Chikungunya virus infection in human microglial C20 cells induces mitochondria-mediated apoptosis.

Introduction: Chikungunya virus (CHIKV) infection is associated with acute clinical manifestations and chronic joint inflammation. CHIKV has emerged as a significant causative agent of central nervous system (CNS) complications, including encephalitis and related sequelae. Microglial cells, crucial for immune responses and tissue repair in the CNS, play a vital role in the host response to viral infections, with their activation potentially leading to either protection or pathology. In this study, the infection biology of CHIKV in the C20 human microglial cell line was investigated. Methods: The permissiveness of C20 cells to CHIKV infection was assessed, and viral replication kinetics were compared to Vero E6 cells. Cytopathic effects of CHIKV infection on C20 cells were examined, along with ultrastructural changes using transmission electron microscopy. Additionally, apoptosis induction, mitochondrial membrane potential, and alterations in cell surface marker expression were evaluated by flow cytometry. Results: CHIKV infection demonstrated permissiveness in C20 cells, similar to Vero cells, resulting in robust viral replication and cytopathic effects. Ultrastructural analysis revealed viral replication, mature virion formation, and distinctive cytoplasmic and nuclear changes in infected C20 cells. CHIKV infection induced significant apoptosis in C20 cells, accompanied by mitochondrial membrane depolarization and altered expression of cell surface markers such as CD11c, CD14, and HLA-DR. Notably, decreased CD14 expression was observed in CHIKV-infected C20 cells. Discussion: The study findings suggest that CHIKV infection induces apoptosis in C20 microglial cells via the mitochondrial pathway, with significant alterations in cell surface marker expression, particularly CD14 that is linked with apoptosis induction. These observations provide valuable insights into the role of human microglial cells in the host response to CHIKV infection and contribute to the knowledge on the neuropathogenesis of this virus.

AAV mediated genome engineering with a bypass coagulation factor alleviates the bleeding phenotype in a murine model of hemophilia B.

It is crucial to develop a long-term therapy that targets hemophilia A and B, including inhibitor-positive patients. We have developed an Adeno-associated virus (AAV) based strategy to integrate the bypass coagulation factor, activated FVII (murine, mFVIIa) gene into the Rosa26 locus using Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 mediated gene-editing. AAV vectors designed for expression of guide RNA (AAV8-gRNA), Cas9 (AAV2 neddylation mutant-Cas9), and mFVIIa (AAV8-mFVIIa) flanked by homology arms of the target locus were validated in vitro. Hemophilia B mice were administered with AAV carrying gRNA, Cas9 (1 × 1011 vgs/mouse), and mFVIIa with homology arms (2 × 1011 vgs/mouse) with appropriate controls. Functional rescue was documented with suitable coagulation assays at various time points. The data from the T7 endonuclease assay revealed a cleavage efficiency of 20-42 %. Further, DNA sequencing confirmed the targeted integration of mFVIIa into the safe-harbor Rosa26 locus. The prothrombin time (PT) assay revealed a significant reduction in PT in mice that received the gene-editing vectors (22 %), and a 13 % decline in mice that received only the AAV-FVIIa when compared to mock treated mice, 8 weeks after vector administration. Furthermore, FVIIa activity in mice that received triple gene-editing vectors was higher (122.5mIU/mL vs 28.8mIU/mL) than the mock group up to 15 weeks post vector administration. A hemostatic challenge by tail clip assay revealed that hemophilia B mice injected with only FVIIa or the gene-editing vectors had significant reduction in blood loss. In conclusion, AAV based gene-editing facilitates sustained expression of coagulation FVIIa and phenotypic rescue in hemophilia B mice.

Challenges in IBD Research 2024: Novel Technologies.

