RESUMO
Despite mounting evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engagement with immune cells, most express little, if any, of the canonical receptor of SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2). Here, using a myeloid cell receptor-focused ectopic expression screen, we identified several C-type lectins (DC-SIGN, L-SIGN, LSECtin, ASGR1, and CLEC10A) and Tweety family member 2 (TTYH2) as glycan-dependent binding partners of the SARS-CoV-2 spike. Except for TTYH2, these molecules primarily interacted with spike via regions outside of the receptor-binding domain. Single-cell RNA sequencing analysis of pulmonary cells from individuals with coronavirus disease 2019 (COVID-19) indicated predominant expression of these molecules on myeloid cells. Although these receptors do not support active replication of SARS-CoV-2, their engagement with the virus induced robust proinflammatory responses in myeloid cells that correlated with COVID-19 severity. We also generated a bispecific anti-spike nanobody that not only blocked ACE2-mediated infection but also the myeloid receptor-mediated proinflammatory responses. Our findings suggest that SARS-CoV-2-myeloid receptor interactions promote immune hyperactivation, which represents potential targets for COVID-19 therapy.
Assuntos
COVID-19/metabolismo , COVID-19/virologia , Interações Hospedeiro-Patógeno , Lectinas Tipo C/metabolismo , Proteínas de Membrana/metabolismo , Células Mieloides/imunologia , Células Mieloides/metabolismo , Proteínas de Neoplasias/metabolismo , SARS-CoV-2/fisiologia , Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação , COVID-19/genética , Linhagem Celular , Citocinas , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Mediadores da Inflamação/metabolismo , Lectinas Tipo C/química , Proteínas de Membrana/química , Modelos Moleculares , Proteínas de Neoplasias/química , Ligação Proteica , Conformação Proteica , Anticorpos de Domínio Único/imunologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Relação Estrutura-AtividadeRESUMO
Gastrointestinal effects associated with Coronavirus Disease 2019 (COVID-19) are highly variable for reasons that are not understood. In this study, we used intestinal organoid-derived cultures differentiated from primary human specimens as a model to examine interindividual variability. Infection of intestinal organoids derived from different donors with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) resulted in orders of magnitude differences in virus replication in small intestinal and colonic organoid-derived monolayers. Susceptibility to infection correlated with angiotensin I converting enzyme 2 (ACE2) expression level and was independent of donor demographic or clinical features. ACE2 transcript levels in cell culture matched the amount of ACE2 in primary tissue, indicating that this feature of the intestinal epithelium is retained in the organoids. Longitudinal transcriptomics of organoid-derived monolayers identified a delayed yet robust interferon signature, the magnitude of which corresponded to the degree of SARS-CoV-2 infection. Interestingly, virus with the Omicron variant spike (S) protein infected the organoids with the highest infectivity, suggesting increased tropism of the virus for intestinal tissue. These results suggest that heterogeneity in SARS-CoV-2 replication in intestinal tissues results from differences in ACE2 levels, which may underlie variable patient outcomes.
Assuntos
COVID-19 , Enzima de Conversão de Angiotensina 2/genética , Humanos , Organoides , SARS-CoV-2RESUMO
Historically, the evolution of bats has been analyzed using a small number of genetic loci for many species or many genetic loci for a few species. Here we present a phylogeny of 18 bat species, each of which is represented in 1,107 orthologous gene alignments used to build the tree. We generated a transcriptome sequence of Hypsignathus monstrosus, the African hammer-headed bat, and additional transcriptome sequence for Rousettus aegyptiacus, the Egyptian fruit bat. We then combined these data with existing genomic and transcriptomic data from 16 other bat species. In the analysis of such datasets, there is no clear consensus on the most reliable computational methods for the curation of quality multiple sequence alignments since these public datasets represent multiple investigators and methods, including different source materials (chromosomal DNA or expressed RNA). Here we lay out a systematic analysis of parameters and produce an advanced pipeline for curating orthologous gene alignments from combined transcriptomic and genomic data, including a software package: the Mismatching Isoform eXon Remover (MIXR). Using this method, we created alignments of 11,677 bat genes, 1,107 of which contain orthologs from all 18 species. Using the orthologous gene alignments created, we assessed bat phylogeny and also performed a holistic analysis of positive selection acting in bat genomes. We found that 181 genes have been subject to positive natural selection. This list is dominated by genes involved in immune responses and genes involved in the production of collagens.
