Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 80
Filter
Add more filters

Publication year range
1.
AIDS Behav ; 28(6): 2113-2130, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38573473

ABSTRACT

We assessed the role of patient-centered care on durable viral suppression (i.e., all viral load test results < 200 copies per ml during 2019) by conducting a retrospective cohort study of clients medically case managed by the Miami-Dade County Ryan White Program (RWP). Summary measures of patient-centered care practices of RWP-affiliated providers were obtained from a survey of 1352 clients. Bayesian network models analyzed the complex relationship between psychosocial and patient-centered care factors. Of 5037 clients, 4135 (82.1%) had durable viral suppression. Household income was the factor most strongly associated with durable viral suppression. Further, mean healthcare relationship score and mean "provider knows patient as a person" score were both associated with durable viral suppression. Healthcare relationship score moderated the association between low household income and lack of durable viral suppression. Although patient-centered care supports patient HIV care success, wrap around support is also needed for people with unmet psychosocial needs.


RESUMEN: Evaluamos el rol de la atención centrada en el paciente en la supresión viral duradera (es decir, todos los resultados de las pruebas de carga viral < 200 copias por ml durante 2019) mediante la realización de un estudio de cohorte retrospectivo de clientes manejados médicamente por el Programa Ryan White del condado de Miami-Dade (RWP). Se obtuvieron medidas resumidas de las prácticas de atención centradas en el paciente de los proveedores afiliados a RWP usando una encuesta de 1352 clientes. Los modelos de redes bayesianos analizaron la relación compleja entre los factores psicosociales y de atención centrada en el paciente. De 5037 clientes, 4135 (82,1%) tenían una supresión viral duradera. Los ingresos del hogar fueron el factor asociado con la supresión viral duradera más fuerte. Además, la puntuación promedia de la relación con proveedores de atención médica y la puntuación promedia de "el proveedor conoce al paciente como persona" fueron asociados con una supresión viral duradera. La puntuación de la relación con proveedores de atención médica moderó la asociación entre los ingresos bajos del hogar y la falta de supresión viral duradera. Aunque la atención centrada en el paciente apoya el éxito de la atención médica del VIH, también se necesita un apoyo integral para las personas con necesidades psicosociales insatisfechas.


Subject(s)
Bayes Theorem , HIV Infections , Patient-Centered Care , Viral Load , Humans , HIV Infections/psychology , HIV Infections/drug therapy , Female , Male , Retrospective Studies , Adult , Middle Aged , Florida/epidemiology , Anti-HIV Agents/therapeutic use
2.
J Behav Med ; 47(2): 282-294, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37946027

ABSTRACT

Women with HIV (WWH) face increased difficulties maintaining adherence to antiretroviral therapy (ART) due to a variety of demographic and psychosocial factors. To navigate the complexities of ART regimens, use of strategies to maintain adherence is recommended. Research in this area, however, has largely focused on adherence interventions, and few studies have examined self-reported preferences for adherence strategies. The purpose and objectives of this study were to explore the use of ART self-management strategies among a diverse sample of WWH, examine demographic and psychosocial differences in strategy use, and assess the association between strategies and ART adherence. The current study presents secondary data of 560 WWH enrolled in the Miami-Dade County Ryan White Program. Participants responded to questionnaire items assessing demographic and psychosocial characteristics, use of adherence strategies, and ART adherence during the past month. Principal component analysis identified four categories among the individual strategies and multivariable binomial logistic regression assessed adherence while controlling for individual-level factors. The majority of WWH reported optimal ART adherence, and nearly all used multiple individual strategies. The number of individual strategies used and preferences for strategy types were associated with various demographic and psychosocial characteristics. Adjusting for demographic and psychosocial characteristics, optimal ART adherence during the past month was associated with the use of four or more individual strategies. When conducting regular assessments of adherence, it may be beneficial to also assess use of adherence strategies and to discuss with WWH how using multiple strategies contributes to better adherence.


