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1.
PLoS One ; 19(4): e0297876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38630764

RESUMO

The COVID-19 pandemic was a socionatural disaster that unprecedentedly disrupted the daily lives of individuals, families, and communities. Prior research indicates that Black American men living in rural contexts, particularly in Southern parts of the United States of America, were disproportionately affected by the psychological and economic effects of the pandemic. Despite these disparities, few studies have examined the pandemic's impact on rural Black American men's social networks. This study aimed to explore the effects of the COVID-19 pandemic on rural Black American men's interpersonal relationships. Informed by the principles of critical ethnography and guided by van Manen's hermeneutic phenomenology, seventeen men were interviewed using a semi-structured interview protocol. Interviews were transcribed and then analyzed using an iterative thematic reduction process consistent with van Manen's approach. Four themes were generated: Familial Reorganization, Adaptive Fatherhood, Rona Romance, and Essential Community. Participants recounted how the pandemic motivated them to improve their relationships with family members and children but contributed additional stress to their romantic relationships. Participants further recounted how their friendships were the least impacted as they were willing to make exceptions to their normal protective protocols to socialize with close friends. Participants also noted feeling disconnected from their wider community because they could not attend church even though their religious beliefs remained unchanged. Findings highlight the need for scholars, clinicians, and policymakers to consider men's relational health when developing and implementing pandemic recovery efforts, as it can significantly influence their ability to recuperate mentally and physically. Future research should be dedicated to (1) investigating the effects of the COVID-19 pandemic on fathers, as prior research has nearly exclusively focused on mothers' experiences and (2) delineating protective effects of rural Black American men's involvement in the Black Church from their individual spiritualities to gain a more comprehensive understanding of the influence of contextual crisis on their long-term health and wellbeing.


Assuntos
Negro ou Afro-Americano , COVID-19 , Relações Interpessoais , Pandemias , População Rural , Humanos , Masculino , Negro ou Afro-Americano/psicologia , Homens/psicologia , Saúde do Homem , Estados Unidos
2.
JAMA Pediatr ; 178(5): 506-508, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38436940

RESUMO

This survey study discusses changes in the proportion of youths who selected "not sure" among other response options to questions about their sexual identity in the National Youth Risk Behavior Survey between 2019 and 2021 and recommends measures to inclusively reflect sexual identities.


Assuntos
Assunção de Riscos , Humanos , Adolescente , Masculino , Feminino , Comportamento Sexual/psicologia , Comportamento do Adolescente/psicologia , Identidade de Gênero , Inquéritos e Questionários
3.
ACS Appl Electron Mater ; 6(2): 748-760, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38435803

RESUMO

Aerosol jet printing (AJP) is an advanced manufacturing technique for directly writing nanoparticle inks onto target substrates. It is an emerging reliable, efficient, and environmentally friendly fabrication route for thin film electronics and advanced semiconductor packaging. This fabrication technique is highly regarded for its rapid prototyping, the flexibility of design, and fine feature resolution. Nickel is an attractive high-temperature packaging material due to its electrical conductivity, magnetism, and corrosion resistance. In this work, we synthesized nickel nanoparticles and formulated an AJP ink, which was printed on various material surfaces. Thermal sintering experiments were performed on the samples to explore the redox behavior and to optimize the electrical performance of the devices. The nickel devices were heated to failure under an argon atmosphere, which was marked by a loss of reflectance and electrical properties due to the dewetting of the films. Additionally, a reduction mechanism was observed from these studies, which resembled that of nucleation and coalescence. Finally, multilayer graphene was grown on a custom-printed nickel thin film using chemical vapor deposition (CVD), establishing a fully additive manufacturing route to patterned graphene.

