-48.7 p<0.002), duration of HIV infection (aOR: 6.6, 95% CI 2.8-16; p<0.0001), duration of antiretroviral therapy ≥9 years (aOR: 0.3, 95% CI 0.2-0.7; p<0.005) and total cholesterol ratio/high-density lipoprotein-cholesterol (CT/HDL-c)(aOR: 2, 95% CI 1.1-3.6; p= 0.034). The mean values of traditional and emergent variables were significantly higher in the previous ART regimen without DTG than in the new regimen with DTG. However, dyslipidemia was detected during the new DTG-based regimen. dyslipidemia was common during the DTG-based regimen. Marital status, low socioeconomic level, duration of HIV infection, duration of antiretroviral treatment beyond 9 years and the TC/HDL-c ratio were identified as determinants of subclinical atherosclerosis in PLHIV on ART hospitalized in the Kinshasa hospital.


Death and End-of-Life Care in Emergency Departments in the US.
There are more than 140 million annual visits to emergency departments (EDs) in the US. The role of EDs in providing care at or near the end of life is not well characterized. To determine the frequency of death in the ED or within 1 month of an ED visit in an all-age, all-payer national database. The retrospective cohort study used patient-level data from the nationally representative Optum clinical electronic health record data set for 2010 to 2020. Data were analyzed from January to March 2022. Age, Charlson Comorbidity Index (CCI), and year of ED encounter. The primary outcome was death in the ED, overall and stratified by age, CCI, or year. A key secondary outcome was death within 1 month of an ED encounter. We extrapolated to make national estimates using US Census and Nationwide Emergency Department Sample data. Among a total of 104 113 518 individual patients with 96 239 939 ED encounters, 205 372 ED deaths were identified in Optum, for whom median (IQR) age was 72 (53 to >80) years, 114 582 (55.8%) were male, and 152 672 (74.3%) were White. ED death affected 0.20% of overall patients and accounted for 0.21% of ED encounters. An additional 603 273 patients died within 1 month of an ED encounter. Extrapolated nationally, ED deaths accounted for 11.3% of total deaths from 2010 to 2019, and 33.2% of all decedents nationally visited the ED within 1 month of their death. The proportion of total national deaths occurring in the ED decreased by 0.27% annually (P for trend = .003) but the proportion who died within 1 month of an ED visit increased by 1.2% annually (P for trend < .001). Compared with all ED encounters, patients with visits resulting in death were older, more likely to be White, male, and not Hispanic, and had higher CCI. Among ED encounters for patients aged older than 80 years, nearly 1 in 12 died within 1 month. This retrospective cohort study found deaths during or shortly after ED care were common, especially among patients who are older and with chronic comorbidities. EDs must identify patients for whom end-of-life care is necessary or preferred and be equipped to deliver this care excellently.


Cross-cultural analysis of students' sexual standards.
Our purpose was to investigate, cross-culturally, university students' premarital sexual standards. A number of predictions were derived from the work of Cristensen, Reiss, and Burr. Data were collected via self-administered questionnaires from over 1100 English-speaking respondents in five "cultures" (four countries). These cultural contexts had a strong effect on the attitudes and behavior of individual respondents. As predicted, the difference in the standards held by males and females was small in highly permissive societies. Negative consequences of premarital intercourse (i.e., guilt) were reported by the highest proportion of sexually experienced respondents in the most restrictive society. An unsuccessful effort was made to predict how the correlation between permissiveness and such variables as religiosity would change in different cultures. Across all five cultures, greater courtship participation, less religiosity, greater physical attractiveness, and spending less time with one's family were associated with greater permissiveness. Finally, students from high-status backgrounds were generally more permissive.


Alterations in the gut microbiota and metabolite profiles of patients with Kashin-Beck disease, an endemic osteoarthritis in China.
Kashin-Beck disease (KBD) is a severe osteochondral disorder that may be driven by the interaction between genetic and environmental factors. We aimed to improve our understanding of the gut microbiota structure in KBD patients of different grades and the relationship between the gut microbiota and serum metabolites. Fecal and serum samples collected from KBD patients and normal controls (NCs) were used to characterize the gut microbiota using 16S rDNA gene and metabolomic sequencing via liquid chromatography-mass spectrometry (LC/MS). To identify whether gut microbial changes at the species level are associated with the genes or functions of the gut bacteria in the KBD patients, metagenomic sequencing of fecal samples from grade I KBD, grade II KBD and NC subjects was performed. The KBD group was characterized by elevated levels of Fusobacteria and Bacteroidetes. A total of 56 genera were identified to be significantly differentially abundant between the two groups. The genera Alloprevotella, Robinsoniella, Megamonas, and Escherichia_Shigella were more abundant in the KBD group. Consistent with the 16S rDNA analysis at the genus level, most of the differentially abundant species in KBD subjects belonged to the genus Prevotella according to metagenomic sequencing. Serum metabolomic analysis identified some differentially abundant metabolites among the grade I and II KBD and NC groups that were involved in lipid metabolism metabolic networks, such as that for unsaturated fatty acids and glycerophospholipids. Furthermore, we found that these differences in metabolite levels were associated with altered abundances of specific species. Our study provides a comprehensive landscape of the gut microbiota and metabolites in KBD patients and provides substantial evidence of a novel interplay between the gut microbiome and metabolome in KBD pathogenesis.


COVID-19 in older adults: Retrospective cohort study in a tertiary hospital in Japan.
We aimed to describe the clinical characteristics, treatment and outcomes of patients with COVID-19 pneumonia, in particular older patients, admitted to tertiary and partner hospitals in Saitama, Japan. We retrospectively reviewed the medical records of patients with COVID-19 pneumonia admitted to tertiary and partner hospitals in Saitama, Japan. Twenty-six patients with COVID-19 were categorized into two groups, i.e., older (≥75 years) and younger adults (≤74 years). We evaluated the clinical characteristics, comorbidities, symptoms, laboratory test results, treatments and outcomes of the patients. The majority of the older patients had comorbidities, such as dementia, cardiovascular disease and bone fractures. Comorbidities were significantly more frequent in older patients than younger patients. No association was found between age and body temperature or the incidence of respiratory failure. White blood cell count was significantly lower in older patients (P = 0.018) and the decrease in lymphocytes was greater in younger patients (P = 0.009). Computed tomography (CT) of all patients showed non-segmental, peripherally dominant ground-glass opacities consistent with COVID-19 pneumonia. In older patients, antiviral drugs, anticoagulants and anti-inflammatory drugs were administered on a compassionate use basis. The difference in mortality between the older and the younger patients was not statistically significant. In older patients, typical clinical symptoms and blood test changes were often absent; however, CT always contained typical findings of COVID-19, suggesting that CT may be a useful diagnostic tool. Our report illustrates that appropriate treatment, taking patient background into consideration, may improve their condition regardless of age. Geriatr Gerontol Int 2020; 20: 1044-1049.


