A membrane-based microfluidic device for mechano-chemical cell manipulation.
We introduce a microfluidic device for chemical manipulation and mechanical investigation of circulating cells. The device consists of two crossing microfluidic channels separated by a porous membrane. A chemical compound is flown through the upper "stimulus channel", which diffuses through the membrane into the lower "cell analysis channel", in which cells are mechanically deformed in two sequential narrow constrictions, one before and one after crossing the stimulus channel. Thus, this system permits to measure cell deformability before and after chemical cues are delivered to the cells within one single chip. The validity of the device was tested with monocytic cells stimulated with an actin-disrupting agent (Cytochalasin-D). Furthermore, as proof of principle of the device application, the effect of an anti-inflammatory drug (Pentoxifylline) was tested on monocytic cells activated with Lipopolysaccharides and on monocytes from patients affected by atherosclerosis. The results show that the system can detect differences in cell mechanical deformation after chemical cues are delivered to the cells through the porous membrane. Diffusion of Cytochalasin-D resulted in a considerable decrease in entry time in the narrow constriction and an evident increase in the velocity within the constriction. Pentoxifylline showed to decrease the entry time but not to affect the transit time within the constriction for monocytic cells. Monocytes from patients affected by atherosclerosis were difficult to test in the device due to increased adhesion to the walls of the microfluidic channel. Overall, this analysis shows that the device has potential applications as a cellular assay for analyzing cell-drug interaction.


A general model of hippocampal and dorsal striatal learning and decision making.
Humans and other animals use multiple strategies for making decisions. Reinforcement-learning theory distinguishes between stimulus-response (model-free; MF) learning and deliberative (model-based; MB) planning. The spatial-navigation literature presents a parallel dichotomy between navigation strategies. In "response learning," associated with the dorsolateral striatum (DLS), decisions are anchored to an egocentric reference frame. In "place learning," associated with the hippocampus, decisions are anchored to an allocentric reference frame. Emerging evidence suggests that the contribution of hippocampus to place learning may also underlie its contribution to MB learning by representing relational structure in a cognitive map. Here, we introduce a computational model in which hippocampus subserves place and MB learning by learning a "successor representation" of relational structure between states; DLS implements model-free response learning by learning associations between actions and egocentric representations of landmarks; and action values from either system are weighted by the reliability of its predictions. We show that this model reproduces a range of seemingly disparate behavioral findings in spatial and nonspatial decision tasks and explains the effects of lesions to DLS and hippocampus on these tasks. Furthermore, modeling place cells as driven by boundaries explains the observation that, unlike navigation guided by landmarks, navigation guided by boundaries is robust to "blocking" by prior state-reward associations due to learned associations between place cells. Our model, originally shaped by detailed constraints in the spatial literature, successfully characterizes the hippocampal-striatal system as a general system for decision making via adaptive combination of stimulus-response learning and the use of a cognitive map.


Combination of extracorporeal shock-wave lithotripsy and dissolution of gallbladder stones with methyl tert-butyl ether: a randomized study.
We conducted a prospective randomized study in gallstone patients to determine whether a combination of extracorporeal shock-wave lithotripsy and subsequent dissolution with methyl tert-butyl ether increases the success rate of methyl tert-butyl ether dissolution and shortens treatment time compared with monotherapy with methyl tert-butyl ether. Fifty patients were randomized into two groups. Twenty-five patients underwent extracorporeal shock-wave lithotripsy before contact dissolution with methyl tert-butyl ether, and 25 patients were treated with methyl tert-butyl ether alone. All patients had at least three stones or stones larger than 30 mm that were radiolucent on x-ray and had densities of less than 140 Hounsfield Units (HU) on computed tomography. Overall, the combined approach neither shortened the treatment time significantly vs. monotherapy with methyl tert-butyl ether nor reduced the time of hospitalization. The success rate was slightly but not significantly increased compared with that of methyl tert-butyl ether therapy alone. The recurrence rate was similar in the two groups after a median follow-up of 1 yr. However, when subgroups of patients with at least one stone larger than 15 mm or with stones with densities of more than 60 HU were analyzed, the clearance rate after 5 mo was significantly higher (p < 0.005 and p < 0.025, respectively) in patients subjected to a combination of extracorporeal shock-wave lithotripsy and methyl tert-butyl ether dissolution. Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether did not expose patients to more adverse effects than did treatment with methyl tert-butyl ether alone.


In silico analysis of putative metal response elements (MREs) in the zinc-responsive genes from Trichomonas vaginalis and the identification of novel palindromic MRE-like motif.
Zinc is an essential micronutrient that plays an important role as a co-factor to several proteins, including zinc-responsive transcription factors. Trichomonas vaginalis is able to survive in the presence of high zinc concentrations in the male urogenital tract. Several genes in T. vaginalis have been shown to respond to changes in zinc concentrations, however, the zinc-dependent mechanism remains undetermined. Recently, we identified in T. vaginalis the zinc finger protein, TvZNF1, which is an ortholog of the mammal metal transcription factor (MTF1). We searched for several of the zinc-responsive genes in T. vaginalis to determine whether if they contain metal response elements (MRE), cis-acting DNA elements that specifically bind MTF1. Six highly conserved over-represented sequence motifs (TvMREs), which share similarity with other eukaryotic MREs, were identified in the zinc-responsive genes in T. vaginalis. We also demonstrated that some of the TvMREs assemble as divalent complexes either as two closely spaced TvMREs or as two overlapping TvMREs forming a palindromic-like sequence: TGCC(N3)GGCA. Electrophoretic mobility shift assays were used to detect the zinc-dependent binding of TvZNF1 and nuclear proteins from T. vaginalis to this specific palindromic motif. Our results support a novel mechanism used by T. vaginalis for the transcriptional regulation of associated zinc-responsive genes through a MTF1/MRE-like system.


Enzyme-free passage of human pluripotent stem cells by controlling divalent cations.
Enzymes used for passaging human pluripotent stem cells (hPSCs) digest cell surface proteins, resulting in cell damage. Moreover, cell dissociation using divalent cation-free solutions causes apoptosis. Here we report that Mg(2+) and Ca(2+) control cell-fibronectin and cell-cell binding of hPSCs, respectively, under feeder- and serum-free culture conditions without enzyme. The hPSCs were detached from fibronectin-, vitronectin- or laminin-coated dishes in low concentrations of Mg(2+) and remained as large colonies in high concentrations of Ca(2+). Using enzyme-free solutions containing Ca(2+) without Mg(2+), we successfully passaged hPSCs as large cell clumps that showed less damage than cells passaged using a divalent cation-free solution or dispase. Under the same conditions, the undifferentiated and early-differentiated cells could also be harvested as a cell sheet without being split off. Our enzyme-free passage of hPSCs under a serum- and feeder-free culture condition reduces cell damage and facilitates easier and safer cultures of hPSCs.


Mechanistic Mathematical Models as a Basis for Digital Twins.
A future-oriented approach is the application of Digital Twins for process development, optimization and finally during manufacturing. Digital Twins are detailed virtual representations of bioprocesses with predictive capabilities. In biotechnology, Digital Twins can be used to monitor processes and to provide data for process control and optimization. Central and crucial components of Digital Twins are mathematical process models, which are capable to describe and predict cultivations with high fidelity. Detailed mechanistic models in particular are suitable for both use in Digital Twins and for the development of process control strategies.In this chapter the requirements that process models must fulfil in order to be used for process optimization and finally in Digital Twins will be described. Different types of models, including mechanistic as well as compartmentalized models, are outlined and their application in Digital Twins and for process optimization is explained. Finally, a structured, compartmentalized process model, which was specifically designed for process optimization and has already been used in Digital Twins, is highlighted.


Expression of a novel dual-functional protein--the antimicrobial peptide LL-37 fused with human acidic fibroblast growth factor in Escherichia coli.
Human acidic fibroblast growth factor (haFGF) stimulates repair of delayed healing which still remains a tremendously world-wide issue. However, most of the patients with delayed healings have to face another creeping problem - microbial infection, which is one of the most frequent complications that still lead to wound healing failure. LL-37/hCAP-18 is the only cathelicidin-derived antimicrobial peptide found in human with a wide range of antimicrobial activities. In the present study, a novel hybrid protein combining LL-37 with haFGF was designed. The DNA sequence encoding recombination fusion protein LL-37-haFGF was subcloned into the pET-21b vector for protein expression in Escherichia coli strain BL21 (DE3). The recombinant protein was expressed as a His-tagged protein and purified using a combination of Ni affinity and CM-Sepharose chromatography at a purity of 95.43% as detected by RP-HPLC and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Antimicrobial activity assays showed that the purified LL-37-haFGF had improved antimicrobial activities in vitro compared with LL-37. Methylthiazoletetrazolium (MTT) assay showed that the purified LL-37-haFGF also had a distinct mitogenic activity in NIH 3T3 cells. These data suggests the recombinant protein LL-37-haFGF has pharmaceutical potential for applications in wound healing.


Otitis externa associated with aquatic activities (swimmer's ear).
Infections of the ear canal may vary in terms of severity. Their frequency and morbidity qualify them as significant aquatic problems. The aquatic environment adds the conditional variable of moisture to the ear canal. Usually bacteria are introduced with the moisture and in the warm environment of the canal multiply, generate debris, invade the canal lining, and generate the symptoms of otitis externa. Fortunately, the incidence of this condition can be minimized by eliminating moisture in the canal. In situations where excessive moisture is likely to be introduced such as in swimmers, scuba divers, and deep sea divers the prophylactic measures of desiccation and acidification of the canal should be used. They are very effective. In the saturation diver, ear canal infections are not likely to resolve without interruption of diving activities. Individuals who have recurring ear canal infections require evaluation by an ear specialist to identify possible remedial problems that can trigger infection. Correction of anatomical problems or underlying dermatoses can prevent recurrences of OE.


Alteration of the redox state of NADPH and glutathione in perfused rabbit lung by paraquat.
The glutathione and NADP+ status of perfused rabbit lung was determined both before and after perfusion with 1 mM paraquat. The pulmonary glutathione redox state was similar to that of liver, having a glutathione/glutathione disulfide ratio of about 240. This ratio was lower in lungs perfused with glucose-free medium, a condition in which NADPH probably becomes limiting. Perfusion with paraquat significantly increased the pulmonary glutathione disulfide content, particularly in the absence of glucose, resulting in a glutathione/glutathione disulfide ratio of less than 100. NADP+ levels in rabbit lung were increased approximately two-fold by perfusion with paraquat in medium containing glucose and three-fold in the absence of glucose.


