Clinical Efficacy of Scaling and Root Planing With Placental Extract Gel Under Magnification in Chronic Periodontitis Patients: A Split-Mouth Study.

Background Chronic localized periodontitis is a prevalent and persistent inflammatory condition in which there is the gradual degradation of the gingiva, periodontal ligament fibers, and alveolar bone loss. The objectives of periodontal therapy encompass not solely the elimination of local factors from the periodontal pocket but also the eradication of the dysbiotic microbial milieu to restore periodontal health. The present study aimed to compare the efficacy of scaling and root planing (SRP) with and without the placement of placental extract gel in the therapeutic management of chronic localized periodontitis under magnification. Materials and methods The present investigation encompassed 40 sites in 20 systemically healthy patients with chronic localized periodontitis. The allocation of the sites was done randomly, resulting in two distinct groups: group I (test site) and group II (control site). Group I was subjected to SRP, followed by the placement of placental extract gel, while group II solely received SRP. Clinical evaluations of pocket probing depth, plaque index, relative attachment level (RAL), gingival index (GI), and bleeding on probing (BoP) were performed at each site at baseline, six weeks, and three months. Results Placental extract gel as an accompaniment to SRP showed significant improvement in clinical parameters like pocket probing depth, RAL, GI, and BoP. Conclusion Placental extract gel may significantly act as a local drug delivery agent in the treatment of localized periodontal pockets.

MRI Evaluation of Microstructural and Perfusion Changes in Patients with Hemsensory Neurological Syndromes.

BACKGROUND: Hemisensory syndrome is characterized by a nondermatomal sensory deficit involving one half of the body. With the conventional imaging techniques, researches find low diagnostic yield in this condition; however, with the advancements in MRI imaging, there is hope to find the pathophysiological basis of hemisensory symptoms. OBJECTIVE: To evaluate microstructural and perfusion changes in brain parenchyma in patients with hemisensory syndrome on MRI with diffusion tensor imaging (DTI) and arterial spin labeling (ASL). MATERIAL AND METHODS: A total of 20 patients with hemisensory symptoms and 10 age-matched controls were enrolled and divided in two study groups - a) case vs. control and b) affected vs. nonaffected cerebral hemisphere in cases. Quantification of absolute cerebral blood flow (aCBF), fractional anisotropy (FA), and mean diffusivity (MD) was done in both groups. RESULTS: On ASL, there was significantly increased aCBF in thalamus on the contralateral-affected side. DTI revealed significantly decreased FA in the thalamus and increased FA in corona radiata of the affected side. There was a significant difference for MD of corona radiata between affected and nonaffected hemisphere. The mean value of MD in corona radiata is decreased on the affected side. CONCLUSION: Changes in advanced neuroimaging techniques like ASL and DTI along the pain processing pathway suggest an alteration in neuronal density and activity at the microstructural level. These findings may provide an insight into the etiopathogenesis of pain syndromes.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

In silico and network pharmacology analysis of fucosterol: a potent anticancer bioactive compound against HCC.

The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein-protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC.

Neuropsychiatric complications of coronavirus disease 2019: Mount Sinai Health System cohort study.

OBJECTIVE: To describe the frequency of neuropsychiatric complications among hospitalized patients with coronavirus disease 2019 (COVID-19) and their association with pre-existing comorbidities and clinical outcomes. METHODS: We retrospectively identified all patients hospitalized with COVID-19 within a large multicenter New York City health system between March 15, 2020 and May 17, 2021 and randomly selected a representative cohort for detailed chart review. Clinical data, including the occurrence of neuropsychiatric complications (categorized as either altered mental status [AMS] or other neuropsychiatric complications) and in-hospital mortality, were extracted using an electronic medical record database and individual chart review. Associations between neuropsychiatric complications, comorbidities, laboratory findings, and in-hospital mortality were assessed using multivariate logistic regression. RESULTS: Our study cohort consisted of 974 patients, the majority were admitted during the first wave of the pandemic. Patients were treated with anticoagulation (88.4%), glucocorticoids (24.8%), and remdesivir (10.5%); 18.6% experienced severe COVID-19 pneumonia (evidenced by ventilator requirement). Neuropsychiatric complications occurred in 58.8% of patients; 39.8% experienced AMS; and 19.0% experienced at least one other complication (seizures in 1.4%, ischemic stroke in 1.6%, hemorrhagic stroke in 1.0%) or symptom (headache in 11.4%, anxiety in 6.8%, ataxia in 6.3%). Higher odds of mortality, which occurred in 22.0%, were associated with AMS, ventilator support, increasing age, and higher serum inflammatory marker levels. Anticoagulant therapy was associated with lower odds of mortality and AMS. CONCLUSION: Neuropsychiatric complications of COVID-19, especially AMS, were common, varied, and associated with in-hospital mortality in a diverse multicenter cohort at an epicenter of the COVID-19 pandemic.

