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1.
J Infect Dis ; 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38181070

RESUMEN

BACKGROUND: Oral human papillomavirus(HPV) infection and the oral microbiome are associated with oropharyngeal cancer. However, population-based data on the association of oral microbiome with oral HPV infection are limited. METHOD: We performed a cross-sectional analysis of 5,496 participants aged 20-59 in National Health and Nutrition Examination Surveys(NHANES):2009-2012. The association between either oral microbiome alpha diversity or beta diversity and oral HPV infection was assessed using multivariable logistic regression or principal coordinate analyses(PCoA) and multivariate analysis of variance(PERMANOVA). RESULTS: For alpha diversity, we found a lower number of observed Amplicon sequence variants(ASVs) (adjusted odds ratio[aOR] = 0.996; 95%CI = 0.992-0.999) and reduced Faith's Phylogenetic Diversity(aOR = 0.95; 95%CI = 0.90-0.99) associated with high-risk oral HPV infection in the overall population. This trend was observed in males for both high-risk and any oral HPV infection. Beta diversity showed differentiation of oral microbiome community by high-risk oral HPV infection as measured by Bray-Curtis dissimilarity (R2 = 0.054%; P = .029) and unweighted UniFrac distance (R2 = 0.046%; P = .045) among the overall population, and associations were driven by males. CONCLUSIONS: Both oral microbiome alpha diversity(within-sample richness and phylogenetic diversity) and beta diversity(heterogeneous dispersion of oral microbiome community) are associated with HPV infection. Longitudinal studies are needed to characterize the role of the microbiome in the natural history of oral HPV infection.

2.
J Infect Dis ; 2023 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-38079216

RESUMEN

INTRODUCTION: Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in HIV CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation. METHODS: Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology (SIV encephalitis). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and qPCR-amplified to detect levels of small RNAs (sRNAs, including microRNAs (miRNAs)) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs). RESULTS: Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA levels in bdEVs during SIV infection. CONCLUSIONS: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.

3.
J Infect Dis ; 228(9): 1274-1279, 2023 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-37379584

RESUMEN

The latent viral reservoir (LVR) remains a major barrier to HIV-1 curative strategies. It is unknown whether receiving a liver transplant from a donor with HIV might lead to an increase in the LVR because the liver is a large lymphoid organ. We found no differences in intact provirus, defective provirus, or the ratio of intact to defective provirus between recipients with ART-suppressed HIV who received a liver from a donor with (n = 19) or without HIV (n = 10). All measures remained stable from baseline by 1 year posttransplant. These data demonstrate that the LVR is stable after liver transplantation in people with HIV. Clinical Trials Registration. NCT02602262 and NCT03734393.


Asunto(s)
Infecciones por VIH , Seropositividad para VIH , Trasplante de Hígado , Humanos , Antirretrovirales/uso terapéutico , Linfocitos T CD4-Positivos , Infecciones por VIH/tratamiento farmacológico , Seropositividad para VIH/tratamiento farmacológico , Provirus , Carga Viral , Latencia del Virus
4.
Clin Infect Dis ; 77(2): 237-241, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-36987595

RESUMEN

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) use between October and December 2020 was characterized using the National Inpatient Sample database. CCP was administered in 18.0% of COVID-19-associated hospitalizations and was strongly associated with older age and increased disease severity. There were disparities in the receipt of CCP by race and ethnicity, geography, and insurance.


Asunto(s)
COVID-19 , Humanos , Estados Unidos/epidemiología , COVID-19/terapia , SARS-CoV-2 , Pacientes Internos , Inmunización Pasiva , Sueroterapia para COVID-19 , Anticuerpos Antivirales
5.
Transfusion ; 63(1): 23-29, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36268708

RESUMEN

BACKGROUND: It is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID-19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers. METHODS: The DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay. RESULTS: TTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS-CoV-2. DISCUSSION: There was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non-pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.


