Angiographic Features of Meningiomas Predicting Extent of Preoperative Embolization.

BACKGROUND AND OBJECTIVES: Preoperative embolization is used as an endovascular adjunct to surgical resection of meningiomas. However, there is no standardized system to assess the efficacy or extent of embolization during the embolization procedure. We sought to establish a purely angiographic grading system to facilitate consistent reporting of the outcome of meningioma embolization and to characterize the anatomic and other features of meningiomas that predict the degree of devascularization achieved through preoperative embolization. METHODS: We identified patients with meningiomas who underwent preoperative cerebral angiography and subsequent resection between 2015 and 2021. Demographic, clinical, and imaging data were collected in a research registry. We defined an angiographic devascularization grading scale as follows: grade 0 for no embolization, 1 for partial embolization, 2 for majority embolization, 3 for complete external carotid artery embolization, and 4 for complete embolization. RESULTS: Eighty consecutive patients were included, 60 of whom underwent preoperative tumor embolization (20 underwent angiography with an intention to treat but ultimately not embolization). Embolized tumors were larger (59.0 vs 35.9 cc; P = .03). Gross total resection, length of stay, and complication rates did not differ among groups. The distribution of arterial feeders differed significantly across tumors in a location-specific manner. Both the tumor location and the identity of arterial feeders were predictive of the extent of embolization. Anterior midline meningiomas were associated with internal carotid (ophthalmic, ethmoidal) supply and lower devascularization grades (P = .03). Tumors fed by meningeal feeders (convexity, falcine, lateral sphenoid wing) were associated with higher devascularization grades (P < .01). The procedural complication rate for tumor embolization was 2.5%. CONCLUSION: Angiographic outcomes can be graded to indicate the extent of tumor embolization. This system may facilitate consistency of reported angiographic results. In addition, arterial feeders vary in a manner predicted by tumor location, and these patterns correlate with typical degrees of devascularization achieved in those tumor locations.

RT-PCR Result of SARS-CoV-2 Viral RNA in Cadavers and Viral Transmission Risk to Handlers.

During the onset of the pandemic, a common research question was asked by the hospital staff, and family members who were handling COVID-19-infected cadavers, "does COVID-19-positive dead body harbor SARS-CoV-2 viral RNA?" Several research findings were reported but due to the lack of proper research findings, the question remained unanswered. The present study was planned to observe the virus transmission risk from cadavers to the handlers. A pilot study was conducted on 54 cadavers who died in COVID-ICU (SARS-CoV-2-positive diagnosed by RT-PCR) during 2021-2022. Skin swab sample from 54 dead bodies and 54 glove samples of handlers were taken within 1 hour of death for the RT-PCR test. Viability results from RT-PCR show that the infection risk was 50% in cadavers, whereas the transmission risk to handlers while handling was 7%, which is minimal. The SARS-CoV-2 viability was high in cases of those died after a long time of infection. Based on the RT-PCR result and data analysis the interpretation of the study was that the SARS-CoV-2 transmission risk from dead bodies to the handlers is minimal but the SARS-CoV-2 viability persists in the cadavers. This fact is helpful for the people who will conduct funeral activities, autopsy staff, and hospital staff handling dead bodies. How to cite this article: Panda B, Singh N, Singh G, Patro ARK, Mohanty AP, Patnaik PK, et al. RT-PCR Result of SARS-CoV-2 Viral RNA in Cadavers and Viral Transmission Risk to Handlers. Indian J Crit Care Med 2024;28(6):614-616.

Advanced neuroimaging of the trigeminal nerve and the whole brain in trigeminal neuralgia: a systematic review.

