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1.
PLoS Pathog ; 19(5): e1011385, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37163552

RESUMO

Kaposi's Sarcoma herpesvirus (KSHV) is the etiologic agent of Kaposi's Sarcoma (KS), a highly vascularized tumor common in AIDS patients and many countries in Africa. KSHV is predominantly in the latent state in the main KS tumor cell, the spindle cell, a cell expressing endothelial cell markers. To identify host genes important for KSHV latent infection of endothelial cells we previously used a global CRISPR/Cas9 screen to identify genes necessary for the survival or proliferation of latently infected cells. In this study we rescreened top hits and found that the highest scoring gene necessary for infected cell survival is the anti-apoptotic Bcl-2 family member Bcl-xL. Knockout of Bcl-xL or treatment with a Bcl-xL inhibitor leads to high levels of cell death in latently infected endothelial cells but not their mock counterparts. Cell death occurs through apoptosis as shown by increased PARP cleavage and activation of caspase-3/7. Knockout of the pro-apoptotic protein, Bax, eliminates the requirement for Bcl-xL. Interestingly, neither Bcl-2 nor Mcl-1, related and often redundant anti-apoptotic proteins of the Bcl-2 protein family, are necessary for the survival of latently infected endothelial cells, likely due to their lack of expression in all the endothelial cell types we have examined. Bcl-xL is not required for the survival of latently infected primary effusion lymphoma (PEL) cells or other cell types tested. Expression of the KSHV major latent locus alone in the absence of KSHV infection led to sensitivity to the absence of Bcl-xL, indicating that viral gene expression from the latent locus induces intrinsic apoptosis leading to the requirement for Bcl-xL in endothelial cells. The critical requirement of Bcl-xL during KSHV latency makes it an intriguing therapeutic target for KS tumors.


Assuntos
Herpesvirus Humano 8 , Sarcoma de Kaposi , Humanos , Apoptose , Células Endoteliais/metabolismo , Herpesvirus Humano 8/fisiologia , Latência Viral/fisiologia
2.
J Infect Dis ; 229(6): 1803-1811, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38366369

RESUMO

BACKGROUND: The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. METHODS: We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging-epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation-estimated telomere length-and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. RESULTS: This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs -1.88 ± 5.07; P < .001) and lower DNA methylation-estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. CONCLUSIONS: Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.


Assuntos
Envelhecimento , Densidade Óssea , Metilação de DNA , Epigênese Genética , Infecções por HIV , Humanos , Feminino , Pessoa de Meia-Idade , Infecções por HIV/genética , Envelhecimento/genética , Densidade Óssea/genética , Adulto , Estudos de Coortes
3.
J Infect Dis ; 229(3): 780-785, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-37947273

RESUMO

The menopausal transition is a pivotal time of cardiovascular risk, but knowledge is limited in HIV. We studied longitudinal carotid artery intima-media thickness (CIMT) in the Women's Interagency HIV Study (2004-2019; 979 women/3247 person-visits; 72% with HIV). Among women with HIV only, those who transitioned had greater age-related CIMT progression compared to those remaining premenopausal (difference in slope = 1.64 µm/year, P = .002); and CIMT increased over time in the pretransition (3.47 µm/year, P = .002) and during the menopausal transition (9.41 µm/year, P < .0001), but not posttransition (2.9 µm/year, P = .19). In women with HIV, menopause may accelerate subclinical atherosclerosis as measured by CIMT.


Assuntos
Aterosclerose , Infecções por HIV , Humanos , Feminino , Espessura Intima-Media Carotídea , Fatores de Risco , Menopausa , Infecções por HIV/complicações
4.
J Infect Dis ; 230(4): 912-918, 2024 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-39011957

RESUMO

Host metabolic dysregulation, especially in tryptophan metabolism, is intricately linked to coronavirus disease 2019 (COVID-19) severity and its postacute sequelae (long COVID). People living with human immunodeficiency virus (HIV; PLWH) experience similar metabolic dysregulation and face an increased risk of developing long COVID. However, whether preexisting HIV-associated metabolic dysregulations contribute in predisposing PLWH to severe COVID-19 outcomes remains underexplored. Analyzing prepandemic samples from PLWH with documented postinfection outcomes, we found specific metabolic alterations, including increased tryptophan catabolism, predicting an elevated risk of severe COVID-19 and the incidence of long COVID. These alterations warrant further investigation for their potential prognostic and mechanistic significance in determining COVID-19 complications.


