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1.
Curr Pharm Des ; 2024 Aug 28.
Article de Anglais | MEDLINE | ID: mdl-39206485

RÉSUMÉ

BACKGROUND AND OBJECTIVE: Alzheimer's Disease (AD) is an enervating and chronic progressive neurodegenerative disorder. Celecoxib (CXB) possesses efficacious antioxidants and has neuroprotective, anti- inflammatory, and immunomodulatory properties. However, the poor bioavailability of CXB limits its therapeutic utility. Thus, this study aimed to evaluate the microencapsulated celecoxib MCXB) for neuroprotection. METHODOLOGY: CXB was screened by molecular docking study using AutoDock (version 5.2), and the following proteins, such as 4EY7, 2HM1, 2Z5X, and 1PBQ were selected for predicting its neuroprotective effect. Scopolamine 20 mg/kg/day for approximately 7 days was administered to albino rats. Pure CXB 100 mg/kg/- day and 200 mg/kg/day, and MCXB 100 mg/kg/day and 200 mg/kg/day were administered, respectively. Further, to assess the oxidative stress, the nitric oxide (NO), superoxide dismutase (SOD), catalase, and lipid peroxidation (LPO) were evaluated using chemical methods. The neurochemical biomarkers like AChE, glutamate, and dopamine were evaluated using the ELISA method. Further, the histopathology of brain cells was carried out to assess the neuro-regeneration and neurodegeneration of the neurons. RESULTS: There was a significant binding interaction of CXB (score -6.3, -6.5, -5.1, -9.1) and donepezil (score- 5.5, -7.6, -7.0, and -8.6) with AchE (4EY7), ß-secretase (2HM1, monoamine oxidase (2Z5X), and glutamate (1PBQ), respectively. MCXB-treated rats (100 mg/kg/day, 200 mg/kg/day) showed increased SOD levels (p < 0.001), whereas NO, catalase, and LPO levels were significantly (p < 0.001) decreased as compared to scopolamine-treated rats. Further, MCXB-treated rats showed a modulatory effect in the level of dopamine and AchE. However, the glutamate level was significantly (p < 0.001) decreased. CONCLUSION: In addition to that, histopathological examination of the hippocampus part showed remarkable improvement in brain cells. So, the findings of the results revealed that MCXB, in a dose-dependent manner, showed a neuroprotective effect against scopolamine-induced AD. This effect may be attributed to the activation of cholinergic pathways.

3.
Can J Ophthalmol ; 2024 Aug 17.
Article de Anglais | MEDLINE | ID: mdl-39163992

RÉSUMÉ

OBJECTIVE: To assess the feasibility of using artificial intelligence (AI) to improve readability of online cataract surgery patient education materials (PEMs) in English and Spanish. PARTICIPANTS: Websites with information dedicated to educating patients about cataract surgery. DESIGN: Comparative cross-sectional study. METHODS: The first 50 patient-oriented websites containing PEMs related to cataract surgery were identified through online search. Website authorship was categorized as an institution, private practice, or medical organization. Websites were assessed qualitatively for information accuracy, the presence of narrative video content, and multilingual availability. Readability of PEMs was assessed using five validated reading formulas. A natural language processing platform was used to simplify PEMs in English and Spanish. Converted PEMs were reassessed for readability and accuracy. RESULTS: A total of 32 institution, 7 private practice, and 11 medical organization sites were included. The overall average original reading grade level was 11.68 ± 1.59. After conversion, overall reading grade level improved to 7.94 ± 0.82 (p < 0.01). The first 10 results had better readability (10.40 ± 1.59) and reading ease (57.51 ± 9.24) compared to the subsequent 40 results (11.99 ± 1.43; p = 0.01; 47.64 ± 8.59; p < 0.01). Converted simplified Spanish text had an average reading ease score of 61.17 ± 5.39 (8-9th grade level). Native Spanish text reading ease improved from 57.41 ± 5.24 to 71.78 ± 5.24 (p < 0.01) following conversion (7th-grade level). CONCLUSION: AI conversion can enhance the readability of online PEMs on cataract surgery, while maintaining accuracy and content integrity, thereby improving accessibility and comprehensibility for a wider audience.