Novel technology is one of the five focus areas of the Challenges in Inflammatory Bowel Disease (IBD) Research 2024 document. Building off the Challenges in IBD Research 2019 document, the Foundation aims to provide a comprehensive overview of current gaps in IBD research and deliver actionable approaches to address them with a focus on how these gaps can lead to advancements in interception, remission, and restoration for these diseases. The document is the result of a multidisciplinary collaboration from scientists, clinicians, patients, and funders and represents a valuable resource for patient-centric research prioritization. Specifically, the Novel Technologies section focuses on addressing key research gaps to enable interception and improve remission rates in IBD. This includes testing predictions of disease onset and progression, developing novel technologies tailored to specific phenotypes, and facilitating collaborative translation of science into diagnostics, devices, and therapeutics. Proposed priority actions outlined in the document include real-time measurement of biological changes preceding disease onset, more effective quantification of fibrosis, exploration of technologies for local treatment of fistulas, and the development of drug delivery platforms for precise, location-restricted therapies. Additionally, there is a strong emphasis on fostering collaboration between various stakeholders to accelerate progress in IBD research and treatment. Addressing these research gaps necessitates the exploration and implementation of bio-engineered novel technologies spanning a spectrum from materials to systems. By harnessing innovative ideas and technologies, there's a collective effort to enhance patient care and outcomes for individuals affected by IBD.

Technology drives medical progress, solving clinical challenges and enhancing patient care in inflammatory bowel disease (IBD). Collaborative efforts focus on addressing research gaps to improve interception, restoration, and remission rates, utilizing innovative technologies for better patient outcomes.

"Mpox in MSM: Tackling Stigma, Minimizing Risk Factors, Exploring Pathogenesis, and Treatment Approaches".

Mpox is a zoonotic disease caused by the monkeypox virus (MPV), primarily found in Central and West African countries. The typical presentation of the disease before the 2022 mpox outbreak includes a febrile prodrome 5-13 days post-exposure, accompanied by lymphadenopathy, malaise, headache, and muscle aches. Unexpectedly, during the 2022 outbreak, several cases of atypical presentations of the disease were reported, such as the absence of prodromal symptoms and the presence of genital skin lesions suggestive of sexual transmission. As per the World Health Organization (WHO), as of March 20, 2024, 94,707 cases of mpox were reported worldwide, resulting in 181 deaths (22 in African endemic regions and 159 in non-endemic countries). The United States Centers for Disease Control and Prevention (CDC) reports a total of 32,063 cases (33.85% of total cases globally), with 58 deaths (32.04% of global deaths) due to mpox. Person-to-person transmission of mpox can occur through respiratory droplets and sustained close contact. However, during the 2022 outbreak of mpox, a high incidence of anal and perianal lesions among MSMs indicated sexual transmission of MPV as a major route of transmission. Since MSMs are disproportionately at risk for HIV transmission, this review discusses the risk factors, transmission patterns, pathogenesis, vaccine, and treatment options for mpox among MSM and people living with HIV (PLWH). Furthermore, we provide a brief perspective on the evolution of the MPV in immunocompromised people like PLWH.

Identification of new stable resistant sources and assessing agro-morphological performance of sponge gourd germplasm against Tomato Leaf curl New Delhi Virus incidence.

Tomato leaf curl New Delhi virus (TolCNDV) causes yellow mosaic disease, which poses a significant biotic constraint for sponge gourd cultivation, potentially resulting in crop loss of up to 100%. In the present investigation, 50 diverse genotypes were screened for 3 years under natural epiphytotic conditions. A subset of 20 genotypes was further evaluated across four different environments. The combined analysis of variance revealed a significant genotype × environment interaction. Eight genotypes consistently exhibited high and stable resistance in the preliminary screening and multi-environment testing. Furthermore, genotype plus genotype × environment interaction biplot analysis identified DSG-29 (G-3), DSG-7 (G-2), DSG-6 (G-1), and DSGVRL-18 (G-6) as the desirable genotypes, which have stable resistance and better yield potential even under diseased conditions. The genotype by yield × trait biplot analysis and multi-trait genotype-ideotype distance index analysis further validated the potential of these genotypes for combining higher yield and other desirable traits with higher resistance levels. Additionally, resistant genotypes exhibited higher activities of defense-related enzymes as compared to susceptible genotypes. Thus, genotypes identified in our study will serve as a valuable genetic resource for carrying out future resistance breeding programs in sponge gourd against ToLCNDV.