4.
Methods Mol Biol ; 2778: 331-344, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38478287

RESUMO

The type 9 secretion system (T9SS) is a recently discovered machinery that both transports cargo proteins across the Gram-negative bacterial outer membrane and attaches them to lipopolysaccharides on the extracellular surface. Outer membrane proteins (OMPs) are key components of the T9SS and are involved in both steps. In this chapter, we describe a method for the in silico modeling of T9SS OMPs and their complexes, and model validation. This is useful when the production of recombinant OMPs is difficult, and these protocols can also be applied to OMP complexes outside of the T9SS.


Assuntos
Proteínas da Membrana Bacteriana Externa , Proteínas de Membrana , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Bactérias/metabolismo
5.
Harm Reduct J ; 21(1): 51, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38402389

RESUMO

BACKGROUND: Primary needle and syringe programs (NSPs) have been integral for the prevention of blood-borne virus (BBV) transmission among people who inject drugs. Despite this, many people who inject drugs face barriers accessing these services, particularly after-hours when most services are closed. To our knowledge, the St Kilda NSP, in Melbourne, Victoria, is the only primary NSP providing 24/7 dedicated stand-alone face-to-face services for people who inject drugs in Australia. We conducted an evaluation of the St Kilda NSP to assess its role and effectiveness in meeting client needs. METHODS: Mixed research methods were used to conduct the evaluation. We analysed four quantitative data sets including the Victorian Needle and Syringe Program Information System data; NSP 'snapshot' survey data; and St Kilda NSP records of after-hours contacts and naloxone training events. Qualitative interviews were conducted with 20 purposively selected NSP clients, which were focused on individual needs, expectations and experiences accessing the service. Interviews were audio recorded and transcribed, and data were analysed thematically. A convergent research design was used to merge the five data sets. RESULTS: St Kilda NSP had 39,898 service contacts in 2018; 72% of contacts occurred outside business hours. Similarly, of 1,185,000 sterile needles and syringes dispatched, 71% were distributed outside business hours. Participants described valuing the after-hours service because drug use patterns did not always align with standard NSP opening hours and after-hours access afforded anonymity when collecting injecting equipment. Narratives highlighted several additional benefits of the 24/7 service, including: access to safer sex equipment; material support; naloxone training; referrals to specialist services; face-to-face emotional and social support from a non-judging worker; and for women involved in sex work in particular, being able to seek refuge when feeling unsafe on the streets. CONCLUSIONS: Our study provides evidence of the social and health benefits (beyond that of preventing BBV transmission) that can be gained through the provision of 24/7 primary NSP services. Findings support the need for the establishment of after-hours primary NSPs in other areas of Australia where active street-based drug markets operate outside business hours and concentrated numbers of people who inject drugs live and spend time.


Assuntos
Drogas Ilícitas , Abuso de Substâncias por Via Intravenosa , Humanos , Feminino , Programas de Troca de Agulhas/métodos , Agulhas , Vitória , Naloxona/uso terapêutico
6.
Artigo em Inglês | MEDLINE | ID: mdl-38330370

RESUMO

OBJECTIVES: Disproportionate exposure to childhood adversity and the effects of racial discrimination take a toll on Black American men's mental health. Despite increasing rates of suicidal behaviors and thoughts among young adult, Black American men, few longitudinal studies examine their risk for suicidal and death ideation (SDI). We tested a developmental model linking childhood adversity (experiences of deprivation and threatening experiences) and emerging adult exposure to racial discrimination to increases in SDI and examined a potential mechanism for these effects, negative relational schemas. METHOD: A sample of 504 Black men (Mage = 20.7) from rural Georgia were recruited with respondent-driven sampling and completed a baseline survey. Men participated in two additional follow-up surveys (Mage = 21.9 and Mage = 23.5). Hypotheses were tested using structural equation modeling. RESULTS: Analyses largely supported the proposed model. Childhood adversities were associated directly with reports of SDI. Childhood deprivation indirectly predicted SDI via negative schemas (ß = 0.03, 95% CI [.014, .046]). Racial discrimination also indirectly predicted SDI via negative relational schemas (ß = 0.01, 95% CI [.001, .018]). CONCLUSION: Study results suggest that clinical and preventive interventions for suicidality should target the influence of racism and adverse experiences and the negative relational schemas they induce. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