ABSTRACT: For trigeminal neuralgia (TN), a major role of imaging is to identify the causes, but recent studies demonstrated structural and microstructural changes in the affected nerve. Moreover, an increasing number of studies have reported central nervous system involvement in TN. In this systematic review, recent quantitative magnetic resonance imaging (MRI) studies of the trigeminal nerve and the brain in patients with TN were compiled, organized, and discussed, particularly emphasizing the possible background mechanisms and the interpretation of the results. A systematic search of quantitative MRI studies of the trigeminal nerve and the brain in patients with TN was conducted using PubMed. We included the studies of the primary TN published during 2013 to 2023, conducted for the assessment of the structural and microstructural analysis of the trigeminal nerve, and the structural, diffusion, and functional MRI analysis of the brain. Quantitative MRI studies of the affected trigeminal nerves and the trigeminal pathway demonstrated structural/microstructural alterations and treatment-related changes, which differentiated responders from nonresponders. Quantitative analysis of the brain revealed changes in the brain areas associated with pain processing/modulation and emotional networks. Studies of the affected nerve demonstrated evidence of demyelination and axonal damage, compatible with pathological findings, and have shown its potential value as a tool to assess treatment outcomes. Quantitative MRI has also revealed the possibility of dynamic microstructural, structural, and functional neuronal plasticity of the brain. Further studies are needed to understand these complex mechanisms of neuronal plasticity and to achieve a consensus on the clinical use of quantitative MRI in TN.

The future of cancer treatment: combining radiotherapy with immunotherapy.

Radiotherapy (RT) and immunotherapy (IT) are the powerful tools for cancer treatment which act through the stimulation of immune response, and evidence suggest that combinatorial actions of these therapies may augment each other's beneficial effect through complex synergistic mechanisms. These molecular strategies are designed to target rapidly dividing cancer cells by either directly or indirectly inducing DNA damage. However, when cells detect DNA damage, they activate a range of signalling pathways known as the DNA damage response (DDR) to repair. Strategies are being developed to interfere with the DDR pathways in cancer cells to ensure their damage-induced degeneration. The stability of a cell's genetic material is largely dependent on the efficacy of DNA repair and therefore, an in-depth understanding of DNA damages and repair mechanism(s) in cancer cells is important to develop a promising therapeutic strategies for ensuring the efficacy of damage-induced tumor cell death. In recent years, a wide range of small molecule drugs have been developed which are currently being employed to combat the DNA repair deficiencies associated with tumor cells. Sequential or concurrent use of these two modalities significantly enhances the anti-tumor response, however with a concurrent probability of increased incidence of symptomatic adverse effects. With advent of newer IT agents, and administration of higher doses of radiation per fraction, such effects are more difficult to predict owing to the paucity of randomized trial data. It is well established that anti cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), anti- Programmed cell death protein 1(PD-1), anti-Programmed cell death one ligand 1 (PD-L1) can be safely administered with RT and many studies have demonstrated survival benefit with such combination for patients with metastatic malignancy. However, the biology of radioimmunotherapy (RT/IT) is still an open area where research need to be focused to determine optimum dosage specially the interaction of the RT/IT pathways to determine optimum dosing schedule. In the current article we have summarised the possible intracellular immunological events that might be triggered when RT and IT modalities are combined with the DDR antagonists and highlighted present clinical practices, outcome, and toxicity profile of this novel treatment strategy.

Assessment of Factors Responsible for Stone-Free Status After Retrograde Intrarenal Surgery.

