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1.
PLoS One ; 19(5): e0303195, 2024.
Article in English | MEDLINE | ID: mdl-38787829

ABSTRACT

BACKGROUND: Disaggregated data is a cornerstone of precision health. Vietnamese Americans (VietAms) are the fourth-largest Asian subgroup in the United States (US), and demonstrate a unique burden of disease and mortality. However, most prior studies have aggregated VietAms under the broader Asian American category for analytic purposes. This study examined the leading causes of death among VietAms compared to aggregated Asian Americans and non-Hispanic Whites (NHWs) during the period 2005-2020. METHODS: Decedent data, including underlying cause of death, were obtained from the National Center for Health Statistics national mortality file from 2005 to 2020. Population denominator estimates were obtained from the American Community Survey one-year population estimates. Outcome measures included proportional mortality, age-adjusted mortality rates per 100,000 (AMR), and annual percent change (APC) in mortality over time. Data were stratified by sex and nativity status. Due to large differences in age structure, we report native- and foreign-born VietAms separately. FINDINGS: We identified 74,524 VietAm decedents over the study period (71,305 foreign-born, 3,219 native-born). Among foreign-born VietAms, the three leading causes of death were cancer (26.6%), heart disease (18.0%), and cerebrovascular disease (9.0%). Among native-born VietAms the three leading causes were accidents (19.0%), self-harm (12.0%), and cancer (10.4%). For every leading cause of death, VietAms exhibited lower mortality compared to both aggregated Asians and NHWs. Over the course of the study period, VietAms witnessed an increase in mortality in every leading cause. This effect was mostly driven by foreign-born, male VietAms. CONCLUSIONS AND RELEVANCE: While VietAms have lower overall mortality from leading causes of death compared to aggregated Asians and NHWs, these advantages have eroded markedly between 2005 and 2020. These data emphasize the importance of racial disaggregation in the reporting of public health measures.


Subject(s)
Asian , Cause of Death , Humans , Male , Female , Vietnam/ethnology , United States/epidemiology , Asian/statistics & numerical data , Middle Aged , Aged , Adult , Adolescent , Young Adult , Death Certificates , Aged, 80 and over , Infant , Child , Mortality/trends
2.
ACS Appl Mater Interfaces ; 16(19): 24961-24975, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38706267

ABSTRACT

Increasingly complex modern gas-monitoring scenarios necessitate advanced sensing capabilities to detect and identify a diverse range of gases under varying conditions. There is a rising demand for individual sensors with multiple responses capable of recognizing gases, identifying components in mixtures, and providing stable responses. Inspired by gas sensors employing multivariable response principles, we develop a nanoporous anodic alumina high-order microcavity (NAA-HOµCV) gas sensor with multiple optical outputs for discriminative gas detection. The NAA-HOµCV architecture, formed by a Fabry-Pérot microcavity with distributed Bragg reflector (DBR) mirrors and an extended-length microcavity layer supporting multiple resonant modes, serves as an effective solid-state fingerprint platform for distinguishing volatile organic compound (VOC) gases. Our research reveals that the coupling strength of light into resonant modes and their evolution depend on the thickness of the DBR mirrors and the dimension of the microcavity layer, which allows us to optimize the discriminative sensing capability of the NAA-HOµCV sensor through structural engineering of the microcavity and photonic crystal mirrors. Gas-sensing experiments conducted on the NAA-HOµCV sensor demonstrate real-time discrimination between physiosorbed VOC gases (isopropanol, ethanol, or acetone) in reversible gas sensing. It also achieves superior ppb-level sensing in irreversible gas sensing of model silane molecules. Our study presents promising avenues for designing compact, cost-effective, and highly efficient gas sensors with tailored properties for discriminative gas detection.

3.
Vision (Basel) ; 8(2)2024 May 12.
Article in English | MEDLINE | ID: mdl-38804355

ABSTRACT

The measurement of corneal sensation allows clinicians to assess the status of corneal innervation and serves as a crucial indicator of corneal disease and eye health. Many devices are available to assess corneal sensation, including the Cochet-Bonnet aesthesiometer, the Belmonte Aesthesiometer, the Swiss Liquid Jet Aesthesiometer, and the newly introduced Corneal Esthesiometer Brill. Increasing the clinical use of in vivo confocal microscopy and optical coherence tomography will allow for greater insight into the diagnosis, classification, and monitoring of ocular surface diseases such as neurotrophic keratopathy; however, formal esthesiometric measurement remains necessary to assess the functional status of corneal nerves. These aesthesiometers vary widely in their mode of corneal stimulus generation and their relative accessibility, precision, and ease of clinical use. The development of future devices to optimize these characteristics, as well as further comparative studies between device types should enable more accurate and precise diagnosis and treatment of corneal innervation deficits. The purpose of this narrative review is to describe the advancements in the use of aesthesiometers since their introduction to clinical practice, compare currently available devices for assessing corneal innervation and their relative limitations, and discuss how the assessment of corneal innervation is crucial to understanding and treating pathologies of the ocular surface.

