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Abstract Background Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy. Methods Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector. Results Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response. Conclusion In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

To determine the effects of organic selenium (0.0-0.6 mg and 0.9 mg Se/Kg diet) and Zn-Cr mixture (100 mg Zn/Kg diet plus 1.5 mg Cr/Kg diet) on broiler chicken performance, carcass traits, blood hematology, and biochemistry under heat stress conditions, this study was conducted. Under temperatures between 30.21 to 31.82 °C, 240 broiler chickens (Ross-308), which were 7-day-old, were randomly assigned to one of six treatments: T1 (control), T2 (100 mg Zn per kg of diet and 1.5 mg Cr per kg of diet), T3 (0.6 mg Se per kg of diet), T4 (0.9 mg Se per kg of diet), T5 (100 mg Zn, 1.5 mg Cr and (LSe), and T6 (100 mg Zn, 1.5 mg Cr and (HSe)). At 35 days old, the chicks fed a diet containing Zn-Cr with low or high organic selenium (organic-Se) outweighed the control group in terms of live body weight, weight gain, and feed conversion ratio ( p < 0.05). In comparison to the control treatment, birds fed diets supplemented with Zn-Cr or organic-Se (LSe, HSe) significantly increased their serum levels of total protein and total antioxidant capacity. However, these additives resulted in a decrease ( p < 0.01) in their serum levels of triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, creatinine, and uric acid. Together, it was found that trace elements (Zn-Cr and organic-Se) may greatly lessen the impacts of heat stress on broilers by promoting growth performance and boosting metabolic processes.

The objective of the study was to evaluate the impact of various concentrations of orange ( Citrus sinensis ) peel meal (OPM), with or without the supplementation of multi-enzymes, on the growth performance, nutrient digestibility, antioxidant properties, and blood metabolic profile of broiler chickens. The experiment was conducted on 240 one-day-old Arbor Acres broiler chicks, assigned to eight dietary treatments with 30 broilers per treatment group. Four dietary orange peel meal (OPM) concentrations were supplemented, namely, the control (without OPM), and with 80, 160, and 240 g/kg of the diet. To each of these diets was added two concentrations of multi-enzyme inclusion (0 or 0.6 g as a combination of 0.5 g of Nutrikem and 0.1 g Optiphos per kg diet) in a completely randomized design in a 4 × 2 factorial arrangement. The experiment lasted until 42 days of age. Body weight gain (BWG) was influenced during the grower period (22-42 days) and the overall period (0-42 days), and the feed conversion ratio (FCR) was significantly improved by supplementations of OPM compared with the control for 22-42 days and overall (0-42 days) periods. Moreover, BWG, FCR during the grower and overall periods, and crude fiber digestibility were improved ( p < 0.01) by multi-enzyme supplementation compared to the non-supplemented groups. Broilers with diets supplemented with OPM had considerably lower abdominal fat ( p < 0.01) than the control. In addition, when compared to the non-supplemented enzyme group, serum T3 and T3/T4 ratios were significantly improved in response to enzyme addition. When compared to the control group, superoxide dismutase (SOD) was significantly higher in the OPM groups, showing the largest improvement in antioxidant response. Interaction effects were observed only for serum SOD levels. Based on our findings, it is recommended that OPM be used as a feed supplement for raising broilers, and adding 0.6 m g/kg of multi-enzymes could provide additional benefits to the performance of broilers.

The remarkable characteristics of graphene make it a model candidate for boosting the effectiveness of nano-adsorbents with high potential owing to its large surface area, π-π interaction, and accessible functional groups that interact with an adsorbate. However, the stacking of graphene reduces its influence adsorption characteristics and also its practical application. On the other hand, the widespread use of aromatic compounds in the industry has aggravated the contamination of the water environment, and how to effectively remove them has become a research hotspot. Herein, we develop the functionalization of silica nanoparticles on graphene oxide nanosheet (FGS) by a facile, cheap, and efficient synthesis protocol for adsorption of Trypan Blue (TB) and Bisphenol A (BPA). It was demonstrated that chemical activation with KOH at high autoclaving temperature successfully transformed rice husk ash (RHA) into FGS. The graphene oxide layered interlamination was kept open by using SiO 2 to expose the interlayers' strong adsorption sites. XRD, EDX, FTIR, Raman spectroscopy, SEM, HR-TEM, and BET surface area are used to investigate the chemical composition, structure, morphology, and textural nature of the as-produced FGS hybrid nanocomposite. The various oxygen-containing functional groups of the hybrid nanocomposites resulted in a significantly increased adsorption capacity, according to experimental findings. In addition, FGS2, the best composite, has a specific surface area of 1768 m 2 g -1 . Based on Langmuir isotherms, the maximal TB dye and BPA removal capacity attained after 30 min were 455 and 500 mg/g, respectively. The Langmuir isotherm model, a pseudo-second-order kinetic model, and an intraparticle diffusion model have all been used to provide mechanistic insights into the adsorption process. This suggests that BPA and TB adsorption on FGS2 is mostly chemically regulated monolayer adsorption. Due to its unique sp 2 -hybridized single-atom-layer structure, the exposed graphene oxide nanosheets' extremely hydrophobic effect, hydrogen bonding, and strong-electron donor-acceptor interaction contributed to their improved adsorption of BPA and TB. According to adsorption thermodynamics, FGS2 adsorption of TB and BPA is a spontaneous exothermic reaction that is aided by lowering the temperature. For adsorption-based wastewater cleanup, the produced nanocomposites with a regulated amount of carbon and silica in the form of graphene oxide and silica can be used. These findings suggest that functionalized GO/SiO 2 hybrid nanocomposites could be a viable sorbent for the efficient and cost-effective removal of aromatic chemicals from wastewater., (© 2022. The Author(s).)