Aim The study aimed to evaluate the predictive factors that determined stone-free rate (SFR) after retrograde intrarenal surgery (RIRS). Materials and methods This prospective study was conducted on 183 patients undergoing RIRS for renal stones. Patients were categorized into two groups, depending on stone-free status one month following the procedure. SFR was defined as the complete absence of stones or stones <4 mm. The parameters studied included patient demographics, presence of hydronephrosis, presence of preoperative double J-stent, abnormal renal anatomy, and stone characteristics (stone burden, stone number, stone density, stone location, lower pole infundibulopelvic angle, and lower pole renal infundibular length (RIL)). Univariate and multivariate analyses were performed to identify risk factors for residual stones. We assessed the predictive ability of the RIRS score and Resorlu-Unsal stone score (RUSS) for evaluating SFR utilizing receiver operating characteristic (ROC) analysis. Results 183 patients were included in the study with a median age of 51 years. 131 (71.6%) patients were declared stone-free after the procedure. The mean stone size and density were 16.9 SD±7.5 mm and 1038 SD±342 Hounsfield units (HU) respectively. Stone-free patients had lower stone size (14.3 mm vs. 23.6 mm, p<0.01) and stone density (970 HU vs. 1211 HU, p<0.01) compared to non-stone-free patients. Patients with residual stones had steeper lower pole renal infundibulopelvic angle (RIPA) (31.3° vs. 40.7°, p<0.01) and longer RIL (26.6 mm vs. 21.1 mm, p<0.01). Stone multiplicity (p<0.01), lower pole stone location (p<0.01), and renal malformations (p<0.01) were significant influencing factors for residual renal stones after RIRS. Multivariate analysis revealed stone size, stone density (HU), and stone location as independent predictors for SFR after RIRS. Among the scoring systems, the RIRS score had the highest diagnostic accuracy for SFR (area under the curve (AUC): -0.882, 95% CI-0.828-0.936). Conclusion Stone size, stone density (HU), and stone number are important predictors of SFR after RIRS. Lower pole stone location and abnormal renal anatomy play a substantial role in determining SFR after RIRS. In lower pole stones, a long RIL and acute RIPA negatively influence SFR. Additionally, the RIRS score was found to be a better predictor for SFR than the RUSS score.

High surface area biochar for the removal of naphthenic acids from environmental water and industrial wastewater.

This study reports the production of biochar adsorbents from two major crop residues (i.e., rice and wheat straw) to remove naphthenic acids from water. The alkali treatment approach was used for biochar activation that resulted in a tremendous increase in their surface area, i.e., up to 2252 and 2314 m2/g, respectively, for rice and wheat straw biochars. Benzoic acid was used as a model compound to optimize critical adsorption parameters. Its maximum monolayer adsorption capacity of 459.55 and 357.64 mg/g was achieved for activated rice and wheat straw biochars. The adsorption of benzoic acid was exothermic (∆H° = - 7.06 and - 3.89 kJ/mol) and identified possibly as physisorption (Gibbs free energy ranges 3.5-4.0 kJ/mol). The kinetic study suggested that adsorption follows pseudo-second-order kinetics with qe2 for rice straw and wheat straw-derived adsorbents at 200 and 194 mg/g, respectively. As adsorbent, the recyclability of activated biochars was noticed with no significant loss in their efficiency for up to ten successive regeneration cycles. The adsorption results were validated using a commercial naphthenic acid mixture-spiked river water and paper/pulp industrial effluent. The activated rice and wheat straw biochars exhibited excellent adsorption efficiency of 130.3 and 74.6 mg/g, respectively. The naphthenic acid adsorption on biochar surface was due to various interactions, i.e., weak van der Waal's, pore filling, π-π stacking, and ionic interactions. This study offers a cost-effective and eco-friendly approach to valorizing agricultural residues for pollutant removal from industrial wastewater, including petroleum refineries.

Successful Percutaneous Closure of Gerbode Defect and Right Atrial-Aortic Fistula Following Infective Endocarditis.

We report a case of infective endocarditis with a septal abscess that was complicated with abnormal blood flow from the left ventricle to the right atrium (Gerbode defect) along with abnormal blood flow from the aorta to the right atrium (atrial-aortic fistula). This is the first reported case of successful correction of both defects by a percutaneous approach.

Phage Mediated Biocontrol: A Promising Green Solution for Sustainable Agriculture.

