Multi-trait stability index for identification of stable green gram (Vigna radiata (L.) Wilczek) genotypes with MYMV resistance.

Multi-environment trials (MET) are crucial for selecting genotypes that are well-suited to different environmental conditions. Incorporating multiple traits in the analysis can provide more reliable recommendations for selecting genotypes with desirable traits, including resistance to the Mungbean Yellow Mosaic Virus (MYMV) and high yield potential. The use of a Multi-Trait Stability Index (MTSI) is a good approach for analyzing the stability of genotypes across multiple traits under MYMV stress. In the present investigation, the performance of thirteen green gram genotypes were evaluated for traits such as yield, plant height, number of branches per plant, and resistance to MYMV. The main objective of the study is to identify highly productive and stable mung bean genotypes resistant to MYMV. MTSI can be calculated by combining information on the performance of genotypes across multiple traits and environmental conditions to provide a single index that indicates the overall stability of genotypes across traits and environments. The results helped to identify two green gram genotypes (Yadadri and JNG-18) that were high-yielding with stable resistance to MYMV stress across multiple environmental conditions. This can provide useful information to breeders for the development of suitable genotypes against MYMV in the affected areas.

Mechanisms of Medial Wall Thinning in Chronic Total Occlusion.

BACKGROUND: The success rate of percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) is lower and the risk for complications higher compared with other non-CTO PCI. Although interventionalists focus on intimal plaque characteristics, the coronary media is an important (especially for techniques involving antegrade dissection and re-entry) but poorly understood structure in CTO PCI. OBJECTIVES: The aim of the present study was to investigate coronary medial wall thinning in CTO lesions and determine how this thinning might affect CTO PCI. METHODS: A total of 2,586 sections were investigated, from arteries with evidence of CTO from 54 subjects (1,383 sections) and arteries without evidence of CTO from 54 subjects with non-coronary-related deaths (1,203 sections) after matching for age, gender, body weight, and body height. RESULTS: The medial thickness in subjects with CTO was lower than that in those with non-coronary-related death (P < 0.001). In subjects with CTO, CTO lesions had thinner medial walls compared with those with lower luminal narrowing (P < 0.001). At the CTO distal segments, the 6- to 12-mm distal segment from the distal end of the CTO had significantly less luminal narrowing (P < 0.001), and similar medial thickness, compared with the distal end of the CTO. Immunohistochemical analysis revealed that short-duration CTO had more cleaved caspase-3-positive cells in media and had significantly more CD3+, CD4+, CD8+, and CD4+CD28null T cells compared with long-duration CTO. CONCLUSIONS: CTO lesions demonstrated coronary medial thinning compared with non-CTO lesions. Further investigation of the cause-and-effect relationship among inflammation, apoptosis, and coronary medial wall thinning is warranted in future mechanistic studies.

Mammalian cell expressed recombinant trimeric spike protein is a potent vaccine antigen and confers near-complete protection against SARS-CoV-2 infection in Hamster.

Numerous vaccine candidates have emerged in the fight against SARS-CoV-2, yet the challenges posed by viral evolution and the evasion of vaccine-induced immunity persist. The development of broadly protective vaccines is essential in countering the threat posed by variants of concern (VoC) capable of eluding existing vaccine defenses. Among the diverse SARS-CoV-2 vaccine candidates, detailed characterization of those based on the expression of the entire spike protein in mammalian cells have been limited. In our study, we engineered a recombinant prefusion-stabilized trimeric spike protein antigen, IMT-CVAX, encoded by the IMT-C20 gene. This antigen was expressed utilizing a suspension mammalian cell line (CHO-S). The establishment of a stable cell line expressing IMT-CVAX involved the integration of the gene into the CHO genome, followed by the expression, purification, and characterization of the protein. To gauge the vaccine potential of adjuvanted IMT-CVAX, we conducted assessments in small animals. Analyses of blood collected from immunized animals included measurements of anti-spike IgG, SARS-CoV-2 neutralization, and responses from GC-B and Tfh cells. Furthermore, the protective efficacy of IMT-CVAX was evaluated using a Hamster challenge model. Our findings indicate that adjuvanted IMT-CVAX elicits an excellent immune response in both mice and hamsters. Notably, sera from animals immunized with IMT-CVAX effectively neutralize a diverse range of SARS-CoV-2 variants. Moreover, IMT-CVAX immunization conferred complete protection to hamsters against SARS-CoV-2 infection. In hACE2 transgenic mice, IMT-CVAX vaccination induced a robust response from GC-B and Tfh cells. Based on our preclinical model assessments, adjuvanted IMT-CVAX emerges as a highly efficacious vaccine candidate. This protein-subunit-based vaccine exhibits promise for clinical development, offering an affordable solution for both primary and heterologous immunization against SARS-CoV-2 variants.