Effects of long-term moderate exercise and increase in number of daily steps on serum lipids in women: randomised controlled trial [ISRCTN21921919].
BACKGROUND: This study was designed to evaluate the effects of a 24-month period of moderate exercise on serum lipids in menopausal women. METHODS: The subjects (40--60 y) were randomly divided into an exercise group (n = 14) and a control group (n = 13). The women in the exercise group were asked to participate in a 90-minute physical education class once a week and to record their daily steps as measured by a pedometer for 24 months. RESULTS: Mean of daily steps was significantly higher in the exercise group from about 6,800 to over 8,500 steps (P < 0.01). In the control group, the number of daily steps ranged from 5,700 to 6,800 steps throughout the follow-up period. A significant interaction between the exercise group and the control group in the changes og total cholesterol (TC), high-density lipoprotein cholesterol (HDLC) and TC : HDLC ratio could be observed (P < 0.05). By multiple regression analysis, the number of daily steps was related to HDLC and TC : HDLC levels after 24 months, and the changes in TC and HDLC concentrations. CONCLUSIONS: These results suggest that daily exercise as well as increasing the number of daily steps can improve the profile of serum lipids.


Use of the Wilshire Equations to Correlate and Extrapolate Creep Data of HR6W and Sanicro 25.
Advanced power plant alloys must endure high temperatures and pressures for durations at which creep data are often not available, necessitating the extrapolation of creep life. Many methods have been proposed to extrapolate creep life, and one of recent significance is a set of equations known as the Wilshire equations. With this method, multiple approaches can be used to determine creep activation energy, increase the goodness of fit of available experimental data, and improve the confidence level of calculating long-term creep strength at times well beyond the available experimental data. In this article, the Wilshire equation is used to extrapolate the creep life of HR6W and Sanicro 25, and different methods to determine creep activation energy, region splitting, the use of short-duration test data, and the omission of very-short-term data are investigated to determine their effect on correlation and calculations. It was found that using a known value of the activation energy of lattice self-diffusion, rather than calculating Q C * from each data set, is both the simplest and most viable method to determine Q C * . Region-splitting improved rupture time calculations for both alloys. Extrapolating creep life from short-term data for these alloys was found to be reasonable.


Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus.
In order to investigate whether short- or long-term glycemic fluctuations could induce oxidative stress and chronic inflammation, we evaluated the relationships between glycemic variability, oxidative stress markers, and high-sensitivity C-reactive protein (hs-CRP). We enrolled 34 patients with type 2 diabetes. As a measure of short-term glycemic variability, mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring system data. For determining long-term glycemic variability, we calculated the standard deviation (SD) of hemoglobin A1c (HbA1c) levels measured over a 2-year period. Levels of oxidative stress markers: 8-iso-prostaglandin F2α (8-iso-PGF2α), thiobarbituric acid-reactive substance (TBARS), 8-hydroxydeoxyguanosine (8-OHdG), and hs-CRP were measured. MAGE was significantly correlated with the SD of HbA1c levels (r = 0.73, p < 0.001) but not with HbA1c level. The levels of hs-CRP, TBARS, 8-OHdG, and 8-iso-PGF2α were significantly correlated with MAGE (r = 0.54, p = 0.001; r = 0.82, p < 0.001; r = 0.70, p < 0.001; r = 0.60, p < 0.001) and the SD of HbA1c levels (r = 0.53, p = 0.001; r = 0.73, p < 0.001; r = 0.69, p < 0.001; r = 0.43, p = 0.01) but not with HbA1c level. Relationships between 8-iso-PGF2α and MAGE or the SD of HbA1c levels remained significant after adjusting for other markers of diabetic control (R(2) = 0.684, R(2) = 0.595, p < 0.001, respectively). Both acute and chronic blood glucose variability can induce oxidative stress and chronic inflammation.


The association between gut microbiota and postoperative delirium in patients.
Postoperative delirium is a common postoperative complication in older patients, and its pathogenesis and biomarkers remain largely undetermined. The gut microbiota has been shown to regulate brain function, and therefore, it is vital to explore the association between gut microbiota and postoperative delirium. Of 220 patients (65 years old or older) who had a knee replacement, hip replacement, or laminectomy under general or spinal anesthesia, 86 participants were included in the data analysis. The incidence (primary outcome) and severity of postoperative delirium were assessed for two days. Fecal swabs were collected from participants immediately after surgery. The 16S rRNA gene sequencing was used to assess gut microbiota. Principal component analyses along with a literature review were used to identify plausible gut microbiota, and three gut bacteria were further studied for their associations with postoperative delirium. Of the 86 participants [age 71.0 (69.0-76.0, 25-75% percentile of quartile), 53% female], 10 (12%) developed postoperative delirium. Postoperative gut bacteria Parabacteroides distasonis was associated with postoperative delirium after adjusting for age and sex (Odds Ratio [OR] 2.13, 95% Confidence Interval (CI): 1.09-4.17, P = 0.026). The association between delirium and both Prevotella (OR: 0.59, 95% CI: 0.33-1.04, P = 0.067) and Collinsella (OR: 0.57, 95% CI: 0.27-1.24, P = 0.158) did not meet statistical significance. These findings suggest that there may be an association between postoperative gut microbiota, specifically Parabacteroides distasonis, and postoperative delirium. However, further research is needed to confirm these findings and better understand the gut-brain axis's role in postoperative outcomes.


Functional neointima characterization of vascular prostheses in human.
The purpose of this study was to evaluate neointimal functionality of synthetic vascular grafts repopulated by host cells after implantation. We obtained reseeded inflow and outflow cannulas of 2 patients undergoing orthotopic heart transplantation after left ventricular assist device implantation 9 and 10 months before. After cell isolation we examined cellular function of reseeded cells and their capability to form a functional endothelial layer applying immunohistologic markers and quantitative Western blot for endothelial nitric oxide synthase activity. Neointima formation in inflow and outflow cannulas differs macroscopically and by histologic appearance. The neointima formation on the surface of the polyethylene terephthalate fiber (Dacron) grafts differs substantially from native aortic vessel wall with respect to cellular and extracellular matrix composition and cellular function. The neointima of Dacron prostheses is composed of cells with rudimentary physiologic endothelial function. We conclude that synthetic matrices are not suitable scaffolds for generating functional cardiovascular implants.