7.
medRxiv ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38260296

RESUMO

Heterosexual couples in romantic relationships are known to influence each other's hypertension risk. However, the role of partners on an individual's hypertension status in same-sex relationships is less understood. Our objective is to characterize the burden of high blood pressure among middle-aged and older couples consisting of men who have sex with men (MSM) and women who have sex with women (WSW) living in the US. Among 81 same-sex couples from the Health and Retirement Study 2006-18, 72.4% (95%CI: 23.4-95.7) MSM couples and 61.0% (95%CI: 30.4-84.8) WSW couples consisted of both partners with hypertension. Same-sex couples demonstrate high concordance of hypertension and related risk factors, suggesting a need to develop novel interventions targeting MSM and WSW couples.

8.
Eur J Psychotraumatol ; 15(1): 2299194, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38197328

RESUMO

Background: In the aftermath of child trauma, post-traumatic stress (PTS) and depression symptoms often co-occur among trauma exposed children and their parents. Studies have used latent class analysis (LCA) to examine PTS and depression symptoms and identify homogeneous subgroups among trauma exposed children. However, little is known about subgroups or classes of PTS and depression reactions of parents of traumatised children.Objectives: (1) Determine PTS and depression symptom classes at 2-9 months post-trauma, and (2) to examine sociodemographic covariates among parents of trauma exposed children.Methods: Using harmonised individual participant data (n = 702) from eight studies (Australia, UK, US) included in the Prospective studies of Acute Child Trauma and Recovery Data Archive (PACT/R), we modelled these phenomena at the symptom level using LCA.Results: Our LCA yielded three solutions: 'high internalizing symptom' class (11%); 'low PTS-high depression' class (17%); and 'low internalizing symptom' class (72%). Parents of children in the 'low PTS-high depression' class were more likely to have children of older age and be part of an ethnic minority, compared to the 'low internalizing symptoms' class. Mothers were more likely to be in the 'high internalizing symptom' class compared to the 'low internalizing symptoms' class.Conclusions: These findings reveal a qualitative structure and relationship between depression and PTS symptoms that highlights the importance of assessing and targeting a broad range of internalising symptoms in post-trauma psychological treatment.


Using harmonised individual participant data from eight studies included in the Prospective studies of Acute Child Trauma and Recovery (PACT/R) Data Archive we identified three distinct classes of parental internalising reactions using Latent Class Analysis.Mothers, family ethnic minority status, and children of older age were associated with distinct classes of problematic symptoms.The findings from the present study highlight the need for assessing and targeting a broad range of internalising symptoms after trauma, and that mothers, parents of older children and families with ethnic minority status might be at risk for elevated symptoms.


Assuntos
Depressão , Transtornos de Estresse Pós-Traumáticos , Criança , Humanos , Etnicidade , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Grupos Minoritários , Pais
10.
Mucosal Immunol ; 17(1): 1-12, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37952849

RESUMO

Type-3 innate lymphoid cells (ILC3) respond to localized environmental cues to regulate homeostasis and orchestrate immunity in the intestine. The intestinal epithelium is an important upstream regulator and downstream target of ILC3 signaling, however, the complexity of mucosal tissues can hinder efforts to define specific interactions between these two compartments. Here, we employ a reductionist co-culture system of murine epithelial small intestinal organoids (SIO) with ILC3 to uncover bi-directional signaling mechanisms that underlie intestinal homeostasis. We report that ILC3 induce global transcriptional changes in intestinal epithelial cells, driving the enrichment of secretory goblet cell signatures. We find that SIO enriched for goblet cells promote NKp46+ ILC3 and interleukin (IL)-22 expression, which can feedback to induce IL-22-mediated epithelial transcriptional signatures. However, we show that epithelial regulation of ILC3 in this system is contact-dependent and demonstrate a role for epithelial Delta-Like-Canonical-Notch-Ligand (Dll) in driving IL-22 production by ILC3, via subset-specific Notch1-mediated activation of T-bet+ ILC3. Finally, by interfering with Notch ligand-receptor dynamics, ILC3 appear to upregulate epithelial Atoh1 to skew secretory lineage determination in SIO-ILC3 co-cultures. This research outlines two complimentary bi-directional signaling modules between the intestinal epithelium and ILC3, which may be relevant in intestinal homeostasis and disease.