Novel dihydropyrimidines as promising EGFR & HER2 inhibitors: Insights from experimental and computational studies.

Dihydropyrimidines are widely recognized for their diverse biological properties and are often synthesized by the Biginelli reactions. In this backdrop, a novel series of Biginelli dihydropyrimidines were designed, synthesized, purified, and analyzed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. Anticancer activity against MCF-7 breast cancer cells was evaluated as part of their cytotoxicity in comparison with the normal Vero cells. The cytotoxicity of dihydropyrimidines ranges from moderate to significant. Among the 38 dihydropyrimidines screened, compounds 16, 21, and 39 exhibited significant cytotoxicity. These 3 compounds were subjected to flow cytometry studies and EGFRwt Kinase inhibition assay using lapatinib as a standard. The study included evaluation for the inhibition of EGFR and HER2 expression at five different concentrations. At a concentration of 1000 nM compound 21 showed 98.51 % and 96.79 % inhibition of EGFR and HER2 expression. Moreover, compounds 16, 21 and 39 significantly inhibited EGFRwt activity with IC50 = 69.83, 37.21 and 76.79 nM, respectively. In addition, 3D-QSAR experiments were conducted to elucidate Structure activity relationships in a 3D grid space by comparing the experimental and predicted cytotoxic activities. Molecular docking studies were performed to validate the results by in silico method. All together, we developed a new series of Biginelli dihydropyrimidines as dual EGFR/HER2 inhibitors.

Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma.

Medulloblastoma is a type of brain cancer that primarily affects children. While chemotherapy has been shown to be effective in treating medulloblastoma, the development of chemotherapy resistance remains a challenge. One potential therapeutic approach is to selectively inhibit the inducible transcription factor called STAT3, which is known to play a crucial role in the survival and growth of tumor cells. The activation of STAT3 has been linked to the growth and progression of various cancers, including medulloblastoma. Inhibition of STAT3 has been shown to sensitize medulloblastoma cells to chemotherapy, leading to improved treatment outcomes. Different approaches to STAT3 inhibition have been developed, including small-molecule inhibitors and RNA interference. Preclinical studies have shown the efficacy of STAT3 inhibitors in medulloblastoma, and clinical trials are currently ongoing to evaluate their safety and effectiveness in patients with various solid tumors, including medulloblastoma. In addition, researchers are also exploring ways to optimize the use of STAT3 inhibitors in combination with chemotherapy and identify biomarkers that can predict treatment that will help to develop personalized treatment strategies. This review highlights the potential of selective inhibition of STAT3 as a novel approach for the treatment of medulloblastoma and suggests that further research into the development of STAT3 inhibitors could lead to improved outcomes for patients with aggressive cancer.

Antibacterial Activity of the Vancomycin and Cefotaxime-Incorporated Total Etch Adhesive System - An In Vitro Study.

