Advancing thalamic neuromodulation in epilepsy: Bridging adult data to pediatric care.

Thalamic neuromodulation has emerged as a treatment option for drug-resistant epilepsy (DRE) with widespread and/or undefined epileptogenic networks. While deep brain stimulation (DBS) and responsive neurostimulation (RNS) depth electrodes offer means for electrical stimulation of the thalamus in adult patients with DRE, the application of thalamic neuromodulation in pediatric epilepsy remains limited. To address this gap, the Neuromodulation Expert Collaborative was established within the Pediatric Epilepsy Research Consortium (PERC) Epilepsy Surgery Special Interest Group. In this expert review, existing evidence and recommendations for thalamic neuromodulation modalities using DBS and RNS are summarized, with a focus on the anterior (ANT), centromedian(CMN), and pulvinar nuclei of the thalamus. To-date, only DBS of the ANT is FDA approved for treatment of DRE in adult patients based on the results of the pivotal SANTE (Stimulation of the Anterior Nucleus of Thalamus for Epilepsy) study. Evidence for other thalamic neurmodulation indications and targets is less abundant. Despite the lack of evidence, positive responses to thalamic stimulation in adults with DRE have led to its off-label use in pediatric patients. Although caution is warranted due to differences between pediatric and adult epilepsy, the efficacy and safety of pediatric neuromodulation appear comparable to that in adults. Indeed, CMN stimulation is increasingly accepted for generalized and diffuse onset epilepsies, with recent completion of one randomized trial. There is also growing interest in using pulvinar stimulation for temporal plus and posterior quadrant epilepsies with one ongoing clinical trial in Europe. The future of thalamic neuromodulation holds promise for revolutionizing the treatment landscape of childhood epilepsy. Ongoing research, technological advancements, and collaborative efforts are poised to refine and improve thalamic neuromodulation strategies, ultimately enhancing the quality of life for children with DRE.

Response of human peripheral blood monocyte-derived macrophages (PBMM) to demineralized and decellularized bovine bone graft substitutes.

The performance of apparently biocompatible implanted bovine bone grafts may be compromised by unresolved chronic inflammation, and poor graft incorporation leading to implant failure. Monitoring the intensity and duration of the inflammatory response caused by implanted bone grafts is crucial. In this study, the ability of demineralized (DMB) and decellularized (DCC) bovine bone substitutes in initiating inflammatory responses to peripheral blood monocyte-derived macrophages (PBMMs) was investigated. The response of PBMMs to bone substitutes was evaluated by using both direct and indirect cell culture, reactive oxygen species (ROS) generation, apoptosis, immunophenotyping, and cytokine production. Analysis of DMB and DCC substitutes using scanning electron microscope (SEM) showed a roughened surface with a size ranging between 500 and 750 µm. PBMMs treated with DMB demonstrated cell aggregation and clumping mimicking lipopolysaccharide (LPS) treated PBMMs and a higher proliferation ability (166.93%) compared to control (100%) and DCC treatments (115.64%; p<0.001) at 24h. This was associated with a significantly increased production of intracellular ROS in PBMMs exposed to DMB substitutes than control (3158.5 vs 1715.5; p<0.001) and DCC treatment (2117.5). The bone substitute exposure also caused an increase in percentage apoptosis which was significantly (p<0.0001) higher in both DMB (27.85) and DCC (29.2) treatment than control (19.383). A significant increase in proinflammatory cytokine expression (TNF-α: 3.4 folds; p<0.05) was observed in DMB substitute-treated PBMMs compared to control. Notably, IL-1ß mRNA was significantly higher in DMB (21.75 folds; p<0.0001) than control and DCC (5.01 folds). In contrast, DCC substitutes exhibited immunoregulatory effects on PBMMs, as indicated by the expression for CD86, CD206, and HLDR surface markers mimicking IL-4 treatments. In conclusion, DMB excites a higher immunological response compared to DCC suggesting decellularization process of tissues dampen down inflammatory reactions when exposed to PBMM.

Dipper throated optimization with deep convolutional neural network-based crop classification for remote sensing image analysis.