4.
Mar Pollut Bull ; 206: 116750, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39083907

RÉSUMÉ

The present study describes the seasonal distribution of microplastics (MPs) and their associated biofilms in the water column of the Netravathi-Gurupura estuary, southwest India. An average abundance of 8.15 (±3.81) particles/l and 1.14 (±0.78) particles/l was observed during the wet and dry seasons, respectively. Fibres, films, and fragments accounted for majority of the microplastics. Polyethylene terephthalate, polyethylene, polyurethane, polyester, polystyrene, and high-density polyethylene were the major polymers. The risk assessment revealed a low Pollution Load Index, but the Polymer Hazard Index showed higher toxicity. Diatoms from nine genera were observed attached to the microplastic samples with Amphora and Navicula spp. reported in both estuaries during both seasons. The considerable diversity of diatoms, along with other microbial groups, in microplastic-associated biofilms in this study, highlights the urgent need to understand the structure and development of microplastic-associated biofilms and their role in the vertical and horizontal transport of microplastics in tropical estuaries.


Sujet(s)
Biofilms , Diatomées , Surveillance de l'environnement , Estuaires , Microplastiques , Saisons , Polluants chimiques de l'eau , Microplastiques/analyse , Polluants chimiques de l'eau/analyse , Inde , Matières plastiques/analyse
7.
Sci Adv ; 10(22): eadn7848, 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38809989

RÉSUMÉ

Streptococcus agalactiae [group B Streptococcus (GBS)] is a leading cause of neonatal meningitis, with late-onset disease (LOD) occurring after gastrointestinal tract colonization in infants. Bacterial membrane lipids are essential for host-pathogen interactions, and the functions of glycolipids are yet to be fully elucidated. GBS synthesizes three major glycolipids: glucosyl-diacylglycerol (Glc-DAG), diglucosyl-DAG (Glc2-DAG), and lysyl-Glc-DAG (Lys-Glc-DAG). Here, we identify the enzyme, IagB, as responsible for biosynthesis of Glc-DAG, the precursor for the two other glycolipids in GBS. To examine the collective role of glycolipids to GBS virulence, we adapted a murine model of neonatal meningitis to simulate LOD. The GBS∆iagB mutant traversed the gut-epithelial barrier comparable to wild type but was severely attenuated in bloodstream survival, resulting in decreased bacterial loads in the brain. The GBS∆iagB mutant was more susceptible to neutrophil killing and membrane targeting by host antimicrobial peptides. This work reveals an unexplored function of GBS glycolipids with their ability to protect the bacterial cell from host antimicrobial killing.


Sujet(s)
Glycolipides , Infections à streptocoques , Streptococcus agalactiae , Streptococcus agalactiae/pathogénicité , Streptococcus agalactiae/immunologie , Streptococcus agalactiae/métabolisme , Animaux , Glycolipides/métabolisme , Glycolipides/immunologie , Souris , Virulence , Infections à streptocoques/immunologie , Infections à streptocoques/microbiologie , Humains , Modèles animaux de maladie humaine , Interactions hôte-pathogène/immunologie , Granulocytes neutrophiles/immunologie , Granulocytes neutrophiles/métabolisme , Mutation
8.
Article de Anglais | MEDLINE | ID: mdl-38698753

RÉSUMÉ

Natural plant sources are essential in the development of several anticancer drugs, such as vincristine, vinblastine, vinorelbine, docetaxel, paclitaxel, camptothecin, etoposide, and teniposide. However, various chemotherapies fail due to adverse reactions, drug resistance, and target specificity. Researchers are now focusing on developing drugs that use natural compounds to overcome these issues. These drugs can affect multiple targets, have reduced adverse effects, and are effective against several cancer types. Developing a new drug is a highly complex, expensive, and time-consuming process. Traditional drug discovery methods take up to 15 years for a new medicine to enter the market and cost more than one billion USD. However, recent Computer Aided Drug Discovery (CADD) advancements have changed this situation. This paper aims to comprehensively describe the different CADD approaches in identifying anticancer drugs from natural products. Data from various sources, including Science Direct, Elsevier, NCBI, and Web of Science, are used in this review. In-silico techniques and optimization algorithms can provide versatile solutions in drug discovery ventures. The structure-based drug design technique is widely used to understand chemical constituents' molecular-level interactions and identify hit leads. This review will discuss the concept of CADD, in-silico tools, virtual screening in drug discovery, and the concept of natural products as anticancer therapies. Representative examples of molecules identified will also be provided.

