Potential application of hydrogel to the diagnosis and treatment of multiple sclerosis.
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. This disorder may cause progressive and permanent impairment, placing significant physical and psychological strain on sufferers. Each progress in MS therapy marks a significant advancement in neurological research. Hydrogels can serve as a scaffold with high water content, high expansibility, and biocompatibility to improve MS cell proliferation in vitro and therapeutic drug delivery to cells in vivo. Hydrogels may also be utilized as biosensors to detect MS-related proteins. Recent research has employed hydrogels as an adjuvant imaging agent in immunohistochemistry assays. Following an overview of the development and use of hydrogels in MS diagnostic and therapy, this review discussed hydrogel's advantages and future opportunities in the diagnosis and treatment of MS.


Neuropsychological deficit and aggressive behavior: a prospective study.
1. Failures in higher cortical executive functions and dyscontrol of aggressive impulses were hypothesized to co-occur in aggressive men. 2. The performance of a sample of violent forensic patients on selected neuropsychological measures (Judgment of Line Orientation, Stroop Color Word Test, Emotion Perception Test, Test Of Nonverbal Intelligence, Wisconsin Card Sorting Test, and Symbol Digit Modalities Test) were used to predict their overt aggressive behavior during a one-year period using the Overt Aggression Scale. 3. Whole-set correlation analyses revealed that scores on the Judgment of Line Orientation, Stroop Color Word Test, and Emotion Perception Test accounted for 57% of the variance of aggression scores. 4. Frequency of aggression, but not severity of aggression, can be predicted using these three scores.


Biological activity of bacterial surface components: bacterial extracts and defined bacterial cell wall components as immunomodulators.
Bacterial extracts obtained from pathogenic strains occurring in lung infections (Broncho Vaxom) or urogenital infections (Urovaxom) as well as defined surface components of Gram-negative bacteria purified from bacteria or obtained by chemical synthesis were tested for their immunomodulatory properties in a murine system. The bacterial extracts were able to act as immunogens inducing an antigen-specific response. Both the bacterial extracts and the purified bacterial cell wall components constituted polyclonal activators of murine splenic B cells, as demonstrated by proliferation assays measuring the incorporation of [3H]thymidine into DNA. They were also able to act as immunoadjuvants increasing the SRBC and the BSA-TNP specific immune response, and could induce tumor cytotoxicity in bone marrow-derived macrophages. The results show that bacterial extracts and defined bacterial surface components constitute immunogens as well as immunomodulators in vitro and in vivo.


Adaptive multi-dimensional Taylor network dynamic surface control for a class of strict-feedback uncertain nonlinear systems with unmodeled dynamics and output constraint.
Unmodeled dynamics and output constraint are very often experienced in many physical applications, while few studies on them simultaneously are constructed. This study concentrates on the problem of adaptive multi-dimensional Taylor network dynamic surface control (MTN-DSC) for a class of strict-feedback uncertain nonlinear systems subjected to unmodeled dynamics and output constraint. The purpose is to make this study more practical, and design a controller with simple structure to improve the system performance. A barrier Lyapunov function is used to restrict the system output to within the prescribed constraint. At each step during the backstepping design process, an MTN is applied to approach the generated unknown composite function stemming from the unknown functions and uncertain disturbances, rather than individually; this simplifies the structure and reduces the complexity of the controllers. Meanwhile, the computational burden is further reduced, as only one parameter is adjusted online, which has the minimum number of parameters to be adjusted. Additionally, DSC technique is introduced to eliminate the inherent "explosion of complexity" problem in traditional backstepping design procedure. Furthermore, it is proved that all signals of the closed-loop system are semi-globally uniformly ultimately bounded, and that the output constraint is never violated. The validity of the proposed control scheme is illustrated through the numerical and applied simulation examples.


Harm perceptions, JUUL dependence, and other tobacco product use among young adults who use JUUL.
The study identified groups of JUUL using young adults based on their use patterns and compared harm perceptions, JUUL dependence, and other tobacco product use among these groups. Online cross-sectional survey data were gathered in March 2019 from 667 undergraduate students who used JUUL weekly (50.4% females, average age: 20.3 years) at a southwest U.S. university. Latent class analysis identified four groups of young adults who used JUUL: 1) Light Social JUUL Using Young Adults (LS, 52.5%) who used JUUL occasionally with friends when drinking alcohol, 2) Daily Sensation Seekers (DSS, 16.2%) who used JUUL daily with alcohol, 3) Daily Activity Driven JUUL Using Young Adults (DAD, 26.0%) who used JUUL daily while drinking, watching media, or studying, and 4) Daily All Occasion JUUL Using Young Adults (DAO, 5.3%) who used JUUL heavily, daily and in various occasions. While all four groups reported some extent of JUUL dependence, DAO reported the highest dependence and were more likely than LS to have used cigarettes and other e-cigarettes besides JUUL. They also tended to believe different pod flavors could cause different types of lung damage while the other groups were unsure/disagreed with this belief. LS were more likely than DSS and DAD to believe that JUUL use indicated openness to new experiences. Young adults with different JUUL use patterns perceived JUUL harms differently and faced varied risks of JUUL dependence and other tobacco product use. Effective cessation interventions should be adapted to meet the needs of these groups.


The effects of indomethacin and interleukin-2 on the proliferation of lymphocytes from patients with lung cancer.
The effects of the addition of indomethacin and interleukin-2 (IL-2) to phytohemagglutinin (PHA)-stimulated lymphocytes from patients with untreated squamous-cell carcinoma of the lung and with chronic obstructive pulmonary disease and from normal individuals were studied. In 13 of 21 patients with lung carcinoma, the response of lymphocytes to PHA stimulation was significantly augmented by indomethacin. In these 13 patients, the nonaugmented PHA response was also significantly depressed, with only 1 patient falling in the normal range. In the other 8 patients, the average PHA reactivity was normal, as was the degree of augmentation by indomethacin. In additional studies, IL-2 was added to PHA-stimulated lymphocytes with and without the addition of indomethacin. In the normal group, IL-2 further increased PHA reactivity by an average of 46.0%. The addition of indomethacin to these cultures increased the PHA reactivity by only 8.8%, which is similar to the indomethacin effect for the PHA-stimulated cells without the addition of IL-2. In the cancer group, the PHA reactivity of 13 of 19 patients was significantly increased by the addition of IL-2. When indomethacin was added simultaneously with IL-2, the proliferative response for 12 of 19 patients was increased significantly more than for the normal controls. Thus, this study indicates that the PHA reactivity of lymphocytes from many lung carcinoma patients is augmented to a greater extent than for normal individuals by inhibiting prostaglandin synthesis. Also, the addition of IL-2 to these PHA-stimulated cultures did not mimic the addition of indomethacin, but instead the effects were usually additive.(ABSTRACT TRUNCATED AT 250 WORDS)


Chitosan/pectin polyelectrolyte complexes: selection of suitable preparative conditions for colon-specific delivery of vancomycin.
The influence of polyelectrolyte complexes composed of chitosan and pectin on the release behaviour of vancomycin has been investigated. Polyelectrolyte complexes between chitosan and pectin were prepared in various pH regions and at different molar ratios by mixing solutions of pectin and chitosan with the same ionic strength. The precipitates were collected by spray-drying and tablets were obtained with the different complexes and vancomycin. FT-IR spectra and TGA thermograms were analysed to study the degree of interactive strength between polyions. In vitro swelling, mucoadhesion and release tests were performed in order to investigate the chitosan/pectin complex ability in the delivery of vancomycin in the gastro-intestinal tract. The results confirmed the formation of polyelectrolyte complexes between pectin and chitosan at pH values in the vicinity of the pKa interval of the two polymers. Chitosan/pectin complexes showed a pH-sensitive swelling ability and drug release behaviour suggesting their possible use for colon-specific localization of vancomycin. Among the different complexes, chitosan/pectin complex prepared in molar ratio of 1:9 showed the highest mucoadhesive properties and a pH-dependent swelling sensitivity suitable for colon-delivery. Moreover, the particular composition of these complexes improved vancomycin availability at alkaline pH on the bases of an enzyme-dependent degradation as confirmed from release studies performed in presence of beta-glucosidase.


In vivo and in vitro genotoxic evaluation of indorenate.
5-Methoxytryptamine, beta-methylcarboxylate hydrochloride (indorenate) is a new antihypertensive serotonin derivative. We evaluated its genotoxic activity using the mouse bone marrow and cytogenetic test and the human lymphocyte culture cytogenetic assay. As endpoints we measured chromosomal aberrations, sister-chromatid exchanges and cellular proliferation kinetics. Our results agree in both systems showing that indorenate is a non-genotoxic agent in these assays.


Double-J Stent Misplacement in the Inferior Vena Cava and Right Atrium: A Urovascular Nightmare.
Ureteral injury may occur during abdominopelvic surgery given its anatomic path and proximity to surrounding organs. We present a case in which a patient required ureteral reimplantation following injury during a hysterectomy. The patient underwent a seemingly uncomplicated robotic ureteral reimplantation with ureteral stent placement. However, postoperative imaging demonstrated extension of the stent from the bladder to the right atrium. It appeared that the gonadal vein was reimplanted rather than the ureter. In a combined urology-vascular surgery case, gonadal vein implantation into the bladder was confirmed. Through-and-through access from the right internal jugular vein to the urethra was established. The ureteral stent was removed and the gonadal vein was embolized, with urology follow-up for planning and scheduling of ureteral reimplantation. Vascular involvement by ureteral stents has considerable risks and often requires further surgery. Ureteral injury can occur even in the hands of experienced surgeons and has a considerable impact on patients. Recognizing important anatomy and using operative techniques to differentiate from nearby structures, such as the gonadal vein, may help in preventing ureteral injury and assisting with repair of ureteral injury. We describe a case in which a patient had an injury to her ureter, the tube that transports urine from the kidney to the bladder. When trying to repair this, a blood vessel (the gonadal vein) instead of the ureter was accidentally connected to the bladder. We discuss the resulting complications and management, similar cases, and important anatomy concepts and surgical techniques to prevent this type of injury.


[Clinical study of picotamide in patients with vascular diseases].
The authors report on a group of 44 patients operated on for vascular disease, treated with antiplatelet therapy (picotamide). These patients were followed up for a period of 12 months with clinical and instrumental controls (Doppler ultrasound) in order to evaluate the evolution of atherosclerotic disease.