Asunto(s)
Anelloviridae , COVID-19 , Infecciones por Citomegalovirus , Infecciones por Virus ADN , Infecciones por Virus de Epstein-Barr , Torque teno virus , Humanos , Estudios Seroepidemiológicos , Herpesvirus Humano 4/genética , COVID-19/terapia , Sueroterapia para COVID-19 , SARS-CoV-2/genética , Anelloviridae/genética , Torque teno virus/genética , Citomegalovirus/genética , ADN , ADN Viral/genética
6.
Am J Transplant ; 22(4): 1253-1260, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34951746

RESUMEN

Vaccine-induced SARS-CoV-2 antibody responses are attenuated in solid organ transplant recipients (SOTRs) and breakthrough infections are more common. Additional SARS-CoV-2 vaccine doses increase anti-spike IgG in some SOTRs, but it is uncertain whether neutralization of variants of concern (VOCs) is enhanced. We tested 47 SOTRs for clinical and research anti-spike IgG, pseudoneutralization (ACE2 blocking), and live-virus neutralization (nAb) against VOCs before and after a third SARS-CoV-2 vaccine dose (70% mRNA, 30% Ad26.COV2.S) with comparison to 15 healthy controls after two mRNA vaccine doses. We used correlation analysis to compare anti-spike IgG assays and focused on thresholds associated with neutralization. A third SARS-CoV-2 vaccine dose increased median total anti-spike (1.6-fold), pseudoneutralization against VOCs (2.5-fold vs. Delta), and neutralizing antibodies (1.4-fold against Delta). However, neutralization activity was significantly lower than healthy controls (p < .001); 32% of SOTRs had zero detectable nAb against Delta after third vaccination compared to 100% for controls. Correlation with nAb was seen at anti-spike IgG >4 Log10 (AU/ml) on the Euroimmun ELISA and >4 Log10 (AU/ml) on the MSD research assay. These findings highlight benefits of a third vaccine dose for some SOTRs and the need for alternative strategies to improve protection in a significant subset of this population.


Asunto(s)
COVID-19 , Trasplante de Órganos , Ad26COVS1 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Trasplante de Órganos/efectos adversos , SARS-CoV-2 , Receptores de Trasplantes , Vacunas Sintéticas , Vacunas de ARNm
7.
Macromol Rapid Commun ; 43(22): e2100925, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35170109

RESUMEN

Currently, rational design of polymer acceptors is desirable but there is still a challenge to develop high-performance all-polymer solar cells (all-PSCs). In this work, brominated thienyl-fused malononitrile-based monomer is employed to copolymerize with indacenodithiophene (IDT) and benzodithiophene (BDT)-based linking units to develop two polymerized small molecule acceptors (PSMAs) PIDT and PBDT, respectively, for all-PSCs. The two PSMAs show similar absorption edges, while PBDT shows a slightly higher lowest unoccupied molecular orbital (LUMO) energy level than PIDT. Benefitted from the relatively high LUMO levels of the two polymer acceptors, notable open-circuit voltage (Voc ) values over 1.0 V are achieved when using them as acceptor to blend with PTQ10 as polymer donor. Particularly, the all-PSC based on PTQ10:PIDT demonstrates a power conversion efficiency of 10.19%, with an outstanding Voc of 1.10 V benefitted from the higher LUMO energy level of PIDT acceptor. The results demonstrate a feasible strategy to design PSMAs by selecting appropriate linking units for increasing the Voc and improving the efficiency of all-PSCs.

