Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.

Dysfunction in sodium channels and their ankyrin scaffolding partners have both been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). In particular, the genes SCN2A, which encodes the sodium channel NaV1.2, and ANK2, which encodes ankyrin-B, have strong ASD association. Recent studies indicate that ASD-associated haploinsufficiency in Scn2a impairs dendritic excitability and synaptic function in neocortical pyramidal cells, but how NaV1.2 is anchored within dendritic regions is unknown. Here, we show that ankyrin-B is essential for scaffolding NaV1.2 to the dendritic membrane of mouse neocortical neurons and that haploinsufficiency of Ank2 phenocopies intrinsic dendritic excitability and synaptic deficits observed in Scn2a+/- conditions. These results establish a direct, convergent link between two major ASD risk genes and reinforce an emerging framework suggesting that neocortical pyramidal cell dendritic dysfunction can contribute to neurodevelopmental disorder pathophysiology.

Development of a Single-Neurosphere Culture to Assess Radiation Toxicity and Pre-Clinical Cancer Combination Therapy Safety.

Radiation therapy (RT) is a crucial treatment modality for central nervous system (CNS) tumors but toxicity to healthy CNS tissues remains a challenge. Additionally, environmental exposure to radiation during nuclear catastrophes or space travel presents a risk of CNS toxicity. However, the underlying mechanisms of radiation-induced CNS toxicity are not fully understood. Neural progenitor cells (NPCs) are highly radiosensitive, resulting in decreased neurogenesis in the hippocampus. This study aimed to characterize a novel platform utilizing rat NPCs cultured as 3D neurospheres (NSps) to screen the safety and efficacy of experimental drugs with and without radiation exposure. The effect of radiation on NSp growth and differentiation was assessed by measuring sphere volume and the expression of neuronal differentiation markers Nestin and GFAP and proliferation marker Ki67. Radiation exposure inhibited NSp growth, decreased proliferation, and increased GFAP expression, indicating astrocytic differentiation. RNA sequencing analysis supported these findings, showing upregulation of Notch, BMP2/4, S100b, and GFAP gene expression during astrogenesis. By recapitulating radiation-induced toxicity and astrocytic differentiation, this single-NSp culture system provides a high-throughput preclinical model for assessing the effects of various radiation modalities and evaluates the safety and efficacy of potential therapeutic interventions in combination with radiation.

Effect of initial anesthetic technique on fetal cord blood gas pH for cesarean deliveries performed for the indication of fetal heart rate abnormalities.

Background: We hypothesized that parturients who had general anesthesia as the initial anesthetic technique for cesarean deliveries performed for fetal heart rate abnormalities would have a lower fetal cord blood gas pH compared to parturients who had regional anesthesia as the initial anesthetic technique. Methods: We searched our electronic medical record for patients who had cesarean deliveries for the indication of fetal heart rate abnormalities from July 1, 2019, to June 30, 2021, at our hospital. An obstetrics resident and a maternal fetal medicine physician determined if the fetal heart tracing was category 2 or 3. Results: A total of 130 and 29 patients with category 2 and 3 fetal heart tracing had regional and general anesthesia as the initial anesthetic technique, respectively. Fourteen and 20 patients with a category 3 fetal heart tracing had regional and general anesthesia as the initial anesthetic techniques, respectively. There were no differences in fetal cord blood gas pH between patients who had regional or general anesthesia as the first attempted anesthetic technique when patients with category 2 and 3 tracings were evaluated separately. Conclusion: The initial anesthetic technique attempted for cesarean delivery was not associated with a worse fetal cord blood gas pH.

Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer.

Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.

Using an Educational Intervention to Map our Surgical Teams' Function, Emotional Intelligence, Communication and Conflict Styles.

