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1.
mBio ; 15(4): e0032624, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38441028

ABSTRACT

Adult females of reproductive age develop greater antibody responses to inactivated influenza vaccines (IIV) than males. How sex, age, and sex steroid concentrations impact B cells and durability of IIV-induced immunity and protection over 4 months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes-determining gene, Sry, was deleted from chromosome Y (ChrY) and transferred to Chr3 to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.IMPORTANCEFemales of reproductive ages develop greater antibody responses to influenza vaccines than males. We hypothesized that female-biased immunity and protection against influenza were mediated by estradiol signaling in B cells. Using diverse mouse models ranging from advanced-age mice to transgenic mice that separate sex steroids from sex chromosome complement, those mice with greater concentrations of estradiol consistently had greater numbers of antibody-producing B cells in lymphoid tissue, higher antiviral antibody titers, and greater protection against live influenza virus challenge. Treatment of aged female mice with estradiol enhanced vaccine-induced immunity and protection against disease, suggesting that estradiol signaling in B cells is critical for improved vaccine outcomes in females.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Male , Animals , Mice , Female , Humans , Estradiol , Antibodies, Viral , Germinal Center , Vaccination , Mice, Transgenic , Vaccines, Inactivated , Antiviral Agents
2.
Child Abuse Negl ; 151: 106718, 2024 May.
Article in English | MEDLINE | ID: mdl-38431991

ABSTRACT

BACKGROUND: Despite existing literature on the link between bullying victimization and psychological well-being, little is known about the potential lasting negative effects of chronic bullying victimization, especially among children from multicultural families (CMF). OBJECTIVE: This study examined the longitudinal association between chronic bullying victimization and life satisfaction among CMF in Korea, and further investigated whether this association differs by immigrant mothers' country of origin. PARTICIPANTS AND SETTING: This study utilized data from the Multicultural Adolescents Panel Study (MAPS) 2011-2019, a nationally representative longitudinal study of CMF in Korea who were between the ages of 9 and 12 at baseline (N = 1375). METHODS: Fixed effects models were employed to address potential bias resulting from unobserved time-invariant confounders. Three theoretical models were proposed to examine the trajectory patterns of change in life satisfaction among chronically bullied children: cumulative effects, immediate-sustained effects, and short-lived effects models. RESULTS: The longitudinal trajectories of change in life satisfaction associated with chronic bullying victimization were consistent with an immediate-sustained effects model. Heterogeneous patterns in the association by mothers' country of origin were observed. A cumulative effects model was supported for children with Southeast Asian mothers, indicating that chronic bullying victimization leads to a cumulative decrease in life satisfaction. For children with Chinese and Japanese mothers, the results supported either immediate-sustained or short-lived effects models. CONCLUSIONS: Efforts to improve the psychological well-being of CMF should consider the potential long-term risk of chronic bullying victimization, particularly among youth with mothers from Southeast Asia.


Subject(s)
Bullying , Crime Victims , Emigrants and Immigrants , Child , Female , Adolescent , Humans , Longitudinal Studies , Bullying/psychology , Republic of Korea/epidemiology , Crime Victims/psychology , Personal Satisfaction
3.
Nutrition ; 122: 112374, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38430845

ABSTRACT

OBJECTIVE: This study aimed to investigate the association between ultra-processed food (UPF) intake and the risk for metabolic syndrome (MetS) in Korean adults. METHODS: The study consisted of 22 688 Korean adults ≥19 y of age from the Korea National Health and Nutrition Examination Survey (KNHANES) 2016-2020. The NOVA classification categorizes foods according to the nature, extent, and purpose of industrial processing. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III criteria and a modified waist circumference cut-off for Korean adults. We estimated the usual percent total food intake from UPFs. We used multivariate logistic regression to assess the association between UPFs and risk for MetS, adjusted for age, sex, education level, income level, smoking status, alcohol drinking, physical activity, and total energy intake. We further analyzed the association of UPFs with each component of MetS. RESULTS: The median usual percent total food intake from UPFs was 22%, and the midpoint of intake ranged from 3% (quartile 1) to 48% (quartile 4). The group with the highest UPF consumption had a 19% higher risk for developing MetS than the lowest quartile of UPF consumption (odds ratio [OR],1.19; 95% confidence interval [CI], 1.06-1.33; Ptrend = 0.006). In analysis of the relationship between UPF intake and MetS components, a higher UPF was associated with an increased risk for hypertension (OR, 1.13; 95% CI, 1.01-1.26; Ptrend = 0.037) and abdominal obesity (OR, 1.19; 95% CI, 1.07-1.33; Ptrend = 0.001), but had no significant association with other components (hyperglycemia, hypertriacylglycerolmia, and low high-density lipoprotein cholesterol, all P > 0.05). CONCLUSION: Higher UPF contribution to total daily food intake is associated with an increased risk for MetS, particularly with a higher risk for hypertension and abdominal obesity.


