Craniosynostosis occurs in approximately 1:2000 live births. It may affect the coronal, sagittal, metopic and lambdoid sutures in isolation or in combination. Although non-syndromic synostoses are more common, over 150 genetic syndromes have been identified. Recent advances in genetic mapping have linked chromosomal mutations with craniosynostotic syndromes. Despite the identification of these genetic mutations, the fundamental biomolecular mechanisms mediating cranial suture biology remain unknown. Today, many laboratories are investigating murine cranial suture biology as a model for human cranial suture development and fusion. Normal murine cranial suture biology is very complex, but evidence suggests that the dura mater provides the biomolecular blueprints (e.g. the soluble growth factors), which guide the fate of the pleuripotent osteogenic fronts. While our knowledge of these dura-derived signals has increased dramatically in the last decade, we have barely begun to understand the fundamental mechanisms that mediate cranial suture fusion or patency. Interestingly, recent advances in both premature human and programmed murine suture fusion have revealed unexpected results, and have generated more questions than answers.
Animal ; Craniosynostoses/*etiology/genetics/surgery ; Fetal Development ; Fetus/*physiology ; Human ; Mutation

OBJECTIVETo evaluate the effect of endothelial progenitor cells (EPCs) mobilization on the healing of calvarial defect in diabetic mice.

METHODS55 type II adult male diabetic mice were included in this study. They were randomly divided into three groups: the non-operative group (n = 5), the experimental group (n = 25) and the control group (n = 25). Two circular bony defects, 3 mm in diameter, were created on the parietal bones of the diabetic mice. Intraperitoneal AMD3100 (10 mg/kg; n = 25) or sterile saline (control group) was administered daily beginning at post-operative day 3 and continuing for 15 days. 5 mice were sacrificed in each group at non-operation, post-operative week 1,2,4, 8,12. Circulation EPC level was measured at pre-operation, post-operative day 7 and day 14. Bony regeneration was assessed with micro-CT at post-operative week 4, 8 and 12. HE staining was performed on all the decalcified bone samples. Immunofluorescent CD31 and osteocalcin staining was performed on calvarial defects at weeks 1, 2, and 4 to assess the vascularity and osteoblast density, respectively.

RESULTSThe mobilization of EPC in diabetic mice almost disappeared one week after trauma, while AMD3100 could dramatically increase the circulation EPC level for a long time after trauma. Compared to control group, the healing percentage of bony defect in the diabetic mice treated with AMD3100 was obviously increased at post-operative week 8 (50.5% vs. 34.8%) and week 12 (50.9% vs. 40.2%). Calvarial defects of AMD3100-treated mice harvested at 1, 2, and 4 weeks demonstrated increased vascularity and osteoblast density, compared to the controls. The difference was most marked in postoperative week 2 (vascularity: 6.11% vs. 2.47%; osteoblast density 2.81% vs. 1.22%, P < 0.01).

CONCLUSIONAMD3100 can improve the healing of calvarial defect in diabetic mice by increasing the vascularity and osteoblast density at the regeneration area.

Animals ; Bone Regeneration ; Diabetes Mellitus, Experimental ; Endothelial Cells ; cytology ; drug effects ; Endothelium, Vascular ; cytology ; Heterocyclic Compounds ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Osteoblasts ; cytology ; Parietal Bone ; Skull ; pathology ; Stem Cells ; cytology ; drug effects ; Wound Healing

