This study investigated the prevalence of smoking, drinking, and physical inactivity and the associated factors of these behaviors in gastric cancer survivors. The baseline data from the nationwide cohort study was used. Four hundred thirty-seven gastric cancer survivors who survived ≥ 2 years from diagnosis and reported completion of treatment were matched with 4,370 controls according to age, sex, education, and household income. The prevalence rates of current smoking and drinking among gastric cancer survivors were 8.7% and 38.3%, which were significantly lower than those among matched controls (p ≤ 0.001), but the prevalence rates of physical inactivity were not significantly different (55.8% vs. 59.9%, p=0.248). In gastric cancer survivors, ≥ 5 years since cancer diagnosis and current drinking contributed to more current smoking; otherwise, age increment and femalewere associatedwith lower current smoking. Thosewith household income ≥ $2,000 and current smokers were more likely to drink and female showed less drinking. Female, currently employed state, and self-rated health status were associated with more physical inactivity. Although gastric cancer survivors showed better health behaviors than controls, suggesting that the diagnosis of cancer may motivate individuals towards healthy behaviors, their current prevalence rates of smoking and drinking were still high, and more than 50% of them were physically inactive. Tailored interventions to improve their health behaviors considering associated factors for the gastric cancer survivors are necessary.

This prospective study aimed to determine the effects of the persistence of overweight for three years and the PLA2G7 V279F polymorphism, as well as the interaction between these factors, on the association of age with blood pressure (BP). Healthy middle-aged subjects with normotensive BP were divided into the normal-weight and overweight groups. The PLA2G7 V279F genotype, BP, lipoprotein-associated phospholipase A₂ (Lp-PLA₂) activity, and oxidized low-density lipoprotein (ox-LDL) were determined. Lp-PLA₂ activity was lower in the F allele subjects (n = 111) than in those with the VV genotype (n = 389). The overweight individuals with the F allele had lower Lp-PLA₂ activity and ox-LDL at both baseline and after three years and lower systolic and diastolic BP and LDL cholesterol after three years compared with those with the VV phenotype. After three years, the overweight subjects with the VV phenotype exhibited greater increases in Lp-PLA₂ activity, systolic BP, and ox-LDL than those with the F allele and normal-weight subjects with the VV phenotype. A multivariate analysis revealed that the PLA2G7 V279F genotype, baseline BMI, changes in Lp-PLA₂ activity and ox-LDL remained independently and positively associated with changes in systolic BP. The simultaneous presence of the PLA2G7 279VV genotype and persistence of overweight synergistically increases the risk for hypertension, whereas lower Lp-PLA₂ activity in PLA2G7 279F allele carriers might offer certain protection against hypertension, even in individuals who have been overweight for over three years.

An 11-month-old castrated male Pomeranian presented with nonunion following a femoral fracture that occurred after femoral head and neck osteotomy. Radiography and computed tomography revealed severe atrophy of the proximal bone fragment and retardation of the ipsilateral distal fragment and tibia. An autogenous bone graft using coccygeal bone was performed, in which three and a half coccyges were placed in succession and fixed using an orthogonal locking plate. To promote bone healing and facilitate proper weight bearing and ambulation, bone morphogenetic proteins, biphasic calcium phosphate, platelet-rich plasma, passive-range-of-motion exercises, transcutaneous electrical nerve stimulation, neuromuscular electrical stimulation, and low-level laser therapy were applied. During the four-year follow-up, it was observed that the previously engrafted bone healed well and maintained stability over a prolonged period, resulting in the patient being able to walk comfortably with good outcomes. However, some degree of lameness was noted in the dog when running owing to limb shortening and joint contracture.

Demineralized bone matrix (DBM) is a widely used allograft material for bone repair, but its handling properties and retention at defect sites can be challenging. Hydroxyethyl cellulose (HEC) has shown promise as a biocompatible carrier for bone graft materials. This study aimed to evaluate the efficacy of DBM combined with cancellous bone putty formed using HEC as an allograft material for bone regeneration in a canine tibial defect model. Experiments were conducted using dogs with proximal tibial defects. Four groups were compared: empty (control group), DBM + HEC (DH), DBM + cancellous bone + HEC (DCH), and DBM + cancellous bone + calcium phosphate + HEC (DCCH). Radiographic, micro-computed tomography (CT), and histomorphometric evaluations were performed 4 and 8 weeks postoperatively to assess bone regeneration. The Empty group consistently exhibited the lowest levels of bone regeneration throughout the study period, indicating that DBM and cancellous bone with HEC significantly enhanced bone regeneration. At week 4, the DCCH group showed the fastest bone regeneration on radiography and micro-computed tomography. By week 8, the DCH group showed the highest area ratio of new bone among all experimental areas, followed by the DH and DCCH groups. This study demonstrated that HEC significantly enhances the handling, mechanical properties, and osteogenic potential of DBM and cancellous bone grafts, making it a promising carrier for clinical applications in canine allograft models. When mixed with allograft cancellous bone, which has high porosity and mechanical strength, it becomes a promising material offering a more effective and reliable option for bone repair and regeneration.