RNA Binding Protein Quaking Promotes Hypoxia-induced Smooth Muscle Reprogramming in Pulmonary Hypertension.
Pulmonary hypertension (PH) is a devastating disease characterized by progressive increases in pulmonary vascular resistance and remodeling, which eventually leads to right ventricular failure and death. The aim of this study was to identify novel molecular mechanisms involved in the hyperproliferation of pulmonary artery smooth muscle cells (PASMCs) in PH. In this study, we first demonstrated that the mRNA and protein expression amounts of QKI (Quaking), an RNA-binding protein, were elevated in human and rodent PH lung and pulmonary artery tissues and hypoxic human PASMCs. QKI deficiency attenuated PASMC proliferation in vitro and vascular remodeling in vivo. Next, we elucidated that QKI increases STAT3 (signal transducer and activator of transcription 3) mRNA stability by binding to its 3' untranslated region. QKI inhibition reduced STAT3 expression and alleviated PASMC proliferation in vitro. Moreover, we also observed that the upregulated expression of STAT3 promoted PASMC proliferation in vitro and in vivo. In addition, as a transcription factor, STAT3 bound to microRNA (miR)-146b promoter to enhance its expression. We further showed that miR-146b promoted the proliferation of smooth muscle cells by inhibiting STAT1 and TET2 (Tet methylcytosine dioxygenase 2) during pulmonary vascular remodeling. This study has demonstrated new mechanistic insights into hypoxic reprogramming that arouses vascular remodeling, thus providing proof of concept for targeting vascular remodeling by directly modulating the QKI-STAT3-miR-146b pathway in PH.


Identification and subcellular localization of the Q gene product of visna virus.
The genome of the sheep visna lentivirus contains an open reading frame, Q, which has a coding potential of 230 amino acid residues. This paper reports the identification and the subcellular localization of the Q ORF-encoded protein detected in lysates of visna virus-infected sheep choroid plexus cells. Sera from sheep either experimentally or naturally infected with visna virus reacted with the bacterially synthesized Q protein indicating that the in vivo expressed Q product is immunogenic. Antibodies raised against a synthetic N-terminal peptide, reacted with either the bacterial Q or the in vitro translated Q protein as well as with the Q protein expressed during cellular infection. This 29 kDa protein is detectable late in the lytic viral cycle, i.e., 72 hr postinfection, and this expression correlates with the late transcription of its 4.8-kb mRNA. These results provide evidence for the first time that the Q ORF is a late gene of visna virus and that the Q protein is located in the cytosol compartment, without evidence of accumulation at the cell membrane, or in cell-free virion particles.


[French translation and validation of Izard's differential emotion scale. Study of the verbal qualification of emotions].
This work presents the validation of a French version of the emotional self rating scale by Izard (Differential Emotion Scale). This scale is based on the theory of the Discrete Emotions which proposes the existence of ten fundamental emotions. This self-rating scale consists of thirty emotional adjectives (three for each emotion). The validation was done by using a non inductive method (by asking the subject to describe his present emotional state) with 84 control subjects. It shows that this version is valid. Main results are first the binarisation of the emotions (positive and negative), then the existence of complex factors with psychopathological meaning after factorial analysis. These results are in agreement with a theory of expressive emotional levels more than with the theory of discrete emotions in psychopathology.


Corticosteroids and β₂-agonists upregulate mitogen-activated protein kinase phosphatase 1: in vitro mechanisms.
Airway remodelling is a consequence of long-term inflammation and MAPKs are key signalling molecules that drive pro-inflammatory pathways. The endogenous MAPK deactivator--MAPK phosphatase 1 (MKP-1)--is a critical negative regulator of the myriad pro-inflammatory pathways activated by MAPKs in the airway. Herein we investigated the molecular mechanisms responsible for the upregulation of MKP-1 in airway smooth muscle (ASM) by the corticosteroid dexamethasone and the β₂-agonist formoterol, added alone and in combination. MKP-1 is a corticosteroid-inducible gene whose expression is enhanced by long-acting β₂-agonists in an additive manner. Formoterol induced MKP-1 expression via the β₂-adrenoceptor and we provide the first direct evidence (utilizing overexpression of PKIα, a highly selective PKA inhibitor) to show that PKA mediates β₂-agonist-induced MKP-1 upregulation. Dexamethasone activated MKP-1 transcription in ASM cells via a cis-acting corticosteroid-responsive region located between -1380 and -1266 bp of the MKP-1 promoter. While the 3'-untranslated region of MKP-1 contains adenylate + uridylate elements responsible for regulation at the post-transcriptional level, actinomycin D chase experiments revealed that there was no increase in MKP-1 mRNA stability in the presence of dexamethasone, formoterol, alone or in combination. Rather, there was an additive effect of the asthma therapeutics on MKP-1 transcription. Taken together, these studies allow us a greater understanding of the molecular basis of MKP-1 regulation by corticosteroids and β₂-agonists and this new knowledge may lead to elucidation of optimized corticosteroid-sparing therapies in the future.


Transcriptional control by PARP-1: chromatin modulation, enhancer-binding, coregulation, and insulation.
The regulation of gene expression requires a wide array of protein factors that can modulate chromatin structure, act at enhancers, function as transcriptional coregulators, or regulate insulator function. Poly(ADP-ribose) polymerase-1 (PARP-1), an abundant and ubiquitous nuclear enzyme that catalyzes the NAD(+)-dependent addition of ADP-ribose polymers on a variety of nuclear proteins, has been implicated in all of these functions. Recent biochemical, genomic, proteomic, and cell-based studies have highlighted the role of PARP-1 in each of these processes and provided new insights about the molecular mechanisms governing PARP-1-dependent regulation of gene expression. In addition, these studies have demonstrated how PARP-1 functions as an integral part of cellular signaling pathways that culminate in gene-regulatory outcomes.


Autoimmune pancreatitis: with special reference to a localized variant.
In 2006, the Japan Pancreas Society revised the diagnostic criteria for autoimmune pancreatitis (AIP) so as to more clearly define its morphological, pathological, and immunological features, as follows: (1) diffuse or segmental narrowing of the main pancreatic duct with an irregular wall and diffuse or localized enlargement of the pancreas recognized by imaging studies; (2) high serum gamma globulin, IgG, or IgG4 levels, or the presence of autoantibodies; and (3) marked interlobular fibrosis and prominent infiltration of lymphocytes and plasma cells in the periductal area, occasionally with lymphoid follicles in the pancreas. Establishing a diagnosis of AIP has become easier with knowledge of its immunological abnormalities, including serum IgG4 levels. However, the localized form of AIP sometimes mimics pancreatic cancer. The rate of focal mass formation in patients with AIP is reportedly 24%-43%; however, there have been few reports on the histological findings of localized AIP, in contrast to mass-forming pancreatitis (MFP). Our review of patients who had undergone resection due to a preoperative diagnosis of MFP with possible cancer revealed 72% to be patients with localized AIP. For the discrimination of these conditions, it is important to recognize the characteristic ultrasonographic findings of AIP, i.e., (1) diffuse or localized enlargement and hypoechogenicity of the pancreas; (2) rarity of calcification, cystic lesions, and peripancreatic fluid collection; (3) thickened layer structure of the bile duct wall; (4) iso/hypervascularity in the swollen portion of the pancreas; (5) attenuation of pancreatic swelling and bile duct wall thickening after steroid therapy; and (6) multiple hypoechoic masses in various organs, including the pancreas. Contrast-enhanced endoscopic ultrasonography is potentially a useful tool in the differential diagnosis and for assessment of the efficacy of steroid therapy by enabling evaluation of the vascularity of the lesions. Along with the presence of IgG4-positive plasma cells, verification of obliterative phlebitis is highly specific for the histological diagnosis of AIP.


Proteoglycans of fetal bovine tendon.
The proteoglycans (PG) of bovine fetal tendon (4-8 months in utero) were extracted with 4 M guanidine HCl and partially purified by ion exchange chromatography. Proteoglycans from fetal tendon were virtually entirely small molecules (Kav approximately equal to 0.55 by Sepharose CL-4B chromatography). These small proteoglycans had dermatan sulfate glycosaminoglycan chains and a core protein (after chondroitinase ABC digestion) with Mr approximately equal to 45,000 on sodium dodecyl sulfate-polyacrylamide gels. By electrophoretic mobility, immunocross-reactivity, and V8 protease sensitivity, these proteoglycans were determined to be of both PG I and PG II types. In contrast, adult tendon contains only the PG II type of small proteoglycan. Proteoglycans synthesized by fetal tendon explant cultures were, by both chromatographic and electrophoretic mobilities, somewhat larger than those extracted from the same tissue. There was no difference in the spectrum of proteoglycans observed between those regions of fetal tendon destined to receive only tensional forces (proximal) and those regions that will be subjected as well to compressive forces (distal) in the adult. These observations indicate that the proteoglycan content and synthetic capability of all regions of fetal tendon are constant and significantly different from those of both the tensional and fibrocartilaginous regions of adult tendon.


NMR investigation of the charge isomers of bovine myelin basic protein.
Myelin basic protein (MBP) isolated from bovine white matter is obtained as a mixture of molecules which can be separated by cation-exchange chromatography at basic pH into three or more charge isomers. The three principal charge isomers of the microheterogeneous myelin basic protein have been isolated, and compared individually by high-resolution H NMR spectroscopy (360 and 400 MHz). In addition to confirming sources of MBP charge microheterogeneity such as fractional deamidation of Gln and loss of C-terminal Arg, NMR difference and spin-echo spectra further suggested (i) the presence of significant oxidation of (both) MBP Met residues to methionine sulfoxide; (ii) the three charge isomers contain equal ratios and absolute contents of mono- and dimethylated Arg; and (iii) the most-cationic isomer is deficient in its content of a putative extra Ala residue vs the other two isomers. Spectral analysis suggested that each MBP charge isomer is itself not a unique molecule, but more likely a mixture of molecules of equal net charge which are modified at any of the indicated functional side chains throughout the 169-residue protein. The results are discussed with respect to the possible consequences of MBP microheterogeneity to protein conformation and function.