Maternal Mortality and COVID-19 Pandemic: Looking Beyond SARS CoV-2 Infection.

Objective: To study the impact of COVID-19 pandemic on maternal mortality ratio, aetiological and modifiable factors for maternal mortality and key interventions performed. Method: Retrospective exploratory study evaluating maternal mortality between April to November 2020 (study group) and 2019 (control group). Results: Demographic variations existed in the two groups. Increased maternal age and illiteracy were significantly more in the study group. Maternal mortality ratio (MMR) was significantly high in the study group (792 vs. 296 p value = 0.0). Hemorrhage accounted for 20% and COVID-19-related maternal deaths accounted for 15% deaths in the study group. Level 3 delay (delay in receiving care/inadequate care) was observed in 35% in the study group and 28% in control group (p value = 0.349). 17.5% of mothers in the study group as compared to 8% of control group were dead on arrival to hospital though not statistically significant (p value = 0.28). Significantly more women in study group died within 24 h of admission (45% vs. 20%, p value 0.04). Among the key interventions, the use of supplemental oxygen was significantly high in study group (p value = 0.02). Conclusion: Maternal mortality ratio was high in the pandemic year because of a significant decline in hospital delivery rate. The lesson learnt from this pandemic needs to be documented to guide better planning in the future to face similar situations.

The Emerging Role of Non-Coding RNAs (ncRNAs) in Plant Growth, Development, and Stress Response Signaling.

Plant species utilize a variety of regulatory mechanisms to ensure sustainable productivity. Within this intricate framework, numerous non-coding RNAs (ncRNAs) play a crucial regulatory role in plant biology, surpassing the essential functions of RNA molecules as messengers, ribosomal, and transfer RNAs. ncRNAs represent an emerging class of regulators, operating directly in the form of small interfering RNAs (siRNAs), microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). These ncRNAs exert control at various levels, including transcription, post-transcription, translation, and epigenetic. Furthermore, they interact with each other, contributing to a variety of biological processes and mechanisms associated with stress resilience. This review primarily concentrates on the recent advancements in plant ncRNAs, delineating their functions in growth and development across various organs such as root, leaf, seed/endosperm, and seed nutrient development. Additionally, this review broadens its scope by examining the role of ncRNAs in response to environmental stresses such as drought, salt, flood, heat, and cold in plants. This compilation offers updated information and insights to guide the characterization of the potential functions of ncRNAs in plant growth, development, and stress resilience in future research.

Racemose neurocysticercosis: a case series.

Neurocysticercosis (NCC) is a common parasitic condition of the central nervous system in certain parts of the world. The racemose variety of NCC is distinct from the commonly seen parenchymal form. It frequently infiltrates the basal cisterns and Sylvian fissures. Imaging plays a vital role in the diagnosis; however, as their signal intensity is similar to cerebrospinal fluid and due to the absence of enhancement in most cases, imaging diagnosis is often difficult on the conventional MRI sequences. Here, we present five cases of racemose NCC to emphasize the importance of a heavily T2-weighted sequence (Fast Imaging Employing Steady-state Acquisition) sequence in the diagnosing this entity.

Effect of biochar on the fate of antibiotic resistant genes and integrons in compost amended agricultural soil.

The persistence and transmission of emerging pollutants such as antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) have caused concern to scientific community. Composting practises are often adapted for the reduction of organic waste or to enhance fertility in agriculture soil but its continuous usage has posed a potential risk of increased abundance of ARGs in soil. Thus, the present study scrutinises the emerging risk of ARGs and MGEs in agriculture soil and its potential mitigation using biochar owing to its proven environmental sustainability and performance. After 30 days incubation, ARG distribution of SulI, SulII, dfrA1, dfrA12, tetA, flor, and ErmA was 50, 37.5, 37.5, 62.5, 42.11, 62.5, and 52.63% in control samples whereas it was 5, 15.78, 21.05, 15.79, 10.53, 21.05, and 31.58%, respectively, for biochar amended samples. Similarly, IntI1 and IntI2 in control and biochar amended samples were 18.75 and 6.25% and 10.53 and 5.26%, respectively. Principal component analysis (PCA) factor suggests that biochar amendment samples showed enhanced value for pH, organic matter, and organic carbon over control samples. Furthermore, Pearson's correlation analysis performed between detected ARGs and MGEs demonstrated the positive and significant correlation at p < 0.05 for both control and biochar amended samples.

