Diversity trends in traumatic brain injury clinical trials in the United States.

BACKGROUND: This study aims to understand the demographic representation of patients in Traumatic Brain Injury (TBI) clinical trials by evaluating the proportions of patients from various demographic categories amongst completed TBI clinical trials in the United States. METHODS: ClinicalTrials.gov was queried for active TBI clinical trials. One hundred and eight completed trials in the United States were selected based on inclusion criteria, and information regarding intervention, setting, age, sex, race, and ethnicity was extracted. 2002-2006 TBI incidence data was obtained from the CDC. Chi-squared testing was applied to analyze the relationship between distributions of race and sex in the collected clinical trials and the national TBI data, and logistic regression was conducted to identify variables that may predict reporting of race or ethnicity. RESULTS: About 53.7% of selected clinical trials reported racial data and 34.3% reported ethnicity data. Logistic regression identified that clinical trials in defined phases were more likely to report racial data (p = 0.047 [1.015, 9.603]). CONCLUSION: Current TBI trials do not consistently report race or ethnicity data. Future efforts to ensure equitable representation in clinical trials may involve reform of recruitment processes and accountability measures implemented within the grant application process to ensure proper racial and ethnicity data reporting.

Highest Achievable Outcomes for Adult Spinal Deformity Corrective Surgery: Does Frailty Severity Exert a Ceiling Effect?

STUDY DESIGN: Retrospective Single-Center Study. OBJECTIVE: To assess the influence of frailty on optimal outcome following ASD corrective surgery. SUMMARY OF BACKGROUND DATA: Frailty is a determining factor in outcomes after ASD surgery and may exert a ceiling effect on best possible outcome. METHODS: ASD patients with frailty measures, baseline and 2-year ODI included. Frailty was classified as Not Frail (NF), Frail (F) and Severely Frail (SF) based on the modified Frailty Index, then stratified into quartiles based on 2-year ODI improvement (most improved designated "Highest"). Logistic regression analyzed relationships between frailty and ODI score and improvement, maintenance, or deterioration. A Kaplan-Meier survival curve was used to analyze differences in time to complication or reoperation. RESULTS: 393 ASD patients were isolated (55.2% NF, 31.0% F, and 13.7% SF), then classified as 12.5% NF-Highest, 17.8% F-Highest, and 3.1% SF-Highest. The SF-group had the highest rate of deterioration (16.7%, P=0.025) at the second postoperative year but the groups were similar in improvement (NF: 10.1%, F: 11.5%, SF: 9.3%, P=0.886). Improvement of SF patients was greatest at 6 months (ΔODI of -22.6±18.0, P<0.001) but NF and F patients reached maximal ODI at 2 years (ΔODI of -15.7±17.9 and -20.5±18.4, respectively). SF patients initially showed the greatest improvement in ODI (NF: -4.8±19.0, F: -12.4±19.3, SF: -22.6±18.0 at 6 months, P<0.001). A Kaplan-Meier survival curve showed a trend of less time to major complication or reoperation by 2 years with increasing frailty (NF: 7.5±0.381 years, F: 6.7±0.511 years, SF: 5.8±0.757 years; P=0.113). CONCLUSIONS: Increasing frailty had a negative effect on maximal improvement, where severely frail patients exhibited a parabolic effect with greater initial improvement due to higher baseline disability, but reached a ceiling effect with less overall maximal improvement. Severe frailty may exert a ceiling effect on improvement and impair maintenance of improvement following surgery. LEVEL OF EVIDENCE: III.

The Impact of Peri-operative Enhanced Recovery After Surgery Protocols on Outcomes Following Adult Cervical Deformity Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To assess the impact of Enhanced recovery after surgery (ERAS) protocols on peri-operative course in adult cervical deformity (ACD) corrective surgery. METHODS: Patients ≥18 yrs with complete pre-(BL) and up to 2-year (2Y) radiographic and clinical outcome data were stratified by enrollment in an ERAS protocol that commenced in 2020. Differences in demographics, clinical outcomes, radiographic alignment targets, peri-operative factors and complication rates were assessed via means comparison analysis. Logistic regression analysed differences while controlling for baseline disability and deformity. RESULTS: We included 220 patients (average age 58.1 ± 11.9 years, 48% female). 20% were treated using the ERAS protocol (ERAS+). Disability was similar between both groups at baseline. When controlling for baseline disability and myelopathy, ERAS- patients were more likely to utilize opioids than ERAS+ (OR 1.79, 95% CI: 1.45-2.50, P = .016). Peri-operatively, ERAS+ had significantly lower operative time (P < .021), lower EBL (583.48 vs 246.51, P < .001), and required significantly lower doses of propofol intra-operatively than ERAS- patients (P = .020). ERAS+ patients also reported lower mean LOS overall (4.33 vs 5.84, P = .393), and were more likely to be discharged directly to home (χ2(1) = 4.974, P = .028). ERAS+ patients were less likely to require steroids after surgery (P = .045), were less likely to develop neuromuscular complications overall (P = .025), and less likely experience venous complications or be diagnosed with venous disease post-operatively (P = .025). CONCLUSIONS: Enhanced recovery after surgery programs in ACD surgery demonstrate significant benefit in terms of peri-operative outcomes for patients.