BACKGROUND/AIMS: Traditionally, patients with acute diverticulitis undergo follow-up endoscopy to exclude colorectal cancer (CRC). However, its usefulness has been debated in this era of high-resolution computed tomography (CT) diagnosis. We assessed the frequency and outcome of endoscopic follow-up for patients with CT-proven acute diverticulitis, according to the confidence in the CT diagnosis. METHODS: Records of patients with CT-proven acute diverticulitis between October 2007 and March 2014 at Sandwell & West Birmingham Hospitals NHS Trust were retrieved. The National Cancer Registry confirmed the cases of CRC. Endoscopy quality indicators were compared between these patients and other patients undergoing the same endoscopic examination over the same period. RESULTS: We identified 235 patients with CT-proven acute diverticulitis, of which, 187 were managed conservatively. The CT report was confident of the diagnosis of acute diverticulitis in 75% cases. Five of the 235 patients were subsequently diagnosed with CRC (2.1%). Three cases of CRC were detected in the 187 patients managed conservatively (1.6%). Forty-eight percent of the conservatively managed patients underwent follow-up endoscopy; one case of CRC was identified. Endoscopies were often incomplete and caused more discomfort for patients with diverticulitis compared with controls. CONCLUSIONS: CRC was diagnosed in patients with CT-proven diverticulitis at a higher rate than in screened asymptomatic populations, necessitating follow-up. CT reports contained statements regarding diagnostic uncertainty in 25% cases, associated with an increased risk of CRC. Follow-up endoscopy in patients with CT-proven diverticulitis is associated with increased discomfort and high rates of incompletion. The use of other follow-up modalities should be considered.
Colorectal Neoplasms* ; Diagnosis ; Diverticulitis* ; Endoscopy ; Follow-Up Studies* ; Humans ; Uncertainty

Clinical reasoning (CR) is a key learning domain for physical therapy educators and a core skill for entry-level practitioners. Integrated clinical experience (ICE) and problem-based learning (PBL) have each been reported to improve interpersonal and social domains, while promoting knowledge acquisition and CR. Unfortunately, studies monitoring CR during ICE with concurrent PBL in physical therapy education are sparse. We hypothesized that ICE with concurrent PBL would be associated with improved self-reported CR in third-year student physical therapists (PTs) in the United States. The Self-Assessment of Clinical Reflection and Reasoning (SACRR) survey was administered to 42 student PTs at the beginning and end of their third and final year of didactic training. Between the pretest and posttest analyses, the participants completed faculty-led ICE and PBL coursework for 16 weeks. The overall SACRR score and 26 individual item scores were examined. The Wilcoxon rank-sum test and paired t-test were used, with statistical significance accepted at P < 0.05. Significant improvements were observed in the overall SACRR score (P < 0.001), including 6 of the 26 survey items centered around decision-making based on experience and evidence, as well as self-reflection and reasoning. ICE with PBL was associated with improved self-assessed CR and reflection in third-year student PTs in the United States. Monitoring the impact of curricular design on CR may improve educators' ability to enhance cognitive and psychomotor skills, which underscores the importance of increasing the explicit use of theoretical frameworks and teaching techniques for coping with uncertainty as a way of enhancing entry-level training.
Education ; Humans ; Ice ; Learning ; Physical Therapists ; Problem-Based Learning ; Self-Assessment ; Uncertainty ; United States

The somatic epigenome can be reprogrammed to a pluripotent state by a combination of transcription factors. Altering cell fate involves transcription factors cooperation, epigenetic reconfiguration, such as DNA methylation and histone modification, posttranscriptional regulation by microRNAs, and so on. Nevertheless, such reprogramming is inefficient. Evidence suggests that during the early stage of reprogramming, the process is stochastic, but by the late stage, it is deterministic. In addition to conventional reprogramming methods, dozens of small molecules have been identified that can functionally replace reprogramming factors and significantly improve induced pluripotent stem cell (iPSC) reprogramming. Indeed, iPS cells have been created recently using chemical compounds only. iPSCs are thought to display subtle genetic and epigenetic variability; this variability is not random, but occurs at hotspots across the genome. Here we discuss the progress and current perspectives in the field. Research into the reprogramming process today will pave the way for great advances in regenerative medicine in the future.
Animals ; Cell Differentiation ; Cellular Reprogramming ; MicroRNAs ; genetics ; Models, Biological ; Pluripotent Stem Cells ; cytology ; metabolism ; Stochastic Processes