Myoglobin modulates the Hippo pathway to promote cardiomyocyte differentiation.

The endogenous mechanisms that propagate cardiomyocyte differentiation and prevent de-differentiation remain unclear. While the expression of the heme protein myoglobin increases by over 50% during cardiomyocyte differentiation, a role for myoglobin in regulating cardiomyocyte differentiation has not been tested. Here, we show that deletion of myoglobin in cardiomyocyte models decreases the gene expression of differentiation markers and stimulates cellular proliferation, consistent with cardiomyocyte de-differentiation. Mechanistically, the heme prosthetic group of myoglobin catalyzes the oxidation of the Hippo pathway kinase LATS1, resulting in phosphorylation and inactivation of yes-associated protein (YAP). In vivo, myoglobin-deficient zebrafish hearts show YAP dephosphorylation and accelerated cardiac regeneration after apical injury. Similarly, myoglobin knockdown in neonatal murine hearts shows increased YAP dephosphorylation and cardiomyocyte cycling. These data demonstrate a novel role for myoglobin as an endogenous driver of cardiomyocyte differentiation and highlight myoglobin as a potential target to enhance cardiac development and improve cardiac repair and regeneration.

Elevated phase amplitude coupling as a depression biomarker in epilepsy.

Depression is prevalent in epilepsy patients and their intracranial brain activity recordings can be used to determine the types of brain activity that are associated with comorbid depression. We performed case-control comparison of spectral power and phase amplitude coupling (PAC) in 34 invasively monitored drug resistant epilepsy patients' brain recordings. The values of spectral power and PAC for one-minute segments out of every hour in a patient's study were correlated with pre-operative assessment of depressive symptoms by Beck Depression Inventory-II (BDI). We identified an elevated PAC signal (theta-alpha-beta phase (5-25 Hz)/gamma frequency (80-100 Hz) band) that is present in high BDI scores but not low BDI scores adult epilepsy patients in brain regions implicated in primary depression, including anterior cingulate cortex, amygdala and orbitofrontal cortex. Our results showed the application of PAC as a network-specific, electrophysiologic biomarker candidate for comorbid depression and its potential as treatment target for neuromodulation.

Genomic insights into virulence, antimicrobial resistance, and adaptation acumen of Escherichia coli isolated from an urban environment.

Populations of common commensal bacteria such as Escherichia coli undergo genetic changes by the acquisition of certain virulence and antimicrobial resistance (AMR) encoding genetic elements leading to the emergence of pathogenic strains capable of surviving in the previously uninhabited or protected niches. These bacteria are also reported to be prevalent in the environment where they survive by adopting various recombination strategies to counter microflora of the soil and water, under constant selection pressure(s). In this study, we performed molecular characterization, phenotypic AMR analysis, and whole genome sequencing (WGS) of E. coli (n = 37) isolated from soil and surface water representing the urban and peri-urban areas. The primary aim of this study was to understand the genetic architecture and pathogenic acumen exhibited by environmental E. coli. WGS-based analysis entailing resistome and virulome profiling indicated the presence of various virulence (adherence, iron uptake, and toxins) and AMR encoding genes, including blaNDM-5 in the environmental isolates. A majority of our isolates belonged to phylogroup B1 (73%). A few isolates in our collection were of sequence type(s) (ST) 58 and 224 that could have emerged recently as clonal lineages and might pose risk of infection/transmission. Mobile genetic elements (MGEs) such as plasmids (predominantly) of the IncF family, prophages, pipolins, and insertion elements such as IS1 and IS5 were also observed to exist, which may presumably aid in the propagation of genes encoding resistance against antimicrobial drugs. The observed high prevalence of MGEs associated with multidrug resistance in pathogenic E. coli isolates belonging to the phylogroup B1 underscores the need for extended surveillance to keep track of and prevent the transmission of the bacterium to certain vulnerable human and animal populations. IMPORTANCE: Evolutionary patterns of E. coli bacteria convey that they evolve into highly pathogenic forms by acquiring fitness advantages, such as AMR, and various virulence factors through the horizontal gene transfer (HGT)-mediated acquisition of MGEs. However, limited research on the genetic profiles of environmental E. coli, particularly from India, hinders our understanding of their transition to pathogenic forms and impedes the adoption of a comprehensive approach to address the connection between environmentally dwelling E. coli populations and human and veterinary public health. This study focuses on high-resolution genomic analysis of the environmental E. coli isolates aiming to understand the genetic similarities and differences among isolates from different environmental niches and uncover the survival strategies employed by these bacteria to thrive in their surroundings. Our approach involved molecular characterization of environmental samples using PCR-based DNA fingerprinting and subsequent WGS analysis. This multidisciplinary approach is likely to provide valuable insights into the understanding of any potential spill-over to human and animal populations and locales. Investigating these environmental isolates has significant potential for developing epidemiological strategies against transmission and understanding niche-specific evolutionary patterns.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