Background: Marginal failure at the resin dentin interface promotes biofilm formation, which further leads to secondary caries and hypersensitivity. This likelihood also increases if residual bacteria are present following cavity preparation. In order to achieve a proper biological seal without jeopardizing bonding, efforts were made to functionalize the adhesive system with antibacterial activity. Aim and objectives: To appraise the antibacterial activity of a total-etch adhesive system against S. mutans with and without incorporation of antibiotics Vancomycin and Cefotaxime. Materials and Method: A commercially available 5th-generation total-etch bonding agent (Te-Econorm) was used. S. mutans broth had been standardized and streaked over Muller-Hinton agar culture medium and round wells about 6 mm in diameter were made in the centre of the agar plates. Each experimental group comprised 10 samples, which include: Group 1 - 30µg Cefotaxime, Group 2- 30µg Cefotaxime + Bonding agent, Group 3- 30µg Vancomycin, Group 4- 30µg Vancomycin + Bonding agent, Group 5- Bonding agent, and Group 6- No material. Inoculated culture plates were examined for the zone of inhibition after incubation at 37° C for 24 hours. Results: There was a significant difference in the mean diameter of zone of inhibition (p=0.000), with the maximum exhibited by Group 4, followed by Group 3 and Group 2. The least zone of inhibition was exhibited by Groups 1 and 5. The negative control showed no zone of inhibition. Conclusion: The combination of Vancomycin and bonding agent had superior antibacterial activity against S. mutans in comparison to cefotaxime and bonding agent.

CD163+ Macrophages Induce Endothelial-to-Mesenchymal Transition in Atheroma.

BACKGROUND: Cell phenotype switching is increasingly being recognized in atherosclerosis. However, our understanding of the exact stimuli for such cellular transformations and their significance for human atherosclerosis is still evolving. Intraplaque hemorrhage is thought to be a major contributor to plaque progression in part by stimulating the influx of CD163+ macrophages. Here, we explored the hypothesis that CD163+ macrophages cause plaque progression through the induction of proapoptotic endothelial-to-mesenchymal transition (EndMT) within the fibrous cap. METHODS: Human coronary artery sections from CVPath's autopsy registry were selected for pathological analysis. Athero-prone ApoE-/- and ApoE-/-/CD163-/- mice were used for in vivo studies. Human peripheral blood mononuclear cell-induced macrophages and human aortic endothelial cells were used for in vitro experiments. RESULTS: In 107 lesions with acute coronary plaque rupture, 55% had pathological evidence of intraplaque hemorrhage in nonculprit vessels/lesions. Thinner fibrous cap, greater CD163+ macrophage accumulation, and a larger number of CD31/FSP-1 (fibroblast specific protein-1) double-positive cells and TUNEL (terminal deoxynucleotidyl transferase-dUTP nick end labeling) positive cells in the fibrous cap were observed in nonculprit intraplaque hemorrhage lesions, as well as in culprit rupture sections versus nonculprit fibroatheroma sections. Human aortic endothelial cells cultured with supernatants from hemoglobin/haptoglobin-exposed macrophages showed that increased mesenchymal marker proteins (transgelin and FSP-1) while endothelial markers (VE-cadherin and CD31) were reduced, suggesting EndMT induction. Activation of NF-κB (nuclear factor kappa ß) signaling by proinflammatory cytokines released from CD163+ macrophages directly regulated the expression of Snail, a critical transcription factor during EndMT induction. Western blot analysis for cleaved caspase-3 and microarray analysis of human aortic endothelial cells indicated that apoptosis was stimulated during CD163+ macrophage-induced EndMT. Additionally, CD163 deletion in athero-prone mice suggested that CD163 is required for EndMT and plaque progression. Using single-cell RNA sequencing from human carotid endarterectomy lesions, a population of EndMT was detected, which demonstrated significant upregulation of apoptosis-related genes. CONCLUSIONS: CD163+ macrophages provoke EndMT, which may promote plaque progression through fibrous cap thinning.

Geochemical fractionation, bioavailability, and ascertaining ecological risk of phosphorus in surface and core sediments of mangroves, western coast of India.