In the current scenario of growing world population, limited cultivable land resources, plant diseases, and pandemics are some of the major factors responsible for declining global food security. Along with meeting the food demand, the maintenance of food quality is also required to ensure healthy consumption and marketing. In agricultural fields, pest infestations and bacterial diseases are common causes of crop damage, leading to massive yield losses. Conventionally, antibiotics and several pesticides have been used to manage and control these plant pathogens. However, the overuse of antibiotics and pesticides has led to the emergence of resistant strains of pathogenic bacteria. The bacteriophages are the natural predators of bacteria and are host-specific in their action. Therefore, the use of bacteriophages for the biocontrol of pathogenic bacteria is serving as a sustainable and green solution in crop protection and production. In this review, we have discussed the important plant pathogens and their impact on plant health and yield loss. Further, we have abridged the role of bacteriophages in the protection of crops from bacterial disease by discussing various greenhouse and field trials. Finally, we have discussed the impact of bacteriophages on the plant microbiome, phage resistance, and legal challenges in the registration and commercial production of bacteriophage-based biopesticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-024-01204-x.

Isoxazole group directed Rh(III)-catalyzed alkynylation using TIPS-EBX.

A highly effective isoxazole directed ortho C-H alkynylation has been developed. Rhodium(III) catalyzed direct di-(and/or mono) alkynylation using a hypervalent iodine reagent (TIPS-EBX) is reported. The reaction proceeds with a wide substrate scope under benign conditions. Preliminary mechanistic studies support this chelation assisted C-H alkynylation.

Mosaic Atoh1 deletion in the chick auditory epithelium reveals a homeostatic mechanism to restore hair cell number.

The mechanosensory hair cell of the vertebrate inner ear responds to the mechanical deflections that result from hearing or change in the acceleration due to gravity, to allow us to perceive and interpret sounds, maintain balance and spatial orientation. In mammals, ototoxic compounds, disease, and acoustic trauma can result in damage and extrusion of hair cells, without replacement, resulting in hearing loss. In contrast, non-mammalian vertebrates can regenerate sensory hair cells. Upon damage, hair cells are extruded and an associated cell type, the supporting cell is transformed into a hair cell. The mechanisms that can trigger regeneration are not known. Using mosaic deletion of the hair cell master gene, Atoh1, in the embryonic avian inner ear, we find that despite hair cells depletion at E9, by E12, hair cell number is restored in sensory epithelium. Our study suggests a homeostatic mechanism can restores hair cell number in the basilar papilla, that is activated when juxtracrine signalling is disrupted. Restoration of hair cell numbers during development may mirror regenerative processes, and our work provides insights into the mechanisms that trigger regeneration.

Inequality in Forensic Medicine in India: The Current Scenario and Way Forward.

Background Forensic Medicine (FM) is one of the core specialties of medicine in India, which serves as a bridge between medical science and India's justice delivery systems. Although FM experts play a crucial role in handling medicolegal cases, there is an increasing deficit of FM experts in India. This may be due to the inadequate postgraduate (PG) seats across the states and the low uptake of PG seats in FM. This study was conducted to explore the current status of PG seats along with the Forensic Medicine Toxicology (FMT)/FM index across Indian states. Methodology In this cross-sectional study, data on the number of PGs in FMT/FM and the institutes offering PG courses in FMT/FM were searched on the official website of the National Medical Commission. The data available on the website until November 2023 were incorporated. The FMT/FM index was calculated at the national and state levels, and the states were graded based on the national FMT/FM index. Results The national FMT/FM PG trainee index was 0.054. Considering this as the reference value, grading of the FMT/FM PG trainee index was done as the highest (1.159 to 0.308), higher than the nation (0.054 but less than 0.308), lower than the nation (0.054 but higher than 0.00), and zero. Among all the states and union territories, Andaman & Nicobar, Arunachal Pradesh, Dadra and Nagar Haveli, Jammu & Kashmir, Lakshadweep, Mizoram, Nagaland, Sikkim, and Ladakh had zero FMT/FM PG index due to non-availability of any PG seats for FMT/FM. In total, 20 states had an FMT/FM PG index higher than India's FMT/FM PG index headed by Pondicherry (1.159), followed by Chandigarh (0.429) and Goa (0.308). Conclusions PG seats were highly deficient in several states, which is more likely to affect justice delivery in the future across these states. This study has a few limitations, as we did not explore the actual intake of these PG seats across different states. We anticipate a lower intake of PG seats due to factors such as low demand, fewer job opportunities, and monetary gain. However, this needs further exploration in future studies.