Impact of congestive heart failure on patients undergoing lumbar spine fusion for adult spine deformity.

Background: With the increasing amount of elective spine fusion patients presenting with cardiac disease and congestive heart failure, it is becoming difficult to assess when it is safe to proceed with surgery. Assessing the severity of heart failure (HF) through ejection fraction may provide insight into patients' short- and long-term risks. Purpose: The purpose of this study was to assess the severity of HF on perioperative outcomes of spine fusion surgery patients. Study Design/Setting: This was a retrospective cohort study of the PearlDiver database. Patient Sample: We enrolled 670,526 patients undergoing spine fusion surgery. Outcome Measures: Thirty-day and 90-day complication rates, discharge destination, length of stay (LOS), physician reimbursement, and hospital costs. Methods: Patients undergoing elective spine fusion surgery were isolated and stratified by preoperative HF with preserved ejection fraction (P-EF) or reduced ejection fraction (R-EF) (International Classification of Diseases-9: 428.32 [chronic diastolic HF] and 428.22 [chronic systolic HF]). Means comparison tests (Chi-squared and independent samples t-tests, as appropriate) compared differences in demographics, diagnoses, comorbidities, procedural characteristics, LOS, 30-day and 90-day complication outcomes, and total hospital charges between those diagnosed with P-EF and those not R-EF. Binary logistic regression assessed the odds of complication associated with HF, controlling for levels fused (odds ratio [OR] [95% confidence interval]). Statistical significance was set at P < 0.05. Results: Totally 670,526 elective spine fusion patients were included. Four thousand and seventy-seven were diagnosed with P-EF and 2758 R-EF. Overall, P-EF patients presented with higher rates of morbid obesity, chronic kidney disease, chronic obstructive pulmonary disease, diabetes mellitus, and hypertension (all P < 0.001). In relation to No-HF, P-EF patients had higher rates of 30-day major complications including pulmonary embolism, pneumonia, cerebrovascular accident (CVA), myocardial infarctions (MI), sepsis, and death (all P < 0.001). Furthermore, P-EF was associated significantly with increased odds of pneumonia (OR: 2.07 [1.64-2.56], P < 0.001) and sepsis (OR: 2.09 [1.62-2.66], P < 0.001). Relative to No-HF, R-EF was associated with significantly higher odds of MI (OR: 3.66 [2.34-5.47]), CVA (OR: 2.70 [1.67-4.15]), and pneumonia (OR: 1.85 [1.40-2.40]) (all P < 0.001) postoperative within 30 days. Adjusting for prior history of MI, CAD, and the presence of a pacemaker R-EF was a significant predictor of an MI 30 days postoperatively (OR: 2.2 [1.14-4.32], P = 0.021). Further adjusting for history of CABG or stent placement, R-EF was associated with higher odds of CVA (OR: 2.11 [1.09-4.19], P = 0.028) and MI (OR: 2.27 [1.20-4.43], P = 0.013). Conclusions: When evaluating the severity of HF before spine surgery, R-EF was associated with a higher risk of major complications, especially the occurrence of a myocardial infarction 30 days postoperatively. During preoperative risk assessment, congestive HF should be considered thoroughly when thinking of postoperative outcomes with emphasis on R-EF.

Comparing the bone regeneration potential between a trabecular bone and a porous scaffold through osteoblast migration and differentiation: A multiscale approach.