9.
Med Biol Eng Comput ; 62(10): 3043-3056, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-38761289

RÉSUMÉ

Medical image denoising has been a subject of extensive research, with various techniques employed to enhance image quality and facilitate more accurate diagnostics. The evolution of denoising methods has highlighted impressive results but struggled to strike equilibrium between noise reduction and edge preservation which limits its applicability in various domains. This paper manifests the novel methodology that integrates an adaptive masking strategy, transformer-based U-Net Prior generator, edge enhancement module, and modified non-local block (MNLB) for denoising brain MRI clinical images. The adaptive masking strategy maintains the vital information through dynamic mask generation while the prior generator by capturing hierarchical features regenerates the high-quality prior MRI images. Finally, these images are fed to the edge enhancement module to boost structural information by maintaining crucial edge details, and the MNLB produces the denoised output by deriving non-local contextual information. The comprehensive experimental assessment is performed by employing two datasets namely the brain tumor MRI dataset and Alzheimer's dataset for diverse metrics and compared with conventional denoising approaches. The proposed denoising methodology achieves a PSNR of 40.965 and SSIM of 0.938 on the Alzheimer's dataset and also achieves a PSNR of 40.002 and SSIM of 0.926 on the brain tumor MRI dataset at a noise level of 50% revealing its supremacy in noise minimization. Furthermore, the impact of different masking ratios on denoising performance is analyzed which reveals that the proposed method showed PSNR of 40.965, SSIM of 0.938, MAE of 5.847, and MSE of 3.672 at the masking ratio of 60%. Moreover, the findings pave the way for the advancement of clinical image processing, facilitating precise detection of tumors in clinical MRI images.


Sujet(s)
Tumeurs du cerveau , Encéphale , Imagerie par résonance magnétique , Rapport signal-bruit , Humains , Imagerie par résonance magnétique/méthodes , Encéphale/imagerie diagnostique , Tumeurs du cerveau/imagerie diagnostique , Maladie d'Alzheimer/imagerie diagnostique , Traitement d'image par ordinateur/méthodes , Algorithmes , Amélioration d'image/méthodes
10.
Nat Med ; 30(4): 1199-1209, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38532223

RÉSUMÉ

Fixed-dose combination (FDC) therapy, also known as polypill therapy, targets risk factors for atherosclerotic cardiovascular disease (ASCVD) and has been proposed as a strategy to reduce global ASCVD burden. Here we conducted a systematic search for relevant studies from 2016-2022 to assess the effects of FDC therapy for prevention of ASCVD. The studies selected include randomized trials evaluating FDC therapy with at least one blood pressure-lowering drug and one lipid-lowering drug. The study data were independently extracted, the quality of evidence was appraised by multiple reviewers and effect estimates were pooled using a fixed-effect meta-analysis when statistical heterogeneity was low to moderate. The main outcomes of the analysis were all-cause mortality, fatal and nonfatal ASCVD events, adverse events, systolic blood pressure, low-density lipoprotein cholesterol and adherence. Among 26 trials (n = 27,317 participants, 43.2% female and mean age range 52.9-76.0), FDC therapy was associated with lower low-density lipoprotein cholesterol and systolic blood pressure, with higher rates of adherence and adverse events in both primary and mixed secondary prevention populations. For studies with a mostly primary prevention population, FDC therapy was associated with lower risk of all-cause mortality by 11% (5.6% versus 6.3%; relative risk (risk ratio) of 0.89; 95% confidence interval 0.78 to 1.00; I2 = 0%; four trials and 16,278 participants) and risk of fatal and nonfatal ASCVD events by 29% (6.1% versus 8.4%; relative risk (risk ratio) of 0.71; 95% confidence interval 0.63 to 0.79; I2 = 0%; five trials and 15,503 participants). One adequately powered trial in an exclusively secondary prevention population showed that FDC therapy reduced the risk of major adverse cardiovascular events by 24%. These findings support adoption and implementation of polypills to lower risk for all-cause mortality and ASCVD.


