Cy Groups Research Articles

Identification of a novel locus C2 controlling canary yellow flesh color in watermelons.

The flesh color of watermelon is an important trait that is determined by carotenoid composition and affects consumers' fruit desirability. Although a complete dominant control by C locus (Cllcyb) for canary yellow flesh (CY) over red flesh has been reported, red and CY colors frequently appear as a mixed pattern in the same flesh (incomplete canary yellow, ICY) in F1 and inbred lines carrying dominant C alleles. Therefore, we examined the genetic control of the mixed color pattern in ICY using whole-genome resequencing of three ICY (ICY group) and three CY inbred lines (CY group), as well as genetic linkage mapping of an F2 population. The segregation pattern in 135 F2 plants indicated that CY is controlled by a single locus (named C 2) dominant over ICY. The whole-genome resequencing of ICY and CY inbred lines revealed an ICY/CY-specific region of approximately 27.60-27.88Mb on Chr. 2 that was polymorphic between the ICY and CY groups. Our genetic map, using nine cleaved amplified polymorphic sequence markers developed based on the single-nucleotide polymorphisms from the ICY/CY-specific region, confirmed that C 2 is located on Chr. 2 and cosegregated with the marker (M7) derived from a non-synonymous single-nucleotide polymorphism of the pentatricopeptide repeat (PPR) gene (ClPPR, Cla97C02G039880). Additionally, 27 watermelon inbred lines of ICY, CY, and red flesh were evaluated using previously reported Cllcyb (C locus)-based markers and our C 2 locus-linked ClPPR-based marker (M7). As a result, dominant alleles at the C 2 locus were required to produce CY, in addition to dominant alleles at the C locus, while a recessive homozygous genotype at the C locus gave the red flesh irrespective of the genotype at the C 2 locus. Using a ClPPR-based cleaved amplified polymorphic sequence developed in this study and Cllcyb-based markers, watermelon cultivars with CY, ICY, and red flesh could be successfully discerned, implying that the combined use of these markers will be efficient for marker-assisted selection of flesh color in watermelon breeding.

Long transportation duration affects nutrient composition, mycotoxins and microbial community in whole-plant corn silage.

Potential nutrient losses and mycotoxin accumulation caused by abnormal fermentation during transportation from cropland to dairy farms leads to the diseases incidence and threatens the health of dairy cows, then further causes financial losses. The aim of this study was to investigate the effects of different transportation times on the nutritional composition, mycotoxins, and microbial communities in whole-plant corn silage (WPCS). Three groups were subjected to different transport times: DY, short (<200 min); ZY, medium time (300-500 min); and CY, long transport time (>600 min). WPCS were collected from the same field, and nutrient composition and microbial composition before and after transportation were analyzed. Our results showed that the temperature of WPCS was higher in the ZY and CY groups than in the DY group (P < 0.01). There were no significant differences in dry matter (DM), crude protein (CP), neutral detergent fiber (NDF), acid detergent fiber (ADF), ether extract (EE) and starch contents after different transportation times (P > 0.05), whereas the starch and water-soluble carbohydrates (WSC) contents in the CY group was significantly decreased after transport (P < 0.05). Similarly, the concentration of vomitoxin in the DY and CY groups declined markedly (P < 0.05) and the zearalenone content in the DY group also significantly decreased after transportation (P < 0.05). Regarding the analysis of microorganisms in WPCS, UniFrac-distance matrices and Shannon indices showed differences in the ZY group (P < 0.05), but fungal diversities were not influenced by the transport time (P > 0.05). In the ZY group, the relative abundance of Lactiplantibacillus decreased significantly after transportation (P > 0.05), but the relative abundances of unidentified_Chloroplast, Pantoea, Gluconobacter, unidentified Acetobacter and Acinetobacter increased markedly (P < 0.05). In addition, the relative abundances of Acetobacter and Gluconobacter in the CY group increased after transport (P < 0.05). Among fungal communities, a total of three, nine, and ten different fungal flora were observed in the DY, ZY, and CY groups, respectively, although no difference was found in fungal diversity. In conclusion, increased temperature, loss of starch, and mycotoxin variation were found with increased transport time. This might be the result of competition between bacteria and fungi, and novel technologies will need to be utilized for further exploration of the mechanism.

Homocoupling of Isocyanide at the Si(II) Center of Borylaminoamidinatosilylene.