Both cell migration and osteogenic differentiation are critical for successful bone regeneration. Therefore, understanding the mechanobiological aspects that govern these two processes is essential in designing effective scaffolds that promote faster bone regeneration. Studying these two factors at different locations is necessary to manage bone regeneration in various sections of a scaffold. Hence, a multiscale computational model was used to observe the mechanical responses of osteoblasts placed in different positions of the trabecular bone and gyroid scaffold. Fluid shear stresses in scaffolds at cell seeded locations (representing osteogenic differentiation) and strain energy densities in cells at cell substrate interface (representing cell migration) were observed as mechanical response parameters in this study. Comparison of these responses, as two critical factors for bone regeneration, between the trabecular bone and gyroid scaffold at different locations, is the overall goal of the study. This study reveals that the gyroid scaffold exhibits higher osteogenic differentiation and cell migration potential compared to the trabecular bone. However, the responses in the gyroid only mimic the trabecular bone in two out of nine positions. These findings can guide us in predicting the ideal cell seeded sites within a scaffold for better bone regeneration and in replicating a replaced bone condition by altering the physical parameters of a scaffold.

The Evolution of Enhanced Recovery After Surgery: Assessing the Clinical Benefits of Developments Within Enhanced Recovery After Surgery Protocols in Adult Cervical Deformity Surgery.

STUDY DESIGN: Retrospective cohort. OBJECTIVE: To investigate the impact of evolving Enhanced Recovery After Surgery (ERAS) protocols on outcomes after cervical deformity (CD) surgery. BACKGROUND: ERAS can help accelerate patient recovery and assist hospitals in maximizing the incentives of bundled payment models while maintaining high-quality patient care. However, there remains a paucity of literature assessing how developments have impacted outcomes after adult CD surgery. METHODS: Patients with operative CD 18 years or older with pre-baseline and 2 years (2Y) postoperative data, who underwent ERAS protocols, were stratified by increasing implantation of ERAS components: (1) early (multimodal pain program), (2) intermediate (early protocol + paraspinal blocks, early ambulation), and (3) late (early/intermediate protocols + comprehensive prehabilitation). Differences in demographics, clinical outcomes, radiographic alignment targets, perioperative factors, and complication rates were assessed through Bonferroni-adjusted means comparison analysis. RESULTS: A total of 131 patients were included (59.4 ± 11.7 y, 45% females, 28.8 ± 6.0 kg/m 2 ). Of these patients, 38.9% were considered "early," 36.6% were "intermediate," and 24.4% were "late." Perioperatively, rates of intraoperative complications were lower in the late group ( P = 0.036). Postoperatively, discharge disposition differed significantly between cohorts, with late patients more likely to be discharged to home versus early or intermediate cohorts [χ 2 (2) = 37.973, P < 0.001]. In terms of postoperative disability recovery, intermediate and late patients demonstrated incrementally improved 6 W modified Japanese Orthopedic Association scores ( P = 0.004), and late patients maintained significantly higher mean Euro-QOL 5-Dimension Questionnaire and modified Japanese Orthopedic Association scores by 1 year ( P < 0.001, P = 0.026). By 2Y, cohorts demonstrated incrementally increasing SWAL-QOL scores (all domains P < 0.028) domain scores versus early or intermediate cohorts. By 2Y, incrementally decreasing reoperation was observed in early versus intermediate versus late cohorts ( P = 0.034). CONCLUSIONS: The present study demonstrates that patients enrolled in an evolving ERAS program demonstrate incremental improvement in preoperative optimization and candidate selection, greater likelihood of discharge to home, decreased postoperative disability and dysphasia burden, and decreased likelihood of intraoperative complications and reoperation rates.

Assessing the Economic Benefits of Enhanced Recovery After Surgery (ERAS) Protocols in Adult Cervical Deformity Patients: Is the Initial Additive Cost of Protocols Offset by Clinical Gains?