Phosphorus (P), a crucial macronutrient, is essential in the maintenance of ecosystem productivity and the biogeochemical processes of other biogenic substances found in marine settings. The aim of the present study is to quantify the different geochemical fractions, bioavailability, and ecological risk of phosphorus in surface and core sediment of mangroves, Gulf of Kachchh (GoK). To better understand the P dynamics, sequential chemical extraction techniques were used to study sediment P pool distribution such as exchangeable P; Fe-bound P; authigenic P; detrital P; and organic P. The total sedimentary P ranged from 539.51 to 7217.24 mg/kg in pre-monsoon and 487.04 to 7180.26 mg/kg in post-monsoon, and was primarily composed of inorganic P. Authigenic P and Fe-bound P were the dominant fractions of P in surface and core sediments, exhibiting a significant long-term P reservoir. Sources such as riverine inputs, industrial and sewage discharge, aquaculture farms, and seaport operations all have an impact on the P dynamics in GoK. Furthermore, organic matter, pH, ORP, and diagenetic processes in sedimentary environment have influenced P retention and release. FeBD:Fe-P ratio indicates the presence of Fe matrices, having strong adsorption potential for P, with the availability of a surplus of Fe(III) (oxy)hydroxides serving as a significant P pool, governing the P dynamics. The P enrichment index (PEI) showed that sediments were highly impacted by anthropogenic P and could cause a high ecological risk. Bioavailable phosphorus (BAP) suggests the availability of an ample amount of bioavailable P fractions (average of 49.70% post-monsoon and 44.64% post-monsoon) in surface sediments. Sites 3, 13, 14, 20, 21, and 26 exhibited considerably higher BAP. Core 1 comprised significantly higher BAP (60.52%). Thus, sediments of GoK could act as a source of P to the overlying water if released from sediments.

Noncovalent synthesis of homo and hetero-architectures of supramolecular polymers via secondary nucleation.

The synthesis of supramolecular polymers with controlled architecture is a grand challenge in supramolecular chemistry. Although living supramolecular polymerization via primary nucleation has been extensively studied for controlling the supramolecular polymerization of small molecules, the resulting supramolecular polymers have typically exhibited one-dimensional morphology. In this report, we present the synthesis of intriguing supramolecular polymer architectures through a secondary nucleation event, a mechanism well-established in protein aggregation and the crystallization of small molecules. To achieve this, we choose perylene diimide with 2-ethylhexyl chains at the imide position as they are capable of forming dormant monomers in solution. Activating these dormant monomers via mechanical stimuli and hetero-seeding using propoxyethyl perylene diimide seeds, secondary nucleation event takes over, leading to the formation of three-dimensional spherical spherulites and scarf-like supramolecular polymer heterostructures, respectively. Therefore, the results presented in this study propose a simple molecular design for synthesizing well-defined supramolecular polymer architectures via secondary nucleation.

Investigation of bisindole-linked pyrimidine moieties: synthesis using strantium-aluminum supported strontium aluminate nanophosphors catalyst, DNA reactivity, and in silico molecular docking studies.

In this communication, an innovative and straightforward protocol for the one-pot catalytic synthesis of bis(indolyl)pyrimidine derivatives and their DNA binding abilities is presented. The synthesis involves the condensation of indole with diverse substituted pyrimidine-5-carbaldehydes, employing cost-effective and reusable Sr-Al supported nanophosphors, specifically strontium aluminate (SrAl2O4), as a catalyst. In particular, this method does not require the use of toxic solvents. The Sr-Al supported nanophosphorus catalyst exhibited sustained activity over multiple cycles and showed no significant decline while maintaining its strictly heterogeneous properties. The bis(indolyl)pyrimidine derivatives were extensively characterized using spectroscopic and analytical techniques. Furthermore, the interaction between these derivatives and CT-DNA was investigated by absorption spectroscopy, viscosity measurement, and in silico molecular docking studies. Photoinduced cleavage studies demonstrated the photonuclease activity of the compound against pUC19 DNA upon exposure to UV-visible radiation.