Assuntos
Quirópteros/genética , Genoma/genética , Seleção Genética/genética , Transcriptoma/genética , Sequência de Aminoácidos , Animais , Estudo de Associação Genômica Ampla/métodos , Filogenia , Alinhamento de SequênciaRESUMO
This study aims to present the current state of knowledge on the DNA-based prediction of human externally visible characteristics of an unknown person based on the crime scene biological material left behind. This DNA sample is referred to as a "biological witness" and the procedure itself is called forensic DNA phenotyping (FDP). The analytic part of this work is based on scholarly articles published between 2015 and 2021. The electronic search of relevant references was conducted according to the PRISMA methodology in March 2021 at EBSCO Discovery Service (EDS) at the Adam Mickiewicz University library and Google Scholar. The molecular basis of FDP, DNA markers used to predict sex, age, biogeographic origin and externally visible traits such as pigmentation (skin, eye and hair colour), hair morphology, facial morphology, presence of freckles, body height, body weight (obesity), male pattern baldness and myopia were described. Furthermore, methodological difficulties resulting from the polygenic inheritance of the studied traits, as well as social and ethical problems accompanying forensic DNA phenotyping were discussed. Finally, key themes for future research related to forensic DNA phenotyping were outlined.
Assuntos
Cor de Olho , Genética Forense , Feminino , Humanos , Masculino , DNA/genética , Genética Forense/métodos , Cor de Cabelo , FenótipoRESUMO
OBJECTIVES: The aim of this study was to assess time intervals between the age at menarche (AM) and age at sexual initiation (ASI) in Polish women born before and after the political transformation period in Poland. METHODS: Participants were 518 women born between 1959 and 2001 in Poland. AM and ASI were based on self-report. Three birth cohorts were distinguished based on the year of birth: I (1959-1979), II (1980-1989), III (1990-2001). Three categories of AM were distinguished: early maturing (<12.0 years), average (12.0-13.0 years), and late maturing (≥14.0 years). Temporal intervals between AM and ASI were calculated. RESULTS: Both AM and ASI decreased in subsequent birth cohorts, with the greatest changes observed in the women born after 1989. No significant differences in the time interval between AM and ASI were observed between birth cohorts. However, the time interval between AM and ASI differed by AM category (H = 74.16; P < .001). The longest time period between AM and ASI occurred in early maturing girls (7.13 years) and the shortest in late maturing girls (3.25 years). CONCLUSIONS: Despite the transformation and decline in both AM and ASI, the time interval between these two characteristics remained stable. Significant differences in the time interval were found among women stratified by AM. The time interval between AM and ASI was longer in girls who matured early in comparison to those maturing late or at the average time.
Assuntos
Desenvolvimento do Adolescente , Menarca , Comportamento Sexual , Adolescente , Fatores Etários , Criança , Feminino , Humanos , Polônia , Fatores Socioeconômicos , Fatores de TempoRESUMO
PURPOSE: To evaluate the relationship between recent stressful life events (SLEs), stress-related symptoms (SRSs), and health-related quality of life (HRQoL) in children beginning primary school. METHODS: A community-based sample of 6- to 8-year-old children (176 boys and 175 girls at baseline) participated in a prospective longitudinal study with three waves of data collection and 1-year interval between subsequent surveys, conducted in the Wielkopolska Province, Poland. Main exposures included nine recent stressful life events and psychosomatic and behavioural symptoms related to stress (SRSs), both self-reported by children. The outcome was total HRQoL assessed by a Polish version of the PedsQL™ 4.0 (Pediatric Quality of Life Inventory) Generic Core Scales questionnaire, 5- to 7-year-old version. To evaluate the relationship between total HRQoL and predictor variables, a latent growth curve (LGC) model using multiple group design (boys and girls) with three waves and two time-varying covariates, the SLEs and SRSs, was applied. RESULTS: An unconditional multi-group LGC model revealed that the total HRQoL changed over time in a linear trajectory. After incorporating to the model, two time-varying covariates, SLEs and SRSs, the first predictor for HRQoL was only significant at the last wave in girls and at two subsequent waves, except for baseline, in boys. The second predictor revealed significant negative impacts on HRQoL over the entire period of time in both boys and girls suggesting that the pathway underlying the association of SLEs with HRQoL may be mediated by SRSs. Mean values of HRQoL at each time points did not show gender differences. CONCLUSIONS: The findings of the present study may help to develop and implement a health and safety protection training programmes addressed to parents, caregivers, and practitioners to make children's lives easier.