OBJECTIVE: The leadership team invited surgical team members to participate in educational sessions that created self and other awareness as well as gathered baseline information about these topics: communication, conflict management, emotional intelligence, and teamwork. DESIGN: Each educational session included an inventory that was completed to help participants understand their own characteristics and the characteristics of their team members. The results from these inventories were aggregated, relationships were identified, and the intervention was evaluated. SETTING: A level 1 trauma center, Baylor Scott and White Health, in central Texas; a 636-bed tertiary care main hospital and an affiliated children's hospital. PARTICIPANTS: An open invitation for all surgical team members yielded 551 interprofessional OR team members including anesthesia, attending physicians, nursing, physician assistants, residents, and administration. RESULTS: Surgeons' communication styles were individual focused, while other team members were group focused. The most common conflict management mode for surgical team members on average was avoiding, and the least common was collaborating. Surgeons primarily used competing mode for conflict management, with avoiding coming in a close second. Finally, the 5 dysfunctions of a team inventory revealed low accountability scores, meaning the participants struggled with holding team members accountable. CONCLUSIONS: Helping team members understand their own and others' strengths and blind spots will help create opportunity for more purposeful and clear communication. Additionally, this knowledge should improve efficiency and safety in the high-stakes environment of the operating room.

Impact of Age, Body Mass Index, and Resection Weight on Postoperative Complications in Reduction Mammaplasty.

BACKGROUND: The authors seek to evaluate the impact of age, body mass index (BMI), and resection weight, on postoperative complications in women undergoing primary bilateral reduction mammaplasty. METHODS: A retrospective review of all primary bilateral reduction mammaplasties between February of 2014 and August of 2018 was performed. Patient demographics, medical comorbidities, tobacco use, BMI, operative technique, operative time, resection weight, and complications were reviewed. RESULTS: Two hundred seventy-seven women were included. Mean age was 35.71 years, and BMI was 30.17 kg/m 2 . An inferior pedicle (53.07%) with Wise pattern resection (53.43%) was used most commonly. The minor complication rate was 49.1%, with superficial wounds (42.1%) occurring most commonly. Thirty-three women (11.9%) required greater than 2 months to heal. The major complication rate was 4.31%. BMI was not associated with minor or major complications on univariate analysis ( P = 0.1003 and P = 0.6163), but was associated with wound healing requiring greater than 2 months ( P = 0.0009), longer operative times ( P = 0.0002), and higher resection weights ( P < 0.00001). Greater age was associated with higher minor complication rates ( P = 0.0048). On multivariate analysis, BMI was associated with wound healing requiring greater than 2 months ( P = 0.0137), and age with minor complications ( P = 0.0180). No factors impacted major complication rates. CONCLUSIONS: Women with higher BMI are more likely to require larger resections, longer operative times, and are at higher risk for wound healing requiring greater than 2 months. Although BMI is an important consideration for determining operative candidacy, the benefits of reduction may outweigh these risks in carefully selected patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Knowledge, Attitudes and Perceptions of Dental Hygiene and Dental Therapy Students towards End-stage Renal Disease: A pilot study.

Purpose Chronic kidney disease is highly prevalent in the general population and can progress to end-stage renal disease (ESRD). The purpose of this pilot study was to assess dental hygiene and dental therapy students' knowledge, attitudes, and perceptions towards ESRD and evaluate the feasibility of a larger scale study.Methods A convenience sample (n=59) of dental hygiene (DH) and dual degree DH/dental therapy students were invited to participate in an electronic survey for the pilot study. The investigator designed survey consisted of a total of 37 items: demographics (4), perceived knowledge, confidence, importance and attitudes (14), knowledge of chronic kidney disease (18). The knowledge questions were adapted from the Chronic Kidney Disease Self-Management Knowledge Tool (CKD-SMKT) with permission. Descriptive statistics and the non-parametric two-sample Wilcoxon rank sum test were used to analyze the data.Results Twenty-five participants completed the survey for a 42% response rate. Fewer than half (36%) perceived having some knowledge regarding ESRD, its oral manifestations (28%) and mental health implications (12%). The importance of managing oral health for ESRD was rated by most respondents as "very important" or "extremely important" (76%). Respondent attitudes indicated high interest (68%) regarding employment in hospital settings to care for individuals with ESRD.Knowledge scores from the CKD-SMKT were low in the categories of general knowledge of ESRD and dental hygiene care modifications for individuals with ESRD.Conclusion Results of this pilot study indicate that using a validated instrument on a national sample is feasible to determine the knowledge, attitudes and perceptions of dental hygiene students regarding ESRD. Future research should include knowledge and awareness of hypertension, diabetes, and the role that management of chronic kidney disease plays in the prevention of ESRD.

Neoadjuvant versus definitive chemoradiation in locally advanced esophageal cancer for patients of advanced age or significant comorbidities.