Subject(s)
Hypertension , Metabolic Syndrome , Adult , Humans , Metabolic Syndrome/etiology , Metabolic Syndrome/complications , Cross-Sectional Studies , Nutrition Surveys , Food, Processed , Obesity, Abdominal/etiology , Obesity, Abdominal/complications , Obesity/epidemiology , Obesity/etiology , Cholesterol , Republic of Korea/epidemiology , Diet/adverse effects , Food Handling , Fast Foods/adverse effects
4.
JCI Insight ; 9(8)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38483534

ABSTRACT

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.


Subject(s)
Antibodies, Viral , COVID-19 Serotherapy , COVID-19 , Hospitalization , Immunization, Passive , SARS-CoV-2 , Humans , COVID-19/immunology , COVID-19/therapy , Antibodies, Viral/blood , Antibodies, Viral/immunology , Immunization, Passive/methods , Hospitalization/statistics & numerical data , SARS-CoV-2/immunology , Male , Female , Middle Aged , Adult , Immunoglobulin G/blood , Immunoglobulin G/immunology , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Double-Blind Method , Aged , Blood Donors/statistics & numerical data , Outpatients
5.
Cultur Divers Ethnic Minor Psychol ; 30(3): 415-424, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38407071

ABSTRACT

OBJECTIVES: Over the past three decades, the number of multicultural families in Korea, defined as a family consisting of a native Korean and a marriage immigrant, has increased significantly. Although bullying victimization among multicultural family youth is rightfully a growing concern, less is known about the effects bullying has on immigrant mothers of children who have been bullying victims. METHOD: Using data from the Multicultural Adolescents Panel Study, this study investigates whether children's bullying victimization is associated with immigrant mothers' acculturative stress and whether this association differs depending on mothers' country of origin (China, Japan, and Southeast Asian countries). RESULTS: Fixed effects estimates revealed that children's bullying victimization is positively associated with their immigrant mother's acculturative stress, and this association is robust to controlling for unobserved time-constant individual-level heterogeneity. When stratified by mother's country of origin, the association was larger and statistically significant only among Southeast Asian mothers. No associations were observed among Japanese and Chinese mothers. CONCLUSIONS: Our findings suggest that interventions aiming to support bullied children should be expanded to also support their immigrant mothers. Policymakers may wish to consider the specific backgrounds and contexts of immigrant mothers, with special attention to Southeast Asian women. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Subject(s)
Acculturation , Bullying , Crime Victims , Emigrants and Immigrants , Mothers , Humans , Emigrants and Immigrants/psychology , Female , Bullying/psychology , Republic of Korea/ethnology , Mothers/psychology , Crime Victims/psychology , Adult , Male , Adolescent , Child , Stress, Psychological/ethnology , Stress, Psychological/psychology , China/ethnology , Japan/ethnology , Asia, Southeastern/ethnology
6.
Case Rep Oncol ; 17(1): 317-328, 2024.
Article in English | MEDLINE | ID: mdl-38404405

ABSTRACT

Introduction: Breast cancer exhibits vast genomic diversity, leading to varied clinical manifestations. Integrating molecular subtyping with in-depth genomic profiling is pivotal for informed treatment choices and prognostic insights. Whole-genome clinical analysis provides a holistic view of genome-wide variations, capturing structural changes and affirming tumor suppressor gene loss of heterozygosity. Case Presentation: Here we detail four unique breast cancer cases from Seoul St. Mary's Hospital, highlighting the actionable benefits and clinical value of whole-genome sequencing (WGS). As an all-in-one test, WGS demonstrates significant clinical utility in these cases, including: (1) detecting homologous recombination deficiency with underlying somatic causal variants (case 1), (2) distinguishing double primary cancer from metastasis (case 2), (3) uncovering microsatellite instability (case 3), and (4) identifying rare germline pathogenic variants in TP53 gene (case 4). Our observations underscore the enhanced clinical relevance of WGS-based testing beyond pinpointing a few driver mutations in conventional targeted panel sequencing platforms. Conclusion: With genomic advancements and decreasing sequencing costs, WGS stands out as a transformative tool in oncology, paving the way for personalized treatment plans rooted in individual genetic blueprints.