Assuntos
Acontecimentos que Mudam a Vida , Qualidade de Vida/psicologia , Criança , Feminino , Humanos , Estudos Longitudinais , Masculino , Polônia , Estudos Prospectivos , Instituições Acadêmicas , Inquéritos e QuestionáriosRESUMO
The increasing prevalence of negative body perceptions among adolescent girls and the tendency towards wishing to be thinner have become a cultural norm in Western culture. Adolescent girls are particularly vulnerable to developing a negative body image due to physical and sexual changes occurring during puberty. This study aimed to evaluate the association between different measures of body image perceptions and different phases of the menstrual cycle after controlling for weight status and other potential confounders in Polish adolescent girls aged 12-18 years. Three-hundred and thirty participants of a cross-sectional survey conducted in 2009, normally cycling and with no eating disorders, completed a background questionnaire and the Stunkard Figure Rating Scale, and their anthropometric measurements were collected. The dependent outcome variables were measures of body image (actual body image, ideal body image and ideal-self discrepancy) and dichotomous body image perception (satisfied versus dissatisfied) adjusted for other predictor factors: socio-demographic variables, menstrual history and cycle phases, and weight status. One-way ANOVA indicated that weight status, age at menarche and menstrual cycle phase were associated with actual body image and rate of ideal-self discrepancy. Ideal body image was associated with weight status and menstrual cycle phase. General logistic regression models were constructed to evaluate associations of body dissatisfaction and all potential predictor variables. The final selected model of the multiple logistic regression analysis using the backward elimination procedure revealed that adjusted for other factors, negative body image was significantly associated with different phases of the menstrual cycle (p trend=0.033) and increasing body weight status (p trend=0.0007). The likelihood of body dissatisfaction was greatest during the premenstrual phase of the menstrual cycle (OR=2.38; 95% CI 1.06, 5.32) and among girls in obesity class I (OR=8.04; 95% CI 2.37, 27.26). The study confirmed the association between body image dissatisfaction in adolescent girls and different phases of the menstrual cycle after controlling for weight status. The issue of negative body self-image is not only of cognitive, but also of practical value as understanding better the factors contributing to the formation of a negative body image may be instrumental in developing preventive health programmes targeted at young people.
Assuntos
Imagem Corporal , Ciclo Menstrual , Adolescente , Peso Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Obesidade , Polônia , Inquéritos e QuestionáriosRESUMO
UNLABELLED: In Poland, there is no data on parental socioeconomic status (SES) as a potent risk factor in adolescent elevated blood pressure, although social differences in somatic growth and maturation of children and adolescents have been recorded since the 1980s. This study aimed to evaluate the association between parental SES and blood pressure levels of their adolescent offspring. A cross-sectional survey was carried out between 2009 and 2010 on a sample of 4941 students (2451 boys and 2490 girls) aged 10-18, participants in the ADOPOLNOR study. The depended outcome variable was the level of blood pressure (optimal, pre- and hypertension) and explanatory variables included place of residence and indicators of parental SES: family size, parental educational attainments and occupation status, income adequacy and family wealth. The final selected model of the multiple multinomial logistic regression analysis (MLRA) with backward elimination procedure revealed the multifactorial dependency of blood pressure levels on maternal educational attainment, paternal occupation and income adequacy interrelated to urbanization category of the place of residence after controlling for family history of hypertension, an adolescent's sex, age and weight status. Consistent rural-to-urban and socioeconomic gradients were found in prevalence of elevated blood pressure, which increased with continuous lines from large cities through small- to medium-sized cities to villages and from high-SES to low-SES familial environments. The adjusted likelihood of developing systolic and diastolic hypertension decreased with each step increase in maternal educational attainment and increased urbanization category. The likelihood of developing prehypertension decreased with increased urbanization category, maternal education, paternal employment status and income adequacy. Weight status appeared to be the strongest confounder of adolescent blood pressure level and, at the same time, a mediator between their blood pressure and parental SES. CONCLUSION: The findings of the present study confirmed socioeconomic disparities in blood pressure levels among adolescents. This calls for regularly performed blood pressure assessment and monitoring in the adolescent population. It is recommended to focus on obesity prevention and socioeconomic health inequalities by further trying to improve living and working conditions in adverse rural environments.