Assuntos
COVID-19 , Infecções por HIV , SARS-CoV-2 , Índice de Gravidade de Doença , Humanos , COVID-19/metabolismo , COVID-19/complicações , COVID-19/epidemiologia , Infecções por HIV/complicações , Masculino , Incidência , Feminino , Pessoa de Meia-Idade , Triptofano/metabolismo , Adulto , Síndrome de COVID-19 Pós-Aguda
5.
Clin Infect Dis ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39324701

RESUMO

BACKGROUND: Sex-specific, long-term, body weight change in persons with HIV (PWH) following switch to regimens containing integrase strand-transfer inhibitors (INSTIs) is unknown. METHODS: We compared PWH enrolled in the MACS/WIHS Combined Cohort Study (2007-2020) who switched/added an INSTI to their antiretroviral therapy (ART) to those remaining on non-INSTI ART and to people without HIV (PWOH), by sex. Follow-up time was time since switch visit (or comparable visit in controls). Linear regression mixed effect models assessed the effects of sex, group (INSTI, non-INSTI, PWOH), and time upon weight and anthropometric measurements (waist, hip, thigh). RESULTS: Of 3464 participants included, women (411 INSTI, 709 Non-INSTI, 818 PWOH) compared to men (223 INSTI, 412 Non-INSTI, 891 PWOH) were younger (47.2 years vs 54.5), majority non-Hispanic Black (65 vs 23%), and had higher mean BMI (31.5 kg/m2 vs 26.9), respectively. Women switching to INSTIs experienced greater absolute and % weight gain compared to men at 5 years: +3.0 kg (95% CI 2.1-3.9) vs +1.8 kg (0.7-2.9) and +4.6% (3.5-5.7) vs +2.3% (1.0-3.6), respectively, [sex*time*study group interaction, p<0.01]. Compared to men, women switching to INSTIs experienced greater hip and thigh circumference gain at 5 years: +2.6 cm (95% CI 1.6-3.6) vs +1.2 cm (0.3-2.1) and +1.5 cm (0.7-2.2) vs -0.2 cm (-0.9, 0.5), respectively, but there were no significant sex differences in waist circumference or waist-hip ratio. CONCLUSIONS: Weight change among PWH over 5 years after switch to INSTI was 2-fold higher in women than men. The cardio-metabolic implications of this difference in weight gain remain unknown.

6.
Immunology ; 172(3): 420-439, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38501302

RESUMO

Latent human cytomegalovirus (hCMV) infection can pose a serious threat of reactivation and disease occurrence in immune-compromised individuals. Although T cells are at the core of the protective immune response to hCMV infection, a detailed characterization of different T cell subsets involved in hCMV immunity is lacking. Here, in an unbiased manner, we characterized over 8000 hCMV-reactive peripheral memory T cells isolated from seropositive human donors, at a single-cell resolution by analysing their single-cell transcriptomes paired with the T cell antigen receptor (TCR) repertoires. The hCMV-reactive T cells were highly heterogeneous and consisted of different developmental and functional memory T cell subsets such as, long-term memory precursors and effectors, T helper-17, T regulatory cells (TREGs) and cytotoxic T lymphocytes (CTLs) of both CD4 and CD8 origin. The hCMV-specific TREGs, in addition to being enriched for molecules known for their suppressive functions, showed enrichment for the interferon response signature gene sets. The hCMV-specific CTLs were of two types, the pre-effector- and effector-like. The co-clustering of hCMV-specific CD4-CTLs and CD8-CTLs in both pre-effector as well as effector clusters suggest shared transcriptomic signatures between them. The huge TCR clonal expansion of cytotoxic clusters suggests a dominant role in the protective immune response to CMV. The study uncovers the heterogeneity in the hCMV-specific memory T cells revealing many functional subsets with potential implications in better understanding of hCMV-specific T cell immunity. The data presented can serve as a knowledge base for designing vaccines and therapeutics.