Assuntos
Interleucina 22 , Linfócitos , Camundongos , Animais , Imunidade Inata , Ligantes , Mucosa Intestinal , Receptores Notch/metabolismo
11.
Am J Infect Control ; 52(3): 312-319, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37741292

RESUMO

BACKGROUND: The COVID-19 pandemic disproportionately impacts youth and young adults (YYA) and YYA with multiple marginalized identities, yet little is known about differences in uptake, testing access, and vaccine concerns among YYA by diverse demographic identities. METHODS: Between 2/2021 and 2/2022, we conducted a national, cross-sectional online survey focused on diverse YYA ages 14 to 24 (n = 983). We explored the prevalence of COVID-19 testing and vaccination among YYA by age, race/ethnicity, and sexual and gender identities. Bivariate and multivariable logistic regression models were developed to estimate associations between individual variables and COVID-19 testing and vaccination. RESULTS: The overall COVID-19 testing and vaccination rates in our sample were high (75.99% and 69.07%, respectively). No differences in testing by demographics were found. Compared to individuals aged 14 to 17 years, those aged 18 to 21 years and 22 to 24 years were over 2 times and 4 times as likely to report receiving a vaccine, respectively. All race/ethnicity groups except for Asian individuals were more likely to report being vaccinated compared to their white peers. CONCLUSIONS: Our findings showed critical disparities in COVID-19 vaccination among YYA with marginalized identities and emphasized the urgency for data collection and research on pandemic prevention for vulnerable YYA populations.


Assuntos
COVID-19 , Identidade de Gênero , Feminino , Adolescente , Adulto Jovem , Humanos , Masculino , Teste para COVID-19 , Vacinas contra COVID-19 , Estudos Transversais , Etnicidade , Pandemias , COVID-19/epidemiologia , COVID-19/prevenção & controle , Comportamento Sexual , Vacinação
12.
Drug Alcohol Rev ; 43(3): 685-687, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37920147

RESUMO

The National Naloxone Reference Group has played a key role in the development of take-home naloxone programs, policy and practice in Australia. In this commentary we detail the origins of the group, some of its main achievements since its inception and its future directions in light of the major policy changes around naloxone that have recently occurred in Australia.


Assuntos
Naloxona , Políticas , Humanos , Austrália , Naloxona/uso terapêutico
13.
Artigo em Inglês | MEDLINE | ID: mdl-38125785

RESUMO

The COVID-19 pandemic is a socionatural disaster that has disrupted the lives of individuals, families, and communities. Youth and young adults (YYA) were uniquely vulnerable to the proximal mental health effects of the pandemic; however, few studies have examined the long-term mental health effects of the pandemic. In the present study, we sought to (a) identity distinctive profiles of COVID-related lifestyle disruptions experienced by YYA, (b) investigate sociodemographic characteristics correlates of profile membership, and (c) examine the extent to which profile membership was prospectively associated with changes in depressive and anxiety symptoms. Hypothesis were tested using latent profile analysis with data from 1055 YYA collected across two time-points, 6-months apart. Results produced a three-class model: low- (11%), moderate- (61%), and high-levels of (28%) disruption. Members of the high levels of disruption group were more likely to identify as Black or Latinx American, bisexual/pansexual, or as transgender or gender diverse in comparison to the low levels of disruption group. Inclusion in the high levels of disruption group was associated with increases in depressive and anxiety symptoms from T1 to T2. YYA from multiple marginalize communities (i. e. those who identified as both racial/ethnic and sexual/gender minorities) experienced the greatest levels of lifestyle disruption related to COVID-19. Consequently, disruptive effects of the COVID-19 pandemic prospectively eroded their mental health. YYA are in urgent need of developmentally appropriate resources to effectively recovery from the pandemic.