Assuntos
Pressão Sanguínea/fisiologia , Disparidades nos Níveis de Saúde , Hipertensão/epidemiologia , Classe Social , Adolescente , Saúde do Adolescente , Antropometria , Determinação da Pressão Arterial , Criança , Estudos Transversais , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pais , Polônia/epidemiologia , Prevalência , Fatores de Risco , Fatores SocioeconômicosRESUMO
BACKGROUND: Genes involved in the IGF-1 aging pathways in the human ovary can be considered strong candidates for predictors of the natural menopause timing. This study evaluates the association between a cytosine-adenine (CA) microsatellite polymorphism in the IGF1 gene promoter P1 and age at natural menopause. METHODS: Genomic DNA was extracted from the peripheral blood, PCR was performed using primers designed to amplify the polymorphic (CA) n repeat of the human IGF1 gene, an allele dose effect for the most common (CA)19 repeats allele, Cox proportional hazard regression models and the Kaplan-Meier cumulative survivorship method with the log-rank test were used to determine statistical significance of studied associations in a sample of 257 Polish women aged 40-58 years. RESULTS: Crude Cox proportional hazard regression analysis confirmed the association between the IGF1 gene polymorphism and the menopause timing (p=0.038). This relationship remained statistically significant after controlling for other menopause confounders in multivariate modelling. Out of the input variables, the (CA)n polymorphism in the IGF1 gene promoter, age at menarche and smoking status were independent covariates of the natural menopause timing (χ2=12.845; df=3; p=0.034). The onset of menopause at a younger age was likely associated with the IGF1 genotype variant not carrying the (CA)19 repeats allele, menarche before the age of 12 and a current cigarette smoker status (HR=1.6). CONCLUSION: This study provides evidence that a common cytosine-adenine (CA) microsatellite repeat polymorphism in the P1 promoter region of the IGF1 gene is an independent predictive factor for age at natural menopause in Caucasian women also after adjusting for other menopause covariates.