Subject(s)
Anti-HIV Agents , HIV Infections , Self-Management , Humans , Female , Anti-HIV Agents/therapeutic use , HIV Infections/psychology , Anti-Retroviral Agents/therapeutic use , Medication Adherence
3.
BMC Med Ethics ; 25(1): 39, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38539213

ABSTRACT

BACKGROUND: Respect is essential to providing high quality healthcare, particularly for groups that are historically marginalized and stigmatized. While ethical principles taught to health professionals focus on patient autonomy as the object of respect for persons, limited studies explore patients' views of respect. The purpose of this study was to explore the perspectives of a multiculturally diverse group of low-income women living with HIV (WLH) regarding their experience of respect from their medical physicians. METHODS: We analyzed 57 semi-structured interviews conducted at HIV case management sites in South Florida as part of a larger qualitative study that explored practices facilitating retention and adherence in care. Women were eligible to participate if they identified as African American (n = 28), Hispanic/Latina (n = 22), or Haitian (n = 7). They were asked to describe instances when they were treated with respect by their medical physicians. Interviews were conducted by a fluent research interviewer in either English, Spanish, or Haitian Creole, depending on participant's language preference. Transcripts were translated, back-translated and reviewed in entirety for any statements or comments about "respect." After independent coding by 3 investigators, we used a consensual thematic analysis approach to determine themes. RESULTS: Results from this study grouped into two overarching classifications: respect manifested in physicians' orientation towards the patient (i.e., interpersonal behaviors in interactions) and respect in medical professionalism (i.e., clinic procedures and practices). Four main themes emerged regarding respect in provider's orientation towards the patient: being treated as a person, treated as an equal, treated without blame or prejudice, and treated with concern/emotional support. Two main themes emerged regarding respect as evidenced in medical professionalism: physician availability and considerations of privacy. CONCLUSIONS: Findings suggest a more robust conception of what 'respect for persons' entails in medical ethics for a diverse group of low-income women living with HIV. Findings have implications for broadening areas of focus of future bioethics education, training, and research to include components of interpersonal relationship development, communication, and clinic procedures. We suggest these areas of training may increase respectful medical care experiences and potentially serve to influence persistent and known social and structural determinants of health through provider interactions and health care delivery.


Subject(s)
HIV Infections , Physicians , Humans , Female , Haiti , Delivery of Health Care , Qualitative Research , Physicians/psychology , HIV Infections/therapy
4.
AIDS Care ; 35(10): 1437-1442, 2023 10.
Article in English | MEDLINE | ID: mdl-35621306

ABSTRACT

This exploratory study examined sex differences in psychosocial and demographic factors associated with sustained HIV viral suppression (SVS). The study population included 6,489 Miami-Dade Ryan White Program (RWP) clients receiving services during 2017; administrative data was analyzed. SVS was defined as having all viral load tests during 2017 below 200 copies/ml. Multilevel logistic regression models accounted for clustering by medical case management site. Models were stratified by sex. Overall, a higher proportion of females did not achieve SVS (23.5%) than males (18.1%). For females (n = 1,503), having acquired HIV perinatally and not having a partner oradult household member were associated with not achieving SVS. For males (n = 4,986), lacking access to food, Black or Haitian race/ethnicity, problematic substance use, and unknown physician were associated with not achieving SVS. For both sexes, younger age, lower household income, ever having an AIDS diagnosis, feeling depressed or anxious, and experiencing homelessness were associated with not achieving SVS. Elements of the transition from adolescent to adult HIV care that may differentially impact female clients and factors associated with disclosure should be explored further. Male clients may require additional support for food security. Improving culturally specific care for Haitian and non-Hispanic Black male clients should also be explored.


Subject(s)
HIV Infections , Adult , Adolescent , Humans , Male , Female , Sex Characteristics , Haiti/epidemiology , Florida/epidemiology , Ethnicity , Viral Load
5.
Women Health ; 63(7): 562-576, 2023 08 09.
Article in English | MEDLINE | ID: mdl-37482891

ABSTRACT

Women, particularly those from racial/ethnic minority groups, experience disparities in HIV care and treatment, and in achieving viral suppression. This study identified barriers and facilitators influencing retention in HIV care and treatment adherence among women belonging to racial/ethnic minority groups. We conducted semi-structured interviews with 74 African American, Hispanic/Latina and Haitian cisgender women receiving care from the Ryan White HIV/AIDS Program in Miami-Dade County, Florida in 2019. Data were analyzed using a thematic analysis approach. The most salient barriers faced by women were competing life priorities, mental health and substance use issues, medication-related concerns and treatment burden, negative experiences with HIV care services, transportation and parking issues and stigma and discrimination. Important facilitators identified by women included taking personal responsibility for health, social support, and patient-friendly and supportive HIV care services. Our findings suggest that HIV care could be enhanced for this population by understanding the non-HIV needs of the women in care, provide more flexible and relevant services in response to the totality of these needs, and simplify and expand access to care and supportive services.