4.
bioRxiv ; 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38585770

ABSTRACT

Human NAT10 acetylates the N4 position of cytidine in RNA, predominantly on rRNA and tRNA, to facilitate ribosome biogenesis and protein translation. NAT10 has been proposed as a therapeutic target in cancers as well as aging-associated pathologies such as Hutchinson-Gilford Progeria Syndrome (HGPS). The ∼120 kDa NAT10 protein uses its acetyl-CoA-dependent acetyltransferase, ATP-dependent helicase, and RNA binding domains in concert to mediate RNA-specific N4-cytidine acetylation. While the biochemical activity of NAT10 is well known, the molecular basis for catalysis of eukaryotic RNA acetylation remains relatively undefined. To provide molecular insights into the RNA-specific acetylation by NAT10, we determined the single particle cryo-EM structures of Chaetomium thermophilum NAT10 ( Ct NAT10) bound to a bisubstrate cytidine-CoA probe with and without ADP. The structures reveal that NAT10 forms a symmetrical heart-shaped dimer with conserved functional domains surrounding the acetyltransferase active sites harboring the cytidine-CoA probe. Structure-based mutagenesis with analysis of mutants in vitro supports the catalytic role of two conserved active site residues (His548 and Tyr549 in Ct NAT10), and two basic patches, both proximal and distal to the active site for RNA-specific acetylation. Yeast complementation analyses and senescence assays in human cells also implicates NAT10 catalytic activity in yeast thermoadaptation and cellular senescence. Comparison of the NAT10 structure to protein lysine and N-terminal acetyltransferase enzymes reveals an unusually open active site suggesting that these enzymes have been evolutionarily tailored for RNA recognition and cytidine-specific acetylation.

5.
Sci Rep ; 14(1): 7717, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565608

ABSTRACT

Despite the significant advances in understanding the genetic architecture of epilepsy, many patients do not receive a molecular diagnosis after genomic testing. Re-analysing existing genomic data has emerged as a potent method to increase diagnostic yields-providing the benefits of genomic-enabled medicine to more individuals afflicted with a range of different conditions. The primary drivers for these new diagnoses are the discovery of novel gene-disease and variants-disease relationships; however, most decisions to trigger re-analysis are based on the passage of time rather than the accumulation of new knowledge. To explore how our understanding of a specific condition changes and how this impacts re-analysis of genomic data from epilepsy patients, we developed Vigelint. This approach combines the information from PanelApp and ClinVar to characterise how the clinically relevant genes and causative variants available to laboratories change over time, and this approach to five clinical-grade epilepsy panels. Applying the Vigelint pipeline to these panels revealed highly variable patterns in new, clinically relevant knowledge becoming publicly available. This variability indicates that a more dynamic approach to re-analysis may benefit the diagnosis and treatment of epilepsy patients. Moreover, this work suggests that Vigelint can provide empirical data to guide more nuanced, condition-specific approaches to re-analysis.


Subject(s)
Epilepsy , Humans , Epilepsy/diagnosis , Epilepsy/genetics , Genomics , Genetic Testing
6.
Front Pharmacol ; 15: 1359427, 2024.
Article in English | MEDLINE | ID: mdl-38567354