Sujet(s)
Athérosclérose , Humains , Athérosclérose/prévention et contrôle , Athérosclérose/traitement médicamenteux , Femelle , Association médicamenteuse , Mâle , Adulte d'âge moyen , Sujet âgé , Maladies cardiovasculaires/prévention et contrôle , Pression sanguine/effets des médicaments et des substances chimiques , Antihypertenseurs/administration et posologie , Antihypertenseurs/usage thérapeutique , Essais contrôlés randomisés comme sujet , Prévention secondaire/méthodes , Facteurs de risque , Cholestérol LDL/sang
11.
RSC Adv ; 14(14): 9646-9655, 2024 Mar 20.
Article de Anglais | MEDLINE | ID: mdl-38525066

RÉSUMÉ

Herein, we report, for the first-time, mesoporous carbon-supported binary and ternary catalysts with different atomic ratios of Pt/MC (100), Pt-Sn/MC (50 : 50), Pt-Re/MC (50 : 50), Pt-Sn-Re/MC (80 : 10 : 10) and Pt-Sn-Re/MC (80 : 115 : 05) prepared using a co-impregnation reduction method as anode components for membraneless ethanol fuel cells (MLEFLs). Mechanistic and structural insights into binary Pt-Sn/MC, Pt-Re/MC and ternary Pt-Sn-Re/MC catalysts were obtained using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and energy-dispersive X-ray spectroscopy (EDX) methods. In particular, chemical characterization via cyclic voltammetry, CO stripping voltammetry and chronoamperometry indicated that Pt-Sn-Re/MC (80 : 15 : 05) had better dynamics toward ethanol oxidation than Pt-Sn-Re/MC (80 : 10 : 10), Pt-Sn/MC (50 : 50) and Pt-Re/MC (50 : 50) catalysts. In terms of the single cell performance of the prepared catalysts, Pt-Sn-Re/MC (80 : 15 : 05) (31.5 mW cm-2) showed a higher power density and current density than Pt-Sn-Re/MC(80 : 10 : 10), Pt-Re/MC (50 : 50) and Pt-Sn/MC (50 : 50) at room temperature. The addition of Re into the binary Pt-Sn catalyst improved its electrical performance for ethanol oxidation in a membraneless ethanol fuel cell. As a result, the ternary-based Pt-Sn-Re/MC (80 : 15 : 05) catalyst demonstrated enhanced performance compared to monometallic and bimetallic catalysts in the ethanol oxidation reaction in a membraneless fuel cell.

12.
Phys Chem Chem Phys ; 26(15): 11531-11544, 2024 Apr 17.
Article de Anglais | MEDLINE | ID: mdl-38323885

RÉSUMÉ

The aqueous solubility of ß-cyclodextrin (ß-CD), a cyclic carbohydrate comprising seven α-D-glucose molecules, is enhanced by 2-hydroxypropyl (2-HP) substitution of the hydroxyl groups at the CD rims. Our thorough analysis of the structural and solvation properties with different degrees of 2-hydroxypropyl substitution on ß-CD using molecular dynamics simulations reveals that the solubility is enhanced at the cost of the structural distortion of the CD cyclic structure. Substitution at the secondary rim predominantly enhances the favourable interactions between CD and water by decreasing CD-CD hydrogen bonding and promoting CD-water hydrogen bonding. However, the effect of substitution at the primary rim on the CD-water interactions is minimal; the hydrogen bonds between water and the primary hydroxyl group in native CD merely get replaced by those between water and 2-HP, since the substitution makes the primary hydroxyl oxygen (O6 atom) inaccessible to water. In contrast, substitution at the primary rim maintains the structural integrity of CD, while substitution at the secondary rim results in structural distortion due to the disruption of the intramolecular hydrogen bond belt, even leading to cavity closure. Certain strategic substitutions of the primary hydroxyl groups can help in the reduction of structural distortion, depending upon the degree of substitution at the secondary hydroxyl rim. A detailed inspection of the simulation trajectory revealed that the tilting of glucose units with the primary hydroxyl oxygen (O6) pointing inward is the primary driver for cavity closure. Even though the dynamics of glucose tilting can influence the kinetics of host-guest complex formation, once the guest is well incorporated into the cavity, glucose tilting is inhibited and the cavity opens up as in native ß-CD.