Subject(s)
HIV Infections , Retention in Care , Humans , Female , HIV Infections/psychology , Florida , Ethnicity , Haiti , Minority Groups , Treatment Adherence and Compliance , Qualitative Research
6.
J Ethn Subst Abuse ; : 1-12, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37729468

ABSTRACT

People with HIV (PWH) from racial/ethnic minority groups may be particularly vulnerable to the effects of the COVID-19 Pandemic. Exacerbated COVID-19-related stressors may lead to maladaptive coping mechanisms such as increased alcohol use. This study examined socioeconomic and psychosocial predictors of increased alcohol use during the first year of the COVID-19 Pandemic among PWH from racial/ethnic minority groups in South Florida. Data were collected from Ryan White Program clients during October 2020-January 2021 using a cross-sectional phone survey, and were analyzed using logistic regression modeling. Among 139 participants, 20% reported increased alcohol use. Findings showed that being unable to buy needed food (adjusted odds ratio [aOR]: 3.37; 95% confidence interval [CI]: 1.01-11.31) and spending more time caring for children (aOR: 5.22, 95% CI: 1.61-16.88) was associated with increased alcohol use during the Pandemic. Providing support to alleviate food insecurity and manage caregiving burden during public health crises like the COVID-19 Pandemic might help prevent increases in alcohol use among PWH.

7.
AIDS Behav ; 26(11): 3576-3588, 2022 Nov.
Article in English | MEDLINE | ID: mdl-35536517

ABSTRACT

The study's objective was to examine variations in viral load (VL) suppression definitions among clients in the Ryan White Program (RWP). Data from clients enrolled in the RWP during 2017 were examined to calculate the proportion of virally suppressed clients using three definitions: recent viral suppression, defined as having a suppressed VL (< 200 copies/mL) in the last test in 2017; maintained viral suppression, having a suppressed VL for both the first and last tests in 2017; and sustained viral suppression, having all tests in 2017 showing suppression. Relative differences across all three definitions were computed. Recent viral suppression measures were higher than maintained and sustained viral suppression measures by 7.0% and 10.1%, respectively. Significant relative differences in definitions by demographic, socioeconomic and clinical status were observed. It may be beneficial for care planning to report not only estimates of recent viral suppression but maintained and sustained viral suppression as well.


Subject(s)
HIV Infections , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Testing , Humans , Sustained Virologic Response , Viral Load
8.
AIDS Care ; 34(5): 615-620, 2022 05.
Article in English | MEDLINE | ID: mdl-33576239

ABSTRACT

The purpose of this study was to assess the prevalence of chlamydia or gonorrhea and factors associated with the diagnoses among people with HIV (PHIV) in the Ryan White Program Part A (RWP) in Miami-Dade County, Florida. We used 2017 calendar year data to identify factors associated with a chlamydia or gonorrhea diagnoses using logistic regression. About 50% of the 7110 PHIV who were ≥18 years old in active Ryan White care in 2017 reported being screened for chlamydia or gonorrhea. Of those screened, 2.3% reported diagnoses of chlamydia, gonorrhea or both. In the adjusted model, compared to PHIV ≥40 years-old, PHIV aged 18-24 and 25-39 years reported higher odds of diagnoses (adjusted odds ratio [aOR] 4.29; 95% confidence interval [CI]: 1.73-10.63 and aOR 4.58; 95% CI; 2.62-7.99 respectively). Those with multiple sexual partners in the last 12 months reported higher odds of diagnoses (aOR 1.67; (95% CI; 1.04-2.69)). Screening rates for chlamydia or gonorrhea are low, relative to CDC guidelines. Interventions are needed to increase rates of screening and targeted behavioral risk reduction techniques are highly recommended among those 18-39 years of age and those who have multiple sexual partners.


