TH Groups Research Articles

Quality analysis of four filling techniques in ovoid root canals prepared with M® instruments

Aims: This study aimed to assess the quality of various filling techniques in ovoid root canals prepared using M® instruments. Materials and Methods: Sixty ovoid root canals underwent endodontic treatment with M® instruments and were subsequently divided randomly into four experimental groups, each employing a different obturation technique: TU - single cone; TL - active lateral condensation; TH - Tagger hybrid; TS - Schilder technique. Digital radiographs were taken in both mesiodistal and buccolingual directions to examine the filled teeth. The percentage of filling material and empty spaces was quantified using Photoshop® software. Data were subjected to statistical analysis using the one-way ANOVA test and T test (? = 0.05). Results: In the TL and TS groups, there was a significantly lower average percentage of unfilled spaces compared to the TU and TH groups (P<0.0001). When analyzing the radiographic directions, the mesiodistal view exhibited the highest mean percentage of unfilled spaces, with differences in filling quality observed only in the TU and TL groups. Conclusions: Active lateral condensation and Schilder techniques demonstrated superior performance in achieving effective filling of ovoid root canals.

Toxicity and transcriptome sequencing analyses of Acipenser schrenckii under titanium dioxide nanoparticles stress

Increasing utilization of titanium dioxide nanoparticles (TiO2-NPs), with a wide range of applications, has resulted in the increased release of the material into the environment. In this study, we combined Illumina short-line RNA sequencing (RNA-Seq) and PacBio Iso-sequencing methods to obtain the transcriptome of Acipenser schrenckii livers treated with 5.27 (TH), 0.527 (TM), and 0.0527 mg/L (TL) TiO2-NPs for 14 days to elucidate the mechanisms underlying the effects of TiO2-NPs on sturgeons. In total, 39.67G subread bases and 31092 de-redundant transcripts (8929 unigenes) were obtained from A. schrenckii livers, with a mean length of 2289 bp. Moreover, 293 differentially expressed genes (DEGs) related to TiO2-NP stress were identified using DESeq; 175, 174, and 62 DEGs were identified in the TH vs. TC, TM vs. TC, and TL vs. TC groups. The Kyoto Encyclopedia of Genes and Genomes pathways of DEGs related to immunity (neuroactive ligand-receptor interaction, rheumatoid arthritis, NF-kappa B signaling pathway, and graft-versus-host disease) were significantly altered by TiO2-NP exposure, and the expression of interleukin-8, a possible biomarker for environmental pollution, was significantly upregulated. The pathways of alpha-linolenic acid metabolism, glycerolipid metabolism, and arachidonic acid metabolism associated with the defense against oxidative stress were also influenced by TiO2-NP exposure. The activity of carboxyl ester lipase involved in glycerolipid metabolism was rapidly downregulated in the TH and TM groups which may play a major role in glycerolipid metabolism regulation. The expression patterns of eight selected genes were generally consistent with the quantitative real-time PCR analysis results.

A diminished sciatic nerve structural integrity is associated with distinct peripheral sensory phenotypes in individuals with type 2 diabetes

Aims/hypothesisQuantitative sensory testing (QST) allows the identification of individuals with rapid progression of diabetic sensorimotor polyneuropathy (DSPN) based on certain sensory phenotypes. Hence, the aim of this study was to investigate the relationship of these phenotypes with the structural integrity of the sciatic nerve among individuals with type 2 diabetes.MethodsSeventy-six individuals with type 2 diabetes took part in this cross-sectional study and underwent QST of the right foot and high-resolution magnetic resonance neurography including diffusion tensor imaging of the right distal sciatic nerve to determine the sciatic nerve fractional anisotropy (FA) and cross-sectional area (CSA), both of which serve as markers of structural integrity of peripheral nerves. Participants were then assigned to four sensory phenotypes (participants with type 2 diabetes and healthy sensory profile [HSP], thermal hyperalgesia [TH], mechanical hyperalgesia [MH], sensory loss [SL]) by a standardised sorting algorithm based on QST.ResultsObjective neurological deficits showed a gradual increase across HSP, TH, MH and SL groups, being higher in MH compared with HSP and in SL compared with HSP and TH. The number of participants categorised as HSP, TH, MH and SL was 16, 24, 17 and 19, respectively. There was a gradual decrease of the sciatic nerve’s FA (HSP 0.444, TH 0.437, MH 0.395, SL 0.382; p=0.005) and increase of CSA (HSP 21.7, TH 21.5, MH 25.9, SL 25.8 mm2; p=0.011) across the four phenotypes. Further, MH and SL were associated with a lower sciatic FA (MH unstandardised regression coefficient [B]=−0.048 [95% CI −0.091, −0.006], p=0.027; SL B=−0.062 [95% CI −0.103, −0.020], p=0.004) and CSA (MH β=4.3 [95% CI 0.5, 8.0], p=0.028; SL B=4.0 [95% CI 0.4, 7.7], p=0.032) in a multivariable regression analysis. The sciatic FA correlated negatively with the sciatic CSA (r=−0.35, p=0.002) and markers of microvascular damage (high-sensitivity troponin T, urine albumin/creatinine ratio).Conclusions/interpretationThe most severe sensory phenotypes of DSPN (MH and SL) showed diminishing sciatic nerve structural integrity indexed by lower FA, likely representing progressive axonal loss, as well as increasing CSA of the sciatic nerve, which cannot be detected in individuals with TH. Individuals with type 2 diabetes may experience a predefined cascade of nerve fibre damage in the course of the disease, from healthy to TH, to MH and finally SL, while structural changes in the proximal nerve seem to precede the sensory loss of peripheral nerves and indicate potential targets for the prevention of end-stage DSPN.Trial registrationClinicalTrials.gov NCT03022721Graphical

