IIa IIc Research Articles

Assessment of the Additive Effect of Remineralizing Agents in Combination With Fluoride Releasing Adhesives in the Prevention of Enamel Decalcification in Orthodontic Patients: An In Vitro Study.

Introduction Incorporation of remineralizing agents with fluoride-releasing bracket adhesives may prevent the development of white spot lesions (WSL) or reverse the established WSL in patients undergoing fixed orthodontic treatment. We aimed to find out how effectively casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and fluoride varnish (FV) can remineralize teeth when mixed with fluoride-releasing orthodontic adhesive. Materials and methods We randomly assigned a total of 60 premolar teeth, therapeutically extracted for orthodontic purposes, into two equal groups. Group I (n = 30) utilized fluoride-releasing adhesive (FR), and Group II (n = 30) bonded with non-fluoride adhesive (NFR). Based on the applied remineralizing agent, we further divided each of the two groups into three equal subgroups of 10: Group IA (FR+FV), Group IB (FR+CPP-ACP), Group IC (control-only FR), Group IIA (NFR+FV), Group IIB (NFR+CPP-ACP), and Group IIC (control-only NFR). Following bonding procedures, all the samples underwent pH cycling for 28 days, where the enamel samples were immersed in 20 ml of demineralizing solution for three hours, followed by immersion in 30 ml of remineralizing solution for 17 hours. The samples were analyzed for shear bond strength (SBS) on a universal testing machine and hardness values (HV) by the Vickers microhardness test (VMT) using the indentation method. We also evaluated the adhesive remnant index (ARI) scores to determine the site of bracket failure. Statistical analysis The shear bond strength (SBS) and hardness value (HV) were expressed as the mean, standard deviation (SD), and median for each subgroup. We used the non-parametric Kruskal-Wallis test to analyze the SBS and HV, followed by the Dunn-Bonferroni test for intra-pair differences. The ARI score was expressed as the frequency of the percentage distribution, and the difference in the distribution of ARI scores between the groups was assessed by the Cochran chi-square test. The probability (p) value equal to or less than 0.05 was considered statistically significant. Results The results show that Group IB, bonded with a fluoride-releasing adhesive and a CPP-ACP remineralizing agent surface treatment, has the highest HV of300.23 units. Group IIC (only NFR) has the lowest hardness of153.3 units, which is statistically significant (p < 0.001). However, the ARI scores are not statistically significant between the groups tested. Conclusion The bond strength of the adhesive and the surface hardness of the enamel increased with the addition of fluoride varnish and CPP-ACP to both the fluoride-releasing and non-fluoride-releasing adhesives.

Computed Tomography Bronchus Sign Subclassification during Radial Endobronchial Ultrasound-Guided Transbronchial Biopsy: A Retrospective Analysis

The presence of computed tomography bronchus sign (CT-BS) substantially increases the diagnostic yield of peripheral pulmonary lesions. However, the clinical significance of subdividing CT-BS remains controversial. We classified bronchus types on CT into six subtypes (CT-BS group I: types Ia-Ic with the bronchus connected within the lesion, group II: types IIa-IIc without connection) to clarify the differences in their characteristics and investigate the factors associated with diagnosis during radial endobronchial ultrasound (rEBUS)-guided bronchoscopy. In total, 1021 cases were analyzed. Our findings in diagnostic yields were that in CT-BS group I, penetrating type Ic was inferior to obstructed type Ia and narrowing type Ib (59.0% vs. 80.0% and 76.3%, p < 0.001, p = 0.004); in CT-BS group II, compressed type IIa showed no difference when compared with invisible type IIb and uninvolved type IIc (IIa: 52.8% vs. IIb: 46.3% and IIc: 35.7%, p = 0.253). Multivariable analysis revealed that bronchus type (types Ia and Ib vs. Ic) was a significant independent predictor of successful diagnosis in CT-BS group I (odds ratio, 1.78; 95% confidence interval, 1.04-3.05; p = 0.035), along with known factors such as rEBUS visualization. CT-BS subclassification may provide useful information regarding the bronchoscopic technique to facilitate accurate diagnosis.