ABSTRACT

Background: Citrus reticulata Blanco essential oil (CBEO) has attracted increasing attention as a potential treatment for depression and anxiety in recent years. However, there is limited evidence regarding the active compounds responsible for its therapeutic effects. In addition, substantial amounts of CBEO and prolonged therapy are often required. This study aims to investigate the rapid acting antidepressant and anxiolytic effects of CBEO, identify the underlying composition as well as optimize its dosage and duration. Methods: CBEO composition was determined using gas chromatography-mass spectrometry (GC-MS), and the corresponding targets were obtained from the SwissTargetPrediction database. Depression-related targets were collected from DisGeNET, GeneCards, Therapeutic Target Database, and Online Mendelian Inheritance in Man. Subsequently, the overlap between CBEO and depression targets was utilized to build a network diagram depicting the relationship between the active ingredients and targets using Cytoscape software. The STRING database facilitated the construction of a protein-protein interaction network, and the Ma'ayan Laboratory Enrichment tool was employed for Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Wiki pathway analyses. Molecular docking was conducted using AutoDock Vina and Discovery Studio Visualizer. Topological analysis predicted the main antidepressant active ingredients in CBEO. A mixture of these compounds was prepared based on their relative GC-MS ratios. Tail suspension test, elevated plus maze, corticosterone-induced PC12 cells, and lipopolysaccharide (LPS)-induced BV2 cells were used to validate the antidepressant and anxiolytic potential of CBEO and CBEO's main bioactive constituents. Results: CBEO contains 18 components that target 121 proteins. We identified 595 targets associated with depression; among them, 29 targets were located between essential oils and depression. Topological results revealed that linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol were the major active compounds of CBEO in the management of depression. GO analysis identified G protein-coupled opioid receptor activity, phospholipase C-activating G protein-coupled receptor, and neuron projections that were mostly related to molecular functions, cellular components, and biological processes. Neuroactive ligand-receptor interactions, chemical carcinogenesis, and calcium signaling pathways were the major pathways identified in KEGG analysis. Molecular docking showed that the main bioactive ingredients of CBEO had favorable binding affinities for Protein-Protein Interaction's hub proteins, including OPRM1, PTGS2, ESR1, SLC6A4, DRD2, and NR3C1. These five compounds were then mixed at 0.8:5:0.6:2:1 (w/w) ratio to form a CBEO antidepressant active compound mixture. An acute intranasal treatment of CBEO (25 mg/kg) only demonstrated an antidepressant effect, whereas the main bioactive compounds combination (12.5 mg/kg) illustrated both antidepressant and anxiolytic effects in mice. Linalool, p-cymene, and terpinene-4-ol exhibited neuroprotective and anti-neuroinflammation in the in vitro study, while these effects were not observed for α-terpinene and α-terpineol. Conclusion: Linalool, p-cymene, α-terpinene, terpinen-4-ol, and α-terpineol cymene might be mainly contributing to CBEO's antidepressant effect by regulating neuroactive ligand-receptor interaction, neuron projection, and receptor signaling pathway. A mixture of these compounds showed rapid antidepressant potential via intranasal administration, which was comparable to that of CBEO. The mixture also exhibited an anxiolytic effect while not seen in CBEO.

7.
Phytomedicine ; 127: 155484, 2024 May.
Article in English | MEDLINE | ID: mdl-38442431

ABSTRACT

BACKGROUND: Intranasal administration has been adopted in traditional medicine to facilitate access to the bloodstream and central nervous system (CNS). In modern medicine, nasal drug delivery systems are valuable for disease treatment because of their noninvasiveness, good absorption, and fast-acting effects. OBJECTIVE: This study aimed to systematically organize preclinical and clinical studies on intranasal herbal medicines to highlight their potential in drug development. METHODS: A comprehensive search for literature until February 2023 was conducted on PubMed and the Web of Science. From the selected publications, we extracted key information, including the types of herbal materials, target diseases, intranasal conditions, methods of toxicity evaluation, main outcomes, and mechanisms of action, and performed quality assessments for each study. RESULTS: Of the 45 studies, 13 were clinical and 32 were preclinical; 28 studies used herbal extracts, 9 used prescriptions, and 8 used natural compounds. The target diseases were rhinosinusitis, influenza, fever, stroke, migraine, insomnia, depression, memory disorders, and lung cancer. The common intranasal volumes were 8-50 µl in mice, 20-100 µl in rats, and 100-500 µl in rabbits. Peppermint oil, Ribes nigrum folium, Melia azedarach L., Elaeocarpus sylvestris, Radix Bupleuri, Da Chuan Xiong Fang, Xingnaojing microemulsion, and Ginsenoside Rb1 emerged as potential candidates for rapid intranasal therapy. The in vivo toxicity assessments were based on mortality, body weight, behavioral changes, mucociliary activity, histopathology, and blood tests. Most intranasal treatments were safe, except for Cyclamen europaeum, Jasminum sambac, Punica granatum L., and violet oil, which caused mild adverse effects. At lower doses, intranasal herbal treatments often show greater effects than oral administration. The actions of intranasal herbal medicine mainly involve regulating inflammation and neurotransmission, with the olfactory bulb and anterior cingulate cortex to be relevant brain regions. CONCLUSION: Intranasal delivery of herbal materials holds promise for enhancing drug delivery efficacy and reducing treatment duration, offering a potential future perspective for developing intranasal therapies for various diseases.


Subject(s)
Administration, Intranasal , Plant Extracts , Animals , Brain , Fever/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Humans
8.
ACS Appl Mater Interfaces ; 16(9): 11787-11799, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38394678

ABSTRACT

The fields of plasmonics and photonic crystals (PCs) have been combined to generate model light-confining Tamm plasmon (TMM) cavities. This approach effectively overcomes the intrinsic limit of diffraction faced by dielectric cavities and mitigates losses associated with the inherent properties of plasmonic materials. In this study, nanoporous anodic alumina PCs, produced by two-step sinusoidal pulse anodization, are used as a model dielectric platform to establish the methodology for tailoring light confinement through TMM resonances. These model dielectric mirrors feature highly organized nanopores and narrow bandwidth photonic stopbands (PSBs) across different positions of the spectrum. Different types of metallic films (gold, silver, and aluminum) were coated on the top of these model dielectric mirrors. By structuring the features of the plasmonic and photonic components of these hybrid structures, the characteristics of TMM resonances were studied to elucidate effective approaches to optimize the light-confining capability of this hybrid TMM model system. Our findings indicate that the coupling of photonic and plasmonic modes is maximized when the PSB of the model dielectric mirror is broad and located within the midvisible region. It was also found that thicker metal films enhance the quality of the confined light. Gas sensing experiments were performed on optimized TMM systems, and their sensitivity was assessed in real time to demonstrate their applicability. Ag films provide superior performance in achieving the highest sensitivity (S = 0.038 ± 0.001 nm ppm-1) based on specific binding interactions between thiol-containing molecules and metal films.