Synthesis and spectroscopic characterization of 13 C4 -labeled 4-cyano-2-oxobutyraldehyde semicarbazone: A metabolite of nitrofurazone.

Nitrofurazone usage in food-producing animals is prohibited in most countries, including the United States. Regulatory agencies regularly monitor its use in domestic, export/import animals' food products by measuring the semicarbazide (SEM) metabolite as a biomarker of nitrofurazone exposure. However, the use of SEM is controversial because it is also produced in food naturally and thus gives false positive results. A cyano-metabolite, 4-cyano-2-oxobutyraldehyde semicarbazone (COBS), is proposed as an alternate specific marker of nitrofurazone to distinguish nitrofurazone from treated or untreated animals. A synthetic method was developed to produce COBS via metallic hydrogenation of nitrofurazone. The product was isolated and characterized by one- and two-dimensional nuclear magnetic spectroscopy (NMR) experiments, Fourier-transform infrared spectroscopy (FT-IR), and mass spectrometry. The developed synthetic procedure was further extended to synthesize isotopically labeled 4-[13 C]-cyano-2-oxo- [2, 3, 4-13 C3 ]-butyraldehyde semicarbazone. Labeled COBS is useful as an internal standard for its quantification in food-producing animals. Thus, the developed method provides a possibility for its commercial synthesis to procure COBS. This is the first synthesis of the alternate specific marker metabolite of nitrofurazone for possible usage in regulatory analysis to solve a real-world problem.

Older adults with epilepsy and COVID-19: Outcomes in a multi-hospital health system.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with high rates of mortality and morbidity in older adults, especially those with pre-existing conditions. There is little work investigating how neurological conditions affect older adults with COVID-19. We aimed to compare in-hospital outcomes, including mortality, in older adults with and without epilepsy. METHODS: This retrospective study in a large multicenter New York health system included consecutive older patients (age ≥65 years) either with or without epilepsy who were admitted with COVID-19 between 3/2020-5/2021. Epilepsy was identified using a validated International Classification of Disease (ICD) and antiseizure medicationbased case definition. Univariate comparisons were calculated using Chi-square, Fisher's exact, Mann-Whitney U, or Student's t-tests. Multivariable logistic regression models were generated to examine factors associated with mortality, discharge disposition and length of stay (LOS). RESULTS: We identified 5384 older adults admitted with COVID-19 of whom 173 (3.21 %) had epilepsy. Mean age was significantly lower in those with (75.44, standard deviation (SD): 7.23) compared to those without epilepsy (77.98, SD: 8.68, p = 0.007). Older adults with epilepsy were more likely to be ventilated (35.84 % vs. 16.18 %, p < 0.001), less likely to be discharged home (21.39 % vs. 43.12 %, p < 0.001), had longer median LOS (13 days vs. 8 days, p < 0.001), and had higher in-hospital death (35.84 % vs. 28.29 %, p = 0.030) compared to those without epilepsy. Epilepsy in older adults was associated with increased odds of in-hospital death (adjusted odds ratio (aOR), 1.55; 95 % CI 1.12-2.14, p = 0.032), non-routine discharge disposition (aOR, 3.34; 95 % CI 2.21-5.03, p < 0.001), and longer LOS (46.46 % 95 % CI 34 %-59 %, p < 0.001). CONCLUSIONS: In models that adjusted for multiple confounders including comorbidity and age, our study found that epilepsy was still associated with higher in-hospital mortality, longer LOS and worse discharge dispositions in older adults with COVID-19 higher in-hospital mortality, longer LOS and worse discharge dispositions in older adults with COVID-19. This work reinforces that epilepsy is a risk factor for worse outcomes in older adults admitted with COVID-19. Timely identification and treatment of COVID-19 in epilepsy may improve outcomes in older people with epilepsy.

