Search

Background Human papillomavirus (HPV) infection is known to promote the development of mucosal squamous cell carcinoma (mSCC), including pathologically high-grade lesions, but its role in cutaneous squamous cell carcinoma (cuSCC) remains unclear, particularly in lesions that are considered high risk. Objective We aimed to determine whether enhanced HPV transcriptional activity can be detected in high-risk cuSCC samples compared with low-grade SCC samples or normal skin. Methods We performed RNA sequencing of cuSCC across 23 risk-stratified skin lesions. A subset of samples was tested for the presence of HPV DNA. High-quality, non-human reads from each sample group were used for viral analysis using Microbiome Coverage Profiler. Results None of the samples analysed had detectable expression of HPV RNA, while 64% of samples tested positive for HPV DNA. All samples were found to have expression of human endogenous retrovirus, and multiple samples showed expression of other viruses. Conclusions Viral and prophage gene expression can be monitored in cuSCC or normal skin biopsies, yet no sample in our study showed evidence of active HPV gene expression despite evidence of HPV genome presence. This suggests HPV transcription does not play a role in differentiating high-risk cuSCCs from low-risk cuSCCs or normal skin.

Background Esophageal squamous cell carcinoma (ESCC) as the most prominent type of esophageal cancer (EC) in developing countries encompasses a substantial contribution of cancer‐related mortalities and morbidities. Cytotoxic T lymphocytes (CTLs) are the major subset of effector T cells against cancer. However, the microRNAs involved in the development and regulation of CTLs could be disrupted in cancers such as EC. Methods Here, we evaluated the population of IL‐10, TGF‐β, IFN‐γ, and IL‐17a‐producing CD3+CD8+ T cells, their association with the circulating levels of miR‐21 and miR‐29b, and their diagnostic and/or prognostic (after 160 weeks of follow‐up) utilities in 34 ESCC patients (12 newly diagnosed: ND, 24 under‐treatment: UT) and 34 matched healthy donors. Results The population of IL‐10 and TGF‐β‐producing CTLs (CD8+ Tregs) were considerably expanded, in addition to the overexpression of miR‐21 in both groups (ND and UT) of ESCC patients, while the frequency of Tc17 and CD8+ Treg cells increased only in UT patients. The expression means of TGF‐β and IL‐10 in CTLs were considered to be excellent biomarkers (1 ≥ area under the curve: AUC ≥0.9) in distinguishing ESCC patients and associated subgroups from healthy subjects. Moreover, the lower expressions of TGF‐β, IL‐17a, IL‐10, and IFN‐γ in CTLs were associated with ESCC better prognosis. Conclusions The association between the impaired function of CD3+ CD8+ T cell subsets and miR‐21 expression could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC., Association between the expression of miR‐21 and miR‐29b with the impaired function of CD8+ T‐cell subsets could be introduced as novel therapeutic targets and powerful diagnostic and prognostic markers for ESCC.

The light scattering and harvesting effects in dye-sensitized solar cells (DSSCs) is studied by controlling morphology, phase composition, and thickness of monolayer and double-layer TiO2 photoanode electrodes. The starting materials for preparation of TiO2 cells, including 25 nm mesoporous anatase nanoparticles, 200 nm anatase microspheres, 10 µm dandelion-like rutile particles and 40 nm nanoparticles containing 80% anatase-20% rutile, are synthesized by evaporation-induced self-assembly, sol-gel, and hydrothermal processes. It was found that the mesoporous anatase nanoparticles may improve light harvesting and dye-sensitization due to their high surface area and small particle size, whereas the microspheres and dandelion-like particles can enhance light scattering effect. The improvement of light harvesting efficiency is obtained by controlling the microstructure and thickness of photoanode electrode to increase dye adsorption. This is achieved by preparation of high surface area TiO2 monolayer film with optimum thickness and good connections between the particles using mesoporous anatase nanoparticles. The influence of film's thickness on photovoltaic characteristics of monolayer DSSCs shows that the optimal thickness around 30 μm results in the highest cell efficiency of 6.31%. The enhancement of light scattering is acheieved by design of a proper scattering layer with desired morphology and phase composition. The dye loading property of the scattering layer is also considered simultaneously. The photovoltaic characteristics of double-layer DSSCs, with total thickness of 30 µm, reveal that the cell efficiency enhances up to 7.54 and 8.91% using a mixture of dandelion-like particles and mesoporous nanoparticles and microspheres and mesoporous nanoparticles, respectively. © 2016 American Institute of Chemical Engineers Environ Prog, 35: 1818–1826, 2016