ENTEROCOCCUS FAECALIS BİYOFİLM ELİMİNASYONUNUN ER:YAG MODALİTELERİNE (PIPS VE SWEEPS) GÖRE KARŞILAŞTIRILMASI

Background and purpose: To determine the effectiveness of novel two Er:YAG lasers, photon-initiated photoacoustic streaming (PIPS\SSP) and shock wave-enhanced emission photoacoustic streaming (SWEEPS\AutoSWEEPS) in terms of removal Enterococcus faecalis (E. faecalis) with or without antimicrobial agents (NaOCl and chlorhexidine gluconate). &#x0D; Methods: Forty-two extracted single-rooted mandibular premolars were prepared, sterilized, and then inoculated with E. faecalis for 4 weeks, and randomly divided into to two main and three subgroups (n= 7). Group Ia ( PIPS + distilled water), Group Ib (PIPS + 5% NaOCl), Group Ic (PIPS + CHX), and Group IIa (SWEEPS + distilled water), Group IIb (SWEEPS + 5% NaOCl), and Group IIc (SWEEPS + CHX). Following incubation for 48 hours at 37°C, the colonies formed (CFU) were counted. &#x0D; Results: NaOCl and CHX activated with PIPS\SSP or SWEEPS\AutoSWEEPS modalities showed significantly higher reduction rates than distilled water activated with both laser-activated methods (p0.05). &#x0D; Interpretation: Even novel laser activation methods or modalities are not sufficient alone to adequately reduce bacterial load and using antimicrobial agents with laser activation is necessary for the best reduction for microbial elimination. Novel SWEEPS\AutoSWEEPS modalıty with the conical 600μm tip showed no increased efficacy compared with PIPS\SSP mode. Besides, smaller fiber tip may increase the success of applications for minimally invasive access cavities and preparation.

THE POSSIBLE HISTOLOGICAL EFFECTS OF DACLATASVIR ON LIVER CELLS OF THE PREGNANT MICE

Introduction: HCV infection is a worldwide health problem. Egypt is one of the highest prevalence in adults. The prevalence of infection in pregnancy is between 1% and 8%. Treatment during pregnancy has been associated with many problems. Unfortunately, till now there is no approval for an antiviral drug to be used in pregnancy. A new group of antiviral agents has emerged known as directing acting antivirals (DAAs). Daclatasvir (DCV) is one of the second generation DAAs that has pangenotypic activity. Aim of the work: was to assess the possible histological effects of daclatasvir on the liver cells of the pregnant mice.Materials and Methods: Forty adult pregnant female mice were divided into two main groups; Group I (control group), included 10 mice which received distilled water. Group II (DCV group): included 30 mice subdivided into three equal groups: group IIa (DCV 12.5 mg/kg), group IIb (DCV 25 mg/kg) and group IIc (DCV 50 mg/kg body weight). They received the drug orally from GD6 to GD15. The pregnant mice were sacrificed (at GD 18-19) under anesthesia and after taking blood samples for biochemical analysis. Liver specimens were processed for histological and morphometric analysis.Results: Maternal toxicity with increased maternal mortalities was observed. Common hepatocellular changes in the three experimental groups showing; disturbed hepatic architecture, hypereosinophilic foci with indistinct boundaries, nuclear alterations, cellular vacuolation and prominent Von-kupffer cells. The presence of basophilic foci was prominent in GIIc. Increased collagen deposition and high levels of liver enzymes were mostly prominent in GIIa more than GIIc and GIIb respectively. These findings were concomitant with idiosyncratic drug induced liver injury (DILI) with pregnancy.In conclusion, DCV administration during pregnancy has a dose-dependent potential risk of DILI. Future studies are recommended to improve maternal outcome.

Synthetic Approaches to New Redox-Active Carbene Ligands

The design of new redox-switchable molecules requires the development of simple and efficient synthetic approaches. This study demonstrates the possibility of ortho-lithiation of ferrocenecarboxaldehyde (aryl)imines (Ia–Ic) followed by the reaction with ketones to give 1,2-disubstituted ferrocenes (IIa–IIc). These products, in turn, can be cyclized by treatment with trimethylsilyl triflate to give the cationic precursors of ferrocene-containing N-heterocyclic carbenes (IIIa–IIIc), in which the heterocycle is annulated to one of the ferrocene cyclopentadienyl ring. Treatment of IIIa–IIIc with a base in the presence of a source of rhodium afforded rhodium carbene complexes (IVa, IVb) in which the carbene ligand resembled cyclic alkylaminocarbenes in the electron-donor properties. Compounds Ib and IVa were studied by X-ray diffraction (CIF file CCDC nos. 2000413 and 2000414, respectively).