Novel Interactomes of Cardiac Noncoding RNA Transcriptome under Altered Thyroid Hormonal States

Background: Noncoding RNAs are emerging as key players in cardiovascular diseases. Both Hypothyroidism (HypoTH; low thyroid hormones [THs]) and hyperthyroidism (HyperTH; high THs) can be deleterious to the heart. We recently showed the involvement of long noncoding RNAs (lncRNAs) in HypoTH under caloric restriction. However, a comprehensive view of the cardiac transcriptome and its interactions under altered TH states is lacking. We hypothesized that cardiac noncoding interaction networks are significantly altered in the cardiac-TH regulatory axis. Methods: In this randomized, blinded study (2.5 mon), adult C57 mixed-sex mice (n=8-10/group; 5 females, 3-5 males) were divided into Control, HypoTH (low iodine diet with oral methimazole), HyperTH (1 microgram [ug]/gram Thyroxine, T4; intraperitoneal) and HypoTH+T3 (similar to HypoTH with oral 12 ug/kilogram/day Triiodothyronine, T3). Morphometrics, ultrasound, immunosorbent assay, Quantitative real-time PCR (qPCR) and whole transcriptome sequencing were performed. Statistical analyses were done by Tukey’s analysis of variance (with post hoc), Benjamini & Hochberg and others using Prism, R, etc. RNA quality was validated by Nanodrop, gel electrophoresis and Bioanalyzer. Results: In mixed-sex mice, HypoTH showed significant cardiac atrophy (whole heart, LV and right ventricle), low serum total T3 and T4 levels (p<0.001), low heart rate, (p<0.01) diminished systolic LV posterior (p<0.05) and septal wall thicknesses (p<0.01) and fractional shortening (-34%; p<0.01) compared to controls. T3 therapy showed feedback inhibition of T4 (p<0.001) and restored all other parameters including LV systolic diameter (p<0.05). Among others, HyperTH had cardiac hypertrophy and increased T3 and T4 (p<0.05) compared to controls (p<0.001). Similar significant results were obtained in males and females. qPCR of shorter-term treatment showed significantly altered lncRNAs in inflammatory and immune pathways. Whole transcriptome sequencing showed numerous differentially expressed, significantly altered and enriched ( GO and KEGG) targets across the groups among all RNA species studied (p-adjusted; padj<0.05). These include novel and known lncRNAs, microRNAs (miRNAs) and messenger (m) RNAs that change in opposite directions in low vs high TH groups. These also include 11 novel circular RNAs (circRNAs; CIRI2) decreased with HyperTH (padj<0.05). We also uncovered novel co-expression and interactions of miRNA-mRNA, miRNA-lncRNA, mRNA-lncRNA, circRNA-miRNA and miRNA-lncRNA-mRNA (including TH receptor alpha; miRanda, Cytoscape) and also splicing and base editing events (padj<0.05). Conclusions: This is the first cross-disciplinary study reporting a comprehensive cardiac transcriptome-wide interactome network of circRNA, lncRNA, miRNA and mRNA in a TH-responsive manner. This offers significant translational potential to develop diadiagnostic and therapeutic targets for cardiac-endocrine co-morbid conditions. NYITCOM at A-State, ABI This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Influence of magnetic iron oxide nanoparticles in reproductive efficiency of adult male rats