Assuntos
Fator de Crescimento Insulin-Like I/genética , Menopausa/genética , Repetições de Microssatélites , Regiões Promotoras Genéticas , Adulto , Estudos Transversais , Feminino , Frequência do Gene , Humanos , Menarca/genética , Pessoa de Meia-Idade , Polimorfismo Genético , Modelos de Riscos Proporcionais , População Branca/genéticaRESUMO
BACKGROUND: Proper age of sexual initiation remains a topical issue in developmental sexology and gynecology Premature sexual début is a risk factor for sexually transmitted diseases (STD) and their consequences: unplanned pregnancy and emotional stress. Consequences of risky sexual behavior (young age of sexual initiation, number of sexual partners or using unsafe contraceptive methods) are more severe for women. State of knowledge about sexual activity of Polish women is still insufficient, whereas patterns of sexual behavior are in the process of undergoing dramatic changes due to the influence of the western culture. OBJECTIVES: Two main aims of the study were: (1) to examine whether age of sexual début and patterns of sexual behavior have changed over the past decades among young Polish women and (2) to consider the medical and legal aspects regarding juvenile patients who are sexually active. MATERIALS AND METHODS: Two hundred women, born within two consecutive decades (1975-1995) in the Wielkopolska region (Poland) were asked to fill in a questionnaire concerning the following: age at sexual initiation and the contraceptive method used at the time, preferred forms of sexual activity current contraceptive methods. Statistical analysis was performed using the Statistica 9.0 software [StatSoft]. Statistical evaluation was based on the chi-square test and analysis of covariance (ANCOVA). RESULTS: The average age of sexual initiation decreased significantly between the two studied cohorts of women and ranged from 18.9 for women born between 1975 and 1984 (cohort I) and 17.6 for women born between 1985 and 1995 (cohort II), regardless of the place of residence. The percentage of women who had their first sexual intercourse by the age of 15 years was 0% in cohort I and 8.2% in cohort II. Other characteristics of sexual activity were similar across the studied cohorts of women. Condom use during the first sexual intercourse was the preferred form of contraception (59.2%). 65% women have reported current contraceptive use. As for the preferred type of intercourse, all women (100%) chose vaginal sex. The most frequent number of sexual intercourses per month was 7 or more (41.7%). CONCLUSIONS: The age of sexual début among Polish women has decreased significantly over the last decades. Premature initiation is believed to increase the risk of unplanned pregnancy STDs and emotional stress. Polish medical and legal circles lack unequivocal stand on how to deal with juvenile patients who are sexually active, expect to receive advice from a gynecologist, a gynecologic examination and prescribed contraceptives.
Assuntos
Anticoncepção/estatística & dados numéricos , Serviços de Planejamento Familiar/legislação & jurisprudência , Nível de Saúde , Comportamento Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/prevenção & controle , Saúde da Mulher/legislação & jurisprudência , Adulto , Distribuição por Idade , Fatores Etários , Atitude Frente a Saúde , Estudos de Coortes , Feminino , Humanos , Polônia/epidemiologia , Gravidez , Gravidez não Planejada , Sexo Seguro/estatística & dados numéricos , Comportamento Sexual/psicologia , Parceiros Sexuais , Infecções Sexualmente Transmissíveis/epidemiologia , Sexo sem Proteção/estatística & dados numéricos , Adulto JovemRESUMO
The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from adolescents. Accuracy of the method was tested in a group of 513 adolescents, almost 11% of subjects were positive for infection with herpes viruses. Correlations with gender, age, and place of residence were sought. A similar incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2, HCMV was detected mostly in the youngest individuals. The same occurrence of all viruses was observed in boys and girls. The mPCR method described is suggested as a useful tool for epidemiologic studies of active herpes infections.
Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Herpes Simples/diagnóstico , Herpesvirus Humano 1/isolamento & purificação , Herpesvirus Humano 2/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Adolescente , Criança , Citomegalovirus/genética , Infecções por Citomegalovirus/epidemiologia , DNA Viral/genética , Células Epiteliais/virologia , Feminino , Herpes Simples/epidemiologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Humanos , Incidência , Masculino , Mucosa Bucal/virologia , PolôniaRESUMO
UNLABELLED: Human papillomaviruses (HPVs) are a very complex group of pathogenic viruses, with more than 80 types, causing human infection. Given the prevalence of HPV infection and its relationship with the development of cervical and many other cancers, HPV vaccine development has been a major public health initiative worldwide in the last decade. The aim of the presented study was to identify HPV DNA by MY-PCR in 4,150 school children and adolescents, aged 10-18 years in the Wielkopolska region, Poland. All individuals were asked to fill in extensive questionnaires; further normal, oral squamous cells were collected from each pupil. Cellular DNA was isolated and used as a MY-PCR template to estimate the incidence of HPV-active infection. Forty five subjects (1.08% of the sample) were carriers of oropharyngeal HPVs. HPV status and variables of interest, such as age, gender, socioeconomical status, and risk factors (smoking and sexual intercourse history, alcohol consumption) were not correlated. The presence of HPVs in the oral cavity was cumulated in several schools of the region. DNA sequencing of MY-PCR products revealed only four HPV genotypes. The most frequent genotype was HPV11 (38/45 HPV-positive cases), while other more rare genotypes were HPV6 (3/45), HPV12 (3/45), and HPV57 (1/45). CONCLUSION: Our findings presented herein, reveal a relatively low prevalance of oropharyngeal HPVs in Polish adolescents and fill an important gap in the knowledge of oral HPV infections of children above 10 years and adolescents.