Update on the epidemiology and transmission of Pneumocystis carinii.
Although Pneumocystis carinii pneumonia is one of the leading causes of morbidity and mortality among patients with the acquired immunodeficiency syndrome, many questions about its epidemiology and transmission remain unanswered. Whereas traditional theory postulates that the disease results from reactivation of latent infection, recent data suggest that active acquisition of infection, either through environmental exposure or person-to-person transmission, may occur. This review summarizes the current state of knowledge about the epidemiology and transmission of P. carinii and reports on evolving techniques that may improve our understanding of this organism in the future.


Egg yolk immunoglobulin (IgY) targeting SARS-CoV-2 S1 as potential virus entry blocker.
COVID-19 pandemic caused by SARS-CoV-2 has become a public health crisis worldwide. In this study, we aimed at demonstrating the neutralizing potential of the IgY produced after immunizing chicken with a recombinant SARS-CoV-2 spike protein S1 subunit. E. coli BL21 carrying plasmid pET28a-S1 was induced with IPTG for the expression of SARS-CoV-2 S1 protein. The recombinant His-tagged S1 was purified and verified by SDS-PAGE, Western blot and biolayer interferometry (BLI) assay. Then S1 protein emulsified with Freund's adjuvant was used to immunize layer chickens. Specific IgY against S1 (S1-IgY) produced from egg yolks of these chickens exhibited a high titer (1:25,600) and a strong binding affinity to S1 (KD = 318 nmol L-1 ). The neutralizing ability of S1-IgY was quantified by a SARS-CoV-2 pseudotyped virus-based neutralization assay with an IC50 value of 0.99 mg ml-1 . In addition, S1-IgY exhibited a strong ability in blocking the binding of SARS-CoV-2 S1 to hACE2, and it could partially compete with hACE2 for the binding sites on S1 by BLI assays. We demonstrated here that after immunization of chickens with our recombinant S1 protein, IgY neutralizing antibodies were generated against the SARS-CoV-2 spike protein S1 subunit; therefore, showing the potential use of IgY to block the entry of this virus. IgY targeting S1 subunit of SARS-CoV-2 could be a promising candidate for pre- and post-exposure prophylaxis or treatment of COVID-19. Administration of IgY-based oral preparation, oral or nasal spray may have profound implications for blocking SARS-CoV-2.


Tailored Tolane-Perfluorotolane Assembly as Supramolecular Base Pair Replacement in DNA.
Arene-fluoroarene interactions offer outstanding possibilities for engineering of supramolecular systems, including nucleic acids. Here, we implement the tolane-perfluorotolane interaction as base pair replacement in DNA. Tolane (THH) and perfluorotolane (TFF) moieties were connected to acyclic backbone units, comprising glycol nucleic acid (GNA) or butyl nucleic acid (BuNA) building blocks, that were incorporated via phosphoramidite chemistry at opposite positions in a DNA duplex. Thermodynamic analyses by UV thermal melting revealed a compelling stabilization by THH/TFF heteropairs only when connected to the BuNA backbone, but not with the shorter GNA linker. Detailed NMR studies confirmed the preference of the BuNA backbone for enhanced polar π-stacking. This work defines how orthogonal supramolecular interactions can be tailored by small constitutional changes in the DNA backbone, and it inspires future studies of arene-fluoroarene-programmed assembly of DNA.


Comprehensive relativistic ab initio and density functional theory studies on PtH, PtF, PtCl, and Pt(NH(3))(2)Cl(2).
Platinum monohydride is taken as an example to compare the performance of various relativistic and correlation approaches, such as all-electron DPT (direct perturbation theory), ECP (effective core potential); RSPT2, RSPT3 (second- and third-order multireference Rayleigh-Schrödinger perturbation theory), CCSD(T) (coupled-cluster with singles, doubles, and perturbative triples), as well as the four-component relativistic density functional theory. It is shown that first-order DPT performs significantly better than the (first-order) Breit-Pauli Hamiltonian. The performance of different approaches for the excitation energies of the platinum diatomics is discussed critically. The molecular spectroscopic constants for PtF and PtCl are predicted for the first time. The geometric data for several isomers of cis- and trans-Pt(NH(3))(2)Cl(2) are reported. The corresponding energetic data are calculated at relativistic all-electron and ECP-CCSD(T) as well as four-component relativistic density functional levels of theory. Contrary to previous results, it is found that the two C(2v) isomers of cis-Pt(NH(3))(2)Cl(2) are marginally separated in energy, which could be ascribed to Cl-H interactions.


Hot stuff: Research and policy principles for heat decarbonisation through smart electrification.
There is a need for major greenhouse gas emission reductions from heating in order to meet global decarbonisation goals. Electricity is expected to meet much of the heat demand currently provided by fossil fuels in the future and heat pumps may have an important role. This electrification transformation is not without challenges. Through a detailed narrative review alongside expert elicitation, we propose four principles for heat decarbonisation via electrification: putting energy efficiency first, valuing heat as a flexible load, understanding the emission impacts of heat electrification and designing electricity tariffs to reward flexibility. As a route to heat decarbonisation, when combined, these principles can offer significant consumer and carbon reduction benefits. In the short term these principles can encourage the smooth integration of heat electrification and in the longer term these principles are expected to reduce the scale of required infrastructural expansion. We propose a number of policy mechanisms which can be used to support these principles including (building) regulation, financial support, carbon standards, energy efficiency obligations and pricing.


Epileptic seizures and cerebral atrophy in alcoholics.
Computed tomography was carried out in two groups of chronic alcoholics diagnosed according to the research diagnostic criteria, one with and the other without epileptic seizures. The sizes of the ventricles and the extracerebral spaces were compared with those of a control group, in order to examine the possible role of cerebral atrophy in precipitating epileptic fits in chronic alcoholics. Although a severe degree of atrophy was demonstrated in both groups, no difference was found between alcoholics with and without seizures. However, by correlating the sizes of different spaces, a more generalized atrophy was found in alcoholics with seizures. Thus, cerebral atrophy in a more generalized form may play a yet undefined role in precipitating epileptic attacks.