This study aimed to investigate the dose-dependent and time-dependent effect of magnetic iron oxide nanoparticles (MIONPs) on reproduction in male rats. Following their synthesis, the physicochemical properties of MIONPs were determined. Sixty-four adult male rats, aged 90 days were randomly assigned to control (C), orally administered with distilled water, and three treated groups, orally administered with 1, 5, 10 mg/kg/day of MIONPs solution (TL, TM, and TH groups, respectively), for 28 days. Each group was allocated to two subgroups, sacrificed after 14 and 28 days of treatment. After each period, the males were weighed and sacrificed. Decreased body weight and genital organ weights were shown in TM and TH groups, at both experimental periods, compared with control in a dose-dependent manner. The serum concentration of GnRH, FSH, LH, and testosterone increased in the TL group and decreased in TM and TH groups compared with control in a dose-dependent and time-dependent manner. At both periods, the lowest expression levels of pituitary FSHβ and LHβ genes and testicular inh-α and LHR genes were recorded in TM and TH groups, and the highest levels were expressed in the TL group. The testis sections of TL males, showed normal architecture, but those from TM and TH groups showed degenerative and necrotic changes, reduced germinal epithelium, vacuolation, and decreased number of spermatocytes apparent. It is concluded that a low dose of MIONPS has a beneficial effect, whereas moderate or high doses have pathological effects on male reproduction.

Comparison Study of Extraction Accuracy of 3D Facial Anatomical Landmarks Based on Non-Rigid Registration of Face Template

(1) Background: Three-dimensional (3D) facial anatomical landmarks are the premise and foundation of facial morphology analysis. At present, there is no ideal automatic determination method for 3D facial anatomical landmarks. This research aims to realize the automatic determination of 3D facial anatomical landmarks based on the non-rigid registration algorithm developed by our research team and to evaluate its landmark localization accuracy. (2) Methods: A 3D facial scanner, Face Scan, was used to collect 3D facial data of 20 adult males without significant facial deformities. Using the radial basis function optimized non-rigid registration algorithm, TH-OCR, developed by our research team (experimental group: TH group) and the non-rigid registration algorithm, MeshMonk (control group: MM group), a 3D face template constructed in our previous research was deformed and registered to each participant's data. The automatic determination of 3D facial anatomical landmarks was realized according to the index of 32 facial anatomical landmarks determined on the 3D face template. Considering these 32 facial anatomical landmarks manually selected by experts on the 3D facial data as the gold standard, the distance between the automatically determined and the corresponding manually selected facial anatomical landmarks was calculated as the "landmark localization error" to evaluate the effect and feasibility of the automatic determination method (template method). (3) Results: The mean landmark localization error of all facial anatomical landmarks in the TH and MM groups was 2.34 ± 1.76 mm and 2.16 ± 1.97 mm, respectively. The automatic determination of the anatomical landmarks in the middle face was better than that in the upper and lower face in both groups. Further, the automatic determination of anatomical landmarks in the center of the face was better than in the marginal part. (4) Conclusions: In this study, the automatic determination of 3D facial anatomical landmarks was realized based on non-rigid registration algorithms. There is no significant difference in the automatic landmark localization accuracy between the TH-OCR algorithm and the MeshMonk algorithm, and both can meet the needs of oral clinical applications to a certain extent.

Citrus tangerine pith extract alleviates hypoxia-induced ileum damage in mice by modulating intestinal microbiota.

Visitors to high altitude are susceptible to hypoxia-induced acute intestinal mucosal barrier injury and severe gastrointestinal disorders, which are life-threatening. Citrus tangerine pith extract (CTPE) is rich in pectin and flavonoids and has been proved to enhance intestinal health and improve gut dysbiosis. In this study, we aim to explore the protective effect of CTPE on ileum injury induced by intermittent hypobaric hypoxia in a mouse model. Balb/c mice were divided into blank normoxia (BN), blank hypobaric hypoxia (BH), hypobaric hypoxia plus CTPE (TH), and hypobaric hypoxia plus Rhodiola extract (RH) groups. From the 6th day of gavage, mice in BH, TH, and RH groups were transferred into a hypobaric chamber at a simulated elevation of 6000 m for 8 hours per day for 10 days. Then half the mice were tested for small intestine movement, and others were used to evaluate intestinal physical barrier function, inflammation, and gut microbiota. Results showed that CTPE reversed the increase of intestinal peristalsis, effectively attenuated impaired structural integrity of ileum, improved the mRNA and protein expression levels of tight junction proteins, and reduced serum D-LA content in mice to alleviate hypoxia-induced mucosal barrier damage. Moreover, CTPE supplementation ameliorated hypoxia-induced intestinal inflammation response by significantly downregulating the proinflammatory cytokines IL-6, TNF-α and IFN-γ. By 16S rDNA gene sequencing of gut microbiota, CTPE significantly increased the abundance of probiotic Lactobacillus, suggesting that CTPE may be used as a prebiotic to regulate ecology of intestinal microorganisms. In addition, Spearman rank correlation analysis revealed that changed gut microbiota were significantly correlated with alteration of intestinal barrier function indexes. Taken together, these results indicate that CTPE effectively alleviates hypoxia-induced intestinal injury in mice and enhances intestinal integrity and barrier function by altering intestinal microbiota composition.

