End-stage ankle arthritis alters dynamic stability during gait as measured by margin of stability between limbs and compared to healthy controls.

OBJECTIVE: This study aimed to assess dynamic stability in individuals with end-stage ankle arthritis compared to healthy controls by evaluating the margin of stability (MoS) during gait. DESIGN: A cohort of 50 participants with end-stage ankle arthritis (AA) and 50 matched healthy controls (HC) were analyzed from an IRB approved database. Kinematic data were collected using an eight-camera motion analysis system, and MoS was calculated based on the extrapolated center of mass (XCoM) and the base of support (BoS). Statistical analysis was performed using a linear mixed effects model with gait speed as a covariate. RESULTS: The analysis revealed a significant interaction between the group (AA vs. HC) and limb (arthritic vs. non-arthritic) at heel-strike and midstance. The non-arthritic limb demonstrated a significantly smaller AP MoS during heel-strike compared to the arthritic limb and either of the limbs of the HC group (p < 0.001). The arthritic limb demonstrated a significantly greater ML MoS during midstance compared to the non-arthritic limb and either of the limbs of the HC group (p < 0.001). AA group had significant slower gait speed (p < 0.001), smaller step length (p = 0.015) and smaller locomotor rehabilitation index (p < 0.001) than HC. CONCLUSION: Individuals with end-stage ankle arthritis exhibit altered dynamic stability during gait, with a significantly smaller AP MoS on the non-arthritic limb at heel-strike and greater ML MoS on the arthritic limb at midstance compared to healthy controls. Our results suggest that individuals with ankle arthritis are less stable when navigating single limb support of the arthritic limb. Further research should further examine the associations with fall risk in patients with ankle arthritis and evaluate the effectiveness of therapeutic interventions targeting these factors.

Self-Evisceration of Intestines as the Initial Presentation of Schizoaffective Disorder.

Schizoaffective disorder is categorized by major mood episodes and symptoms of schizophrenia that include disorganized speech, delusions, paranoia, and hallucinations. It is associated with risk factors, including a history of abuse and cannabis use, and patients are typically diagnosed in adolescence and young adulthood. In this case report, we describe the unusual case of a 39-year-old male patient with undiagnosed schizoaffective disorder who self-eviscerated his intestines during an episode of psychosis. He received an emergent exploratory laparotomy with a partial colectomy. After medical stabilization and reorientation, the patient recalled a 10-year history of paranoia associated with significant cannabis use, despite otherwise functioning appropriately in society. During a two-week hospital course, his paranoia and hallucinations were remitted on olanzapine and valproic acid. In addition to discussing his presentation and recollection of the incident, we also discuss similar cases of self-mutilation in nonsuicidal patients and the relationship between cannabis use and schizophrenia spectrum disorders.

Superior inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis: linking dietary fiber to cancer prevention.

Intake of dietary fiber may protect against colon cancer. The anticancer property is associated with an increased production of short chain fatty acids (SCFAs), including acetate, propionate and butyrate, during dietary fiber fermentation in the colon. However, the mechanisms remain to be determined. We hypothesized that butyrate exhibits a stronger inhibitory potential against colon cancer cell proliferation compared with acetate and propionate. We determined the half maximal inhibitory concentrations (IC50) of SCFAs in HCT116 human colon cancer cell proliferation by examining cell growth curves. At 24- and 48-hour time points, IC50 (mmol/L) concentrations of acetate, propionate, and butyrate were [66.0 and 29.0], [9.2 and 3.6], and [2.5 and 1.3], respectively. Consistent with the greater anti-proliferative effect, butyrate exhibits >3-fold stronger potential for inducing cell cycle arrest at the G2 phase with a drop in S-phase fraction (including c-Myc/p21 signaling) and apoptosis when compared with acetate and propionate. Subsequently, we focused on the effect of butyrate on apoptotic gene expression. Using a PCR array analysis, we identified 17 pro-apoptotic genes, 6 anti-apoptotic genes, and 4 cellular mediator genes with >1-fold increase or decrease in mRNA levels out of 93 apoptosis related genes in butyrate-treated HCT116 cells when compared with untreated HCT116 cells. These genes were mainly involved in the TNF, NFκB, CARD, and BCL-2 regulated pathways. Taken together, our data indicate a greater inhibitory efficacy of butyrate over propionate and acetate against human colon cancer cell proliferation via cell cycle arrest and apoptosis.

Butyrate Inhibits Deoxycholic-Acid-Resistant Colonic Cell Proliferation via Cell Cycle Arrest and Apoptosis: A Potential Pathway Linking Dietary Fiber to Cancer Prevention.

SCOPE: Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits colon cancer preventive effects. In contrast, a high fat intake increases fecal secondary bile acids, such as deoxycholic acid (DCA, a potential cancer promoter), which selectively enrich mutant epithelial cells with an abnormally high resistance to DCA-induced apoptosis in the colon. This study is conducted to test the hypothesis that physiological concentrations of butyrate inhibit DCA-resistant colonic cell proliferation. METHODS AND RESULTS: With human HCT-116 cells as parental colonic cells, a human DCA-resistant colonic cell line (DCA-RCL) is developed. DCA treatment increases apoptosis and intracellular reactive oxygen species (an apoptotic trigger) at a rate threefold greater in HCT-116 cells than in DCA-RCL cells. Subsequently, 41 apoptosis related genes (including signaling pathways) with greater than onefold (mRNA) change in DCA-RCL cells are identified compared with HCT-116 cells. Moreover, butyrate treatment inhibits DCA-RCL cell proliferation with similar efficacy when compared with HCT116 cells via cellular myelocytomatosis oncogene (c-Myc)/p38 mitogen-activated protein kinase pathway. CONCLUSION: It is demonstrated that butyrate inhibits DCA-RCL cell proliferation at the cellular and molecular level. These data provide a proof of concept that butyrate can protect against colon carcinogenesis through a specific targeting of DCA-resistant colonic cells.