Clinical reasoning (CR) is a key learning domain for physical therapy educators and a core skill for entry-level practitioners. Integrated clinical experience (ICE) and problem-based learning (PBL) have each been reported to improve interpersonal and social domains, while promoting knowledge acquisition and CR. Unfortunately, studies monitoring CR during ICE with concurrent PBL in physical therapy education are sparse. We hypothesized that ICE with concurrent PBL would be associated with improved self-reported CR in third-year student physical therapists (PTs) in the United States. The Self-Assessment of Clinical Reflection and Reasoning (SACRR) survey was administered to 42 student PTs at the beginning and end of their third and final year of didactic training. Between the pretest and posttest analyses, the participants completed faculty-led ICE and PBL coursework for 16 weeks. The overall SACRR score and 26 individual item scores were examined. The Wilcoxon rank-sum test and paired t-test were used, with statistical significance accepted at P < 0.05. Significant improvements were observed in the overall SACRR score (P < 0.001), including 6 of the 26 survey items centered around decision-making based on experience and evidence, as well as self-reflection and reasoning. ICE with PBL was associated with improved self-assessed CR and reflection in third-year student PTs in the United States. Monitoring the impact of curricular design on CR may improve educators' ability to enhance cognitive and psychomotor skills, which underscores the importance of increasing the explicit use of theoretical frameworks and teaching techniques for coping with uncertainty as a way of enhancing entry-level training.

BACKGROUND/AIMS: Gastroparesis-like syndrome (GLS) is defined as gastroparesis-like symptoms with normal gastric scintigraphy. While the efficacy of gastric electrical stimulation (GES) in gastroparesis is well known, the utility of GES in GLS is largely unknown. Our aim was to clarify the role of GES in GLS. We implanted consecutive patients with symptoms of gastroparesis with temporary gastric electrical stimulation and observed changes in gastric scintigraphy and total symptom score. METHODS: Five hundred and fifty-one patients suffering from symptoms of gastroparesis (nausea, vomiting, bloating/distension, anorexia/early satiety, and abdominal pain) with negative endoscopy underwent gastric scintigraphy with analysis of 1) solid radio-nuclide gastric emptying at 1, 2, and 4 hours (% remaining); 2) area under the gastric emptying curve (AUC) at 1, 2, and 4 hours; and 3) total gastric emptying test (GET) (the sum of 1, 2, and 4 hour values). Patients were stratified into: delayed gastric emptying, normal gastric emptying, and rapid gastric emptying (Appendix). Of the 551 patients in the larger cohort, 379 had implantation of temporary gastric electrical stimulation (tGES). Gastrointestinal symptoms and gastric emptying were com -pared pre and post tGES implantation. RESULTS: After tGES, 2 hour gastric retention decreased (P < 0.01) for the delayed patients, and increased (P < 0.001) for normal and rapid patients. These changes were accompanied by improvements (P < 0.001) in vomiting, nausea, and total symptom scores in all 3 subgroups. CONCLUSIONS: Gastric electrical stimulation may be an effective therapy for treating the symptoms of gastroparesis with normal gastric emptying. Further exploration of endoscopic electrical stimulation as a treatment for gastroparesis-like symptoms with non-delayed gastric emptying is needed.
Abdominal Pain ; Cohort Studies ; Electric Stimulation ; Endoscopy ; Gastric Emptying ; Gastroparesis ; Humans ; Nausea ; Radionuclide Imaging ; Vomiting

Purpose: This study was performed to evaluate the association between mechanical bowel preparation (MBP) and perioperative outcomes following nephrectomy in the minimally invasive surgery (MIS) era. Methods: All partial and radical nephrectomies between 2019 and 2021 from the National Surgical Quality Improvement Program database were evaluated. Thirty-day perioperative outcomes were compared between groups where MBP was performed vs. not, in both the MIS and open surgery (OS) cohorts. A propensity score matching technique was utilized within MIS cases to control for covariates. The chi-square and t tests were used to determine significance. Results: A total of 11,869 cases met the inclusion criteria and were included in the analysis.Of these, 8,204 (69.1%; comprising 65.3% robotic and 34.7% laparoscopic) underwent MIS, while 3,655 (30.9%) underwent OS. The rate of MBP was higher in the MIS group (16.0% vs.10.0%, p < 0.001). Within the MIS group, MBP was associated with reduced rates of postoperative ileus (0.9% vs. 1.9%, p = 0.02), while other complications were comparable.Propensity score matching showed no association between MBP and postoperative ileus.However, a lower rate of 30-day readmission in the MBP group became statistically significant (4.4% vs. 6.4%, p = 0.01). Conversely, patients in the MBP group also demonstrated higher rates of pneumonia (1.29% vs. 0.46%, p = 0.002) and pulmonary embolism (0.6% vs. 0%, p < 0.001) after matching. Conclusion MBP practice prior to nephrectomy is infrequent in both OS and MIS cases, with minor differences in perioperative outcomes for patients undergoing MIS. Routine MBP should continue to be excluded from the standard of care for nephrectomy in the MIS era.