Speech understanding in diffuse steady noise in typically hearing and hard of hearing listeners.

Spatial cues can facilitate segregation of target speech from maskers. However, in clinical practice, masked speech understanding is most often evaluated using co-located speech and maskers (i.e., without spatial cues). Many hearing aid centers in France are equipped with five-loudspeaker arrays, allowing masked speech understanding to be measured with spatial cues. It is unclear how hearing status may affect utilization of spatial cues to segregate speech and noise. In this study, speech reception thresholds (SRTs) for target speech in “diffuse noise” (target speech from 1 speaker, noise from the remaining 4 speakers) in 297 adult listeners across 9 Audilab hearing centers. Participants were categorized according to pure-tone-average (PTA) thresholds: typically-hearing (TH; ≤ 20 dB HL), mild hearing loss (Mild; >20 ≤ 40 dB HL), moderate hearing loss 1 (Mod-1; >40 ≤ 55 dB HL), and moderate hearing loss 2 (Mod-2; >55 ≤ 65 dB HL). All participants were tested without aided hearing. SRTs in diffuse noise were significantly correlated with PTA thresholds, age at testing, as well as word and phoneme recognition scores in quiet. Stepwise linear regression analysis showed that SRTs in diffuse noise were significantly predicted by a combination of PTA threshold and word recognition scores in quiet. SRTs were also measured in co-located and diffuse noise in 65 additional participants. SRTs were significantly lower in diffuse noise than in co-located noise only for the TH and Mild groups; masking release with diffuse noise (relative to co-located noise) was significant only for the TH group. The results are consistent with previous studies that found that hard of hearing listeners have greater difficulty using spatial cues to segregate competing speech. The data suggest that speech understanding in diffuse noise provides additional insight into difficulties that hard of hearing individuals experience in complex listening environments.

Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-β and NF-κB expression in rats with pig serum-induced liver fibrosis.

Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-β1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-β1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-β1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

Evaluating Different Low-intensity Extracorporeal Shockwave Therapy Intensities in the Treatment of Peyronie's Disease in a Rat Model

ABSTRACT Introduction Low-intensity extracorporeal shockwave therapy (Li-ESWT) is postulated to have physiologic effects including neo-angiogenesis, upregulation of vasoactive endothelial growth factors, nerve recovery, reduction of fibrotic changes, cavernosal tissue remodeling, and reduction in sympathetic tone. To date, randomized clinical trials have failed to demonstrate a change in penile curvature, with mixed results on erectile function, in Peyronie's disease (PD) patients. Objective To evaluate the treatment effect of Li-ESWT for amelioration of PD-associated fibrosis and PD-associated erectile dysfunction using a rat model of PD. Methods 32 adult male Sprague-Dawley rats were divided evenly into four groups: sham (S), control (T), low setting Li-ESWT (TL), and high setting Li-ESWT (TH). Normal saline was injected into the tunica albuginea (TA) of the sham group. Transforming growth factor beta-1 (TGF-B1) was injected into the TA of the remaining groups to induce Peyronies-like fibrosis. After 5 weeks of TGF-B1 induction, treatment with Li-ESWT shockwave (UroGold 100™) was initiated. Treatment was delivered biweekly for 3 weeks (6 total sessions). Device settings were 600 shocks at 3 Hz, at level 6 (0.093 mJ/mm2) for the Low group and at level 12 (0.125 mJ/mm2) for the High group. Two weeks after the end of treatment, erectile function was measured by ratio of intracavernosal pressure (ICP) to mean arterial pressure (MAP). Histological analysis by H&amp;E and Trichrome staining was performed. Western blot analysis of Collagens I (COL1A1), III (COL3A1), elastin, alpha-smooth muscle actin (a-SMA), and TGF-B1 was performed. Results There was no significant difference demonstrated in erectile function between T control group and TL and TH groups (P &amp;gt; 0.05). However, there seems to be a trend in decreased amount of fibrosis upon examination of the prepared histologic sections. Animals in the TL and TH groups had decreased COL1A1, COL3A1, elastin, and TGF-B1 expression in the TA compared to the T group. a-SMA expression in the treatment groups was found to be increased compared to both S and T groups. Conclusions Our preliminary data shows that Li-ESWT treatments, at different intensities, may decrease fibrosis induced by TGF-B1 TA injections. Additionally, Li-ESWT was not found to have conclusive positive effects on erectile function. Disclosure Yes, this is sponsored by industry/sponsor: Sexual Medicine Society of North America Clarification Industry funding only - investigator initiated and executed study Any of the authors act as a consultant, employee or shareholder of an industry for: Endo Pharmaceuticals