Ultrasonic imaging of normal fetal response to external vibratory acoustic stimulation.
Fetal facial reactions and response decrement patterns to external noise stimulation were studied to characterize normal fetal neurobehavior in the third trimester. Response decrement, or habituation, is thought to reflect higher central nervous system function. Two hundred women with uncomplicated pregnancies, who were subsequently delivered of healthy infants at term, were studied between 26 and 41 weeks' gestation. After ultrasound views of the fetal face were obtained, a vibratory acoustic stimulus was applied repetitively to the maternal abdomen near the fetal head. Response decrement was defined as cessation of all components of the facial reaction, except eye blinking, over two sequential stimuli. Three response patterns were scored: (1) no startle, (2) startle without response decrement, and (3) response decrement by 12 stimuli. Whereas only 53% of fetuses between 26 and 27 weeks displayed startle reaction, all fetuses displayed startle responses by 28 weeks. As gestational age advances, an increasing number of fetuses exhibit response decrement, from no decrement at 26 to 27 weeks to 100% decrement at 40 to 41 weeks. A maturation of neurobehavioral response patterns takes place in normal third-trimester pregnancies. Response decrement testing may be a useful tool for in utero neurologic evaluation.


Schisandrol B protects against cholestatic liver injury by inhibiting pyroptosis through pregnane X receptor.
Previously, we demonstrated that Schisandrol B (SolB) protected against lithocholic acid (LCA)-induced cholestatic liver injury (CLI) through pregnane X receptor (PXR). Additionally, growing evidence has revealed that pyroptosis is involved in CLI. Whether the hepatoprotective effect of SolB driven by PXR activation is related to pyroptosis in CLI remains unclear. First, the hepatoprotective effect of SolB was confirmed, as evidenced by the decreased mortality, morphological and histopathological changes, and biochemical parameters. The upregulated serum lactic dehydrogenase (LDH) level, increased number of TUNEL-positive cells, and formation of hepatocyte membrane pores induced by LCA were significantly alleviated after SolB pretreatment, indicating that SolB attenuated LCA-induced hepatocyte damage. Further analysis revealed that both NOD-like receptor protein 3 (NLRP3) inflammasome-induced canonical pyroptosis and apoptosis protease activating factor-1 (Apaf-1) pyroptosome-induced noncanonical pyroptosis were significantly inhibited after SolB pretreatment, as illustrated by the decreased expression levels of NLRP3, ASC, caspase-1, and GSDMD and the levels of Apaf-1, caspase-11 p20, caspase-3 p20, and GSDME. Furthermore, the activation of the NF-κB and FoxO1 signaling pathways was inhibited after SolB pretreatment. In addition, the activation of PXR via SolB was proven by luciferase reporter gene assays and the upregulation of PXR targets. The results illustrated that SolB could significantly inhibit NLRP3 inflammasome-induced canonical pyroptosis through the PXR/NF-κB/NLRP3 axis and inhibit Apaf-1 pyroptosome-induced noncanonical pyroptosis through the PXR/FoxO1/Apaf-1 axis. Collectively, this study revealed that SolB protected against CLI by inhibiting pyroptosis through PXR, providing new insights for understanding the molecular mechanism of SolB as a promising anti-cholestatic agent.


Carrier-mediated transport of folate compounds in L1210 cells. Initial rate kinetics and extent of duality of entry routes for folic acid and diastereomers of 5-methyltetrahydrohomofolate in the presence of physiological anions.
Comparison of the kinetic parameters for influx of highly purified [3H]folic acid versus [3H]methotrexate in L1210 cells under anionic buffer conditions showed a marked discordancy. In addition, the kinetics for influx of [3H]folic acid were unchanged in variant L1210 cells defective in [3H]methotrexate transport. In these variant cells, the Vmax for methotrexate was reduced 17-fold and the Km was increased 3-fold. The results show that [3H]folic acid influx is mediated by a system which has a low affinity, but a 20-fold higher capacity, for folate compounds than the classical high-affinity system mediating [3H]methotrexate influx. Since the latter system also exhibits very low affinity for [3H]folic acid, it would not be expected to contribute significantly to the total influx of [3H]folic acid. The high-capacity system for [3H]folic acid influx is different from that believed to mediate pterin influx in L1210 cells since it was not inhibited by adenine, a potent inhibitor of pterin influx. However, exposure of cells to [3H]folic acid in a nonanionic buffer resulted in marked stimulation of initial influx, and a fraction of influx under these conditions was inhibited by methotrexate. These results suggest that anions modulate the extent of multiplicity of [3H]folic acid influx by their known effects on the high-affinity, reduced folate/methotrexate system. The diastereomers, at carbon 6, of [14C]5-methyltetrahydrohomofolate shared both transport systems. The influx Km for the natural diastereomer was one-half that of the unnatural form for both transport systems. Both diastereomers showed a much greater differential in affinity between the two transport systems than did [3H]folic acid. Our results suggest that an analog which could be effectively transported by the low-affinity/high-capacity route may be useful in the treatment of tumors resistant to methotrexate due to a defective high-affinity/low capacity influx system. We also found that incubation of L1210 cells with [3H]folic acid or the natural diastereomer [14C]5-methyltetrahydrohomofolate for 10 min resulted in the formation of a nonexchangeable fraction of radioactivity amounting to 20-40% of the total accumulation. This non-exchangeable fraction may be explained by the accumulation of metabolites other than polyglutamates. Preloading of cells with methotrexate prior to incubation with [3H]folic acid prevented the accumulation of radioactivity as a nonexchangeable fraction.


Microdosimetry applied to nanosecond pulsed electric fields: a comparison on a single cell between real and ideal waveforms.
A microdosimetric analysis using ideal and real pulses was carried out in this paper. To perform this goal, authors employed an algorithm developed recently for nsPEF based on Laplace's equation and able to take into account cell compartment dispersivity. A comparison between biphasic real and ideal waveforms was carried out. The ideal pulse induced the highest pore density efficiency, hence evidencing that a device optimization to avoid waveform degradation and losses has a fundamental impact on the performances of the delivered pulses at the single cell level.


Head and neck high-field imaging: oncology applications.
Head and neck imaging has benefited from 1.5 T magnetic resonance (MR) imaging, providing faster sequences, better soft tissue evaluation, and 3-axis imaging, with less radiation and iodine-based contrast injection. The US Food and Drug Administration has approved human MR imaging at high-field strength up to 4 T in clinical practice. 3 T MR imaging has become widely available, with the hope of significant advance in the evaluation of the head and neck region. This article reviews the benefits, disadvantages, and challenges of high-field imaging of the head and neck region, focusing on the imaging of head and neck cancer.