9.
Facial Plast Surg ; 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38378042

ABSTRACT

Deficits in corneal innervation lead to neurotrophic keratopathy (NK). NK is frequently associated with facial palsy, and corneal damage can be accelerated by facial palsy deficits. Corneal nerves are important regulators of limbal stem cells, which play a critical role in epithelial maintenance and healing. Nonsurgical treatments of NK have undergone recent innovation, and growth factors implicated in corneal epithelial renewal are a promising therapeutic avenue. However, surgical intervention with corneal neurotization (CN) remains the only definitive treatment of NK. CN involves the transfer of unaffected sensory donor nerve branches to the affected cornea, and a variety of donor nerves and approaches have been described. CN can be performed in a direct or indirect manner; employ the supraorbital, supratrochlear, infraorbital, or great auricular nerves; and utilize autograft, allograft, or nerve transfer alone. Unfortunately, comparative studies of these factors are limited due to the procedure's novelty and varied recovery timelines after CN. Regardless of the chosen approach, CN has been shown to be a safe and effective procedure to restore corneal sensation and improve visual acuity in patients with NK.

10.
bioRxiv ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38370824

ABSTRACT

Sirtuins, a class of highly conserved histone/protein deacetylases, are heavily implicated in senescence and aging. The regulation of sirtuin proteins is tightly controlled both transcriptionally and translationally and via localization within the cell. While Sirtiun proteins are implicated with aging, how their levels are regulated during aging across cell types and eliciting tissue specific age-related cellular changes is unclear. Here, we demonstrate that SIRT7 is targeted for degradation during senescence and liver aging. To uncover the significance of SIRT7 loss, we performed proteomics analysis and identified a new SIRT7 interactor, the HMG box protein NUCKS1. We found that the NUCKS1 transcription factor is recruited onto chromatin during senescence and this is mediated by SIRT7 loss. Further, depletion of NUCKS1 delayed senescence upon DNA damage leading to reduction of inflammatory gene expression. Examination of NUCKS1 transcriptional regulation during senescence revealed gene targets of transcription factors NFKB1, RELA, and CEBPß. Consistently, in both Sirt7 KO mouse liver and in naturally aged livers, Nucks1 was recruited to chromatin. Further, Nucks1 was bound at promoters and enhancers of age-related genes, including transcription factor Rela, and, moreover, these bound sites had increased accessibility during aging. Overall, our results uncover NUCKS1 as a novel interactor of SIRT7, and show that loss of SIRT7 during senescence and liver aging promotes NUCKS1 chromatin binding to regulate metabolic and inflammatory genes.

11.
Biomed Pharmacother ; 171: 116164, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38242042

ABSTRACT

BACKGROUND: Pterocarpus santalinus L. essential oil (PSEO) is traditionally employed for treating fever and mental aberrations. We aim to explore the antidepressant potential of intranasal PSEO in social defeat stress (SDS)-expose mice and identify its mechanisms and components. METHODS: PSEO components were analyzed using gas chromatography-mass spectrometry (GC-MS). C57BL/6 mice underwent a 10-day SDS with intranasal PSEO (10, 20 mg/kg) for 21 days. Efficacy was evaluated through changes in behaviors and serum corticosterone (CORT), hippocampal neurotransmitter, and inflammatory cytokine levels. In vitro effects were examined using primary hippocampal neurons, PC12 and BV2 cells. RESULTS: GC-MS identified 22 volatile compounds in PSEO, and (+)-ledene (16.7%), cedrol (13.5%), and isoaromadendrene epoxide (7.0%) as major components. PSEO (20 mg/kg) significantly reversed SDS-induced social withdrawal, increased open-area explorations in the open field test (OFT) and elevated plus maze (EPM) test, and reduced immobility time in the tail suspension test (TST) and forced swimming test (FST). PSEO downregulated serum CORT and hippocampal interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, while increasing hippocampal gamma-aminobutyric acid (GABA), norepinephrine (NE), and serotonin (5-HT) levels. PSEO (0.1, 1, 10 µg/mL) reduced neurotoxicity and neuroinflammation in PC12 and BV2 cells, respectively. PSEO (10 µg/mL) enhanced glutamic acid decarboxylase 6 (GAD6)- and GABA B receptor 1 (GABABR1)-positive puncta in the hippocampal neurons and FM1-43 fluorescence intensity. CONCLUSION: Intranasal PSEO exhibited antidepressant-like effects on SDS-exposed mice, potentially through modulating stress hormone, neurotransmission, and neuroinflammation. Further investigation into the pharmacokinetics, bioavailability, and mechanisms of (+)-ledene, cedrol, and isoaromadendrene epoxide is needed.