Two borylaminoamidinatosilylenes (L)[(1,5-C8H14)B(Ar)N]Si (L = PhC(NtBu)2, Ar = 2,6-iPr2C6H3 (1)) and (L)[(1,5-C8H14)B(Ar')N]Si (Ar' = 2,4,6-Me3C6H2 (2)) have been prepared and utilized to investigate the reaction toward isocyanide. Reactions of 1 with the respective CN-2,6-Me2C6H3 and CNCy (Cy = cyclo-C6H11) produced compounds (L)Si(NAr)C(N-2,6-Me2C6H3)B(1,5-C8H14)(CN-2,6-Me2C6H3) (3) and (L)Si(NAr)C(NCy)C(NCy)B(1,5-C8H14)(CNCy) (4). Reactions of 2 with the respective CNCy and CN-2,6-Me2C6H3 yielded compounds cyclo-(L)SiN(Ar')C(NCy)B(1,5-C8H14)C(NCy) (5) and cyclo-(L)[(1,5-C8H14)B(Ar')N]SiC(CN-2,6-Me2C6H3)N(2,6-Me2C6H3)C(N-2,6-Me2C6H3) (6). Compounds 3-6 have different compositions and structures from each other. Density functional theory (DFT) calculations suggest initial formation of (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar)N]Si (A), (L)[(1,5-C8H14)B(←:CNCy)(Ar)N]Si (A'), (L)[(1,5-C8H14)B(←:CNCy)-(Ar')N]Si (A″), and (L)[(1,5-C8H14)B(←:CN-2,6-Me2C6H3)(Ar')N]Si (A‴) as the respective intermediates. The as-followed transition states TS, TS1', TS1″, and TS‴ all feature probable Si:→C(═N):→B bonding with different Gibbs energies of 7.24, 2.46, 3.86, and 6.59 kcal/mol, respectively, due to variation among the Ar, Ar', 2,6-Me2C6H3, and Cy groups in these species, and reacted in different ways.

The location of PSEN1 pathogenic variants in transmembrane vs. cytoplasmic domains may alter neurodegenerative and cognitive trajectories: Findings from the DIAN study

AbstractBackgroundThough pathogenic variations in PSEN1 leading to Autosomal Dominant Alzheimer's disease (ADAD) are all highly penetrant, there is substantial inter‐individual variability in the rates of cognitive decline and biomarker change observed in ADAD. We hypothesized that this inter‐individual variability may be associated with the location of the pathogenic variant within PSEN1. We tested this hypothesis using biomarker and cognitive data from the Dominantly Inherited Alzheimer Network (DIAN) observational study.MethodPSEN1 pathogenic variant carriers [grouped based on whether their ADAD genotype affected transmembrane (PSEN1 TM; N = 125) or cytoplasmic (PSEN1 CY; N = 62) domains] and non‐carriers [NC; N = 176] enrolled in DIAN underwent clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF). Linear mixed effects models with a restricted cubic spline were used to determine cross‐sectional differences in clinical and biomarker measures between NC, PSEN1 TM, and PSEN1 CY groups, across the disease course (estimated years to symptom onset; EYO).ResultBackground characteristics are reported in Table 1. PSEN1 CY and PSEN1 TM groups had elevated β‐amyloid (PiB‐PET) and phosphorylated‐tau levels (CSF pTauT181) compared to NC, but these biomarker measures were not different between PSEN1 TM and CY groups (Figure 1a‐b). Additionally, the PSEN1 TM group had decreased glucose metabolism compared to NC but was similar to the PSEN1 CY group (Figure 1c). However, we observed that PSEN1 TM carriers had significantly smaller hippocampal volume, greater lateral ventricle volume, and greater cognitive impairment (Figure 1d‐f) across EYO as compared to PSEN1 CY carriers.ConclusionDespite similar β‐amyloid PET and CSF pTauT181 levels across EYO, individuals with pathogenic variants affecting transmembrane domains in PSEN1 may have more rapid progression of disease as measured by cognitive function and neurodegeneration as compared to those with variants affecting cytoplasmic domains. These results have implications both for understanding the heterogeneity in ongoing ADAD clinical trials and for better understanding the pathobiology of ADAD.