We aimed to review computed tomography and magnetic resonance angiography of congenital anomalies of pulmonary veins. Total anomalous pulmonary venous return shows all pulmonary veins drain abnormally in another site rather than left atrium. Imaging can detect anomalous veins either supracardiac, infracardiac, or mixed. Partial anomalous pulmonary venous return shows some pulmonary vein have abnormal drainage that well delineated with computed tomography angiography. Scimitar syndrome is a type of partial anomalous pulmonary venous return where the pulmonary veins of the right lung drain infracardiac and is associated with right lung hypoplasia and dextrocardia. Pseudoscimitar show anomalous vein that takes a tortuous course and drains into the left atrium producing a false-positive scimitar sign. Cor triatriatum shows septum divide left atrium with proximal chamber receives blood flow from the pulmonary veins. Levoatriocardinal vein is an anomalous connection between the left atrium and anomalous vein from systemic venous system that is embryo logically derived from the cardinal veins. Computed tomography angiography can detect pulmonary vein stenosis, atresia, hypoplasia, and varix. Imaging is important for intimal diagnosis and detects the anomalous vessels and its connection, presence of stenosis, and associated other congenital cardiac anomalies. Also, it is a great role in assessment of patients after surgery.

Background and Aim: Extremely poor prognosis in hepatocellular carcinoma (HCC) patients with progressing disease was denoted by vascular invasion. Cytokeratin 18 (CK18) has been shown to be overexpressed in hepatocellular carcinoma so it is a valuable tumor marker; however, its role in vascular invasion is still unclear. This study aimed to predict CK18 as a predictive marker for macrovascular malignant invasion., Methods: The present study was conducted on three groups of patients: group I included 91 HCC patients without macrovascular invasion, group II included 34 HCC patients with radiological evidence of vascular invasion, and group III included 110 control individuals subdivided into IIIA as healthy blood donors and IIIB as post-HCV cirrhotic patients without HCC., Results: ROC curve of M30 fragments of CK18 was constructed for discrimination between HCC with and without macrovascular invasion. Optimum cutoff value was 304.5 ng/mL (AUC = 0.997, P < 0.001), sensitivity (100%) and specificity (98.8%). Regression analysis was conducted for prediction of macrovascular invasion within HCC patients. The following variables: higher levels of AST, M30, bilirubin, and AFP, lower levels of serum albumin, larger tumor size, child B score, and multiple lesions were associated with vascular invasion in univariate analysis. While in multivariate analysis, higher levels of AST and bilirubin and elevated levels of M30 and AFP serum were considered independent predictors for macrovascular invasion in HCC patients., Conclusion: The present study suggests that increased M30 fragments of CK18 levels may be useful as a possible marker of early tumor invasiveness.