OBJECTIVE: To assess the financial impact of Enhanced Recovery After Surgery (ERAS) protocols and cost-effectiveness in cervical deformity corrective surgery. STUDY DESIGN: Retrospective review of prospective CD database. BACKGROUND: Enhanced Recovery After Surgery (ERAS) can help accelerate patient recovery and assist hospitals in maximizing the incentives of bundled payment models while maintaining high-quality patient care. However, the economic benefit of ERAS protocols, nor the heterogeneous components that make up such protocols, has not been established. METHODS: Operative CD patients ≥18 y with complete pre-(BL) and up to 2-year(2Y) postop radiographic/HRQL data were stratified by enrollment in Standard-of-Care ERAS beginning in 2020. Differences in demographics, clinical outcomes, radiographic alignment targets, perioperative factors, and complication rates were assessed through means comparison analysis. Costs were calculated using PearlDiver database estimates from Medicare pay scales. QALY was calculated using NDI mapped to SF6D using validated methodology with a 3% discount rate to account for a residual decline in life expectancy. RESULTS: In all, 127 patients were included (59.07±11.16 y, 54% female, 29.08±6.43 kg/m 2 ) in the analysis. Of these patients, 54 (20.0%) received the ERAS protocol. Per cost analysis, ERAS+ patients reported a lower mean total 2Y cost of 35049 USD compared with ERAS- patients at 37553 ( P <0.001). Furthermore, ERAS+ patients demonstrated lower cost of reoperation by 2Y ( P <0.001). Controlling for age, surgical invasiveness, and deformity per BL TS-CL, ERAS+ patients below 70 years old were significantly more likely to achieve a cost-effective outcome by 2Y compared with their ERAS- counterparts (OR: 1.011 [1.001-1.999, P =0.048]. CONCLUSIONS: Patients undergoing ERAS protocols experience improved cost-effectiveness and reduced total cost by 2Y post-operatively. Due to the potential economic benefit of ERAS for patients incorporation of ERAS into practice for eligible patients should be considered.

Perceptions, Experiences, and Patterns of Cannabis Use in Individuals with Mood and Anxiety Disorders in the Context of Cannabis Legalization and Medical Cannabis Program in Canada - A Qualitative Study.

INTRODUCTION: Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders. METHODS: Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU. The thematic analysis focused on phases of CU and sources of cannabis products and information. RESULTS: Reported motivations for initiation of CU included curiosity, peer pressure, and dissatisfaction with conventional treatments. Factors such as psychotropic effects and coping with mental health symptoms and insomnia contributed to the continuation of CU. More negative effects, including cognitive dysfunction, worsening of mood, and anxiety symptoms, were acknowledged with ongoing CU. Concerning findings included common initiation of CU before age 18, combined medical and recreational CU, rare consultation of medical professionals on CU, and potential effects and harms. DISCUSSION: Findings indicate individual complexity of motivations, perceptions, and patterns of CU in the study population. The reported potential beneficial effects of specific cannabis products should be further investigated. Findings emphasize patient-provider dialogue on both CU and conventional treatments. Information from this study can contribute to and inform the development of education, prevention, and intervention strategies.

Assessing the effects of prehabilitation protocols on post-operative outcomes in adult cervical deformity surgery: does early optimization lead to optimal clinical outcomes?

PURPOSE: To investigate the effect of a prehabilitation program on peri- and post-operative outcomes in adult cervical deformity (CD) surgery. METHODS: Operative CD patients ≥ 18 years with complete baseline (BL) and 2-year (2Y) data were stratified by enrollment in a prehabilitation program beginning in 2019. Patients were stratified as having undergone prehabilitation (Prehab+) or not (Prehab-). Differences in pre and post-op factors were assessed via means comparison analysis. Costs were calculated using PearlDiver database estimates from Medicare pay-scales. RESULTS: 115 patients were included (age: 61 years, 70% female, BMI: 28 kg/m2). Of these patients, 57 (49%) were classified as Prehab+. At baseline, groups were comparable in age, gender, BMI, CCI, and frailty. Surgically, Prehab+ were able to undergo longer procedures (p = 0.017) with equivalent EBL (p = 0.627), and shorter SICU stay (p < 0.001). Post-operatively, Prehab+ patients reported greater reduction in pain scores and greater improvement in quality of life metrics at both 1Y and 2Y than Prehab- patients (all p < 0.05). Prehab+ patients reported significantly less complications overall, as well as less need for reoperation (all p < 0.05). CONCLUSION: Introducing prehabilitation protocols in adult cervical deformity surgery may aid in improving patient physiological status, enabling patients to undergo longer surgeries with lessened risk of peri- and post-operative complications.

Patterns for Child Protective Service Referrals in a Pediatric Burn Cohort.