Immunomodulatory and antioxidant effects of hydroxytyrosol in cyclophosphamide-induced immunosuppressed broilers

As an important olive component, hydroxytyrosol (HT) has good medicinal and health effects. However, its importance in alleviating immune suppression in broilers has not been established. Therefore, we aimed at evaluating the immunomodulatory and antioxidant effects of HT in immune suppressed broilers. Immune suppressed broiler models were established via intraperitoneal injection of 80 mg/kg cyclophosphamide (Cy). Thirty two Cobb 500 male broilers were randomly allocated into 4 groups of 8 each. Broilers in the model (Cy) and HT treatment (Cy+HT) groups were intraperitoneally administered with Cy (80 mg/kg BW) once a day for 3 d. From the 4th d, broilers in the Cy+HT and HT groups were treated with 0.5 mL of 200 mg/L HT solution, once a day, for 7 d. The Cy and Con groups were orally administered with normal saline. On the 14th and 28th d, serum and duodenal samples were obtained for testing. It was found that HT increased villi height (VH)/crypt depth (CD) ratio in the duodenum and suppressed serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels. Moreover, it elevated the expressions of CD4+ and CD8+ T lymphocytes. HT upregulated the mRNA expression levels of interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-10 (IL-10), enhanced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and downregulated malondialdehyde (MDA) levels in Cy-induced immune-suppressed broilers. In conclusion, HT can alleviate immune-suppression as well as enhance immunity and antioxidant activities in the local mucosa of small intestines in broilers. Therefore, it can be used as an immune stimulant. More studies should be performed to confirm our findings and to elucidate on the mechanisms of HT.

Abatacept is Efficacious in the Treatment of Older Patients with csDMARD-Refractory Rheumatoid Arthritis: A Prospective, Multicenter, Observational Study.

IntroductionAbatacept efficacy in older patients with rheumatoid arthritis (RA) has been primarily demonstrated via retrospective comparisons with younger patients. The objective of this study was to compare efficacy of abatacept in older vs. younger patients with RA, and efficacy of abatacept with that of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) in both age groups.MethodsThis prospective, multicenter, observational study (UMIN000014913) enrolled csDMARD-refractory patients without previous biological DMARD treatment. Abatacept (A) or csDMARDs (C) were administered at the treating physician’s discretion to older (O, ≥ 65 years) and younger (Y, 20–64 years) patients, producing AO, AY, CO, and CY groups. Clinical efficacy after 24 weeks was evaluated using European League Against Rheumatism (EULAR) erythrocyte sedimentation rate response criteria.ResultsOverall, 202 patients were evaluated. Compared with the CO group, more patients in the AO group achieved a EULAR good or moderate response (p < 0.0001). Compared with the CY group, more patients in the AY group achieved a EULAR good or moderate response (p < 0.01). Similar proportions of patients in the AO and AY groups achieved a EULAR good response or a good or moderate response. Few adverse events were reported.ConclusionsThis prospective study demonstrated that abatacept is efficacious and safe in older patients with RA and a history of being refractory to csDMARDs. Abatacept was shown to be more efficacious than adding or switching to a new csDMARD in both younger and older csDMARD-refractory patients with RA.Trial RegistrationUMIN000014913.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-021-00356-2.

The importance of the genetic diversity of the HcRNAV ssRNA virus in the viral-based bloom control of the dinoflagellate Heterocapsa circularisquama

The HcRNAV virus has been used to control the blooms of the harmful dinoflagellate Heterocapsa circularisquama through the spraying of autochthonous sediment containing HcRNAV from prior blooms. When using natural substances for harmful algal bloom (HAB) control, the effects on local ecosystems must be ascertained and minimized. Specifically, HcRNAV is a single-stranded RNA virus which replicates with an extremely high mutation rate, leading to significant genetic diversity. Here we demonstrate the genetic diversity of HcRNAV in natural sediments analyzed through the use of the clone library approach and Next Generation Sequencing (NGS) analysis based on the major capsid protein (MCP) sequence of HcRNAV. The sediment samples were collected over four developmental phases, including low- and high- density phases of H. circularisquama blooms in the saltwater Lake Kamo, Niigata, and Mikawa Bay, Aichi, Japan. The HcRNAV sequences obtained from both methods were divided into only two groups (UA2 and CY groups), with most of the sequences classified into the UA2 group. Haplotype network analysis, which is used to reveal the genealogical relationships among haplotypes, has indicated that the HcRNAV sequences varied according to time and location. This analysis suggested that HcRNAV does not randomly diversify, thus indicating that the diversity of HcRNAV might be undergoing a process of natural selection. Furthermore, the present cluster in the haplotype network was consistent with the cross-reactivity tests infecting the H. circularisquama strains with isolated HcRNAV clones. These results suggest that HcRNAV consists of several clusters that are evolving as genetically diverse populations, termed quasispecies. Hence, our findings indicate that for effective utilization, it is necessary to collect and pool sediments containing HcRNAV from multiple local sites and periods to provide more diversity in the viral populations used for bloom control.