Sex is a major effect modifier between body composition and mortality in patients with cirrhosis assessed for liver transplantation.
Body composition predicts mortality in patients with cirrhosis. The impact of sex on this association is unknown. We investigated the impact of sex on this association in patients with cirrhosis assessed for liver transplantation. This single-centre retrospective cohort study included adults assessed for liver transplantation. Nutritional status was assessed using the Royal Free Hospital-Global Assessment (RFH-GA). Body composition at the third lumbar vertebrae was determined. SarcopeniaSMI was defined as Skeletal Muscle Index <50 cm2 /m2 in males and <39 cm2 /m2 in females. SarcopeniaPMI was defined as the sex-specific 25th percentile of the Psoas Muscle Index. Patients were assessed for the occurrence of liver transplantation and death. Analyses were stratified by sex. The cohort comprised 628 patients, including 199 females and 429 males. Both groups were similar in terms of baseline liver disease severity by Model for End-stage Liver Disease (MELD) (p = .98) and nutritional status (p = .24). SarcopeniaSMI was present in 41% of males compared to 27% of females (p < .001). In the male cohort, when adjusted for age and MELD, sarcopeniaPMI (aHR 1.74, 95% CI 1.08-2.80) and RFH-GA (aHR 1.40, 95% CI 1.03-1.90) remained independent predictors of mortality. Adipose tissue had no impact on outcomes in males. In female patients, adipose tissue (TATI or VATI depending on the multivariable model) was independently associated with mortality, whereas sarcopenia and malnutrition were not. This study demonstrates that male patients were susceptible to low muscle mass, whereas female patients were not. Future research in this patient population should minimize sex-related bias and present data for both groups separately.


Dynamics of quantum measurements employing two Curie-Weiss apparatuses.
Two types of quantum measurements, measuring the spins of an entangled pair and attempting to measure a spin at either of two positions, are analysed dynamically by apparatuses of the Curie-Weiss type. The outcomes comply with the standard postulates.This article is part of the themed issue 'Second quantum revolution: foundational questions'.


Synthesis and Exfoliation of a New Layered Mesoporous Zr-MOF Comprising Hexa- and Dodecanuclear Clusters as Well as a Small Organic Linker Molecule.
A new layered mesoporous Zr-MOF of composition [Zr30O20(OH)26(OAc)18L18] was synthesized by employing 5-acetamidoisophthalic acid (H2L) using acetic acid as the solvent. The new MOF, denoted as CAU-45, exhibits a honeycomb structure of stacked layers which comprise both hexa- and dodecanucelar zirconium clusters. Its structure was solved from submicrometer-sized crystals by continuous rotation electron diffraction (cRED). Liquid phase exfoliation and size selection were successfully performed on the material.


Implications of cellobiohydrolase glycosylation for use in biomass conversion.
The cellulase producing ascomycete, Trichoderma reesei (Hypocrea jecorina), is known to secrete a range of enzymes important for ethanol production from lignocellulosic biomass. It is also widely used for the commercial scale production of industrial enzymes because of its ability to produce high titers of heterologous proteins. During the secretion process, a number of post-translational events can occur, however, that impact protein function and stability. Another ascomycete, Aspergillus niger var. awamori, is also known to produce large quantities of heterologous proteins for industry. In this study, T. reesei Cel7A, a cellobiohydrolase, was expressed in A. niger var. awamori and subjected to detailed biophysical characterization. The purified recombinant enzyme contains six times the amount of N-linked glycan than the enzyme purified from a commercial T. reesei enzyme preparation. The activities of the two enzyme forms were compared using bacterial (microcrystalline) and phosphoric acid swollen (amorphous) cellulose as substrates. This comparison suggested that the increased level of N-glycosylation of the recombinant Cel7A (rCel7A) resulted in reduced activity and increased non-productive binding on cellulose. When treated with the N-glycosidase PNGaseF, the molecular weight of the recombinant enzyme approached that of the commercial enzyme and the activity on cellulose was improved.


Comparative transcriptome findings reveal the neuroinflammatory network and potential biomarkers to early detection of ischemic stroke.
Ischemic stroke accounts for 70-80% of all stroke cases, leading to over two million people dying every year. Poor diagnosis and late detection are the major causes of the high death and disability rate. In the present study, we used the middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomic analysis, followed by a systematic advanced bioinformatic analysis, including gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA). We aimed to identify novel biomarkers for the early detection of ischemic stroke. In addition, we aimed to delineate the molecular mechanisms underlying the development of ischemic stroke, in which we hoped to identify novel therapeutic targets for treating ischemic stroke. In the comparative transcriptomic analysis, we identified 2657 differentially expressed genes (DEGs) in the brain tissue of the MCAO model. The gene enrichment analysis highlighted the importance of these DEGs in oxygen regulation, neural functions, and inflammatory and immune responses. We identified the elevation of angiopoietin-2 and leptin receptor as potential novel biomarkers for early detection of ischemic stroke. Furthermore, the result of IPA suggested targeting the inflammasome pathway, integrin-linked kinase signaling pathway, and Th1 signaling pathway for treating ischemic stroke. The results of the present study provide novel insight into the biomarkers and therapeutic targets as potential treatments of ischemic stroke.


Vertical profiles of community and activity of methanotrophs in landfill cover soils of different age.
Aerobic CH4 oxidation is an important process controlling CH4 release from landfills to the atmosphere. The aim of this study was to investigate the link between CH4 oxidation activity and methanotrophs abundance and diversity in landfill cover soils of different age. Among the three investigated sites, the highest CH4 emission occurred at the active landfill area with the range of 1371-2242 mg m(-2) day. The CH4 oxidation activities of landfill cover soils were 1·07-1·21 μmol g(-1) h(-1) in the landfill area of 7-16 years, which was 7-17 times higher than those in the active landfill area. The relative abundance of methanotrophs assessed by quantification of pmoA gene was about 1·7 × 10(6) -2·4 × 10(7) copies g(-1) in the landfill cover soils. The CH4 oxidation activity was positively correlated with pmoA copy number in the landfill cover soil of each site, respectively. Type II methanotrophs (Methylocystis) and type I methanotrophs including Methylosoma, Methylocaldum and Methylococcus were all present in the landfill cover soils. Compared to type I methanotroph, type II methanotroph, Methylocystis, was more abundant in the acidic landfill cover soils. Oxidation activity and community structure of methanotrophs varied with depth and age of landfill cover soils. These findings provide new fundamental information regarding the activity and diversity of methanotrophs in landfill cover soils of different age that may aid predicting and modelling CH4 flux from landfills.


Differences in the origins of kinetochore-positive and kinetochore-negative micronuclei: A live cell imaging study.
Micronuclei (MNi) are extensively used to evaluate genotoxicity and chromosomal instability. Classification of kinetochore-negative (K-MNi) and kinetochore-positive micronuclei (K+MNi) improves the specificity and sensitivity of the micronucleus (MN) test; however, the fundamental differences in the origins of K-MNi and K+MNi have not been addressed due to the limitations of traditional methods. In the current study, HeLa CENP B-GFP H2B-mCherry cells were constructed in which histone 2B (H2B) and centromere protein B (CENP B) were expressed as fusion proteins to monomeric Cherry (mCherry) and EGFP, respectively. MNi were identified using H2B-mCherry; K+MN contained CENP B-GFP, while K-MN did not. Long-term live cell imaging was conducted to examine MN formation in the dual-color fluorescent HeLa cells. The results suggested that K-MNi were derived from kinetochore-negative displaced chromosomes (K-DCs), kinetochore-negative lagging chromosomes (K-LCs) and fragments of broken chromosome bridges (CBs) during late mitotic stages. The results also indicated that K+MNi are derived from kinetochore-positive displaced chromosomes (K+DCs), kinetochore-positive lagging chromosomes (K+LCs), and fragments of broken CBs. Different aberrant chromosomes emerged during mitosis at different frequencies and developed into K-MNi and/or K+MNi in the daughter cells at different rates. K+LCs formed K+MNi at a higher frequency than K+DCs, and K-LCs formed K-MNi at a higher rate than K-DCs; however, broken CBs transformed into K-MNi and/or K+MNi. In summary, these results show that K-MNi and K+MNi have different origins in HeLa cells and that each mechanism of MN formation contributes differently to the overall number of K-MNi and K+MNi.


Multistage classification identifies altered cortical phase- and amplitude-coupling in Multiple Sclerosis.
Distinguishing groups of subjects or experimental conditions in a high-dimensional feature space is a common goal in modern neuroimaging studies. Successful classification depends on the selection of relevant features as not every neuronal signal component or parameter is informative about the research question at hand. Here, we developed a novel unsupervised multistage analysis approach that combines dimensionality reduction, bootstrap aggregating and multivariate classification to select relevant neuronal features. We tested the approach by identifying changes of brain-wide electrophysiological coupling in Multiple Sclerosis. Multiple Sclerosis is a demyelinating disease of the central nervous system that can result in cognitive decline and physical disability. However, related changes in large-scale brain interactions remain poorly understood and corresponding non-invasive biomarkers are sparse. We thus compared brain-wide phase- and amplitude-coupling of frequency specific neuronal activity in relapsing-remitting Multiple Sclerosis patients (n = 17) and healthy controls (n = 17) using magnetoencephalography. Changes in this dataset included both, increased and decreased phase- and amplitude-coupling in wide-spread, bilateral neuronal networks across a broad range of frequencies. These changes allowed to successfully classify patients and controls with an accuracy of 84%. Furthermore, classification confidence predicted behavioral scores of disease severity. In sum, our results unravel systematic changes of large-scale phase- and amplitude coupling in Multiple Sclerosis. Furthermore, our results establish a new analysis approach to efficiently contrast high-dimensional neuroimaging data between experimental groups or conditions.


Inhibitory effect of imperatorin on insulin-like growth factor-1-induced sebum production in human sebocytes cultured in vitro.
Acne is a common skin disease that originates in the sebaceous gland. The pathogenesis of acne is very complex, involving the increase of sebum production and perifollicular inflammation. In this study, we screened the anti-lipogenic material and demonstrated its effect using cultured human sebocytes. Normal human sebocytes were cultured by explanting the sebaceous glands. To evaluate the anti-lipogenic effect, sebocytes were treated with test materials and (14)C-acetate incorporation assay was performed. To screen the anti-lipogenic materials, we tested the effect of many herbal plant extracts. We found that Angelica dahurica extract inhibited the insulin-like growth factor-1 (IGF-1)-induced sebum production in terms of squalene synthesis in sebocytes. Furthermore, imperatorin isolated from A. dahurica showed remarkable inhibitory effect on squalene production as well as squalene synthase promoter activity. To investigate the putative action mechanism, we tested the effect of imperatorin on intracellular signaling. The results showed that imperatorin inhibited IGF-1-induced phosphorylation of Akt. In addition, imperatorin significantly down-regulated PPAR-γ and SREBP-1, the important transcription factors for lipid synthesis. These results suggest that imperatorin has a potential for reducing sebum production in sebocytes, and can be applicable for acne treatment.