Vestibular Schwannoma International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS Study.

PURPOSE: The present study assesses the safety and efficacy of stereotactic radiosurgery (SRS) versus observation for Koos grade 1 and 2 vestibular schwannoma (VS), benign tumors affecting hearing and neurological function. METHODS AND MATERIALS: This multicenter study analyzed data from Koos grade 1 and 2 VS patients managed with SRS (SRS group) or observation (observation group). Propensity score matching balanced patient demographics, tumor volume, and audiometry. Outcomes measured were tumor control, serviceable hearing preservation, and neurological outcomes. RESULTS: In 125 matched patients in each group with a 36-month median follow-up (P = .49), SRS yielded superior 5- and 10-year tumor control rates (99% CI, 97.1%-100%, and 91.9% CI, 79.4%-100%) versus observation (45.8% CI, 36.8%-57.2%, and 22% CI, 13.2%-36.7%; P < .001). Serviceable hearing preservation rates at 5 and 9 years were comparable (SRS 60.4% CI, 49.9%-73%, vs observation 51.4% CI, 41.3%-63.9%, and SRS 27% CI, 14.5%-50.5%, vs observation 30% CI, 17.2%-52.2%; P = .53). SRS were associated with lower odds of tinnitus (OR = 0.39, P = .01), vestibular dysfunction (OR = 0.11, P = .004), and any cranial nerve palsy (OR = 0.36, P = .003), with no change in cranial nerves 5 or 7 (P > .05). Composite endpoints of tumor progression and/or any of the previous outcomes showed significant lower odds associated with SRS compared with observation alone (P < .001). CONCLUSIONS: SRS management in matched cohorts of Koos grade 1 and 2 VS patients demonstrated superior tumor control, comparable hearing preservation rates, and significantly lower odds of experiencing neurological deficits. These findings delineate the safety and efficacy of SRS in the management of this patient population.

A Pilot Study on the Proteomics Profile of Serum Exosome-Enriched Extracellular Vesicles from Normal versus Individuals with Obesity-Related Insulin Resistance.

OBJECTIVE: Circulating exosome-enriched extracellular vesicles (EVs) have drawn considerable importance in obesity-related insulin-resistance (IR). We sought to compare the proteomics profile of serum exosomes from normal individuals and those with obesity and IR. METHODS: We isolated serum exosomes from male subjects with obesity and insulin resistance (Ob-IR, HOMA-IR > 2.0) and lean/overweight insulin-sensitive (Normal (N), HOMA-IR < 2.0) individuals. The differential protein expression between the two groups was detected by a label-free quantitative mass spectrometry analysis followed by GO annotation and ingenuity pathway analysis (IPA). RESULTS: We identified 23 upregulated and 46 downregulated proteins between Ob-IR and N groups. Some of these proteins are involved in altering insulin signaling (VPS13C, TBC1D32, TTR, and ADIPOQ), inflammation (NFκB and CRP), and B-cell proliferation/activation (IGLV4-69, IGKV1D-13, and IGHV4-28). GO analysis revealed that the differentially expressed proteins (DEPs) are mainly involved in regulating immune cell activation and are located in extracellular space. IPA analysis showed that top molecules mediating IR, inflammation and B-cell activation were upregulated in Ob-IR subjects compared to N subjects. CONCLUSIONS: Serum exosomal proteins can be used as biomarkers to identify the future risk of diabetes and a therapeutic target to prevent or slow down the progression of diabetes in high-risk individuals.

The efficient applications of native flora for phytorestoration of mine tailings: a pan-global survey.