Assuntos
Alphapapillomavirus/genética , Boca/virologia , Orofaringe/virologia , Adolescente , Alphapapillomavirus/classificação , Alphapapillomavirus/isolamento & purificação , Criança , Estudos Transversais , Feminino , Genótipo , Humanos , Incidência , Masculino , Polônia/epidemiologia , Reação em Cadeia da Polimerase , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
Higher stress reactivity during adolescence is a vulnerability marker of exposure to various environmental stressors. This study aimed to investigate the association between a high level of perceived stress experienced by adolescents and stressful stimuli induced from school environment, peer, and parental relationships. The data used were from a cross-sectional, observational study conducted in a stratified sample of 1846 adolescents (13-18 years) in the Wielkopolska province, Poland. Data were collected through self-administered questionnaires and anthropometric measurements. Perceived stress was assessed using the Perceived Stress Scale (PSS-10). The association of a high level of perceived stress with school-induced exposures was determined using multivariate logistic regression after adjusting for gender, age, height and weight status and interpersonal relationships (STATISTICA 13.1). It was found that girls were over three times more likely than boys to experience a high level of perceived stress. Moreover, girls appeared to be more vulnerable than boys to school-related stressors and weight status, while boys to stressors that can arise from interpersonal relationships. School environment was the only predictor factor of high perceived stress level with a large effect size in both boys (OR = 4.45; 95% CI: 3.11-6.36) and girls (OR = 6.22; 95% CI: 4.18-7.59). Given the findings of the present study, preventive programs are critical to mitigate the effect of stress from school on adolescents' health and well-being.
Assuntos
Comportamento do Adolescente , Instituições Acadêmicas , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Polônia/epidemiologia , Estresse Psicológico/epidemiologia , Inquéritos e QuestionáriosRESUMO
Epidemic RNA viruses seem to arise year after year leading to countless infections and devastating disease. SARS-CoV-2 is the most recent of these viruses, but there will undoubtedly be more to come. While effective SARS-CoV-2 vaccines are being deployed, one approach that is still missing is effective antivirals that can be used at the onset of infections and therefore prevent pandemics. Here, we screened FDA-approved compounds against SARS-CoV-2. We found that atovaquone, a pyrimidine biosynthesis inhibitor, is able to reduce SARS-CoV-2 infection in human lung cells. In addition, we found that berberine chloride, a plant-based compound used in holistic medicine, was able to inhibit SARS-CoV-2 infection in cells through direct interaction with the virion. Taken together, these studies highlight potential avenues of antiviral development to block emerging viruses. Such proactive approaches, conducted well before the next pandemic, will be essential to have drugs ready for when the next emerging virus hits.
Assuntos
Antivirais/farmacologia , Atovaquona/farmacologia , Berberina/farmacologia , SARS-CoV-2/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , Células Epiteliais Alveolares , Animais , Berberina/química , Proliferação de Células/efeitos dos fármacos , Cloretos/química , Cloretos/farmacologia , Chlorocebus aethiops , Sinergismo Farmacológico , Humanos , Proguanil/farmacologia , Células Vero , Vírion/efeitos dos fármacosRESUMO
Understanding antibody responses to SARS-CoV-2 is indispensable for the development of containment measures to overcome the current COVID-19 pandemic. Recent studies showed that serum from convalescent patients can display variable neutralization capacities. Still, it remains unclear whether there are specific signatures that can be used to predict neutralization. Here, we performed a detailed analysis of sera from a cohort of 101 recovered healthcare workers and we addressed their SARS-CoV-2 antibody response by ELISA against SARS-CoV-2 Spike receptor binding domain and nucleoprotein. Both ELISA methods detected sustained levels of serum IgG against both antigens. Yet, the majority of individuals from our cohort generated antibodies with low neutralization capacity and only 6% showed high neutralizing titers against both authentic SARS-CoV-2 virus and the Spike pseudotyped virus. Interestingly, higher neutralizing sera correlate with detection of -IgG, IgM and IgA antibodies against both antigens, while individuals with positive IgG alone showed poor neutralization response. These results suggest that having a broader repertoire of antibodies may contribute to more potent SARS-CoV-2 neutralization. Altogether, our work provides a cross sectional snapshot of the SARS-CoV-2 neutralizing antibody response in recovered healthcare workers and provides preliminary evidence that possessing multiple antibody isotypes can play an important role in predicting SARS-CoV-2 neutralization.