Assuntos
Linfócitos T CD8-Positivos , Infecções por Citomegalovirus , Citomegalovirus , Células T de Memória , Receptores de Antígenos de Linfócitos T , Análise de Célula Única , Linfócitos T Citotóxicos , Transcriptoma , Humanos , Citomegalovirus/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Células T de Memória/imunologia , Células T de Memória/metabolismo , Linfócitos T Citotóxicos/imunologia , Linfócitos T CD8-Positivos/imunologia , Memória Imunológica , Perfilação da Expressão Gênica , Linfócitos T CD4-Positivos/imunologia
7.
Small ; 20(33): e2401144, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38552250

RESUMO

On-demand switch on/off blood clogging is of paramount importance for the survival of mammals, for example as a quick response to seal damage wounds to minimize their bleeding rate. This mechanism is a complex chain process from initiated red blood cell aggregation at the target location (open wound) that quickly seals on a macroscopic scale the damaged flash. Inspired by nature an on-demand switchable particle clogging mechanism is developed with high spatial resolution down to micrometer size using light as an external non-invasive stimulation. Particle clogging can be adjusted on demand strong enough to even withstand pressure-driven fluid flow, additionally building up walls of aggregated particles, which stop the momentum of big particles under shear. The principle relies on a photosensitive surfactant, which induces under light illumination a long-ranged lateral attractive phoretic-osmotic activity of silica microparticles forcing them to aggregate. The strength of aggregation and therefore motion reduction or even stop of the particles against the fluid flow depends on the ratio between the aggregation strength and the velocity of the particles. The aggregation strength can be precisely controlled by the applied light intensity and adjusted particle concentration. Increasing both parameters results in a stronger aggregation tendency.

8.
Small ; : e2403546, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967188

RESUMO

In this article, a novel strategy is presented to selectively separate a mixture of equally sized microparticles but differences in material composition and surface properties. The principle relies on a photosensitive surfactant, which makes particles under light illumination phoretically active. The latter hovers microparticles from a planar interface and together with a superimposed fluid flow, particles experience a drift motion characteristic to its interfacial properties. The drift motion is investigated as a function of applied wavelength, demonstrating that particles composed of different material show a unique spectrally resolved light-induced motion profile. Differences in those motion profile allow a selective fractioning of a desired particle from a complex particle mixture made out of more than two equally sized different particle types. Besides that, the influence of applied wavelength is systematically studied, and discussed the origin of the spectrally resolved chemical activity of microparticles from measured photo-isomerization rates.

9.
J Virol ; 97(10): e0096223, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37787534

RESUMO

IMPORTANCE: Rotavirus is a leading cause of severe diarrhea in young children. Like other fecal-oral pathogens, rotaviruses encounter abundant, constitutively expressed defensins in the small intestine. These peptides are a vital part of the vertebrate innate immune system. By investigating the impact that defensins from multiple species have on the infectivity of different strains of rotavirus, we show that some rotaviral infections can be inhibited by defensins. We also found that rotaviruses may have evolved resistance to defensins in the intestine of their host species, and some even appropriate defensins to increase their infectivity. Because rotaviruses infect a broad range of animals and rotaviral infections are highly prevalent in children, identifying immune defenses against infection and how they vary across species and among viral genotypes is important for our understanding of the evolution, transmission, and zoonotic potential of these viruses as well as the improvement of vaccines.