8.
J Clin Apher ; 37(5): 468-475, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36053868

RESUMEN

BACKGROUND: Automated red cell exchange (RCE) is a common treatment for patients with sickle cell disease (SCD). Two key parameters are used to determine the volume of blood for RCE to reduce sickle hemoglobin (eg, HbS): fraction of cells remaining (FCR) and target hematocrit. We evaluated how the calculated FCR-using the manufacturer's algorithm-impacted blood utilization and incidence of acute care encounters. STUDY DESIGN AND METHODS: Retrospective chart review was conducted of 15 adults with SCD who underwent chronic RCE from July 1, 2015 to August 31, 2019. Blood utilization and acute care encounters were compared across three time periods: (a) when a fixed FCR of 30% was used (12 months); (b) transition period during which physicians made ad hoc changes to the FCR (25 months); (c) algorithm phase when a procedural FCR between 30% and 50% was selected using an algorithm generated by the manufacturer's built-in software to target a HbS fraction of 8% post-procedure (12 months). Wilcoxon signed rank test was used to determine statistical significance. RESULTS: Median blood utilization per procedure decreased from 2398 mL (interquartile range [IQR]: 2271-2759 mL) during the fixed FCR phase to 1887 mL (IQR: 1495-2241 mL) during the algorithm phase (P < 0.001). Similarly, median number of units transfused decreased from 10 (9-11) to 7 (5-9) during the respective phases (P < 0.001). Visits to the emergency department were 1 (0-4) in the fixed FCR phase and 0 (0-3) in the algorithm phase. CONCLUSION: Algorithm-based selection of a procedural FCR significantly reduced blood utilization (~21%) without appearing to increase acute care encounters.


Asunto(s)
Anemia de Células Falciformes , Hemoglobina Falciforme , Adulto , Algoritmos , Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/métodos , Eritrocitos , Objetivos , Hemoglobina Falciforme/análisis , Humanos , Estudios Retrospectivos
9.
J Clin Microbiol ; 59(12): e0118621, 2021 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-34469185

RESUMEN

Serologic point-of-care tests to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information. To address this, we developed a novel antibody test leveraging hemagglutination, employing a dry card format currently used for typing ABO blood groups. Two hundred COVID-19 patient and 200 control plasma samples were reconstituted with O-negative red blood cells (RBCs) to form whole blood and added to dried viral-antibody fusion protein, followed by a stirring step and a tilting step, 3-min incubation, and a second tilting step. The sensitivities of the hemagglutination test, Euroimmun IgG enzyme-linked immunosorbent assay (ELISA), and receptor binding domain (RBD)-based CoronaChek lateral flow assay were 87.0%, 86.5%, and 84.5%, respectively, using samples obtained from recovered COVID-19 individuals. Testing prepandemic samples, the hemagglutination test had a specificity of 95.5%, compared to 97.3% and 98.9% for the ELISA and CoronaChek, respectively. A distribution of agglutination strengths was observed in COVID-19 convalescent-phase plasma samples, with the highest agglutination score (4) exhibiting significantly higher neutralizing antibody titers than weak positives (2) (P < 0.0001). Strong agglutinations were observed within 1 min of testing, and this shorter assay time also increased specificity to 98.5%. In conclusion, we developed a novel rapid, point-of-care RBC agglutination test for the detection of SARS-CoV-2 antibodies that can yield semiquantitative information on neutralizing antibody titer in patients. The 5-min test may find use in determination of serostatus prior to vaccination, postvaccination surveillance, and travel screening.


Asunto(s)
COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Ensayo de Inmunoadsorción Enzimática , Hemaglutinación , Pruebas de Hemaglutinación , Humanos , Pandemias , Sistemas de Atención de Punto , Sensibilidad y Especificidad
10.
Transfusion ; 61(8): 2277-2289, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34213026

RESUMEN

BACKGROUND: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients. METHODS: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion. RESULTS: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission. CONCLUSIONS: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.


Asunto(s)
Transfusión Sanguínea , Heridas por Arma de Fuego/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Heridas por Arma de Fuego/sangre , Heridas por Arma de Fuego/epidemiología , Adulto Joven
12.
PLoS One ; 19(1): e0297206, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38271344