WHAT IS THE MAJOR FACTOR ON THE KIDNEY INJURY INDUCED BY HYPERTENSION OR HYPERHOMOCYSTEINEMIA

Objective: As we all know kidney injury could be induced by hypertension or hyperhomocysteinemia (HHcy). What is the major factor? HHcy plays a synergistic role with hypertension in vascular injury; however, the relationship between HHcy and hypertension in renal injury remains unclear. Here, we sought to evaluate the relationship between HHcy and hypertension in the context of renal injury and to elucidate the mechanism of action underlying this relationship. Design and method: Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were randomized into WKY, WKY+HHcy, SHR, and SHR+HHcy groups. Blood pressure, plasma homocysteine, creatinine, serum malondialdehyde (MDA), serum superoxide dismutase (SOD), and urinary albumin creatinine ratio (UACR) were measured. mRNA and protein expression levels of NOX2, NOX4, and nephrin in the kidneys were also examined. Results: The WKY+HHcy group exhibited lower serum SOD levels, relative to the WKY group, along with higher levels of both serum MDA and UACR. Similar effects were observed in the SHR+HHcy group, relative to the SHR group. Moreover, compared with the levels in the WKY+HHcy group, mean SOD levels in the SHR+HHcy group were lower, while mean MDA and UACR levels were higher. Higher mRNA and protein expression levels of NOX2 and NOX4, along with lower mRNA and protein expression levels of nephrin, were observed in the kidneys of WKY+HHcy and SHR+HHcy rats, relative to SHR and WKY controls, respectively. Furthermore, the mRNA and protein levels of NOX2 and NOX4 were higher and the mRNA and protein levels of nephrin were lower in the SHR+HHcy group than in the WKY+HHcy group. In addition, compared with WKY+HHcy group, the UACR level of SHR group was higher. Conclusions: HHcy appears to synergistically increase hypertensive renal damage by enhancing oxidative stress. However, hypertension remains a major risk factor for renal impairment compared to HHcy.

Protective role of SIRT1-mediated Sonic Hedgehog signaling pathway in the preeclampsia rat models.

To explore the role of silent information regulator 1 (SIRT1)-mediated Sonic Hedgehog (SHH) pathway in reduced uterine perfusion pressure (RUPP) model of preeclampsia (PE) in rats. The pregnant rats were divided into sham, RUPP, RUPP + rSIRT1 (recombinant SIRT1 protein), RUPP + rSHH (recombinant SHH protein), and RUPP + rSIRT1+ Cy (cyclopamine, an SHH pathway inhibitor) groups, followed by the determination of mean arterial pressure (MAP) and pregnancy outcome. The gene or protein expression was determined by enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction (qRT-PCR), or Western blotting. RUPP rats showed increases MAP with the lower levels of vascular endothelial growth factor (VEGF) and nitrite and nitrate (NOx), as well as the higher levels of soluble FMS-like tyrosine kinase-1 (sFlt-1), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in maternal plasma, which was attenuated after rSIRT1 or rSHH treatment. Besides, the improvement in the pregnancy outcome was seen in the rats from the RUPP + rSIRT1/rSHH groups as compared with the RUPP group. However, the therapeutic effect of rSIRT1 was reversed by cyclopamine. Placenta tissues of RUPP rats manifested the down-regulations of SIRT1, Patched-1 (PTCH1), and GLI family zinc finger 2 (GLI2), which were up-regulated in the RUPP + rSIRT1 group. SIRT1 was down-regulated while SHH pathway was inhibited in the placental tissue of PE rats. SIRT1 improved the blood pressure, angiogenic imbalance, inflammation, and pregnancy outcome in PE rats via SHH pathway, supporting its potential use for the treatment of PE.

The protective effects of resveratrol pretreatment in cyclophosphamide-induced rat ovarian injury: an vivo study

Objectives To explore whether resveratrol (Res) pretreatment could exert a protective effect on cyclophosphamide (Cy) induced ovarian toxicity in a rat model. Methods Twenty-four female 7-week old Sprague-Dawley rats were randomly divided into four groups: Con, administered with vehicle solutions; Cy, treated with Cy; Res + Cy, treated with Cy + Res combined; Res, treated with Res. After 21 d of treatments, the rats were euthanized and blood samples were collected to evaluate the levels of anti-Müllerian hormone (AMH). The Ovaries were processed for immunohistochemical and western blotting. Results Cy-treat caused the decrease of body weights and ovarian weight. AMH was lower in Cy group, whereas AMH levels were similar among other groups. Histomorphology showed a large number of primordial follicles were activated in Cy groups, whereas the primordial follicles were inhibited in the Res and Res + Cy groups. The expressions of Sirt1, Foxo3a were up-regulated and p53, Caspase-3, and Bax were down-regulated in Res + Cy and Res groups (p < .05). Conclusions Res can prevent the primordial follicle activation and decrease apoptosis induced by Cy. Res may be an effective protection for ovarian function during chemotherapy, which means a new nonsurgical application for protection of ovarian reserve.