Accuracy of lung and diaphragm ultrasound in predicting successful extubation in extremely preterm infants: A prospective observational study.
Chest ultrasound has emerged as a promising tool in predicting extubation readiness in adults and children, yet its utility in preterm infants is lacking. Our aim was to assess the utility of lung ultrasound severity score (LUSS) and diaphragmatic function in predicting extubation readiness in extremely preterm infants. In this prospective cohort study, preterm infants < 28 weeks gestational age (GA) who received invasive mechanical ventilation for ≥12 h were enrolled. Chest ultrasound was performed before extubation. The primary outcome was lung ultrasound accuracy for predicting successful extubation at 3 days. Descriptive statistics and logistic regression were done using SPSS version 22. We enrolled 45 infants, of whom 36 (80%) were successfully extubated. GA and postmenstrual age (PMA) at extubation were significantly higher in the successful group. The LUSS was significantly lower in the successful group compared to failed group (11.9 ± 3.2 vs. 19.1 ± 3.1 p < 0.001). The two groups had no statistically significant difference in diaphragmatic excursion or diaphragmatic thickness fraction. Logistic regression analysis controlling for GA and PMA at extubation showed LUSS was an independent predictor for successful extubation (odd ratio 0.46, 95% confidence interval [0.23-0.9], p = 0.02). The area under the receiver operating characteristic curve was 0.95 (p ˂ 0.001) for LUSS, and a cut-off value of ≥15 had 95% sensitivity and 85% specificity in detecting extubation failure. In extremely preterm infants, lung ultrasound has good accuracy for predicting successful extubation. However, diaphragmatic measurements were not reliable predictors.


Expressions of VEGF and its receptors in rat corpus luteum during interferon alpha administration in early and pseudopregnancy.
It is accepted that angiogenesis plays an important role in the development of the corpus luteum (CL) and is probably necessary for normal lutein cell function. A number of drugs currently being tested in clinical trials as possible angiogenesis inhibitors were not originally developed with the intention of suppressing tumor angiogenesis. Interferon alpha (IFN-alpha) is one of the notable examples of such 'accidental angiogenesis inhibitors' and daily administration of IFN-alpha is known to suppress tumor growth, tumor vascularization, and down-regulation of various growth factors. We investigated the effects of IFN-alpha treatment on the expression of vascular endothelial growth factor (VEGF), and its receptors KDR and Flt-1, and CD34 in CL during the first week of pseudopregnancy and pregnancy in hormonally induced rat ovaries by immunohistochemistry and Western blot techniques. Basal body temperatures of the drug-treated rats, as an indicator of treatment effect, were determined daily and were increased significantly when compared to controls (38.03 +/- 0.18 vs. 36.6 +/- 0.1 degrees C), respectively. The effect of IFN-alpha treatment was minimal when the entire week was evaluated, however, the expression of VEGF decreased at 3rd, 5th, and 7th days of both pregnancy and pseudopregnancy, when compared to the 1st day, whereas there was not a such alteration in the untreated rats regarding these days. The daily subcutaneous administrations of 672.500 U IFN-alpha2b had minimal effects on the expressions of VEGF, and its two receptors KDR and Flt-1 in either pregnant or pseudopregnant corpora lutea utilizing HSCORE.


The impact of investor sentiment on firms' green total factor productivity-facilitator or inhibitor?
Investor sentiment does not only have negative impacts. It may also improve green total factor productivity by invigorating funds. This research constructs a new indicator at the firm level to measure the green total factor productivity of firms. We research the effect of investor sentiment on firms' green total factor productivity using a sample of Chinese heavy polluters listed on Shanghai and Shenzhen A-shares between 2015 and 2019. Through a series of tests, the mediating role of agency costs and financial situations is confirmed. It is discovered that the digitization of businesses facilitates the effect of investor sentiment on the green total factor productivity of businesses. And when managerial competence reaches a certain threshold, the impact of investor sentiment on green total factor productivity is amplified. Tests for heterogeneity reveal that high investor sentiment has a larger impact on green total factor productivity in firms with superior supervision.


The carboxypeptidase ACE shapes the MHC class I peptide repertoire.
The surface presentation of peptides by major histocompatibility complex (MHC) class I molecules is critical to CD8(+) T cell-mediated adaptive immune responses. Aminopeptidases have been linked to the editing of peptides for MHC class I loading, but carboxy-terminal editing is thought to be due to proteasome cleavage. By analysis of wild-type mice and mice genetically deficient in or overexpressing the dipeptidase angiotensin-converting enzyme (ACE), we have now identified ACE as having a physiological role in the processing of peptides for MHC class I. ACE edited the carboxyl terminus of proteasome-produced MHC class I peptides. The lack of ACE exposed new antigens but also abrogated some self antigens. ACE had substantial effects on the surface expression of MHC class I in a haplotype-dependent manner. We propose a revised model of peptide processing for MHC class I by introducing carboxypeptidase activity into the process.


"I expected little, although I learned a lot": perceived benefits of participating in HIV risk reduction sessions among women engaged in sex work in Uganda.
The global HIV burden remains a public health concern. Women engaged in sex work (WESW) are at higher risk of acquiring HIV compared to the general adult population. Uganda reports high rates of HIV prevalence among WESW. While WESW in Uganda have long been the subject of surveillance studies, they have not been targeted by theory-informed HIV prevention intervention approaches. In this study, we explored the perceived benefits of an evidence-based HIV risk reduction intervention that was implemented as part of a combination intervention tested in a clinical trial in Uganda. As part of a larger randomized clinical trial, we conducted semi-structured in-depth interviews with 20 WESW selected using a stratified purposive sampling. All interviews were conducted in Luganda, language spoken in the study area, and audio-recorded. They were transcribed verbatim and translated to English. Thematic analysis was used to analyze the data. WESW's narratives focused on: (1) condom use; (2) alcohol/drug consumption; (3) PrEP use; (4) "handling" customers; and (5) "massaging" customers. WESW agreed that male condom was one of the important learning points for them and planned to continue using them while female condoms were received with mixed reactions. Many women appreciated receiving information about the risks of consuming alcohol and drugs, and discussed how they reduced/ eliminated their consumption. PrEP information was appreciated though identified by fewer WESW. Handling a client was discussed as a helpful strategy for safer sex through improved ability to convince customers to use condoms or avoiding sex. Massaging was also beneficial to avoid penetrative sex, but similar to female condom, massaging also yielded mixed perceptions. WESW found the intervention beneficial and described ways in which it improved their ability to engage in safer sex and stay healthy. The fact that WESW identified other strategies beyond condom use as helpful underlines the importance of adopting a comprehensive approach to behavioral interventions targeting HIV prevention even when combined with other interventions. Additionally, WESW's narratives suggest that incorporating the tenets of social cognitive theory and harm reduction approaches in HIV prevention among this population can result in risk behavior change.


Retinal arterial Aβ40 deposition is linked with tight junction loss and cerebral amyloid angiopathy in MCI and AD patients.
Vascular amyloid beta (Aβ) protein deposits were detected in retinas of mild cognitively impaired (MCI) and Alzheimer's disease (AD) patients. We tested the hypothesis that the retinal vascular tight junctions (TJs) were compromised and linked to disease status. TJ components and Aβ expression in capillaries and larger blood vessels were determined in post mortem retinas from 34 MCI or AD patients and 27 cognitively normal controls and correlated with neuropathology. Severe decreases in retinal vascular zonula occludens-1 (ZO-1) and claudin-5 correlating with abundant arteriolar Aβ40 deposition were identified in MCI and AD patients. Retinal claudin-5 deficiency was closely associated with cerebral amyloid angiopathy, whereas ZO-1 defects correlated with cerebral pathology and cognitive deficits. We uncovered deficiencies in blood-retinal barrier markers for potential retinal imaging targets of AD screening and monitoring. Intense retinal arteriolar Aβ40 deposition suggests a common pathogenic mechanism of failed Aβ clearance via intramural periarterial drainage.


Mutational analysis of TlyA from Brachyspira hampsonii reveals two key residues conserved in pathogenic bacteria responsible for oligomerization and hemolytic activity.
TlyA proteins are expressed in a variety of pathogenic bacteria and possess dual hemolytic and ribosomal RNA methyltransferase functions. While the mechanism of TlyA mediated rRNA methylation is well understood, relatively little is known about the mechanism of TlyA induced hemolysis. TlyA protein from the pig pathogen Brachyspira hampsonii was heterologously expressed and purified from an E. coli host. Hemolytic activity and rRNA methylation were assessed in vitro. Site-directed mutagenesis was used to mutate amino acids believed to be involved in TlyA mediated hemolysis. Purified TlyA-His protein exhibited both hemolytic and rRNA methyltransferase activities in vitro, with partial inhibition of hemolysis observed under reducing conditions. Mutation of cysteine 80 to alanine impaired hemolytic activity. A C27A/C93A mutant was capable of dimerizing under non-reducing conditions, indicating that a C80-C80 disulfide bond is involved in TlyA oligomerization. A mutation conserved in several avirulent Brachyspira species (S9K) completely abolished hemolytic activity of TlyA. This loss of activity was attributed to impaired oligomerization in the S9K mutant, as assessed by ITC and size-exclusion chromatography experiments. Oligomeric assembly and hemolytic activity of TlyA from Brachyspira hampsonii is dependent on the formation of an intermolecular C80-C80 disulfide bond and noncovalent interactions involving serine 9. The conservation of these amino acids in TlyA proteins from pathogenic bacteria suggests a correlation between tlyA gene mutations and bacterial virulence. Our results further elucidate the mechanisms underlying TlyA mediated hemolysis and provide evidence of a conserved mechanism of oligomerization for TlyA family proteins.