Mine tailings are the discarded materials resulting from mining processes after minerals have been extracted. They consist of leftover mineral fragments, excavated land masses, and disrupted ecosystems. The uncontrolled handling or discharge of tailings from abandoned mine lands (AMLs) poses a threat to the surrounding environment. Numerous untreated mine tailings have been abandoned globally, necessitating immediate reclamation and restoration efforts. The limited feasibility of conventional reclamation methods, such as cost and acceptability, presents challenges in reclaiming tailings around AMLs. This study focuses on phytorestoration as a sustainable method for treating mine tailings. Phytorestoration utilizes existing native plants on the mine sites while applying advanced principles of environmental biotechnology. These approaches can remediate toxic elements and simultaneously improve soil quality. The current study provides a global overview of phytorestoration methods, emphasizing the specifics of mine tailings and the research on native plant species to enhance restoration ecosystem services.

Physiological and molecular insights into the allelopathic effects on agroecosystems under changing environmental conditions.

Allelopathy is a natural phenomenon of competing and interfering with other plants or microbial growth by synthesizing and releasing the bioactive compounds of plant or microbial origin known as allelochemicals. This is a sub-discipline of chemical ecology concerned with the effects of bioactive compounds produced by plants or microorganisms on the growth, development and distribution of other plants and microorganisms in natural communities or agricultural systems. Allelochemicals have a direct or indirect harmful effect on one plant by others, especially on the development, survivability, growth, and reproduction of species through the production of chemical inhibitors released into the environment. Cultivation systems that take advantage of allelopathic plants' stimulatory/inhibitory effects on plant growth and development while avoiding allelopathic autotoxicity is critical for long-term agricultural development. Allelopathy is one element that defines plant relationships and is involved in weed management, crop protection, and microbial contact. Besides, the allelopathic phenomenon has also been reported in the forest ecosystem; however, its presence depends on the forest type and the surrounding environment. In the present article, major aspects addressed are (1) literature review on the impacts of allelopathy in agroecosystems and underpinning the research gaps, (2) chemical, physiological, and ecological mechanisms of allelopathy, (3) genetic manipulations, plant defense, economic benefits, fate, prospects and challenges of allelopathy. The literature search and consolidation efforts in this article shall pave the way for future research on the potential application of allelopathic interactions across various ecosystems.

The relevance of biologically effective dose for pain relief and sensory dysfunction after Gamma Knife radiosurgery for trigeminal neuralgia: an 871-patient multicenter study.

OBJECTIVE: Recent studies have suggested that biologically effective dose (BED) is an important correlate of pain relief and sensory dysfunction after Gamma Knife radiosurgery (GKRS) for trigeminal neuralgia (TN). The goal of this study was to determine if BED is superior to prescription dose in predicting outcomes in TN patients undergoing GKRS as a first procedure. METHODS: This was a retrospective study of 871 patients with type 1 TN from 13 GKRS centers. Patient demographics, pain characteristics, treatment parameters, and outcomes were reviewed. BED was compared with prescription dose and other dosimetric factors for their predictive value. RESULTS: The median age of the patients was 68 years, and 60% were female. Nearly 70% of patients experienced pain in the V2 and/or V3 dermatomes, predominantly on the right side (60%). Most patients had modified BNI Pain Intensity Scale grade IV or V pain (89.2%) and were taking 1 or 2 pain medications (74.1%). The median prescription dose was 80 Gy (range 62.5-95 Gy). The proximal trigeminal nerve was targeted in 77.9% of cases, and the median follow-up was 21 months (range 6-156 months). Initial pain relief (modified BNI Pain Intensity Scale grades I-IIIa) was noted in 81.8% of evaluable patients at a median of 30 days. Of 709 patients who achieved initial pain relief, 42.3% experienced at least one pain recurrence after GKRS at a median of 44 months, with 49.0% of these patients undergoing a second procedure. New-onset facial numbness occurred in 25.3% of patients after a median of 8 months. Age ≥ 63 years was associated with a higher probability of both initial pain relief and maintaining pain relief. A distal target location was associated with a higher probability of initial and long-term pain relief, but also a higher incidence of sensory dysfunction. BED ≥ 2100 Gy2.47 was predictive of pain relief at 30 days and 1 year for the distal target, whereas physical dose ≥ 85 Gy was significant for the proximal target, but the restricted range of BED values in this subgroup could be a confounding factor. A maximum brainstem point dose ≥ 29.5 Gy was associated with a higher probability of bothersome facial numbness. CONCLUSIONS: BED and physical dose were both predictive of pain relief and could be used as treatment planning goals for distal and proximal targets, respectively, while considering maximum brainstem point dose < 29.5 Gy as a potential constraint for bothersome numbness.