Aim: This randomized clinical trial was designed to evaluate the effect of pulsed electromagnetic field therapy (PEMF) in the management of patients with discogenic lumbar radiculopathy., Methods: Forty patients suffering from lumbar radiculopathy due to lumbar disc prolapse were randomly assigned to one of two groups: a study group that included 20 patients who received PEMF therapy and a control group that included 20 patients who received placebo treatment. Both groups were evaluated at bases line and after 3 weeks by using a visual analogue scale (VAS) (0-10), somatosensory evoked potentials (SSEPs) for selected dermatomes and Modified Oswestry Low Back Pain Disability Questionnaire (OSW), and findings were compared before and after treatment., Results: Significant differences were observed between both groups before and after application of PEMF therapy relative to VAS (P=0.024), total OSW (P<0.001), and other domains of OSW score (pain intensity [P=0.009], personal care [P=0.01], lifting [P<0.001], walking [P<0.001], sitting [P<0.001], standing [P<0.001], sleeping [P<0.001], social life [P<0.001] and employment [P=0.003]). Other significant differences were observed between both groups relative to SSEP latency and amplitude of the evaluated dermatomes on the right side (P=0.022 and P=0.001, respectively), and left side latency and amplitude (P=0.016 and P=0.002, respectively)., Conclusion: PEMF therapy is an effective method for the conservative treatment of lumbar radiculopathy caused by lumbar disc prolapse. In addition to improvement of clinically observed radicular symptoms, PEMF also seems effective in reducing nerve root compression as evidenced by improvement of SSEP parameters after treatment., (© 2012 The Authors International Journal of Rheumatic Diseases © 2012 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.)

Background: Control of itch is an important issue in the treatment of atopic dermatitis (AD). Itch is mediated by a variety of pruritogens, including histamine, and promoted by neurite outgrowth in the epidermis of AD patients, probably due to the release of nerve growth factor., Objectives: We investigated the effects of orally administered olopatadine hydrochloride (olopatadine) on itching, itching mediators, and neuritogenic action in a mouse model., Materials and Methods: NC/Nga mice were treated topically with Dermatophagoides farinae body (Dfb) extract twice weekly for 4 weeks to induce AD-like lesions. They were concomitantly given oral olopatadine, distilled deionized water, or topical tacrolimus during the last 2 weeks., Results: Olopatadine significantly suppressed scratching, improved the dermatitis score, inhibited neurite outgrowth, and decreased the elevated inflammatory markers, growth factors and histamine content in the lesional skin, and serum concentration of Dfb-specific IgE. Notably, olopatadine treatment increased semaphorin 3A expression in the epidermis., Conclusions: Our study confirms the pleiotropic effects of olopatadine, i.e. inhibition of inflammation and neurite extension into the epidermis., (Copyright © 2010 S. Karger AG, Basel.)

Background: Sepsis remains the leading cause of death in critically ill patients. One of the primary organs affected by sepsis is the lung, presenting as the Acute Respiratory Distress Syndrome (ARDS). Organ damage in sepsis involves an alteration in gene expression, making gene transfer a potential therapeutic modality. This work examines the feasibility of applying simian virus 40 (SV40) vectors for pulmonary gene therapy., Methods: Sepsis-induced ARDS was established by cecal ligation double puncture (2CLP). SV40 vectors carrying the luciferase reporter gene (SV/luc) were administered intratracheally immediately after sepsis induction. Sham operated (SO) as well as 2CLP rats given intratracheal PBS or adenovirus expressing luciferase served as controls. Luc transduction was evaluated by in vivo light detection, immunoassay and luciferase mRNA detection by RT-PCR in tissue harvested from septic rats. Vector abundance and distribution into alveolar cells was evaluated using immunostaining for the SV40 VP1 capsid protein as well as by double staining for VP1 and for the surfactant protein C (proSP-C). Immunostaining for T-lymphocytes was used to evaluate the cellular immune response induced by the vector., Results: Luc expression measured by in vivo light detection correlated with immunoassay from lung tissue harvested from the same rats. Moreover, our results showed vector presence in type II alveolar cells. The vector did not induce significant cellular immune response., Conclusion: In the present study we have demonstrated efficient uptake and expression of an SV40 vector in the lungs of animals with sepsis-induced ARDS. These vectors appear to be capable of in vivo transduction of alveolar type II cells and may thus become a future therapeutic tool.