[Hyperhomocysteine, methylenetetrahydrofolate reductase gene, and other risk factors in ischemic stroke].
To investigate the relation between plasma homocysteine (Hcy) and cerebral ischemic diseases and that between polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and cerebral ischemic diseases. The plasma homocysteine (Hcy) and genetic polymorphism of MTHFR among forty-nine cases with ischemic cerebral diseases, including 25 with acute cerebral infarction (CI) and 25 with transient ischemic attacks (TIA), were investigated. Fifty-five age- and sex-matched healthy persons were used as controls. All the subjects underwent brain CT, carotid duplex, transcranial Doppler examination, plasma Vitamin B(12) and folic acid examination, besides examination of plasma Hcy and nucleotide 677 MTHFR genotypes. The effects of age, liver function, renal function, smoking, drinking, plasma vitamin B(12), and folic acid were analyzed. The mean plasma Hcy was significantly higher in the CI group and TIA group (17.4 +/- 7.6 micromol/L and 16.6 +/- 5.2 micromol/L) compared with that in the control group (12.6 +/- 5.2 micromol/L, P < 0.01). The odds ratio was 3.26 (95% CI, 1.05 approximately 10.09, P < 0.01). The Hcy concentration was significantly higher in persons with T/T genotype than in those with C/C or CT. There was no significant difference of frequency of mutant alleles (T) in site 677 of MTHFR gene and in frequency of homozygote T/T among the patients and controls (52.0% vs. 44.0%, P < 0.05 and 26% vs. 20.0%, P > 0.05). The difference of Hcy was significant between those being T/T homozygotic and those not being T/T homozygotic in different groups. There was no statistical correlation between plasma Hcy level and extra- and intracranial stenosis of cerebral artery. Increase of BUN and smoking were significantly correlated with increase of Hcy (P < 0.05). The concentrations of plasma Vitamin B(12) and folic acid were significantly correlated with that of Hcy. Homozygote of mutant MTHFR gene C677T causes hyperhomocystinemia. There is a significantly association between hyperhomocystinemia and ischemic cerebrovascular disease. The frequency of mutation in MTHFR genotype is higher in Chinese than in Caucasians. In addition to gene mutation, renal function and smoking are related to increase of plasma Hcy. No correlation between genotype of MTHFR and stroke is found.


Evaluation of left ventricular rotation by two-dimensional speckle tracking method and real-time three-dimensional echocardiography: comparison with MRI tagging method.
Recently, it has become possible to evaluate left ventricular (LV) torsion by two-dimensional (2D) speckle tracking images. However, LV torsion is a three-dimensional (3D) performance, which per se cannot be assessed by the 2D speckle tracking method. The present study investigated the accuracy of the 2D speckle tracking method and real-time 3D echocardiography in measuring LV rotation, comparing with the MRI tagging method. We assessed LV apical rotation using the 2D speckle tracking method, real-time 3D echocardiography, and MRI tagging method in 26 normal subjects, and compared the results of these three methods. LV apical rotation was measured just before the level in which the posterior papillary muscle was absorbed into the free wall. The degree of LV apical rotation evaluated by the 2D speckle tracking method (Δθ 2D) was significantly smaller than that evaluated by 3D echocardiography (Δθ 3D) and the MRI tagging method (Δθ MRI) (Δθ 2D 7.3 ± 2.8°; Δθ 3D 8.8 ± 3.4°; Δθ MRI 9.0 ± 3.4°; Δθ 2D vs. Δθ 3D, p = 0.0001; Δθ 2D vs. Δθ MRI, p < 0.0001). There were good correlations among Δθ 2D, Δθ 3D, and Δθ MRI, but agreement between Δθ 3D and Δθ MRI (mean difference 0.14 ± 1.43°) was better than that between Δθ 2D and Δθ MRI (mean difference 1.68 ± 1.89°). The degree of LV apical rotation was underestimated with the 2D speckle tracking method compared with the MRI tagging method, whereas it could be precisely measured by 3D echocardiography.


The inverse hazard law: blood pressure, sexual harassment, racial discrimination, workplace abuse and occupational exposures in US low-income black, white and Latino workers.
Research on societal determinants of health suggests the existence of an "inverse hazard law," which we define as: "The accumulation of health hazards tends to vary inversely with the power and resources of the populations affected." Yet, little empirical research has systematically investigated this topic, including in relation to workplace exposures. We accordingly designed the United for Health study (Greater Boston Area, Massachusetts, 2003-2004) to investigate the joint distribution and health implications of workplace occupational hazards (dust, fumes, chemical, noise, ergonomic strain) and social hazards (racial discrimination, sexual harassment, workplace abuse). Focusing on blood pressure as our health outcome, we found that among the 1202 low-income multi-racial/ethnic working class participants in our cohort - of whom 40% lived below the US poverty line - 79% reported exposure to at least one social hazard and 82% to at least one high-exposure occupational hazard. Only sexual harassment, the least common social hazard, was associated with elevated systolic blood pressure (SBP) among the women workers. By contrast, no statistically significant associations were detectable between the other additional highly prevalent social and occupational hazards and SBP; we did, however, find suggestive evidence of an association between SBP and response to unfair treatment, implying that in a context of high exposure, differential susceptibility to the exposure matters. These results interestingly contrast to our prior findings for this same cohort, in which we found associations between self-reported experiences of racial discrimination and two other health outcomes: psychological distress and cigarette smoking. Likely explanations for these contrasting findings include: (a) the differential etiologic periods and pathways involving somatic health, mental health, and health behaviors, and (b) the high prevalence of adverse exposures, limiting the ability to detect significant associations. As clarified by the "inverse hazard law," to understand health inequities, research is needed that contrasts exposures and health status population-wide, not just among those most inequitably exposed.


Long-term effect of sleeve gastrectomy surgery on Hormonal Profile, Semen Parameters and sexual functions of obese infertile men; a prospective observational study.
The effect of bariatric surgery on impaired semen parameters, hormonal profile and sexual function remains controversial to some extent. To look at the long-term effects of sleeve gastrectomy on hormonal profiles, sperm parameters, and sexual function in infertile men with severe obesity. This prospective study included fifty-four obese patients with primary or secondary infertility who were scheduled for sleeve gastrectomy between February 2018 and March 2021. All participants were given a sperm analysis and a serum hormone profile before, 12, and 18 months after surgery. We used the International Index of Erectile Function questionnaire to assess sexual function. There was a significant correlation between weight loss after sleeve gastrectomy and improvement in lipid profile (p < 0.05). No significant detectable effect of post-gastrectomy weight loss on patients with diabetes mellitus, hypertension, or obstructive sleep apnea. As regards the hormonal profile, sex hormone binding globulin, total and free testosterone improved significantly after 12- and 18-months following sleeve gastrectomy. There was a significant increase in sperm count and total sperm number during the follow-up after sleeve gastrectomy (p < 0.05), however, there were no significant changes in other semen parameters. Concerning sexual function, sexual desire, erectile function, and satisfaction improved significantly at 12 and 18 months after surgery. Weight loss through sleeve gastrectomy surgery significantly improves testosterone deficiency, sexual performance, and Sperm count in obese infertile men.


Variation in diagnostic NAFLD/NASH read-outs in paired liver samples from rodent models.
In animal models of non-alcoholic fatty liver disease (NAFLD), assessment of disease severity and treatment effects of drugs rely on histopathological scoring of liver biopsies. However, little is known about the sampling variation in liver samples from animal models of NAFLD, even though several histopathological hallmarks of the disease are known to be affected by sampling variation in patients. The aim of this study was to assess the sampling variation in multiple paired liver biopsies from three commonly used diet-induced rodent models of NAFLD. Eight male C57BL/6 mice, 8 male Sprague Dawley rats and 16 female Hartley guinea pigs were fed a NAFLD-inducing high-fat diet for 16 weeks (mice and rats), 20 or 24 weeks (guinea pigs). After the initial diet period, liver sections were sampled and subsequently assessed by histopathological scoring and biochemical analyses. Fibrosis was heterogeneously distributed throughout the liver in mice, manifesting as both intra- and interlobular statistically significant differences. Hepatic triglyceride content showed interlobular differences in mice, and both intra- and interlobular differences in guinea pigs (24-week time point) all of which were statistically significant. Also, hepatic cholesterol content was subject to significant intra-lobular sampling variation in mice, and hepatic glycogen content differed significantly between lobes in mice and guinea pigs. Dependent on animal model, both histopathological and biochemical end-points differed between sampling sites in the liver. Based on these findings, we recommend that sample site location is highly standardized and properly reported in order to minimize potential sampling variation and to optimize reproducibility and meaningful comparisons of preclinical studies of NAFLD.


Effects of ganglionic and beta-adrenergic blockade on cardiovascular responses to the bisenoic prostaglandins and their precursor arachidonic acid.
Arachidonic acid (AA) 300 mug/kg, and PGE2, 5 mug/kg consistently produced a decrease in systemic arterial pressure in anesthetized dogs. PGF2alpha, 5 mug/kg, produced a pressor response. All three compounds increased myocardial contractile force, but the magnitude of the change following AA was less prominent. After ganglionic blockade, the depressor response to AA and PGE2 persisted and the pressor response to PGF2alpha was augmented. Myocardial contractile force did not increase following AA in ganglion-blocked animals indicating that the cardiac responses observed before hexamethonium were mediated by the baroreceptor reflexes. A much larger dose of AA (900 mug/kg) resulted in a small positive inotropic effect on the heart. This possibly represents a direct cardiac effect of AA, or may be indicative of increased biosynthesis of an intermediate endoperoxide, or PGE2 and PGF2alpha. Both PGE2 and PGF2alpha have a direct positive inotropic effect on the heart. The persist cardiac effects of PGE2 and PGF2 after beta-adrenergic blockade suggests that these compounds may not interact with the beta-receptors of the myocardium.


Genome-wide expression profiling of microRNAs in poplar upon infection with the foliar rust fungus Melampsora larici-populina.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression of target mRNAs involved in plant growth, development, and abiotic stress and pathogen responses. Previous studies have reported miRNAs in Populus that respond to abiotic stresses, such as cold, heat, drought, flooding, high salt and mechanical stress. However, little is known about the regulatory roles of these molecules in the Populus response to the stress of foliar rust fungal infection. Here, we identified the miRNA profiles of Populus after inoculation with Melampsora larici-populina using high-throughput sequencing and bioinformatics analysis. Quantitative real-time PCR (qRT-PCR) was used to validate the expression levels of 10 miRNAs. A total of 90 known miRNAs belonging to 42 families and 378 novel miRNAs were identified from three small-RNA libraries of Populus szechuanica infected with M. larici-populina isolates Sb052 and Th053 and a control. Comparative analysis revealed that the expression of 38 known miRNAs and 92 novel miRNAs in P. szechuanica after infection with different rust fungus isolates showed significant differences, and more miRNAs were suppressed during rust infection. Among the differentially expressed miRNAs, 7 known and 20 novel miRNAs were relevant to the rust fungus infection, and according to KEGG (Kyoto Encyclopaedia of Genes and Genomes) pathway analysis, these miRNAs primarily regulate genes encoding disease-resistance proteins, serine/threonine protein kinases, transcription factors, and related proteins. QRT-PCR analysis indicated that most miRNAs were up-regulated in the Sb052 library and down-regulated in the Th053 library at 48 h post-inoculation (hpi). These results demonstrate that the expression of miRNAs was altered in poplar under stress associated with M. larici-populina infection, and different temporal dynamics were observed in incompatible and compatible libraries. These findings suggest important roles for miRNA regulation in Populus upon infection with foliar rust fungus.