BACKGROUND: Pediatric non-accidental trauma often necessitates the involvement of protective services. However, the subjectivity and lack of standardization of referral infrastructure may result in some discrepancies between referral patterns and instances of child abuse. METHODS: An institutional retrospective chart review was conducted between 2015 and 2021, in which all cases of patients under the age of 14 who suffered a burn injury and received a child protective service (CPS) consult were reviewed. Baseline demographics and characteristics were defined. Multivariate analysis was utilized to identify predictors of CPS involvement, while the regression analysis was employed to parse associations between burn injuries and CPS involvement. RESULTS: Between July 2015 and December 2021, 340 patients (median age two years, IQR: 1-6 years) under the age of 14 who experienced a burn injury were evaluated. Forty-four (12.9%) of the patients' cases received a CPS referral, of which three (0.9%) resulted in a CPS intervention. The most common mechanism of burn within the cohort was scald (241 patients, 70.9%). The median total body surface area (TBSA) was 3.0% (IQR: 1.0%-6.0%), and 76 (22.4%) suffered a high TBSA (>75th percentile). Caucasian race (p < 0.001) and scald mechanisms (p = 0.014) were associated with higher TBSA. When considering how such injuries translated to CPS referrals, increasing age was found to be associated with a decreased likelihood of CPS involvement. Meanwhile, the Black race (p = 0.027) and increasing area deprivation index (ADI) (p = 0.038) were associated with CPS involvement. Those with CPS involvement experienced a greater length of hospital stay (p = 0.001). Black race and intensive care unit level of care were found to be positive predictors of CPS involvement. In total, three (6.82%) of the 44 cases with CPS involvement were found to be substantiated. The three children who required CPS intervention were discharged to foster care settings. CONCLUSION: Hospitalized pediatric burn injuries must be investigated due to concern of child abuse, yet external factors such as race and socioeconomic status may play a role in the involvement of CPS. Such referrals may not always be substantiated and could lead to further injurious sequelae for children and their families.

Antioxidant and Trilayered Electrospun Small-Diameter Vascular Grafts Maintain Patency and Promote Endothelialisation in Rat Femoral Artery.

Vascular grafts with a small diameter encounter inadequate patency as a result of intimal hyperplasia development. In the current study, trilayered electrospun small-diameter vascular grafts (PU-PGACL + GA) were fabricated using a poly(glycolic acid) and poly(caprolactone) blend as the middle layer and antioxidant polyurethane with gallic acid as the innermost and outermost layers. The scaffolds exhibited good biocompatibility and mechanical properties, as evidenced by their 6 MPa elastic modulus, 4 N suture retention strength, and 2500 mmHg burst pressure. Additionally, these electrospun grafts attenuated cellular oxidative stress and demonstrated minimal hemolysis (less than 1%). As a proof-of-concept, the preclinical evaluation of the grafts was carried out in the femoral artery of rodents, where the conduits demonstrated satisfactory patency. After 35 days of implantation, ultrasound imaging depicted adequate blood flow through the grafts, and the computed vessel diameter and histological staining showed no significant stenosis issue. Immunohistochemical analysis confirmed matrix deposition (38% collagen I and 16% elastin) and cell infiltration (42% for endothelial cells and 55% for smooth muscle cells) in the explanted grafts. Therefore, PU-PGACL + GA showed characteristics of a clinically relevant small-diameter vascular graft, facilitating re-endothelialization while preserving the anticoagulant properties of the synthetic blood vessels.

Tuning light-driven oxidation of styrene inside water-soluble nanocages.

Selective functionalization of innate sp2 C-H bonds under ambient conditions is a grand synthetic challenge in organic chemistry. Here we combine host-guest charge transfer-based photoredox chemistry with supramolecular nano-confinement to achieve selective carbonylation of styrene by tuning the dioxygen concentration. We observe exclusive photocatalytic formation of benzaldehyde under excess O2 (>1 atm) while Markovnikov addition of water produced acetophenone in deoxygenated condition upon photoexcitation of confined styrene molecules inside a water-soluble cationic nanocage. Further by careful tuning of the nanocage size, electronics, and guest preorganization, we demonstrate rate enhancement of benzaldehyde formation and a complete switchover to the anti-Markovnikov product, 2-phenylethan-1-ol, in the absence of O2. Raman spectroscopy, 2D 1H-1H NMR correlation experiments, and transient absorption spectroscopy establish that the site-selective control on the confined photoredox chemistry originates from an optimal preorganization of styrene molecules inside the cavity. We envision that the demonstrated host-guest charge transfer photoredox paradigm in combination with green atom-transfer reagents will enable a broad range of sp2 carbon-site functionalization.

Targeting 'histone mark': Advanced approaches in epigenetic regulation of telomere dynamics in cancer.