Subject(s)
Depression , Oils, Volatile , Polycyclic Sesquiterpenes , Pterocarpus , Mice , Animals , Depression/chemically induced , Oils, Volatile/pharmacology , Neuroinflammatory Diseases , Social Defeat , Mice, Inbred C57BL , Antidepressive Agents/pharmacology , Hippocampus , Corticosterone , Tumor Necrosis Factor-alpha/metabolism , Behavior, Animal , Synaptic Transmission , Epoxy Compounds/pharmacology , Disease Models, Animal
12.
J Ethnopharmacol ; 324: 117775, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38224793

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Perillae Folium, the leaves and twigs of Perilla frutescens (L.) Britton, has been included in many traditional Chinese medicine herbal formulas to treat depression. However, the precise antidepressant mechanism of the essential oil from Perillae Folium (PFEO) has not been fully investigated. AIM OF THE STUDY: To assess the effects and potential mechanisms of PFEO on depression using animal models and network pharmacology analysis. MATERIALS AND METHODS: PFEO was intranasally administered to a mouse model of social defeat stress (SDS). The antidepressant effects of PFEO on SDS-induced mice were evaluated using behavioral tests. Enzyme-linked immunosorbent assay (ELISA) and western blot were performed to measure the levels of depression-related biomarkers in the hippocampus and serum of the mice. The chemical compounds of PFEO were determined using gas chromatography-mass spectrometry (GC-MS). Network pharmacology and molecular docking analyses were conducted to investigate the potential bioactive components of PFEO and the mechanisms underlying the antidepressant effects. To validate the mechanisms of the bioactive compounds, in vitro models using PC12 and BV2 cells were established and the blood-brain barrier (BBB) permeability was evaluated. RESULTS: The intranasal administration of PFEO suppressed SDS-induced depression in mice by increasing the time spent in the social zone and the social interactions in the social interaction test and by decreasing the immobility time in the tail suspension and forced swimming tests. Moreover, the PFEO treatment reduced the SDS-induced anxiety-like behavior, as inferred from the increased activity in the central zone observed in the open field test and in the open arms observed in the elevated plus maze test. PFEO administration recovered the SDS-induced decrease in the levels of 5-HT, NE, gamma-aminobutyric acid (GABA), and p-ERK in the hippocampus of mice. Furthermore, the increased serum corticosterone level was also attenuated by the PFEO treatment. A total of 21 volatile compounds were detected in PFEO using GC-MS, among which elemicin (15.52%), apiol (15.16%), and perillaldehyde (12.79%) were the most abundant ones. The PFEO compounds targeted 32 depression-associated genes, which were mainly related to neural cells and neurotransmission pathways. Molecular docking indicated good binding affinities between the bioactive components of PFEO (apiol, ß-caryophyllene, elemicin, and myristicin) and the key targets, including ACHE, IL1B, IL6, MAOB, SLC6A2, SLC6A3, SLC6A4, and tumor necrosis factor. Among the four compounds, ß-caryophyllene, elemicin, and myristicin were more effective in reducing neurotoxicity and neuroinflammation. Elemicin showed the highest BBB permeability rate. CONCLUSIONS: This study shows the antidepressant activities of PFEO in an SDS-induced mouse model and suggests its potential mechanisms of action: regulation of the corticosterone levels, hippocampal neurotransmitters, and ERK signaling. Apiol, ß-caryophyllene, elemicin, and myristicin may be the main contributors to the observed effects induced by PFEO. Further studies are needed to fully elucidate the underlying mechanisms and the main PFEO bioactive components.


Subject(s)
Allylbenzene Derivatives , Depression , Dioxolanes , Oils, Volatile , Polycyclic Sesquiterpenes , Pyrogallol/analogs & derivatives , Animals , Mice , Depression/drug therapy , Oils, Volatile/pharmacology , Oils, Volatile/therapeutic use , Corticosterone , Administration, Intranasal , Molecular Docking Simulation , Social Defeat , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Behavior, Animal , Hippocampus , Disease Models, Animal
13.
Trop Med Infect Dis ; 9(1)2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38276637