Plasma level of metastasis-associated lung adenocarcinoma transcript 1 is associated with liver damage and predicts development of hepatocellular carcinoma.
Recent studies have shown that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was overexpressed in many human solid cancers, however, its roles in plasma of hepatocellular carcinoma (HCC) patients were unclear. The aim of this study was to investigate the significance of plasma MALAT1 levels in HCC patients. Plasma samples were collected from pre-operative HCC, hepatic disease patients, and healthy controls, and tissue samples from HCC patients and colorectal cancer patients with liver metastasis. Plasma and tissue MALAT1 levels were measured. Plasma MALAT1 levels were progressively and significantly higher in HCC patients than hepatic disease patients, and higher in hepatic disease patients than healthy controls. The expression of MALAT1 in HCC tissue was slightly higher than that in paired non-cancerous liver tissue, but not significant. The expression of MALAT1 in the non-cancerous liver tissue of 20 HCC patients was significantly higher than that in normal liver tissue of 13 colorectal cancer patients. In contrast, plasma MALAT1 levels were significantly low in HCC patients with hepatitis B infection, and significantly high in patients with liver damage B or liver cirrhosis. In a receiver-operator curve analysis of HCC and hepatic disease patients, the cut-off value of plasma MALAT1 was 1.60 and the area under the curve was 0.66. Plasma MALAT1 levels were not correlated with α-fetoprotein or protein induced by vitamin K absence II, whereas sensitivity and specificity for the detection of HCC with the combination of MALAT1, α-fetoprotein, and protein induced by vitamin K absence II were 88.6% and 75%, respectively. In conclusion, the plasma MALAT1 level is associated with liver damage, and has clinical utility for predicting development of HCC.


Selective quantitative analysis of the intensity of immunohistochemical reactions.
The present study reports a new method for the densitometric measurement of the intensity of immunohistochemical reactions. This method is based on a programm for the Kontron VIDAS image analysis system and has been designed for the measurement of small differences in the relative intensity of immunohistochemical reactions. Immunohistochemistry was performed with the avidin-biotin-peroxidase complex and diaminobenzidine-HCl and H2O2 for enzyme visualization. Several methods for shade correction and image processing were elaborated. The study was carried out on gerbil Purkinje cells using monoclonal antibodies raised against calbindin D28k. Prerequesites of correct measurement were standardized preparation, i.e., identical thickness of the paraffin sections, identical performance of immunohistochemistry, and avoidance of any counterstaining. The evaluation of small intensity differences of immunohistochemical reactions was found to be feasible either by substractive shade correction and standardized normalization or by shade correction by division by a reference image and standardized thresholding. Small differences in antigen concentration were not detectable without additional image processing.


TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice.
The abundance of inflammatory mediators in injured joint indicates innate immune reactions activated during temporomandibular joint osteoarthritis (TMJOA) progression. Toll-like receptor 4 (TLR4) can mediate innate immune reaction. Herein, we aimed to investigate the expression profile and effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice. The expression of TLR4 and NFκB p65 in the synovium of TMJOA patients was measured by immunohistochemistry, Western blotting and RT-PCR. H&E and Masson staining were utilized to assess the damage of cartilage and subchondral bone of the discectomy-induced TMJOA mice. A TLR4 inhibitor, TAK-242, was used to assess the effect of TLR4 in the cartilage and subchondral bone of the discectomy-induced TMJOA mice by Safranin O, micro-CT, immunofluorescence and immunohistochemistry. Western blotting was used to quantify the expression and effect of TLR4 in IL-1β-induced chondrocytes. The expression of TLR4 and NFκB p65 was elevated in the synovium of TMJOA patients, compared with the normal synovium. TLR4 elevated in the damaged cartilage and subchondral bone of discectomy-induced TMJOA mice, and the rate of TLR4 expressing chondrocytes positively correlated with OA score. Intraperitoneal injections of TAK-242 ameliorate the extent of TMJOA. Furthermore, TLR4 promotes the expression of MyD88/NFκB, pro-inflammatory and catabolic mediators in cartilage of discectomy-induced TMJOA. Besides, TLR4 participates in the production of MyD88/NFκB, pro-inflammatory and catabolic mediators in IL-1β-induced chondrocytes. TLR4 contributes to the damage of cartilage and subchondral bone in discectomy-induced TMJOA mice through activation of MyD88/NFκB and release of pro-inflammatory and catabolic mediators.


Lack of association of MTHFR rs1801133 polymorphism and CTCFL mutations with sperm methylation errors in infertile patients.
To find out whether the MTHFR rs1801133 polymorphism is a risk factor for male infertility in the Spanish population. To determine if a pattern of sperm DNA hypomethylation at the paternally imprinted loci H19-ICR and/or IG-DMR is related to the MTHFR rs1801133 polymorphism and/or CTCFL mutations. One hundred and seven samples from individuals who sought consultation for fertility problems and twenty-five semen samples from sperm donors were analyzed. The MTHFR rs1801133 SNP was analyzed in all samples by the PCR-RFLP method. We compared the distribution of the genotypes between control and infertile populations and among the groups of patients with altered seminal parameters. In those patients with the most severe hypomethylation pattern (n = 12) we also analyzed the CTCFL protein-coding exons by sequencing. There were no significant differences in the distribution of the genotypes among the control and infertile populations. Moreover, none of the genotypes were associated, neither to the characteristics of the seminogram, nor to the presence of sperm DNA hypomethylation. We did not identify frameshift, nonsense or missense mutations of the CTCFL gene. The MTHFR rs1801133 polymorphism is not associated with male infertility in the Spanish population. Neither the MTHFR polymorphism, nor CTCFL mutations explain a pattern of sperm hypomethylation at paternally imprinting loci.


Study on the characteristics of zeolite-promoted thermal decomposition of H2O2 for efficient NO oxidation.
The H2O2 evaporation rate directly affected the oxidation of NO by H2O2. Green zeolite and synthetic mordenite were selected to promote H2O2 thermal decomposition and NO oxidation. The effects of different zeolites, evaporation conditions, temperatures, and reactant concentrations on the NO oxidation ratio were explored. The promotion mechanism of zeolite on NO oxidation by H2O2 thermal decomposition was explained. The results show that the zeolite surface can significantly accelerate the H2O2 evaporation rate to obtain a high NO oxidation ratio. The hydrophilicity and rich pore structure of zeolite enable the rapid diffusion and evaporation of droplets on the zeolite surface. Compared with the green zeolite with the mesoporous structure, the synthetic mordenite with the hierarchical pore structure has a more obvious promotion effect on the NO oxidation by H2O2 thermal decomposition. The reason is that the synthetic mordenite contains micropores, resulting in a larger specific surface area, and the mesoporous structure is conducive to the mass transfer and diffusion of H2O2 on its surface. The product of NO oxidation is mainly NO2, which proves that ·OH plays a major role in the process.


Crimean Congo hemorrhagic fever among the one-humped camel (Camelus dromedaries) in Central Sudan.
Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonotic disease caused by Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the genus Nairovirus in the family Bunyaviridae. CCHF is typically asymptomatic in animals but can be highly fatal in humans approaching case fatality rate of approximately 30%. In the present investigation, a cross sectional study was conducted to determine the prevalence of CCHF and to identify the potential risk factors associated with CCHFV seropositivity among the one-humped camel (Camelus dromedaries) in Central Sudan. A total of 361 camels selected randomly from six localities were employed in the study. Sera sampled were tested for the presence of CCHFV-specific immunoglobulin G (IgG) antibodies using enzyme-linked immunosorbent assay (ELISA). CCHFV seropositivity was recorded in 77 out of 361 animals accounting for a prevalence rate of 21.3%. Age (OR = 3.6, CI = 1.72-7.79, p-value = 0.026); locality (OR = 5.85, CI = 1.81-18.83, p- value = 0.003), tick number (OR = 4.6, CI = 1.37-9.81, P-value 0.04); tick control (OR = 2.2, CI, 1.11-4.35, P-value = 0.023) and breed (OR = 6.60, CI = 2.38-18.36, P-value = 0.001) were recorded as potential risk factors for contracting CCHF. The prevalence of CCHF is significantly high among camels in Khartoum State, Sudan. Age, breed, locality and tick control are considered as potential risk factors for contracting CCHF. This study would be expected to reduce the impact on the livelihood of pastoral communities and ultimately avoid disease spread in human.


Clinical and genomic characterization of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma.
Recent studies suggest that a significant proportion of cancers undergo neutral tumor evolution. We applied neutral evolution model in HNSCC patients from The Cancer Genome Atlas (TCGA). To ensure the accuracy of classification results, a sample with the purity of tumor <0.7 was excluded. A tumor sample was considered to evolve neutrally if R2 ≥ 0.98. We found that about 16% of HNSCC patients undergo neutral tumor evolution. We showed that neutral evolution HNSCC patients have better prognosis and higher activities of immune response pathways, and the numbers of co-occurring mutation events and significantly positive selection mutations are significantly less than non-neutral evolution HNSCC patients. In conclusion, we described a comprehensive clinical and genomic characteristics of neutral tumor evolution in Head and Neck Squamous Cell Carcinoma (HNSCC), and provided evidence that the evolution history of HNSCC has both clinical and biological implications.


Developing School-based Telehealth Programs as an Equity Strategy for Education and Health Care.
School-based telehealth programs have shown potential to address both educational and health needs of elementary students in North Carolina. A Cone Health prototype in areas of endemic poverty and low health literacy allowed for the creation of on-demand care that kept children in school, decreased early dismissals, and reduced the burden and cost of urgent health care on families.


The ubiquitin conjugating enzyme Ube2W regulates solubility of the Huntington's disease protein, huntingtin.
Huntington's disease (HD) is caused by a CAG repeat expansion that encodes a polyglutamine (polyQ) expansion in the HD disease protein, huntingtin (HTT). PolyQ expansion promotes misfolding and aggregation of mutant HTT (mHTT) within neurons. The cellular pathways, including ubiquitin-dependent processes, by which mHTT is regulated remain incompletely understood. Ube2W is the only ubiquitin conjugating enzyme (E2) known to ubiquitinate substrates at their amino (N)-termini, likely favoring substrates with disordered N-termini. By virtue of its N-terminal polyQ domain, HTT has an intrinsically disordered amino terminus. In studies employing immortalized cells, primary neurons and a knock-in (KI) mouse model of HD, we tested the effect of Ube2W deficiency on mHTT levels, aggregation and neurotoxicity. In cultured cells, deficiency of Ube2W activity markedly decreases mHTT aggregate formation and increases the level of soluble monomers, while reducing mHTT-induced cytotoxicity. Consistent with this result, the absence of Ube2W in HdhQ200 KI mice significantly increases levels of soluble monomeric mHTT while reducing insoluble oligomeric species. This study sheds light on the potential function of the non-canonical ubiquitin-conjugating enzyme, Ube2W, in this polyQ neurodegenerative disease.