Effect of nitazoxanide and spiramycin metronidazole combination in acute experimental toxoplasmosis

Successful treatment of Toxoplasma gondii infection is difficult to attain. This study was designed to evaluate the efficacy of sulfamethoxazole-trimethoprim (SMZ-TMP), as the reference drug, nitazoxanide (NTZ), spiramycin (SP) and SP-metronidazole against the virulent RH T. gondii strain in acute experimental toxoplasmosis. One hundred Swiss albino mice were divided into control and experimental groups. Each mouse was infected with 2500 tachyzoites. Twenty infected untreated mice were used as control. The experimental group was subdivided into four subgroups (20 mice each); IIa SMZ-TMP, IIb NTZ, IIc SP and IId SP-metronidazole. All drugs were in tablet form, and were administered orally in suspension, for a period of seven days. Assessment of each drug efficacy was achieved through the study of mice survival time, mortality rate, parasite load, viability and morphological studies of tachyzoites by scanning electron microscope (SEM). The obtained results showed that SMZ-TMP, SP and SP-metronidazole were effective against acute murine toxoplasmosis and caused deformities in the tachyzoites ultrastructure. SP-metronidazole gave the best results on both mice survival rate and parasite load in the brain and liver. SMZ-TMP induced formation of prominent filaments extending from the deformed tachyzoites. NTZ showed little effect. In conclusion, all used drugs succeeded to prolong the survival time of the mice. SP-metronidazole gave the foremost effect on both mice survival rate and parasite load in the liver, spleen and brain. As this combination is nontoxic to human, it is promising for the treatment of human toxoplasmosis.

Heterogeneity of Streptococcus anginosus ß-hemolysis in relation to CRISPR/Cas.

Streptococcus anginosus is a commensal of the oral mucosa that can cause severe invasive infections. A considerable proportion of Streptococcus anginosus strains are ß-hemolytic due to the presence of an SLS-like gene cluster. However, the majority of strains do not display ß-hemolysis. To investigate ß-hemolysin heterogeneity in S. anginosus, we determined the presence of sag genes and correlated it with the presence of CRISPR/Cas genes in a collection of ß-hemolytic and non-ß-hemolytic strains. All of the ß-hemolytic strains carried the sag gene cluster. In contrast to other streptococci, clinical S. anginosus strains that do not display ß-hemolysis do not harbor sag genes. Phylogenetic analysis of the ß-hemolytic strains revealed that they belong to two previously defined clusters within S. anginosus. Correlation with CRISPR/Cas genes showed a significant difference for the presence of CRISPR/Cas in ß-hemolytic versus non-ß-hemolytic isolates. The presence of the CRISPR/Cas type IIA or type IIC locus is associated with the absence of sag genes; in 65% of the non-ß-hemolytic strains a CRISPR/Cas locus was found, while only 24% of ß-hemolytic strains carry CRISPR/Cas genes. Further analysis of the spacer content of the CRISPR systems revealed the presence of multiple self-targeting sequences directed against S. anginosus genes. These results support the hypothesis that horizontal gene transfer is involved in the acquisition of ß-hemolysin genes and that CRISPR/Cas may limit DNA uptake in S. anginosus.

AcrIIA5 Inhibits a Broad Range of Cas9 Orthologs by Preventing DNA Target Cleavage

CRISPR-Cas9 is an adaptive immune system for prokaryotes to defend against invasive genetic elements such as phages and has been used as a powerful tool for genome editing and modulation. To overcome CRISPR immunity, phages encode anti-CRISPR proteins (Acrs) to inhibit Cas9, providing an efficient "off-switch" tool for Cas9-based applications. Here, we characterized AcrIIA5, which is a Cas9 inhibitor discovered in a virulent phage of Streptococcus thermophilus. We found that AcrIIA5 is a potent and broad-spectrum inhibitor of CRISPR-Cas9, which can inhibit diverse Cas9 orthologs of type II-A, type II-B, and type II-C. AcrIIA5 inhibits Cas9 by preventing DNA target cleavage, but DNA target binding of Cas9 is unaffected. Importantly, it can affect the activity of the RuvC nuclease domain of Cas9 independent of the HNH nuclease domain. Our work expands the diversity of the inhibitory mechanisms used by Acrs and provides the guidance for developing controlling tools in Cas9-based applications.