ABSTRACT

COVID-19 significantly disrupted tuberculosis (TB) services in Vietnam. In response, the National TB Program (NTP) integrated TB screening using mobile chest X-rays into COVID-19 vaccination events. This prospective cohort study evaluated the integrated model's yield, treatment outcomes, and costs. We further fitted regressions to identify risk factors and conduct interrupted time-series analyses in the study area, Vietnam's eight economic regions, and at the national level. At 115 events, we conducted 48,758 X-ray screens and detected 174 individuals with TB. We linked 89.7% to care, while 92.9% successfully completed treatment. The mean costs per person diagnosed with TB was $547. TB risk factors included male sex (aOR = 6.44, p < 0.001), age of 45-59 years (aOR = 1.81, p = 0.006) and ≥60 years (aOR = 1.99, p = 0.002), a history of TB (aOR = 7.96, p < 0.001), prior exposure to TB (aOR = 3.90, p = 0.001), and symptomatic presentation (aOR = 2.75, p < 0.001). There was a significant decline in TB notifications during the Delta wave and significant increases immediately after lockdowns were lifted (IRR(γ1) = 5.00; 95%CI: (2.86, 8.73); p < 0.001) with a continuous upward trend thereafter (IRR(γ2) = 1.39; 95%CI: (1.22, 1.38); p < 0.001). Similar patterns were observed at the national level and in all regions but the northeast region. The NTP's swift actions and policy decisions ensured continuity of care and led to the rapid recovery of TB notifications, which may serve as blueprint for future pandemics.

14.
Asian Spine J ; 17(6): 1051-1058, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37946340

ABSTRACT

STUDY DESIGN: This study is a retrospective cohort study. PURPOSE: This study aims to determine whether preoperative neuroforaminal stenosis (FS) severity is associated with motor function patient-reported outcome measures (PROMs) following anterior cervical discectomy and fusion (ACDF). OVERVIEW OF LITERATURE: Cervical FS can significantly contribute to patient symptoms. While magnetic resonance imaging (MRI) has been used to classify FS, there has been limited research into the impact of FS severity on patient outcomes. METHODS: Patients undergoing primary, elective 1-3 level ACDF for radiculopathy at a single academic center between 2015 and 2021 were identified retrospectively. Cervical FS was evaluated using axial T2-weighted MRI images via a validated grading scale. The maximum degree of stenosis was used for multilevel disease. Motor symptoms were classified using encounters at their final preoperative and first postoperative visits, with examinations ≤3/5 indicating weakness. PROMs were obtained preoperatively and at 1-year follow-up. Bivariate analysis was used to compare outcomes based on stenosis severity, followed by multivariable analysis. RESULTS: This study included 354 patients, 157 with moderate stenosis and 197 with severe stenosis. Overall, 58 patients (16.4%) presented with upper extremity weakness ≤3/5. A similar number of patients in both groups presented with baseline motor weakness (13.5% vs. 16.55, p =0.431). Postoperatively, 97.1% and 87.0% of patients with severe and moderate FS, respectively, experienced full motor recovery (p =0.134). At 1-year, patients with severe neuroforaminal stenosis presented with significantly worse 12-item Short Form Survey Physical Component Score (PCS-12) (33.3 vs. 37.3, p =0.049) but demonstrated a greater magnitude of improvement (Δ PCS-12: 5.43 vs. 0.87, p =0.048). Worse stenosis was independently associated with greater ΔPCS-12 at 1-year (ß =5.59, p =0.022). CONCLUSIONS: Patients with severe FS presented with worse preoperative physical health. While ACDF improved outcomes and conferred similar motor recovery in all patients, those with severe FS reported much better improvement in physical function.

15.
Int J Hypertens ; 2023: 1933783, 2023.
Article in English | MEDLINE | ID: mdl-37886230

ABSTRACT

Background: Perindopril is an ACE inhibitor that aids in both blood pressure regulation and homocysteine reduction. Objectives: Our study aimed to evaluate the results of controlling blood pressure and blood homocysteine levels by perindopril in patients with primary hypertension. Materials and Methods: A cross-sectional descriptive study with a longitudinal follow-up was conducted on 105 primary hypertensive patients treated with perindopril. Results: The results of our study showed that after 6 weeks of treatment with perindopril, the proportion of patients with the target blood pressure (BP) level accounted for 70.5%, the rate of grade 1 hypertension decreased from 61.0% to 25.7%, grade 2 blood pressure decreased from 17.1% to 3.8%, and there was no case of grade 3 hypertension. At the same time, we also found that the rate of BP control in the group of patients who controlled Hcy below a threshold of 15 µmol/L was significantly higher than in the other group (p < 0.05). Concerning the efficacy of decreasing homocysteine in blood, we discovered that after 6 weeks of treatment with perindopril, the proportion of patients with elevated homocysteine reduced considerably from 74.3% to 40% (p < 0.05). In addition, the homocysteine concentration was 4.33 mol/L lower after treatment than before treatment (95% CI: 3.69-4.97) (p < 0.05). Conclusion: Perindopril helps control blood pressure and reduces blood homocysteine levels in patients with primary hypertension.