The addition of surgery to chemoradiation for esophageal cancer has not shown a survival benefit in randomized trials. Patients with more comorbidities or advanced age are more likely to be given definitive chemoradiation due to surgical risk. We aimed to identify subsets of patients in whom the addition of surgery to chemoradiation does not provide an overall survival (OS) benefit. The National Cancer Database was queried for patients with locally advanced esophageal cancer who received either definitive chemoradiation or neoadjuvant chemoradiation followed by surgery. Bivariate analysis was used to assess the association between patient characteristics and treatment groups. Log-rank tests and Cox proportional hazards models were performed to assess for differences in survival. A total of 15,090 with adenocarcinoma and 5,356 with squamous cell carcinoma met the inclusion criteria. Patients treated with neoadjuvant chemoradiation and surgery had significantly improved survival by Cox proportional hazards model regardless of histology if <50, 50-60, 61-70, or 71-80 years old. There was no significant benefit or detriment in patients 81-90 years old. Survival advantage was also significant with a Charlson/Deyo comorbidity condition score of 0, 1, 2, and ≥3 in adenocarcinoma squamous cell carcinoma with scores of 2 or ≥3 had no significant benefit or detriment. Patients 81-90 years old or with squamous cell carcinoma and a Charlson/Deyo comorbidity score ≥ 2 lacked an OS benefit from neoadjuvant chemoradiation followed by surgery compared with definitive chemoradiation. Careful consideration of esophagectomy-specific surgical risks should be used when recommending treatment for these patients.

Geographic location or experience: Using PRISM to understand how people seek flood risk information.

Flooding is increasing worldwide, and with climate change, people need help understanding these changing conditions and that their flood risk may also change. This study extends the planned risk information seeking model (PRISM) into the flood risk domain and examines the antecedents that explain flood risk information seeking behavior. Using a survey reflective of the population in the state of Texas (N = 1079), this study includes an operationalization of risk perception specific to the complexity of floods and explores two key moderators in the PRISM model. Findings suggest that using PRISM to elaborate flood risk information seeking behaviors explains 48% of the variance in information seeking intent and 37% of the variance in affective risk perception. Using multigroup modeling, the findings also reveal that simply living in an area at high risk for floods does not significantly impact any relationships in the model. However, having experience with flooding increases the strength of risk perception paths-in particular, perceived probability of flood risk-and better explains flood risk information seeking. Suggestions for how to use communication to influence risk perceptions and information seeking, as well as future directions for research, are also discussed.

Multi-center matched cohort study of convalescent plasma for hospitalized patients with COVID-19.

BACKGROUND: Although frequently used in the early pandemic, data on the effectiveness of COVID-19 convalescent plasma (CCP) remain mixed. We investigated the effectiveness and safety of CCP in hospitalized COVID-19 patients in real-world practices during the first two waves of the pandemic in a multi-hospital healthcare system in Texas. METHODS AND FINDINGS: Among 11,322 hospitalized patients with confirmed COVID-19 infection from July 1, 2020 to April 15, 2021, we included patients who received CCP and matched them with those who did not receive CCP within ±2 days of the transfusion date across sites within strata of sex, age groups, days and use of dexamethasone from hospital admission to the match date, and oxygen requirements 4-12 hours prior to the match date. Cox proportional hazards model estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for effectiveness outcomes in a propensity score 1:1 matched cohort. Pre-defined safety outcomes were described. We included 1,245 patients each in the CCP treated and untreated groups. Oxygen support was required by 93% of patients at the baseline. The pre-defined primary effectiveness outcome of 28-day in-hospital all-cause mortality (HR = 0.85; 95%CI: 0.66,1.10) were similar between treatment groups. Sensitivity and stratified analyses found similar null results. CCP-treated patients were less likely to be discharged alive (HR = 0.82; 95%CI: 0.74, 0.91), and more likely to receive mechanical ventilation (HR = 1.48; 95%CI: 1.12, 1.96). Safety outcomes were rare and similar between treatment groups. CONCLUSION: The findings in this large, matched cohort of patients hospitalized with COVID-19 and mostly requiring oxygen support at the time of treatment, do not support a clinical benefit in 28-day in-hospital all-cause mortality for CCP. Future studies should assess the potential benefits with specifically high-titer units in perhaps certain subgroups of patients (e.g. those with early disease or immunocompromised).