[New faunal and biological observations on ticks (Acari: Ixodoidea) in Abruzzo and other regions of Italy (IV)].
More than 300 new records of ticks (Acari, Ixodoidea) from Abruzzo and other Italian regions are reported. Short notes on the bioecology of every species are also given.


Continuity of care and health care cost among community-dwelling older adult veterans living with dementia.
To estimate the causal impact of continuity of care (COC) on total, institutional, and noninstitutional cost among community-dwelling older veterans with dementia. Combined Veterans Health Administration (VHA) and Medicare data in Fiscal Years (FYs) 2014-2015. FY 2014 COC was measured by the Bice-Boxerman Continuity of Care (BBC) index on a 0-1 scale. FY 2015 total combined VHA and Medicare cost, institutional cost of acute inpatient, emergency department [ED], long-/short-stay nursing home, and noninstitutional long-term care (LTC) cost for medical (like skilled-) and social (like unskilled-) services were assessed controlling for covariates. An instrumental variable for COC (change of residence by more than 10 miles) was used to account for unobserved health confounders. Community-dwelling veterans with dementia aged 66 and older, enrolled in Traditional Medicare (N = 102 073). Mean BBC in FY 2014 was 0.32; mean total cost in FY 2015 was $35 425. A 0.1 higher BBC resulted in (a) $4045 lower total cost; (b) $1597 lower acute inpatient cost, $119 lower ED cost, $4368 lower long-stay nursing home cost; (c) $402 higher noninstitutional medical LTC and $764 higher noninstitutional social LTC cost. BBC had no impact on short-stay nursing home cost. COC is an effective approach to reducing total health care cost by supporting noninstitutional care and reducing institutional care.


Embryotoxic and teratogenic effects of styrene derivatives on sea urchin development.
The effects of styrene and some of its derivatives on the fertilization and differentiation of sea urchins was investigated. When one of the gametes was pretreated for a few minutes, it was ascertained that the test substances act on the haploid nucleus, producing specific changes in the differentiation of the embryo. By this test system directly acting, weak mutagens may be detected.


Investigation of seawater mineral promoted pyrolysis at low temperature for improving the adsorption capabilities of biochar.
Naturally abundant seawater mineral was employed to engineer banana pseudostem and bamboo biochars through pyrolysis at different low temperatures for improving their adsorption capabilities for methylene blue (MB) and tetracycline (TC). The adsorption capabilities were greatly enhanced as the biochars were pyrolyzed at 300 °C with 50/1 (mL/g) dosage of seawater to biomass. For instance, the engineered banana pseudostem biochar exhibited 8.00 and 6.54 times higher adsorption capabilities than the corresponding pristine biochar for MB (447.79 mg/g vs 55.96 mg/g) and TC (100.59 mg/g vs 16.75 mg/g) at 25 °C, respectively. The characterization results indicated that a large number of carboxylates, lactone acid salts, and alkoxides were generated on the engineered biochar and a high cation exchange capacity was gained. The adsorption of MB was mainly attributed to cation exchange complying with hydrogen bonding and electrostatic interaction, whereas the adsorption of TC was realized by hydrogen bonding and complexation.


Effects of selective cyclooxygenase-2 inhibitor robenacoxib on primary cells derived from feline injection-site sarcoma.
Feline injection-site sarcomas (FISSs) are highly invasive malignant mesenchymal neoplasms that arise from injection sites in cats. Although the tumorigenesis of FISSs is still uncertain, there is a consensus that FISS is associated with chronic inflammation caused by irritation of injection-related trauma and foreign chemical substances. Chronic inflammation can provide a proper microenvironment for tumour development, which has been known as one of the risk factors of tumorigenesis in many tumours. To investigate the tumorigenesis of FISS and screen for its potential therapeutic targets, cyclooxygenase-2 (COX-2), an inflammation-enhancing enzyme, was selected as a target for this study. In vitro experiments using FISS- and normal tissue-derived primary cells and robenacoxib, a highly selective COX-2 inhibitor, were performed. The results demonstrated that expression of COX-2 could be detected in formalin-fixed and paraffin-embedded FISS tissues and FISS-derived primary cells. Cell viability, migration and colony formation of FISS-derived primary cells were inhibited, and cell apoptosis was enhanced by robenacoxib in a dose-dependent manner. However, susceptibility to robenacoxib varied in different lines of FISS primary cells and was not completely correlated with COX-2 expression. Our results suggest that COX-2 inhibitors could be potential adjuvant therapeutics against FISSs.


Functional R2R3-MYB transcription factor NsMYB1, regulating anthocyanin biosynthesis, was relative to the fruit color differentiation in Nitraria sibirica Pall.
Nitraria sibirica Pall. is an economic plant with two kinds of fruit color, widely spreads in the Qinghai Tibet Plateau. The chemical analysis and pharmacological evaluation had been carried out for several tens of years, the mechanism behind the fruit color differentiation is still unclear. In this manuscript, the chemical analysis of the extractions showed that the chemical composition of fruit color was anthocyanin, and two kind of Nitraria sibirica Pall. were caused by the content differentiation with the same anthocyanin kinds. Cyanidin-3-[2"-(6'"-coumaroyl)-glucosyl]-glucoside (C3G) was the major anthocyanin. Transcriptome analysis and the qRT-PCR revealed that the structural genes relative to anthocyanin biosynthesis except CHS, F3'5'H and ANS were up-regulated in the peels of BF (Black fruit) compared with the peels of RF (Red fruit), which indicated that transcript factor should be the reason for the expression difference of the structure genes. In the unigenes of the transcript factor MYB and bHLH, relative to anthocyanin, only NsMYB1 (Cluster 8422.10600), was high-expression and up-expression in the peels of BF. NsMYB1 encoded the same length protein with four amino acid differences in the RF and BF, and both contained the intact DNA, HTH-MYB and SANT domains. NsMYB1 was close to the AtMYB114, AtMYB113 and AtPAP1, regulating anthocyanin biosynthesis, in phylogenetic relationship. Both NsMYB1r and NsMYB1b could promote the transcript of the structural genes, and induced the anthocyanin accumulation in all tissues of transgenic tobacco. The insertion of 'TATA' in the promoter of NsMYB1r gave one more promoter region, and was the reason for higher transcripts in black fruit possibly. Cyanidin-3-[2''-(6'"-coumaroyl)-glucosyl]-glucoside was the major anthocyanin in black fruit of Nitraria sibirica Pall.. NsMYB1 was a functional R2R3-MYB transcription factor, regulated the anthocyanin biosynthesis, and led to the fruit color differentiation in Nitraria sibirica Pall.