Evaluation of six different types of sequential conditioning regimens for allogeneic stem cell transplantation in relapsed/refractory acute myelogenous leukemia – a study of the Acute Leukemia Working Party of the EBMT

The Acute Leukemia Working Party (ALWP) of the EBMT assessed the outcome of allogeneic stem cell transplantation (alloSCT) in patients with relapsed/refractory AML (r/rAML) evaluating six sequential conditioning regimens (SR) groups. A total of 2132 patients were included. LFS at 2 years was 28.9%, 33.6%, 35.3%, 20.6%, 24.4%, and 27% for the FLAMSA-TBI4, FLAMSA-Chemo, Mel-Flu-TBI8, Mel-Treo-Flu, Thio-ETO-Cy-Bu2-Flu, and Clo-ARAC-(Bu2/TBI4)-Cy groups, respectively. In patients <55 years of age Mel-Flu-TBI8 had the best LFS, which was statistically significant only in comparison to the Mel-Treo-Flu group, while in patients ≥55 years LFS was best with FLAMSA-Chemo without significant differences compared to FLAMSA-TBI4 and Mel-Flu-TBI8. Furthermore, best NRM rates were obtained with the two FLAMSA regimens groups. Our study suggests that in younger (<55 years) patients a more intense regimen might be used whereas in older (≥55 years) patients the focus might be more on tolerability.

Yacon (Smallanthus sonchifolius): Effect on Integrity of Intestinal Barrier, Inflammatory Response and Oxidative Stress in Animal Model of Colon Cancer (P06-052-19)

ObjectivesTo investigate the prebiotic effect of yacon, source of fructooligosaccharides (FOS), on the integrity of the intestinal barrier, inflammatory response and oxidative stress in rats with induced colon cancer. Methods44 adult Wistar rats were distributed into 4 groups: S (without colon cancer and yacon; n = 10); C (with colon cancer without yacon; n = 12); Y (without colon cancer with yacon; n = 10); and CY (with colon cancer and yacon; n = 12). Animals of groups S and C received AIN-93 M diet and animals of groups Y and CY received the same diet but added with yacon flour containing 28.95% FOS, to provide 5% FOS in the diet, for 16 weeks. From week 4 to 8, the animals of C and CY groups received an intraperitoneal dose of 25 mg/kg body weight of 1.2-dimethylhydrazine (DMH-Sigma®) once a week. In the last week, 24h-urine collection was performed for intestinal permeability analysis using lactulose and mannitol. Blood sample was collected for the analysis of IL-10 and IL-12 cytokines (Milliplex® Map, Luminex®) and total antioxidant capacity - TAC (Elabscience®). Large intestine was collected for intraluminal pH, short chain fatty acids - SCFA (HPLC) and immunoglobulin A – sIgA (Cloud-Clone®) analysis. Normal distributed data were analyzed by Two-way ANOVA, followed by Newman-Keuls (p < 0.05), using GraphPad Prism®, version 7. ResultsCancer-induced animals showed higher TNF-α, SCFA (acetate, propionate and butirate), and lower TAC. Yacon reduced intraluminal pH and lactulose/mannitol ratio, increased propionic acid in the feces, but showed no effect on IL-10, IL-12, TNF-α, and IL-10/IL-12 ratio. The levels of sIgA were increased only in the group fed yacon without cancer (group Y). Mannitol and TAC were higher in CY group, showing a significant interaction of yacon and colon cancer. ConclusionsYacon reduced pH, intestinal permeability and the oxidative stress associated with colon cancer. The local immunity (sIgA) was raised, although no effect was observed on cytokines with yacon consumption. Yacon is a rich source of FOS wich improves the intestinal barrier and mucosal immunity, particularly in healthy animals. Funding SourcesCNPq, FAPES.