Telomere integrity is required for the maintenance of genome stability and prevention of oncogenic transformation of cells. Recent evidence suggests the presence of epigenetic modifications as an important regulator of mammalian telomeres. Telomeric and subtelomeric regions are rich in epigenetic marks that regulate telomere length majorly through DNA methylation and post-translational histone modifications. Specific histone modifying enzymes play an integral role in establishing telomeric histone codes necessary for the maintenance of structural integrity. Alterations of crucial histone moieties and histone modifiers cause deregulations in the telomeric chromatin leading to carcinogenic manifestations. This review delves into the significance of histone modifications and their influence on telomere dynamics concerning cancer. Additionally, it highlights the existing research gaps that hold the potential to drive the development of therapeutic interventions targeting the telomere epigenome.

Point-of-care impedimetric aptasensor to detect the luteinizing hormone.

Luteinizing hormone (LH) is a useful biomarker for identifying ovulation events in the cows to predict the time of ovulation to achieve a high success rate of conception following artificial insemination. Although antibody-based radioimmunoassay and enzyme-linked immunosorbent assay are being used for LH measurement, these techniques are expensive, time-consuming, and require expertise and sophisticated laboratory facilities. So, there is a need for a field-applicable, affordable, easy-to-use method for LH detection. For developing such a specific, quantitative, and inexpensive system, an aptamer-based smartphone-enabled aptasensor has been investigated. The aptamer was used instead of the antibody as a biorecognition element due to its comparative stability at ambient temperature, ease of synthesis, and cost-effectiveness. Electrochemical impedance spectroscopy has been used to obtain label-free detection of LH within 20 min in ~ 20 µL sample volume. The screen-printed gold electrode is compatible with a smartphone-enabled miniaturized device (Sensit Smart; Palmsens BV, The Netherlands) and was fabricated with the aptamer to detect LH in biological fluids (limit of detection 0.80 and 0.61 ng/mL in buffer and undiluted/unprocessed serum, respectively, with the dynamic range of detection of 0.01 to 50 ng/mL). All the data were obtained in the 10 kHz to 0.10 Hz frequency range at a bias potential of 0.30 V with an alternating potential of 10 mV. The clinical relevance of the sensor was evaluated in 10 serum samples collected from dairy animals which established a high correlation with standard LH-ELISA (κ > 0.87). The aptasensor can be stored at room temperature for 30 days without any significant loss in electrochemical sensing ability.

Targeting the 'DNA methylation mark': Analysis of early epigenetic-alterations in children chronically exposed to arsenic.

Chronic exposure to arsenic causes adverse health effects in children. Aberrant epigenetic modifications including altered DNA methylation pattern are one of the major steps towards malignant transformation of cells. Our group has previously identified significant alteration in DNA methylation mark in arsenic exposed adults, affecting major biological pathways. Till date, no information is available exploring the altered DNA methylation mark in telomere regulation and altered mitochondrial functionality in association with DNA damage in arsenic-exposed children. Our study aims in identifying signature epigenetic pattern associated with telomere lengthening, mitochondrial functionality and DNA damage repair in children with special emphasis on DNA methylation. Biological samples (blood and urine) and drinking water were collected from the children aged between 5 and 16 years of arsenic exposed areas (N = 52) of Murshidabad district and unexposed areas (N = 50) of East Midnapur districts, West Bengal, India. Methylation-specific PCR was performed to analyse subtelomeric methylation status and promoter methylation status of target genes. Results revealed altered DNA methylation profile in the exposed children compared to unexposed. Promoter hypermethylation was observed in MLH1 and MSH2 (p < 0.05 and p < 0.001) indicating inefficiency in DNA damage repair. Hypomethylation in mitochondrial D-loop (p < 0.05) and TFAM promoter region (p < 0.05) along with increased mitochondrial DNA copy number among exposed children was also observed. Significant increase in telomere length and region specific subtelomeric hypermethylation (XpYp, p < 0.05) was found. Analysis of S-Adenosyl Methionine (SAM) and 8-oxoDG level revealed significant depletion of SAM (p < 0.001) and elevated oxidative DNA damage (p < 0.001) respectively in arsenic toxicity. Our study identified key methylation patterns in arsenic-exposed children which may act as an early predictive biomarker in the near future. Further in-depth studies involving large sample size and transcriptomic analysis are required for understanding the mechanistic details.

Outcomes and survival analysis of adult cervical deformity patients with 10-year follow-up.