Plaque rupture and morphological characteristics of the culprit lesion in acute coronary syndromes without significant angiographic lesion: analysis by intravascular ultrasound.
To evaluate by intravascular ultrasound (IVUS) the characteristics of the culprit lesion with plaque rupture without significant angiographic stenosis after acute coronary syndromes (ACS). After ACS, IVUS was performed in 68 patients (46.8 years±11.9) without significant angiographic stenosis (31±15%). Plaque rupture was defined as a cavity within the plaque, communicating with the arterial lumen and having an overlying residual fibrous cap fragment. Qualitative analysis defined the type of plaque, and quantitative analysis evaluated plaque plus media area, plaque volume, plaque burden, and arterial remodeling index. Patients were divided into two groups: Group I with plaque rupture (25 patients) and Group II without plaque rupture (43 patients). All patients with rupture showed soft or mixed plaque but no calcified plaque. In Group I, plaque rupture was associated with a larger plaque burden (49.8±12.3% vs. 39.8±12.1%, P<.0005), a more significant plaque plus media area (7.44±2.9 vs. 5.24±2.4mm(2), P<.001), a greater plaque volume (151.9±103.4 vs. 99.2±81.6mm(3), P<.007), and a higher ratio of plaque volume over length (8.0±3.8 vs. 5.6±3.7mm(3)/mm, P<.003). In Group I, positive remodeling was more frequent than intermediate remodeling (P<.03) or negative remodeling (P<.005). In Group II, there was no significant difference between the three types of remodeling. The plaque ruptures responsible for ACS frequently appear on voluminous plaques with a large plaque burden and positive arterial remodeling.


Clinical characteristics of first-admitted patients with ICD-10 schizotypal disorder.
The clinical picture of schizotypal disorders is rarely comprehensively described. To describe psychopathological profiles of patients with ICD-10 schizotypal disorder. A total of 151 first-admitted patients (with affective and somatic disorders excluded) were given a comprehensive psychopathological evaluation, including the Bonn Scale for the Assessment of Basic Symptoms. Patients with schizotypal disorder (n=50) were compared with those with psychosis (n=51) and those outside the schizophrenia spectrum (other diagnoses, n=50) on a number of psychopathological scales. Patients with schizotypal disorder scored intermediately between patients with psychosis and other diagnoses on scales related to positive and negative symptoms, disorders of emotional contact and formal thought disorder, but had the same scores as patients with schizophrenia for subtle aberrations of subjective experience. Schizotypal criteria were not normally distributed with an excess of patients between 2 and 6 criteria. Family history of schizophrenia was equally elevated among those with schizotypal disorder and those with psychosis. ICD-10 schizotypy represents a milder, less psychotic, variant of schizophrenia but there is no clear-cut division between the two disorders.


Relationship between status of plasma atrial natriuretic peptide and heart rate variability in human subjects.
A relationship may exist between plasma atrial natriuretic peptide (P-ANP) and heart rate variability (HRV), which reflects the activity of the autonomic nervous system. We performed a survey in human subjects to examine the relationship between P-ANP and HRV parameters. Three ethnic groups (Han, Uygur, and Kazakh) provided blood and urine samples and underwent 24-h ambulatory blood pressure monitoring and 24-h ECG recording (24-h Holter ECG). There was a positive correlation between P-ANP and HF, as well as a negative correlation between P-ANP and the LF/HF ratio, in all subjects from the 3 ethnic groups. There was no association of BP with any of the blood, urinary, and HRV parameters. Our results suggested the possibility of a relationship between P-ANP and HRV, which reflects autonomic activity. These findings are consistent with the previous report of a close relationship between ANP and cardiac parasympathetic and/or sympathetic activity.


Controlled Fabrication of Microparticles with Complex 3D Geometries by Tunable Interfacial Deformation of Confined Polymeric Fluids in 2D Micromolds.
Polymeric microparticles with complex shapes have attracted substantial attention in many application areas because particle shape is a critical parameter to impart programmable functionalities. The formation of specific three-dimensional (3D) microstructures in a simple, scalable, and controllable manner is difficult. Here, we report the controlled fabrication of microparticles with complex 3D shapes based on the simple tuning of mold swelling and capillarity. Specifically, a photocurable solution loaded in micromolds is spatially deformed into complex shapes depending on the degree of molding swelling and capillarity, thereby producing polymeric microparticles with controlled 3D shapes upon photopolymerization. The results show that highly uniform microparticles with controlled two-dimensional (2D) and 3D shapes were fabricated from identical 2D micromolds via the simple tuning of the wetting fluids. This technique can be extended to produce highly complex microarchitectures with controlled 3D geometric domains via 2D mold designs. Finally, multicompartment microparticles with independently controlled 3D shapes for each compartment are produced by a simple combination of fabrication sequences. We envision that this strategy of producing 3D microarchitectures from easily designed simple micromolds could provide a path to new materials and new properties.


The problematic prospects for prevention in the classroom: should alcohol education programs be expected to reduce drinking by youth?
Junior and senior high-school students completed a questionnaire, either once or twice (in successive years), providing measures of variables in three principal sets: (1) curricular variables, those typically addressed in contemporary alcohol education programs (knowledge about alcohol, attitudes toward alcohol, decision-making skills and self-esteem); (2) drinking behavior; and (3) noncurricular variables (demographic and social-psychological traits that typically characterize students before they are exposed to alcohol education programs). Bivariate analyses suggested that the curricular variables are related to drinking behavior, whereas multivariate analyses indicated that these same variables contribute little to the explanation of adolescent drinking when adjusted for the noncurricular variables, most of which are logically and/or chronologically prior to curriculum exposure. It is concluded that contemporary alcohol education programs do address variables that, when considered alone, appear to be related to drinking. However, these same variables make such a small independent contribution to drinking behavior that it is unlikely even a highly successful classroom intervention directed at these variables would do much to prevent alcohol use or abuse by youth.