Safety of DW-MSC infusion in patients with low clinical risk COVID-19 infection: a randomized, double-blind, placebo-controlled trial

BackgroundDue to their immunomodulatory properties, mesenchymal stem cells (MSCs) have been proposed to have therapeutic potential to improve clinical outcomes in COVID-19. However, the safety and efficacy profile of MSC infusion therapy in patients with non-severe COVID-19 infection has not been completely established; there is, in particular, a substantial void in the literature on dose-dependent studies of MSC infusion in patients with low clinical risk COVID-19 infection.MethodsThis phase 1 double-blind, placebo-controlled, randomized clinical trial examines the safety, feasibility, and tolerability of 2 doses (high and low) of DW-MSC in patients with low clinical risk COVID-19. A total of 9 patients were enrolled in this study and randomized into low-dose (TL), high-dose (TH), and placebo (C) groups. Subjects in the TL and TH groups received single intravenous infusions of 5.0 × 107 cells and 1.0 × 108 cells, respectively. The main outcome was the occurrence of treatment-emergent adverse events (TEAE) during the 28-day study period. Vital signs and various inflammatory markers were also monitored weekly during the observation period.ResultsThere were no apparent differences in clinical characteristics between study groups (TL, TH, and C) at baseline. All patients did not show the progression of severity during the study period. During the course of the study, 6 episodes of TEAE were observed in 5 subjects; however, none of the TEAEs were severe. During the follow-up period, 8 subjects recovered and were discharged from the hospital without complications. A subject exhibited abnormal liver function biomarkers at the end of the study period. Changes in inflammatory markers throughout the clinical course were not vastly different across study groups.ConclusionsOur clinical trial has provided reliable results regarding the safety of MSCs in low clinical risk COVID-19 subjects treated with MSCs. However, further confirmation of the therapeutic efficacy aspects of MSC will require large-scale randomized controlled trials in subjects with varying severity profiles for COVID-19.Trial registrationClinicalTrials.gov, NCT04535856. Registered 2 September 2020, https://clinicaltrials.gov/ct2/show/NCT04535856

DNA methylation plays an important role in iron-overloaded Tibetans.

The prevalence of iron overload in Tibetans in Tibet is higher than that in Han. DNA methylation (DNAm) is closely related to iron metabolism and iron level. Nevertheless, the epigenetic status of Tibetans with iron overload is unknown, and we therefore aimed to explore whether the phenomenon observed in the Tibetan population is regulated by epigenetics. The results showed that 2.26% of cytosine was methylated in the whole genome, and that the rate of CG cytosine methylation was higher in individuals in the iron overload (TH) group than in those in the iron normal (TL) group. We analyzed differentially methylated genes (DMGs) in whole-genome bisulfite sequencing data from the TH and TL groups of high-altitude Tibetans. Protein-protein interaction and pathway analyses of candidate DMGs related to iron uptake and transport showed that epigenetic changes in 10 candidate genes (ACO1, CYBRD1, FLVCR1, HFE, HMOX2, IREB2, NEDD8, SLC11A2, SLC40A1 and TFRC) are likely to relate to iron overload. This work reveals, for the first time, changes of DNAm in Tibetan people with iron overload, which suggest that DNAm is a mechanism underlying differences in iron content between individuals in the high-altitude Tibetan population. Our findings should contribute to the study of iron metabolism and the overall health status of Tibetans.