Assuntos
Anticorpos Neutralizantes/imunologia , COVID-19/imunologia , SARS-CoV-2/imunologia , Adulto , Anticorpos Antivirais/imunologia , COVID-19/terapia , Estudos de Coortes , Estudos Transversais , Ensaio de Imunoadsorção Enzimática/métodos , Epitopos/imunologia , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Testes de Neutralização/métodos , Pandemias , SARS-CoV-2/patogenicidade , Soro/imunologia , Glicoproteína da Espícula de Coronavírus/imunologiaRESUMO
In an increasingly interconnected world, the exposure and subsequent spread of emergent viruses has become inevitable. This is particularly true for Aedes (Ae.) mosquito-vectored viruses, whose range has increased over the past decade from tropical to temperate regions. However, it is unclear if all populations of Ae. mosquitoes in temperate New York City are able to successfully replicate and transmit arboviruses. To answer this question, we reared Ae. albopictus mosquitoes living in a temperate climate from three locations in New York City. We first sequenced the salivary antiviral protein D7 from individual mosquitoes in each population and found single nucleotide variants that are both shared and unique for each Ae. albopictus population. We then fed each population chikungunya virus (CHIKV) via an artificial blood meal. All three mosquito populations could be infected with CHIKV, yet viral titers differed between populations at 7 days post infection. Moreover, we found that these mosquitoes could transmit CHIKV to mice, and that virus RNA reached the saliva as early as two days post infection. Upon sequencing of the saliva CHIKV genomic RNA, we found mutations at sites correlated with increased transmission and virulence. These studies show that NYC Ae. albopictus populations can be infected with and transmit CHIKV, CHIKV is able to evolve in these mosquitoes, and that host salivary factors display population-specific diversity. Taken together, these studies highlight the need to study how distinct mosquito populations control viral infections, both at the virus and host level.
Assuntos
Aedes/virologia , Febre de Chikungunya/transmissão , Vírus Chikungunya/fisiologia , Proteínas de Insetos/metabolismo , Mosquitos Vetores/virologia , Proteínas e Peptídeos Salivares/metabolismo , Animais , Febre de Chikungunya/virologia , Vírus Chikungunya/genética , Feminino , Humanos , Proteínas de Insetos/genética , Masculino , Camundongos Endogâmicos C57BL , Mosquitos Vetores/genética , Mosquitos Vetores/metabolismo , Cidade de Nova Iorque , Proteínas e Peptídeos Salivares/genética , Especificidade da Espécie , Replicação ViralRESUMO
The objective of this study was to develop age- and gender-specific reference ranges for blood pressure in a large national database on blood pressure levels throughout childhood and adolescence in young Poles. A prospective cross-sectional study was performed in 2002-2005 in the representative sampling sites, selected randomly from the entire Poland. Altogether, 6,447 school pupils, aged 7-18 years, were involved in the study of which 3,176 were boys and 3,271 were girls. Statistical analysis was performed using STATISTICA for Windows 7.1. The normal range of blood pressure, determined by age and the category of body height percentiles, revealed percentiles values which might serve as reference values to identify cases of high normal blood pressure (the mean blood pressure between 90th and 95th percentiles for age and gender) and hypertension (the mean blood pressure equals or exceeds the 95th percentiles on at least three occasions).