A site-specific phosphorylation in FSTL1 determines its promigratory role in wound healing.

Follistatin like-1 (FSTL-1) is a secreted glycoprotein of mesenchymal in origin. In human skin, FSTL1 is upregulated in the epidermal keratinocytes upon acute injury and is required for the migration of keratinocytes. Failure to upregulate FSTL1 leads to the lack of keratinocyte migration and the non-healing nature of diabetic foot ulcer (DFU). FSTL1 undergoes extensive post-translational modification (PTM) at specific residues. Glycosylation at N144, N175 and N180, are the only experimentally demonstrated PTM in FSTL1, wherein, N180 and N144 glycosylations have been found to be critical for its function in cardiac tissue regeneration and pre-adipocyte differentiation, respectively. However, it is not known if PTMs other than glycosylation occurs in FSTL1 and how it impacts its pro-migratory function. Using in-silico analysis of mass spectrometric datasets, we found a novel PTM, namely, Serine 165 (S165) phosphorylation in FSTL1. To address the role of S165 phosphorylation in its pro-migratory function, a phosphorylation defective mutant of FSTL1 (S165A) was constructed by converting serine 165 to alanine and over expressed in 293T cells. S165A mutation did not affect the secretion of FSTL1 in vitro. However, S165A abolished the pro-migratory effect of FSTL1 in cultured keratinocytes likely via its inability to facilitate ERK signaling pathway. Interestingly, bacterially expressed recombinant FSTL1, trans-dominantly inhibited wound closure in keratinocytes highlighting the prime role of FSTL1 phosphorylation for its pro-migratory function. Further, under high glucose conditions, which inhibited scratchwound migration of keratinocytes, we noticed a significant decrease in S165 phosphorylation. Taken together, our results reveal a hitherto unreported role of FSTL1 phosphorylation PTM with profound implications in wound healing.

Probing the influence of strontium doping and annealing temperature on the structure and biocompatibility of hydroxyapatite nanorods.

Among numerous biologically important metal cations, strontium (Sr2+) has received much attention in bone tissue regeneration because of its osteoinductive properties combined with its ability to inhibit osteoclast activity. In this study, strontium-doped hydroxyapatite (Sr-HAp) nanorods with varying molar ratios of Ca : Sr (10 : 0, 9 : 1, 5 : 5, 3 : 7 and 0 : 10) were synthesized using the chemical precipitation technique. The synthesized Sr-HAp nanostructures were characterized using powder X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy, energy dispersive X-ray spectroscopy, and Raman and Fourier transform infrared (FTIR) spectroscopies to understand their structural and morphological features, and composition. XRD results revealed the formation of HAp nanostructures, whose unit cell volume increased as a function of the dopant level. The reaction process investigation showed the formation of hydroxyapatite (HAp), strontium apatite (SAp) and various Sr-HAp phases. FESEM micrographs displayed the morphological transformation of Sr-HAp from nanorods to nanosheets upon increasing the dopant level. In the FTIR spectra, the bands of the PO43- group shifted towards a lower wavenumber upon increasing the dopant concentration in Sr-HAp that signifies the structural distortion due to the presence of a large amount of strontium ions. The peaks of PO43- and OH- vibrations in the Raman spectra were further analysed to corroborate the structural distortion of Sr-HAp. Selected area electron diffraction patterns obtained using TEM reveal the reduced crystallinity of Sr-HAp due to Sr-doping, which is in line with the XRD results. Finally, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the synthesized Sr-HAp has no toxic effect on the survival and growth of mesenchymal stem cells. In summary, the synthesized novel Sr-HAp nanorods exhibit great promise for bone tissue engineering applications.

Establishment of Age Specific Reference Interval for Aminoacids and Acylcarnitine in Dried Blood Spot by Tandem Mass Spectrometry.