13.
J Cataract Refract Surg ; 50(6): 578-584, 2024 Jun 01.
Article de Anglais | MEDLINE | ID: mdl-38305420

RÉSUMÉ

PURPOSE: To evaluate subjective and objective outcomes after combined implantation of an extended depth-of-focus (EDOF) intraocular lens (IOL) and a combined technology multifocal lens (CT-IOL). SETTING: 2 clinical practices (Carolina Eyecare Physicians, Center For Sight) in the United States. DESIGN: Prospective, unmasked, multicenter, nonrandomized bilateral eye study. METHODS: Patients interested in reducing their dependence on spectacles were implanted with an EDOF IOL in the dominant eye and a CT-IOL in the nondominant eye. Refractive and visual acuity (VA) data at various distances (4 m, 66 cm, 40 cm, and 33 cm) were collected 3 months postsurgery, along with the distance-corrected binocular defocus curve and responses to questionnaires related to spectacle independence, visual disturbances, and overall visual function. RESULTS: Data from 37 participants were analyzed. The distance-corrected binocular defocus curve showed a mean VA better than 0.1 logMAR (20/25) at all vergences from +1.00 to -2.50 diopters (D). 36 participants (97%) had an uncorrected binocular VA of 0.3 logMAR or better, at all test distances. 70% of participants (26/37) reported never wearing spectacles at any distance, and 84% (31/37) were "completely" or "mostly" satisfied with their overall vision after surgery. Halos were the disturbance reported most frequently and reported as most bothersome, with difficulty driving at night the most common visual function issue. Difficulty reading was the next most reported issue. Overall eyesight was rated as "excellent" or "good" by 92% (34/37) of participants. CONCLUSIONS: This combined EDOF/CT-IOL approach was well-tolerated by participants and provided some potential benefits relative to bilateral implantation of either lens.


Sujet(s)
Pose d'implant intraoculaire , Phacoémulsification , Presbytie , Pseudophakie , Réfraction oculaire , Vision binoculaire , Acuité visuelle , Humains , Études prospectives , Acuité visuelle/physiologie , Presbytie/physiopathologie , Presbytie/chirurgie , Vision binoculaire/physiologie , Mâle , Femelle , Adulte d'âge moyen , Sujet âgé , Réfraction oculaire/physiologie , Pseudophakie/physiopathologie , Satisfaction des patients , Lentilles intraoculaires , Enquêtes et questionnaires , Lentilles intraoculaires multifocales , Dominance oculaire/physiologie , Perception de la profondeur/physiologie , Conception de prothèse
14.
Am J Ophthalmol ; 258: 14-21, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-37793479

RÉSUMÉ

PURPOSE: To report the heterogeneity in methodology of clinical trials submitted to the US Food and Drug Administration (FDA) for approval of topical dry eye treatments. DESIGN: Comparative analysis of clinical trials' methods. METHODS: We reviewed the online, publicly available FDA database, application review files, ClinicalTrials.gov registry records, and journal articles for each FDA-approved topical dry eye treatment. For each trial, we extracted information about the study, patient demographics, treatment names and doses, sample size in each arm, and the measurement instrument in a systematic fashion. RESULTS: Fourteen trials were included that assessed 5 topical treatments for dry eye (cyclosporine 0.05%, cyclosporine 0.09%, lifitegrast 5%, and loteprednol 0.25% eye drops and varenicline 0.03-mg nasal spray). Median treatment duration was 12 weeks (range, 2-24 weeks). In all trials, treatments, including varying concentrations of the same treatment, were compared with vehicle. Twelve trials (85.7%) evaluated a primary clinician-measured clinical sign, and 10 trials (71.4%) evaluated a primary patient-reported symptom. Corneal staining was the most frequently evaluated clinical sign primary outcome, reported in half (6 of 12) of the trials, and was graded using 4 different scoring systems. Conjunctival staining, conjunctival hyperemia, and tear production were each measured using 2 different scoring systems. Ocular discomfort, the only patient-reported symptom primary outcome, was measured using 5 different instruments. CONCLUSION: A variety of outcome measures were used in these clinical trials. Clinically meaningful dry eye outcome measures and standardized measurements can optimize the assessment of and comparison of therapeutic benefits.