AMMI and GGE biplot analysis of genotype by environment interaction for yield and yield contributing traits in confectionery groundnut.

The global market has a high demand for premium edible grade groundnut, particularly for table use. India, in particular, exhibits significant potential for exporting confectionary grade large seeded groundnut. The environment plays a significant impact in influencing the expression of seed traits, which subsequently affects the confectionary quality of groundnut genotypes. The states of Gujarat and Rajasthan in India are prominent producers of high-quality groundnuts specifically used for confectionary purposes. The current study was conducted with 43 confectionery groundnut genotypes at Junagadh, Gujarat, and Bikaner, Rajasthan, with the goals of understanding genotype-by-environment interaction (GEI) effects and identifying stable, high yielding confectionery quality groundnut genotypes using AMMI and GGE biplot models. Pod yield per plant (PYP), number of pods per plant (NPP), hundred kernel weight (HKW), and shelling percent (SP) were estimated. The interplay between the environment and genotype has had a notable impact on the manifestation of confectionary grade characteristics in peanuts. The results from the Interaction Principal Component Analysis (IPCA) indicate that HKW contributed 76.68% and 18.95% towards the Global Environmental Index (GEI) through IPCA1 and IPCA2, respectively. Similarly, NPP contributed 87.52% and 8.65%, PYP contributed 95.87% and 2.1%, and SP contributed 77.4% and 16.22% towards GEI through IPCA1 and IPCA2, respectively. Based on the ranking of genotypes, the ideal genotypes were PBS 29079B for HKW, PBS 29230 for NPP. The genotypes PBS 29233 and PBS 29230 exhibited superior performance and stability in terms of pod yield, hundred kernel weight, number of pods per plant, and shelling percentage across various sites. These breeding lines have the potential to be developed for the purpose of producing confectionary grade groundnut with larger seeds, in order to fulfil the growing demand for export.

Pediatric cerebral cavernous malformations and stereotactic radiosurgery: an analysis of 50 cases from a multicentric study.

OBJECTIVE: Cerebral cavernous malformations (CCMs) are the second most common vascular anomaly affecting the CNS in children. Although stereotactic radiosurgery (SRS) has been proposed as an alternative to microsurgery in the management of selected cases in adults, there is a paucity of studies focusing on pediatric patients. The aim of this study was to present the outcomes and associated risks of SRS in this subgroup of patients. METHODS: This retrospective multicenter study included pediatric patients treated with single-session SRS for CCMs. The annual hemorrhage rate (AHR) was calculated before and after SRS in hemorrhagic lesions. The Engel classification was used to describe post-SRS epileptic control. Adverse radiation effects (AREs) and the occurrence of new neurological deficits were recorded. RESULTS: The study included 50 patients (median age 15.1 [IQR 5.6] years) harboring 62 CCMs. Forty-two (84%) and 22 (44%) patients had a history of hemorrhage or epilepsy prior to SRS, respectively. The AHR from diagnosis to SRS excluding the first hemorrhage was 7.19 per 100 CCM-years, dropping to 3.15 per 100 CCM-years after treatment. The cumulative risk of first hemorrhage after SRS was 7.4% (95% CI 0%-14.3%) at 5 years and 23.6% (95% CI 0%-42.2%) at 10 years. Eight hemorrhagic events involving 6 CCMs in 6 patients were recorded in the post-SRS follow-up period; 4 patients presented with transient symptoms and 4 with permanent symptoms. Of the 22 patients with pre-SRS seizures, 11 were seizure free at the last follow-up (Engel class I), 6 experienced improvement (Engel class II or III), 5 had no improvement (Engel class IVA or IVB), and 1 experienced worsening (Engel class IVC). Radiographic AREs were documented in 14.5% (9/62) of CCMs, with 4 being symptomatic. CONCLUSIONS: Single-session SRS reduces the CCM hemorrhage rate in the pediatric population and provides adequate seizure control.