The Extended Screening for Inborn Errors of Metabolism is done for aminoacidopathies, fatty acid oxidation disorders and organic acid disorders. In a single dried blood spot, the tandem mass spectrometry is capable of measuring multiple analytes like amino acids, acylcarnitines, nucleosides, succinylacetone and lysophosphatidylcholines. This study was proposed to establish age specific reference internal for aminoacids and acylcartinitine in dried blood spot by tandem mass spectrometry. A total of 480 apparently healthy children were enrolled for the study and sub classified into four groups as follows: Group A: 0-1 month, Group B: 1 month-1 year, Group C: 1-5 year and Group D: 5-12 years each having 120 participants. Sample size were calculated as per CLSI approved guidelines. Tables 1 and 2 presents the age-specific percentile distribution of aminoacids and acylcarnitines established from healthy subjects as per rank-based method recommended by the IFCC and CLSI. Tables 3, 4 and 5 presents the cut-off values of primary and secondary marker/ratios for screening of aminoacidopathies, fatty acid oxidation disorders and organic acid disorders respectively. As a general principle, the interpretation of extended newborn screening results should be based on age specific cut-off established by the laboratory for primary analyte concentration and secondary analyte concentration/ ratios. This study was useful in establishing age specific cut-off values for various amino acids and acylcarnitines in South Indian population. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text].

Perceived Stress, Blood Biomarkers, and Cognitive Functioning in Older Adults.

INTRODUCTION: There is a substantial gap in knowledge regarding how perceived stress may influence the relationship between serum-measured biomarkers for Alzheimer's disease and cognitive decline. METHODS: This study consists of 1118 older adult participants from the Chicago Health and Aging Project (CHAP) (60% Black participants and 63% female participants). Linear mixed effects regression models were conducted to examine the role of perceived stress in the association between three blood biomarkers: total tau (t-tau), glial fibrillary acid protein (GFAP), and neurofilament light chain (NfL) on global cognitive decline. Stratified analysis by stress level was also conducted to evaluate the associations between each blood biomarker and baseline cognitive function and decline. All models adjusted for age, race, sex, education, time, and their interactions with time. RESULTS: The interaction of stress, NfL concentration, and time was statistically significant on global cognition ( ß = -0.064 [SE = 0.028], p = .023) and on episodic memory ( ß = -0.097 [SE = 0.036], p = .007). CONCLUSIONS: Greater stress level worsens the association between high NfL concentration and cognitive decline. Stress management interventions may be helpful to reduce the rate of cognitive decline in individuals with high concentrations of NfL.

Anticancer potential of novel symmetrical and asymmetrical dihydropyridines against breast cancer via EGFR inhibition: molecular design, synthesis, analysis and screening.

A series of novel symmetrical and asymmetrical dihydropyridines (HD 1-15) were designed, subjected to in silico ADMET prediction, synthesized, analyzed by IR, NMR, Mass analytical techniques and evaluated against epidermal growth factor receptor (EGFR) as inhibitors against Breast cancer. The results of predicted ADMET studies demonstrated the drug-likeness properties of the reported compounds. The in vitro cytotoxicity assessment of the synthesized compounds revealed that all of them showed good activity (IC50 ranging from 16.75 to 66.54 µM) towards MCF-7 breast cancer cells compared to the standard drug, Lapatinib (IC50 = 2.02 µM). Among these, compounds HD-6, HD-7, and HD-8 displayed the most potent activity with IC50 value of 21.26, 16.75, and 18.33 µM, respectively. Cytotoxicity of all compounds was tested on normal vero cells for comparison at different concentrations using the MTT assay. In addition to the MTT assay, the potent dihydropyridines derivatives were screened for EGFRwt kinase inhibition assay at concentrations ranging from 1 nM to 360 nM. Among the three compounds tested, HD-8 showed reasonably good inhibition with an IC50 value of 15.90 ± 1.20 nM compared to a standard Lapatinib IC50 value of 10.28 ± 1.01 nM. Based on the molecular docking study against EGFR, the most active derivatives HD-7 and HD-8 were docked against the active site of the protein and showed better binding affinity than the standard lapatinib. Additionally, molecular dynamics (MD) simulations were performed to explore the stability of the protein-ligand complex, its dynamic behavior, and the binding affinity.