[Clinical diagnosis of fungal keratitis by confocal microscopy].
To illustrate the value of confocal microscope in the diagnosis of fungal keratitis. In vivo confocal microscopy was performed on 43 patients of suspected fungal keratitis. The results were compared to that of smears and biopsies. Fungal filaments were imaged in 31 of 43 patients' corneas. Fungal keratitis was diagnosed in 32 patients based on clinical signs and all the methods of examinations. The positive rate of confocal microscopy is 96.9%. Confocal microscopy can be a rapid, effective and noninvasive imaging technique, and it is helpful in the diagnosis, treatment and study of fungal keratitis.


Syndecan-2 and -4 expressed on activated primary human CD4+ lymphocytes can regulate T cell activation.
Syndecans bind to cell adhesion molecules, growth factors and cytokines, and can act as coreceptors, and in this way modulate leukocyte cell function. Here, expression of the syndecans on primary human CD4 T cells was examined. Cell stimulation dramatically increased the amount of syndecan-4, and in a lower extent that of syndecan-2. Expression of syndecan-2 and -4 show different induction kinetics. Whereas syndecan-4 expression is fast and significant, that of syndecan-2 is more delayed and short-lived decreasing its mRNA expression at day 4. Both CD45RA+ naive and CD45RA- memory CD4 T cells express syndecan-2 and -4 upon activation. When incubated with human peripheral blood lymphocytes in a mixed leukocyte reaction, anti-syndecan-4 but not anti-syndecan-2 antibodies, decreased T cell proliferation. However, cross-linking of cell-bound syndecan-2 or syndecan-4 via immobilized antibodies blocked proliferation and decreased TNF production of T cells in the presence of optimal levels of anti-CD3. These findings suggest that syndecan-2 and -4 act as inhibitors of T cell activation. We also investigated the role that MAPK signalling pathways play in control of syndecan expression in T cells. We show that production of syndecan-2 but not syndecan-4 requires signaling via p38 MAP kinase alpha/beta in T CD4 cells. As mechanisms that confer syndecan-2 expression are unknown, we analyse the chromatin hypersensitivity of syndecan-2 promoter proximal region in Jurkat T cells and endothelial cells. The analysis reveals a chromatin accessible site in the +3.5kb intronic region, concomitant with a region showing high evolutionary conservation. We isolate and analyse 5'-flanking regions of human syndecan-2 gene, by transfection assays. The +3.5kb hypersensitive site in the intronic region demonstrates basal promoter activity in Jurkat. This study provides evidence for the up-regulation of syndecan-2 and -4 in human primary CD4 T cells during in vitro activation and suggest an inhibitory role for these syndecans in CD4 T cells.


The impact of audiovisual biofeedback on 4D functional and anatomic imaging: Results of a lung cancer pilot study.
The impact of audiovisual (AV) biofeedback on four dimensional (4D) positron emission tomography (PET) and 4D computed tomography (CT) image quality was investigated in a prospective clinical trial (NCT01172041). 4D-PET and 4D-CT images of ten lung cancer patients were acquired with AV biofeedback (AV) and free breathing (FB). The 4D-PET images were analyzed for motion artifacts by comparing 4D to 3D PET for gross tumor volumes (GTVPET) and maximum standardized uptake values (SUVmax). The 4D-CT images were analyzed for artifacts by comparing normalized cross correlation-based scores (NCCS) and quantifying a visual assessment score (VAS). A Wilcoxon signed-ranks test was used for statistical testing. The impact of AV biofeedback varied widely. Overall, the 3D to 4D decrease of GTVPET was 1.2±1.3cm(3) with AV and 0.6±1.8cm(3) for FB. The 4D-PET increase of SUVmax was 1.3±0.9 with AV and 1.3±0.8 for FB. The 4D-CT NCCS were 0.65±0.27 with AV and 0.60±0.32 for FB (p=0.08). The 4D-CT VAS was 0.0±2.7. This study demonstrated a high patient dependence on the use of AV biofeedback to reduce motion artifacts in 4D imaging. None of the hypotheses tested were statistically significant. Future development of AV biofeedback will focus on optimizing the human-computer interface and including patient training sessions for improved comprehension and compliance.


Aging with alcohol-related brain damage: Critical brain circuits associated with cognitive dysfunction.
Alcoholism is associated with brain damage and impaired cognitive functioning. The relative contributions of different etiological factors, such as alcohol, thiamine deficiency and age vulnerability, to the development of alcohol-related neuropathology and cognitive impairment are still poorly understood. One reason for this quandary is that both alcohol toxicity and thiamine deficiency produce brain damage and cognitive problems that can be modulated by age at exposure, aging following alcohol toxicity or thiamine deficiency, and aging during chronic alcohol exposure. Pre-clinical models of alcohol-related brain damage (ARBD) have elucidated some of the contributions of ethanol toxicity and thiamine deficiency to neuroinflammation, neuronal loss and functional deficits. However, the critical variable of age at the time of exposure or long-term aging with ARBD has been relatively ignored. Acute thiamine deficiency created a massive increase in neuroimmune genes and proteins within the thalamus and significant increases within the hippocampus and frontal cortex. Chronic ethanol treatment throughout adulthood produced very minor fluctuations in neuroimmune genes, regardless of brain region. Intermittent "binge-type" ethanol during the adolescent period established an intermediate neuroinflammatory response in the hippocampus and frontal cortex, that can persist into adulthood. Chronic excessive drinking throughout adulthood, adolescent intermittent ethanol exposure, and thiamine deficiency all led to a loss of the cholinergic neuronal phenotype within the basal forebrain, reduced hippocampal neurogenesis, and alterations in the frontal cortex. Only thiamine deficiency results in gross pathological lesions of the thalamus. The behavioral impairment following these types of treatments is hierarchical: Thiamine deficiency produces the greatest impairment of hippocampal- and prefrontal-dependent behaviors, chronic ethanol drinking ensues mild impairments on both types of tasks and adolescent intermittent ethanol exposure leads to impairments on frontocortical tasks, with sparing on most hippocampal-dependent tasks. However, our preliminary data suggest that as rodents age following adolescent intermittent ethanol exposure, hippocampal functional deficits began to emerge. A necessary requirement for the advancement of understanding the neural consequences of alcoholism is a more comprehensive assessment and understanding of how excessive alcohol drinking at different development periods (adolescence, early adulthood, middle-aged and aged) influences the trajectory of the aging process, including pathological aging and disease.


Improving transitions between clinical placements.
Students regularly transition between clinical learning environments as they rotate through their clinical placements. These transitions are stressful for learners, as they must navigate unfamiliar policies, people and physical spaces. It is important to reduce cognitive overload at the start of each placement through appropriate inductions. Our governance processes found there was significant variation between induction processes at our affiliated teaching-hospital sites: our aim was to optimise and standardise these. We opted for induction websites for each of our affiliated hospital sites, as these could be dynamically updated and quality assured. Our websites were informed by a conceptual framework of the clinical learning environment and the theory of sociomateriality. We co-produced them with students and other stakeholders through iterative evaluation and improvement cycles. To elicit end-user analysis, we conducted three focus groups with 19 students. We used the technology acceptance model to inform our topic guide and coding categories. Students reported that the websites were useful, easy to use, and fulfilled a significant unmet need. Induction websites can be optimised through the involvement of a range of stakeholders and the application of theory. They can be pushed to students before each new placement and used to scaffold in-person inductions. Further research is needed to explore the wider impacts of improved site inductions on participation and engagement with clinical learning opportunities and on student satisfaction and experience.


Clinical Teaching Fellows, the new norm?-Experiences of fellows and education faculty.
In the United Kingdom, there is an increasing tendency for doctors in the first 2 years after graduation, to step off the training pathway and take up Clinical Teaching Fellow (CTF) positions. We aimed to explore stakeholder experiences of CTF positions to inform future planning and support. Individual semi-structured interviews with 10 stakeholders (five CTFs and five education faculty members) from one institution in England were conducted. Interviews explored the participants' views of the CTF position, its benefits and challenges. Inductive thematic analysis was performed. CTFs and education faculty views strongly aligned and three themes were identified. These were (1) developing a career, (2) developing confidence and competence as a clinical teacher and (3) developing a position that works for all. Participants reported that the CTF position allowed time for specialty decision making and curriculum-vitae strengthening and provide CTFs with the opportunity to work autonomously and to establish a better work-life balance by stepping away from training pressures and focusing on other aspects of life. There were differing thoughts on how the position should be structured, although retaining a clinical role with boundaries to constrain competing responsibilities was important. A brief hiatus in clinical training, where individuals feel supported to progress personally and professionally and to renew their energy for the next steps of clinical training, seems important. The ideologies of providing the CTFs with autonomy, time to explore options, recharge and form connections with colleagues should be considered when structuring the posts.


Changes in the chemical and physicochemical properties of the solid fraction of cattle slurry during composting using different aeration strategies.
Replacement of peat as a growing medium by a renewable material, such as an organic waste, is an issue of concern since harvesting of peat has a considerable environmental impact and, actually, it is a non-renewable resource. Cattle manure is a readily available organic waste, which means that once it goes through the composting process, it can be used as an alternative to peat, specifically, the solid fraction obtained from mechanical liquid-solid separation of cattle slurry (SF). Studies have shown it to be suitable for such uses. The purpose of this study was to detect possible changes in the physicochemical and chemical properties of SF when it is composted using different aeration strategies, with an emphasis on the changes that would make it feasible for use as a substrate. With this aim in mind, an experiment was designed with three aeration strategies that would be used during composting. The first consisted of applying air through a static method (forced ventilation). The second involved improving aeration by adding a bulking agent and a dynamic turning method. In the third strategy, aeration was carried out by turning (control). The results show that the different aeration strategies had a clear effect on the evolution of pH, electrical conductivity (EC), nitrate-N, ammonia-N and bicarbonate content. Nitrification was favored under good aeration conditions using the static composting method, probably due to the greater availability of ammonia-N that was transformed into nitrate-N. In general, the low buffering capacity allowed for a reduction of the pH during the curing stage of composting (in conjunction with low temperatures during this period), a characteristic that favors the use of this compost as a growing medium. We also conclude that measuring bicarbonate levels during composting could be used as an indicator of the possible acidification of the material and as a way of evaluating the level of material aeration.