10.
J Virol ; 97(3): e0006023, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36916912

RESUMO

Adeno-associated viruses (AAVs) are being developed as gene therapy vectors due to their low pathogenicity and tissue tropism properties. However, the efficacy of these vectors is impeded by interactions with the host immune system. One potential immune barrier to vector transduction is innate immune host defense peptides, such as alpha-defensins, which are potent antiviral agents against other nonenveloped viruses. To investigate the interaction between AAVs and alpha-defensins, we utilized two closely related AAV serotypes, AAV1 and AAV6. Although their capsids differ by only six residues, these two serotypes exhibit markedly different tissue tropisms and transduction efficiencies. Using two abundant human alpha-defensins, enteric human defensin 5 (HD5) and myeloid human neutrophil peptide 1 (HNP1), we found both serotype-specific and defensin-specific effects on AAV infection. AAV6 infection was uniformly neutralized by both defensins at low micromolar concentrations; however, inhibition of AAV1 infection was profoundly influenced by the timing of defensin exposure to the virus relative to viral attachment to the cell. Remarkably, these differences in the defensin-dependent infection phenotype between the viruses are completely dictated by the identity of a single, surface-exposed amino acid (position 531) that varies between the two serotypes. These findings reveal a determinant for defensin activity against a virus with unprecedented precision. Furthermore, they provide a rationale for the investigation of other AAV serotypes not only to understand the mechanism of neutralization of defensins against AAVs but also to design more efficient vectors. IMPORTANCE The ability of adeno-associated viruses (AAVs) to infect and deliver genetic material to a range of cell types makes them favorable gene therapy vectors. However, AAV vectors encounter a wide variety of host immune factors throughout the body, which can impede efficient gene delivery. One such group of factors is the alpha-defensins, which are a key component of the innate immune system that can directly block viral infection. By studying the impact that alpha-defensins have on AAV infection, we found that two similar AAV serotypes (AAV1 and AAV6) have different sensitivities to inhibition. We also identified a single amino acid (position 531) that differs between the two AAV serotypes and is responsible for mediating their defensin sensitivity. By investigating the effects that host immune factors have on AAV infection, more efficient vectors may be developed to evade intervention by the immune system prior to gene delivery.


Assuntos
Dependovirus , Vetores Genéticos , alfa-Defensinas , Humanos , alfa-Defensinas/metabolismo , Aminoácidos/metabolismo , Dependovirus/imunologia , Dependovirus/fisiologia , Terapia Genética
11.
J Neurovirol ; 30(2): 122-130, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38472641

RESUMO

Sleep disturbances are prevalent in women with HIV (WWH). Tryptophan-kynurenine (T-K) pathway metabolites are associated with alterations in actigraphy derived sleep measures in WWH, although may not always correlate with functional impairment. We investigated the relationship between T-K pathway metabolites and self-reported daytime dysfunction in WWH and women without HIV (WWoH). 141 WWH on stable antiretroviral therapy and 140 demographically similar WWoH enrolled in the IDOze Study had targeted plasma T-K metabolites measured using liquid chromatography-tandem mass spectrometry. We utilized the daytime dysfunction component of the Pittsburgh Sleep Quality Index (PSQI) to assess functional impairment across HIV-serostatus. Lower levels of 5-hydroxytryptophan and serotonin were associated with greater daytime dysfunction in all women. In WWH, daytime dysfunction was associated with increased kynurenic acid (R = 0.26, p < 0.05), and kynurenic acid-tryptophan (KA-T) ratio (R = 0.28, p < 0.01). WWH with daytime dysfunction had a 0.7 log fold increase in kynurenic acid compared to WWH without daytime dysfunction. Kynurenic acid levels and the KA-T ratio were associated with daytime dysfunction in WWH but not in WWoH. Longitudinal studies are needed to establish a causal relationship and directionality between T-K metabolic changes and sleep impairment in WWH.


Assuntos
Infecções por HIV , Cinurenina , Triptofano , Humanos , Triptofano/metabolismo , Triptofano/sangue , Feminino , Cinurenina/metabolismo , Cinurenina/sangue , Adulto , Infecções por HIV/metabolismo , Infecções por HIV/complicações , Infecções por HIV/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/fisiopatologia , Pessoa de Meia-Idade , Ácido Cinurênico/sangue , Ácido Cinurênico/metabolismo , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/fisiopatologia , Serotonina/metabolismo , Serotonina/sangue , Redes e Vias Metabólicas , 5-Hidroxitriptofano/metabolismo , Cromatografia Líquida
12.
Phys Rev Lett ; 132(20): 208401, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38829088

RESUMO

In many biopolymer solutions, attractive interactions that stabilize finite-sized clusters at low concentrations also promote phase separation at high concentrations. Here we study a model biopolymer system that exhibits the opposite behavior, whereby self-assembly of DNA oligonucleotides into finite-sized, stoichiometric clusters tends to inhibit phase separation. We first use microfluidics-based experiments to map a novel phase transition in which the oligonucleotides condense as the temperature increases at high concentrations of divalent cations. We then show that a theoretical model of competition between self-assembly and phase separation quantitatively predicts changes in experimental phase diagrams arising from DNA sequence perturbations. Our results point to a general mechanism by which self-assembly shapes phase boundaries in complex biopolymer solutions.