Unraveling the evolutionary dynamics of toxin-antitoxin systems in diverse genetic lineages of Escherichia coli including the high-risk clonal complexes.

IMPORTANCE: Large-scale genomic studies of E. coli provide an invaluable opportunity to understand how genomic fine-tuning contributes to the transition of bacterial lifestyle from being commensals to mutualists or pathogens. Within this context, through machine learning-based studies, it appears that TA systems play an important role in the classification of high-risk clonal lineages and could be attributed to their epidemiological success. Due to these profound indications and assumptions, we attempted to provide unique insights into the ordered world of TA systems at the population level by investigating the diversity and evolutionary patterns of TA genes across 19 different STs of E. coli. Further in-depth analysis of ST-specific TA structures and associated genetic coordinates holds the potential to elucidate the functional implications of TA systems in bacterial cell survival and persistence, by and large.

A case of acute-onset paraplegia due to spinal tuberculosis in term pregnancy.

Acute paraplegia in pregnancy is uncommon but can result from pathology including Guillain-Barre syndrome, acute transverse myelitis, and spinal tuberculosis, also known as Pott's disease of the spine. India has a high incidence of tuberculosis (2.8 million cases annually) therefore spinal tuberculosis is a particularly important disease to consider during pregnancy. Management of spinal tuberculosis in pregnancy poses a challenge especially at term gestation as immobilization of the spine and maintaining supination is difficult, particularly at delivery.

Facile synthesis of 14 C-nitrofurazone from 14 C-urea.

The veterinary drug nitrofurazone (5-nitro-2-furaldehyde semicarbazone) exhibits excellent antimicrobial properties but its application in food-producing animals is prohibited. The illegal use of nitrofurazone is regularly monitored by food regulatory agencies. Currently, semicarbazide (SEM) is used as a marker of nitrofurazone exposure. However, the use of SEM as a marker of nitrofurazone is under scrutiny after evidence of a high incidence of false positive tests. To overcome the current dilemma, it is necessary to identify a nitrofurazone-specific marker analyte which requires conducting nitrofurazone metabolism studies in food-producing animals. The use of carbon-14 labeled nitrofurazone would facilitate metabolism studies and structural elucidation of nitrofurazone metabolites of possible utility as a marker compound. In the present work, a synthetic method is described to procure radiolabeled nitrofurazone that incorporates 14 C- carbon at the semicarbazide moiety. The method incorporates 14 C-carbon via employing readily available and more economically affordable [14 C]-urea compared with [14 C]-semicarbazide. To the best of our knowledge, there is no report on the synthesis of 5-nitro-2-furaldehyde [14 C]-semicarbazone from 14 C-urea. The developed method involves monoamination of [14 C]-urea followed by a condensation reaction with 5-nitro-2-furaldehyde to produce 5-nitro-2-furaldehyde [14 C]-semicarbazone in 85% yield with greater than 98% radiochemical purity.

A multicenter retrospective study of patients treated in the thalamus with responsive neurostimulation.

Introduction: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy. Methods: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or bilateral thalamic RNS leads implanted in the CMN or ANT for at least 6 months were included. Primary objectives were to describe the implant location and determine changes in the frequency of disabling seizures at 6 months, 1 year, 2 years, and > 2 years. Secondary objectives included documenting seizure free periods, anti-seizure medication regimen changes, stimulation side effects, and serious adverse events. In addition, the global clinical impression scale was completed. Results: Twelve patients had at least one lead placed in the CMN, and 13 had at least one lead placed in the ANT. The median baseline seizure frequency was 15 per month. Overall, the median seizure reduction was 33% at 6 months, 55% at 1 year, 65% at 2 years, and 74% at >2 years. Seizure free intervals of at least 3 months occurred in nine patients. Most patients (60%, 15/25) did not have a change in anti-seizure medications post RNS placement. Two serious adverse events were recorded, one related to RNS implantation. Lastly, overall functioning seemed to improve with 88% showing improvement on the global clinical impression scale. Discussion: Meaningful seizure reduction was observed in patients who suffer from drug resistant epilepsy with unilateral or bilateral RNS in either the ANT or CMN of the thalamus. Most patients remained on their pre-operative anti-seizure medication regimen. The device was well tolerated with few side effects. There were rare serious adverse events. Most patients showed an improvement in global clinical impression scores.