Detection of antibodies against benzo[a]pyrene in blood sera of lung cancer patients by ELISA using human recombinant idiotypic and anti-idiotypic antibodies.
Aim of this study was to develop and apply an ELISA method for assessment of the levels of endogenous antibodies against benzo[a]pyrene (Bp) in blood sera of lung cancer (LC) patients. ELISA was developed and applied for the detection of endogenous idiotypic and anti-idiotypic antibodies against Bp in human blood sera using recombinant human idiotypic and anti-idiotypic antibodies against Bp. Serum samples of LC patients (n = 22) and healthy donors (n = 24) were analyzed by the new method. Statistical analysis showed that in sera of LC patients the levels of endogenous idiotypic and anti-idiotypic antibodies against Bp were significantly higher than in healthy donors. A logistic regression model for the LC detection utilizing such predictors as the serum levels of idiotypic and anti-idiotypic antibodies against Bp, smoking status, and age, identified LC patients with 83% specificity and 82% sensitivity. The proposed method could be further developed as additional lung cancer screening tool.


K(2)CO(3)-catalyzed Michael addition-lactonization reaction of 1,2-allenyl ketones with electron-withdrawing group substituted acetates. An efficient synthesis of alpha-pyrone derivatives.
[reaction: see text] Alpha-pyrone derivatives were synthesized via the base catalyzed or promoted reaction of 1,2-allenyl ketones and electron-withdrawing group substituted acetates. The reaction was believed to proceed through a Michael addition C-C double-bond migration-lactonization process.


Reported lactose tolerance of members of various racial/ethnic groups in Hawaii and Asia.
Subjects from various racial/ethnic groups in Hawaii and homeland Chinese, Japanese, and Koreans reported on their milk drinking in childhood and adulthood, as well as on whether or not milk drinking produced symptoms of intolerance. Intolerance was comparatively infrequent in all groups, although significant differences existed between groups in the frequency with which they manifested symptoms and in discomfort scores. Differences between Hawaiian subjects of Asian ancestry and homeland Asians in the frequency of reported symptoms, in mean discomfort scores, and in amount of milk needed to produce symptoms, as well as the high proportion of symptomatology among Hapa-Haoles (persons of Caucasian and Oriental ancestry) and other data reported herein, are not supportive of the usual genetic explanation of lactose tolerance and are supportive of the belief that dietary practice influences tolerance.


Combination therapies in multiple sclerosis.
The last years have seen enormous progress in our understanding of pathophysiology of multiple sclerosis. In addition, the armamentarium of available immunomodulatory or immunosuppressive therapies has greatly increased, especially for the relapsing remitting form of the disease. Since their therapeutic efficacy is often limited in individual patients, it is conceivable that combination therapies may bring improved clinical efficacy while managing increasing side effects and toxicity. The combination of agents with additive or synergistic modes of action is of particular interest. Combination of the two classes of recognised firstline treatment, a beta-interferon and glatiramer acetate is currently under evaluation in a large Phase III trial. However, there are theoretical reasons for thinking that such a combination may not be particularly beneficial. None of the combination studies performed with beta-interferons to date have shown unequivocal evidence of benefit, including combinations with statins, natalizumab and azathioprine. On the other hand, for glatiramer acetate, the combination with mitoxantrone used as induction therapy may be of interest and preliminary data on combination with minocycline are also promising.


Comprehension and Data-Sharing Behavior of Direct-To-Consumer Genetic Test Customers.
The aim of this study was to evaluate current direct-to-consumer (DTC) genetic customers' ability to interpret and comprehend test results and to determine if honest brokers are needed. One hundred and twenty-two customers of the DTC genetic testing company 23andMe were polled in an online survey. The subjects were asked about their personal test results and to interpret the results of two mock test cases (type 2 diabetes and multiple sclerosis), where results were translated into disease probability for an individual compared to the public. When asked to evaluate the risk, 72.1% correctly assessed the first case and 77% were correct on the second case. Only 23.8% of those surveyed were able to interpret both cases correctly. x03C7;2 and logistic regression were used to interpret the results. Participants who took the time to read the DTC test-provided supplemental material were 3.93 times (p = 0.040) more likely to correctly interpret the test results than those who did not. The odds for correctly interpreting the test cases were 3.289 times (p = 0.011) higher for those who made more than USD 50,000 than those who made less. Survey results were compared to the Health Information National Trends Survey (HINTS) phase 4 cycle 3 data to evaluate national trends. Most of the subjects were able to correctly interpret the test cases, yet a majority did not share their results with a health-care professional. As the market for DTC genetic testing grows, test comprehension will become more critical. Involving more health professionals in this process may be necessary to ensure proper interpretations.


Epidemiology of Insomnia: Prevalence, Course, Risk Factors, and Public Health Burden.
This article summarizes epidemiologic evidence on insomnia, including the prevalence, incidence, and risk factors, as well as its course and consequences. Approximately 10% of the adult population suffers from an insomnia disorder and another 20% experiences occasional insomnia symptoms. Women, older adults, and people with socioeconomic hardship are more vulnerable to insomnia. Insomnia is often a chronic condition, with a 40% persistence rate over a 5-year period. Insomnia is a significant public health problem that should be addressed at the individual level with appropriate clinical care and at the population level with large-scale sleep health interventions.


Prospective evaluation of a protocol for using transabdominal ultrasound to screen for short cervix.
We sought to evaluate a recently proposed protocol whereby transabdominal ultrasound of the cervix might be used as a prescreen to select women to undergo or to forgo measurement of cervical length via transvaginal ultrasound (CLvag). This was a prospective cohort study. Measurements of cervical length via transabdominal ultrasound (CLabd) and CLvag were made in women with singleton pregnancy during routine obstetrical ultrasound examination at 18(0/7) to 23(6/7) weeks of gestation. The transabdominal screen was considered positive if CLabd was ≤36 mm with the maternal bladder full or ≤35 mm with the bladder empty, or adequate imaging of the cervix could not be obtained. Sensitivity, specificity, predictive values, and likelihood ratios of a positive screen to detect a short cervix (CLvag ≤25 mm) were calculated. An interim analysis identified several technical problems with CLabd measurements, so the protocol was extensively revised. Under the revised protocol, 1580 women were included. Adequate views of the cervix were obtained via transabdominal imaging in 46% of subjects with the bladder empty and 56% with the bladder full. The correlation between CLabd and CLvag was poor (r = 0.38). Of the 17 patients with a short cervix, 15 had suboptimal transabdominal exams (screen positive) and 2 had CLabd ≤35 mm with bladder empty (screen positive). Sensitivity of the screen was 100% (95% confidence interval, 80.5-100%) but specificity was only 32.2% (95% confidence interval, 29.9-34.6%) and screen positive rate was 66.3%. Several technical problems and limitations of transabdominal imaging of the cervix are shown. Using modern, high-resolution ultrasound equipment, we were unable to adequately image the cervix via transabdominal ultrasound in half the cases. Although we confirmed that a CLabd cutoff value of 35-36 mm is appropriate for detection of short cervix, the technique for measuring CLabd is fraught with technical problems. Practitioners must validate the technique in their own practice before adopting this or similar prescreening protocols. We decided not to adopt this protocol.


Isolation of a secY homologue from Bacillus subtilis: evidence for a common protein export pathway in eubacteria.
Genetic and biochemical studies have shown that the product of the Escherichia coli secY gene is an integral membrane protein with a central role in protein secretion. We found the Bacillus subtilis secY homologue within the spc-alpha ribosomal protein operon at the same position occupied by E. coli secY. B. subtilis secY coded for a hypothetical product 41% identical to E. coli SecY, a protein thought to contain 10 membrane-spanning segments and 11 hydrophilic regions, six of which are exposed to the cytoplasm and five to the periplasm. We predicted similar segments in B. subtilis SecY, and the primary sequences of the second and third cytoplasmic regions and the first, second, fourth, fifth, seventh, and tenth membrane segments were particularly conserved, sharing greater than 50% identity with E. coli SecY. We propose that the conserved cytoplasmic regions interact with similar cytoplasmic secretion factors in both organisms and that the conserved membrane-spanning segments actively participate in protein export. Our results suggest that despite the evolutionary differences reflected in cell wall architecture, Gram-negative and Gram-positive bacteria possess a similar protein export apparatus.


Enhanced β-Amyrin Synthesis in Saccharomyces cerevisiae by Coupling An Optimal Acetyl-CoA Supply Pathway.
β-Amyrin is a plant-derived triterpenoid skeleton with wide applications in food and medical industry. β-Amyrin biosynthesis in Saccharomyces cerevisiae is derived from the mevalonate pathway with cytosolic acetyl-CoA as a precursor. In this work, endogenous and several heterologous acetyl-CoA synthesis pathways were coupled to β-amyrin production and a combinational acetyl-CoA supply route was demonstrated to be optimal due to more balanced redox cofactors, much lower energy consumption, and glucose utilization as well as significantly enhanced β-amyrin production (a 200% increase compared to the original β-amyrin-producing strain). Further disruption of an acetyl-CoA competing pathway led to a 330% increase in β-amyrin production as compared to the original strain. Finally, the engineered strain harboring the optimal pathway configuration achieved a final β-amyrin production of 279.0 ± 13.0 mg/L in glucose fed-batch fermentation, which is the highest as ever reported. This work provides an efficient platform for triterpenoid biosynthesis in Saccharomyces cerevisiae.


Preliminary investigation of the use of newborn dried blood spots for screening pyridoxine-dependent epilepsy by LC-MS/MS.
α-AASA and P6C were measured retrospectively in original newborn DBS of five patients with PDE using a LC-MS/MS method we developed previously. Both α-AASA and P6C were elevated markedly in the three newborn DBS stored at -20°C. At room temperature, α-AASA and P6C in DBS appeared stable for 3 days and then decreased by up to 70% after 14 days but remained much higher than control, indicating newborn screening for PDE is feasible.