14.
Prev Sci ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37906357

RESUMO

The spread of the monkeypox virus (mpox) in 2022 primarily within the sexual networks of men who have sex with men (MSM) triggered a potentially stigmatizing public health response in the USA. Despite mpox being primarily spread through skin-to-skin contact, most messaging has promoted abstinence and/or reduction in sexual risk behaviors. More research is needed on decreases in sexual risk behaviors among sexual and gender minority (SGM) youth and young adults (YYA) related to the most recent mpox epidemic and whether there are factors associated with these decreases in sexual risk behavior. Participants within an ongoing cohort study of SGM YYA who reside in Illinois were offered the opportunity to participate in an mpox survey between September 10th and September 20th, 2022. Analyses looked at demographic factors associated with sexual activity since the start of the outbreak, as well as associations with two sexual risk reduction factors. Survey participation was 68.7% (322/469). Three-quarters of participants (82.6%) reported sexual activity since June 1st. Most sexually active participants (83.5%) adopted at least one sexual risk reduction behavior due to mpox. Black and Latinx individuals were less likely to be sexually active but more likely to report risk reduction behaviors (31.3% and 22.6%, respectively). Participants who received the mpox vaccine were more likely to report sexual activity. SGM YYA in Illinois reported that their sexual behaviors were impacted by the mpox outbreak. However, associations between vaccination and sexual behavior demonstrate that those who are vaccinated do adopt protective methods despite not decreasing sexual activity. Therefore, sex-positive communications and harm reduction messaging may be more appropriate as opposed to abstinence-only prevention, which can further stigmatize an already marginalized group.

15.
Artigo em Inglês | MEDLINE | ID: mdl-37810174

RESUMO

Objective: Prior epidemic literature suggests that the rapid proliferation of Monkeypox (Mpox) within the United States may trigger severe stress reactions that increase the risk of developing secondary traumatic stress among young adults most at risk of exposure. The present exploratory study aimed to investigate the degree to which proximity to Mpox (i.e. knowing people who acquired Mpox), was associated with symptoms of secondary traumatization. Method: An online survey was administered to 253 participants enrolled in Keeping it LITE, a prospective U.S. cohort study of ethnically diverse, sexually active, sexual and gender minority persons ages 19-39 in September 2022. A multiple linear regression was used to examine the association between proximity to Mpox and secondary traumatic stress (STS) symptoms. Results: Study findings demonstrated that Mpox morbidity was low (1%); however, 37% of participants reported knowing at least one person diagnosed with Mpox. For most individuals, this person was a friend (28%). 16% of participants were found to have at least one indicator of Mpox-related STS. Results of our multiple linear regression demonstrated a positive association between an individual's indirect exposure to Mpox via their interpersonal relationships and STS symptoms. Conclusions: Findings suggest that the more adults' interpersonal relationships are saturated with people who have acquired Mpox, the more likely they are to develop symptoms of secondary traumatization. These findings provide tentative initial evidence that secondary exposure to Mpox via one's social network may undermine adults' mental health even after the conclusion of the outbreak.