Subject(s)
Chlamydia , Gonorrhea , HIV Infections , Adolescent , Adult , Florida/epidemiology , Gonorrhea/diagnosis , Gonorrhea/epidemiology , Gonorrhea/prevention & control , HIV Infections/diagnosis , HIV Infections/epidemiology , Humans , Prevalence , Sexual Partners , Young Adult
9.
AIDS Behav ; 25(7): 2252-2258, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33471241

ABSTRACT

The study's objective was to identify the association between sustained viral suppression (all viral load tests < 200 copies/ml per year) and patterns of co-occurring risk factors including, mental health, substance use, sexual risk behavior, and adverse social conditions for people with HIV (PWH). Latent class analysis followed by multivariable logistic regression was conducted for 6554 PWH in the Miami-Dade County Ryan White Program during 2017, and a five-class model was selected. Compared to Class 1 (no risk factors), the odds of achieving sustained viral suppression was significantly lower for Class 2 (mental health) (aOR: 0.67; 95% CI 0.54-0.83), Class 3 (substance use and multiple sexual partners) (0.60; 0.47-0.76), Class 4 (substance use, multiple sexual partners, and domestic violence) (0.71; 0.55-0.93), and Class 5 (mental health, substance use, multiple sexual partners, domestic violence, and homelessness) (0.26; 0.19-0.35). Findings indicate the need for targeted interventions that address these syndemic factors.


Subject(s)
HIV Infections , Substance-Related Disorders , Florida/epidemiology , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Latent Class Analysis , Substance-Related Disorders/epidemiology , Sustained Virologic Response , Syndemic
10.
BMC Public Health ; 20(1): 326, 2020 Mar 13.
Article in English | MEDLINE | ID: mdl-32169065

ABSTRACT

BACKGROUND: HIV viral suppression is associated with health benefits for people living with HIV and a decreased risk of HIV transmission to others. The objective was to identify demographic, psychosocial, provider and neighborhood factors associated with sustained viral suppression among gay, bisexual, and other men who have sex with men. METHODS: Data from adult men who have sex with men (MSM) enrolled in the Miami-Dade County Ryan White Program (RWP) before 2017 were used. Sustained viral suppression was defined as having an HIV viral load < 200 copies/ml in all viral load tests in 2017. Three-level (individual, medical case management site, and neighborhood) cross-classified mixed-effect models were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for sustained viral suppression. RESULTS: Of 3386 MSM, 90.8% were racial/ethnic minorities, and 84.4% achieved sustained viral suppression. The odds of achieving sustained viral suppression was lower for 18-24 and 25-34 year-old MSM compared with 35-49 year-old MSM, and for non-Latino Black MSM compared with White MSM. Those not enrolled in the Affordable Care Act, and those with current AIDS symptoms and a history of AIDS had lower odds of achieving sustained viral suppression. Psychosocial factors significantly associated with lower odds of sustained viral suppression included drug/alcohol use, mental health symptoms, homelessness, and transportation to appointment needs. Individuals with an HIV physician who serves a larger volume of RWP clients had greater odds of sustained viral suppression. Neighborhood factors were not associated with sustained viral suppression. CONCLUSION: Despite access to treatment, age and racial disparities in sustained viral suppression exist among MSM living with HIV. Addressing substance use, mental health, and social services' needs may improve the ability of MSM to sustain viral suppression long-term. Furthermore, physician characteristics may be associated with HIV outcomes and should be explored further.