RESUMEN

An ultrasonic phased array defect extraction method based on adaptive region growth is proposed, aiming at problems such as difficulty in defect identification and extraction caused by noise interference and complex structure of the detected object during ultrasonic phased array detection. First, bilateral filtering and grayscale processing techniques are employed for the purpose of noise reduction and initial data processing. Following this, the maximum sound pressure within the designated focusing region serves as the seed point. An adaptive region iteration method is subsequently employed to execute automatic threshold capture and region growth. In addition, mathematical morphology is applied to extract the processed defect features. In the final stage, two sets of B-scan images depicting hole defects of varying sizes are utilized for experimental validation of the proposed algorithm's effectiveness and applicability. The defect features extracted through this algorithm are then compared and analyzed alongside the histogram threshold method, Otsu method, K-means clustering algorithm, and a modified iterative method. The results reveal that the margin of error between the measured results and the actual defect sizes is less than 13%, representing a significant enhancement in the precision of defect feature extraction. Consequently, this method establishes a dependable foundation of data for subsequent tasks, such as defect localization and quantitative and qualitative analysis.


Asunto(s)
Sonido , Ultrasonido , Algoritmos , Análisis por Conglomerados , Semillas
13.
Microbiol Spectr ; 12(1): e0328623, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38009954

RESUMEN

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.


Asunto(s)
COVID-19 , Humanos , COVID-19/terapia , Sueroterapia para COVID-19 , Interleucina-6 , SARS-CoV-2 , Citocinas , Inmunización Pasiva
14.
Artículo en Inglés | MEDLINE | ID: mdl-24100567

RESUMEN

(2R,3R)-2,3-Butanediol dehydrogenase (R,R-BDH) from Bacillus coagulans 2-6 is a zinc-dependent medium-chain alcohol dehydrogenase. Recombinant R,R-BDH with a His6 tag at the C-terminus was expressed in Escherichia coli BL21 (DE3) cells and purified by Ni2+-chelating affinity and size-exclusion chromatography. Crystals were grown by the hanging-drop vapour-diffusion method at 289 K. The crystallization condition consisted of 8%(v/v) Tacsimate pH 4.6, 18%(w/v) polyethylene glycol 3350. The crystal diffracted to 2.8 Šresolution in the orthorhombic space group P212121, with unit-cell parameters a=88.35, b=128.73, c=131.03 Å.


Asunto(s)
Oxidorreductasas de Alcohol/química , Bacillus/enzimología , Cristalización , Cristalografía por Rayos X , Electroforesis en Gel de Poliacrilamida
15.
Artículo en Inglés | MEDLINE | ID: mdl-23908047

RESUMEN

Alanine dehydrogenase (L-AlaDH) from Bacillus megaterium WSH-002 catalyses the NAD⁺-dependent interconversion of L-alanine and pyruvate. The enzyme was expressed in Escherichia coli BL21 (DE3) cells and purified with a His6 tag by Ni²âº-chelating affinity chromatography for X-ray crystallographic analysis. Crystals were grown in a solution consisting of 0.1 M HEPES pH 8.0, 12%(w/v) polyethylene glycol 8000, 8%(v/v) ethylene glycol at a concentration of 15 mg ml⁻¹ purified protein. The crystal diffracted to 2.35 Å resolution and belonged to the trigonal space group R32, with unit-cell parameters a = b = 125.918, c = 144.698 Å.


Asunto(s)
Alanina-Deshidrogenasa/química , Bacillus megaterium/enzimología , Proteínas Bacterianas/química , Alanina-Deshidrogenasa/aislamiento & purificación , Proteínas Bacterianas/aislamiento & purificación , Cristalización , Cristalografía por Rayos X
16.
Artículo en Inglés | MEDLINE | ID: mdl-24192355

RESUMEN

Alanine dehydrogenase (OF4Ald) from the alkaliphilic Bacillus pseudofirmus OF4 was expressed and purified with a His6 tag in a form suitable for X-ray crystallographic analysis. Crystals were grown by the hanging-drop vapour-diffusion method at 289 K using a solution consisting of 0.1 M Tris-HCl pH 8.0, 0.2 M LiSO4, 22%(w/v) PEG 3350. X-ray diffraction data were collected to 2.8 Šresolution. The crystal belonged to the triclinic space group P1, with unit-cell parameters a = 88.04, b = 105.59, c = 120.53 Å, α = 88.37, ß = 78.77, γ = 82.65°.