16.
Pharmaceutics ; 15(10)2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37896214

ABSTRACT

The findings from Pareto charts, main effect plots, and interaction plots demonstrate the importance of polymer concentration. Increasing concentration improves the inhibition percentage and decreases the MIC50. However, the primary factor that influences these changes is chitosan (CS). Additionally, the interaction between CS and PVP, along with other polymers, plays a crucial role in achieving better antimicrobial effects. These results enhance our understanding of the antimicrobial properties of the studied polymers and offer valuable insights for developing effective antimicrobial formulations. The MIC50 value of M1-M16 was at a polymer percentage of 12.5%. At 12.5% polymer percentage, with the limits of [PVA], [PEG], and [PVP] being 0.002-0.004 g/mL and [CS] being 0.001-0.002 g/mL, using the 2-level full factorial method, the inhibition percentage is equal to 174.1 - 27,812 PVA - 18,561 PVP - 25,960 PEG - 38,752 CS + 9,263,047 PVA*PVP + 10,430,763 PVA*PEG + 15,397,157 PVA*CS + 7,088,313 PVP*PEG + 7,841,221 PVP*CS + 14,228,046 PEG*CS - 3,367,292,860 PVA*PVP*PEG - 5,671,998,721 PVA*PVP*CS - 6,619,041,275 PVA*PEG*CS - 3,917,095,529 PVP*PEG*CS + 2,273,661,969,470 PVA*PVP*PEG*CS. Theoretically, the most economical concentrations of PVA, PVP, PEG, and CS are 0.002, 0.002, 0.002, and 0.001 mg/mL at a concentration of 12.5% to reach an inhibition percentage of 99.162%, which coincides with the MBC value.

17.
J Craniovertebr Junction Spine ; 14(3): 292-298, 2023.
Article in English | MEDLINE | ID: mdl-37860025

ABSTRACT

Background: Few studies regarding ossification of the posterior longitudinal ligament (OPLL) outside of Asia currently exist in the literature. A set of patients with multilevel cervical OPLL causing symptomatic myelopathy or radiculopathy from a North American sample is analyzed. Objective: The objective of this study was to describe the demographics, radiographic findings, and surgical outcomes of a cohort of North American patients with degenerative spondylosis presenting for operative management of multilevel (>3 segments) cervical OPLL. Materials and Methods: Forty-three patients diagnosed with multilevel cervical OPLL and degenerative spondylosis presenting with symptomatic cervical myelopathy or radiculopathy were surgically treated over a 9-year period at a single tertiary care academic medical center. Radiographic measurements were performed on preoperative computed tomography and magnetic resonance imaging images of the cervical spine. Clinical outcomes included pre- and postoperative Nurick scores, 90-day readmission, complication, and revision surgery rates. Results: The mean age was 66.1 ± 10.9 years with a mean latest follow-up time of 32.7 ± 16.4 months. Most patients had previous diagnoses of obesity (70.7%) and hypertension (55.8%). At least one-quarter of patients were diagnosed with type 2 diabetes (34.9%), hyperlipidemia (41.9%), cardiovascular disease (25.6%), or chronic kidney disease (25.3%). The most common OPLL subtype was segmental (39.5%) and spanned a mean of 3.54 ± 1.48 segments. Myelopathic symptoms were present in 88.4% of patients. All patients experienced significant neurologic improvement at 3-week and latest follow-up (P < 0.001 for both). Conclusions: Obesity, diabetes, and other metabolic derangements in patients with existing cervical spondylosis may be risk factors for a particularly aggressive form of multilevel OPLL. Various operative approaches may be employed to achieve adequate neurologic recovery. Further workup for OPLL in patients with these risk factors may prove beneficial to ensure appropriate operative management.