Anti-CRISPR AcrIIA5 Potently Inhibits All Cas9 Homologs Used for Genome Editing

SUMMARYCRISPR-Cas9 systems provide powerful tools for genome editing. However, optimal employment of this technology will require control of Cas9 activity so that the timing, tissue specificity, and accuracy of editing may be precisely modulated. Anti-CRISPR proteins, which are small, naturally occurring inhibitors of CRISPR-Cas systems, are well suited for this purpose. A number of anti-CRISPR proteins have been shown to potently inhibit subgroups of CRISPR-Cas9 systems, but their maximal inhibitory activity is generally restricted to specific Cas9 homologs. Since Cas9 homologs vary in important properties, differing Cas9s may be optimal for particular genome-editing applications. To facilitate the practical exploitation of multiple Cas9 homologs, here we identify one anti-CRISPR, called AcrIIA5, that potently inhibits nine diverse type II-A and type II-C Cas9 homologs, including those currently used for genome editing. We show that the activity of AcrIIA5 results in partial in vivo cleavage of a single-guide RNA (sgRNA), suggesting that its mechanism involves RNA interaction.

Comparison of treatment efficacy between hyaluronic acid and arthrocentesis plus hyaluronic acid in internal derangements of temporomandibular joint

The aim of the study was to compare the effectiveness of hyaluronic acid (HA) injection and arthrocentesis plus HA injection for treating disc displacement with reduction (DDwR) and disc displacement without reduction (DDwoR). In this randomized clinical trial, patients were divided into 2 main groups: group I (DDwR) and group II (DDwoR). Sub-groups were made depending on allocated treatment: group Ia (arthrocentesis plus HA), group Ib (single HA), group Ic (control), group IIa (arthrocentesis plus HA), group IIb (single HA), and group IIc (control). The primary outcome variable was maximum pain on chewing, while maximum pain at rest, maximum non-assisted and assisted mouth opening, chewing efficiency, temporomandibular joint (TMJ) sounds, quality of life, treatment tolerability, and treatment effectiveness were secondary outcomes. The influences of individual study variables (gender, involved side, and duration of symptoms) on clinical outcomes were also examined. The study consisted of 116 TMJs of 90 patients (n = 45 in both main groups, TMJs = 58) aged 15–82 years. At the 6-month follow-up, improvement in all parameters, except for TMJ sounds, was recorded in all treatment groups, with no improvements in control groups. Notably, arthrocentesis plus HA showed superior improvement in chewing efficiency (p = 0.041) and quality of life (p = 0.047) of group I and quality of life (p = 0.004) in group II, compared to single HA. Furthermore, the duration of symptoms correlated with clinical outcomes. Both procedures successfully improved the symptoms of DDwR and DDwoR patients, but arthrocentesis plus HA injection seemed superior.

Subclassification and Treatment Results of Ethanol Embolotherapy of Type II Arteriovenous Malformations of the Extremity and Body

To evaluate the safety and efficacy of ethanol and coil embolization of type II arteriovenous malformation (AVM) according to a new subtype classification. Eighty-four type II AVMs in the body or extremity of 79 patients who underwent AVM treatment from 1996 to 2017 were retrospectively subclassified according to the angiographic morphology of the draining vein as type IIa (arterioles shunt to focal segment of single draining vein), type IIb (arterioles shunt to venous sac with multiple draining veins), and type IIc (arterioles shunt along long segment of draining vein). Coil and ethanol embolization of the focal or long segment of the draining vein or the venous sac was performed with direct puncture or transvenous approach according to subtype. Treatment outcomes, number of treatment sessions, and complications were analyzed. AVM cure (ie, complete embolization) rates were 95%, 76%, and 65% in types IIa, IIb, and IIc AVMs, respectively. The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs (P= .015). Median numbers of treatment sessions were 1 in types IIa and IIb AVMs and 2.5 in type IIc AVMs, with a significant difference between type IIc and the other 2 types (P < .05). Minor complications occurred in 20% of patents and major complications occurred in 7%. The cure rate of type IIa AVMs was significantly better than that of type IIc AVMs, which also required significantly more treatment sessions than the other 2 types.