Assuntos
Determinação da Pressão Arterial/estatística & dados numéricos , Pressão Sanguínea , Estudantes/estatística & dados numéricos , Adolescente , Antropometria , Estatura , Índice de Massa Corporal , Peso Corporal , Criança , Estudos Transversais , Diástole , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão , Masculino , Polônia/epidemiologia , Estudos Prospectivos , Padrões de Referência , Valores de Referência , Distribuição por Sexo , Inquéritos e Questionários , SístoleRESUMO
The age-specific decline in secretion of androgens and gonadotrophins in men result in negative changes in their libido, and a variety of psychological and neurovegetative symptoms. The purpose of this paper is to describe a diversity of symptoms accompanying male's ageing in relation to their biological status, socio-economic background and lifestyle behaviours. The study sample consisted of 2509 men whose age ranged between 30 and 97 years, and who voluntarily completed anonymous questionnaire. The educational attainement, marital status, place of residence, financial situation, physical activity and smoking habit were used to assess demographic and socio-economic status of the studied men. A set of symptoms accompanying male's ageing, were classified as somatic (FOSM) and psychological (POSM). Biological status of each man was assessed using index of physiological reserve (WRF) a criterion of biological age. All computations were run using Statistica 7.1 programme package. The level of significance was set at p < or = 0.05. Men who did not experience somatic and psychological symptoms were more likely to be younger (< 50 years) residents of medium cities. Those who had experienced almost all symptoms were more likely to be from the older group (> 50 years) of single men (including bachelors, widowers and divorced). The findings revealed that variation of somatic symptoms accompanying male's ageing (FOSM) was in 24% explained (R2 = 0.24) by the set of variables: index of physiological reserve (WRF), calendar age, place of residence, smoking habit and financial situation. Whereas that of POSM, was in 26% explained by index of physiological reserve (WRF), place of residence, marital status and smoking habit. The concluding statement should be stated that somatic and psychological symptoms accompanying male's ageing are associated with negative age-related physiological changes in the organism along with negative changes in family and professional lives.
Assuntos
Envelhecimento/fisiologia , Envelhecimento/psicologia , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Depressão/epidemiologia , Escolaridade , Fadiga/epidemiologia , Humanos , Libido , Estilo de Vida , Masculino , Estado Civil/estatística & dados numéricos , Pessoa de Meia-Idade , Debilidade Muscular/epidemiologia , Polônia/epidemiologia , Vigilância da População , Transtornos do Sono-Vigília/epidemiologia , Fatores Socioeconômicos , Inquéritos e QuestionáriosRESUMO
AIMS: The purpose of the study is to estimate whether the cognitive, functioning and emotional impairments in patients with Alzheimer's disease are related to lifestyle behaviours in the stage of life prior to the diagnosis of the disease. METHODS: Altogether, 65 patients with Alzheimer's disease, 55 women and 10 men, participants of the day center, run by the Wielkopolska Association of Alzheimer's Disease and residents of the Senior Nursing Home in Koprzywnica, were examined. Cognitive, functioning and emotional impairments of patients as well as lifestyle behaviours in the stage of life prior to the diagnosis of AD were estimated using AD-specific questionnaire, which were completed by caregivers. Qantitative and qualitative analyses were run using appropriate statistical procedures available in the Statistica 7.1 programme [StatSoft. Inc.2005 Statistica for Windows]. RESULTS: The findings revealed that patients with AD aged 70 years and older were likely to be more frequently impaired with daily life functioning than their younger counterparts. Patients with a higher attainment of education were more frequently impaired with cognitive than emotional problems and depression. Of all the variables in question, calendar age, educational attainment and intellectual activity in the stage of life prior to the diagnosis of disease were most significant in explaining the variation in the current impairments. Persons who were younger and intellectually active prior to the disease, were likely to be suffering less from the burden of AD than the older and less intellectually active counterparts. CONCLUSIONS: The association between educational attainment and intellectual activity in the stage of life prior to the occurrence of AD, and the burden of AD, found in the study, indicates that a lifelong intellectual activity may help to reduce disabilities and improve the patients' quality of life.