[Risk factors associated with non-alcoholic fatty liver disease: a case-control study].
To establish the factors associated with the presence of non-alcoholic fatty liver disease (NAFLD) and evaluate the influence of each component constituting the metabolic syndrome (MS) and the risk of developing NAFLD. We performed a multicenter, population-based, observational, analytical study of cases and controls. A case was defined as any patient fulfilling the inclusion criteria and presenting NAFLD by abdominal echography for any reason. A control was randomly selected for each case, from the same health center and of the same age and sex. All the cases underwent anamnesis, physical examination, complete biochemical analyses and determination of MS according to the National Cholesterol Education Program-Adult Treatment Panel III criteria. All the controls also underwent an abdominal echography. We included 327 cases and 377 controls with a mean age of 56 ± 12 years for the cases and of 55 ± 13 years for the controls (range: 17 and 80 years); 52.0% of the cases were males and 49.1% of males were controls. The risk factors associated with NAFLD were obesity (odds ratio [OR] 3.82, 95% confidence interval [95% CI] 2.19-6.66), MS (OR 1.73, 95% CI 1.09-2.75), insulin resistance (OR 3.65, 95% CI 2.18-6.12), and an increase in alanine aminotransferase (ALT) (OR 4.72, 95% CI 2.58-8.61) and gamma glutamyl transferase values (GGT) (OR 1.95, 95% CI 1.14-3.34). The components of the MS best predicting NAFLD were hyperglycemia (OR 1.65, 95% CI1.06-2.56) and triglyceride values (OR 1.75, 95% CI1.13-2.72). The independent variables associated with NAFLD were obesity, insulin resistance and elevated ALT and GGT. The components of MS best predicting NAFLD were hyperglycemia and an increase in triglyceride values.


[Giant cell tumor of the third metacarpal bone: a case report].
A case of giant-cell tumor of the third metacarpal bone is reported, treated with resection and reconstruction by iliac graft. At a 5 years follow-up, the cosmetic and functional results of the hand are good.


Toxicity of graphene oxide to white rot fungus Phanerochaete chrysosporium.
With the wide production and applications of graphene and its derivatives, their toxicity to the environment has received much attention nowadays. In this study, we investigated the toxicity of graphene oxide (GO) to white rot fungus (Phanerochaete chrysosporium). GO was prepared by modified Hummers method and well characterized before use. P. chrysosporium was exposed to GO at the concentrations of 0-4 mg/mL for 7 d. The fresh and dry weights, pH values of culture media, structures, ultrastructures, IR spectra and activities of the decomposition of pollutants were measured to reveal the hazards of GO to P. chrysosporium. Our results indicated that low concentrations of GO stimulated the growth of P. chrysosporium. The exposure to GO induced more acidic pH values of the culture media after 7 d. GO induced the disruption of the fiber structure of P. chrysosporium, while at 4 mg/mL some very long and thick fibers were formed. Such changes were reflected in the scanning electron microscopy investigations, where the disruption of fibers was observed. In the ultrastructural investigations, the shape of P. chrysosporium cells changed and more vesicles were found upon the exposure to GO. The infrared spectroscopy analyses suggested that the chemical compositions of mycelia were not changed qualitatively. Beyond the toxicity, GO did not alter the activities of P. chrysosporium at low concentrations, but led to the complete loss of activity at high concentrations. The implication to the ecological safety of graphene is discussed.


Plasmodium yoelii infection of BALB/c mice results in expansion rather than induction of CD4(+) Foxp3(+) regulatory T cells.
Recently, we demonstrated elevated numbers of CD4(+) Foxp3(+) regulatory T (Treg) cells in Plasmodium yoelii-infected mice contributing to the regulation of anti-malarial immune response. However, it remains unclear whether this increase in Treg cells is due to thymus-derived Treg cell expansion or induction of Treg cells in the periphery. Here, we show that the frequency of Foxp3(+) Treg cells expressing neuropilin-1 (Nrp-1) decreased at early time-points during P. yoelii infection, whereas percentages of Helios(+) Foxp3(+) Treg cells remained unchanged. Both Foxp3(+) Nrp-1(+) and Foxp3(+) Nrp-1(-) Treg cells from P. yoelii-infected mice exhibited a similar T-cell receptor Vβ chain usage and methylation pattern in the Treg-specific demethylation region within the foxp3 locus. Strikingly, we did not observe induction of Foxp3 expression in Foxp3(-) T cells adoptively transferred to P. yoelii-infected mice. Hence, our results suggest that P. yoelii infection triggered expansion of naturally occurring Treg cells rather than de novo induction of Foxp3(+) Treg cells.


Combined use of CYFRA 21-1 and CA 125 predicts survival of patients with metastatic NSCLC and stable disease in IMpower150.
Patients with non-small cell lung cancer (NSCLC) and stable disease (SD) have an unmet clinical need to help guide early treatment adjustments. To evaluate the potential of tumor biomarkers to inform on survival outcomes in NSCLC SD patients. This post hoc analysis included 480 patients from the IMpower150 study with metastatic NSCLC, treated with chemotherapy, atezolizumab and bevacizumab combinations, who had SD at first CT scan (post-treatment initiation). Patients were stratified into high- and low-risk groups (overall survival [OS] and progression-free survival [PFS] outcomes) based on serum tumor biomarker levels. The CYFRA 21-1 and CA 125 biomarker combination predicted OS and PFS in patients with SD. Risk of death was ~4-fold higher for the biomarker-stratified high-risk versus low-risk SD patients (hazard ratio [HR] 3.80; 95% confidence interval [CI] 3.02-4.78; p < 0.0001). OS in patients with the low- and high-risk SD was comparable to that in patients with the CT-defined partial response (PR; HR 1.10; 95% CI 0.898-1.34) and progressive disease (PD) (HR 1.05; 95% CI 0.621-1.77), respectively. The findings were similar with PFS, and consistent across treatment arms. Biomarker testing shows potential for providing prognostic information to help direct treatment in NSCLC patients with SD. Prospective clinical studies are warranted. gov: NCT02366143.