Difference in Mortality Rate by Type of Anticoagulant in Elderly Patients with Cardiovascular Disease after Hip Fractures.

BackgroundThe purpose of this study was to investigate the difference in mortalilty rate between cardiovascular disease (CVD) patients and non-CVD patients after hip fracture surgery performed in elderly patients. In addition, we compared the effect of CVD medication on mortality after hip fracture surgery.MethodsPatients who underwent surgery for femoral intertrochanteric or neck fracture from January 2003 to December 2013 were enrolled in this study. After applying exclusion criteria, we categorized patients into group I (833 patients, non-CVD group) and group II (811 patients, CVD group). The CVD group was subcategorized as group IIa (332 patients, no medication), group IIb (381 patients, antiplatelet agents), and group IIc (98 patients, anticoagulation agents). Cumulative mortality rate at 30 days, 60 days, 3 months, and 1 year were compared between the groups.ResultsIn the 1,644 patients, the cumulative mortality rate at 30 days, 60 days, 3 months, and 1 year was 0.1%, 0.5%, 0.7%, and 8.2%, respectively, in group I and 1.0%, 1.6%, 2.5%, and 8.8%, respectively, in group II (p = 0.02, p = 0.03. p = 0.01, and p = 0.72, respectively). In the 811 group II patients, the cumulative mortality rate at 30 days, 60 days, 3 months, and 1 year was 0.3%, 0.6%, 1.2%, and 6.6%, respectively, in group IIa; 0.8%, 1.6%, 2.1%, and 9.4%, respectively, in group IIb; and 4.1%, 5.1%, 8.2%, and 13.3%, respectively, in group IIc (p = 0.003, p = 0.01, p = 0.004, and p = 0.10, respectively).ConclusionsCVD increases short-term mortality within 30 days, 60 days, and 3 months in elderly hip fracture patients. The use of anticoagulants in CVD patients increases the rate of surgical delay and short-term mortality within 30 days, 60 days, and 3 months.

Mechanisms and regulation of epithelial phosphate transport in ruminants: approaches in comparative physiology.

Ruminants have a unique utilization of phosphate (Pi) based on the so-called endogenous Pi recycling to guarantee adequate Pi supply for ruminal microbial growth and for buffering short-chain fatty acids. Large amounts of Pi enter the gastrointestinal tract by salivary secretion. The high saliva Pi concentrations are generated by active secretion of Pi from blood into primary saliva via basolateral sodium (Na+)-dependent Pi transporter type II. The following subsequent intestinal absorption of Pi is mainly carried out in the jejunum by the apical located secondary active Na+-dependent Pi transporters NaPi IIb (SLC34A2) and PiT1 (SLC20A1). A reduction in dietary Pi intake stimulates the intestinal Pi absorption by increasing the expression of NaPi IIb despite unchanged plasma 1,25-dihydroxyvitamin D3 concentrations, which modulate Pi homeostasis in monogastric species. Reabsorption of glomerular filtrated plasma Pi is mainly mediated by the Pi transporters NaPi IIa (SLC34A1) and NaPi IIc (SLC34A3) in proximal tubule apical cells. The expression of NaPi IIa and the corresponding renal Na+-dependent Pi capacity were modulated by high dietary phosphorus (P) intake in a parathyroid-dependent manner. In response to reduced dietary Pi intake, the expression of NaPi IIa was not adapted indicating that renal Pi reabsorption in ruminants runs at a high level allowing no further increase when P intake is diminished. In bones and in the mammary glands, Na+-dependent Pi transporters are able to contribute to maintaining Pi homeostasis. Overall, the regulation of Pi transporter activity and expression by hormonal modulators confirms substantial differences between ruminant and non-ruminant species.

Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes mellitus.

Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/β (Pparδ/β), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.

Fibroblast growth factor 23 is upregulated in the kidney in a chronic kidney disease rat model.