Problem: With the rapid advancement of remote sensing technology is that the need for efficient and accurate crop classification methods has become increasingly important. This is due to the ever-growing demand for food security and environmental monitoring. Traditional crop classification methods have limitations in terms of accuracy and scalability, especially when dealing with large datasets of high-resolution remote sensing images. This study aims to develop a novel crop classification technique, named Dipper Throated Optimization with Deep Convolutional Neural Networks based Crop Classification (DTODCNN-CC) for analyzing remote sensing images. The objective is to achieve high classification accuracy for various food crops. Methods: The proposed DTODCNN-CC approach consists of the following key components. Deep convolutional neural network (DCNN) a GoogleNet architecture is employed to extract robust feature vectors from the remote sensing images. The Dipper throated optimization (DTO) optimizer is used for hyper parameter tuning of the GoogleNet model to achieve optimal feature extraction performance. Extreme Learning Machine (ELM): This machine learning algorithm is utilized for the classification of different food crops based on the extracted features. The modified sine cosine algorithm (MSCA) optimization technique is used to fine-tune the parameters of ELM for improved classification accuracy. Results: Extensive experimental analyses are conducted to evaluate the performance of the proposed DTODCNN-CC approach. The results demonstrate that DTODCNN-CC can achieve significantly higher crop classification accuracy compared to other state-of-the-art deep learning methods. Conclusion: The proposed DTODCNN-CC technique provides a promising solution for efficient and accurate crop classification using remote sensing images. This approach has the potential to be a valuable tool for various applications in agriculture, food security, and environmental monitoring.

Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension.

Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.

Correction: Evaluation of the osteogenic potential of demineralized and decellularized bovine bone granules following implantation in rat calvaria critical-size defect model.

[This corrects the article DOI: 10.1371/journal.pone.0294291.].

Economic Burden of Inpatient Care for Mitral Regurgitation in Maryland.

BACKGROUND: Mitral regurgitation (MR) is the most common valvular disease in the United States and increases the risk of death and hospitalization. The economic burden of MR in the United States is not known. METHODS AND RESULTS: We analyzed inpatient hospitalization data from the 1 221 173 Maryland residents who had any in-state admissions from October 1, 2015, to September 30, 2019. We assessed the total charges for patients without MR and for patients with MR who underwent medical management, transcatheter mitral valve repair or replacement, or surgical mitral valve repair or replacement. During the study period, 26 076 inpatients had a diagnosis of MR. Compared with patients without MR, these patients had more comorbidities and higher inpatient mortality. Patients with medically managed MR incurred average total charges of $23 575 per year; MR was associated with $10 559 more in charges per year and an incremental 3.1 more inpatient days per year as compared with patients without MR. Both surgical mitral valve repair or replacement and transcatheter mitral valve repair or replacement were associated with higher charges as compared with medical management during the year of intervention ($47 943 for surgical mitral valve repair or replacement and $63 108 for transcatheter mitral valve repair or replacement). Annual charges for both groups were significantly lower as compared with medical management in the second and third years postintervention. CONCLUSIONS: MR is associated with higher mortality and inpatient charges. Patients who undergo surgical or transcatheter intervention incur lower charges compared with medically managed MR patients in the years after the procedure.

A multi-center comparison of surgical techniques for corpus Callosotomy in pediatric drug-resistant epilepsy.