[Epidemiologic situation on pneumonia incidence in population of Sverdlovsk region in 2006-2007 and goals for improving of system for epidemiologic surveillance].
Personalized system for registration of community-acquired pneumonia cases instituted in Sverdlovsk region in 2002 is able to provide completeness of identification, accounting, and registration of pneumonia cases as well as to organize regular medical follow-up for survived persons. In addition, the automated system allows to conduct operative and retrospective analysis of morbidity according to area, age and social groups with identification of casual and risk factors as well as to timely organize the complex of preventive measures in an area.


Salinity studies with drought-resistant species of Sporobolus.
Dry matter productivity under saline conditions was compared in 5 desiccation-tolerant "resurrection" grasses and one desiccation sensitive species, all in the genus Sporobolus. S. stapfianus was the most salt tolerant, requiring 215 mole NaCl m-3 to reduce shoot dry matter increments to 50% of increments in plants not treated with salt. (This was comparable to published values for the salt tolerant grass Diplachne fusca.) S. lampranthus was salt sensitive, requiring 35 mol m-3 for 50% control yields. S. festivus, S. aff. Fimbriatus, and the deisccation sensitive S.pyramidalis was moderately tolerant (150-170 mol m-3). The moderate salt resistance of S. aff. fimbriatus was attributed mainly to exclusion of NaCl by roots. Salt export through leaf surfaces was a minor factor. Half of the leaf mesophyll cells survived 50 min immersion in 200 mol NaCl m-3. Plants of S. aff. fimbriatus and S. pyramidalis tolerated a broad range of soil pH. Plants of 4 desiccation tolerant Sporobolus species survived air-dryness following 3 weeks pretreatment with salinities up to 200 mol m-3.


Gonadotropin (LH, FSH) levels in serum and cyst fluid in epithelial tumors of the ovary.
The aim of this work was to determine gonadotropin (LH, FSH) levels in serum and cyst fluid in various type of ovarian epithelial neoplasms (benign, borderline, malignant) and to compare them with levels in benign cysts. Additionally we decided to estimate if there were some significant correlations between serum and ovarian cyst fluid in gonadotropin levels in all investigated groups. The study group included 74 patients before (n=36) and after (n=38) menopause, divided into four groups depending on the histopathologic diagnosis. Serum and cyst fluid levels of LH and FSH were determined in all patients. We found statistically significant differences concerning LH and FSH levels in serum and cyst fluid between malignant and borderline tumors, between malignant tumors and benign cystadenomas and between malignant tumors and non-neoplastic cysts. We also found statistically significant correlations between serum and cyst fluid as to FSH and LH levels in patients with borderline tumors. There were no statistically significant correlations between serum and cyst fluid as to FSH and LH levels in patients with malignant epithelial tumors (group 1) and in patients with benign cystadenomas (group 3). High FSH and LH levels in cyst fluid of malignant epithelial tumors of the ovary are in line with the gonadotropin theory of tumor growth. Simultaneous determination of various types inhibin levels appears to be an interesting topic for our future research.


Collateral myocardial blush in inferior wall myocardial infarction: a new diagnostic tool to differentiate between occluded right coronary and circumflex arteries.
The infarct-related artery (IRA) in inferior wall myocardial infarction (IMI) may be problematic to identify due to occasional instances in which the right coronary (RCA) and left circumflex (CX) arteries are both occluded. We sought to investigate if impaired collateral myocardial blush (CMBG) identifies the correct IRA. Between 2002 and 2010, we retrospectively analyzed 1907 patients who underwent primary angioplasty at our institution. Of these, 44 had an IMI together with total occlusion of both the RCA and CX. Thirty of these had good collaterals to both distal vessels. Ten of this group had impaired CMBG, indicating the IRA. In 2 patients, angioplasty was attempted in the wrong artery in retrospect. The correct IRA may be difficult to identify in patients with IMI and occlusion of both RCA and CX arteries. Impaired CMBG is a new tool to aid in this challenge.


Flexible Acceptance Condition of Generics from a Probabilistic Viewpoint: Towards Formalization of the Semantics of Generics.
Formalization of the semantics of generics has been considered extremely challenging for their inherent vagueness and context-dependence that hinder a single fixed truth condition. The present study suggests a way to formalize the semantics of generics by constructing flexible acceptance conditions with comparative probabilities. Findings from our in-depth psycholinguistic experiment show that two comparative probabilities-cue validity and prevalence-indeed construct the flexible acceptance conditions for generics in a systematic manner that can be applied to a diverse types of generics: Acceptability of IS_A relational generics is mostly determined by prevalence without interaction with cue validity; feature-describing generics are endorsed acceptable with high cue validity, albeit mediated by prevalence; and acceptability of feature-describing generics with low cue validity is mostly determined by prevalence irrespective of cue validity. Such systematic patterns indicate a great potential for the formalization of the semantics of generics.


Supraomohyoid neck dissection. Is it diagnostic or therapeutic?
The supraomohyoid neck dissection (SOHND) is often performed in patients with cancer of the oral cavity, where there is no clinical or radiologic evidence of regional metastases. When on pathologic examination positive neck nodes are found, however, some consider it a curative operation, whereas others regard it as a staging procedure only. We retrospectively reviewed 43 patients with cancer of the oral cavity who had a SOHND during the period from 1991 to 1994. All patients were staged as having N0 disease and had a total of 48 SOHNDs (38 unilateral, 5 bilateral). The follow-up period was at least 2 years. Seven of 48 N0-staged necks showed occult metastasis (15%). Two of these patients received postoperative radiotherapy. One of 7 (14%) patients with pathologic node-positive disease on the SOHND side developed recurrent ipsilateral neck disease during the follow-up period, whereas 4 (10%) recurrences developed in 41 necks that were pathologically staged as N0. Survival was 88% for patients with pathologically N0 necks versus 86% for patients with pathologically N+; disease. Supraomohyoid neck dissection is an effective staging procedure; however, in this group of patients, neck recurrence and patient survival after SOHND appear not to be related to pathology N stage. Also, SOHND with or without adjuvant radiotherapy appears to control the neck in the majority of patients, attesting to therapeutic efficacy. A prospective study is needed, however, to see if a "wait and see" policy does not achieve similar long-term outcome.


Cue usage in memory for location when orientation is fixed.
In previous research, it was demonstrated that including one or three cues surrounding a circular field had no effect on spatial memory for dot locations when the field's orientation was fixed, but that there were very large effects when orientation varied across trials (Fitting, Wedell, & Allen, 2007). In four new experiments, we explored the use of external cues in the fixed orientation environment, using 0, 4, 8, or 24 cues and manipulating task difficulty. In Experiments 1-3, the angular bias data supported the use of four quadrant-based prototypes regardless of cue condition, but there were clear cue effects on radial prototype locations. Increasing the number of cues enhanced accuracy of spatial memory for targets closer to cues. In Experiment 4, we severely challenged memory by using multiple targets and a filled delay before estimation. Doing so demonstrated an effect of cues on the categorical structuring of memory. Collectively, findings indicate that when orientation is fixed, cues bolster fine-grain memory, but that they only alter the default categorical scheme when memory demands are high.


A Rapid Method to Determine Growth-Limiting Nutrient Concentrations for Yeast in a Microplate Spectrophotometer.
Determining the minimal concentration of a substance-whether a compound used to inhibit cell growth or a growth-limiting nutrient-can be an arduous process. Carrying out the experiment in flasks or tubes and estimating cell density in a single-sample spectrophotometer has been a routine method of choice due to the ease of measurement and standardized conversions from optical density measurements to cell concentrations. However, when dealing with dozens or more samples, several challenges arise, including increased processing time, increased risk of contamination through repeated sampling, and an increased risk of confounding one sample for another. The protocol described here details a rapid method to estimate cell concentrations for such experiments using a microplate spectrophotometer. Using a microplate spectrophotometer to measure optical density of many cultures can be automated for high throughput and benefits from a reduced risk of contamination. Since one of the caveats of a microplate spectrophotometer is its low saturation limit, we further describe how to convert optical density readings of the microplate spectrophotometer into its single-sample spectrophotometric equivalent. To further illustrate the applicability of this protocol, we compare OD600 readings generated using a microplate spectrophotometer and a single-sample spectrophotometer for different nutrient starvations and show that the results are comparable. Overall, this method reduces the required resources, reduces the risk of contamination, and allows for faster processing of samples. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Generating an equation to convert microplate spectrophotometer readings to single-sample spectrophotometric values Basic Protocol 2: Evaluating growth-limiting nutrient concentrations using a microplate spectrophotometer.


Analysis of bone mineral content in horizontally HIV-infected children naïve to antiretroviral treatment.
Low bone mass is a frequent finding in HIV-infected individuals. Reduced bone mass has been found in vertically infected children who are receiving antiretroviral treatment. Little is known about bone mass in horizontally infected young patients who are naïve to antiretroviral therapy. We measured the bone mineral content (BMC) at the lumbar spine and in the whole skeleton by using dual-energy X-ray absorptiometry (DXA) in 16 HIV-infected children (age 9.3 +/- 3.9 years) naïve to antiretroviral treatment, and in 119 healthy children (age 9.7 +/- 3.3 years). Thirteen patients were also pair-matched by anthropometric measures, sex, and age with healthy children. Median spine BMC of HIV-infected children was 14.9 g (8.2-39.2 g), and whole body BMC was 1106.1 g (55.5-2344.1 g). Spine BMC of healthy children was 18.6 g (6.8-52.2 g), and whole body BMC was 1213.5 g (541.0-2722.0 g). Multivariate analysis showed a mean difference of spine BMC values of 0.004 g (P = 0.64) between the two groups. Similarly, the whole body BMC difference between the two groups (0.001 g) was not statistically significant (P = 0.55). Mean spine BMC measurements in the case-control evaluation were 21.1 g (9.7 g) (patients), and 22.3 g (6.9 g) (controls). Whole body BMC measurements of patients and controls were 1258.5 g (539.6 g) and 1311.1 g (479.2 g), respectively. In both cases the differences were not significant. The duration of HIV infection did not relate to BMC values. In conclusion, horizontally HIV-infected children naïve to antiretroviral therapy have bone mineral measurements comparable to those of healthy children.