8.
Sci Rep ; 14(1): 498, 2024 01 04.
Article in English | MEDLINE | ID: mdl-38177229

ABSTRACT

We aimed to determine the effect of optic disc tilt on deep learning-based optic disc classification. A total of 2507 fundus photographs were acquired from 2236 eyes of 1809 subjects (mean age of 46 years; 53% men). Among all photographs, 1010 (40.3%) had tilted optic discs. Image annotation was performed to label pathologic changes of the optic disc (normal, glaucomatous optic disc changes, disc swelling, and disc pallor). Deep learning-based classification modeling was implemented to develop optic-disc appearance classification models with the photographs of all subjects and those with and without tilted optic discs. Regardless of deep learning algorithms, the classification models showed better overall performance when developed based on data from subjects with non-tilted discs (AUC, 0.988 ± 0.002, 0.991 ± 0.003, and 0.986 ± 0.003 for VGG16, VGG19, and DenseNet121, respectively) than when developed based on data with tilted discs (AUC, 0.924 ± 0.046, 0.928 ± 0.017, and 0.935 ± 0.008). In classification of each pathologic change, non-tilted disc models had better sensitivity and specificity than the tilted disc models. The optic disc appearance classification models developed based all-subject data demonstrated lower accuracy in patients with the appearance of tilted discs than in those with non-tilted discs. Our findings suggested the need to identify and adjust for the effect of optic disc tilt on the optic disc classification algorithm in future development.


Subject(s)
Deep Learning , Eye Abnormalities , Glaucoma , Optic Disk , Male , Humans , Middle Aged , Female , Optic Disk/diagnostic imaging , Optic Disk/pathology , Tomography, Optical Coherence/methods , Eye Abnormalities/pathology , Glaucoma/diagnosis , Glaucoma/pathology
9.
J Adolesc Health ; 74(4): 828-836, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38069939

ABSTRACT

PURPOSE: This study aims to examine the association between bullying victimization and depressive symptoms among youth from multicultural families in Korea, while distinguishing between the effects of entering and exiting bullying victimization. This study also investigates whether parental education moderates this association. METHODS: Using data from the Multicultural Adolescent Panel Survey, a nationally representative sample of children from multicultural families in Korea, this study employed novel asymmetric fixed-effects models that separately assess the effects of entering and exiting bullying victimization. Interaction models were conducted to consider the moderating roles of maternal and paternal college attainment. RESULTS: Conventional fixed-effects models showed that bullying victimization is significantly associated with an increase in depressive symptoms (b = 0.261). Asymmetric fixed-effects models suggest that the magnitude of the entry effect (b = 0.299) was significantly larger than that of the exit effect (b = -0.237). Furthermore, maternal college education amplified the mental health benefits of exiting from bullying victimization but did not buffer the harmful effects of entering bullying victimization. Gender-stratified analyses indicate that this protective effect of maternal college education was only significant for girls. Paternal college education, on the other hand, did not moderate either the entry or exit effects of bullying victimization. DISCUSSION: The study's findings on the asymmetric effects of bullying victimization on depressive symptoms emphasize the importance of providing follow-up care and mental health support for multicultural family youth who have experienced bullying, with particular attention to those with a history of victimization.


Subject(s)
Bullying , Crime Victims , Child , Female , Adolescent , Humans , Depression/psychology , Surveys and Questionnaires , Parents
10.
Soc Sci Med ; 341: 116539, 2024 01.
Article in English | MEDLINE | ID: mdl-38160611

ABSTRACT

Previous studies have found that those with precarious jobs report lower levels of life satisfaction than those with non-precarious jobs. However, it is unclear whether transitioning into and out of precarious jobs has differential effects on life satisfaction. This study examines the association between employment status transitions and life satisfaction, as well as gender differences in these associations. Data from the Korean Welfare Panel Study (N = 9,792) from 2006 to 2020 were used in this study. A novel asymmetric fixed effects model was employed to separately estimate the association for transitioning into and out of precarious employment. Gender heterogeneity was estimated by including an interaction term of gender and employment transition. Standard fixed effects estimates showed that precarious employment is negatively associated with life satisfaction (b = -0.048). Asymmetric fixed effects models revealed that transitioning out of precarious employment is associated with increased life satisfaction (b = 0.051), while transitioning into a precarious job is not significantly associated with life satisfaction. These asymmetric associations were more pronounced for men than women. This study provides evidence that, especially for men, the association for transitioning out of precarious employment is significantly larger than the association for transitioning into precarious employment. Policies that facilitate the transition into stable employment are likely to enhance the quality of life for employed individuals.