Assuntos
DNA , Modelos Químicos , Transição de Fase , DNA/química , Temperatura Alta , Oligonucleotídeos/química , Separação de Fases
13.
Biomacromolecules ; 25(9): 6164-6180, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39164913

RESUMO

Prostate cancer (PC) is the fifth leading cause of cancer-related deaths among men worldwide. Prostate-specific membrane antigen (PSMA), a molecular target of PC, is clinically used for the treatment and diagnosis of PC using radioligand approaches. However, no PSMA-based chemotherapies have yet been approved by the FDA. Here, we present a novel therapeutic approach using PSMA-targeted 2-deoxyglucose-dendrimer (PSMA-2DG-D) for targeted delivery of a potent tyrosine kinase inhibitor, cabozantinib (Cabo), selectively to PC cells. PSMA-2DG-D demonstrates intracellular localization in PSMA (+) PC cells through PSMA-mediated internalization. This PSMA-specific targeting translates to enhanced efficacy of Cabo compared to the free drug when conjugated to PSMA-2DG-D. Furthermore, systemically administered fluorescently labeled PSMA-2DG-D-Cy5 specifically targets PSMA (+) tumors with minimal off-target accumulation in the PC3-PIP tumor xenograft mouse model. This demonstrates that the PSMA-2DG-D platform is a promising new delivery system for potent chemotherapeutics, where systemic side effects are a significant concern.


Assuntos
Antígenos de Superfície , Dendrímeros , Desoxiglucose , Glutamato Carboxipeptidase II , Neoplasias da Próstata , Piridinas , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/metabolismo , Animais , Camundongos , Desoxiglucose/farmacologia , Desoxiglucose/química , Piridinas/química , Piridinas/administração & dosagem , Piridinas/farmacologia , Glutamato Carboxipeptidase II/metabolismo , Glutamato Carboxipeptidase II/antagonistas & inibidores , Dendrímeros/química , Antígenos de Superfície/metabolismo , Anilidas/farmacologia , Anilidas/administração & dosagem , Anilidas/farmacocinética , Anilidas/química , Nanomedicina/métodos , Linhagem Celular Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Sistemas de Liberação de Medicamentos/métodos
14.
AIDS Behav ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39222185

RESUMO

Older women with HIV face challenges to their quality of life, including neurocognitive decline, early-onset menopause, and chronic health issues. Chief among these concerns is depression, the most common psychiatric comorbidity among people living with HIV, with rates twice as high among women as men. However, tailored interventions among older women living with HIV and depression are lacking. Following the ADAPT-ITT framework to adapt existing interventions for cultural relevance among groups of people living with HIV, the study team revised an evidence-based intervention, the 'Stress Management and Relaxation Training/Expressive Supportive Therapy Women's Project (SMART/EST),' for online implementation. Working with two community stakeholders, the study team conducted focus groups, theater testing, and manual adaptation. This resulted in the development of e-SMART/EST, an online teletherapy group co-facilitated by a Licensed Psychologist and a credentialed Peer Counselor. The adapted, eight-session weekly intervention was tested with an exploratory pilot sample of eight older women (55 years and older) with HIV and depression. Participants rated the acceptability, feasibility, and appropriateness of the intervention, as well as symptoms of depression and HIV-related quality of life before and after the group. The e-SMART/EST Women's Project demonstrated high acceptability, feasibility, and appropriateness. Engagement was high, as women attended an average of 6.8 sessions. In qualitative interviews, participants reported peer co-facilitation, culturally relevant themes (e.g., HIV-related minority stress, critical consciousness, grief, and sex and pleasure), mindfulness techniques, and cohesion with other women as main favorable elements of the intervention. Barriers to online implementation included technological issues, distractions due to remote participation, and hindered emotional attunement compared with in-person group therapy. Findings support further research to test similar interventions in full-scale trials with older women living with depression and HIV.