Diabetes mellitus (DM) is the single most common cause of erectile dysfunction (ED) seen in clinical practice. Evaluation of penile arterial insufficiency in diabetic patients currently entails expensive and invasive testing. We assessed the diagnostic value of certain peripheral and cavernous blood markers as predictors of penile arterial insufficiency in diabetic men with ED. This study was conducted on a total of 51 subjects in three groups: 26 impotent diabetics, 15 psychogenic impotent men and 10 normal age matched control males. All subjects underwent standard ED evaluation including estimation of postprandial blood sugar and serum lipid profile. Peripheral venous levels of nitric oxide (NO), lipoprotein(a) (LP(a)), malondialdehyde (MDA) and glycosylated hemoglobin (HbA1c) were obtained in all subjects. Patients in the two impotent groups underwent additional measurement of NO, LP(a) and MDA levels in cavernous blood. They also underwent intracavernosal injection (ICI) of a trimix (papaverine, prostaglandin E1 and phentolamine mixture) and pharmaco-penile duplex ultrasonography (PPDU). Compared to patients in the psychogenic group, diabetic men had significantly lower erectile response to ICI (P<0.001), lower peak systolic velocity (PSV) (P<0.001), and smaller increase in cavernosal artery diameter (CAD) (P<0.001). Peripheral and cavernous levels of both LP(a) and MDA were higher in the diabetic group as compared to the psychogenic ED group (P<0.001), while the values of peripheral venous and cavernous NO were lower (P<0.001) in the diabetic men. Comparison of biochemical marker assays with the PPDU results showed a significant negative correlation between both venous and cavernous LP(a) and MDA levels on the one hand, and PSV, and the percentage of CAD increase on the other. At the same time, peripheral and cavernous NO levels had a significant positive correlation with the same parameters. Lipoprotein(a), MDA and NO levels were better predictors of low PSV than HbA1c, cholesterol or triglyceride levels. The finding of high levels of LP(a) and MDA with low levels of NO in the peripheral and cavernous venous blood of diabetic men with ED correlates strongly with severity of ED as measured by PPDU. This provides a rationale for further studies of biochemical markers as a surrogate for traditional invasive testing in the diagnosis of penile arterial insufficiency.

Efficient reconstitution of defective genes in hepatocytes could be used to treat various liver and systemic diseases through gene therapy. To explore the potential of SV40-based vectors in liver gene therapy, we constructed SV/luc, an SV40 T-antigen replacement transduction vector, that was propagated on COS and COT cells, which supply the SV40 T-antigen in trans. For liver targeting, BALB/C mice were injected via the tail vein with SV/luc stocks containing 3 x 10(6) to 10(8) transducing units in a volume of 1-2 ml. Luciferase activity was monitored with a light-detection cooled charged-coupled device (CCCD) camera, which enables continuous in vivo measurement of luc expression. The SV40 vector proved to be efficient in gene delivery to the liver, leading to long-term (> or =107 days) transgene expression in hepatocytes. Optimal results were obtained with 3 x 10(6) to 3 x 10(7) transducing units. The hydrodynamic vector delivery method caused transient liver inflammatory changes, with full recovery within days. Low levels of SV40-neutralizing antibodies were detected in the sera of treated mice; however, there was no indication of vector or transgene-specific cellular immune responses. Vectors packaged in vitro, using recombinant capsid proteins and plasmid DNA, were also effective in liver transduction. These results suggest that SV40 vectors may be useful for liver gene therapy.

Simian virus 40 (SV40) vectors are efficient vehicles for gene delivery to hematopoietic and hepatic cells. To ensure their replication incompetence and because of safety considerations, it is critical that the vectors do not contain T-antigen sequences. Available packaging cell lines for T-antigen replacement vectors, COS and CMT4, contain considerable sequence identity with the vectors, leading to homologous recombination and reacquisition of the T-antigen gene. We constructed a packaging cell line, COT18, with minimal sequence identity to the vector. Vector stocks produced by passaging on COT18 had high transducing activity and undetectable levels of T-antigen-positive, replication-competent contaminants. This cell line provides a means for the preparation of safe SV40 vector stocks., (Copyright 2002 Elsevier Science (USA))

A study of the spectrum of beta-thalassemia mutations in the southern part of the West Bank of the Palestinian Authority revealed the presence of 10 different beta-globin mutations. The study included 41 patients and 54 carriers of beta-thalassemia and sickle cell anemia. The spectrum of mutations observed was typically Mediterranean. However, their relative frequencies was unique. The predominant allele was IVS-I-6 (T-->C), with an exceptionally high frequency of 48.5% for this mutation. The homozygous IVS-I-6 patients had widely variable clinical presentations, from typical transfusion-dependent thalassemia major to non-transfusion-dependent thalassemia intermedia phenotype. Since it is so widespread in these West Bank populations, the IVS-I-6 mutation may date back to ancient times. The nonsense mutation at codon 37 (G-->A) was found at a relatively high frequency of 11.3%, supporting the hypothesis that it originated in this region. The other mutations, at decreasing frequencies ranging from 9.5-1.5%, were: IVS-I-110 (G-->A), frameshift codon 5 (- CT), IVS-I-1 (G-->A), IVS-II-1 (G-->A), Hb S [beta6(A3)Glu-->Val], frameshift codons 8/9 (+G), codon 39 (C-->T), and -30 (T-->A). Our findings will improve health care for the Palestinian population, and also has implications for the study of the origin and spread of thalassemia in the Middle East.