The effect of 24-week belimumab treatment withdrawal followed by treatment restart in patients with SLE: an open-label, non-randomised 52-week study

BackgroundTreatment goals for patients with systemic lupus erythematosus (SLE) include minimising disease activity and reducing the risk of flares. Although belimumab is effective at reducing disease activity and risk of severe flares, it was previously unknown what the clinical effects were upon treatment discontinuation. The objective of this study was to assess the impact of temporary withdrawal of intravenous (IV) belimumab in patients with SLE.MethodsThis multicentre, open-label, non-randomised, 52-week study (GSK Study BEL116027; NCT02119156) recruited patients with SLE and stable low disease activity, of whom those on belimumab 10 mg/kg IV plus standard therapy either discontinued belimumab for 24 weeks and then restarted belimumab 10 mg/kg IV every 4 weeks (q4w) for 28 weeks (treatment holiday [TH] group), or continued on belimumab 10 mg/kg IV plus standard therapy q4w for 52 weeks (treatment continuation [TC] group). The primary endpoint was median time to first Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) Flare Index flare. Secondary and other endpoints included rate of any flare, time to severe flare, time to renal flare and rebound (SELENA-SLEDAI score exceeding parent study baseline). Data on rebound phenomenon in patients with any disease level of SLE who had permanently withdrawn from further belimumab treatment (long-term discontinuation group [LTD]) were also assessed. Safety was assessed.ResultsThe primary endpoint was not evaluable in the TH (n = 12) and TC (n = 29) groups as fewer than half of patients flared. Unadjusted flare rates per patient-year were 1.0 during treatment discontinuation and 0.3 during treatment restart (0.6 overall) in the TH group and 0.6 in the TC group; there were no severe or renal flares. No TH patients rebounded; 2 (6.9%) TC patients rebounded; 2 (5.1%) patients in the LTD group rebounded. There were no new safety signals.ConclusionsTwenty-four-week belimumab discontinuation did not appear to increase the risk of flares or rebound in patients with low SLE disease activity; flare rates were low in both groups. Further studies may help to fully determine the effect of belimumab discontinuation.Trial registrationClinicalTrials.gov, NCT02119156. Registered on April 21, 2014.

Pulpal response to mineral trioxide aggregate containing phosphorylated pullulan-based capping material.

This study aimed to evaluate the pulpal responses of monkey's pulp after direct pulp capping (DPC) with the novel mineral trioxide aggregate containing phosphorylated pullulan-based material (MTAPPL). Seventy-two teeth were randomly divided into four groups: MTAPPL; Nex-Cem MTA (NX); TheraCal LC (TH); and Dycal (DY). Histopathological changes in the pulps were observed at days 3, 7 and 70. On day 3, mild inflammatory responses were observed in the MTAPPL, no to moderate inflammatory responses in the TH, whereas moderate inflammatory responses in the NX and DY. No mineralized tissue formation (MTF) was observed in all groups. On day 7, no or mild inflammatory responses were observed in all groups. Initial MTF was observed except for DY. No inflammation with complete MTF including presence of odontoblast-like cells was observed in the MTAPPL, NX and TH groups at day 70. These findings indicate that MTAPPL could be an efficient DPC material.

Rapid Review on the Effectiveness of Telehealth Interventions for the Treatment of Behavioral Health Disorders.

The Psychological Health Center of Excellence conducted a rapid review of the literature to investigate the effectiveness of behavioral health treatments (i.e., evidence-based psychotherapy and psychiatry) delivered in person compared to telehealth (TH; i.e., video teleconference and telephone). The rapid review methods included a systematic search of a single database (PubMed), hand-searching of relevant systematic reviews, dual screening, single-person data abstraction verified by a second person, and dual risk of bias assessment. Due to heterogeneity across studies, no quantitative analyses were conducted. Twenty-two randomized controlled trials (RCTs), eight of which were non-inferiority trials, evaluated the effectiveness of TH via telephone or video teleconferencing compared to in-person (IP) delivery for patient populations with posttraumatic stress disorder, depression, and mixed diagnoses. The majority of RCTs and all but one of the eight non-inferiority trials found that clinical outcomes did not differ between TH and IP treatment delivery. Two studies found that subgroups with higher symptom severity (hopelessness and anxiety disorders, respectively) in the TH group had worse treatment-related outcomes than IP participants with similar symptom profiles. The majority of studies found no significant differences in satisfaction with care, quality of the therapeutic alliance, or study discontinuation between TH and IP groups. Based on evidence from 22 RCTs, the use of TH platforms, including video conference and telephone modalities, generally produces similar outcomes as face-to-face provision of psychotherapy and psychiatry services.