BACKGROUND: Previous studies have demonstrated that adult cervical deformity patients may be at increased risk of death in conjunction with increased frailty or a weakened physiologic state. However, such studies have often been limited by follow-up duration, and longer-term studies are needed to better assess temporal changes in ACD patients and associated mortality risk. PURPOSE: To assess if patients with decreased comorbidities and physiologic burden will be at lessened risk of death for a greater length of time after undergoing adult cervical deformity surgery. STUDY DESIGN/SETTING: Retrospective review. PATIENT SAMPLE: Two hundred ninety ACD patients. OUTCOME MEASURES: Morbidity and mortality data. METHODS: Operative ACD patients ≥18 years with pre-(BL) and 10-year (10Y) data were included. Patients were stratified as expired versus living, as well as temporally grouped by Expiration prior to 5Y or between 5Y and 10Y. Group differences were assessed via means comparison analysis. Backstep logistic regression identified mortality predictors. Kaplan-Meier analysis assessed survivorship of expired patients. Log rank analysis determined differences in survival distribution groups. RESULTS: Sixty-six total patients were included (60.97±10.19 years, 48% female, 28.03±7.28 kg/m2). Within 10Y, 12 (18.2% of ACD cohort) expired. At baseline, patients were comparable in age, gender, BMI, and CCI total on average (all p>.05). Furthermore, patients were comparable in BL HRQLs (all p>.05). However, patients who expired between 5Y and 10Y demonstrated higher BL EQ5D and mJOA scores than their earlier expired counterparts at 2Y (p<.021). Furthermore, patients who presented with no CCI markers at BL were significantly more likely to survive until the 5Y-10Y follow-up window. Surgically, the only differences observed between patients who survived until 5Y was in undergoing osteotomy, with longer survival seen in those who did not require it (p=.003). Logistic regression revealed independent predictors of death prior to 5Y to be increased BMI, increased frailty, and increased levels fused (model p<.001). KM analysis found that by Passias et al frailty, not frail patients had mean survival time of 170.56 weeks, versus 158.00 in frail patients (p=.949). CONCLUSIONS: Our study demonstrates that long-term survival after cervical deformity surgery may be predicted by baseline surgical factors. By optimizing BMI, frailty status, and minimizing fusion length when appropriate, surgeons may be able to further assist ACD patients in increasing their survivability postoperatively.

Chirality-induced Lineage Enforcement of Mechanosensitive Mesenchymal Stem Cells Across Germ Layer Boundaries.

Mesenchymal to epithelial transition (MET) is instrumental in embryogenesis, tissue repair, and wound healing while the epithelial to mesenchymal transition (EMT) plays role in carcinogenesis. Alteration in microenvironment can modulate cellular signaling and induce EMT and MET. However, modulation of microenvironment to induce MET has been relatively less explored. In this work, effect of matrix stiffness in mediating MET in umbilical cord-derived mesenchymal stem cells (UCMSC) is investigated. Differential segregation of cell fate determinant proteins is one of the key factors in mediating altered stem cell fates through MET even though the genesis of apicobasal polarity remains ambiguous. Herein, it is also attempted to decipher if microenvironment-induced asymmetric cell division has a role to play in driving the cells toward MET. UCMSC cultured on stiffer PDMS matrices resulted in significantly (p < 0.05) higher expression of mechanotransduction proteins. It was also observed that stiffer matrices mediated significant (p < 0.05) upregulation of the polarity proteins and cell fate determinant protein, and epithelial marker proteins over lesser stiff substrates. On the contrary, expression of inflammatory and mesenchymal markers was reduced significantly (p < 0.05) on the stiffer matrices. Cell cycle analysis showed a significant increase in the G1 phase among the cells seeded on stiffer matrices. Transcriptomic studies validated higher expression of epithelial markers genes and lower expression of EMT markers. The transition from mesenchymal to epithelial phenotype depending on the gradation in matrix stiffness is successfully demonstrated. A computational machine learning model was developed to validate stiffness-MET correlation with 94% accuracy. The cross-boundary trans-lineage differentiation capability of MSC on bioengineered substrates can be used as a potential tool in tissue regeneration, organogenesis, and wound healing applications. In our present study, we deciphered the correlation between YAP/TAZ mechanotransduction pathway, EMT signaling pathway, and asymmetric cell division in mediating MET in MSC in a substrate stiffness-dependent manner. It is inferred that the stiffer PDMS matrices facilitate the transition from mesenchymal to epithelial state of MSC. Further, our study also proposed a scoring system to sort MSC from an intermediate hybrid E/M population while undergoing graded MET on matrices of different stiffnesses using a machine learning technique. This proposed scoring system can provide information regarding the E/M state of MSC on different bioengineered constructs based on their biophysical properties which may help in the proper choice of biomaterials in complex tissue-engineering applications.