Sujet(s)
Syndromes de l'oeil sec , Humains , Syndromes de l'oeil sec/diagnostic , Syndromes de l'oeil sec/traitement médicamenteux , Ciclosporine , Solutions ophtalmiques/usage thérapeutique , Administration par voie topique , Conjonctive
15.
Ophthalmology ; 131(4): 499-506, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-37852419

RÉSUMÉ

PURPOSE: To assess the web accessibility and readability of patient-oriented educational websites for cataract surgery. DESIGN: Cross-sectional electronic survey. PARTICIPANTS: Websites with information dedicated to educating patients about cataract surgery. METHODS: An incognito search for "cataract surgery" was performed using a popular search engine. The top 100 patient-oriented cataract surgery websites that came up were included and categorized as institutional, private practice, or medical organization according to authorship. Each site was assessed for readability using 4 standardized reading grade-level formulas. Accessibility was assessed through multilingual availability, accessibility menu availability, complementary educational video availability, and conformance and adherence to the Web Content Accessibility Guidelines (WCAG) 2.0. A standard t test and chi-square analysis were performed to assess the significance of differences with regard to readability and accessibility among the 3 authorship categories. MAIN OUTCOME MEASURES: The main outcome measures were the website's average reading grade level, number of accessibility violations, multilingual availability, accessibility menu availability, complementary educational video availability, accessibility conformance level, and violation of the perceivable, operable, understandable, and robust (POUR) principles according to the WCAG 2.0. RESULTS: A total of 32, 55, and 13 sites were affiliated with institutions, private practice, and other medical organizations, respectively. The overall mean reading grade was 11.8 ± 1.6, with higher reading levels observed in private practice websites compared with institutions and medical organizations combined (12.1 vs. 11.4; P = 0.03). Fewer private practice websites had multiple language options compared with institutional and medical organization websites combined (5.5% vs. 20.0%; P = 0.03). More private practice websites had accessibility menus than institutions and medical organizations combined (27.3% vs. 8.9%; P = 0.038). The overall mean number of WCAG 2.0 POUR principle violations was 17.1 ± 23.1 with no significant difference among groups. Eighty-five percent of websites violated the perceivable principle. CONCLUSIONS: Available patient-oriented online information for cataract surgery may not be comprehensible to the general public. Readability and accessibility aspects should be considered when designing these resources. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Sujet(s)
Extraction de cataracte , Cataracte , Humains , Études transversales , Éducation du patient comme sujet , Compréhension , Internet
16.
J Pediatr ; 265: 113816, 2024 Feb.
Article de Anglais | MEDLINE | ID: mdl-37931699

RÉSUMÉ

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.


Sujet(s)
Maladies transmissibles , Carence en vitamine A , Enfant , Mâle , Nourrisson , Nouveau-né , Femelle , Grossesse , Humains , Enfant d'âge préscolaire , Rétinol/effets indésirables , Études transversales , Mortinatalité , Carence en vitamine A/complications , Carence en vitamine A/épidémiologie , Vitamines , Foie
17.
ACS Appl Bio Mater ; 7(2): 564-578, 2024 Feb 19.
Article de Anglais | MEDLINE | ID: mdl-36847611