Interactive effect of 6 weeks of High-intensity interval training and quercetin supplementation on expression of some tumor angiogenesis markers in female mice with breast cancer

Background: About angiogenesis, metastasis of breast cancer and exercise, Many studies have been done in recent decades to better understand of regulatory mechanisms. The purpose of this study was to investigate the Interactive effect of high-intensity interval training (HIIT) and quercetin supplementation (Q) on the expression of key angiogenic factors in tumor tissue of mouse with breast cancer. Methods: Twenty-four female Balb/C mouse were injected with estrogen receptor-dependent breast cancer cells MC4L2 and then divided into three groups of tumor (T), tumor + of high-intensity interval training (TH) and tumor + high-intensity interval training + quercetin (THQ). The TH and THQ groups ran the treadmill 3 days a week for 6 weeks and each session 1 hour. The THQ group received 110 mg / kg quercetin solution for 6 weeks, 3 days a week with training. After completion of the work, the mouse were sacrificed and their tumor tissue removed and frozen in liquid nitrogen And stored at -70 ° C. Expression of TIE-2 and VEGF-A genes was measured by REAL TIME-PCR. ΔCt, ΔΔCt, and Fold change were calculated with the relevant statistical tests at the significant level (P &lt;0.05) by GENEX software. Results: The results showed that THQ interaction significantly decreased the expression of TIE-2 and VEGF-A genes in TH and THQ groups compared to T group. In addition, quercetin in THQ group significantly decreased TIE-2 and VEGF-A gene expression compared to TH group. Conclusion: interaction of HIIT and Q supplementation are probably effective in inhibiting tumor angiogenesis.

Telmisartan Self-Nanoemulsifying Drug Delivery System, Compared With Standard Telmisartan, More Effectively Improves Hepatic Fibrosis in Rats.

Background:This study was designed to examine effects of telmisartan; an angiotensin receptor blocker; self-nanoemulsifying drug delivery system (SNEDDS) in reversing already-established hepatic fibrosis.Method:Forty rats were given thioacetamide (200 mg/kg, intraperitoneally) twice/week for 8 weeks then divided into 5 groups (n = 8), PC and 4 treated groups. Treatments were given orally for another 2 months as follows: telmisartan low and high doses (TL and TH: 1.8 and 3.6 mg/kg/day) and telmisartan SNEDDS at the same doses (TLS and THS). At end of treatment, blood was obtained and liver was isolated.Results:Rats showed significant elevations of plasma ALT and AST and hepatic IL-6, TNF-α, and MDA, significant reductions of plasma albumin, hepatic GSH, and body weight, and hepatic histopathological damage. All treatments except for TL significantly reversed these thioacetamide-induced changes. THS group showed significant differences from all groups. Regarding ratio of free telmisartan concentration in hepatic homogenate to that of plasma, TH and TLS groups showed non-significant variation between each other while THS group showed significant differences from them. No significant changes were detected in blood pressure, hemoglobin, white blood cells, and platelets.Conclusion:Telmisartan SNEDDS, compared with telmisartan, more effectively reversed chronic hepatic fibrosis with good safety profile.

New considerations on pathways involved in acute traumatic coagulopathy: the thrombin generation paradox

BackgroundAn acute traumatic coagulopathy (ATC) is observed in about one third of severely traumatized patients. This early, specific, and endogenous disorder is triggered by the association of trauma and hemorrhage. The early phase of this condition is characterized by the expression of a bleeding phenotype leading to hemorrhagic shock and the late phase by a prothrombotic profile leading to multiple organ failure. The physiopathology of this phenomenon is still poorly understood. Hypotheses of disseminated intravascular coagulation, activated protein C-mediated fibrinolysis, fibrinogen consumption, and platelet functional impairment were developed by previous authors and continue to be debated. The objective of this study was to observe general hemostasis disorders in case of ATC to confront these hypotheses.MethodFour groups of 15 rats were compared: C, control; T, trauma; H, hemorrhage; and TH, trauma and hemorrhage. Blood samples were drawn at baseline and 90 min. Thrombin generation tests, platelet aggregometry, and standard hemostasis tests were performed.ResultsSignificant differences were observed between the baseline and TH groups for aPTT (17.9 ± 0.8 s vs 24.3 ± 1.4 s, p < 0.001, mean ± SEM), MAP (79.7 ± 1.3 mmHg vs 43.8 ± 1.3 mmHg, p < 0.001, mean ± SEM), and hemoglobin (16.5 ± 0.1 g/dL vs 14.1 ± 0.3 g/dL, p < 0.001, mean ± SEM), indicating the presence of an hemorrhagic shock due to ATC. Compared to all other groups, coagulation factor activities were decreased in the TH group, but endogenous thrombin potential was (paradoxically) higher than in group C (312 ± 17 nM/min vs. 228 ± 23 nM/min; p = 0.016; mean ± SEM). We also observed a subtle decrease in platelet count and function in case of ATC and retrieved an inversed linear relationship between fibrinogen concentration and aPTT (intercept, 26.53 ± 3.16; coefficient, − 3.40 ± 1.26; adjusted R2: 0.1878; p = 0.0123).ConclusionsThe clinical-biological profile that we observed, combining normal thrombin generation, fibrinogen depletion, and a hemorrhagic phenotype, reinforced the hypothesis of activated protein C mediated-fibrinolysis. The key role of fibrinogen, but not of the platelets, was confirmed in this study. The paradoxical preservation of thrombin generation suggests a protective mechanism mediated by rhabdomyolysis in case of major trauma. Based on these results, we propose a new conception concerning the pathophysiology of ATC.