Comparison of weight captured via electronic health record and cellular scales to the gold-standard clinical method.
Obtaining body weights remotely could improve feasibility of pragmatic trials. This investigation examined whether weights collected via cellular scale or electronic health record (EHR) correspond to gold standard in-person study weights. The agreement of paired weight measurements from cellular scales were compared to study scales from a weight loss intervention and EHR-collected weights were compared to study scales from a weight loss maintenance intervention. Differential weight change estimates between intervention and control groups using both pragmatic methods were compared to study collected weight. In the Log2Lose feasibility weight loss trial, in-person weights were collected bi-weekly and compared to weights collected via cellular scales throughout the study period. In the MAINTAIN weight loss maintenance trial, in-person weights were collected at baseline, 14, 26, 42 and 56 weeks. All available weights from the EHR during the study period were obtained. On average, in Log2Lose cellular scale weights were 0.6 kg (95% CI: -2.9, 2.2) lower than in-person weights; in MAINTAIN, EHR weights were 2.8 kg (SE: -0.5, 6.0) higher than in-person weights. Estimated weight change using pragmatic methods and study scales in both studies were in the same direction and of similar magnitude. Both methods can be used as cost-effective and real-world surrogates within a tolerable variability for the gold-standard. NCT02691260; NCT01357551.


The time-dependent protective effect of hyperbaric oxygen on neuronal cell apoptosis in carbon monoxide poisoning.
The progressive clinical course with delayed neurological damage in carbon monoxide (CO) poisoning may be due to neuron apoptosis. The usefulness of hyperbaric oxygen (HBO) in different time periods after CO exposure in neuronal cell apoptosis reduction has not been evaluated thus far. The aim was to evaluate HBO efficacy in reducing neuronal apoptosis in different time periods after CO exposure. Wistar rats were exposed to 3000 ppm CO in air for 60 min and 100% oxygen at a pressure of three bar for 30 min 0-12 h after CO exposure. The apoptosis was evaluated by immunohistochemical analysis with antibodies against activated caspase-3 and the percentage of caspase-3 positive hippocampal ganglionic cells was reported. It was shown that CO poisoning results in ganglionic cell apoptosis. The percentage of apoptotic cells in rats exposed to CO was the highest (32%), whereas the percentage of apoptotic cells in rats exposed to HBO 0 and 1 h after CO was similar with a lower percentage than rats exposed to CO. The percentage of apoptotic cells in rats exposed to HBO 3 and 5 h after CO was similar with a lower percentage than rats exposed to HBO 0 and 1 h after CO. The percentage of apoptotic cells in rats exposed to HBO 7-12 h after CO was similar with a higher percentage than rats exposed to HBO 5 h after CO. HBO has a time-dependent protective effect on CO-induced neuron apoptosis with the highest efficiency at 3 and 5 h after CO poisoning.


Cell cycle and enzymatic activity alterations induced by ROS production in human neuroblastoma cells SH-SY5Y exposed to Fumonisin B1, Ochratoxin A and their combination.
The presence of mycotoxins such as Fumonisin B1(FB1) and Ochratoxin A (OTA) in food and feed has become a threat to human and animal health since they can produce several afflictions. Different mechanisms of action by which they exercise their cytotoxic activity have been attributed to them, including the production of reactive oxygen species (ROS). For this reason, a measurement of the production of ROS species, and an evaluation of the intrinsic cell enzymatic antioxidant activity, including glutathione peroxidase (GPx), glutathione transferase (GTS), and catalase (CAT) together with a cytotoxicity and cell cycle assay have been performed in undifferentiated SH-SY5Y cells exposed to FB1, OTA and [FB1 + OTA] after 24 h and 48 h. FB1 and OTA. Monitoring of intracellular ROS production was carried out by the H2-DCFDA probe; while spectrometry analysis of absorbances was used for measuring GPx, GST and CAT activity. Finally, cell proliferation and cell cycle distribution were studied by flow cytometry. When cells were treated with OTA, an increase in GPx and GST activity was observed compared to FB1 and [FB1 + OTA]; conversely, a decrease in CAT activity was observed when cells were exposed to OTA coinciding with the results observed for ROS measurement. Regarding the cell cycle, when cells were exposed to OTA, a decrease in G0/G1 was detected, revealing an arrest of cell division for SH-SY5Y cells at the concentrations studied.


The siRNA-Mediated Down-Regulation of Vascular Endothelial Growth Factor Receptor1.
Angiogenesis is an important biological process involved in the proliferation of endothelial cells, tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is considered as a prominent regulator of angiogenesis which exerts the aforementioned effect(s) through its respective receptors (VEGFR1 and VEGFR2). VEGF receptors are targeted as a therapeutic candidate for cancer growth inhibition. RNAi as a new and promising strategy has provided a useful means to specifically suppress gene expression in cancer cells. The current study aimed to down-regulate expression of the VEGFR1 using siRNA. This experimental study designed specific siRNAs against VEGFR1. Total RNA was extracted from human umbilical vain endothelial cell (HUVEC) and subsequently cDNA was synthetized. PCR was performed using specific primers to amplify the target gene. After double digestion and purification, the gene was cloned into pEFGP-N1 expression vector. Then, AGS cells were transfected with recombinant pEGFP-N1 using lipofectamin. The gene expression and down-regulation were evaluated by fluorescence scanning, reverse transcription PCR (RT-PCR) and Western blot techniques. Fluorescent scanning, RT-PCR (27.68%) and western blot analysis (31.06%) showed that the expression of VEGFR1 was suppressed effectively. The results of the current study showed that specifically designed siRNA can be considered as an appropriate strategy to suppress gene expression and might be a promising tool to prevent angiogenesis.


TNT particle size distributions from detonated 155-mm howitzer rounds.
To achieve sustainable range management and avoid or minimize environmental contamination, the Army needs to know the amount of explosives deposited on ranges from different munitions and how these are degraded and transported under different geological and climatic conditions. The physical form of the deposited explosives has a bearing on this problem, yet the shapes and size distributions of the explosive particles remaining after detonations are not known. We collected residues from 8 high-order and 6 low-order non-tactical detonations of TNT-filled 155-mm rounds. We found significant variation in the amount of TNT scattered from the high-order detonations, ranging from 0.00001 to 2% of the TNT in the original shell. All low-order detonations scattered percent-level amounts of TNT. We imaged thousands of TNT particles and determined the size, mass and surface-area distributions of particles collected from one high-order and one low-order detonation. For the high-order detonation, particles smaller than 1 mm contribute most of the mass and surface area of the TNT scattered. For the low-order detonation, most of the scattered TNT mass was in the form of un-heated, centimeter-sized pieces whereas most of the surface area was again from particles smaller than 1 mm. We also observed that the large pieces of TNT disintegrate readily, giving rise to many smaller particles that can quickly dissolve. We suggest picking up the large pieces of TNT before they disintegrate to become point sources of contamination.


A comparison of clinical manifestations of Japanese encephalitis between children and adults in Gansu Province, Northwest China (2005-2020).
Japanese encephalitis (JE), a mosquito-borne zoonotic disease, has emerged as a major public health concern around the world. Previous research has shown that JE has serious sequelae, and the recent shift in the population from children to adults presents a significant challenge for JE treatment and prevention. Therefore, we examined the differences in clinical manifestations (clinical symptoms, clinical signs, complications, and clinical typing) of JE between children and adults over the 15 years in Gansu Province to provide a theoretical basis for better response to JE treatment. Clinical typing was found to be statistically significant in the child versus adult groups and the groups with or without vaccination. Only the dysfunction of consciousness differed statistically between children with and without vaccination, whereas neurological symptoms such as vomiting (jet vomiting), irritability, drowsiness, convulsions, and hyperspasmia differed statistically between children and adults, and the rest of the symptoms did not differ statistically. Only pupil size changes were statistically different in clinical signs between the children with and without vaccination, while blood pressure changes, change in pupil size, positive meningeal stimulation signs, and positive pathological reflexes (increased muscle tone and Babinski's sign) were statistically different between adults and children. Bronchopneumonia was the most common complication, especially in adults. Therefore, the authors believe that children and adults differ in some clinical manifestations and propose that efforts should be directed toward developing individualized treatment plans for different age groups and employing more effective supportive treatment for various populations. In addition, we suggest expanding the coverage of the JE vaccine and increasing overall vaccination rates and adopting multiple measures in conjunction with JE prevention and control.


The management of bone defect using long non-coding RNA as a potential biomarker for regulating the osteogenic differentiation process.
Tissue engineered bone brings hope to the treatment of bone defects, and the osteogenic differentiation of stem cells is the key link. Inducing osteogenic differentiation of stem cells may be a potential approach to promote bone regeneration. In recent years, lncRNA has been studied in the field increasingly, which is believed can regulate cell cycle, proliferation, metastasis, differentiation and immunity, participating in a variety of physiology and pathology processes. At present, it has been confirmed that certain lncRNAs regulate the osteogenesis of stem cells and take part in mediating signaling pathways including Wnt/β-catenin, MAPK, TGF-β/BMP, and Notch pathways. Here, we provided an overview of lncRNA, reviewed its researches in the osteogenic differentiation of stem cells, emphasized the importance of lncRNA in bone regeneration, and focused on the roles of lncRNA in signaling pathways, in order to make adequate preparations for applying lncRNA to bone tissue Engineering, letting it regulate the osteogenic differentiation of stem cells for bone regeneration.


Synthesis of elements with fractional-order impedance based on homogenous distributed resistive-capacitive structures and genetic algorithm.
The work proposes a synthesis method of capacitive fractional-order impedance element which is composed of homogenous distributed resistive-capacitive (RC) structures (lines). The method employs genetic algorithm and searches for optimal connection schemes and parameters of the partial RC structures. The synthesis algorithm is described in detail including the coding of the properties of the structures for the purpose of the genetic algorithm. The user interface of the design tool is introduced and the input and output parameters of the synthesis are explained. The algorithm was verified by computer simulations and particularly by measurements of element samples fabricated in thick-film technology. The results correspond to the required impedance characteristics, which confirm the validity of the synthesis method.


Activation and aponeurosis morphology affect in vivo muscle tissue strains near the myotendinous junction.
Hamstring strain injury is one of the most common injuries in athletes, particularly for sports that involve high speed running. The aims of this study were to determine whether muscle activation and internal morphology influence in vivo muscle behavior and strain injury susceptibility. We measured tissue displacement and strains in the hamstring muscle injured most often, the biceps femoris long head muscle (BFLH), using cine DENSE dynamic magnetic resonance imaging. Strain measurements were used to test whether strain magnitudes are (i) larger during active lengthening than during passive lengthening and (ii) larger for subjects with a relatively narrow proximal aponeurosis than a wide proximal aponeurosis. Displacement color maps showed higher tissue displacement with increasing lateral distance from the proximal aponeurosis for both active lengthening and passive lengthening, and higher tissue displacement for active lengthening than passive lengthening. First principal strain magnitudes were averaged in a 1cm region near the myotendinous junction, where injury is most frequently observed. It was found that strains are significantly larger during active lengthening (0.19 SD 0.09) than passive lengthening (0.13 SD 0.06) (p<0.05), which suggests that elevated localized strains may be a mechanism for increased injury risk during active as opposed to passive lengthening. First principal strains were higher for subjects with a relatively narrow aponeurosis width (0.26 SD 0.15) than wide (0.14 SD 0.04) (p<0.05). This result suggests that athletes who have BFLH muscles with narrow proximal aponeuroses may have an increased risk for BFLH strain injuries.