15.
AIDS Behav ; 28(6): 1912-1922, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38478322

RESUMO

Heavy drinking among people living with HIV (PLWH) reduces ART adherence and worsens health outcomes. Lengthy interventions are not feasible in most HIV care settings, and patients infrequently follow referrals to outside treatment. Utilizing visual and video features of smartphone technology, we developed HealthCall as an electronic means of increasing patient involvement in a brief intervention to reduce drinking and improve ART adherence. The objective of the current study is to evaluate the efficacy of HealthCall to improve ART adherence among PLWH who drink heavily when paired with two brief interventions: the National Institute on Alcoholism and Alcohol Abuse (NIAAA) Clinician's Guide (CG) or Motivational Interviewing (MI). Therefore, we conducted a 1:1:1 randomized trial among 114 participants with alcohol dependence at a large urban HIV clinic. Participants were randomized to one of three groups: (1) CG only (n = 37), (2) CG and HealthCall (n = 38), or (3) MI and HealthCall (n = 39). Baseline interventions targeting drinking reduction and ART adherence were ~ 25 min, with brief (10-15 min) booster sessions at 30 and 60 days. The outcome was ART adherence assessed using unannounced phone pill-count method (possible adherence scores: 0-100%) at 30-day, 60-day, 3, 6, and 12 months. Analyses were conducted using generalized linear mixed models with pre-planned contrasts. Of the 114 enrolled patients, 58% were male, 75% identified as Black/African American, 28% were Hispanic, and 62% had less than a high school education. The mean age was 47.5 years (standard deviation [SD] 10 years) and the mean number of years since they were diagnosed with HIV was 18.6 (SD 7.6). Participants assigned to HealthCall to extend the CG had increased levels of ART adherence at 60-day and 6-month follow-up (compared to CG only), although there was no statistically significant difference by 12-month follow-up. Participants who were assigned to HealthCall to extend the MI never had statistically significant higher levels of ART adherence. These results suggest that the use of a smartphone app can be used to initially extend the reach of a brief drinking intervention to improve ART adherence over a short period of time; however, sustained long-term improvements in ART adherence after intervention activity ends remains a challenge.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adesão à Medicação , Entrevista Motivacional , Smartphone , Humanos , Masculino , Feminino , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Pessoa de Meia-Idade , Adulto , Fármacos Anti-HIV/uso terapêutico , Alcoolismo/terapia , Alcoolismo/psicologia , Resultado do Tratamento
16.
Int J Eat Disord ; 57(7): 1542-1554, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38469980

RESUMO

OBJECTIVE: The association between eating disorders (EDs) and harmful substance use (substance use that causes psychosocial impairment) is well recognized in the literature, and military veterans may be at heightened risk for both issues due to deployment-related stressors. However, little is known about which ED-related symptoms are associated with harmful substance use in veterans, and whether gender plays a differential role in this relationship. Our aims were to: (1) examine gender differences in ED-related symptoms; and (2) examine whether ED-related symptoms differentially predict harmful substance use in US veteran men and women who had recently separated from service. METHOD: This study was based on a nationally representative four-wave longitudinal sample of post-9/11 veterans (N = 835; 61.2% female). Longitudinal mixed modeling was used to test whether specific ED-related behaviors at baseline predicted harmful substance use at follow-ups. RESULTS: We replicated gendered patterns of ED-related symptoms observed in civilian populations, wherein men had higher weight-and-body-related concerns (including excessive exercise and muscle building) and negative attitude toward obesity, and women had higher bulimic and restricting symptoms. For women, alcohol, drug, and marijuana problems were predicted by higher bulimic symptoms, whereas for men, these problems were predicted by higher restricting symptoms. CONCLUSION: Gender played a differential role in the relationship between EDs and harmful substance use. Bulimic symptoms were the most robust predictor for harmful substance use among veteran women, whereas restricting was the most robust predictor for harmful substance use among veteran men. PUBLIC SIGNIFICANCE: The current study found that veteran women had higher bulimic symptoms (characterized by binge eating and purging) and restricting than veteran men. In women, bulimic symptoms predicted future harmful use of alcohol, marijuana, and other drugs. In contrast, veteran men had higher weight-and-body-related concerns (characterized by excessive exercise and muscle building) than veteran women. In men, restricting symptoms predicted future harmful use of alcohol, marijuana, and other drugs.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Transtornos Relacionados ao Uso de Substâncias , Veteranos , Humanos , Masculino , Feminino , Veteranos/psicologia , Veteranos/estatística & dados numéricos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/epidemiologia , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Adulto , Estados Unidos/epidemiologia , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores Sexuais
17.
Int J Eat Disord ; 57(4): 892-902, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38239071