16.
J Assoc Nurses AIDS Care ; 34(6): 538-547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37738524

RESUMO

ABSTRACT: Methamphetamine (Meth) use is a contributor to poor health outcomes among young Black American gay, bisexual, and other men who have sex with men (YB-GBMSM). Emerging research indicates that socioeconomic instability may be a salient antecedent of meth use as men may be encouraged to engage in health-eroding activities, such as survival sex, to care for themselves, and then cope with instability-related stress via use of substances. We examined the degree to which indicators of socioeconomic instability, including homelessness and food insecurity, would directly, and indirectly, predict increases in meth use, via survival sex engagement. Hypotheses were tested using mediated path analysis with data from 100 YB-GBMSM in Atlanta, Georgia. Preliminary analysis results demonstrated positive associations between engaging in survival sex, food insecurity, homelessness, and living with HIV. Findings demonstrated that homelessness and food insecurity were directly associated with increased survival sex engagement but were not directly associated with meth use. Homelessness and food insecurity were indirectly associated with increased severity of meth use, via increased engagement in survival sex. Socioeconomic instability and survival sex engagement may be important intervention targets for future meth use intervention/prevention programming. Integrating programmatic components that address homelessness and food insecurity may decrease YB-GBMSM's need to rely on survival sex to meet their needs and decrease their likelihood of using meth as a result.


Assuntos
Infecções por HIV , Metanfetamina , Minorias Sexuais e de Gênero , Masculino , Humanos , Adulto Jovem , Homossexualidade Masculina , Estudos Transversais , Fatores Socioeconômicos
17.
PLoS One ; 18(8): e0289821, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561729

RESUMO

HIV-related stigma is a barrier to engagement in care for young adults living with HIV. Other intersecting forms of stigma (e.g., racism, sexism, homophobia), may worsen HIV-related stigma and impact engagement in care. From November 2020 to February 2021, we conducted 20 in-depth qualitative interviews among young adults living with HIV attending a large, comprehensive HIV care center in Atlanta, Georgia. Semi-structured interview guides based on Earnshaw and Chaudoir's HIV Stigma Framework and the theory of intersectionality facilitated discussion around experiences with various forms of stigma and its possible influence on healthcare engagement. Using the social-ecological model, we used thematic analysis to contextualize how young adults living with HIV experienced intersectional stigma and enacted, anticipated, and internalized HIV stigma in both healthcare and non-healthcare settings. Most participants identified as male, Black/African American, and gay. Participants described stigma at intrapersonal, interpersonal, clinic, and community levels. Intrapersonal stigma was associated with delayed care seeking, isolation, and fear of disclosure. Interpersonal stigma included discrimination from family and friends and avoidance of close relationships to elude disclosure. At the clinic level, stigma included negative experiences with staff in HIV and non-HIV healthcare settings, which contributed to decreased engagement in care. Stigma in the community included differential treatment from employers, community leaders, and religious community and was associated with feelings of helplessness related to current societal inequalities. Coping/motivating mechanisms for stigma included prioritizing health, eliciting support from the medical care team and peers. Our findings show different intersecting stigmas are barriers to healthcare at multiple levels for young adults living with HIV, potentially exacerbating existing health and social disparities. To improve engagement in care among young adults living with HIV, future interventions should address the different mechanisms of stigma at community, clinic, interpersonal and intrapersonal levels by enhancing social support and improving healthcare structural competency.


Assuntos
Infecções por HIV , Enquadramento Interseccional , Humanos , Masculino , Adulto Jovem , Georgia/epidemiologia , Pesquisa Qualitativa , Estigma Social
18.
Exp Appl Acarol ; 91(1): 99-110, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37584844

RESUMO

Soft ticks from the Ornithodoros genus are vectors of relapsing fever (RF) spirochetes around the world. In Mexico, they were originally described in the 19th century. However, few recent surveillance studies have been conducted in Mexico, and regions where RF spirochetes circulate remain vague. Here, the presence of soft ticks in populated areas was assessed in two sites from the Mexican states of Aguascalientes and Zacatecas. Argasidae ticks were collected, identified by morphology and mitochondrial 16S rDNA gene sequencing, and tested for RF borreliae. The specimens in both sites were identified as Ornithodoros turicata but no RF spirochetes were detected. These findings emphasize the need to update the distribution of these ticks in multiple regions of Mexico and to determine the circulation of RF borreliosis in humans and domestic animals.