Knowledge and behaviors of veterinary students about rabies: A descriptive study from Turkey.
This study aimed to obtain data on the knowledge, behavior, and immunization status of veterinary students about rabies. The population of this descriptive study consisted of all the 770 students of a veterinary faculty (response rate 85.7%; n = 660). A survey was conducted querying the knowledge and behaviors of the participants about rabies. Of the surveyed students 28.6% (n = 189) stated that they were exposed to animal bites at least once, and 50.3% (n = 95) of these students stated that they were vaccinated following the exposure. Of the participants, 23.6% (n = 156) indicated that they received protective rabies treatment (prophylactic vaccination). About 32.9% (n = 217) of the students taking part in the study had pets at home. Around 70.7% (n = 153) of these students stated that their animals were vaccinated against rabies. A significant relationship was found between having a pet and being bitten by an animal (P < 0.001). 50.5% (n = 333) of the students who participated in the study were competent in knowledge, while 48.3% were competent in behavior. Students competent in knowledge or behavior were considerably more in the clinical classes compared to preclinical classes. A significant relationship in favor of men was found between the sexes concerning both knowledge and behavior levels. The study revealed deficiencies in the students' awareness levels regarding rabies. Ascertaining a sufficient amount of theory and practice courses on rabies in the veterinary faculty curriculum, starting from earlier classes will contribute to the knowledge and behaviors of the students.


A sensitive aptasensor for adenosine based on the quenching of Ru(bpy)(3)(2+)-doped silica nanoparticle ECL by ferrocene.
A reusable signal on aptasensor for adenosine based on the quenching of Ru-SNPs electrochemiluminescence by ferrocene was developed.


Monitoring of fracture healing. Update on current and future imaging modalities to predict union.
Fracture nonunion causes considerable patient morbidity and an associated burden to society. Traditional reliance on radiographs to monitor union has limitations as bridging callus of long bone fractures can take three or more months to occur. Computed Tomographic (CT) scanning is becoming increasingly popular and can evaluate bridging callus in the late stages of healing to confirm union. The use of dynamic contrast enhanced Magnetic Resonance Imaging (MRI) and advances in nuclear imaging may yield benefits in the assessment of the infected nonunion. Emerging evidence supports the use of ultrasound to detect bridging callus prior to radiographic confirmation and it may be of use to predict patients at high risk of nonunion. This paper is part of a Supplement supported by The Osteosynthesis and Trauma Care Foundation (OTCF).


Cytotoxic T lymphocyte lines reactive against murine plasmacytoma antigens: dissociation of cytotoxicity and Lyt-2 expression.
The relationship between cell surface antigen expression and function in cytotoxic T cells directed against a non-H-2-restricted plasmacytoma antigen was examined using Lyt-2- variants of a continuous T cell line. This cytotoxic cell line originally had expressed Lyt-2 on all the cells as detected by flow microfluorometry, but after several months of culture, Lyt-2- variants spontaneously developed. Using cell sorting and limiting dilution cloning, Lyt-2- and Lyt-2+ cell lines were obtained, cultured and analyzed. These analyses indicated that such cytotoxic cells had similar activity regardless of Lyt-2 phenotype. This observation supports the concept that the Lyt-2 molecule is not obligatory for recognition and killing by cytotoxic T cells and emphasizes the need to clarify the precise relationship between cell surface phenotype and T cell function.


Mex3B: a coreceptor to present dsRNA to TLR3.
Toll-Like Receptors (TLRs) play critical roles in the early innate immune response to invading pathogens by sensing microorganisms; a number of accessory molecules have been shown to assist microbial recognition by TLRs. In a recent paper in Cell Research, Yang et al. demonstrate that Mex3B is associated with TLR3 in the endosomes and promotes dsRNA binding and proteolytic processing of TLR3, suggesting that Mex3B acts as a coreceptor of TLR3 in response to dsRNA.


Acute and additive toxicity of ten photosystem-II herbicides to seagrass.
Photosystem II herbicides are transported to inshore marine waters, including those of the Great Barrier Reef, and are usually detected in complex mixtures. These herbicides inhibit photosynthesis, which can deplete energy reserves and reduce growth in seagrass, but the toxicity of some of these herbicides to seagrass is unknown and combined effects of multiple herbicides on seagrass has not been tested. Here we assessed the acute phytotoxicity of 10 PSII herbicides to the seagrass Halophila ovalis over 24 and/or 48 h. Individual herbicides exhibited a broad range of toxicities with inhibition of photosynthetic activity (∆F/F(m)') by 50% at concentrations ranging from 3.5 μg l(-1) (ametryn) to 132 μg l(-1) (fluometuron). We assessed potential additivity using the Concentration Addition model of joint action for binary mixtures of diuron and atrazine as well as complex mixtures of all 10 herbicides. The effects of both mixture types were largely additive, validating the application of additive effects models for calculating the risk posed by multiple PSII herbicides to seagrasses. This study extends seagrass ecotoxicological data to ametryn, metribuzin, bromacil, prometryn and fluometuron and demonstrates that low concentrations of PSII herbicide mixtures have the potential to impact ecologically relevant endpoints in seagrass, including ∆F/F(m)'.


Defensive style and treatment outcome among men alcoholics.
In a follow-up study of alcoholic patients, those with higher levels of denial had lower rates of rehospitalization and higher rates of treatment completion than those who relied on other defense mechanisms.


Precision, time, and cost: a comparison of three sampling designs in an emergency setting.
The conventional method to collect data on the health, nutrition, and food security status of a population affected by an emergency is a 30 x 30 cluster survey. This sampling method can be time and resource intensive and, accordingly, may not be the most appropriate one when data are needed rapidly for decision making. In this study, we compare the precision, time and cost of the 30 x 30 cluster survey with two alternative sampling designs: a 33 x 6 cluster design (33 clusters, 6 observations per cluster) and a 67 x 3 cluster design (67 clusters, 3 observations per cluster). Data for each sampling design were collected concurrently in West Darfur, Sudan in September-October 2005 in an emergency setting. Results of the study show the 30 x 30 design to provide more precise results (i.e. narrower 95% confidence intervals) than the 33 x 6 and 67 x 3 design for most child-level indicators. Exceptions are indicators of immunization and vitamin A capsule supplementation coverage which show a high intra-cluster correlation. Although the 33 x 6 and 67 x 3 designs provide wider confidence intervals than the 30 x 30 design for child anthropometric indicators, the 33 x 6 and 67 x 3 designs provide the opportunity to conduct a LQAS hypothesis test to detect whether or not a critical threshold of global acute malnutrition prevalence has been exceeded, whereas the 30 x 30 design does not. For the household-level indicators tested in this study, the 67 x 3 design provides the most precise results. However, our results show that neither the 33 x 6 nor the 67 x 3 design are appropriate for assessing indicators of mortality. In this field application, data collection for the 33 x 6 and 67 x 3 designs required substantially less time and cost than that required for the 30 x 30 design. The findings of this study suggest the 33 x 6 and 67 x 3 designs can provide useful time- and resource-saving alternatives to the 30 x 30 method of data collection in emergency settings.


Near-field dynamics and plume dispersion after an on-road truck: Implication to remote sensing.
Apart from the aerodynamic performance (efficiency and safety), the wake after an on-road vehicle substantially influences the tailpipe pollutant dispersion (environment). Remote sensing is the most practicable measures for large-scale emission control. Its reliability, however, is largely dictated by how well the complicated vehicular flows and instrumentation constraint are tackled. Specifically, the broad range of motion scales and the short sampling duration (less than 1 s) are the most prominent ones. Their impact on remote sensing has not been studied. Large-eddy simulation (LES) is thus employed in this paper to look into the dynamics and the plume dispersion after an on-road heavy-duty truck at speed U∞ so as to elucidate the transport mechanism, examine the sampling uncertainty and develop the remedial measures. A major recirculation of size comparable to the truck height h is induced collectively by the roof-level prevailing flows, side entrainment and underbody wall jet. The tailpipe is enclosed by dividing streamlines so the plume is carried back to the truck right after emission. The recirculation augments the pollutant mixing, resulting in a more homogeneous pollutant distribution together with a rather high fluctuating concentration (over 20% of the time-averaged concentrations). The plume ascends mildly before being purged out of the major recirculation to the far field by turbulence, leading to a huge reduction in pollutant concentration (an order of magnitude) outside the near wake. In the far-field, the plume is higher than the tailpipe and disperses in a conventional Gaussian distribution manner. Under this circumstance, a sampling duration for remote sensing longer than h/U∞ would be prone to underestimating the tailpipe emission.


Impact of area-level socioeconomic status and accessibility to treatment on life expectancy after a cancer diagnosis in Queensland, Australia.
This study quantifies geographic inequities in loss of life expectancy (LOLE) by area-level socioeconomic status (SES) and accessibility to treatment. Analysis was conducted using a population-based cancer-registry cohort (n = 371,570) of Queensland (Australia) residents aged 50-89 years, diagnosed between 1997-2016. Flexible parametric survival models were used to estimate LOLE by area-level SES and accessibility for all invasive cancers and the five leading cancers. The gain in life years that could be achieved if all cancer patients experienced the same relative survival as those in the least disadvantaged-high accessibility category was estimated for the 2016 cohort. For all invasive cancers, men living in the most disadvantaged areas lost 34 % of life expectancy due to their cancer diagnosis, while those from the least disadvantaged areas lost 25 %. The corresponding percentages for women were 33 % and 23 %. Accessibility had a lower impact on LOLE than SES, with patients from low accessibility areas losing 0-4 % more life expectancy than those from high accessibility areas. For cancer patients diagnosed in 2016 (n = 24,423), an estimated 101,387 life years will be lost. This would be reduced by 19 % if all patients experienced the same relative survival as those from the least disadvantaged-high accessibility areas. The impact of a cancer diagnosis on remaining life expectancy varies by geographical area. Establishing reasons why area disadvantage impacts on life expectancy is crucial to inform subsequent interventions that could increase the life expectancy of cancer patients from more disadvantaged areas.