The hormone fibroblast growth factor 23 (FGF23) is secreted from bone and is involved in phosphorus (P) metabolism. FGF23 mainly binds the FGF receptor, which interacts with αKlotho in the kidney or parathyroid and regulates Na-dependent phosphate co-transporter type IIa (NaPi-IIa) and type IIc (NaPi-IIc) expression, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) activity, and parathyroid hormone (PTH) secretion. In this study, we utilized hemi-nephrectomized rats fed a high-P diet (HP Nx), rats subjected to a partial nephrectomy (PN) and rats with doxorubicin-induced renal failure (DXR) as chronic kidney disease (CKD) animal models and analyzed the P metabolism and FGF23 expression in the kidneys in each CKD model. We cultured HK2 cells with a high level of P, 1,25(OH)2D3 or transforming growth factor-β1 (TGFβ1) to investigate the FGF23 expression mechanism. In both the HP Nx and PN rats, the blood FGF23 and PTH levels were increased. However, the 1,25(OH)2D3 level was increased in the HP Nx rats and decreased in the PN rats. In all three animal models, the mRNA expression of αKlotho, NaPi-IIa and NaPi-IIc was decreased, and the mRNA expression of TGFβ1, collagen1a1, osteopontin and FGF23 was elevated in the kidney. FGF23 protein and mRNA were expressed at high levels in the extended tubule epithelium, which was an osteopontin-positive region in the HP and PN rats. FGF23 and osteopontin mRNAs were expressed in HK2 cells incubated with TGFβ1; however, these levels were not altered in HK2 cells incubated with 1,25(OH)2D3 and high P levels in vitro. Altogether, FGF23 is expressed in the kidneys in CKD model rats. Following stimulation with TGFβ1, the injured renal tubular epithelial cells are strongly suspected to express both FGF23 and osteopontin. FGF23 produced in the kidney might contribute to P metabolism in subjects with CKD.

Unloading-induced atrophy and decreased oxidative capacity of the soleus muscle in rats are reversed by pre- and postconditioning with mild hyperbaric oxygen

Our aim was to determine the effects of pre‐ and/or postconditioning with mild hyperbaric oxygen (1.25 atmospheric pressure, 36% oxygen for 3 h/day) on the properties of the soleus muscle that was atrophied by hindlimb suspension‐induced unloading. Twelve groups of 8‐week‐old rats were housed under normobaric conditions (1 atmospheric pressure, 20.9% oxygen) or exposed to mild hyperbaric oxygen for 2 weeks. Ten groups then were housed under normobaric conditions for 2 weeks with their hindlimbs either unloaded via suspension or not unloaded. Six groups subsequently were either housed under normobaric conditions or exposed to mild hyperbaric oxygen for 2 weeks: the suspended groups were allowed to recover under reloaded conditions (unrestricted normal cage activity). Muscle weights, cross‐sectional areas of all fiber types, oxidative capacity (muscle succinate dehydrogenase activity and fiber succinate dehydrogenase staining intensity) decreased, and a shift of fibers from type I to type IIA and type IIC was observed after hindlimb unloading. In addition, mRNA levels of peroxisome proliferator‐activated receptor γ coactivator‐1α decreased, whereas those of forkhead box‐containing protein O1 increased after hindlimb unloading. Muscle atrophy and decreased oxidative capacity were unaffected by either pre‐ or postconditioning with mild hyperbaric oxygen. In contrast, these changes were followed by a return to nearly normal levels after 2 weeks of reloading when pre‐ and postconditioning were combined. Therefore, a combination of pre‐ and postconditioning with mild hyperbaric oxygen can be effective against the atrophy and decreased oxidative capacity of skeletal muscles associated with hindlimb unloading.