Quantifying abnormal writing kinematics in writer's cramp using a novel software platform.

BACKGROUND: Writer's cramp is a task-specific focal hand dystonia, which is diagnosed clinically. Quantification of defect in WC is done using clinical scales, while digitized platforms are lacking. OBJECTIVE: To design and test a platform that can differentiate and quantify the abnormal kinematics of writing using a software interface and to validate it in adult-onset isolated writer's cramp (WC). METHODS: A native platform was designed using Java and Wacom Intuos pro tablet and the data analyzed using a MATLAB-based platform called Large Data-Based Evaluation of Kinematics in Handwriting (LEKH). We standardized this new platform by comparing the handwriting between patients with WC and age, and gender and education-matched healthy controls, using standard tasks to assess the kinematics. RESULTS: Comparison of the writing of right-handed WC patients (N = 21) and 39 healthy controls (N = 39) showed that patients differed from controls in the frequency of strokes (P < 0.001), number of inversions of velocity (P < 0.001), number of breaks (P = 0.02), air time and paper time (P < 0.001). CONCLUSIONS: Using the LEKH platform, the kinematic profile of patients with WC could be differentiated from healthy controls. Studies in larger samples will be needed to derive statistical models that can differentiate the flexion and extension types of WC which can help in muscle selection and to quantify the effects of treatment.

Comparative analysis of supra-orbital keyhole approach and pterional approach for surgical clipping of intracranial anterior circulation aneurysms in patients with favorable Hunt and Hess grades.

INTRODUCTION: Traditional large craniotomies have been the standard for aneurysm surgery. However, minimally invasive "keyhole" approaches have gained popularity for aneurysm clipping in recent years. This study focuses on Supra-Orbital Keyhole Approach (SOKHA),its use in clipping of aneurysms of the anterior Circle of Willis. Here we share the experiences of a tertiary care center regarding aneurysm clipping using SOKHA. MATERIALS AND METHODS: We retrospectively reviewed 166 cases involving aneurysm clipping, with 62 patients undergoing SOKHA and 104 patients undergoing the pterional approach. Factors evaluated included patient demographics, aneurysm characteristics, incidence of intraoperative complications, temporary-clipping usage, and postoperative clinical outcomes. Glasgow Outcome Scale scores were utilized to assess clinical outcomes. RESULTS: The study found that both the SOKHA and pterional approaches were similar in terms of age distribution, Hunt and Hess grades, and the incidence of hydrocephalus. The majority of aneurysms in both groups were anterior communicating artery aneurysms.Hydrocephalus was observed in 14.5 % of SOKHA cases and 13.5 % of pterional cases. Intraoperative aneurysm rupture occurred in 8.1 % of SOKHA cases and 7.7 % of pterional cases. There were no mortalities in the SOKHA group, while the pterional group had 1.92 % mortality rate. At the last follow-up, 77.4 % of SOKHA cases and 75.9 % of pterional cases had a favorable outcome (Glasgow Outcome Scale IV and V), with no significant difference. CONCLUSION: SOKHA offers the advantage of potential cosmetic benefit with neurological outcomes comparable to those of the traditional pterional approach, in properly selected patients.

Dietary fats and the APOE-e4 risk allele in relation to cognitive decline: a longitudinal investigation in a biracial population sample.