TAME trial: a multi-arm phase II randomised trial of four novel interventions for malnutrition enteropathy in Zambia and Zimbabwe - a study protocol.
Severe acute malnutrition (SAM) in children in many countries still carries unacceptably high mortality, especially when complicated by secondary infection or metabolic derangements. New therapies are urgently needed and we have identified mucosal healing in the intestine as a potential target for novel treatment approaches. The TAME trial (Therapeutic Approaches for Malnutrition Enteropathy) will evaluate four novel treatments in an efficient multi-arm single-blind phase II design. In three hospitals in Zambia and Zimbabwe, 225 children with SAM will be randomised to one of these treatments or to standard care, once their inpatient treatment has reached the point of transition from stabilisation to increased nutritional intake. The four interventions are budesonide, bovine colostrum or N-acetyl glucosamine given orally or via nasogastric tube, or teduglutide given by subcutaneous injection. The primary endpoint will be a composite score of faecal inflammatory markers, and a range of secondary endpoints include clinical and laboratory endpoints. Treatments will be given daily for 14 days, and evaluation of the major endpoints will be at 14 to 18 days, with a final clinical evaluation at 28 days. In a subset of children in Zambia, endoscopic biopsies will be used to evaluate the effect of interventions in detail. The study has been approved by the University of Zambia Biomedical Research Ethics Committee (006-09-17, dated 9th July, 2018), and the Joint Research Ethics Committee of the University of Zimbabwe (24th July, 2019). Caregivers will provide written informed consent for each participant. Findings will be disseminated through peer-reviewed journals, conference presentations and to caregivers at face-to-face meetings. NCT03716115; Pre-results.


Mammalian island biogeography: effects of area, isolation and vagility.
In this paper I reviewed mammalian biogeography for 19 archipelagoes and tested the applicability of the equilibrium theory of island biogeography to mammalian faunas in general. The species-area and species-isolation relationships of terrestrial mammals were consistent with the basic predictions of the equilibrium theory. The z-values for the species-area relationship did not differ significantly from Preston's canonical value of 0.26 (P>0.50), and the modal z-value for non-volant mammals was 0.25. Moreover, z-values increased with isolation and decreased with vagility of the fauna in question. Furthermore, the strength of the species-isolation correlation was negatively correlated with island area and vagility (P<0.001).


A descriptive analysis of first trimester urinary concentrations of 14 bisphenol analogues in the MIREC Canadian pregnancy cohort.
Concern over the health effects of BPA, particularly for the developing fetus, has led to an increasing use of bisphenol analogues in industrial and consumer products, which may be as hormonally active as BPA. Biomonitoring data for many bisphenol analogues, especially in pregnant populations, are limited. We measured concentrations of 14 bisphenol analogues in 1st trimester urine samples (n = 1851) from the Maternal-Infant Research on Environmental Chemicals (MIREC) Canadian pregnancy cohort (2008-2011). We examined patterns of exposure according to sociodemographic and sampling characteristics as well as occupation and frequency of consumption of canned fish within the previous 3 months. BPA was detected in 89% of participants with a specific gravity standardized geometric mean concentration of 0.990 μg/L. Biphenol 4,4' (BP 4,4'), 4,4'-dihydroxydiphenyl ether (DHDPE), and bisphenol E (BPE) were detected in >97% of participants. Bisphenol F (BPF) and bisphenol S (BPS) were detected in >60% of participants. Specific gravity standardized geometric mean concentrations of these 5 compounds ranged from 0.024 to 0.564 μg/L. Nine bisphenol analogues were detected in <9% of participants. Concentrations of BP 4,4', DHDPE, and BPE were higher in younger women and those with higher pre-pregnancy BMI, lower household income, lower education, and among smokers. We found a similar pattern of differences in BPF for age, education, and smoking status while BPS similarly differed across categories of pre-pregnancy BMI. Participants who were unemployed or working in the service industry had higher molar sum of 7 bisphenol analogues than those working in healthcare, education, or an office setting. Canned fish consumption was not related to bisphenol analogue concentrations. BP 4,4', DHDPE, BPE, BPF, and BPS were highly detected in 1st trimester urine samples in this large pan-Canadian pregnancy cohort. This suggests widespread exposure to these analogues around 2008-2011 and warrants further investigation into associations with health outcomes.


Large-scale transcriptome profiles reveal robust 20-signatures metabolic prediction models and novel role of G6PC in clear cell renal cell carcinoma.
Clear cell renal cell carcinoma (ccRCC) is the most common and highly malignant pathological type of kidney cancer. We sought to establish a metabolic signature to improve post-operative risk stratification and identify novel targets in the prediction models for ccRCC patients. A total of 58 metabolic differential expressed genes (MDEGs) were identified with significant prognostic value. LASSO regression analysis constructed 20-mRNA signatures models, metabolic prediction models (MPMs), in ccRCC patients from two cohorts. Risk score of MPMs significantly predicts prognosis for ccRCC patients in TCGA (P < 0.001, HR = 3.131, AUC = 0.768) and CPTAC cohorts (P = 0.046, HR = 2.893, AUC = 0.777). In addition, G6PC, a hub gene in PPI network of MPMs, shows significantly prognostic value in 718 ccRCC patients from multiply cohorts. Next, G6Pase was detected high expressed in normal kidney tissues than ccRCC tissues. It suggested that low G6Pase expression significantly correlated with poor prognosis (P < 0.0001, HR = 0.316) and aggressive progression (P < 0.0001, HR = 0.414) in 322 ccRCC patients from FUSCC cohort. Meanwhile, promoter methylation level of G6PC was significantly higher in ccRCC samples with aggressive progression status. G6PC significantly participates in abnormal immune infiltration of ccRCC microenvironment, showing significantly negative association with check-point immune signatures, dendritic cells, Th1 cells, etc. In conclusion, this study first provided the opportunity to comprehensively elucidate the prognostic MDEGs landscape, established novel prognostic model MPMs using large-scale ccRCC transcriptome data and identified G6PC as potential prognostic target in 1,040 ccRCC patients from multiply cohorts. These finding could assist in managing risk assessment and shed valuable insights into treatment strategies of ccRCC.


Construction of epidermal growth factor fusion protein with cell adhesive activity.
A novel protein for controlling cellular functions was constructed by combining functional units of various proteins. The Arg-Gly-Asp (RGD) sequence functioning as a cell adhesive function, an epidermal growth factor (EGF) as a cell growth function, and a hydrophobic sequence (E12) as an efficient assembling function, were combined and incorporated into one molecule. The fusion protein, designated ERE-EGF, was produced in Escherichia coli and purified with affinity chromatography using a His-tag. The ERE-EGF coated on an unmodified hydrophobic surface of a cell-culture plate (through the hydrophobic E12 moiety) retained both cell adhesive activity (through the RGD sequence) and cell growth activity (through the EGF moiety).


Effective out-of-operating room airway management for physicians not traditionally trained in airway management.
There is a dearth of literature about the safety and practicality of intubation performed by an internal medicine (IM) or any other nonanesthesia, nonemergency physician. The objectives of the study were to describe abbreviated airway management training guidelines for IM physicians staffing the emergency department and to compare the success rates between intubations performed by anesthesia and IM physicians, respectively. In this study, 272 consecutive out-of-operating room intubations performed by anesthesia and IM physicians were evaluated after creating and implementing an abbreviated intubation training protocol. Of 165 intubations attempted by IM physicians and 107 intubations attempted by the anesthesia service, the rates of successful intubation were 93% and 99%, respectively (P = 0.02). There were no other statistically significant differences in outcomes. Procedurally oriented IM fellows could provide a temporary solution to hospitals that currently do not have the resources to provide full-time, in-house anesthesiology or emergency physicians for management of the emergent airway.


New synthetic routes to thyroid hormone analogs: d6-sobetirome, 3H-sobetirome, and the antagonist NH-3.
New synthetic routes for the preparation of isotopically labeled versions of thyroid hormone agonist sobetirome were developed using Knochel's iodine-magnesium exchange. A more efficient synthesis of the thyroid hormone antagonist NH-3 was developed from a common intermediate in the sobetirome route. Using the new synthetic routes, d6- and 3H-sobetirome were prepared for their use in studying biodistribution and the cellular uptake of sobetirome. The new route to NH-3 allows for a more rapid and efficient synthesis and provides access to an advanced intermediate to facilitate antagonist analog production in the final bond-forming synthetic step.


Classification of Lateral Patellar Instability in Children and Adolescents.
There is significant heterogeneity in the literature related to the causes and treatment of patellar instability. To address the multifactorial issue of patellar instability, the first task is to classify the instability pattern. Once a classification system is developed, future studies can differentiate between treatment recommendations and outcomes for each instability pattern. Existing classification systems do not include the entire spectrum of patellar instability patterns. The aim of this article is to review the nomenclature and existing patellar instability classification systems and analyze the different patterns into a comprehensive system.


Latent profile analysis of depression in non-hospitalized elderly patients with hypertension and its influencing factors.
Hypertension is a common chronic disease in the elderly, which seriously affects people's physical and mental health, leading to anxiety, depression and other symptoms. To analyze the types of depression that may occur in elderly patients with non-hospitalized hypertension and explore its influencing factors can reduce the level of depression and improve the quality of life. Based on the data of the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS), latent profile analysis (LPA) was used to establish the potential profile model of elderly hypertensive patients with depression, and multiple logistic regression analysis was employed to explore the influencing factors of patients with depression. 3514 elderly patients with hypertension could be divided into three potential characteristics of depression: low-level (13.9 %), medium-level (51.9 %) and high-level (34.2 %). Multiple logistic regression showed that anxiety, IADL, age, exercise, economic level, hearing difficulty, self-reported health and visual function predicted the depression of the medium-level in the comparison between the low-level and the medium-level; taking low levels as a reference, anxiety, IADL, co-residence of interviewee, age, exercise, self-reported health marital status and visual function can predict the depression of high-level; anxiety, exercise, self-reported health and marital status predicted the depression of the high-level in the comparison between the medium-level and the high-level. (1) This study is a cross-sectional study; (2) due to data limitations, other influencing factors may be ignored. Depression in elderly patients with hypertension was divided into three potential profiles, which had obvious classification characteristics.