Mitochondrial metabolism is highly responsive to nutrient availability and ongoing activity in neuronal circuits. The molecular mechanisms by which brain cells respond to an increase in cellular energy expenditure are largely unknown. Mild mitochondrial uncoupling enhances cellular energy expenditure in mitochondria and can be induced with 2,4-dinitrophenol (DNP), a proton ionophore previously used for weight loss. We found that DNP treatment reduces mitochondrial membrane potential, increases intracellular Ca(2+) levels and reduces oxidative stress in cerebral cortical neurons. Gene expression profiling of the cerebral cortex of DNP-treated mice revealed reprogramming of signaling cascades that included suppression of the mammalian target of rapamycin (mTOR) and insulin--PI3K - MAPK pathways, and up-regulation of tuberous sclerosis complex 2, a negative regulator of mTOR. Genes encoding proteins involved in autophagy processes were up-regulated in response to DNP. CREB (cAMP-response element-binding protein) signaling, Arc and brain-derived neurotrophic factor, which play important roles in synaptic plasticity and adaptive cellular stress responses, were up-regulated in response to DNP, and DNP-treated mice exhibited improved performance in a test of learning and memory. Immunoblot analysis verified that key DNP-induced changes in gene expression resulted in corresponding changes at the protein level. Our findings suggest that mild mitochondrial uncoupling triggers an integrated signaling response in brain cells characterized by reprogramming of mTOR and insulin signaling, and up-regulation of pathways involved in adaptive stress responses, molecular waste disposal, and synaptic plasticity. Physiological bioenergetic challenges such as exercise and fasting can enhance neuroplasticity and protect neurons against injury and neurodegeneration. Here, we show that the mitochondrial uncoupling agent 2,4-dinitrophenol (DNP) elicits adaptive signaling responses in the cerebral cortex involving activation of Ca(2+) -CREB and autophagy pathways, and inhibition of mTOR and insulin signaling pathways. The molecular reprogramming induced by DNP, which is similar to that of exercise and fasting, is associated with improved learning and memory, suggesting potential therapeutic applications for DNP.

Aims The aim of this study was to evaluate the effect of various disease-modifying therapies (DMT) on quality of life in multiple sclerosis (MS). Methods This was a three-arm parallel study with balanced randomization in which 90 newly diagnosed, definite MS subjects referred to Ghaem Medical Center, Mashhad, Iran were enrolled between 2006 and 2009. Patients were randomly allocated into three DMT groups: Avonex, Rebif and Betaferon. Health-related quality of life was assessed in MS patients at baseline and 12 months after treatment with DMT using the MS Quality of Life-54 questionnaire. Results Both mental and physical health scores improved within all three treatment groups after 12 months of treatment; however, this increase was only significant in the mental health composite in the Betaferon group (P = 0.024). Betaferon had the highest mental health score change (14.04) while this change was 7.26 for Avonex (P = 0.031) and 5.08 for Rebif (P = 0.017). A physical health composite score comparison among the three treatment groups revealed no significant results. Conclusions With a positive impact of DMT on mental and physical dimensions of QOL in MS patients, initiation of treatment soon after diagnosis is recommended. In MS patients with more mental issues and fewer physical disabilities, Betaferon might be considered as a better choice of treatment.

Background and Objective: A novel, noninvasive technology, utilizing suction-coupled radiofrequency (RF) heating and ultra-short pulse duration, high-voltage electrical pulses was studied for its efficacy and safety on adipose tissue reduction. Methods: Twenty-one subjects underwent treatment of their abdominal fat once weekly for 6 weeks. Clinical outcomes including abdominal circumference, adipose tissue thickness (measured by ultrasound), adipose tissue weight, body weight, and clinical photographs were obtained at visits 1 and 3 months after last treatment. Adverse events were recorded. Three subjects, who were undergoing a future elective abdominoplasty, were treated withthesameprotocol,butononlyonesideoftheabdomen before abdominoplasty. Biopsies from the RF-treated and untreated sides were harvested during abdominoplasty and cultured; measurements of adipocyte size and shape, rate of apoptosis, collagen production, and dermal thickness were determined. Results:Significantclinicalimprovements(P