Densitometric method for assessment of six specialized metabolites in four Sida sp. and its congener Abutilon indicum: Targeted metabolomics, greenness assessment, and chemometrics analysis.

Sida is one of the most diverse genera, with about 200 species distributed in tropical and subtropical regions of the world. Among 18 species distributed in India, Sida acuta, Sida cordifolia, Sida rhombifolia, and Sida cordata are used in traditional medicines along with its possible adulterant Abutilon indicum for several therapeutic uses. The non-availability of marker-based validated methods for the identification and classification of these species leads to adulteration. Indoloquinoline and quinazoline are the major bioactive alkaloids distributed in Sida spp. First time, a simple, economical and high throughput method was developed and validated for the simultaneous determination of 20-hydroxyecdysone (1), vasicine (2), vasicinone (3), cryptolepine (4), quindolinone (5), and cryptolepinone (6) using HPTLC-UV densitometry. The method was validated to meet globally accepted ICH guidelines. The method was sensitive with LOD and LOQ ranging from 0.38-0.63 and 1.57-2.12 µg/band. The samples were spiked at 3 different concentrations, the recovery values were 93.49-98.88%. In addition, the greenness index of the HPTLC method was estimated using four different greenness assessment techniques. Targeted HPTLC analysis indicated the distribution of specialized metabolites in Sida spp. and A. indicum. However, the occurrence of cryptolepine in A. indicum was not reported in the literature, so this was further confirmed by liquid chromatographic studies of the samples from different locations. The chromatographic data was statistically evaluated by principal component analysis (PCA) and hierarchical clustering (HCA). HPTLC-based targeted metabolite quantitation explains the adulteration/substitution in Sida raw material and derived herbal preparations.

16S rRNA metagenomic profiling of red amaranth grown organically with different composts and soils.

In recent years organic food is gaining popularity as it is believed to promote better human health and improve soil sustainability, but there are apprehensions about pathogens in organic produces. This study was designed to understand the effect of different composts and soils on the status of the microbiome present in organically grown leafy vegetables. 16S rRNA metagenomic profiling of the leaves was done, and data were analyzed. It was found that by adding composts, the OTU of the microbiome in the organic produce was higher than in the conventional produce. The beneficial genera identified across the samples included plant growth promoters (Achromobacter, Paenibacillus, Pseudomonas, Sphingobacterium) and probiotics (Lactobacillus), which were higher in the organic produce. Some pathogenic genera, viz., plant pathogenic bacteria (Cellvibrio, Georgenia) and human pathogenic bacteria (Corynebacterium, Acinetobacter, Streptococcus, Streptomyces) were also found but with relatively low counts in the organic produce. Thus, the present study highlights that organic produce has lesser pathogen contamination than the conventional produce. KEY POINTS: • 16S rRNA metagenomics profiling done for organic red amaranth cultivar • Microbial richness varied with respect to the soil and compost type used • The ratio of beneficial to pathogenic genera improves with the addition of compost.

Unveiling the potential of membrane in climate change mitigation and environmental resilience in ecosystem.