OBJECTIVES: Corpus callosotomy (CC) is used to reduce seizures, primarily in patients with generalized drug-resistant epilepsy (DRE). The invasive nature of the procedure contributes to underutilization despite its potential superiority to other palliative procedures. The goal of this study was to use a multi-institutional epilepsy surgery database to characterize the use of CC across participating centers. METHODS: Data were acquired from the Pediatric Epilepsy Research Consortium (PERC) Surgery Database, a prospective observational study collecting data on children 0-18 years referred for surgical evaluation of DRE across 22 U.S. pediatric epilepsy centers. Patient, epilepsy, and surgical characteristics were collected across multiple CC modalities. Outcomes and complications were recorded and analyzed statistically. RESULTS: Eighty-three patients undergoing 85 CC procedures at 14 participating epilepsy centers met inclusion criteria. Mean age at seizure onset was 2.3 years (0-9.4); mean age for Phase I evaluation and surgical intervention were 9.45 (.1-20) and 10.46 (.2-20.6) years, respectively. Generalized seizure types were the most common (59%). Complete CC was performed in 88%. The majority of CC procedures (57%) were via open craniotomy, followed by laser interstitial thermal therapy (LiTT) (20%) and mini-craniotomy/endoscopic (mc/e) (22%). Mean operative times were significantly longer for LiTT, whereas mean estimated blood loss was greater in open cases. Complications occurred in 11 cases (13%) and differed significantly between surgical techniques (p < .001). There was no statistically significant difference in length of postoperative stay across approaches. Mean follow-up was 12.8 months (range 1-39). Favorable Engel outcomes were experienced by 37 (78.7%) of the patients who underwent craniotomy, 10 (58.8%) with LiTT, and 12 (63.2%) with mc/e; these differences were not statistically significant. SIGNIFICANCE: CC is an effective surgical modality for children with DRE. Regardless of surgical modality, complication rates are acceptable and seizure outcomes generally favorable. Newer, less-invasive, surgical approaches may lead to increased adoption of this efficacious therapeutic option for pediatric DRE.

Neurodevelopmental outcomes in a cohort of Australian families with self-limited familial epilepsy of neonatal/infantile onset.

OBJECTIVES: To determine: i) seizure recurrence; ii) developmental disability; iii) co-morbidities and risk factors in self-limited familial neonatal and/or infantile epilepsy (SeLFE) in a multigenerational study. METHODS: Families were retrospectively recruited from epilepsy databases (2021-2022) in 2 paediatric hospitals, Sydney, Australia. Eligible families had 2 first degree relatives with seizures and underwent genetic testing. Demographics/clinical data were collected from interviews and medical records. Vineland Adaptive Behaviour Scales-Third Edition measured adaptive function. RESULTS: Fifteen families participated. Fourteen had a genetic diagnosis (93%): 11 pathogenic; PRRT2 (n=4), KCNQ2 (n=3), SCN2A (n=4), 3 likely pathogenic; KCNQ2 (n=1), SCN8A (n=2). Seizures affected 73 individuals (ages 1-76 years); 30 children and 20 adults had in-depth phenotyping. Ten of 50 individuals (20%) had seizure recurrence, aged 8-65 years. Median time from last neonatal/infantile seizure was 11.8/12.8 years. Predictors of recurrence were high seizure number (p=0.05) and longer treatment duration (p=0.03). Seven children had global developmental delay (GDD): mild (n=4), moderate (n=1) and severe (n=2). Vineland-3 identified 3 had low-average and 3 had mild-moderately impaired functioning. The majority (82%) were average. GDD was associated with older age at last seizure (p=0.03), longer epilepsy duration (p=0.02), and higher number of anti-seizure medications (p=0.05). Four children had speech delay, 5 (10%) had Autism Spectrum Disorder. Paroxysmal kinesiogenic dyskinesia (n=5) occurred in 4 families and hemiplegic migraine (n=8) in 3 families. CONCLUSIONS: Individuals with SeLFE have a small risk of recurrent seizures (20%) and neurodevelopmental disability. Significant predictors are higher seizure number and longer epilepsy duration. Developmental surveillance is imperative.

Phytic acid effect on periodontal ligament fibroblast: An in-vitro study.

