Raybladt6226

Pain is a common condition among people with hemophilia (PWH), negatively impacting quality of life. However, effective treatment remains a challenge. This two-arm, parallel randomized controlled pilot trial aimed to examine the three-month effects of hypnosis intervention on clinical and psychosocial variables, and on the inflammatory profile of PWH.

The study was conducted between January and October 2018, in a Reference Center for Congenital Coagulopathies. Adult (age ≥18) patients were randomized to experimental group (EG) or control group (CG). The EG received four weekly hypnosis sessions plus treatment-as-usual, and the CG maintained treatment-as-usual only. Outcomes were evaluated at one week and three months post-intervention and included pain, joint status, health-related quality of life (HRQoL), emotional state and inflammatory profile (leukocytes, C-reactive protein, cytokines). The randomization sequence was computer-generated, and allocation was concealed until enrolment. The outcome assessor was blind to allocation, but blinding of the participants was not possible due to the differences in procedure.

Twenty patients were randomized to EG (n=10; 8 analyzed) or CG (n=10; 10 analyzed). Two-way mixed ANOVA showed significant time×group interactions on pain interference with normal work and with relations with other people, and on perception of health status. The EG significantly improved in pain interference with normal work and perception of health status. There was no report of harm.

Hypnosis may be a promising intervention to manage hemophilia-related pain and promote HRQoL, with benefits lasting up to three months.

Hypnosis may be a promising intervention to manage hemophilia-related pain and promote HRQoL, with benefits lasting up to three months.

Mature hepatocytes have limited expansion capability in culture and rapidly loose key functions. Recently however, tissue culture conditions have been developed that permit rodent hepatocytes to proliferate and transform into progenitor-like cells with ductal characteristics in vitro. Analogous cells expressing both hepatic and duct markers can be found in human cirrhotic liver in vivo and may represent an expandable population.

An in vitro culture system to expand epithelial cells from human end stage liver disease organs was developed by inhibiting the canonical TGF-β, Hedgehog and BMP pathways.

Human cirrhotic liver epithelial cells became highly proliferative in vitro. Both gene expression and DNA methylation site analyses revealed that cirrhosis derived epithelial liver cells were intermediate between normal hepatocytes and cholangiocytes. Mouse hepatocytes could be expanded under the same conditions and retained the ability to re-differentiate into hepatocytes upon transplantation. In contrast, human cirrhotic liver derived cells had only low re-differentiation capacity.

Epithelial cells of intermediate ductal-hepatocytic phenotype can be isolated from human cirrhotic livers and expanded in vitro. Unlike their murine counterparts they have limited liver repopulation potential.