Background Both vitamin D deficiency and inflammation have been linked to cardiovascular disease, the major cause of death in diabetes. In this study, the effects of daily intake of vitamin D-fortified yoghourt drink (doogh )o n systemic inflammatory biomarkers in subjects with type 2 diabetes (T2D) were investigated. Subjects and methods In this 12-week randomized controlled trial, T2D subjects received either plain doogh (PD; containing 170 mg calcium and no detectable vitamin D/250 mL, n1=50) or vitamin D3-fortified doogh (FD; containing 170 mg calcium and 500 IU/250 mL, n2=50) twice a day. Glycemic status, body fat mass and systemic inflammatory biomarkers including serum highly sensitive C-reactive protein (hsCRP), serum amyloid A (SAA), interleukin(IL)-2, IL-6, IL-10 and tumour necrosis factor (TNF)-a were evaluated at the beginning and after the intervention. Data were expressed as either mean SD or median (interquartile range) whenever they had either normal or non-normal distribution, respectively. Results In the patients receiving the vitamin D fortified drink, compared with those receiving the unfortified drink, a significant increase in serum 25(OH)D was accompanied by significant changes in TNF-a (57.9 (264.6) versus +106.3 (683.2), p=0.044), IL-6 (6.3 (69.2), p=0.002), hsCRP (0.39 (1.50) versus +0.8 (1.52), p

How to cite this article Ghandchi Z., Neyestani T.R., Saboor Yaraghi A.-A., Eshraghian M.-R., Gharavi A., Shariatzadeh N., Kalayi A. & Houshiarrad A. (2012) Vitamin D status and the predictors of circulating T helper 1-type immunoglobulin levels in Iranian subjects with type 1 diabetes and their siblings: a case-control study. J Hum Nutr Diet. 25, 365–372 Abstract Background: Vitamin D status has been linked to both T helper (Th)1/Th2 balance and susceptibility to type 1 diabetes (T1D). The present study aimed to evaluate vitamin D status and its relation to Th1/Th2 balance in subjects with T1D, their siblings and unrelated healthy controls during autumn and winter 2008–2009. Methods: A case–control study was conducted on subjects with T1D (n1 = 60) and two control groups comprising nondiabetic siblings (n2 = 60) and unrelated healthy controls (n3 = 60). Assessments of dietary intake, anthropometry, intact parathyroid hormone (iPTH) and 25(OH)D were performed. Serum levels of immunoglobulin (Ig)G2 and IgE, as well as the IgG2/IgE ratio, were used to evaluate Th1/Th2 balance. Vitamin D status was defined based on circulating 25(OH)D as deficiency

BACKGROUND: Painful invasive procedures are frequently performed on preterm infants admitted to a neonatal intensive care unit (NICU). The aim of the present study was to investigate current pain management in Austrian, German and Swiss NICU and to identify factors associated with improved pain management in preterm infants. METHODS: A questionnaire was sent to all Austrian, German and Swiss pediatric hospitals with an NICU (n = 370). Pain assessment and documentation, use of analgesics for 13 painful procedures, presence of written guidelines for pain management and the use of 12 analgesics and sedatives were examined. RESULTS: A total of 225 units responded (61%). Pain assessment and documentation and frequent analgesic therapy for painful procedures were performed more often in units using written guidelines for pain management and in those treating >50 preterm infants at

The pharmacokinetics of the antimalarial drug (+/-)-halofantrine are stereoselective in humans and rats. To better understand the stereoselective metabolism of the drug to its primary metabolite, desbutylhalofantrine (DHF), a series of in vitro and in vivo experiments were undertaken in the rat. Formation of (-)-DHF exceeded that of (+)-DHF in liver microsomes [(-):(+) ratio of intrinsic formation clearances = 1.4]. In contrast, in intestinal microsomes no significant stereoselectivity was noted in the formation of the DHF enantiomers. Intestinal microsomes were also less efficient at producing the DHF enantiomers than were liver microsomes. Based on kinetic analysis of the DHF formation, there appeared to be more than one enzyme involved in the biotransformation. (+/-)-Ketoconazole (KTZ) effectively inhibited the formation of both DHF enantiomers by both liver and intestinal microsomes, although the reduction was more marked in liver microsomes. Through a combination of the use of CYP antibodies and recombinant CYP isoenzymes, the involvement of CYP 2B1/2, 3A1, 3A2, 1A1, 2C11, 2C6, 2D1, and 2D2 were implicated in the metabolism of halofantrine to DHF. Of these, CYP3A1/2 and CYP2C11 appeared to be the primary isoenzymes involved, although CYP2C11 showed greater (+)-DHF than (-)-DHF formation, whereas for CYP3A1 it was similar to the isolated rat liver microsomes. In vivo, oral (+/-)-KTZ caused significant increases in plasma halofantrine and decreases in DHF enantiomer plasma concentrations.