Ameliorating impaired cardiac function in myocardial infarction using exosome-loaded gallic-acid-containing polyurethane scaffolds.

Myocardial infarction (MI) can be tackled by implanting cardiac patches which provide mechanical support to the heart. However, most tissue-engineered scaffolds face difficulty in attenuating oxidative stress, maintaining mechanical stability, and regenerating damaged cardiomyocytes. Here, we fabricated elastic cryogels using polyurethane modified with antioxidant gallic acid in its backbone (PUGA) and further coated them with decellularized extracellular matrix (dECM) to improve adhesiveness, biocompatibility and hemocompatibility. The scaffold was functionalized with exosomes (EXO) isolated from adipose-derived stem cells having regenerative potential. PUGA-dECM + EXO was tested in a rat model with induced MI where echocardiography after 8 weeks of implantation showed significant recovery in treatment group. Histological analysis revealed a decrease in fibrosis after application of patch and promotion of angiogenesis with reduced oxidative stress was shown by immunostaining. Expression of cardiac tissue contractile function marker was also observed in treatment groups. Thus, the proposed biomaterial has a promising application to be utilized as a patch for cardiac regeneration. More detailed studies with larger animal species are needed for using these observations for specific applications.

Risk of spinal surgery among individuals who have been re-vascularized for coronary artery disease.

HYPOTHESIS: Revascularization is a more effective intervention to reduce future postop complications. METHODS: Patients undergoing elective spine fusion surgery were isolated in the PearlDiver database. Patients were stratified by having previous history of vascular stenting (Stent), coronary artery bypass graft (CABG), and no previous heart procedure (No-HP). Means comparison tests (chi-squared and independent samples t-tests, as appropriate) compared differences in demographics, diagnoses, and comorbidities. Binary logistic regression assessed the odds of 30-day and 90-day postoperative (postop) complications associated with each heart procedure (Odds Ratio [95 % confidence interval]). Statistical significance was set p < 0.05. RESULTS: 731,173 elective spine fusion patients included. Overall, 8,401 pts underwent a CABG, 24,037 pts Stent, and 698,735 had No-HP prior to spine fusion surgery. Compared to Stent and No-HP patients, CABG patients had higher rates of morbid obesity, chronic kidney disease, and diabetes (p < 0.001 for all). Meanwhile, stent patients had higher rates of PVD, hypertension, and hyperlipidemia (all p < 0.001). 30-days post-op, CABG patients had significantly higher complication rates including pneumonia, CVA, MI, sepsis, and death compared to No-HP (all p < 0.001). Stent patients vs. No-HF had higher 30-day post-op complication rates including pneumonia, CVA, MI, sepsis, and death. Furthermore, adjusting for age, comorbidities, and sex Stent was significantly predictive of a MI 30-days post-op (OR: 1.90 [1.53-2.34], P < 0.001). Additionally, controlling for levels fused, stent patients compared to CABG patients had 1.99x greater odds of a MI within 30-days (OR: 1.99 [1.26-3.31], p = 0.005) and 2.02x odds within 90-days postop (OR: 2.2 [1.53-2.71, p < 0.001). CONCLUSION: With regards to spine surgery, coronary artery bypass graft remains the gold standard for risk reduction. Stenting does not appear to minimize risk of experiencing a post-procedure cardiac event as dramatically as CABG.

The Circular Rebound Tool: A tool to move companies towards more sustainable circular business models.

Companies design circular business models through experimentation. However, most companies do not consider the environmental impact of their new business model ideas during experimentation, an iterative phase of high uncertainty. Previous research shows that companies typically use 'rules of thumb' to estimate environmental impact in this stage due to limited time and reliable information to guide decision-making. This might prevent innovators from detecting unintended rebound effects that offset positive environmental gains of new business models. To mitigate this and let innovators think more profoundly about rebound effects during the circular business model experimentation phase, we propose an evidence-based business model ideation tool, the Circular Rebound Tool, designed around lifecycle thinking, the zero-waste hierarchy, and increased rebound effects awareness. The tool's development follows the design science research method, undergoing continuous improvement through 15 workshops. Our tool can help business innovators gain insights into the environmental impact of their early-stage business ideas.