Histologic, Histomorphometric, and Osteogenesis Comparative Study of a Novel Fabricated Nanocomposite Membrane Versus Cytoplast Membrane

The present study compared the invivo efficacy of a novel synthesized polycaprolactone (PCL)/polyethylene glycol (PEG)/bioactive glass (BG) nanocomposite membrane versus a cytoplast (Cy) membrane in terms of the average percentage of new bone formation and inflammation levels. In the present interventional animal study, 12 male New Zealand rabbits were tested. In the parietal bone of the rabbits, 24 defects were prepared (2 defects for each rabbit), which were divided into 3 equal groups (Cy, PCL, and control). Each rabbit's calvarial bone was prepared for the histologic and histomorphometric survey. The amount of regenerated bone (ie, length, area, percentage), necrosis rate, fibrosis (fibrosis plus and percentage), and inflammation in the standard defects of parietal bone in the rabbits were examined and compared after 10weeks. A significant difference was found between the Cy and PCL groups regarding the mean area and thickness of the bone. We also found a significant difference in the bone length, area, and percentage formed between PCL and control groups. Also, the rate of fibrous tissue formation was significantly different statistically between the PCL and control groups. The results showed the influence of the PCL membrane in generating more bone and less fibrous tissue. In all 3 groups, negligible inflammation and no necrosis was observed. The results of the present study have shown that combining PCL, PEG, and BGs could be promising for bone regeneration in jaw defects, around dental implants, and in oral and maxillofacial defects.

Preservation Methods Influence the Biomechanical Properties of Human Lateral Menisci: An Ex Vivo Comparative Study of 3 Methods.

Background:Three main meniscal preservation methods have been used over the past decade: cryopreservation, freezing, and freezing with gamma irradiation.Hypothesis:All 3 preservation methods will result in similar biomechanical properties as defined by tensile and compression testing.Study Design:Controlled laboratory study.Methods:A total of 24 human lateral menisci were collected from patients who underwent total knee arthroplasty. Inclusion criteria were patients younger than 70 years with primary unilateral (medial) femorotibial knee osteoarthritis. Each meniscus was divided into 2 specimens cross-sectionally. One specimen was systematically cryopreserved and constituted the control (Cy; –140°C), and the other specimen was used for either the simple frozen group (Fr; –80°C) or the frozen+irradiated group (FrI; –80°C + 25-kGy irradiation). Compression and tensile tests were performed to analyze the elasticity modulus (Young modulus) in compression, the elasticity modulus in tension, the tensile force at failure, and the rupture profile of the tensile stress-strain curve.Results:A significant difference in the mean compression elasticity modulus was observed between the Cy and Fr groups (28.86 ± 0.77 vs 37.26 ± 1.08 MPa, respectively; P < .001) and between the Cy and FrI groups (28.86 ± 0.77 vs 45.92 ± 1.09 MPa, respectively; P < .001). A significant difference in the mean tensile elasticity modulus was also observed between the Cy and Fr groups (11.66 ± 0.97 vs 19.97 ± 1.37 MPa, respectively; P = .008) and between the Cy and FrI groups (11.66 ± 0.97 vs 45.25 ± 1.39 MPa, respectively; P < .001). There were no significant differences between the control and study groups in tensile force at failure. The analysis of the stress-strain curve revealed a slow-slope curve with a nonabrupt rupture (ductile material) for the Cy samples versus a clear rupture of the curve for the Fr and FrI samples (more fragile material).Conclusion:Cryopreservation allows for more elastic and less fragile tissue compared with simple freezing or freezing plus irradiation.Clinical Relevance:The study results exhibit the detrimental effect of simple freezing and freezing plus irradiation on human meniscal mechanical properties. If these effects occur in menisci prepared for allograft procedures, important differences could appear in the graft’s mechanical behavior and thus patient outcomes.

Evaluation of active dried yeast in the diets of feedlot steers-I: Effects on feeding performance traits, the composition of growth, and carcass characteristics1.