Purpose: This study was performed to evaluate the association between mechanical bowel preparation (MBP) and perioperative outcomes following nephrectomy in the minimally invasive surgery (MIS) era. Methods: All partial and radical nephrectomies between 2019 and 2021 from the National Surgical Quality Improvement Program database were evaluated. Thirty-day perioperative outcomes were compared between groups where MBP was performed vs. not, in both the MIS and open surgery (OS) cohorts. A propensity score matching technique was utilized within MIS cases to control for covariates. The chi-square and t tests were used to determine significance. Results: A total of 11,869 cases met the inclusion criteria and were included in the analysis.Of these, 8,204 (69.1%; comprising 65.3% robotic and 34.7% laparoscopic) underwent MIS, while 3,655 (30.9%) underwent OS. The rate of MBP was higher in the MIS group (16.0% vs.10.0%, p < 0.001). Within the MIS group, MBP was associated with reduced rates of postoperative ileus (0.9% vs. 1.9%, p = 0.02), while other complications were comparable.Propensity score matching showed no association between MBP and postoperative ileus.However, a lower rate of 30-day readmission in the MBP group became statistically significant (4.4% vs. 6.4%, p = 0.01). Conversely, patients in the MBP group also demonstrated higher rates of pneumonia (1.29% vs. 0.46%, p = 0.002) and pulmonary embolism (0.6% vs. 0%, p < 0.001) after matching. Conclusion MBP practice prior to nephrectomy is infrequent in both OS and MIS cases, with minor differences in perioperative outcomes for patients undergoing MIS. Routine MBP should continue to be excluded from the standard of care for nephrectomy in the MIS era.

Purpose: This study was performed to evaluate the association between mechanical bowel preparation (MBP) and perioperative outcomes following nephrectomy in the minimally invasive surgery (MIS) era. Methods: All partial and radical nephrectomies between 2019 and 2021 from the National Surgical Quality Improvement Program database were evaluated. Thirty-day perioperative outcomes were compared between groups where MBP was performed vs. not, in both the MIS and open surgery (OS) cohorts. A propensity score matching technique was utilized within MIS cases to control for covariates. The chi-square and t tests were used to determine significance. Results: A total of 11,869 cases met the inclusion criteria and were included in the analysis.Of these, 8,204 (69.1%; comprising 65.3% robotic and 34.7% laparoscopic) underwent MIS, while 3,655 (30.9%) underwent OS. The rate of MBP was higher in the MIS group (16.0% vs.10.0%, p < 0.001). Within the MIS group, MBP was associated with reduced rates of postoperative ileus (0.9% vs. 1.9%, p = 0.02), while other complications were comparable.Propensity score matching showed no association between MBP and postoperative ileus.However, a lower rate of 30-day readmission in the MBP group became statistically significant (4.4% vs. 6.4%, p = 0.01). Conversely, patients in the MBP group also demonstrated higher rates of pneumonia (1.29% vs. 0.46%, p = 0.002) and pulmonary embolism (0.6% vs. 0%, p < 0.001) after matching. Conclusion MBP practice prior to nephrectomy is infrequent in both OS and MIS cases, with minor differences in perioperative outcomes for patients undergoing MIS. Routine MBP should continue to be excluded from the standard of care for nephrectomy in the MIS era.