Narrative Economics, Public Policy and Mental Health.
General public's mental health can be affected by the public policy response to a pandemic threat. Britain, Italy and Sweden have had very distinct approaches to the COVID-19 pandemic: early lock-down, delayed lock-down and no-lock-down. We develop a novel narrative economics of language Culture-Based Development approach, and using Google trend data for seed keywords, death and suicide, we reach two main conclusions: (i) while countries had a pre-existing culturally relative disposition towards death-related anxiety, the sensitivity to the public policy towards COVID-19 was also country specific; (ii) however, significant spillovers from one specific national lockdown public policy to another country's mental health are identified.


Autism-like symptoms by exposure to air pollution and valproic acid-induced in male rats.
Exposure to air pollution during prenatal or neonatal periods is associated with autism spectrum disorder (ASD) according to epidemiology studies. Furthermore, prenatal exposure to valproic acid (VPA) has also been found to be associated with an increased prevalence of ASD. To assess the association between simultaneous exposure to VPA and air pollutants, seven exposure groups of rats were included in current study (PM2.5 and gaseous pollutants exposed - high dose of VPA (PGE-high); PM2.5 and gaseous pollutants exposed - low dose of VPA (PGE-low); gaseous pollutants only exposed - high dose of VPA (GE-high); gaseous pollutants only exposed - low dose of VPA (GE-low); clean air exposed - high dose of VPA (CAE-high); clean air exposed - low dose of VPA (CAE-low) and clean air exposed (CAE)). The pollution-exposed rats were exposed to air pollutants from embryonic day (E0) to postnatal day 42 (PND42). In all the induced groups, decreased oxidative stress biomarkers, decreased oxytocin receptor (OXTR) levels, and increased the expression of interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNF-α) were found. The volumes of the cerebellum, hippocampus, striatum, and prefrontal decreased in all induced groups in comparison to CAE. Additionally, increased numerical density of glial cells and decreased of numerical density of neurons were found in all induced groups. Results show that simultaneous exposure to air pollution and VPA can cause ASD-related behavioral deficits and air pollution reinforced the mechanism of inducing ASD ̉s in VPA-induced rat model of autism.


Alkylthioacetic acid (3-thia fatty acids)--a new group of non-beta-oxidizable, peroxisome-inducing fatty acid analogues. I. A study on the structural requirements for proliferation of peroxisomes and mitochondria in rat liver.
The induction of peroxisome proliferation was examined in rat liver after administration of equal concentrations (1 mmol/kg body weight) of 1,10-bis(carboxymethylthiodecane) (BCMTD), 1-mono(carboxymethylthiotetradecane) (CMTTD), 1-mono(carboxymethylthiooctane) (CMTO), 1-mono(carboxyethylthiotetradecane) (CETTD), palmitic acid and hexadecanedioic acid (HDDA). BCMTD, a non-beta-oxidizable and non-omega-oxidizable sulphur-substituted fatty acid analogue was considerably more potent than CMTTD (only non-beta-oxidizable) in inducing enlargement of the liver and increasing peroxisomal activities (monitored by peroxisomal beta-oxidation, palmitoyl-CoA hydrolase and catalase activities). Morphometric analysis of randomly selected hepatocytes revealed that BCMTD and CMTTD treatment increased the number and size of peroxisomes and the relative volume fraction of the peroxisomes. All these cellular responses were more marked with BCMTD than compared with CMTTD. CMTO, a non-beta-oxidizable fatty acid analogue containing a lower hydrophobic alkyl-end than CMTTD and CETTD (a beta-oxidizable fatty acid analogue), showed a slight increase (1.4-1.8-fold) of peroxisomal beta-oxidation and caused marginally morphological changes of peroxisomes compared with CMTTD and BCMTD. The most striking effect of the alkylthiopropionic acid (CETTD) was an enhancement of the hepatic triacylglycerol level. Palmitic acid and hexadecanedioic acid only marginally affected the peroxisomal activities, but no morphological changes of peroxisomes and fat droplets were observed. The presented data strongly suggest that a minimal structural requirement for a peroxisome proliferator may be (1) a carboxylic acid group linked to (2) a hydrophobic backbone which (3) cannot be beta-oxidized i.e., the fatty acid analogues have a sulphur atom in the beta-position. It is also conceivable that blockage for omega-oxidation may potentiate the peroxisome-proliferating activities in as much as BCMTD was more potent than CMTTD. Two mitochondrial marker enzymes, carnitine palmitoyltransferase and succinate phenazine methosulphate oxidoreductase were differently affected after administration of the investigated compounds. Furthermore, BCMTD and CMTTD as well as HDDA treatments increased the number of mitochondria, but the mitochondria tended to be smaller. The overall results presented here indicate that the structural requirements for proliferation of mitochondria are not identical to those for proliferation of peroxisomes.


Respiratory Syncytial Virus-An Update for Prenatal and Primary Health Providers.
Respiratory syncytial virus (RSV) infection is a significant cause of morbidity and mortality among infants aged younger than 1 year, adults aged 65 years or older, and immunocompromised persons. Limited data exist on RSV infection in pregnancy and further research is needed. Strides are being made to develop vaccines, including vaccines for maternal immunization, as well as monoclonal antibodies for disease prevention.


Evaluating the microbial aerosol generated by dental instruments: addressing new challenges for oral healthcare in the hospital infection.
Using a rotary instrument or ultrasonic instrument for tooth preparation is a basic operation in the dental clinic that can produce a significant number of droplets and aerosols. The dental droplet and aerosol can lead to the transfer of harmful germs. The goal of this study was to analyze the properties of microbiological aerosol created by droplets and aerosol generated by three common tooth-preparation instruments. Streptococcus mutans UA159 was used as the biological tracer to visualize the droplets and aerosols. The passive sampling method was used to map the three-dimensional spatial distribution and the six-stage Andersen microbial sampler (AMS) was used as the active sampling method to catch aerosol particles at a specific time. The aerosol concentration is related to instruments, three-dimensional spatial distribution, and dissipation time. Most aerosols were generated by air turbines. More microorganisms are concentrated at the 1.5 m plane. The majority of the post dental procedure contamination was detected within the 0-10-min period and it decreased rapidly within 30 min. This study is conducive to the proposal and improvement of relevant infection control measures in dental procedures and provides a basis for the assessment of measures, reducing the risk of nosocomial infection.


Preparation of tea glycoprotein and its application as a calibration standard for the quantification and molecular weight determination of tea glycoprotein in different tea samples by high-performance gel-permeation chromatography.
Tea glycoprotein (TGC) was purified by Sephadex G-100 gel filtration, and its purity and molecular weight (MW) were determined by high performance gel permeation chromatography. The gel permeation chromatography (GPC) elution behavior of TGC on an Ultrahydrogel 500 (7.8x300 mm) column was studied using a mobile phase with various concentrations of NaCl. A dextran T system was found to be unsuitable as MW calibration standards in GPC because the MW of TGC was changed with the change of ionic concentration in the mobile phase. Thus, the purified TGC obtained in this study was standardized and used instead as the calibration standards for the determination and comparison of TGCs in tea samples collected from different geographic locations and species varieties. The GPC was run at 35 degrees C on an Ultrahydrogel 500 column (7.8x300 mm) with a refractive index detector. Distilled water was used as the mobile phase at a flow rate of 0.6 ml.min(-1). The calibration curve was linear over the TGC concentration range of 0.604-6.04 mg.ml(-1), with a correlation coefficient of r=0.9997. The TGC mass recovery ranged from 80.4 to 93.2%, with a relative standard deviation of 5.42%. The assay method developed in this paper was found to be simple, reproducible, and reliable and, thus, ideally suitable for the quality control of TGC-derived products and raw materials.


Progress in inflammatory neuropathy -the legacy of Dr Jack Griffin.
The past quarter of a century has brought incredible advances in our understanding of inflammatory neuropathies, and the insights into Guillain-Barré syndrome (GBS) began in the 1990s with the seminal work of Dr Jack Griffin and his colleagues. In this essay, we provide a tribute to Jack, and review the recent progress in a field that he termed his personal favourite. In particular, we discuss the new developments in our understanding and diagnosis of inflammatory neuropathies, the recent emergence of the node of Ranvier and the paranode as sites of intensive investigation, and the mechanistic evidence that is providing a platform for therapeutic development studies.


The readability of psychosocial wellness patient resources: improving surgical outcomes.
Patient education is increasingly accessed with online resources and is essential for patient satisfaction and clinical outcomes. The average American adult reads at a seventh grade level, and the National Institute of Health (NIH) and the American Medical Association (AMA) recommend that information be written at a sixth-grade reading level. Health literacy plays an important role in the disease course and outcomes of all patients, including those with depression and likely other psychiatric disorders, although this is an area in need of further study. The purpose of this study was to collect and analyze written, online mental health resources on the Veterans Health Administration (VA) website, and other websites, using readability assessment instruments. An internet search was performed to identify written patient education information regarding mental health from the VA (the VA Mental Health Website) and top-rated psychiatric hospitals. Seven mental health topics were included in the analysis: generalized anxiety disorder, bipolar, major depressive disorder, posttraumatic stress disorder, schizophrenia, substance abuse, and suicide. Readability analyses were performed using the Gunning Fog Index, the Flesch-Kincaid Grade Level, the Coleman-Liau Index, the SMOG Readability Formula, and the Automated Readability Index. These scores were then combined into a Readability Consensus score. A two-tailed t-test was used to compare the mean values, and statistical significance was set at P < 0.05. Twelve of the best hospitals for psychiatry 2016-2017 were identified. Nine had educational material. Six of the nine cited the same resource, The StayWell Company, LLC (StayWell Company, LLC; Yardley, PA), for at least one of the mental health topics analyzed. The VA mental health website (http://www.mentalhealth.va.gov) had a significantly higher readability consensus than six of the top psychiatric hospitals (P < 0.05, P = 0.0067, P = 0.019, P = 0.041, P = 0.0093, P = 0.0054, and P = 0.0093). The overall average readability consensus for mental health information on all websites analyzed was 9.52. Online resources for mental health disorders are more complex than recommended by the NIH and AMA. Efforts to improve readability of mental health and psychosocial wellness resources could benefit patient understanding and outcomes, especially in patients with lower literacy. Surgical outcomes are correlated with patient mental health and psychosocial wellness and thus can be improved with more appropriate levels of readability of psychosocial wellness resources.