BACKGROUND: APOE-e4 is the strongest genetic risk factor for Alzheimer's disease. However, the influence of APOE-e4 on dietary fat intake and cognition has not been investigated. OBJECTIVE: We aim to examine the association of types of dietary fat and their association to cognitive decline among those with and without the APOE-e4 allele. METHODS: The study included 3,360 Chicago Health and Aging Project (CHAP) participants from four Southside Chicago communities. Global cognition was assessed using a composite score of episodic memory, perceptual speed, MMSE, and diet using a 144-item food frequency questionnaire. APOE genotype was assessed by the hME Sequenom mass-array platform. Longitudinal mixed-effect regression models were used to examine the association of dietary fat and the APOE-e4 allele with cognitive decline, adjusted for age, sex, education, smoking status, and calorie intake. RESULTS: The present study involved 3,360 participants with a mean age of 74 at baseline, 62% African Americans, 63% females, and a mean follow-up of 7.8 years. Among participants with the APOE-e4 risk allele, higher intakes of total and saturated fat (SFA) were associated with a faster decline in global cognition. Among individuals with the APOE-e4 risk allele, a 5% increase in calories from SFA was associated with a 21% faster decline (ß = -0.0197, P = 0.0038). In contrast, a higher intake of long-chain n-3 polyunsaturated fatty acids (LC-n3 PUFA) was associated with a slower rate of decline in global cognition among APOE-e4 carriers. Specifically, for every 1% energy increment from LC-n3 PUFA, the annual rate of global cognitive decline was slower by 0.024 standardized unit (SD 0.010, P = 0.023), about 30.4% slower annual cognitive decline. Higher SFA or other types of dietary fat were not associated with cognitive decline among APOE-e4 non-carriers. CONCLUSIONS: Our study found a significant association between SFA and faster cognitive decline, LC-n3 PUFA and slower cognitive decline among those with the APOE-e4 allele. Our findings suggested that higher intake of SFA might contribute faster cognitive decline in combination with APOE-e4 whereas LC-n3 PUFA might compensate the adverse effects of APOE-e4. The interaction between intakes of different types of dietary fat and APOE-e4 on cognitive function warrants further research.

A randomized controlled trial of medication adherence and management of risk factors for secondary prevention of stroke (MaMoRS) using a smartphone-based application.

BACKGROUND: There are little data on the use of smartphone-based applications for medication adherence and risk-factor control for the secondary prevention of stroke in low-and-middle-income countries (LMICs). AIMS: The aim was to determine whether a smartphone-based app improved medication adherence, risk-factor control, and provided health education to stroke survivors for lifestyle and behavioral modifications. METHODS: An unblinded, single-center randomized controlled double arm trial with 1:1 allocation among stroke survivors was performed in South India. The primary outcome was medication adherence, with co-primary outcomes of lifestyle and behavioral factors and control of vascular risk factors, at 3 and 6 months. RESULTS: Among 351 stroke survivors screened, 209 were recruited. The mean (standard deviation (SD)) age of the intervention (n = 105) group was 60 (12) years and that of the control (n = 104) group was 60 (10) years. In the primary outcome, mean medication adherence significantly improved in the intervention group with a between group difference of 0.735 (95% confidence interval (CI) = 0.419 to 1.050), p < 0.001. Being in intervention group (OR = 4.5; 95% CI = 2.3 to 8.9), stroke recurrence (OR = 3.3 (95% CI = 1.9 to 7.8)), and regular physician visits (OR = 2.1; 95% CI = 1.0 to 4.4) were significant predictors of good medication adherence. Considering the co-primary outcomes, compared to the control group, participants in the intervention group had a greater improvement in self-reported healthy diet intake (p = 0.003), intake of fruits (p = 0.005), and were physically more active (p = 0.001). At 6 months, mean fasting blood sugar (p = 0.005) and high-density lipoprotein cholesterol higher (p = 0.024) in the intervention group. CONCLUSIONS: The use of a mobile app is an effective method to improve medication adherence and risk-factor control in stroke survivors and is feasible in LMICs like India. DATA ACCESS STATEMENT: Data used during the study are available from the corresponding author on request. TRIAL REGISTRATION: The study is registered in Clinical Trial Registry of India (CTRI/2022/06/042980).