Asunto(s)
Alanina-Deshidrogenasa/química , Bacillus/enzimología , Proteínas Bacterianas/química , Secuencia de Aminoácidos , Cristalización , Cristalografía por Rayos X , Electroforesis en Gel de Poliacrilamida , Datos de Secuencia Molecular , Alineación de Secuencia
17.
Food Chem X ; 20: 100881, 2023 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-37767060

RESUMEN

Gray sufu is a traditional fermented bean product with strong flavor in China, but traditional fermentation methods often lead to its off-flavor. This study was performed to investigate the flavor quality characteristics of gray sufu fermented using L. mesenteroides F24. Results showed 220 volatile compounds in gray sufu, among which alcohols and esters were the main volatiles. Inoculation with L. mesenteroides F24 considerably affected the contents of flavor substances in gray sufu and substantially increased the main flavor compounds. In addition, 29 kinds of key volatile compounds were identified by analyzing the ROAVs. Four unique key flavor substances were found in gray sufu inoculated with L. mesenteroides F24. This study is the first report on the feasibility of L. mesenteroides F24 as a promising starter culture to improve the flavor quality of gray sufu. The results provide a theoretical basis for improving the processing and quality control of gray sufu.

18.
bioRxiv ; 2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37034720

RESUMEN

Introduction: Antiretroviral treatment regimens can effectively control HIV replication and some aspects of disease progression. However, molecular events in end-organ diseases such as central nervous system (CNS) disease are not yet fully understood, and routine eradication of latent reservoirs is not yet in reach. Brain tissue-derived extracellular vesicles (bdEVs) act locally in the source tissue and may indicate molecular mechanisms in HIV CNS pathology. Regulatory RNAs from EVs have emerged as important participants in HIV disease pathogenesis. Using brain tissue and bdEVs from the simian immunodeficiency virus (SIV) model of HIV disease, we profiled messenger RNAs (mRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), seeking to identify possible networks of RNA interaction in SIV infection and neuroinflammation. Methods: Postmortem occipital cortex tissue were collected from pigtailed macaques: uninfected controls and SIV-infected subjects (acute phase and chronic phase with or without CNS pathology). bdEVs were separated and characterized in accordance with international consensus standards. RNAs from bdEVs and source tissue were used for sequencing and qPCR to detect mRNA, miRNA, and circRNA levels. Results: Multiple dysregulated bdEV RNAs, including mRNAs, miRNAs, and circRNAs, were identified in acute infection and chronic infection with pathology. Most dysregulated mRNAs in bdEVs reflected dysregulation in their source tissues. These mRNAs are disproportionately involved in inflammation and immune responses, especially interferon pathways. For miRNAs, qPCR assays confirmed differential abundance of miR-19a-3p, let-7a-5p, and miR-29a-3p (acute SIV infection), and miR-146a-5p and miR-449a-5p (chronic with pathology) in bdEVs. In addition, target prediction suggested that several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in small RNA levels in bdEVs during SIV infection. Conclusions: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.