The use of active dried yeast (ADY) in the diets of feedlot steers may improve feed efficiency, growth performance, and reduce days on feed. Strategic timing of ADY inclusion in the diet may increase feed conversion or aid in the dietary transition from growing to finishing diets. One hundred twenty steers, blocked by weight, were fed four diets for 164 d: grower (70 d), first transition diet (7 d), second transition diet for (7 d), and finisher (80 d) in a GrowSafe System. Four treatment sequences of ADY inclusion were evaluated in a Balaam's design where steers were fed a control diet before and after the grower phase (CC), control before and ADY after the grower phase (CY), ADY before and control after the grower phase (YC), and ADY before and after the grower phase (YY). A random coefficients model was used to evaluate the following variables of interest: feeding performance and growth traits, including biometric measurements and carcass ultrasound measurements, and carcass characteristics. Treatment was a fixed effect and block was a random effect. Treatment did not affect feeding performance or behavior (P ≥ 0.14). The rate of change of biometric measurements were not different (P ≥ 0.16) across treatment groups except for rib girth circumference, which was greater for the YY and CY groups intermediate for the CC group and least for the YC group (0.828 and 0.809 vs. 0.751 vs. 0.666 cm/d, respectively; P < 0.01). Faster growth rates of rib girth circumference resulted in larger final measurements for steers that were finished on ADY (P < 0.01). Ultrasound measurements (backfat, LM area, intra-muscular fat, and rump fat) were not different across treatments (P ≥ 0.15). However, there was a tendency for the YC group to have a slower rate of back fat deposition than other treatment groups (P = 0.09). Steers' final shrunk BWs did not differ (P = 0.61), but shrink percentage was greater for CC than for YY groups (3.7% vs. 2.7%, respectively; P = 0.05). Carcass characteristics were not different across treatments (P ≥ 0.20). Crude fat, CP, ash and moisture analyses of the 9th to 11th rib section were not different across treatments, and there was no difference in adjusted final shrunk BW (P ≥ 0.45). Feeding the ADY strain used in this study to growing and finishing feedlot steers increased rib girth circumference development rate and reduced shrink loss without affecting feeding behavior, feeding performance, or carcass characteristics.

Increased frequency of acute reactions to iodinated contrast media after anti-CTLA-4 immunomodulating antibodies in cancer patients

Background: The aim of this study was to investigate whether cancer immunotherapy, in particular with immune checkpoint inhibitors, increased the incidence of allergy-like immediate adverse reactions to iodinated contrast media (ICM) with respect to “standard” cancer chemotherapy or targeted therapy. Methods: We retrospectively evaluated the incidence of contrast-enhanced computed tomography (CECT)-related immediate adverse reactions (ARs) in cancer patients undergoing treatment. Using an institutional radiological database (Elefante, Agfa), we identified all consecutive cancer patients who performed at least one CECT after starting any medical cancer treatment at our institute between January 1, 2006 and December 31, 2014. All patients were outpatients and with a performance status of 0-1 by ECOG scale. Each ICM-related AR was classified according to the American College of Radiology Manual on Contrast Media, version 10.1 as “allergy-like” or “physiologic” and graded as mild, moderate, or severe. Results: The final database included 3,521 patients who underwent first- or second-line systemic treatment for metastatic disease and were re-evaluated at the end of treatment with CECT. Fifty-nine of the 3521 patients received ipilimumab (Ipi), 75 received cytokines (Cy), and the remaining 3,387 received non-immunologic agents (CHT). The mean number of CT scans performed before the index CT scan did not significantly differ between groups (p = 0.190). Overall, 71 (2%) patients developed ICM-ARs. The distribution of events among the groups was: 11.9% of reactions in Ipi patients (7/59), 5.3% in ts (4/75), and 1.8% in the CHT ones (60/3,387) with a p < 0.001 that indicates a significant statistically difference between treatment groups and reactions number. All the ARs registered in the Ipi and Cy groups were allergy-like reactions, while 10% of the ARs observed in the CHT group were of the physiologic type (6/60). Conclusions: Our data show that immunological cancer treatments, Ipi in particular, considerably increase the risk of developing CECT-related immediate adverse reactions with respect to non-immunologic agents. Although these findings now need to be validated in larger prospective studies, they serve as a “wake-up call” to radiologists to closely monitor patients who have previously received cancer immunotherapy with anti- CTLA 4-antibodies when using ICM in order to reduce the risk of potentially severe immediate adverse reactions.

Synthesis, structures and biomolecular interactions of new silver(i) 5,5-diethylbarbiturate complexes of monophosphines targeting Gram-positive bacteria and breast cancer cells.