RESUMO

OBJECTIVE: There is a lack of consensus in defining "significant weight loss" when diagnosing atypical anorexia nervosa (atypical AN) and no guidelines exist for setting target weight (TW). The current study aimed to identify community providers' practices related to the diagnosis of atypical AN and the determination of TW. A secondary aim was to evaluate whether professional discipline impacted "significant weight loss" definitions. METHOD: A variety of providers (N = 141; 96.4% female) completed an online survey pertaining to diagnostic and treatment practices with atypical AN. Descriptive statistics were computed to characterize provider-based practices and Fisher's exact tests were used to test for differences in diagnostic practices by professional discipline. Thematic analysis was used to examine open-ended questions. RESULTS: Most (63.97%) providers diagnosed atypical AN in the absence of any weight loss if other AN criteria were met, but doctoral-level psychologists and medical professionals were less likely to do so compared to nutritional or other mental health professionals. Most providers found weight gain was only sometimes necessary for atypical AN recovery. Qualitative responses revealed providers found atypical AN to be a stigmatizing label that was not taken seriously. Providers preferred to use an individualized approach focused on behaviors, rather than weight when diagnosing and treating atypical AN. DISCUSSION: Lack of diagnostic clarity and concrete treatment guidelines for atypical AN may result in substantial deviations from the DSM-5-TR criteria in real-world practice. Clinically useful diagnostic definitions for restrictive eating disorders and evidence-based treatment guidelines for TW and/or other relevant recovery metrics are needed. PUBLIC SIGNIFICANCE: The current study found variability in how community providers diagnose and determine target recovery weight for atypical anorexia nervosa (atypical AN). Many providers viewed the diagnosis of atypical AN as stigmatizing and preferred to focus on behaviors, rather than weight. This study underscores the importance of creating a clinically useful diagnostic definition and guidelines for recovery for atypical AN backed by empirical evidence that providers may implement in practice.


Assuntos
Anorexia Nervosa , Humanos , Feminino , Masculino , Anorexia Nervosa/diagnóstico , Anorexia Nervosa/terapia , Anorexia Nervosa/psicologia , Redução de Peso , Manual Diagnóstico e Estatístico de Transtornos Mentais
18.
Curr Microbiol ; 81(8): 251, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954017

RESUMO

A new area of biotechnology is nanotechnology. Nanotechnology is an emerging field that aims to develope various substances with nano-dimensions that have utilization in the various sectors of pharmaceuticals, bio prospecting, human activities and biomedical applications. An essential stage in the development of nanotechnology is the creation of nanoparticles. To increase their biological uses, eco-friendly material synthesis processes are becoming increasingly important. Recent years have shown a lot of interest in nanostructured materials due to their beneficial and unique characteristics compared to their polycrystalline counterparts. The fascinating performance of nanomaterials in electronics, optics, and photonics has generated a lot of interest. An eco-friendly approach of creating nanoparticles has emerged in order to get around the drawbacks of conventional techniques. Today, a wide range of nanoparticles have been created by employing various microbes, and their potential in numerous cutting-edge technological fields have been investigated. These particles have well-defined chemical compositions, sizes, and morphologies. The green production of nanoparticles mostly uses plants and microbes. Hence, the use of microbial nanotechnology in agriculture and plant science is the main emphasis of this review. The present review highlights the methods of biological synthesis of nanoparticles available with a major focus on microbially synthesized nanoparticles, parameters and biochemistry involved. Further, it takes into account the genetic engineering and synthetic biology involved in microbial nanobiosynthesis to the construction of microbial nanofactories.