Paragenesis and fluid evolution of the Halasu III porphyry Cu deposit, East Junggar (NW China): Implications for the Paleozoic multiphase superimposing mineralization in the Central Asian Orogenic Belt

The Halasu III deposit, an important Cu deposit in the southernmost part of the Halasu porphyry Cu belt, is situated in the East Junggar block in NW China. Copper and Mo sulfide mineralization commonly occurs as disseminations or veinlets, and is mainly associated with Devonian granodiorite porphyry. Our detailed field geological investigation identified late-stage high grade Cu sulfide-bearing veining superimposed on the earlier porphyry Cu–Mo mineralization.Four hydrothermal alteration and mineralization stages were identified, namely the early epidote alteration (Stage I), porphyry-style alterations (Stage II comprising II-A potassic, II-B propylitic and II-C phyllic alteration sub-stages), late veining (Stage III) and supergene processes (Stage IV) in the northern- and southern mineralization zones at Halasu III. Multiphase granodiorite- and alkali granite dykes intruded the Beitashan Formation volcanic rocks, generating the early epidote alteration. Potassic alteration (Stage II-A) occurred in and around the NNW-treading granodiorite dykes, while the propylitic alteration (Stage II-B) occurred in the intrusions or volcanic wall rocks around the potassic zone. These early alteration assemblages were overprinted by the subsequent, structurally-controlled phyllic alteration (Stage II-C) confined within the granodiorite porphyry. Late veins (Stage III) include sulfide-bearing (Stage III-A) and sulfide-barren (Stage III-B) ones. Supergene process (Stage IV), represented by hematite and jarosite replacing primary sulfides, extends tens of meters down depth and is commonly fracture-controlled.Three fluid inclusion (FI) types were recognized, namely Type A (single-phase), B (liquid–vapor two-phase) and C (liquid–vapor–solid three-phase). For Type B FIs, those of potassic alteration homogenized at 183–347°C, with corresponding salinities of 6.2–17.8wt.% NaCl equiv. The propylitic and phyllic FIs homogenized at 172–425°C and 231–352°C, respectively, with the corresponding salinities of 0.9–14.0wt.% NaCl equiv. and 0.4–10.5wt.% NaCl equiv. The sulfide-bearing vein FIs homogenized at 243–410°C (Stage III-A-1), 260–362°C (Stage III-A-2) and 117–235°C (Stage III-A-3), along with the corresponding salinities of 1.9–9.2wt.% NaCl equiv., 1.1–6.7wt.% NaCl equiv. and 6.5–17.1wt.% NaCl equiv., respectively. The sulfide-barren vein FIs yielded homogenization temperatures of 260–380°C (Stage III-B-1) and 114–297°C (Stage III-B-2), with corresponding salinities of 1.7–9.8wt.% NaCl equiv. and 0.2–13.6wt.% NaCl equiv., respectively. We suggest that hydrothermal veins at Halasu III may have undergone complex and superimposing alteration due to the episodic reopening of the preexisting veins, with Stage III-A-3 veining overprinting the phyllic alteration and Stage III-A-2 veining. Stage III-B-2 veining superimposed on the potassic alteration, as well as on Stages III-A-1 and III-B-1 veining.Paragenetic sequence and fluid evolution at Halasu III indicate that these complex hydrothermal alteration stages were formed in accordance with the regional tectonic evolution. These various alteration and mineralization stages at Halasu III deposit reveal a prolonged history of magmatic and hydrothermal processes extending episodically from the Middle Devonian to Middle Permian, wherein early mineralization was overprinted by late hydrothermal events. Such superimposed mineralization may occur commonly in the Paleozoic Central Asia Orogenic Belt.

Evaluation of serum aminotransaminases and bilirubin in different treatment regimens for chronic hepatitis C virus

Hepatitis C virus (HCV) affects more than 180 million people worldwide and it is the leading cause of chronic liver disease .The aim of this study is to detect liver enzymes and bilirubin levels before and after different anti viral therapies in Egyptian chronic hepatitis C infected patients. One hundred and fifty patients with chronic HCV infection who have anti HCV antibodies detected by ELISA were selected to undergo Real-Time polymerase chain reaction (RT-PCR) ; of them 30 blood samples were positive for HCV antibodies and negative for HCV RNA (control group I) and 120 blood samples were positive for HCV antibodies and positive for HCV RNA (diseased group II) which is subdivided into four groups according to the received treatment; interferon and ribavirin (group IIa), interferon, sofosbuvir and ribavirin (group IIb), sofosbuvir and ribavirin (group IIc) and herbal therapy (group IId). Results revealed; after treatment there was a statistical significant reduction in the mean values of ALT in group IIa, group IIb and group IIc (mean: 38.00, 45.5 and 36.00 U/L respectively; P 0.05). AST levels showed a non significant increase after treatment in group IIa (mean: 43.7 U/L; P>0.05), a non significant decrease in group IIb and group IId (mean: 40.03 and 39.80 U/L respectively; P>0.05) and an extremely significant decrease after treatment in group IIc (mean: 28.30 U/L; P 0.05), a non significant increase after treatment in group IIb (mean: 0.811 mg/dL; P>0.05) and an extremely significant increase in group IIc (mean: 1.05 mg/dL; P 0.05). In conclusion, Serum ALT is a normal value after all treatment regimens included in our study; serum AST is slightly elevated in combination therapy of pegylated interferon plus ribavirin while serum bilirubin is highly elevated in case of sofosbuvir dual therapy than sofosbuvir trible therapy.