19.
Ther Adv Neurol Disord ; 16: 17562864231180736, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37529719

RESUMEN

Background: Stiff person syndrome spectrum disorders (SPSD) are a rare group of disabling neuroimmunological disorders. SPSD often requires immune therapies, especially in the setting of inadequate response to symptomatic treatments. The safety and efficacy of therapeutic plasma exchange (TPE) in SPSD remains uncertain. Objectives: To describe the safety, tolerability, and efficacy of TPE in patients with SPSD. Design: A retrospective observational study. Methods: A retrospective review of SPSD patients seen at Johns Hopkins Hospital (JHH) from 1997 to 2021 was performed. Patient demographics/history, examination/diagnostic findings, treatment response, and TPE-related complications were recorded. Assessment for any associations between clinical characteristics, including age, sex, clinical phenotype, and time on immunotherapy, and response to TPE 3 months after treatment was performed. A subgroup of 18 patients treated with TPE at JHH and 6 patients treated with TPE at outside institutions were evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment. Literature review of SPSD and TPE was also conducted. Results: Thirty-nine SPSD patients were treated with TPE (21 at JHH and 18 at outside institutions); median age 48 years, 77% female, median modified Rankin Scale 3; mean initial anti-GAD65 antibody titer was 23,508 U/mL. Twenty-four patients (62%) had classic SPS, 10 (26%) had SPS-plus, 2 (5%) had progressive encephalomyelitis with rigidity and myoclonus, and 3 (8%) had pure cerebellar ataxia. All patients were on symptomatic treatments, 30 (77%) previously received IVIg, and 3 (8%) previously received rituximab. Four patients (10%) had a TPE-related adverse event. One developed asymptomatic hypotension, another had both line thrombosis and infection, and two had non-life-threatening bleeding events. Twenty-three (59%) patients reported improvement in symptoms after TPE. Of the subgroup of 24 patients evaluated for any change in usage of symptomatic medications 3 months after the TPE treatment, 14 (58%) required fewer GABAergic symptomatic medications. Literature review identified 57 additional patients with SPSD; 43 (75%) reported temporary improvement after TPE. Conclusion: The majority of patients treated with TPE had improvement. Moreover, most patients evaluated for any change in usage of symptomatic medications after the TPE treatment no longer required as much symptomatic medications months after TPE. TPE appears safe and well-tolerated in SPSD. Further studies are needed to assess the long-term efficacy of TPE in SPSD and identify which patients may benefit the most from TPE.

20.
Lancet Reg Health Am ; 22: 100503, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37214769

RESUMEN

Background: Firearm injury (FI) is the leading cause of death in children and adolescents in the United States (US). We describe the epidemiology of pediatric FI-associated emergency department (ED) visits and hospitalizations in the US stratified by race and ethnicity. Methods: Data on pediatric (0-17-year-olds) FI were analyzed using the 2019 Nationwide Emergency Department Sample (NEDS) and Kids' Inpatient Database (KID), the largest all-payer databases in the US for ED visits and pediatric hospitalizations, respectively. FI encounters were stratified by race and ethnicity. Poisson regression was used to identify factors associated with in-hospital mortality. Sampling weights were applied to generate nationally representative estimates. Findings: There were 7017 pediatric ED visits with FI (NEDS); 85.0% (5961/7017) were male and 73.0% (5125/7017) were adolescents (15-17 years). Overall, 5.5% (384/7017) died in the ED; 53.1% (3727/7017) of ED encounters did not result in hospitalization. There were 2817 pediatric FI hospitalizations (KID); 84.1% (2369/2817) were male and 71.6% (2018/2817) were adolescents; 51.4% (1447/2817) of FI were unintentional, 42.8% (1207/2817) were assault-related, and 5.8% (163/2817) were self-inflicted. Black children had the highest proportion (52.6%; 1481/2817) of hospitalizations among all race and ethnicities (p < 0.0001 vs. White). White children had the highest proportion of hospitalizations for self-inflicted injuries (16.6% [91/551] vs. 4.9% [25/504; p < 0.0001] in Hispanics and 1.7% [24/1481] in Blacks; p < 0.0001). The majority (56.5%; 1591/2817) of hospitalizations were patients from low-income zip codes (median annual-household-income <$44,000); 70% (1971/2817) had Medicaid as the primary insurance payer. Overall, 8.0% (225/2817) died during FI-associated hospitalizations. Self-inflicted injuries had the highest in-hospital mortality (prevalence ratio = 8.20, 95% CI = 6.06-11.10 vs. unintentional). Interpretation: Black children and children with lower household incomes were disproportionately impacted by FI resulting from assaults and accidents, while White children had the highest proportion of self-inflicted FI injuries. Public health and legal policy interventions are needed to prevent pediatric FI. Funding: US National Institutes of Health.

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