OBJECTIVES: This study evaluated phytic acid (IP6) effect on the viability, alkaline phosphatase (ALP) activity and calcium release of human periodontal ligament (HPDL) cells in optimal (OGL) and elevated glucose level (EGL) in cell culture media. MATERIALS AND METHODS: Cells were seeded in OGL (1000mg/L) or EGL (4500 mg/L) media. IP6 was added at 0.005%, 0.01% or 0.02% concentrations for 24 or 48h, and XTT assay was performed. Cell differentiation and calcium release in presence of 0.02% IP6 in OGL or EGL in non-osteogenic or osteogenic media were analyzed using ALP assay and alizarin red staining, respectively. RESULTS: In OGL, IP6 enhanced the viability of the cells at both exposure times (P<0.05). However, IP6 lowered the viability of the cells with the presence of EGL compared to the control at both exposure times, except for 0.02% IP6 which showed comparable viability to the control at 48 h. In OGL and EGL, ALP activity of the cells was not affected by the presence of IP6 in non-osteogenic media; however, in osteogenic media IP6 lowered the ALP activity. Meanwhile, calcium release was the highest with IP6 within osteogenic media of EGL. CONCLUSIONS: IP6 effects on the HPDL cells were dependent on IP6 concentration, time of exposure, glucose levels and the osteogenic condition of the media. CLINICAL RELEVANCE: This study gives insights on the potential therapeutic effect of IP6 as adjunctive periodontal therapy in patients with diabetes.

Evaluation of the osteogenic potential of demineralized and decellularized bovine bone granules following implantation in rat calvaria critical-size defect model.

The aim of this study was to compare the ability of demineralized (DMB) and decellularized (DCC) bovine bone granules to support bone regeneration in rat calvaria critical-size defects. DMB and DCC were prepared using a previously published method. The granule size used ranged between 500 and 750 µm. A total of forty-eight Sprague-Dawley rats were divided into two groups (n = 24). A pair of 5 mm diameter defects were created on the calvaria of the rats in the right and left parietal bone in both groups. Group A animals received DMB granules and Group B received DCC granules in the right parietal defect side while the left parietal untreated defect acted as sham surgery for both groups. Four animals per group were euthanized in a CO2 chamber at day 7, 14 and 21 post-surgery and the calvaria implantation site biopsy harvested was subjected to osteogenic gene expression analysis. Another four animals per group were euthanized at days 15, 30 and 60 post surgery and the calvaria implantation site biopsy harvested was subjected to histological, immunohistochemistry, RAMAN spectroscopy and Micro-CT analysis at the mentioned time points. Statistical analysis was conducted using t-tests and ANOVA. Histomorphometry showed significantly higher new bone formation in the DCC sites (p<0.05) compared to DMB. Both DMB and DCC implantation sites showed distinct staining for osteocalcin and osteopontin proteins compared to their respective sham sites. By day 21 after implantation, DCC sites demonstrated significantly elevated mRNA levels of osteonectin (p<0.001), osteopontin (p<0.001), osteocalcin (p<0.0001), ALP (p<0.01), and BMP-2 (p<0.001) compared to DMB. However, VEGF expression showed no significant differences at this time point between the two groups. Micro-CT analysis also showed enhanced defect closure and higher bone density in DCC implanted sites while RAMAN spectra demonstrated increased abundance of collagen and bone minerals, especially, PO43- ions than DMB. In conclusion, both DMB and DCC granules demonstrated favorable osteogenic potential in critical-sized defects, with DCC exhibited superior osteoconductive, osteoinductive and osteogenesis properties.

Distribution of U and 210PO in groundwater of Kodagu district, Karnataka, India.

Trace amounts of uranium along with its decay products are found in varying levels in natural soil, rocks, water and air. They are a matter of significant concern due to their carcinogenic nature. In the present work, the distribution of U and 210Po in groundwater of Kodagu District, Karnataka, India, was studied. The concentration of total U in groundwater samples was estimated using LASER and LED fluorimeter, and the activity of 210Po in groundwater was studied using electrochemical deposition followed by alpha counting method. The concentration of U and 210Po varied from 0.4 to 8.8 µgl-1 and 0.47 to 4.35 mBql-1, respectively. The ingestion dose due to U and 210Po in groundwater varied from 0.33 to 7.17 and 0.41 to 3.81 µSv y-1, respectively. The estimated U activity was found to be well below the standard safe limits of 30 µgl-1 in drinking water, as recommended by WHO and USEPA. The 210Po activity was low compared with the recommended 100 mBql-1 standard of WHO.

Hierarchical Development of Physical Frailty and Cognitive Impairment and Their Association With Incident Cardiovascular Disease.

