SEM-2/SoxC regulates multiple aspects of C. elegans postembryonic mesoderm development.

Development of multicellular organisms requires well-orchestrated interplay between cell-intrinsic transcription factors and cell-cell signaling. One set of highly conserved transcription factors that plays diverse roles in development is the SoxC group. C. elegans contains a sole SoxC protein, SEM-2. SEM-2 is essential for embryonic development, and for specifying the sex myoblast (SM) fate in the postembryonic mesoderm, the M lineage. We have identified a novel partial loss-of-function sem-2 allele that has a proline to serine change in the C-terminal tail of the highly conserved DNA-binding domain. Detailed analyses of mutant animals harboring this point mutation uncovered new functions of SEM-2 in the M lineage. First, SEM-2 functions antagonistically with LET-381, the sole C. elegans FoxF/C forkhead transcription factor, to regulate dorsoventral patterning of the M lineage. Second, in addition to specifying the SM fate, SEM-2 is essential for the proliferation and diversification of the SM lineage. Finally, SEM-2 appears to directly regulate the expression of hlh-8, which encodes a basic helix-loop-helix Twist transcription factor and plays critical roles in proper patterning of the M lineage. Our data, along with previous studies, suggest an evolutionarily conserved relationship between SoxC and Twist proteins. Furthermore, our work identified new interactions in the gene regulatory network (GRN) underlying C. elegans postembryonic development and adds to the general understanding of the structure-function relationship of SoxC proteins.

Comparison of patient demographics and patient-specific risk factors for readmissions following open reduction and internal fixation for acetabular fractures.

PURPOSE: Acetabular fractures are highly complex injuries often resulting from high-energy trauma. The gold standard treatment for these injuries has become open reduction internal fixation (ORIF). The purpose of this study is to further this understanding and investigate how (1) patient demographics and (2) patient-specific risk factors affect 90-day readmission rates. METHODS: A retrospective, nationwide query of private insurance database from January 1st, 2010 to October 31st, 2020 was performed using ICD-9, ICD-10, and CPT codes. Patients who underwent acetabular ORIF and were readmitted within 90 days following index procedure were included, patients who were not readmitted served as controls. Patients were divided by demographics and specific risk factors associated with readmission. RESULTS: The query yielded a total of 3942 patients. Age and sex were found to be non-significant contributing risk factors to 90-day readmissions. Data also showed that statistically significant comorbidities included arrhythmia, cerebrovascular disease, coagulopathy, fluid and electrolyte abnormalities, and pathologic weight loss. CONCLUSION: This study illustrated how several patient-specific risk factors may contribute to increased 90-day readmission risk following acetabular ORIF. A heightened awareness of these comorbidities in patients requiring acetabular ORIF is required to improve patient outcomes and minimize rates of readmission. Further investigation is needed to improve patient outcomes, and increase awareness of potential post-operative complications in these higher-risk patient populations.

Crohn's disease is associated with higher rates of implant-related complications following primary total knee arthroplasty.

INTRODUCTION: In Western countries, there has been a rise in the prevalence of Crohn's Disease (CD) and primary total knee arthroplasty (TKA). This study delves deeper into the effects of CD on TKA patients by examining (1) the length of in-hospital stay (LOS); (2) the rates of readmission; (3) complications related to implants; and (4) the costs associated with care. METHODS: A retrospective analysis using the PearlDiver database was conducted, encompassing the time frame between January 1st, 2005 and March 31st, 2014, focusing on patients who underwent TKA and were either diagnosed with CD or not. Patients with CD were paired with control subjects at a 1:5 ratio based on age, gender, and medical comorbidities. The analysis comprised a total of 96,229 patients (CD = 16,039; non-CD = 80,190). RESULTS: Patients with CD had a notably longer hospital stay (3 v. 2 days, p < 0.0001) and faced significantly higher rates of 90-day readmissions and complications (19.80% v. 14.91%, OR: 1.40, p < 0.0001; 6.88% v. 4.88%, OR: 1.43, p < 0.0001 respectively). Additionally, CD patients incurred greater expenses on the surgery day ($18,365.98 v. $16,192.00) and within 90 days post-surgery ($21,337.46 v. $19,101.42). CONCLUSION: This study demonstrates longer in-hospital LOS, higher rates of readmissions, implant-related complications, and costs of care among CD patients following primary TKA.

Safety and Efficacy of a Single-Stage versus Two-Stage Intramedullary Nailing for Synchronous Impending or Pathologic Fractures of Bilateral Femur for Oncologic Indications: A Systematic Review.

Although intramedullary nail (IMN) fixation is the standard of care for most impending and/or complete pathologic fractures of the femur, the optimal timing/sequence of the IMN in cases of synchronous bilateral femoral disease in advanced cancer is not well established. Thus, we compared the outcomes of single-stage (SS) vs. two-stage (TS) IMN of the bilateral femur with a systematic review of the literature on this topic. Bilateral SS and TS IMN cases were identified from 14 studies extracted from four databases according to PRISMA guidelines. Safety (complications, reoperations, mortality, survival, blood loss, and transfusion) and efficacy (length of stay [LOS], time to start rehabilitation and adjuvant therapy, functional scores, and cost) were compared between the groups. A total of 156 IMNs in 78 patients (36 SS and 42 TS) were analyzed. There were one surgical (infection in TS requiring reoperation; p = 0.860) and fifteen medical complications (five in SS, ten in TS; p = 0.045), with SS being associated with lower rates of total and medical complications. Survival, intraoperative mortality, and postoperative same-admission mortality were similar. No cases of implant failure were reported. Data on LOS, rehabilitation, and adjuvant therapy were scarcely reported, although one study favored SS over TS. No study compared cost or functional scores. Our study is the largest and most comprehensive of its kind in supporting the safety and efficacy of a SS bilateral femur IMN approach in these select patients. Further investigations with higher levels of evidence are warranted to optimize treatment protocols for this clinical scenario.

Exposure to Sevoflurane, But Not Ketamine, During Early-life Brain Development has Long-Lasting Effects on GABAA Receptor Mediated Inhibitory Neurotransmission.

Understanding the different mechanisms associated with different anesthetic targeted receptors is critical towards identifying accurate long-term outcome measures as a result of early-life anesthetic exposure. We examined changes in GABAA receptor mediated neurotransmission by a predominately GABAA receptor targeted anesthetic, sevoflurane or a predominately NMDA receptor targeted anesthetic, ketamine. Postnatal day 7 male mice were exposed to sevoflurane or ketamine and examined as adults for changes in inhibitory neurotransmission and its associated change in induced seizure activity. Paired pulse stimulation experiment showed that early-life sevoflurane treated mice had significantly less hippocampal CA1 inhibition later in life. There was significantly increased CA1 excitatory output in the sevoflurane treated group compared to the no sevoflurane treated group after the GABA agonist muscimol. Similar to our previously established data for early-life sevoflurane, here we established early-life ketamine administration resulted in neurodevelopmental behavioral changes later in life. However, muscimol did not produce a significant difference on the excitatory CA1 output between early-life ketamine group and saline group. While sevoflurane treated mice showed significantly higher induced seizure intensities and shorter latency periods to reach seizure intensity stage 5 (Racine score) compared with no sevoflurane treated mice, this phenomenon was not observed in the ketamine vs. saline treated groups. Early-life sevoflurane, but not ketamine, exposure reduced GABAergic inhibition and enhanced seizure activity later in life. The results indicate that early-life exposure to different anesthetics lead to distinct long-term effects and their unique pathways require mechanistic studies to understand induced long-lasting changes in the brain.