Subject(s)
Job Security , Quality of Life , Male , Humans , Female , Health Status , Employment , Occupations
11.
bioRxiv ; 2023 Nov 27.
Article in English | MEDLINE | ID: mdl-38077071

ABSTRACT

Adult females of reproductive ages develop greater antibody responses to inactivated influenza vaccine (IIV) than males. How sex, age, and sex steroid changes impact B cells and durability of IIV-induced immunity and protection over 4-months post-vaccination (mpv) was analyzed. Vaccinated adult females had greater germinal center (GC) B cell and plasmablast frequencies in lymphoid tissues, higher neutralizing antibody responses 1-4 mpv, and better protection against live H1N1 challenge than adult males. Aged mice, regardless of sex, had reduced B cell frequencies, less durable antibody responses, and inferior protection after challenge than adult mice, which correlated with diminished estradiol among aged females. To confirm that greater IIV-induced immunity was caused by sex hormones, four core genotype (FCG) mice were used, in which the testes determining gene, Sry, was deleted from ChrY and transferred to Chr3, to separate gonadal sex (i.e., ovaries or testes) from sex chromosome complement (i.e., XX or XY complement). Vaccinated, gonadal female FCG mice (XXF and XYF) had greater numbers of B cells, higher antiviral antibody titers, and reduced pulmonary virus titers following live H1N1 challenge than gonadal FCG males (XYM and XXM). To establish that lower estradiol concentrations cause diminished immunity, adult and aged females received either a placebo or estradiol replacement therapy prior to IIV. Estradiol replacement significantly increased IIV-induced antibody responses and reduced morbidity after the H1N1 challenge among aged females. These data highlight that estradiol is a targetable mechanism mediating greater humoral immunity following vaccination among adult females.

12.
Res Sq ; 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-38014049

ABSTRACT

Critically ill people with COVID-19 have greater antibody titers than those with mild to moderate illness, but their association with recovery or death from COVID-19 has not been characterized. In 178 COVID-19 patients, 73 non-hospitalized and 105 hospitalized patients, mucosal swabs and plasma samples were collected at hospital enrollment and up to 3 months post-enrollment (MPE) to measure virus RNA, cytokines/chemokines, binding antibodies, ACE2 binding inhibition, and Fc effector antibody responses against SARS-CoV-2. The association of demographic variables and >20 serological antibody measures with intubation or death due to COVID-19 was determined using machine learning algorithms. Predictive models revealed that IgG binding and ACE2 binding inhibition responses at 1 MPE were positively and C1q complement activity at enrollment was negatively associated with an increased probability of intubation or death from COVID-19 within 3 MPE. Serological antibody measures were more predictive than demographic variables of intubation or death among COVID-19 patients.

13.
IDCases ; 34: e01907, 2023.
Article in English | MEDLINE | ID: mdl-37867567

ABSTRACT

Rhabditiasis, caused by Rhabditis nematode, has long been recognized as a veterinary concern, however, human infection is exceedingly rare. For the first time in Bangladesh, this study confirmed human rhabditiasis infecting a 12-year-old child. The identification was made based on morphometric features and confirmed by amplifying the mitochondrial cox1 gene. During microscopical examination of stool samples, heavy infection with several developmental stages (larvae, adult males, and females) of nematodes was observed. Following morphometric analysis, the nematode was identified as Rhabditis sp. The features used in confirming the species were elongated tail, bulbous enlargement of mid-esophagus, and presence of adult males passed in the stool. The results of the phylogenetic analysis showed that isolates of Rhabditis sp. belonged to distinct clades alongside S. stercoralis.

14.
Immun Ageing ; 20(1): 43, 2023 Aug 29.
Article in English | MEDLINE | ID: mdl-37644610

ABSTRACT

BACKGROUND: Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to generate hypotheses as to the biological mechanism underpinning the AE reported. RESULTS: A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. CONCLUSIONS: These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