Clinical Characteristics and Treatment Responses of Patients in Delirious Mania: A Case Series.

BACKGROUND: Delirious mania (DM) is a severe psychiatric condition having rapid onset of delirium, mania, and psychosis. It is an emergency condition as it has acute onset and is characterized by extreme hyperactivity. Catatonic signs may also be present. Very few cases have been reported from India, hence making it imperative to study its clinical characteristics and possible treatment, which can help in providing care to such patients in emergency settings. CLINICAL CASES DESCRIPTION: This paper describes four cases with a diagnosis of DM - demography, clinical features, investigations, treatment. All the patients had an acute onset and rapid progression of symptoms, with clinical symptoms of talkativeness, increased psychomotor activity, decreased need for sleep, aggressive and violent behavior, increased libido, increased appetite with delusion of grandiosity, disorientation to time/place/person, impaired memory of recent events, impaired attention with fluctuating course, negativism, echolalia, and echopraxia. CONCLUSION: There is a high likelihood of misdiagnosing DM in the absence of diagnostic guidelines. There should be an active search for the underlying aetiology in all cases of DM. Atypical antipsychotics and mood stabilizers may be used to treat less severe forms of DM. Modified electric convulsive treatment and intravenous benzodiazepines elicit a good response.

Bioactivity of Calcium Silicate-Based Endodontic Materials: A Comparative in vitro Evaluation.

Background: Bioactivity refers to the ability of a material to interact with living organisms or biological systems in a way that elicits a specific response. In the context of materials science and medicine, bioactivity is particularly important because it can determine the suitability of material for various applications. Objective: To evaluate and compare different commercially available calcium silicate-based materials regarding: 1. Morphological and elemental analysis at the dentin/material interface. 2. Calcium and silicon release and uptake by adjacent root canal dentine by evaluating the calcium and silicon incorporation depth in adjacent root canal dentin. Materials and Methods: This study examined four calcium silicate-based cements: Biodentine, MTA Angelus, BioAggregate, and MTA Plus. One hundred extracted human teeth with intact apices and no cavities were selected. Root sections measuring 3 mm in length were created at the mid-root level using low-speed diamond discs. Bioactivity was evaluated at 1, 7, 30, and 90 days, respectively. Results: The principal composition of the interfacial dentine layer and incorporation of calcium and silicon into dentine was measured at 1, 7, 30, and 90 days. Statistical analysis was performed by multiple comparisons using post hoc Tukey HSD. Conclusion: All the materials have shown bioactivity, i.e. release of calcium, silicon, and their uptake in the adjacent dentin in the presence of phosphate-buffered saline.

Epidemiology and impact of chronic disease multimorbidity in India: a systematic review and meta-analysis.

Objectives: This is the first systematic review and meta-analysis of the prevalence of multimorbidity, its risk factors including socioeconomic factors, and the consequences of multimorbidity on health systems and broader society in India. Methods: A systematic review of both published and grey literature from five databases (Medline, Embase, EBSCO, Scopus, and ProQuest) was conducted including original studies documenting prevalence or patient outcomes associated with multimorbidity among adults in India. We excluded studies that did not explicitly mention multimorbidity. Three independent reviewers did primary screening based on titles and abstracts followed by full-text review for potential eligibility. The risk of bias was independently assessed by two reviewers following the Appraisal Tool for Cross-Sectional Studies. We presented both qualitative and quantitative (through meta-analysis) summaries of the evidence. The protocol for this study was prospectively registered with PROSPERO (CRD42021257281). Results: The review identified 5442 articles out of which 35 articles were finally included in this study. Twenty-three studies were based on the primary data while 12 used secondary data. Eleven studies were conducted in hospital/primary care setting while 24 were community-based. The pooled prevalence of multimorbidity based on (n=19) studies included for meta-analysis was 20% (95% CI: 19% to 20%). The most frequent outcomes were increased healthcare utilization, reduced health-related quality of life, physical and mental functioning. Conclusion: We identified a wide variance in the magnitude of multimorbidity across age groups and regions with most of the studies from eastern India. Nation-wide studies, studies on vulnerable populations and interventions are warranted.