Perceptions of interprofessional collaboration in education of dentists and dental hygienists and the impact on dental practice in the Netherlands: A qualitative study.
The purpose of this study was to evaluate the perceptions of dentists and dental hygienists regarding their own and each other's roles in interprofessional collaboration following a clinical interprofessional educational programme (CIEP) as part of their graduate programme at Radboud university medical center (Radboudumc) and HAN University of Applied Sciences (HAN UAS), Nijmegen, the Netherlands, respectively. Perceptions were obtained at the end of their study (2014) and two years after their graduation (2016). A qualitative study was conducted using a questionnaire with open-ended questions. Sixty-two dentists and thirty-eight dental hygienists were invited. Theory-based analyses were applied in combination with principles of Grounded Theory to analyse and synthesise the collected data from the open-ended questions. At baseline, 100% responded. At follow-up, thirty-two dentists (51.6%) and twenty-six dental hygienists (68.4%) responded; twenty-seven dentists (43.5%) and eighteen dental hygienists (47.4%) were included. Many similarities were found between baseline and follow-up regarding perceptions of each other's expertise and responsibility, learning from and with each other, and the behaviour of students and the "novice" professionals in interprofessional collaboration. Both dentists and dental hygienists experienced the CIEP as useful for interprofessional collaboration. The "novice" dentists and dental hygienists indicated that in dental practices interprofessional collaboration was less common. The CIEP resulted in more understanding amongst dentists and dental hygienists with regard to interprofessional roles, but in practice the "novice" dentists and dental hygienists face difficulties in applying the interprofessional roles.


Recurrent ameloblastoma of the jaws. A follow-up study.
Twenty-six cases of recurrent ameloblastoma of the jaws within a 15-year period are presented. They represent 8.9% of all cases of ameloblastoma seen in this period. The highest incidence was found in the third decade of life. There is a higher incidence of recurrences in the mandible (16/26) as compared to the maxilla (6/26). Over 80% of the recurrences presented within five years of primary surgery, emphasising the need for adequate and intensive follow-up during this critical period. Three patients whose lesions were operated on in the mandible showed similar lesions in the maxilla after a period of time. Conservative procedures at primary surgery produced the most recurrences. The cure rate for surgery of maxillary ameloblastoma was comparatively poor. The need for good visibility, adequate access and radical surgery in maxillary ameloblastoma is stressed.


The respiratory effects of reversing midazolam sedation with flumazenil in the presence or absence of narcotics.
The purpose of this study was to determine the effects of reversal of sedation with flumazenil (F), in the presence or absence of opiates, on arterial oxygen saturation (SaO2) and end-tidal CO2 (ETCO2). Twenty-four patients undergoing surgery and epidural anaesthesia were studied. Twelve patients (Group A) were orally premedicated with diazepam and 0.1 mg.kg-1 morphine i.m. Intraoperative sedation consisted of midazolam 0.1 mg.kg-1 and pethidine 0.7 mg.kg-1 i.v. Twelve patients (Group B) were premedicated with diazepam and sedated intraoperatively with 0.1 mg.kg-1 midazolam. In the recovery room, six patients in each group were randomly allocated to receive 1 mg of flumazenil while the others were allowed to awaken spontaneously (control). Sedation (eyes open vs closed), SaO2, ETCO2, respiratory rate, blood pressure and pulse were non-invasively monitored for 90 min. Administration of flumazenil resulted in a statistically significant increase in the number of patients with eyes open in both groups at 5 min, lasting 15 min in Group A and 30 min in Group B patients. An increase in SaO2 from 15-45 min after injection of flumazenil was observed only in Group B. No significant difference between groups in any other parameter was found. We concluded that reversal of benzodiazepine (BZ) sedation with flumazenil improved SaO2 in patients sedated with only BZ; in the presence of BZ and opiates, flumazenil did not affect respiratory parameters.


Enforced mobilization, early oral feeding, and balanced analgesia improve convalescence after colorectal surgery.
A postoperative regimen using a multimodal approach with enforced mobilization and early oral nutrition has been reported to improve convalescence but has not been compared with other postoperative regimens. Forty patients undergoing elective colorectal surgery were randomly allocated to an intervention group receiving comprehensive information on the importance of mobilization, balanced anesthesia, and postoperative analgesia including epidural local anesthetics and enforced postoperative mobilization or a control group receiving anesthesia without epidural local anesthetics, postoperative analgesia with epidural morphine, and mobilization without fixed goals. All patients were offered early oral nutrition. The regimens were compared by means of ambulation time and physical activity, voluntary muscle strength, pulmonary function, and body composition. The ambulation time improved substantially within 22 h in the intervention group versus 3 h in the control group on day 1 (P = 0.0004) and within 8 h versus 2 h on day 4 (P = 0.0003). The voluntary strength of the quadriceps muscle decreased by 3% in the intervention group versus 15% in the control group on day 7 (P = 0.04). Two months postoperatively, the difference between groups was the same (P = 0.02). This active per- and postoperative regimen based on a multimodal approach improved ambulation time and muscle function during admission and late convalescence.


Characteristics and outcomes of acute hepatitis of unknown etiology in Egypt: first report of adult adenovirus-associated hepatitis.
Several outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in 2022 in many countries, with adenovirus identified as the etiological agent in most of them. We aimed to evaluate the characteristics and outcomes of AHUE cases in Egypt. Hospitalized patients with acute hepatitis were included in the study. Drug-induced, alcoholic hepatitis, autoimmune hepatitis, and Wilson's disease were identified either by medical history or by routine laboratory diagnosis. Molecular and serological approaches were used to investigate common viral causes of hepatitis, such as hepatitis A-E viruses, cytomegalovirus, Epstein-Barr virus, herpes simplex viruses (HSV1/2), adenovirus, parvovirus B19, and coxsackie virus. A total of 42 patients were recruited and divided into two groups: 24 cases of unknown hepatitis after excluding the common causes and 18 cases of known hepatitis. About two-thirds of the patients were male (61.9%), and the mean age was 34.55 ± 16.27 years. Jaundice, dark urine, abdominal pain and diarrhea were recorded at a higher incidence in group 1, while jaundice and fever were frequent in group 2. Fulminant hepatitis occurred in 28.6% of the cases, but the two groups did not differ significantly in terms of patient outcome, duration of hospitalization, ascites, and development of fulminant hepatitis. Adenovirus was detected in five cases (20.8%) in group 1, and one case co-infecting with hepatitis E virus in group 2. Herpes simplex virus 1/2, coxsackie virus, and parvovirus B19 were not detected in any case, while etiologies of 75% of the cases were still not confirmed. One out of the six adenovirus-infected patients died. The outcome significantly correlated with the severity of the liver disease. This is the first report describing etiologies and characteristics of AHUE cases in Egypt, and interestingly, adenovirus was detected in adults. Further studies are required to determine the prevalence of this newly emerging viral hepatitis pathogens.