15.
Cell Chem Biol ; 30(7): 726-738.e4, 2023 07 20.
Article in English | MEDLINE | ID: mdl-37354908

ABSTRACT

Understanding the mechanisms of antibody-mediated neutralization of SARS-CoV-2 is critical in combating the COVID-19 pandemic. Based on previous reports of antibody catalysis, we investigated the proteolysis of spike (S) by antibodies in COVID-19 convalescent plasma (CCP) and its contribution to viral neutralization. Quenched fluorescent peptides were designed based on S epitopes to sensitively detect antibody-mediated proteolysis. We observed epitope cleavage by CCP from different donors which persisted when plasma was heat-treated or when IgG was isolated from plasma. Further, purified CCP antibodies proteolyzed recombinant S domains, as well as authentic viral S. Cleavage of S variants suggests CCP antibody-mediated proteolysis is a durable phenomenon despite antigenic drift. We differentiated viral neutralization occurring via direct interference with receptor binding from that occurring by antibody-mediated proteolysis, demonstrating that antibody catalysis enhanced neutralization. These results suggest that antibody-catalyzed damage of S is an immunologically relevant function of neutralizing antibodies against SARS-CoV-2.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Proteolysis , Pandemics , COVID-19/therapy , COVID-19 Serotherapy , Spike Glycoprotein, Coronavirus , Peptide Hydrolases , Antibodies, Neutralizing , Epitopes , Antibodies, Viral
16.
medRxiv ; 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37131659

ABSTRACT

BACKGROUND: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis. RESULTS: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01. CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460. FUNDING: Defense Health Agency and others.

18.
Chemistry ; 29(33): e202300080, 2023 Jun 13.
Article in English | MEDLINE | ID: mdl-36997502

ABSTRACT

Self-replication of nucleic acids in the absence of enzymes represents an important and poorly understood step in the origin of life as such reported systems are strongly hindered by product inhibition. Studying one of the few successful examples of enzymatic DNA self-replication based on a simple ligation chain reaction, lesion-induced DNA amplification (LIDA), can shed light on how this fundamental process may have originally evolved. To identify the unknown factors that lead LIDA to overcome product inhibition we have employed isothermal titration calorimetry and global fitting of time-dependent ligation data to characterize the individual steps of the amplification process. We find that incorporating the abasic lesion into one of the four primers substantially decreases the stability difference between the product and intermediate complexes compared with complexes without the abasic group. In the presence of T4 DNA ligase this stability gap is further reduced by two orders of magnitude revealing that the ligase also helps overcome product inhibition. Kinetic simulations reveal that the intermediate complex stability and the magnitude of the ligation rate constant significantly impact the rate of self-replication, suggesting that catalysts that both facilitate ligation and stabilize the intermediate complex might be a route to efficient nonenzymatic replication.


Subject(s)
DNA Ligases , Nucleic Acid Amplification Techniques , DNA Ligases/chemistry , DNA Ligases/genetics , DNA Ligases/metabolism , Catalysis , DNA/chemistry , DNA Replication
19.
Res Sq ; 2023 Feb 08.
Article in English | MEDLINE | ID: mdl-36798418

ABSTRACT

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5-8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to elucidate a possible biological mechanism for the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

20.
Sci Rep ; 13(1): 133, 2023 01 04.
Article in English | MEDLINE | ID: mdl-36599848

ABSTRACT

Accurate diagnosis by precise identification of causative agents is essential for the effectiveness of any control interventions. Despite high zoonotic potential, available literature on hookworms in Bangladesh is still scarce and nonspecific. The objective of this study was to determine the occurrence of hookworms in public locations across northeastern Bangladesh (Sylhet metropolitan area) using integrated parasitological and molecular assays. A total of 130 samples (80 soil and 50 environmental canine feces) were collected and examined using modified flotation technique and formalin-ether sedimentation methods. Modified plate culture was used to isolate larvae. The identification was made based on morphometric features and confirmed by amplifying the ITS region of the nuclear rDNA. Overall, 66.2% (86/130) of examined samples were positive for hookworms infection. Characteristic eggs (61-68 × 29-37 µm) and/or larvae of hookworms were observed in 73.8% (59/80) soils and 54.0% (27/50) environmental fecal samples. Rhabditiform larvae (0.48-0.54 × 0.04-0.07 mm) were observed in cultured samples. Genetic analysis of rDNA sequences revealed the presence of Ancylostoma caninum and Ancylostoma ceylanicum. In this study, hookworms' contamination of the public environment was substantial. To the best of our knowledge, this is the first molecular proof of A. caninum and A. ceylanicum observed in urban public environment in Bangladesh.


Subject(s)
Dog Diseases , Hookworm Infections , Animals , Dogs , Ancylostomatoidea/genetics , Bangladesh , Hookworm Infections/epidemiology , Ancylostoma/genetics , Feces , DNA, Ribosomal , Soil , Larva , Dog Diseases/epidemiology
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