A 17-month-old domestic short-hair cat was referred due to a non-union in the left tibia. The initial repair, conducted 3 months prior at another animal hospital, involved an intramedullary (IM) pin and wire to address a comminuted fracture. Unfortunately, the wire knot caused a skin tract, resulting in osteomyelitis. Although the wire knot was removed at that hospital, the draining tract persisted, continuously discharging exudate. Upon evaluation, the first surgery was reassessed and revised, involving the removal of the IM pin and the application of external skeletal fixation alongside an antibiotic susceptibility test. After 118 days post-revision surgery, while some cortical continuity was observed, a significant bone defect persisted, posing a substantial risk of refracture should the implant be removed. A second revision surgery was performed, utilizing a bone plate combined with cancellous bone autograft, recombinant human bone morphogenetic protein-2, and xenograft featuring a canine-derived cancellous chip mixed with demineralized bone matrix. Remarkably, the bone completed its healing within 105 days following the subsequent surgery. Radiography demonstrated successful management of the large bone defect up to the 2-year postoperative check-up. During telephone follow-ups for 3.5 years after surgery, no complications were identified, and the subject maintained a favorable gait.

Spliceosomal mutations account for the most frequent class of mutations in patients with MDS and CMML, yet the mechanism by which these mutations perform their driver function is not well understood. Moreover, no genetically engineered murine models for expression of spliceosomal gene mutations from their endogenous loci have been reported. Given the genetic heterogeneity of primary patient samples, we generated a model for conditional expression of the commonly occurring SRSF2P95H mutation from the endogenous murine locus of Srsf2. We compared expression of the Srsf2P95H mutation with genetic inactivation of 0, 1 or 2 copies of Srsf2 to understand the biological and mechanistic consequences of spliceosomal mutations relative to loss-of-function. Mx1-cre Srsf2P95H/wildtype mice exhibited significant morphologic dysplasia, leukopenia, macrocytic anemia, and preserved bone marrow (BM) cellularity as early as 2 weeks after mutation expression (Figure A). Moreover, Mx1-cre Srsf2P95H/wildtype mice exhibited an increase in hematopoietic stem/progenitor cells (HSPCs) with an increase in lineage-negative Sca1+ c-Kit+ cells (LSK cells) in S-phase and early apoptosis. In competitive transplantation, Srsf2P95H mice HPSCs were expanded in the BM at 16 weeks post-transplantation despite having a reduced contribution to peripheral blood chimerism. In contrast, mice with homozygous deletion of Srsf2 exhibited anemia and leukopenia due to BM aplasia with striking loss of HSPCs (Figure B). Collectively, these data show that Srsf2 is required for hematopoiesis, while mutations in Srsf2 provide a competitive advantage at the level of HSPCs but impair differentiation into mature circulating blood elements. Next, to identify transcriptional and post-transcriptional alterations caused by SRSF2 mutations, we performed deep RNA-seq on sorted HSPC populations from wildtype and Srsf2P95H mice, stable K562 cell lines ectopically expressing an empty vector or a single allele of SRSF2 (WT, P95H, P95L, P95R), as well as primary CMML and AML patient samples. We quantified global changes in splicing of ~125,000 alternative splicing events and ~160,000 constitutive splice junctions associated with SRSF2 mutations in these datasets. Intersection of differentially spliced genes in primary murine HSPC, CMML, and AML samples identified 75 genes that were differentially spliced in association with SRSF2 mutations in murine HSPCs and at least one primary patient cohort. Many of the genes that were differentially spliced in SRSF2 mutant cells participate in biological processes of known importance in myeloid malignancies. For example, a cassette exon of EZH2 that alters the reading frame likely to induce nonsense-mediated decay was promoted by SRSF2 mutations, while a frame-preserving cassette exon of BCOR was repressed by SRSF2 mutations. We next sought to determine how SRSF2 mutations alter SRSF2Õs normal role in RNA splicing. As SRSF2 recognizes exonic splicing enhancer (ESE) elements within the pre-mRNA to promote exon recognition, we hypothesized that SRSF2 mutations might alter its normal sequence-specific activity. To test this, we performed an ab initio motif identification screen to identify motifs that were enriched or depleted in cassette exons promoted versus repressed in primary Srsf2P95H cells relative to wildtype. This analysis identified CCAG and GGTG as the most enriched and depleted consensus motifs, respectively. A recent solution structure of SRSF2 in complex with RNA revealed that SRSF2 normally recognizes the motifs CCNG and GGNG equally well. Analysis of the spatial distribution of CCNG and GGNG motifs across genomic loci containing cassette exons that were promoted or repressed in association with SRSF2 mutations revealed that CCNG and GGNG were respectively enriched and depleted specifically over the cassette exons, and not over the flanking introns or exons, that were differentially spliced in association with SRSF2 mutations (Figure C). Together, our data indicate that mutant SRSF2 drives widespread changes in splicing due to alterations in its sequence-specific recognition of exonic splicing enhancers. The biological as well as molecular data here identify an effect of the SRSF2P95H mutation distinct from haploinsufficient or complete loss of SRSF2 and reveal that mutations in SRSF2 alter ESE preference to contribute to key aspects of MDS.