Assuntos
Argasidae , Borrelia , Ornithodoros , Febre Recorrente , Humanos , Animais , Febre Recorrente/epidemiologia , Borrelia/genética , Animais Domésticos
19.
J Pharmacol Toxicol Methods ; 123: 107300, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37524151

RESUMO

This editorial prefaces the annual themed issue on safety pharmacology (SP) methods published since 2004 in the Journal of Pharmacological and Toxicological Methods (JPTM). We highlight here the content derived from the recent 2022 Safety Pharmacology Society (SPS) and Canadian Society of Pharmacology and Therapeutics (CSPT) joint meeting held in Montreal, Quebec, Canada. The meeting also generated 179 abstracts (reproduced in the current volume of JPTM). As in previous years the manuscripts reflect various areas of innovation in SP including a comparison of the sensitivity of cross-over and parallel study designs for QTc assessment, use of human-induced pluripotent stem cell (hi-PSC) neuronal cell preparations for use in neuropharmacological safety screening, and hiPSC derived cardiac myocytes in assessing inotropic adversity. With respect to the latter, we anticipate the emergence of a large data set of positive and negative controls that will test whether the imperative to miniaturize, humanize and create a high throughput process is offset by any loss of precision and accuracy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacologia , Humanos , Canadá , Avaliação Pré-Clínica de Medicamentos/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Farmacologia/métodos , Congressos como Assunto
20.
mSystems ; 8(4): e0119322, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37436062

RESUMO

Periodontal disease is a chronic inflammatory disease in which the oral pathogen Porphyromonas gingivalis plays an important role. Porphyromonas gingivalis expresses virulence determinants in response to higher hemin concentrations, but the underlying regulatory processes remain unclear. Bacterial DNA methylation has the potential to fulfil this mechanistic role. We characterized the methylome of P. gingivalis, and compared its variation to transcriptome changes in response to hemin availability. Porphyromonas gingivalis W50 was grown in chemostat continuous culture with excess or limited hemin, prior to whole-methylome and transcriptome profiling using Nanopore and Illumina RNA-Seq. DNA methylation was quantified for Dam/Dcm motifs and all-context N6-methyladenine (6mA) and 5-methylcytosine (5mC). Of all 1,992 genes analyzed, 161 and 268 were respectively over- and under-expressed with excess hemin. Notably, we detected differential DNA methylation signatures for the Dam "GATC" motif and both all-context 6mA and 5mC in response to hemin availability. Joint analyses identified a subset of coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify altered methylation and expression responses to hemin availability in P. gingivalis, with insights into mechanisms regulating its virulence in periodontal disease. IMPORTANCE DNA methylation has important roles in bacteria, including in the regulation of transcription. Porphyromonas gingivalis, an oral pathogen in periodontitis, exhibits well-established gene expression changes in response to hemin availability. However, the regulatory processes underlying these effects remain unknown. We profiled the novel P. gingivalis epigenome, and assessed epigenetic and transcriptome variation under limited and excess hemin conditions. As expected, multiple gene expression changes were detected in response to limited and excess hemin that reflect health and disease, respectively. Notably, we also detected differential DNA methylation signatures for the Dam "GATC" motif and both all-context 6mA and 5mC in response to hemin. Joint analyses identified coordinated changes in gene expression, 6mA, and 5mC methylation that target genes involved in lactate utilization and ABC transporters. The results identify novel regulatory processes underlying the mechanism of hemin regulated gene expression in P. gingivalis, with phenotypic impacts on its virulence in periodontal disease.


Assuntos
Hemina , Doenças Periodontais , Humanos , Hemina/farmacologia , Porphyromonas gingivalis/genética , Metilação de DNA/genética , Doenças Periodontais/genética , Transportadores de Cassetes de Ligação de ATP/genética , Expressão Gênica
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