A series of new silver(i) 5,5-diethylbarbiturate (barb) complexes with the formulas [Ag2(μ-barb)2(PPh3)2] (1), [Ag(barb)(PPh2Cy)] (2), [Ag(barb)(PPhCy2)] (3) and [Ag(barb)(PCy3)] (4) (PPh3 = triphenylphosphine, PPh2Cy = diphenylcyclohexylphosphine, PPhCy2 = dicyclohexylphenylphosphine and PCy3 = tricyclohexylphosphine) were synthesized and fully characterized by elemental analysis, IR, NMR, ESI-MS and X-ray crystallography. All the complexes display a significant affinity towards DNA with a groove binding mode and also strongly bind to BSA via hydrophobic interactions. Lipophilicity increases from 1 to 4 with an increasing number of Cy groups in the phosphine ligands. Screening of the in vitro antimicrobial activity of 1-4 against the strains of Gram-negative (S. typhimurium ATCC 14028, E. coli ATCC 25922 and O157:H7) and Gram-positive (L. garvieae 40456, S. aureus ATCC 25923, and ATCC 33591) bacteria demonstrated that all the complexes exhibit very high activity and specific selectivity against the Gram-positive bacteria, compared to AgNO3 and silver sulfadiazine. Furthermore, the growth inhibitory effects of 1-4 on four human cancer cell lines (MCF-7, PC-3, A549 and HT-29) showed that 4 has a potent cytotoxic activity against MCF-7 cells, significantly higher than cisplatin and carboplatin. The effects of the complexes on the inhibition of the cells are closely related to their lipophilicity as well as DNA/protein binding. The induction of apoptosis of MCF-7 cells treated with 4 was probed through Hoechst 33342 staining, Annexin V positivity and caspase 3/7 activity. In addition, increased ROS levels in the presence of 4 are most likely responsible for damage to both mitochondria and genomic DNA.

The Effect of Chair Yoga on Biopsychosocial Changes in English- and Spanish-Speaking Community-Dwelling Older Adults with Lower-Extremity Osteoarthritis

ABSTRACTChair yoga (CY), a mind-body therapy, is a safe nonpharmacological approach for managing osteoarthritis (OA) in older adults who cannot participate in standing exercise. However, there is no linguistically tailored CY program for those with limited English proficiency (LEP). This 2-arm randomized controlled trial compared the effects of a linguistically tailored yoga program (English and Spanish versions) on the outcomes of pain, physical function, and psychosocial factors compared to the effects of a linguistically tailored Health Education Program (HEP; English and Spanish versions). Participants with lower-extremity OA, recruited from 2 community sites, completed the Spanish (n = 40) or English (n = 60) version of twice-weekly 45-min CY or HEP sessions for 8 weeks. Data were collected at baseline, 4 weeks, 8 weeks, and 1- and 3-month follow-ups. English and Spanish CY groups (but neither HEP language group) showed significant decreases in pain interference. Measures of OA symptoms, balance, depression, and social activities were not significantly different between English and Spanish versions of CY and English and Spanish versions of HEP. It was concluded that the Spanish and English versions of CY and HEP were equivalent. Linguistically tailored CY could be implemented in aging-serving communities for persons with LEP.

Impact of cyclophosphamide dose of conditioning on the outcome of allogeneic hematopoietic stem cell transplantation for aplastic anemia from human leukocyte antigen-identical sibling.

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

The anti-osteoporosis effects of CSN1S2 protein of goat milk and yoghurt on a complete Freund's adjuvant-induced rheumatoid arthritis model in rats

This study aimed to evaluate the anti-osteoporosis effect of CSN1S2 protein from goat milk and yoghurt on a complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) model in rats. Twenty-four rats were randomly divided into six groups: control (untreated) group (C), group treated with CSN1S2 (CM) protein from goat milk, group treated with CSN1S2 protein from goat yoghurt (CY), RA group, RA group treated with CSN1S2 protein from goat milk (RAM), and RA group treated with goat yoghurt (RAY). Mineral elements and mesostructure were analyzed using X-ray fluorescence and scanning electron microscopy. Bone histomorphometry was analyzed using the BoneJ software. One way analysis of variance and Tukey post hoc tests were used to analyze and compare the means of all variables between groups. The phosphorus levels were not significantly different between treatment groups relative to the control group (p > 0.05), but were significantly higher in the CM and RAY groups relative to that observed in the CY group (p < 0.05). CSN1S2 protein of goat milk repaired the collagen structure in the femur trabecular bone. The trabecular thickness and volume were significantly lower in CM and CY groups relative to the control group (p < 0.05). The trabecular volume also decreased significantly in the CM group relative to the control group (p < 0.05). The trabecular thickness was significantly lower in the CY group relative to the CM group (p < 0.05), but the trabecular separation and trabecular volume were significantly greater (p < 0.05). The trabecular volumes were significantly elevated in the RAM and RAY groups relative to the CM group (p < 0.05). The trabecular thickness was significantly higher in the RAY group relative to the CM and CY groups (p < 0.05). CSN1S2 protein of goat milk is better than goat yoghurt in repairing femur crystallization and mesostructure in CFA-induced rheumatoid arthritis in rats.