Prospective Evaluation of Risk Factors Responsible for Infection Following Retrograde Intrarenal Surgery.

OBJECTIVE: The study aimed to identify the various risk factors for infective complications following retrograde intrarenal surgery (RIRS). MATERIALS AND METHODS: The study was conducted over one year, and the incidence of infectious complications after RIRS was calculated. Patients were divided into two groups based on the presence and absence of infective complications and were compared in terms of preoperative and operative characteristics. The complications were assessed and graded according to the Modified Clavien classification system (MCCS). The Fisher's exact test, Student's t-test, and Mann-Whitney U test were used for univariate analysis. Multivariate logistic regression analysis was used to identify independent risk factors for postoperative urinary tract infection (UTI). RESULTS: Out of 165 patients in the study, 27 (16.7%) patients developed UTI within one month of undergoing RIRS. The most frequent complication was fever, which occurred in 13 (7.8%) patients. When stratified by MCCS, 13 were grade I, nine were grade II, four were grade III, and one was a grade IV complication. High stone burden, concomitant diabetes mellitus, and multiple renal stones were identified as substantial risk factors for postoperative UTI in univariate analysis. On multivariate analysis, preoperative UTI and prolonged operative time were found to have a significant association with postoperative UTI. CONCLUSION: The present study demonstrated that preoperative UTI and prolonged operative time are independent factors responsible for postoperative UTI. Large stone burden, stone multiplicity, and diabetes mellitus contribute to a higher risk for UTI following RIRS.

How Does HF-DFT Achieve Chemical Accuracy for Water Clusters?

Bolstered by recent calculations of exact functional-driven errors (FEs) and density-driven errors (DEs) of semilocal density functionals in the water dimer binding energy [Kanungo, B. J. Phys. Chem. Lett. 2024, 15, 323-328], we investigate approximate FEs and DEs in neutral water clusters containing up to 20 monomers, charged water clusters, and alkali- and halide-water clusters. Our proxy for the exact density is r2SCAN 50, a 50% global hybrid of exact exchange with r2SCAN, which may be less correct than r2SCAN for the compact water monomer but importantly more correct for long-range electron transfers in the noncompact water clusters. We show that SCAN makes substantially larger FEs for neutral water clusters than r2SCAN, while both make essentially the same DEs. Unlike the case for barrier heights, these FEs are small in a relative sense and become large in an absolute sense only due to an increase in cluster size. SCAN@HF, short for SCAN evaluated on the Hartree-Fock (HF) density, produces a cancellation of errors that makes it chemically accurate for predicting the absolute binding energies of water clusters. Likewise, adding a long-range dispersion correction to r2SCAN@HF, as in the composite method HF-r2SCAN-DC4, makes its FE more negative than in r2SCAN@HF, permitting a near-perfect cancellation of FE and DE. r2SCAN by itself (and even more so, r2SCAN evaluated on the r2SCAN 50 density), is almost perfect for the energy differences between water hexamers, and thus probably also for liquid water away from the boiling point. Thus, the accuracy of composite methods like SCAN@HF and HF-r2SCAN-DC4 is not due to the HF density being closer to the exact density, but to a compensation of errors from its greater degree of localization. We also give an argument for the approximate reliability of this unconventional error cancellation for diverse molecular properties. Finally, we confirm this unconventional error cancellation for the SCAN description of the water trimer via Kohn-Sham inversion of the CCSD(T) density.

α-Bromoacetate as a Mild and Safe Brominating Agent in the Light-Driven Vicinal Dibromination of Unactivated Alkenes and Alkynes.