Carbon capture technologies are becoming increasingly crucial in addressing global climate change issues by lowering CO2 emissions from industrial and power generation activities. Post-combustion carbon capture, which uses membranes instead of adsorbents, has emerged as one of promising and environmentally friendly approaches among these technologies. The operation of membrane technology is based on the premise of selectively separating CO2 from flue gas emissions. This provides a number of different benefits, including improved energy efficiency and decreased costs of operation. Because of its adaptability to changing conditions and its low impact on the surrounding ecosystem, it is an appealing choice for a diverse array of uses. However, there are still issues to be resolved, such as those pertaining to establishing a high selectivity, membrane degradation, and the costs of the necessary materials. In this article, we evaluate and explore the prospective applications and roles of membrane technologies to control climate change by post-combustion carbon capturing. The primary proposition suggests that the utilization of membrane-based carbon capture has the potential to make a substantial impact in mitigating CO2 emissions originating from industrial and power production activities. This is due to its heightened ability to selectively absorb carbon, better efficiency in energy consumption, and its flexibility to various applications. The forthcoming challenges and potential associated with the application of membranes in post-carbon capture are also discussed.

Clinical outcomes following stereotactic radiosurgery for cerebral cavernous malformations of the basal ganglia and thalamus.

OBJECTIVE: There are few reports of outcomes following stereotactic radiosurgery (SRS) for the management of cerebral cavernous malformations (CCMs) of the basal ganglia or thalamus. Therefore, the authors aimed to clarify these outcomes. METHODS: Centers participating in the International Radiosurgery Research Foundation were queried for CCM cases managed with SRS from October 2001 to February 2021. The primary outcome of interest was hemorrhage-free survival (HFS) with a secondary outcome of symptomatic adverse radiation events (AREs). Assessment of the association of prognostic factors with HFS was conducted via Kaplan-Meier analysis and log-rank test. Chi-square tests were conducted to assess potential factors associated with the incidence of AREs. RESULTS: Seventy-three patients were identified. The median patient age was 43.5 years (range 4.4-79.5 years). Fifty-nine (80.8%) patients had hemorrhage prior to SRS. The median treatment volume was 0.9 cm3 (range 0.07-10.1 cm3) with a median margin prescription dose (MPD) of 12 Gy (range 10-20 Gy). One-, 3-, 5-, and 10-year HFS were 93.0%, 89.9%, 89.9%, and 83.0%, respectively, with one hemorrhage-related death approximately 1 year after SRS and nearly 60% and 30% of patients having improvement or stability of symptoms, respectively. There was no correlation between lesion size or MPD and HFS. Seven (9.6%) patients experienced AREs (MPDs > 12 Gy in all cases). Lesion size > 1.0 cm3 was correlated with the incidence of an ARE (p = 0.019). Forty-two (93.3%) of 45 patients treated with an MPD ≤ 12 Gy experienced neither hemorrhage nor AREs following SRS versus 17 (60.7%) of 28 patients treated with an MPD > 12 Gy (p = 0.0006). CONCLUSIONS: SRS is a reasonable treatment strategy and confers clinical stability or improvement and hemorrhage avoidance in patients harboring CCMs of the basal ganglia or thalamus. An MPD of approximately 12 Gy is recommended for the management of CCM.

Inducible caspase 9-mediated suicide gene therapy using AAV6 vectors in a murine model of breast cancer.