Temperature and humidity index (THI)-induced rumen bacterial community changes in goats.

The rumen microbiome is thought to play an important role in maintaining normal gastrointestinal metabolism and nutrient absorption in ruminants. The present study was designed to investigate the effect of heat stress on the rumen microbiome of goats using 16S rRNA sequencing technology. Six female goats were randomly allocated into two control metabolic chambers: A and B (in which the temperature and humidity could be precisely controlled with a precision deviation of ± 0.5°C and ± 5%, with three goats/chamber). Dynamic changes in the rumen bacterial community were detected under 16 gradually increasing temperature and humidity indexes (THIs). Heat stress had no significant effect on alpha diversity but affected the main phyla and genera of the goat rumen microbiota. With a deeper level of heat stress, the TH groups formed a distinct cluster that differed from that of the control check (CK) group. The dominant phylum transitioned from Firmicutes to Bacteroidetes, and co-exclusion occurred between these two phyla. With the increase in THI, the content of probiotics in the Lachnospiraceae_ND3007_group (P < 0.05) decreased, and the abundance of pathogenic bacteria, such as Erysipelotrichaceae_UCG-004 and Treponema_2, increased; however, the difference between the groups was not significant (P > 0.05). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict bacterial function, and we found that the ambient environment significantly affected the balance between carbohydrate and energy metabolism (P < 0.05). In conclusion, heat stress changed the composition of rumen microbes and affected metabolic function. This experiment provides a theoretical basis for exploring the effects of environmental factors on the rumen of goats.

Candidate genes associated with the effect of rosiglitazone on glycemic control and cardiovascular system in the treatment of type 2 diabetes mellitus.

In the present study, candidate genes affected by rosiglitazone to exert glycemic control in the treatment of type 2 diabetes mellitus (T2DM) and associated with its adverse cardiovascular effects were identified using a bioinformatics analysis. The gene expression profiles of the dataset GSE36875 from the Gene Expression Omnibus database, including heart samples from 5 non-diabetic control mice (NC), 5 untreated diabetic mice (NH) and 5 rosiglitazone-treated diabetic mice (TH), were used to identify differentially expressed genes (DEGs) in the NC vs. NH, NC vs. TH and TH vs. NH groups. Subsequently, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enriched by the DEGs were determined. Furthermore, genes associated with the action of rosiglitazone were identified using Short Time-series Expression Miner, which were then subjected to enrichment analysis in gene ontology (GO) terms in the category biological process (BP), and networks of the GO terms, KEGG pathways and genes associated with the action of rosiglitazone were constructed. Finally, biological abnormalities associated with these genes were identified using WebGestalt. A set of 791 DEGs in three groups (NC vs. NH, NC vs. TH and NH vs. TH) were identified. Subsequently, 72 DEGs [e.g., apolipoprotein (Apo)A1, ApoA5, cytochrome P450 (Cyp)2c37, Cyp2J5, Cyp2b9 and Cyp2b10] were identified as genes associated with the action of rosiglitazone. In addition, a network of 13 GO terms in the category BP, 6 KEGG pathways and 41 genes associated with the action of rosiglitazone was constructed, with major terms/pathways including oxidation/reduction, lipid transport, peroxisome proliferator-activated receptor signaling pathway and metabolism of xenobiotics by Cyp. Finally, 15 biological abnormalities (including abnormal triglyceride levels, abnormal cholesterol homeostasis, abnormal lipid homeostasis) associated with these genes were identified. ApoA1, ApoA5, Cyp2c37, Cyp2J5, Cyp2b9 and Cyp2b10 were differently expressed after rosiglitazone treatment, which may be accountable for affecting cardiovascular outcomes and glycemic control in T2DM. The present results may expand the current understanding of the mechanism of action of rosiglitazone to exert glycemic control in T2DM, as well as its effects on the cardiovascular system.