Brocksaunders8798

In 2017, all people with severe haemophilia B (PWSHB) in Ireland switched from standard half-life (SHL) recombinant FIX (rFIX) to rFIX Fc fusion protein (rFIXFc) prophylaxis.

To evaluate prophylaxis regimens, bleeding rates and factor usage for two years of rFIXFc prophylaxis in a real-world setting.

Data collected retrospectively from electronic diaries and medical records of PWSHB for a two-year period on rFIXFc prophylaxis were compared with paired baseline data on SHL rFIX treatment.

28 PWSHB (≥18years) were enrolled, and at switchover 79% were receiving prophylaxis and 21% episodic treatment with SHL rFIX. At 24months following switchover, all remained on rFIXFc prophylaxis with reduced infusion frequency; median dose per infusion once weekly (55IU/kg, 20/28), every 10days (63IU/kg, 2/28) or every 14days (98IU/kg, 6/28). Median annualised bleed rate improved significantly on rFIXFc prophylaxis (2.0 versus 3.3 on SHL FIX) (p=0.01). Median FIX trough level with once-weekly infusions was 0.09IU/ml (0.06-0.14IU/ml). Management of bleeding episodes was similar with rFIXFc and SHL rFIX; one infusion was sufficient to treat 74% and 77% of bleeds, respectively, with similar total median treatment per bleeding episode. Factor consumption reduced by 28% with rFIXFc prophylaxis (57IU/kg/week, range 40-86IU/kg/week) compared with SHL rFIX (79IU/kg/week, range 44-210IU/kg/week) (p=0.002).

This study provides important insights into real-world experience of switching to rFIXFc prophylaxis in an adult population, demonstrating high rates of prophylaxis, with reduced infusion frequency, bleeding and FIX consumption.

This study provides important insights into real-world experience of switching to rFIXFc prophylaxis in an adult population, demonstrating high rates of prophylaxis, with reduced infusion frequency, bleeding and FIX consumption.

The motor protein, Myosin 5a (Myo5a) is known to play a role in inhibitory neurotransmission in gastric fundus. However, there is no information regarding the relative expression of total Myo5a, or of its alternative exon splice variants, across the stomach. This study investigated the differential distribution of Myo5a variants expressed within distinct anatomical regions of murine stomach.

The distribution of Myo5a protein and mRNA in the stomach was assessed by immunofluorescence microscopy and fluorescent in situ hybridization. Quantitative PCR, restriction enzyme analysis, and electrophoresis were used to identify Myo5a splice variants and quantify their expression levels in the fundus, body, antrum, and pylorus.

Myo5a protein colocalized with βIII-Tubulin in the myenteric plexus, and with synaptophysin in nerve fibers. Total Myo5a mRNA expression was lower in pylorus than in antrum, body, or fundus (p<0.001), which expressed equivalent amounts of Myo5a. However, Myo5a splice variants were differentially expressed across the stomach. VU0463271 ic50 While the ABCE splice variant predominated in the antrum and body regions, the ACEF/ACDEF variants were enriched in fundus and pylorus.

Myo5a splice variants varied in their relative expression across anatomically distinguishable stomach regions and might mediate distinct physiological functions in gastric neurotransmission.

Myo5a splice variants varied in their relative expression across anatomically distinguishable stomach regions and might mediate distinct physiological functions in gastric neurotransmission.Working memory is a basic human cognitive function. However, the genetic signatures and their biological pathway remain poorly understood. In the present study, we tried to clarify this issue by exploring the potential associations and pathways among genetic variants, brain morphometry and working memory performance. We first carried out association analyses between 2-back accuracy and 212 image-derived phenotypes from 1141 Human Connectome Project (HCP) subjects using a linear mixed model (LMM). We found a significantly positive correlation between the left cuneus volume and 2-back accuracy (T = 3.615, p = 3.150e-4, Cohen's d = 0.226, corrected using family-wise error [FWE] method). Based on the LMM-based genome-wide association study (GWAS) on the HCP dataset and UK Biobank 33 k GWAS summary statistics, we identified eight independent single nucleotide polymorphisms (SNPs) that were reliably associated with left cuneus volume in both UKB and HCP dataset. Within the eight SNPs, we found a negative correlation between the rs76119478 polymorphism and 2-back accuracy accuracy (T = -2.045, p = .041, Cohen's d = -0.129). Finally, an LMM-based mediation analysis elucidated a significant effect of left cuneus volume in mediating rs76119478 polymorphism on the 2-back accuracy (indirect effect = -0.007, 95% BCa CI = [-0.045, -0.003]). These results were also replicated in a subgroup of Caucasians in the HCP population. Further fine mapping demonstrated that rs76119478 maps on intergene CTD-2315A10.2 adjacent to protein-encoding gene DAAM1, and is significantly associated with L3HYPDH mRNA expression. Our study suggested this new variant rs76119478 may regulate the working memory through exerting influence on the left cuneus volume.

The recent conceptualization of ghrelin as a stress hormone suggested that its chronic alterations may have a role in maintaining overeating behaviors in subjects with eating disorders (EDs) reporting childhood traumatic experiences. The aim of this study was to investigate the alterations of ghrelin levels in patients with EDs, their associations with early trauma, binge and emotional eating, and possible moderation/mediation models.

Sixty-four patients with EDs and 42 healthy controls (HCs) had their plasma ghrelin levels measured and completed questionnaires evaluating general and ED-specific psychopathology, emotional eating, and childhood traumatic experiences.

Participants with anorexia nervosa had higher ghrelin levels than HCs in body mass index (BMI)-adjusted comparisons. Moreover, patients reporting a history of childhood trauma had higher ghrelin levels. Childhood sexual abuse (CSA), BMI, and self-induced vomiting were independent predictors of ghrelin levels. Moderation analyses showed that ghrelin levels were associated with binge and emotional eating only for higher levels of childhood trauma.