Breast carcinoma has one of the highest incidence rates (11.7%), with significant clinical heterogeneity. Although conventional chemotherapy and surgical resection are the current standard of care, the resistance and recurrence, after these interventions, necessitate alternate therapeutic approaches. Cancer gene therapy for breast cancer with the suicide gene is an attractive option due to their directed delivery into the tumor. In this study, we have developed a novel treatment strategy against breast cancer with recombinant adeno-associated virus (AAV) serotype 6 vectors carrying a suicide gene, inducible Caspase 9 (iCasp9). Upon treatment with AAV6-iCasp9 vectors and the chemical inducer of dimerizer, AP20187, the viability of murine breast cancer cells (4T1) was significantly reduced to ∼40%-60% (mock control 100%). Following intratumoral delivery of AAV6-iCasp9 vectors in an orthotopic breast cancer mouse model, we observed a significant increase in iCasp9 transgene expression and a significant reduction in tumor growth rate. At the molecular level, immunohistochemical analysis demonstrated subsequent activation of the effector caspase 3 and cellular death. These data highlight the potential of AAV6-iCasp9-based suicide gene therapy for aggressive breast cancer in patients.

Assessing the climate change impact on the habitat suitability of the range-restricted bird species (Catreus wallichii) in the Indian Himalayan ecosystem.

Climate change profoundly impacts ecosystems' function and composition, changing living organisms' habitats. The Indian Himalayan ecosystem (IHE) is particularly susceptible and vulnerable to the effects of climate change. However, our understanding of how climate change affects the habitats of range-restricted and vulnerable avifauna in the IHE still needs to be improved. Hence, we employed ensemble species distribution modelling to examine the potential habitat shift of the cheer pheasant (Catreus wallichii) under climate change scenarios (representative concentration pathways, RCPs) i.e. RCP 4.5, RCP 6.0 and RCP 8.5) by 2050 and 2070. The study revealed a noticeable expansion of climatically suitable habitats, indicating a shift towards higher altitudes that would become more favourable and suitable under future climates. The model predicted an area of very highly suitable habitat (1247.4 km2), followed by highly suitable (2747.9 km2), moderately suitable (4002.3 km2), low suitable (4952.2 km2) and rarely suitable (4236 km2) in the current scenario. The projection of larger areas was falling into the "no change", followed by the "high suitable" and "low suitable" classes, for both the years 2050 and 2070 across all the RCPs. Furthermore, the projections indicated a consistent trend of increasing suitability for the cheer pheasant at higher elevations and a decline at lower elevations across RCPs for 2050 and 2070. Moreover, the mean diurnal temperature range was identified as the crucial driving factor, followed by isothermally and precipitation, influencing the species' shift towards suitable habitats at higher altitudes. The study can aid policymakers in developing effective conservation strategies to protect Himalayan range-restricted bird species in the face of climate change.

Short- and Long-Term Retentivity of Knowledge by Various Teaching Methods in Medical Education and Perception of Students Towards Them: A Comparative Study in a Medical University Hospital of Northern India.

BACKGROUND: To develop doctors with appropriate knowledge of health and diseases, reasonable medical abilities, and a positive attitude toward patients and their families, it is important to reexamine the methods used to educate and train medical school students. To establish which is best for both medical students and professors, the various teaching and learning methodologies must be compared and analyzed. This study attempts to determine the preferred medical education techniques among medical students as well as the caliber of the classes they attend. METHODS: This is a before-and-after study conducted among 480 first- (240) and second-year (240) undergraduate students. Students were divided into three groups. Each group was assigned a teacher who was responsible for teaching four short topics according to the common understanding and knowledge level of both year students in four different ways: traditional blackboard method, offline PowerPoint presentation, online PowerPoint presentation, and online annotative. Application-based learning and self-learning were the other two teaching methods conducted in a monitored environment. An MCQ-based pre- and post-test were taken to assess the improvement, and a feedback form was filled out by each student to assess their perception. To assess long-term retention, a surprise follow-up test was conducted after 15 days. RESULTS: For all the teaching methods except for traditional blackboard and online presentation, there was a significant improvement in the post-test scores as compared to the pre-test scores (p<0.05). Retentivity was more remarkable in online application-based and self-learning methods. 77.2% of the study participants preferred offline presentation as the mode of teaching. CONCLUSION: Retention was found to be highest in self-directed and application-based learning. So, students should be encouraged and motivated for self-study after every lecture, whatever the teaching method used by teachers.