RÉSUMÉ

Short surfactant-like amphiphilic peptide, A3K, resembling a surfactant with a hydrophobic tail (A3) and a polar headgroup (K), is experimentally determined to form a membrane. Although the peptides are known to exist as ß-strands, the exact packing architecture stabilizing the membrane is unknown. Earlier simulation studies have reported successful packing configurations through trial and error. In this work, we present a systematic protocol to identify the best peptide configurations for different packing patterns. The influence of stacking peptides in square and hexagonal packing geometry with the neighboring peptides in parallel and antiparallel orientations was explored. The best peptide configurations were determined from the free energy of bringing 2-4 peptides together as a bundle that can be stacked into a membrane. The stability of the assembled bilayer membrane was further investigated through molecular dynamics simulation. The role of peptide tilting, interpeptide distance, the nature and the extent of interactions, and the conformational degrees of freedom on the stability of the membrane is discussed. The consistency with the experimental findings suggests hexagonal antiparallel as the most relevant molecular architecture.


Sujet(s)
Simulation de dynamique moléculaire , Peptides , Peptides/composition chimique , Conformation moléculaire , Tensioactifs
18.
Cornea ; 2023 Nov 28.
Article de Anglais | MEDLINE | ID: mdl-38016014

RÉSUMÉ

PURPOSE: ChatGPT is a commonly used source of information by patients and clinicians. However, it can be prone to error and requires validation. We sought to assess the quality and accuracy of information regarding corneal transplantation and Fuchs dystrophy from 2 iterations of ChatGPT, and whether its answers improve over time. METHODS: A total of 10 corneal specialists collaborated to assess responses of the algorithm to 10 commonly asked questions related to endothelial keratoplasty and Fuchs dystrophy. These questions were asked from both ChatGPT-3.5 and its newer generation, GPT-4. Assessments tested quality, safety, accuracy, and bias of information. Chi-squared, Fisher exact tests, and regression analyses were conducted. RESULTS: We analyzed 180 valid responses. On a 1 (A+) to 5 (F) scale, the average score given by all specialists across questions was 2.5 for ChatGPT-3.5 and 1.4 for GPT-4, a significant improvement (P < 0.0001). Most responses by both ChatGPT-3.5 (61%) and GPT-4 (89%) used correct facts, a proportion that significantly improved across iterations (P < 0.00001). Approximately a third (35%) of responses from ChatGPT-3.5 were considered against the scientific consensus, a notable rate of error that decreased to only 5% of answers from GPT-4 (P < 0.00001). CONCLUSIONS: The quality of responses in ChatGPT significantly improved between versions 3.5 and 4, and the odds of providing information against the scientific consensus decreased. However, the technology is still capable of producing inaccurate statements. Corneal specialists are uniquely positioned to assist users to discern the veracity and application of such information.

19.
bioRxiv ; 2023 Oct 17.
Article de Anglais | MEDLINE | ID: mdl-37873101

RÉSUMÉ

Bacterial membranes are complex and dynamic, arising from an array of evolutionary pressures. One enzyme that alters membrane compositions through covalent lipid modification is MprF. We recently identified that Streptococcus agalactiae MprF synthesizes lysyl-phosphatidylglycerol (Lys-PG) from anionic PG, and a novel cationic lipid, lysyl-glucosyl-diacylglycerol (Lys-Glc-DAG), from neutral glycolipid Glc-DAG. This unexpected result prompted us to investigate whether Lys-Glc-DAG occurs in other MprF-containing bacteria, and whether other novel MprF products exist. Here, we studied protein sequence features determining MprF substrate specificity. First, pairwise analyses identified several streptococcal MprFs synthesizing Lys-Glc-DAG. Second, a restricted Boltzmann machine-guided approach led us to discover an entirely new substrate for MprF in Enterococcus , diglucosyl-diacylglycerol (Glc2-DAG), and an expanded set of organisms that modify glycolipid substrates using MprF. Overall, we combined the wealth of available sequence data with machine learning to model evolutionary constraints on MprF sequences across the bacterial domain, thereby identifying a novel cationic lipid.

20.
PLoS One ; 18(9): e0292046, 2023.
Article de Anglais | MEDLINE | ID: mdl-37768936

RÉSUMÉ

BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability.

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