BACKGROUND: Frailty and cognitive impairment (CI) are geriatric conditions that lead to poor health outcomes among older adults with cardiovascular disease. The association between their temporal patterns of development and cardiovascular risk is unknown. OBJECTIVES: This study aims to examine the 5-year cardiovascular outcomes by the pattern of development of frailty and CI in older adults without a history of coronary artery disease. METHODS: We used the National Health and Aging Trends Study, linked to Medicare data. Frailty was measured using the physical frailty phenotype. CI was measured using the AD8 Dementia Screening Interview, measured cognitive performance, or self-report by patient or caregiver for a diagnosis given by a physician. The primary outcome was incident major adverse cardiovascular event at 5 years. RESULTS: Of a total 2,189 study participants aged 65 and older, 38.5% were male. In this study population, 154 (7%) participants developed frailty first, 829 (38%) developed CI first, and 195 (9%) participants developed both simultaneously (frail-CI group). Those who developed frailty and CI simultaneously were older, more likely to be female, and had multiple chronic conditions. The frail-CI group had the highest risk of major adverse cardiovascular event (hazard ratio [HR]: 1.81; 95% CI: 1.47-2.23) followed by frail first (HR: 1.46; 95% CI: 1.17-1.81) and CI first (HR: 1.31; 95% CI: 1.15-1.50). Frailty first was associated with the greater risk of stroke (HR: 1.49; 95% CI: 1.06-2.09) compared to the intact group. CONCLUSIONS: The simultaneous development of frailty and CI is associated with an increased risk of adverse cardiovascular outcomes including death compared with the development of each syndrome alone. Diagnostics to detect frailty and CI are critical in assessment of cardiovascular risk in the older population.

Outcomes among patients undergoing transcatheter aortic valve replacement with very low baseline gradients.

Background: While there is evidence that patients with low-flow, low-gradient aortic stenosis (AS) benefit from transcatheter aortic valve replacement (TAVR), data are lacking regarding outcomes of patients with a very low gradient (VLG). Methods: In this retrospective, single-center study of patients with severe AS who underwent TAVR, three groups were defined using baseline mean aortic valve gradient: VLG (≤25 mmHg), low gradient (LG, 26-39 mmHg), and high gradient (HG, ≥40 mmHg). The primary outcome was the composite of Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 of <45, decrease in KCCQ-12 of ≥10 compared with baseline, or death at 1 year. Results: One-thousand six patients were included: 571 HG, 353 LG, and 82 VLG. The median age was 82.1 years [interquartile range (IQR) 76.3-86.9]; VLG patients had more baseline comorbidities compared with the other groups. The primary outcome was highest at 1 year in the VLG group (VLG, 46.7%; LG, 29.9%; HG, 23.1%; p = 0.002), with no difference between groups after adjustment for baseline characteristics. At baseline, <30% of VLG patients had an excellent or good (50-100) KCCQ-12, whereas more than 75% and 50% had an excellent or good KCCQ-12 at 30-day and 1-year follow-up, respectively. Conclusion: Although patients with VLG undergoing TAVR have a higher rate of poor outcomes at 1 year compared with patients with LG and HG severe AS, this difference is largely attributable to baseline comorbidities. Patients with severe AS undergoing TAVR have significant improvement in health status outcomes regardless of resting mean gradient.

Prediction of the superimposed laser shot number for copper using a deep convolutional neural network.

Image-based deep learning (IBDL) is an advanced technique for predicting the surface irradiation conditions of laser surface processing technology. In pulsed-laser surface processing techniques, the number of superimposed laser shots is one of the fundamental and essential parameters that should be optimized for each material. Our primary research aims to build an adequate dataset using laser-irradiated surface images and to successfully predict the number of superimposed shots using the pre-trained deep convolutional neural network (CNN) models. First, the laser shot experiments were performed on copper targets using a nanosecond YAG laser with a wavelength of 532 nm. Then, the training data were obtained with the different superimposed shots of 1 to 1024 in powers of 2. After that, we used several pre-trained deep CNN models to predict the number of superimposed laser shots. Based on the dataset with 1936 images, VGG16 shows a high validation accuracy, higher sensitivity, and more than 99% precision than other deep CNN models. Utilizing the VGG16 model with high sensitivity could positively impact the industries' time, efficiency, and overall production.