Cholesterol is an important molecule that plays a key role in regulating cellular differentiation and function. Although the possible role of lipids has been implicated in regulating osteoblastic cells, the role of cholesterol in that process is not well defined. In this study we have examined the role of the cellular cholesterol biosynthetic pathway on osteoblastic differentiation of marrow stromal cells (MSCs). Treatment of pluripotent mouse MSCs M2-10B4 with inhibitors of the cholesterol biosynthetic pathway mevastatin or mevinolin inhibited the maturation of these cells into functional osteoblastic cells. This was determined by the inhibition of the activity and expression of alkaline phosphatase (ALP), a key enzyme involved in differentiation and mineralization of osteoblastic cell cultures, as well as inhibition of mineralization. Mevastatin treatment did not affect expression of the osteoblast-specific gene osteocalcin (OCN). Furthermore, promoter-reporter studies in MSCs showed that mevastatin inhibited activity of the ALP gene promoter, suggesting regulation by derivatives of the cholesterol biosynthetic pathway. The effects of mevastatin and mevinolin were reversed by mevalonate but not by geranylgeraniol or farnesol, intermediates in the cholesterol biosynthetic pathway. Altogether, these results suggest that products of the cholesterol biosynthetic pathway are important for proper development of MSCs into functional osteoblastic cells capable of forming a mineralized matrix. Identification of those molecules may provide new therapeutic approaches to prevent the decline in osteoblastic activity in osteoporosis and aging.

Summary The behavior of beam-to-column connections is significantly complicated because it depends on the material, nonlinear relationship between different members, and contact of connecting elements. Their hysteretic response exhibits highly inelastic characteristics and continuous variation in stiffness, strength, and ductility. Therefore, accurate hysteretic models of bolted connections are essential to accurate seismic assessment and design. Composed (Hybrid) modeling approach is presented to represent the complex hysteretic behavior of I beam-to-concrete-filled-tube (CFT) column bolted connection. For the purpose in this study, experimental evaluation of I beam-to-CFT column connection with bolted end-plate under cyclic loading is done. It must be mentioned to make the connection easily applicable practically and also prepare the column flanges continuity, a connection with the bolts penetrated into the CFT column are used since using the stiffeners in hollow sections is not easily applicable. In the composed mechanical–informational modeling framework, the conventional mechanical model is complemented by information-based model components. Finally, moment–rotation curves of composed model have been compared with experimental results. Comparison showed that the composed model has a good agreement with experimental results. A newly designed specimen for validation purpose of the composed modeling was made and experimented. Composed model was well applied to predict the behavior of new connections. The presented results show that the composed model has a good ability to predict of hysteretic behavior.

Objective To determine the frequencies at which either a valine or leucine occurs at position 247 in the β2-glycoprotein I (β2GPI) gene of normal individuals of the Caucasian, African American, and Asian ethnic groups and to compare these data with those in patients with the antiphospholipid syndrome (APS), with and without anti-β2GPI antibodies. Methods The DNA segment containing the position-247 polymorphism was amplified by seminested polymerase chain reaction, and the polymorphism was detected by restriction endonuclease digestion. DNA samples from 370 healthy controls of different racial backgrounds were analyzed, and the results were compared with those from 149 APS patients (66 primary; 83 secondary). Allele and genotype frequencies were compared using Fisher's exact test. When significant differences were detected, pairwise comparisons were made using Fisher's exact test with a Bonferroni adjustment. Results Allele and genotype expression was significantly different (P < 0.0001 for both) among the 3 races, with the V allele and the VV genotype occurring most often among Caucasians, less among African Americans, and least among Asians. Conversely, the V allele and the VV genotype were found more frequently among Asian APS patients than among controls (P = 0.0028 and P = 0.0023, respectively). No significant differences in allele or genotype frequencies were seen in comparisons of the Caucasian or the African American patients with appropriate controls. The differences in allele and genotype frequencies seen in the Asian APS patients were restricted to the anti-β2GPI–positive patients (P = 0.0018 and P = 0.0005, respectively). Conclusion In Asian patients with APS, expression of a V at position 247, especially in the homozygous state, is significantly associated with the presence of anti-β2GPI antibodies and, therefore, can be viewed as a major risk factor in this ethnic group (odds ratio 9.19 and 16.33, respectively).