Light-induced vicinal dibromination of unactivated alkenes and alkynes has been demonstrated by using methyl α-bromoacetate as a mild brominating agent. A near-visible light (370 nm) light-emitting diode (LED) mediates this simple dibromination reaction under mild conditions with the inexpensive and nontoxic α-bromoacetate. The reaction proceeds well with both terminal and internal alkenes and alkynes and those contained in N/O-heterocycles, indicating its versatility in synthesizing dibrominated organic compounds.

Long Non-Coding RNAs as Determinants of Thyroid Cancer Phenotypes: Investigating Differential Gene Expression Patterns and Novel Biomarker Discovery.

Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations.

Diagnostic markers of acute encephalitis syndrome and COVID-associated multisystem inflammatory syndrome in children from Southern India.

Acute encephalitis syndrome (AES) in children poses a significant public health challenge in India. This study aims to explore the utility of host inflammatory mediators and neurofilament (NfL) levels in distinguishing etiologies, assessing disease severity, and predicting outcomes in AES. We assessed 12 mediators in serum (n = 58) and 11 in cerebrospinal fluid (CSF) (n = 42) from 62 children with AES due to scrub typhus, viral etiologies, and COVID-associated multisystem inflammatory syndrome (MIS-C) in Southern India. Additionally, NfL levels in serum (n = 20) and CSF (n = 18) were examined. Clinical data, including Glasgow coma scale (GCS) and Liverpool outcome scores, were recorded. Examining serum and CSF markers in the three AES etiology groups revealed notable distinctions, with scrub typhus differing significantly from viral and MIS-C causes. Viral causes had elevated serum CCL11 and CCL2 compared with scrub typhus, while MIS-C cases showed higher HGF levels than scrub typhus. However, CSF analysis showed a distinct pattern with the scrub typhus group exhibiting elevated levels of IL-1RA, IL-1ß, and TNF compared with MIS-C, and lower CCL2 levels compared with the viral group. Modeling the characteristic features, we identified that age ≥3 years with serum CCL11 < 180 pg/mL effectively distinguished scrub typhus from other AES causes. Elevated serum CCL11, HGF, and IL-6:IL-10 ratio were associated with poor outcomes (p = 0.038, 0.005, 0.02). Positive CSF and serum NfL correlation, and negative GCS and serum NfL correlation were observed. Median NfL levels were higher in children with abnormal admission GCS and poor outcomes. Measuring immune mediators and brain injury markers in AES provides valuable diagnostic insights, with the potential to facilitate rapid diagnosis and prognosis. The correlation between CSF and serum NfL, along with distinctive serum cytokine profiles across various etiologies, indicates the adequacy of blood samples alone for assessment and monitoring. The association of elevated levels of CCL11, HGF, and an increased IL-6:IL-10 ratio with adverse outcomes suggests promising avenues for therapeutic exploration, warranting further investigation.

Dynamic Nuclear Polarization Using Electron Spin Cluster.

Dynamic nuclear polarization (DNP) utilizing narrow-line electron spin clusters (ESCs) to achieve nuclear spin resonance matching (ESC-DNP) by microwave irradiation is a promising way to achieve NMR signal enhancements with a wide design scope requiring low microwave power at high magnetic field. Here we present the design for a trityl-based tetra-radical (TetraTrityl) to achieve DNP for 1H NMR at 7 T, supported by experimental data and quantum mechanical simulations. A slow-relaxing (T1e ≈ 1 ms) 4-ESC is found to require at least two electron spin pairs at <8 Å e-e spin distance to yield 1H ESC-DNP enhancement, while squeezing the rest of the e-e spin distances to <12 Å results in optimal 1H ESC-DNP enhancements. Fast-relaxing ESCs (T1e ≈ 10 µs) are found to require a weakly coupled narrow-line radical (sensitizer) to extract polarization from the ESC. These results provide design principles for achieving a power-efficient DNP at high field via ESC-DNP.