Is It Feasible to Reduce Academic Stress in Net-Zero Energy Buildings? Reaction from ChatGPT.

We may lessen the detrimental effects of global warming on human thought processes by reducing greenhouse gas emissions, encouraging sustainability, and giving adaption measures top priority. The purpose of the letter is to draw attention to the necessity of net-zero energy buildings (NZEB) in academic institutions in order to reduce academic stress, promote well-being, and improve cognitive functions. While some levels of stress might be advantageous, excessive and mismanaged stress can be detrimental to students' well-being. To foster a healthy academic atmosphere, it is essential to offer resources, support networks, and stress-reduction techniques. As human authors, we thoroughly edited ChatGPT's responses to create this letter.

Target-agnostic drug prediction integrated with medical record analysis uncovers differential associations of statins with increased survival in COVID-19 patients.

Drug repurposing requires distinguishing established drug class targets from novel molecule-specific mechanisms and rapidly derisking their therapeutic potential in a time-critical manner, particularly in a pandemic scenario. In response to the challenge to rapidly identify treatment options for COVID-19, several studies reported that statins, as a drug class, reduce mortality in these patients. However, it is unknown if different statins exhibit consistent function or may have varying therapeutic benefit. A Bayesian network tool was used to predict drugs that shift the host transcriptomic response to SARS-CoV-2 infection towards a healthy state. Drugs were predicted using 14 RNA-sequencing datasets from 72 autopsy tissues and 465 COVID-19 patient samples or from cultured human cells and organoids infected with SARS-CoV-2. Top drug predictions included statins, which were then assessed using electronic medical records containing over 4,000 COVID-19 patients on statins to determine mortality risk in patients prescribed specific statins versus untreated matched controls. The same drugs were tested in Vero E6 cells infected with SARS-CoV-2 and human endothelial cells infected with a related OC43 coronavirus. Simvastatin was among the most highly predicted compounds (14/14 datasets) and five other statins, including atorvastatin, were predicted to be active in > 50% of analyses. Analysis of the clinical database revealed that reduced mortality risk was only observed in COVID-19 patients prescribed a subset of statins, including simvastatin and atorvastatin. In vitro testing of SARS-CoV-2 infected cells revealed simvastatin to be a potent direct inhibitor whereas most other statins were less effective. Simvastatin also inhibited OC43 infection and reduced cytokine production in endothelial cells. Statins may differ in their ability to sustain the lives of COVID-19 patients despite having a shared drug target and lipid-modifying mechanism of action. These findings highlight the value of target-agnostic drug prediction coupled with patient databases to identify and clinically evaluate non-obvious mechanisms and derisk and accelerate drug repurposing opportunities.

Evaluation of decellularization process for developing osteogenic bovine cancellous bone scaffolds in-vitro.

Current immunological issues in bone grafting regarding the transfer of xenogeneic donor bone cells into the recipient are challenging the industry to produce safer acellular natural matrices for bone regeneration. The aim of this study was to investigate the efficacy of a novel decellularization technique for producing bovine cancellous bone scaffold and compare its physicochemical, mechanical, and biological characteristics with demineralized cancellous bone scaffold in an in-vitro study. Cancellous bone blocks were harvested from a bovine femoral head (18-24 months old) subjected to physical cleansing and chemical defatting, and further processed in two ways. Group I was subjected to demineralization, while Group II underwent decellularization through physical, chemical, and enzymatic treatments. Both were then freeze-dried, and gamma radiated, finally producing a demineralized bovine cancellous bone (DMB) scaffold and decellularized bovine cancellous bone (DCC) scaffold. Both DMB and DCC scaffolds were subjected to histological evaluation, scanning electron microscopy/energy-dispersive X-ray spectroscopy (SEM/EDS), fourier-transform infrared spectroscopy (FTIR), quantification of lipid, collagen, and residual nucleic acid content, and mechanical testing. The osteogenic potential was investigated through the recellularization of scaffolds with human osteoblast cell seeding and examined for cell attachment, proliferation, and mineralization by Alizarin staining and gene expression. DCC produced a complete acellular extracellular matrix (ECM) with the absence of nucleic acid content, wider pores with extensive interconnectivity and partially retaining collagen fibrils. DCC demonstrated a higher cell proliferation rate, upregulation of osteogenic differentiation markers, and substantial mineralized nodules production. Our findings suggest that the decellularization technique produced an acellular DCC scaffold with minimal damage to ECM and possesses osteogenic potential through the mechanisms of osteoconduction, osteoinduction, and osteogenesis in-vitro.