Assuntos
Nanopartículas , Nanotecnologia , Nanotecnologia/métodos , Nanopartículas/química , Bactérias/metabolismo , Bactérias/genética , Biotecnologia/métodos , Biologia Sintética/métodos , Nanoestruturas/química
19.
Am J Drug Alcohol Abuse ; 50(1): 54-63, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37956200

RESUMO

Background: Many clinical and population-based research studies pivoted from in-person assessments to phone-based surveys due to the COVID-19 pandemic. The impact of these transitions on survey response remains understudied, especially for people living with HIV. Given that there are gender-specific trends in alcohol and substance use, it is particularly important to capture these data for women.Objective: Identify factors associated with responding to an alcohol and substance use phone survey administered during the COVID-19 pandemic in the Women's Interagency HIV Study, a multicenter US prospective cohort of women living with and without HIV.Methods: We used multivariable logistic regression to assess for associations of pre-pandemic (April-September 2019) sociodemographic factors, HIV status, housing status, depressive symptoms, alcohol use, and substance use with response to an early-pandemic (August-September 2020) phone survey.Results: Of 1,847 women who attended an in-person visit in 2019, 78% responded to a phone survey during the pandemic. The odds of responding were lower for women of Hispanic ethnicity (aOR 0.47 95% CI 0.33-0.66, ref=Black/African American) and those who reported substance use (aOR 0.63 95% CI 0.41-0.98). By contrast, the odds were higher for White women (aOR 1.64 95% CI 1.02-2.70, ref=Black/African American) and those with stable housing (aOR 1.74 95% CI 1.24-2.43).Conclusions: Pivoting from an in-person to phone-administered alcohol and substance use survey may lead to underrepresentation of key subpopulations of women who are often neglected in substance use and HIV research. As remote survey methods become more common, investigators need to ensure that the study population is representative of the target population.


Assuntos
COVID-19 , Infecções por HIV , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estados Unidos/epidemiologia , Feminino , Estudos Prospectivos , Infecções por HIV/epidemiologia , Infecções por HIV/complicações , Pandemias , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , COVID-19/epidemiologia
20.
Arch Psychiatr Nurs ; 48: 51-58, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38453282

RESUMO

Sexual minority men (SMM) in Zambia face significant challenges including stigma, discrimination, and mental health issues, which further impact their HIV-related risk behaviors. This study aimed to investigate the associations between enacted stigma, substance abuse, HIV-related behaviors, and mental health (i.e., depression, anxiety, and post-traumatic stress disorder [PTSD] symptoms) among SMM in Zambia. SMM aged 18-35 years who reported having multiple and/or concurrent sexual partners or low and/or inconsistent condom use in the past three months were recruited from four districts in Zambia between February and November 2021. Participants completed an anonymous interviewer-administered survey. Key variables of interest were compared between participants with higher vs. lower levels of enacted stigma. Independent samples t-tests were used for continuous variables, and chi-squared tests were used for categorical variables. A total of 197 eligible SMM participated in the study (mean age = 24.41 years). Participants with a higher level of enacted stigma showed a higher level of anxiety symptoms (χ2 = 12.91, p ≤ .001), PTSD symptoms (χ2 = 7.13, p < .01), tobacco use (χ2 = 10.47, p < .01), cannabis use (χ2 = 5.90, p < .05), and a higher number of sexual partners (t = 1.99, p < .05) in the past three months. Stigma reduction interventions may help mitigate substance abuse, HIV-related behaviors, and adverse mental health outcomes among SMM in Zambia. Health care providers, especially psychiatric-mental health nurses, can incorporate strategies for recognizing and addressing stigma into their practice through training and integrate multiple resources to create an inclusive and non-judgmental environment for SMM to improve their well-being.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Masculino , Humanos , Adulto Jovem , Adulto , Saúde Mental , Homossexualidade Masculina/psicologia , Zâmbia/epidemiologia , Estigma Social , Transtornos Relacionados ao Uso de Substâncias/psicologia
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