Cardiology co-management of rheumatoid arthritis patients with coronary artery disease as an intervention reduces hospitalization rates and adverse event occurrence.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic autoimmune disease with important cardiovascular (CV) implications. CV disease represents over half of RA patient deaths and causes significant morbidity. CV manifestations in RA can be complex, raising concerns for adequate patient management and provider-dependent roles. METHODS: This is a retrospective study of patients diagnosed with RA and coronary artery disease (CAD). Patients were identified and filtered via EPIC Database search engine. Parameters were set from January 1, 2014, to December 31, 2020. Inclusion criteria consisted of patients who met diagnostic criteria for both RA and CAD. A total of 399 patients met criteria. RESULTS: Of the 399 identified patients, 272 were female (68.2%) and 127 were male (31.8%) with a median age of 73 (range 26-98). The population was further divided into two groups: those with established cardiology care versus those without. Patients without cardiology follow-up experienced significantly more hospitalizations (RR 1.63 95% CI 1.12, 2.38), higher rates of adverse events including myocardial infarction (MI) (RR 4.82 95% CI 1.94, 11.98), heart failure (HF) (OR 15.81 95% CI 3.54, 70.52), and stroke (RR 2.55 95% CI 1.29, 5.03). Patients not followed by cardiology also had numerical increases in CV death (4 deaths compared to none in those with cardiology follow) and all-cause mortality (HR 1.03 95% CI 0.63, 1.67). CONCLUSION: Patients with regular cardiology follow-up demonstrated fewer cardiac-related adverse events. This suggests that co-management may have a role in adverse cardiac event risk reduction and should therefore be an early consideration. Key Points • Rheumatoid arthritis patients demonstrate higher rates of coronary disease compared to the general population. Traditional cardiac risk factors may not be entirely responsible for this phenomenon • Hospitalization rates and adverse event occurrence are significantly higher in patients with single-provider care (rheumatology only) compared to dual provider care (rheumatology and cardiology) • Cardiology co-management should be an early consideration in the management of RA patients • Early screening, risk stratification of coronary disease, and utilization of appropriate treatment algorithms are important to decrease morbidity and mortality.

The cost of elective nodal coverage in prostate cancer: Late quality of life outcomes and dosimetric analysis with 0, 45 or 54 Gy to the pelvis.

Purpose: Elective pelvic lymph node radiotherapy (PLNRT) in prostate cancer is often omitted from definitive (n = 267) and post prostatectomy (n = 160) radiotherapy (RT) due to concerns regarding toxicity and efficacy. Data comparing patient-reported outcome measures (PROMs) with or without PLNRT is limited. Our long-term supposition is that PLNRT, particularly to higher doses afforded by IMRT, will decrease pelvic failure rate in select patients. We aim to establish the impact of two different PLNRT doses on long term quality of life (QOL). Methods and materials: Prostate cancer patients (n = 428) recorded baseline scores using the Expanded Prostate Cancer Index Composite (EPIC), prior to definitive or post-prostatectomy RT. PLNRT, if given, was prescribed to 45 or 54 Gy at 1.8 Gy per fraction. New EPIC scores were recorded 20-36 months after radiotherapy. Absolute change in each domain subscale and summary score was recorded, along with if these changes met minimally important difference (MID) criteria. A separate multivariate analysis (MVA) was performed for each measure. Subsequent dosimetric analysis was performed. Results: Frequency of a MID decline was significantly greater with PLNRT to 54 Gy for urinary function, incontinence, and overall. No urinary decline was correlated with PLNRT to 45 Gy. PLNRT to 54 Gy was significant for decline in urinary function, bother, irritative, incontinence, and overall score in one or both MVA models while 45 Gy was not. Postoperative status was significant for decline in urinary function, incontinence, and overall. Amongst postoperative patients, there was significantly greater decline in urinary function score in the salvage setting. Neither 54 nor 45 Gy significantly affected bowel subscale or overall score decline. Conclusions: Using conventional fractionation, adding PLNRT to 54 Gy, but not 45 Gy, correlates with worse urinary QOL, with postoperative patients experiencing a steeper decline. PLNRT had no significant impact on bowel QOL with either dose.