The impact of a statewide payment reform on transcatheter aortic valve replacement (TAVR) utilization and readmissions.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is an increasingly used but relatively expensive procedure with substantial associated readmission rates. It is unknown how cost-constrictive payment reform measures, such as Maryland's All Payer Model, impact TAVR utilization given its relative expense. This study investigated the impact of Maryland's All Payer Model on TAVR utilization and readmissions among Maryland Medicare beneficiaries. METHODS: This was a quasi-experimental investigation of Maryland Medicare patients undergoing TAVR between 2012 and 2018. New Jersey data were used for comparison. Longitudinal interrupted time series analyses were used to study TAVR utilization and difference-in-differences analyses were used to investigate post-TAVR readmissions. RESULTS: During the first year of payment reform (2014), TAVR utilization among Maryland Medicare beneficiaries dropped by 8% (95% confidence interval [CI]: -9.2% to -7.1%; p < 0.001), with no concomitant change in TAVR utilization in New Jersey (0.2%, 95% CI: 0%-1%, p = 0.09). Longitudinally, however, the All Payer Model did not impact TAVR utilization in Maryland compared to New Jersey. Difference-in-differences analyses demonstrated that implementation of the All Payer Model was not associated with significantly greater declines in 30-day post-TAVR readmissions in Maryland versus New Jersey (-2.1%; 95% CI: -5.2% to 0.9%; p =0.1). CONCLUSIONS: Maryland's All Payer Model resulted in an immediate decline in TAVR utilization, likely a result of hospitals adjusting to global budgeting. However, beyond this transition period, this cost-constrictive reform measure did not limit Maryland TAVR utilization. In addition, the All Payer Model did not reduce post-TAVR 30-day readmissions. These findings may help inform expansion of globally budgeted healthcare payment structures.

Responsive Neurostimulation in Drug-Resistant Pediatric Epilepsy: Findings From the Epilepsy Surgery Subgroup of the Pediatric Epilepsy Research Consortium.

BACKGROUND: Responsive neurostimulation (RNS), a closed-loop intracranial electrical stimulation system, is a palliative surgical option for patients with drug-resistant epilepsy (DRE). RNS is approved by the US Food and Drug Administration for patients aged ≥18 years with pharmacoresistant partial seizures. The published experience of RNS in children is limited. METHODS: This is a combined prospective and retrospective study of patients aged ≤18 years undergoing RNS placement. Patients were identified from the multicenter Pediatric Epilepsy Research Consortium Surgery Registry from January 2018 to December 2021, and additional data relevant to this study were retrospectively collected and analyzed. RESULTS: Fifty-six patients received RNS during the study period. The mean age at implantation was 14.9 years; the mean duration of epilepsy, 8.1 years; and the mean number of previously trialed antiseizure medications, 4.2. Five patients (9%) previously trialed dietary therapy, and 19 patients (34%) underwent prior surgery. Most patients (70%) underwent invasive electroencephalography evaluation before RNS implantation. Complications occurred in three patients (5.3%) including malpositioned leads or transient weakness. Follow-up (mean 11.7 months) was available for 55 patients (one lost), and four were seizure-free with RNS off. Outcome analysis of stimulation efficacy was available for 51 patients: 33 patients (65%) were responders (≥50% reduction in seizure frequency), including five patients (10%) who were seizure free at follow-up. CONCLUSIONS: For young patients with focal DRE who are not candidates for surgical resection, neuromodulation should be considered. Although RNS is off-label for patients aged <18 years, this multicenter study suggests that it is a safe and effective palliative option for children with focal DRE.