The effect of Illinois Medicaid coverage of induced abortion on patient access at the University of Illinois in Chicago.
Beginning January 1, 2018, Illinois House Bill 40 (HB40) requires Medicaid coverage of induced abortion. The objective of this study was to describe the impact of HB40 on gestational age at time of induced abortion at a single academic medical center in Chicago, IL. We used Current Procedural Terminology (CPT) codes to identify patients who induced abortion one year before (2016) and one year immediately after (2018) HB40 implementation. We collected demographic and clinical information from the electronic medical record. We used ANOVA and Chi-square tests to evaluate differences in gestational age and patient characteristics before and after the policy change. Patient characteristics and indication for induced abortion before (N = 274) and after (N= 249) HB40 were similar. The mean gestational age of induced abortion was higher after HB40 (83.3 days ± 38.9 days vs 91.6 days ± 38.0 days, p = 0.01). While not statistically significant, the proportion of second trimester (>14 weeks) induced abortions increased (32.8% vs 40.6%, p = 0.07). After HB40, a smaller proportion of patients paid out-of-pocket for abortion care (2.4% vs 40.5%, p < 0.001) and more patients had an abortion with sedation (37.3% vs 49.8%, p = 0.007). After passage of HB40, the gestational age at time of induced abortion increased by a median of eight days, access to abortion care was less costly to patients and more procedures were completed with sedation. To further the impact of HB40, increased awareness of expanded coverage continues to be essential. With Medicaid coverage of induced abortion in Illinois, out-of-pocket cost decreased and sedation use increased in our academic medical center. To further the impact of HB40, increased awareness of expanded coverage continues to be essential.


Opalescent grouped vesicles over the face: an important indicator of staphylococcal septicemia.
We present a report of three cases with vesicles containing opalescent fluid grouped over the face and scattered on the trunk and limbs. Culture of the fluid aspirated from the vesicles grew Staphylococcus aureus in two of the three cases. The observation of vesicles grouped on the face in a sick febrile child should prompt the diagnosis of a severe staphylococcal septicemia.


Thrombophilia gene mutations predict venous thromboembolism in ambulatory cancer patients receiving chemotherapy.
Inherited thrombophilia and cancer both independently increase the risk of venous thromboembolism (VTE). However, whether the increased VTE risk associated with inherited thrombophilia exists in cancer patients is less clear. Our objective was to determine the influence of inherited thrombophilia on VTE and bleeding risk in moderate-to-high-risk ambulatory cancer patients receiving chemotherapy. We conducted a post hoc analysis using blood samples from patients enrolled in the AVERT trial to determine if previously recognized thrombophilia gene mutations (prothrombin factor [F] II G20210A, FXI, fibrinogen gamma, serpin family A member 10, FV K858R, FXIII, FV Leiden [FVL], and ABO blood) were associated with VTE or bleeding during the 7-months after starting chemotherapy. Logistic regression was used to compare heterozygous and homozygous mutations (combined) to wild-type. VTE rates, bleeding rates, and risk differences for mutations stratified by prophylactic anticoagulation use were calculated. Of the 447 patients, there were 39 VTE and 39 bleeding events. The odds of VTE were significantly increased with FVL mutation and non-O blood type (odds ratio [OR]: 5.2; 95% CI: 1.9-14.7 and OR: 2.7; 95% CI: 1.2-6.1, respectively). The use of anticoagulation prophylaxis resulted in complete protection in FVL patients, whereas those not receiving anticoagulation had a VTE rate of 119 per 100 patient-years. Lower VTE rates were also observed in non-O blood type patients taking prophylactic anticoagulation. No other thrombophilia genes tested were significantly associated with VTE or bleeding. Our results indicate that FVL mutation and ABO blood type may be important VTE predictors in cancer patients starting chemotherapy.


Phase-resolved nonlinear response of a two-dimensional electron gas under femtosecond intersubband excitation.
Strong electric-field transients resonant to intersubband transitions in n-type modulation-doped GaAs/AlGaAs quantum wells induce coherent Rabi oscillations, which are demonstrated by a phase-resolved measurement of the light emitted by the sample. The time evolution of the intersubband polarization is influenced by Coulomb-mediated many-body effects. The subpicosecond period and the phase of the Rabi oscillations are controlled by the properties of the midinfrared driving pulse.


Evaluation of wall motion abnormality by comparing values of cardiac output obtained by M-mode and Doppler echocardiography: Parameter revealing wall motion abnormality in stress echocardiography.
Dobutamine and dipyridamole stress echocardiographies are both well able to detect myocardial ischemia resulting from coronary diseases by recognizing the regional wall motion abnormality (WMA). Here we report a method for describing WMA in detail. In pharmacological stress echocardiography, because of difficulties in recognizing the two-dimensional pattern, accuracy sometimes depends upon the skill of the operator. Two stroke volumes obtained using the M-mode and Doppler methods were examined to detect abnormal regional cardiac function by the dipyridamole stress test. Stroke volume obtained by the M-modereflects regional cardiac function and that estimated from the outflow using the Doppler methodreflects total cardiac function. These two stroke volumes were compared in normal subjects and patients with coronary-diseases. The results indicated consistent discrepancies between these two stroke volume in the ischemic hearts as a results of coronary stenosis, whereas changes in stroke volumes in the normal subjects showed the same tendency. This method of combining information about the regional and total functions is thus useful in examining the WMA and regional cardiac function, although it can not be applied to subjects whose stroke volume does not increase under stress.


Auditory signal detectability and facilitation of simple reaction time in psychiatric patients and non-patients.
Patients diagnosed on the basis of structured interviews as having affective psychoses were less sensitive in detecting the presence of a transient auditory signal than were schizophrenic patients or non-patients. Patients with affective psychoses also benefited more (their reaction time was more reduced) than the other two groups from the presence of a second auditory transient.


Allergy to chlorhexidine: beware of the central venous catheter.
The example reported here illustrates the frequent belief that "innocent" products such as central venous catheters do not produce allergic reactions. However, they might be impregnated with chlorhexidine and elicit serious life-threatening anaphylaxis in patients with allergy to this antiseptic agent.


Active learning model for extracting elastic modulus of cell on substrate.
The cell elastic modulus (Ec) is widely used as the mechanics-based marker to analyze the biological effects of substrates on cells. However, the employment of the Hertz model to extract the apparent Ec can cause errors due to the disobedience of the small deformation assumption and the infinite half-space assumption, as well as an inability to deduct the deformation of the substrate. So far, no model can effectively solve the errors caused by the above-mentioned aspects simultaneously. In response to this, herein, we propose an active learning model to extract Ec. The numerical calculation with finite element suggests the good prediction accuracy of the model. The indentation experiments on both hydrogel and cell indicate that the established model can efficiently reduce the error caused by the method of extracting Ec. The application of this model may facilitate our understanding about the role of Ec in correlating the stiffness of substrate and the biological behavior of cell.


Repetitive and compulsive behavior after Early-Life-Pain associated with reduced long-chain sphingolipid species.
Pain in early life may impact on development and risk of chronic pain. We developed an optogenetic Cre/loxP mouse model of "early-life-pain" (ELP) using mice with transgenic expression of channelrhodopsin-2 (ChR2) under control of the Advillin (Avil) promoter, which drives expression of transgenes predominantly in isolectin B4 positive non-peptidergic nociceptors in postnatal mice. Avil-ChR2 (Cre +) and ChR2-flfl control mice were exposed to blue light in a chamber once daily from P1-P5 together with their Cre-negative mother. ELP caused cortical hyperexcitability at P8-9 as assessed via multi-electrode array recordings that coincided with reduced expression of synaptic genes (RNAseq) including Grin2b, neurexins, piccolo and voltage gated calcium and sodium channels. Young adult (8-16 wks) Avil-ChR2 mice presented with nociceptive hypersensitivity upon heat or mechanical stimulation, which did not resolve up until one year of age. The persistent hypersensitivy to nociceptive stimuli was reflected by increased calcium fluxes in primary sensory neurons of aged mice (1 year) upon capsaicin stimulation. Avil-ChR2 mice behaved like controls in maze tests of anxiety, social interaction, and spatial memory but IntelliCage behavioral studies revealed repetitive nosepokes and corner visits and compulsive lickings. Compulsiveness at the behavioral level was associated with a reduction of sphingomyelin species in brain and plasma lipidomic studies. Behavioral studies were done with female mice. The results suggest that ELP may predispose to chronic "pain" and compulsive psychopathology in part mediated by alterations of sphingolipid metabolism, which have been previously described in the context of addiction and psychiatric diseases.


Interleukin-1 receptor mediates the interplay between CD4+ T cells and ocular resident cells to promote keratinizing squamous metaplasia in Sjögren's syndrome.
Keratinizing squamous metaplasia (SQM) of the ocular mucosal epithelium is a blinding corneal disease characterized by the loss of conjunctival goblet cells (GCs), pathological ocular surface keratinization and tissue recruitment of immune cells. Using the autoimmune regulator (Aire)-deficient mouse as a model for Sjögren's syndrome (SS)-associated SQM, we identified CD4(+) T lymphocytes as the main immune effectors driving SQM and uncovered a pathogenic role for interleukin-1 (IL-1). IL-1, a pleiotropic cytokine family enriched in ocular epithelia, governs tissue homeostasis and mucosal immunity. Here, we used adoptive transfer of autoreactive CD4(+) T cells to dissect the mechanism whereby IL-1 promotes SQM. CD4(+) T cells adoptively transferred from both Aire knockout (KO) and Aire/IL-1 receptor type 1 (IL-1R1) double KO donors conferred SQM to severe-combined immunodeficiency (scid) recipients with functional IL-1R1, but not scid recipients lacking IL-1R1. In the lacrimal gland, IL-1R1 was primarily immunolocalized to ductal epithelium surrounded by CD4(+) T cells. In the eye, IL-1R1 was expressed on local mucosal epithelial and stromal cells, but not on resident antigen-presenting cells or infiltrating immune cells. In both tissues, autoreactive CD4(+) T-cell infiltration was only observed in the presence of IL-1R1-postive resident cells. Moreover, persistent activation of IL-1R1 signaling led to chronic immune-mediated inflammation by retaining CD4(+) T cells in the local microenvironment. Following IL-1R1-dependent infiltration of CD4(+) T cells, we observed SQM hallmarks in local tissues-corneal keratinization, conjunctival GC mucin acidification and epithelial cell hyperplasia throughout the ocular surface mucosa. Proinflammatory IL-1 expression in ocular epithelial cells significantly correlated with reduced tear secretion, while CD4(+) T-cell infiltration of the lacrimal gland predicted the development of ocular SQM. Collectively, data in this study indicated a central role for IL-1 in orchestrating a functional interplay between immune cells and resident cells of SS-targeted tissues in the pathogenesis of SQM.