In this article, a new video coding system is proposed which takes advantage of both intrascale and interscale similarities present in video sequences. Each block in every frame is approximated with a linear combination of members of an adaptive library of blocks constructed for that block. This library is made up of some fixed blocks (e.g., DCT basis blocks) and some adaptive blocks. The adaptive library blocks are blocks of the same size or larger blocks that are shrunk, taken from the previous frame. For each block in every frame, a rate-distortion optimized fully orthogonal matching pursuit algorithm is used to determine how many and which ones of the members of the library constructed for that block should be selected and linearly combined to approximate the block most efficiently in terms of bit rate and rms error. Simulation results on sample gray-scale video sequence “Miss America” suggests that this method has promising coding performance in terms of PSNR and bit rate,especially compared to other published fractal-based video compression methods. © 1998 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 9, 305–319, 1998

Lupus anticoagulants, commonly found in the immunoglobulin fraction of patients with the antiphospholipid syndrome (APS), and the normal plasma protein beta 2-glycoprotein 1 (beta 2GP1) may both contribute to the in vitro impairment of prothrombin activation associated with the APS. We examined the effects upon prothrombin activation supported by phospholipid vesicles of plasma IgG preparations from APS patients in the presence and absence of beta 2GP1. Using a purified system for measurement of prothrombin activation to thrombin, we demonstrated significant phospholipid concentration-dependent inhibition of prothrombin activation in the absence of beta 2GP1 by 11 consecutive patient IgG preparations. The degree of inhibition of prothrombin activation by equivalent concentrations of patient IgG correlated well with the extent of prolongation of the plasma clotting time in lupus anticoagulant assays of whole patient plasma. Additional studies with eight patient IgG preparations indicated that the addition of beta 2GP1 to patient IgG-phospholipid vesicle mixtures resulted in either independently additive inhibition by the two protein species (six cases) or potential inhibition of beta 2GP1 of the IgG inhibitory activity demonstrable in the absence of beta 2 GP1 (two cases). In addition, beta 2GP1-independent inhibition of prothrombin activation also occurred with three patient IgG preparations obtained by affinity binding to cardiolipin.

A new recyclable catalyst is utilized to promote the double Heck reaction of 1,4-dihalobenzenes.

Recent studies have suggested that the lupus anticoagulant (LA) may be specific for prothrombin, prothrombin-phospholipid complexes, or beta 2 glycoprotein 1 (beta 2GP1) rather than phospholipids. We performed a series of experiments to determine whether LA is indeed phospholipid specific. IgG was purified from sera of six patients with the antiphospholipid syndrome (APS) and 10 healthy controls. The six IgG-APS preparations had both LA and anticardiolipin (aCL) activity. Incubation of the six IgG-APS preparations with cardiolipin (CL), phosphatidylserine (PS), phosphatidylcholine (PC), or PS/PC (20:80) liposomes in Tris-buffered saline, resulted in loss of LA activity from the supernatant. We postulated that loss of activity might have resulted from absorption of IgG LA antibodies by phospholipids, a dilutional effect, or the presence of phospholipids in the supernatant causing 'by-pass' of IgG LA inhibitory activity. To distinguish between these possibilities, we re-isolated IgG from the supernatants and re-tested them for LA activity. IgG re-isolated from the PS. CL and PS/PC supernatants had no LA activity, but LA activity remained in the PC supernatant. This suggested that IgG with LA activity was absorbed by negatively charged but not by zwitterionic phospholipids. In like manner, PS, CL and PS/PC, but not PC liposomes, absorbed IgG with aCL activity. Mixtures of the phospholipid liposomes with beta 2GP1 did not modify the absorption of IgG with LA or aCL activity. Finally, we demonstrated that IgG eluted from immunoglobulin-cardiolipin liposome complexes had LA activity. Based on these findings, we conclude that at least one population of antibodies with LA activity is phospholipid specific.

A generic approach to high temperature stable, functionalized polyimides for nonlinear optics has been developed and the resulting polyimides exhibit excellent temporal stability in dipole orientation at elevated temperatures, such as 150{degrees}C. Large second harmonic generation coefficients and electro-optic coefficients have been achieved. These polyimides exhibit good solubility in common organic solvents and can be easily processed into thin films. A variety of nonlinear optical chromophores have been incorporated into the polyimide backbones, which enabled us to systematically study the structure-property relationship.