Epithelial cells of intermediate ductal-hepatocytic phenotype can be isolated from human cirrhotic livers and expanded in vitro. Unlike their murine counterparts they have limited liver repopulation potential.CXCR4 plays an important role in colorectal cancer (CRC) development and metastasis. Some previous studies have indicated CXCR4 as a therapeutic target in cancer. CXCR4 is known as a direct target of miR-146a. The present study aimed to investigate how exogenous induction of miR-146a affects CXCR4 gene and protein expression and also proliferation, apoptosis and migration of CRC cells. Transfection of Caco-2 and SW480 cells by a synthetic miR-146a mimic led to downregulation of CXCR4 expression at both gene and protein levels. It also downregulated expression of several miR-146a targets, including GSK3B, IRAK1, TRAF6, AKT2, SMAD4, EGFR and NFKB1, mostly in SW480 cells. Overexpression of miR-146a resulted in a partial cell cycle arrest in the both cell lines, while the apoptotic rate was also decreased. In regards to epithelial-mesenchymal transition factors, VIM was downregulated in the both cell lines, but SNAI1 was upregulated in Caco-2 cells. The wound closure assay showed a reduction in cell migration in SW480 cells, but an opposite effect was detected in Caco-2 cells following transfection with miR-146a mimic. Bcl-2 apoptosis Therefore, our results are indicating that overexpression of miR-146a, despite downregulation of oncogenic CXCR4, may not lead to a universal tumor suppressive effect in all CRC cells, and this is possibly due to differences in miR-146a effects on signaling pathways in each cell type. Selection of miR-146a for tumor suppression requires enough details regarding the signaling profile of cancer cells otherwise it may produce unexpected outcome.Double-strand breaks are repaired by error-free homologous recombination or by relatively error-prone pathways that directly join broken ends. Both types of repair have been extensively studied in Saccharomyces cerevisiae using enzymes HO or I-SceI, which create breaks with 4-nt 3' overhangs. In the current study, a galactose-regulated zinc-finger nuclease (ZFN) designed to cleave the Drosophila rosy locus was used to generate breaks with 4-nt 5' overhangs at out-of-frame cleavage sites inserted into the yeast LYS2 gene. Mutagenic repair was examined following selection of prototrophs on lysine-deficient medium containing galactose or surviving colonies on galactose-containing rich medium. Following cleavage of the original rosy spacer (ACGAAT), most Lys+ colonies contained 1- or 4-bp insertions at the cleavage site while most survivors had either a 2-bp insertion or a large deletion. Small insertions reflected nonhomologous end joining (NHEJ) and large deletions were the product of microhomology-mediated end joining (MMEJ). Changing the original ACGAAT spacer to either AGCAAT, ACGCGT or CTATTA altered the molecular features of NHEJ events as well as their frequency relative to MMEJ. Altering the optimal 6-bp spacer size between the zinc-finger protein binding sites to 5 bp or 7 bp eliminated the effect of continuous ZFN expression on survival, but Lys+ prototrophs were still generated. Analysis of Lys+ revertants after cleavage of the 5-bp spacer indicated that both the position and spacing of ZFN-generated nicks were variable. Results provide insight into effects of overhang sequence on mutagenic outcomes and demonstrate ZFN cleavage of 5- or 7-bp spacers in vivo.RAD51 paralogs are key components of the homologous recombination (HR) machinery. Mouse mutants have been reported for four of the canonical RAD51 paralogs, and each of these mutants exhibits embryonic lethality, although at different gestational stages. However, the phenotype of mice deficient in the fifth RAD51 paralog, XRCC3, has not been reported. Here we report that Xrcc3 knockout mice exhibit midgestational lethality, with mild phenotypes beginning at about E8.25 but severe developmental abnormalities evident by E9.0-9.5. The most obvious phenotypes are small size and a failure of the embryo to turn to a fetal position. A knockin mutation at a key ATPase residue in the Walker A box results in embryonic lethality at a similar stage. Death of knockout mice can be delayed a few days for some embryos by homozygous or heterozygous Trp53 mutation, in keeping with an important role for XRCC3 in promoting genome integrity. Given that XRCC3 is a unique member of one of two RAD51 paralog complexes with RAD51C, these results demonstrate that both RAD51 paralog complexes are required for mouse development.Helicases involved in genomic maintenance are a class of nucleic-acid dependent ATPases that convert the energy of ATP hydrolysis into physical work to execute irreversible steps in DNA replication, repair, and recombination. Prokaryotic helicases provide simple models to understand broadly conserved molecular mechanisms involved in manipulating nucleic acids during genome maintenance. Our understanding of the catalytic properties, mechanisms of regulation, and roles of prokaryotic helicases in DNA metabolism has been assembled through a combination of genetic, biochemical, and structural methods, further refined by single-molecule approaches. Together, these investigations have constructed a framework for understanding the mechanisms that maintain genomic integrity in cells. This review discusses recent single-molecule insights into molecular mechanisms of prokaryotic helicases and translocases.Poor performance in executive functions is observed in individuals with eating disorders (EDs). These impairments have usually been associated with the presence of comorbid psychopathology or with higher severity of EDs. However, few studies have explored the interaction between illness duration and deficits in executive functions. The present study investigates the association between ED duration and performance in decision-making, inhibitory control, and cognitive flexibility in the anorexia nervosa restrictive subtype (AN-R), bulimic/purging subtype (AN-BP), and binge spectrum disorders (BSDs) (namely, bulimia nervosa and binge eating disorder) among 116 women with EDs compared with 123 women healthy controls (HCs). Using cumulative survival analysis, we estimated the risk of deficits related to illness duration. Predictors of executive dysfunctions were assessed by regression analysis, including as potential predictors illness duration, severity of general psychopathology, and ED symptomatology. Results showed poor decision-making and cognitive flexibility in participants with EDs compared with HCs. ED duration was associated with poor inhibitory control in the AN-BP group and poor cognitive flexibility in the BSD group. The illness duration increased the risk of presenting early deficits in executive function. In decision-making and inhibitory control, the AN-R group showed the earliest deficits, whereas in cognitive flexibility it was the BSD group. ED duration predicted impaired cognitive flexibility in the BSD group and impaired inhibitory control in the AN-BP group, whereas the severity of general psychopathological symptoms was a predictor of impaired cognitive flexibility in individuals with AN-R. These results highlight the relevance of illness duration in executive dysfunctions in EDs.Attentional biases to threatening stimuli have been suggested to play a key role in the onset and course of schizophrenia. However, current research has not completely demonstrated this assumption. The aim of this eye-tracking study was to shed light on the underlying psychological mechanisms of schizophrenia by examining the attentional processing of socio-emotional information. Forty-four individuals with schizophrenia and 47 healthy controls were assessed in a 3-s free-viewing task with a social scene (i.e., happy, threatening, or neutral) in competition with a non-social one to determine the effects of emotional information on the different stages of the attentional processing. The location and latency of initial fixations (i.e., initial orienting), the firs-pass fixations and gaze duration (i.e., attentional engagement), and the percentage of total duration and total fixations (i.e., attentional maintenance) were analyzed. It was found that the schizophrenia group showed longer first-pass gaze duration, as well as higher percentage of total fixations and total duration toward threatening scenes in relation to the non-social ones, compared to controls.