Cost-effectiveness of cimetidine maintenance therapy in chronic gastric and duodenal ulcer.
The effects of cimetidine maintenance therapy on the socioeconomic life of patients with peptic ulcers in the 3 years after healing and the extent to which treatment was cost-effective were studied. Three hundred eleven patients with healed ulcers (184 gastric, 127 duodenal) were studied for periods of up to 3 years; 261 patients (152 gastric ulcer, 109 duodenal ulcer) completed the 3-year follow-up. Cimetidine (400 mg at night) was compared with placebo in a double-blind, randomized prospective study. Intention-to-treat analysis was used. In the placebo group, the major costs of ulcer disease in gastric ulcer patients were attributable to endoscopic procedures and absenteeism; in duodenal ulcer patients, the major costs were endoscopic procedures, absenteeism, and surgery. Cimetidine was cost-effective in both gastric ulcer and duodenal ulcer patients in the first 2 years after healing. Over the 3-year period it was also cost-effective, but no benefit was seen in the third year.


LncRNA NEAT1 is upregulated in recurrent aphthous stomatitis (RAS) and has predictive values.
LncRNA NEAT1 promotes inflammatory responses, which contribute to recurrent aphthous stomatitis (RAS). This study focused on the involvement of NEAT1 in RAS. RT-qPCR and ELISA were performed to determine the expression of NEAT1 and proinflammatory factors (IL-2, IL-1β, and TNF-α) in plasma from patients with a history of RAS and showing symptom (n = 80, S-RAS group), people with a history of RAS but showing no symptom (n = 80, NS-RAS group), and controls without a history of RAS (n = 80, Control group). Correlation analysis was performed with Pearson's correlation coefficient. S-RAS group received treatmen,t and plasma levels of NEAT1 and proinflammatory factors were compared before and after treatment. S-RAS group was followed up for 12 months, and the recurrence was recorded. Plasma NEAT1, IL-2, IL-1β, and TNF-α levels were the highest in the S-RAS group, followed in turn by NS-RAS and control groups. NEAT1 was positively and significantly correlated with IL-2, IL-1β, and TNF-α across S-RAS and NS-RAS samples, but not control samples. After treatment, plasma levels of NEAT1, IL-2, IL-1β, and TNF-α decreased significantly. Moreover, a higher recurrence rate was observed during the follow-up in patients with high plasma NEAT1 levels. NEAT1 is upregulated in RAS and correlated with multiple proinflammatory factors. Moreover, NEAT1 has predictive values for RAS.


A modified Tessari method for producing more foam.
This study aimed to develop a modified Tessari method for producing more sclerosing foam in treatment of extensive venous malformations. Sclerosing foam was produced by using Tessari method and the modified Tessari method. The procedure of the later was as follows: prepared foam in a sclerosant-air ratio of 1:4; connected three disposable 10 ml syringes to two medical three-way taps; drawn 4 ml of liquid sclerosant into one syringe and 16 ml averagely of air into the other two; then moved the plungers of all syringes back and forth for 20 times to produce sclerosing foam. The volume and foam half time (FHT) of foam produced by the two methods were compared. The average volume of sclerosing foam produced by Tessari method and the modified Tessari method were 9.8 and 19.7 ml, and assessed to have statistical difference. The FHT of foam produced by the two methods were 120 and 150 s, and assessed to have statistical difference. In conclusion, the modified Tessari method could produce more fresh and stable sclerosing foam.


Comparison between magnetic resonance hysterosalpingography and conventional hysterosalpingography: direct visualization of the fallopian tubes using a novel MRI contrast agent mixture.
Magnetic resonance hysterosalpingography (MR-HSG) is a promising technique in the work-up of female infertility. Few existing MR-HSG studies focus on the comparison between MR-HSG with gold standard examination. To compare the diagnostic value of MR-HSG with conventional HSG in patients receiving both exams in one day. This study included 33 infertile women who completed pelvic MR scanning, HSG, and MR-HSG in that order. A traditional HSG contrast agent (iohexol) and a magnetic resonance imaging (MRI) contrast agent (1 mL gadopentetate dimeglumine (Gd-DTPA) blended with 100 mL iohexol) were used to achieve image enhancement. Inter-observer and inter-modality agreements of HSG and MR-HSG exams were assessed. The results were calculated by using the kappa test. Three radiologists who were blinded to the clinical data independently reviewed the MR images. Extratubal abnormalities were analyzed. A total of 62 fallopian tubes of 33 women were included in the study. MR-HSG imaging findings to depict tubal patency were similar to these of HSG (AUC 0.911, sensitivity 0.821, specificity 1.000, positive predictive values 1.000, and negative predictive values 0.872). Pairwise inter-observer agreement among three observers and inter-modality agreement of the diagnosis were excellent (mean kappa 0.863 and 0.835, respectively). In addition, 29 extratubal abnormalities in 21 patients were found on pelvic MR scanning. MR-HSG and HSG demonstrated similar results in assessing tubal patency. Because it offers the comprehensive assessment of female pelvic structures, and avoids ionizing radiation, MR-HSG may be used as an alternative imaging technique for evaluation of female infertility.


Bone marrow fat content in relation to bone remodeling and serum chemistry in intact and ovariectomized dogs.
It was previously shown that 11 months after ovariectomy the volume fraction of trabecular bone in the spine and 11th rib medullary canal of Beagle dogs (6 control, 9 ovariectomized) was significantly reduced. In this paper it is shown that these changes are accompanied by increased marrow fat volume in the 11th rib (59.0 +/- 9.5% vs. 44.3 +/- 10.0%). Conversely, the volume fraction of functional (hematopoietic) cells in the marrow was reduced by ovariectomy. Additionally, variations in marrow fat volume were tested for correlation with 22 other variables pertinent to bone physiology. Marrow fat volume was significantly positively correlated with serum osteocalcin, rib trabecular bone porosity, rib cross-sectional area, and gains in body weight. It was negatively correlated with serum estrogen concentrations and the extent of rib trabecular surfaces labeled with tetracycline.


Spatiotemporal variability during gait initiation in Parkinson's disease.
During gait initiation (GI), consistency of foot placement while stepping is important in making successful transitions from a state of stable static posture to an unstable state of dynamic locomotion. In populations characterized by gait dysfunction and postural instability, such as persons with Parkinson's disease (PD), the ability to generate a consistent stepping pattern during GI may be essential in the prevention of falls. However, little is known about GI variability in persons with PD as compared to their healthy elderly peers. Therefore, this study investigated spatiotemporal variability during the first two steps of GI in 46 persons with idiopathic PD and 49 healthy age-matched adults. Stepping characteristics, including the length, width, and time of the first two steps of GI as well as their coefficients of variation (CV) were compared between groups. Persons with PD initiated gait with significantly shorter steps (swing step length=.463 vs. .537 m, stance step length=.970 vs. 1.10 m) and higher variability in step length (swing step CV=8.82 vs. 5.45, stance step CV=6.76 vs. 3.61). Persons with PD also showed significantly higher variability in the time of the swing step (swing step CV=10.0 vs. 7.4). GI variability did not differ significantly between disease stages in persons with PD. Because greater variability in these measures during gait is related to an increased risk of falls, we propose that higher GI variability may play a considerable role in falls frequently observed during transitions from quiet standing in PD.


Characteristics of the transport of carnitine into the cauda epididymidis of the rat as ascertained by luminal perfusion in vitro.
An in vitro luminal perfusion technique was used to monitor the transepithelial movement of [3H]L-carnitine into the cauda epididymal lumen of rats. Movement of the volume marker [14C]inulin into the lumen was limited while the transport of [3H]L-carnitine was saturable and was dependent on respiratory energy. The transport of L-carnitine (50 microM) was significantly inhibited by 500 microM D-carnitine, palmitoyl L-carnitine and deoxycarnitine but not by trimethylammonium iodide, trimethyl phosphate, acetyl-L-carnitine, choline, betaine, gamma-aminobutyric acid or DL-carnitinamide. The Kt (116 microM) and Vmax (0.1 nmol/30 min/cm) for the carriers were calculated from the present data and as the Kt is about twice the normal plasma concentration of carnitine, the rate of transport by the pump is presumed to be limited by the plasma concentration.


High-risk criteria for the physiologically difficult paediatric airway: A multicenter, observational study to generate validity evidence.
Single-center studies have identified risk factors for peri-intubation cardiac arrest in the emergency department (ED). The study objective was to generate validity evidence from a more diverse, multicenter cohort of patients. We completed a retrospective cohort study of 1200 paediatric patients who underwent tracheal intubation in eight academic paediatric EDs (150 per ED). The exposure variables were 6 previously studied high-risk criteria for peri-intubation arrest: (1) persistent hypoxemia despite supplemental oxygen, (2) persistent hypotension, (3) concern for cardiac dysfunction, (4) post-return of spontaneous circulation (ROSC), (5) severe metabolic acidosis (pH < 7.1), and (6) status asthmaticus. The primary outcome was peri-intubation cardiac arrest. Secondary outcomes included extracorporeal membrane oxygenation (ECMO) cannulation and in-hospital mortality. We compared all outcomes between patients that met one or more versus no high-risk criteria, using generalized linear mixed models. Of the 1,200 paediatric patients, 332 (27.7%) met at least one of 6 high-risk criteria. Of these, 29 (8.7%) suffered peri-intubation arrest compared to zero arrests in patients meeting none of the criteria. On adjusted analysis, meeting at least one high-risk criterion was associated with all 3 outcomes - peri-intubation arrest (AOR 75.7, 95% CI 9.7-592.6), ECMO (AOR 7.1, 95% CI 2.3-22.3) and mortality (AOR 3.4, 95% 1.9-6.2). Four of 6 criteria were independently associated with peri-intubation arrest: persistent hypoxemia despite supplemental oxygen, persistent hypotension, concern for cardiac dysfunction, and post-ROSC. In a multicenter study, we confirmed that meeting at least one high-risk criterion was associated with paediatric peri-intubation cardiac arrest and patient mortality.


Synthesis of 1H-pyrrolo[3,2-h]quinoline-8-amine derivatives that target CTG trinucleotide repeats.
We describe a new molecular design, synthesis, and investigation of small molecules that bind to CTG trinucleotide repeats in DNA. 1H-Pyrrolo[3,2-h]quinoline-8-amine (PQA) has a tricyclic aromatic system with unique non-linear hydrogen-bonding surface complementary to thymine. We have synthesized a series of PQA derivatives with different alkylamino linkers. These PQAs showed binding to pyrimidine bulge DNAs and CNG (N=T and C) repeats depending on the linker structure, while quinoline derivatives lacking the pyrrole ring showed much lower binding affinity. PQA is a useful molecular unit for both CTG and CCG repeat binding.