Premature Neural Progenitor Cell Differentiation Into Astrocytes in Retinoic Acid-Induced Spina Bifida Rat Model.

During embryonic spinal cord development, neural progenitor cells (NPCs) generate three major cell lines: neurons, oligodendrocytes, and astrocytes at precise times and locations within the spinal cord. Recent studies demonstrate early astrogenesis in animal models of spina bifida, which may play a role in neuronal dysfunction associated with this condition. However, to date, the pathophysiological mechanisms related to this early astrocytic response in spina bifida are poorly understood. This study aimed to characterize the development of early astrogliosis over time from Pax6+, Olig2+, or Nkx2.2+ NPCs using a retinoic acid-induced spina bifida rat model. At three gestational ages (E15, E17, and E20), spinal cords from fetuses with retinoic acid-induced spina bifida, their healthy sibling controls, or fetuses treated with the vehicle control were analyzed. Results indicated that premature astrogliosis and astrocytic activation were associated with an altered presence of Pax6+, Olig2+, and Nkx2.2+ NPCs in the lesion compared to the controls. Finally, this response correlated with an elevation in genes involved in the Notch-BMP signaling pathway. Taken together, changes in NPC patterning factor expression with Notch-BMP signaling upregulation may be responsible for the altered astrogenesis patterns observed in the spinal cord in a retinoic acid-induced spina bifida model.

Impact of Patient and Operative Factors on Nipple-Areola Complex Sensation after Bilateral Reduction Mammaplasty.

Background: Alteration of nipple-areola complex (NAC) sensation following reduction mammoplasty is commonly reported and may impact patient satisfaction. The goal of this study was to evaluate the patient and procedural factors that influence the rates of subjective NAC sensation change. Methods: A retrospective review of all patients who underwent primary bilateral reduction mammoplasty between January 2014 and August 2018 at the senior author's institution was performed. The primary outcome measured was subjective NAC sensation via digital stimulation of the NAC with the patient reporting sensation as decreased, unchanged, or increased. Results: In total, 274 patients met inclusion criteria. NAC sensation was decreased in 19% of breasts, unchanged in 74%, and increased in 7.3%. Patients who underwent vertical pattern, superomedial pedicle reductions were more likely to report a decrease in sensation than those who underwent Wise pattern, inferior pedicle reductions (26% versus 13%; P = 0.0025). Patients with minor complications were more likely to report decreased NAC sensation than those who did not (23% versus 15%; P = 0.0264). The only factor found to be associated with increased sensation was operative time. Conclusions: Patients were more likely to report decreased sensation if a vertical skin resection, superomedial pedicle was chosen, or if patients experienced a minor complication. The only factor found to correlate with increased NAC sensation was longer operative times.

Dural substitutes for spina bifida repair: past, present, and future.

PURPOSE: The use of materials to facilitate dural closure during spina bifida (SB) repair has been a highly studied aspect of the surgical procedure. The overall objective of this review is to present key findings pertaining to the success of the materials used in clinical and pre-clinical studies. Additionally, this review aims to aid fetal surgeons as they prepare for open or fetoscopic prenatal SB repairs. METHODS: Relevant publications centered on dural substitutes used during SB repair were identified. Important information from each article was extracted including year of publication, material class and sub-class, animal model used in pre-clinical studies, whether the repair was conducted pre-or postnatally, the bioactive agent delivered, and key findings from the study. RESULTS: Out of 1,121 publications, 71 were selected for full review. We identified the investigation of 33 different patches where 20 and 63 publications studied synthetic and natural materials, respectively. From this library, 43.6% focused on clinical results, 36.6% focused on pre-clinical results, and 19.8% focused on tissue engineering approaches. Overall, the use of patches, irrespective of material, have shown to successfully protect the spinal cord and most have shown promising survival and neurological outcomes. CONCLUSION: While most have shown significant promise as a therapeutic strategy in both clinical and pre-clinical studies, none of the patches developed so far are deemed perfect for SB repair. Therefore, there is an opportunity to develop new materials and strategies that aim to overcome these challenges and further improve the outcomes of SB patients.

C-Reactive Protein Is a Poor Marker of Baseline Inflammation in Prostate Cancer and Response to Radiotherapy or Androgen Ablation.