Evaluation of serum iron and ferritin in different treatment regimens for chronic hepatitis C virus

This work aims to develop a biochemical study on the effect of both interferon containing treatment regimens and interferon free regimens on serum iron and serum ferritin in patients with chronic hepatitis C and to evaluate the role of iron in the severity and course of disease. Blood samples from one hundred fifty patients aged from 25 to 57 years old were withdrawn; of them 30 blood samples were positive for HCV antibodies and negative for HCV RNA (control group I) and 120 blood samples were positive for HCV antibodies and positive for HCV RNA (diseased group II) which is subdivided into four groups according to the received treatment; interferon and ribavirin (group IIa), interferon, sofosbuvir and ribavirin (group IIb), sofosbuvir and ribavirin (group IIc) and herbal therapy (group IId). After treatment there was an extremely significant decrease in iron levels (94 ± 16.96 µg/dL) in group IIa, , while there was an extremely significant increase in iron levels after treatment in group IIb and group IIc (160.4 ± 37.53 µg/dL and 183.7 ± 37.36 µg/dL), respectively. Group IId showed a non significant decrease in iron levels after treatment (150.5 ± 21.35 µg/dL). For ferritin levels, group IIa, group IIb and group IIc showed significant increase in serum ferritin levels after treatment (157.6 ± 13.44, 99.5 ±14.99, and 96.63 ± 15.22 ng/mL), respectively. On the other hand, group IId showed a non significant increase in ferritin levels after treatment (90.93 ± 6.883 ng/mL). It can be concluded that serum ferritin increases in HCV patients treated with combined pegylated interferon--alfa (PEG-IFN)-ribavirin than the other treatment regimens. In addition, Serum iron decreases in HCV patients treated with combined PEG-IFN-

Conformational dynamics of stem II of the U2 snRNA.

The spliceosome undergoes dramatic changes in both small nuclear RNA (snRNA) composition and structure during assembly and pre-mRNA splicing. It has been previously proposed that the U2 snRNA adopts two conformations within the stem II region: stem IIa or stem IIc. Dynamic rearrangement of stem IIa into IIc and vice versa is necessary for proper progression of the spliceosome through assembly and catalysis. How this conformational transition is regulated is unclear; although, proteins such as Cus2p and the helicase Prp5p have been implicated in this process. We have used single-molecule Förster resonance energy transfer (smFRET) to study U2 stem II toggling between stem IIa and IIc. Structural interconversion of the RNA was spontaneous and did not require the presence of a helicase; however, both Mg2+ and Cus2p promote formation of stem IIa. Destabilization of stem IIa by a G53A mutation in the RNA promotes stem IIc formation and inhibits conformational switching of the RNA by both Mg2+ and Cus2p. Transitioning to stem IIa can be restored using Cus2p mutations that suppress G53A phenotypes in vivo. We propose that during spliceosome assembly, Cus2p and Mg2+ may work together to promote stem IIa formation. During catalysis the spliceosome could then toggle stem II with the aid of Mg2+ or with the use of functionally equivalent protein interactions. As noted in previous studies, the Mg2+ toggling we observe parallels previous observations of U2/U6 and Prp8p RNase H domain Mg2+-dependent conformational changes. Together these data suggest that multiple components of the spliceosome may have evolved to switch between conformations corresponding to open or closed active sites with the aid of metal and protein cofactors.