18.
Global Spine J ; : 21925682231201249, 2023 Sep 06.
Article in English | MEDLINE | ID: mdl-37671756

ABSTRACT

STUDY DESIGN: Prospective Cohort Study. OBJECTIVES: The purpose of this study was to prospectively evaluate the impact of preoperative dysphagia on the postoperative incidence and severity of dysphagia in patients undergoing ACDF at multiple institutions. METHODS: After IRB approval, patients over 18 years of age who underwent an elective ACDF for degenerative conditions were prospectively enrolled at two academic centers from 2018 to 2021. Preoperative dysphagia was self-reported by patients through a pre-operative questionnaire on a binary basis. Patients completed dysphagia surveys (Bazaz, Dysphagia Short Questionnaire, 10-item Eating Assessment Tool) to assess dysphagia severity during their preoperative visit, and these dysphagia surveys were repeated immediately postoperatively, at two weeks and again at six, 12, and 24 weeks postoperatively. Patients were stratified into three subgroups based on dysphagia status preoperatively and immediately postoperatively and compared using ANOVA tests or Kruskal-Wallis tests for continuous variables and Pearson chi-square analysis or Fisher's Exact test for categorical variables. RESULTS: A total of 168 patients (23 with preoperative dysphagia, 145 without preoperative dysphagia) met study criteria and were enrolled in the study. Patients with preoperative dysphagia had less frequent alcohol consumption (23.8% vs 53.7%, P = .0210), and higher rates of dysphagia at 2-weeks (77.8% vs 38.7%, P = .004) and 24-weeks (43.8% vs 14.8%, P = .010) postoperatively. These patients also had higher severity scores for dysphagia on the Bazaz (P = .001), DSQ (P = .012), EAT10 (P = .022) questionnaires at the 2-week follow-up period, higher DSQ scores (P = .036) at the 6-week follow-up period, higher EAT-10 scores (P = .009) at the 12-week follow-up period, and higher Bazaz (P = .001), DSQ (P = .002), and EAT-10 (P = .005) scores at the 24-week follow-up period. There were no differences in demographic, medical history, surgical variables, rates of ENT consultation, length of stay, or other in-hospital events between groups. CONCLUSIONS: Patients undergoing ACDF who had preoperative dysphagia have prolonged postoperative dysphagia and greater dysphagia severity. Surgeons should be aware of the risk of prolonged dysphagia severity that may persist past 24 weeks after surgery when discussing clinical decisions with patients.

19.
Nat Commun ; 14(1): 5758, 2023 09 16.
Article in English | MEDLINE | ID: mdl-37717006

ABSTRACT

Cells within the tumour microenvironment (TME) can impact tumour development and influence treatment response. Computational approaches have been developed to deconvolve the TME from bulk RNA-seq. Using scRNA-seq profiling from breast tumours we simulate thousands of bulk mixtures, representing tumour purities and cell lineages, to compare the performance of nine TME deconvolution methods (BayesPrism, Scaden, CIBERSORTx, MuSiC, DWLS, hspe, CPM, Bisque, and EPIC). Some methods are more robust in deconvolving mixtures with high tumour purity levels. Most methods tend to mis-predict normal epithelial for cancer epithelial as tumour purity increases, a finding that is validated in two independent datasets. The breast cancer molecular subtype influences this mis-prediction. BayesPrism and DWLS have the lowest combined numbers of false positives and false negatives, and have the best performance when deconvolving granular immune lineages. Our findings highlight the need for more single-cell characterisation of rarer cell types, and suggest that tumour cell compositions should be considered when deconvolving the TME.


Subject(s)
Mammary Neoplasms, Animal , Music , Animals , Tumor Microenvironment , Cell Lineage , RNA-Seq
20.
World Neurosurg ; 179: e296-e304, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37633493

ABSTRACT

OBJECTIVE: To establish the relationship between the magnitude of foraminal stenosis and 1) improvement in patient-reported outcomes, 2) improvement in motor function after lumbar decompression surgery, and 3) difference in surgical outcomes. METHODS: Patients who underwent one-level posterior lumbar decompression for radiculopathy were retrospectively identified. Patient demographics and surgical characteristics were collected through a query search and manual chart review of the electronic medical records. Foraminal stenosis was determined on magnetic resonance imaging and graded using Lee et al.'s validated methodology as none, mild, moderate, or severe. Surgical outcomes, motor function, and patient-reported outcome measures (PROMs) were compared based on the amount of stenosis (mild vs. moderate vs. severe). Bivariant and multivariant analyses were performed. RESULTS: Severe stenosis demonstrated more 90-day readmissions (0.00% vs. 0.00% vs. 8.57%, respectively, P = 0.019), though this effect did not remain significant on multivariate analysis (P = 0.068). There was no association between stenosis severity and the degree of functional impairment or PROMs preoperatively. Patients with moderate or severe preoperative foraminal stenosis showed improvement in all PROMs after surgery (P < 0.05) except the mental component of the Short Form 12 survey. Notably, central stenosis grade was insignificantly different between groups (P = 0.358). Multivariable logistic regression analysis did not identify any significant independent predictors of surgical outcomes or changes in PROMs. CONCLUSIONS: We demonstrated that regardless of foraminal stenosis severity preoperatively, patients have a similar improvement in PROMs, surgical outcomes, and restoration of motor function after lumbar decompression surgery for radiculopathy.


Subject(s)
Radiculopathy , Spinal Stenosis , Humans , Constriction, Pathologic/diagnostic imaging , Constriction, Pathologic/surgery , Constriction, Pathologic/etiology , Spinal Stenosis/complications , Spinal Stenosis/diagnostic imaging , Spinal Stenosis/surgery , Retrospective Studies , Radiculopathy/diagnostic imaging , Radiculopathy/etiology , Radiculopathy/surgery , Decompression, Surgical/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Treatment Outcome
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