Introduction C-reactive protein (CRP) is an acute-phase reactant used as a general marker for inflammation. Isolated levels have been associated with prostate cancer development, prostate-specific antigen (PSA), Gleason score, and treatment response. We seek to establish whether CRP levels reflect inflammation caused by prostate cancer by comparing levels at various points of time before, during, and after therapy. Materials and methods A total of 209 patients had a complete blood count (CBC), PSA, and CRP taken at up to four different time points. Labs were performed up to one week prior to androgen ablation via leuprolide injection (pre-AA), up to one week prior to radiotherapy (RT) (pre-RT), within one week of RT completion (post-RT), and three months following RT completion (FU [follow-up]). Results Significant relationships were found between CRP and WBC pre-AA (p-value=0.0050), pre-RT (p-value=0.0170), and post-RT (p-value=0.0113), but not at FU (p=.096). CRP had no significant relationship with PSA or lymphocytes at any time points. PSA was significantly affected by androgen ablation but lymphocytes, WBCs, and CRP were not. No CRP levels were associated with risk groups or FU-PSA. Lymphatic radiation fields significantly decreased WBCs and lymphocytes but not CRP. PSA, WBC, and lymphocytes all significantly decreased from pre-RT to post-RT, followed by a significant recovery. CRP did not significantly change during any of these periods and was not significantly related to changes in PSA, WBCs, or lymphocytes. Conclusion CRP is not a sensitive marker of the acute inflammatory effects of non-metastatic prostate cancer and treatment response with androgen ablation or radiation therapy.

Time Course Transcriptome Analysis of Spina Bifida Progression in Fetal Rats.

A better understanding of the transcriptomic modifications that occur in spina bifida may lead to identify mechanisms involved in the progression of spina bifida in utero and the development of new therapeutic strategies that aid in spinal cord regeneration after surgical interventions. In this study, RNA-sequencing was used to identify differentially expressed genes in fetal spinal cords from rats with retinoic acid-induced spina bifida at E15, E17, and E20. Gene ontology, KEGG, and protein-protein interaction analysis were conducted to predict pathways involved in the evolution of the disease. Approximately 3000, 1000 and 300 genes were differentially expressed compared to the control groups at E15, E17 and E20, respectively. Overall, the results suggest common alterations in certain pathways between gestational time points, such as upregulation in p53 and sonic hedgehog signaling at E15 and E17 and downregulation in the myelin sheath at E17 and E20. However, there were other modifications specific to gestational time points, including skeletal muscle development at E15, downregulated glucose metabolism at E17, and upregulated inflammation at E20. In conclusion, this work provides evidence that gestational age during spina bifida repair may be a significant variable to consider during the development of new regenerative therapeutics approaches.

Bone Density Changes Following Radiotherapy to Vertebral Metastases.

Introduction Patients have increasing longevity and time for bone healing following radiotherapy (RT) for treatment of bone metastases (BM). Attempts to assess the treatment response of bone metastases have been either limited or heavily subjective. Our goal was to try to quantitate cancer-involved bone changes after RT using changes in bone mineral density (BMD) from computer tomographic (CT) imaging. Methods Retrospectively, 117 spinal metastases were identified that received RT with follow-up CT scans >9 months following CT simulation. Contoured volumes included: the metastasis (gross tumor volume; GTV); the involved vertebra (gross bone volume; GBV); a total lytic volume (Lyt); a dominant lytic volume (Domlyt); a control volume, and the nearest uninvolved, unirradiated vertebra (control bone volume; CBV). The Hounsfield-density calibration curve was used to measure the density of these volumes before and after treatment. Results Whether using raw or control-adjusted changes, the absolute and percent change in density of the GBV, GTV, Lyt, and Domlyt volumes all significantly increased (each p<0.0001). The increase in the density of Domlyt volumes was greater than that of Lyt volumes (p=0.0465), which were greater than GTV (p=0.0065), which were greater than GBV (p<0.0001). On multivariate analysis, only the biologically effective dose (BED) dose significantly correlated with GTV density change (p=0.0175). K means clustering created groups by initial lesion size, GTV, or GBV density. A significant difference in GTV density change was not detected between any groups. Conclusion Increases in BMD are associated with healing regardless of lesion size or initial density. A prospective study to determine whether long-term control is related to early density measurements is needed.