Subject(s)
HIV Infections/therapy , Health Status Disparities , Homosexuality, Male/statistics & numerical data , Sustained Virologic Response , Adult , Age Factors , Ethnicity/statistics & numerical data , Florida , HIV Infections/ethnology , Health Personnel/statistics & numerical data , Homosexuality, Male/ethnology , Homosexuality, Male/psychology , Humans , Male , Middle Aged , Patient Protection and Affordable Care Act/statistics & numerical data , Program Evaluation , Residence Characteristics/statistics & numerical data
11.
J Biol Chem ; 289(34): 23596-608, 2014 Aug 22.
Article in English | MEDLINE | ID: mdl-24970892

ABSTRACT

Plasma kallikrein (pKal) proteolytically cleaves high molecular weight kininogen to generate the potent vasodilator and the pro-inflammatory peptide, bradykinin. pKal activity is tightly regulated in healthy individuals by the serpin C1-inhibitor, but individuals with hereditary angioedema (HAE) are deficient in C1-inhibitor and consequently exhibit excessive bradykinin generation that in turn causes debilitating and potentially fatal swelling attacks. To develop a potential therapeutic agent for HAE and other pKal-mediated disorders, we used phage display to discover a fully human IgG1 monoclonal antibody (DX-2930) against pKal. In vitro experiments demonstrated that DX-2930 potently inhibits active pKal (Ki = 0.120 ± 0.005 nM) but does not target either the zymogen (prekallikrein) or any other serine protease tested. These findings are supported by a 2.1-Å resolution crystal structure of pKal complexed to a DX-2930 Fab construct, which establishes that the pKal active site is fully occluded by the antibody. DX-2930 injected subcutaneously into cynomolgus monkeys exhibited a long half-life (t½ ∼ 12.5 days) and blocked high molecular weight kininogen proteolysis in activated plasma in a dose- and time-dependent manner. Furthermore, subcutaneous DX-2930 reduced carrageenan-induced paw edema in rats. A potent and long acting inhibitor of pKal activity could be an effective treatment option for pKal-mediated diseases, such as HAE.


Subject(s)
Antibodies/immunology , Kallikreins/immunology , Amino Acid Sequence , Animals , Catalytic Domain , Crystallography, X-Ray , Enzyme-Linked Immunosorbent Assay , Humans , Kallikreins/blood , Molecular Sequence Data , Rats , Rats, Sprague-Dawley , Surface Plasmon Resonance
12.
FEBS J ; 2024 Sep 22.
Article in English | MEDLINE | ID: mdl-39308084

ABSTRACT

The tumour microenvironment (TME) is a dynamic nexus where cancer cell metabolism and the immune system intricately converge, with nucleotide metabolism (NM) playing a pivotal role. This review explores the critical function of NM in cancer cell proliferation and its profound influence on the TME and immune landscape. NM is essential for DNA and RNA synthesis and is markedly upregulated in cancer cells to meet the demands of rapid growth. This metabolic rewiring fuels cancer progression, but also shapes the TME, impacting the function and viability of immune cells. The altered nucleotide milieu in the TME can suppress immune response, aiding cancer cell evasion from immune surveillance. Drug discoveries in the field of NM have revealed different therapeutic strategies, including inhibitors of nucleotide synthesis and drugs targeting salvage pathways, which are discussed thoroughly in this review. Furthermore, the emerging strategy of combining NM-targeted therapies with immunotherapies is emphasised, particularly their effect on sensitising tumours to immune checkpoint inhibitors and enhancing overall treatment efficacy. The Human Genome Project paved the way for personalised medicine, countering the established 'one size fits all' approach to cancer treatment. Advances in understanding the TME and NM have spurred interest in personalised therapeutic strategies. This review highlights the potential of leveraging individual tumour metabolic profiles to guide treatment selection, aiming to optimise efficacy and minimise adverse effects. The strategic importance of targeting NM in cancer therapy and its synergistic potential with immunotherapies offers a path towards more effective and personalised cancer treatments.

13.
J Acquir Immune Defic Syndr ; 95(4): 329-341, 2024 04 01.
Article in English | MEDLINE | ID: mdl-38133577

ABSTRACT

BACKGROUND: Racial/ethnic minority groups with HIV in the United States are particularly vulnerable to COVID-19 consequences and can significantly benefit from increased uptake of COVID-19 vaccines. This study identified factors associated with full COVID-19 vaccination among people with HIV. SETTING: Ryan White HIV/AIDS Program in Miami-Dade County, FL. METHODS: Data were collected from 299 Ryan White HIV/AIDS Program adult clients during January-March 2022 using a cross-sectional phone survey. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). All analyses were weighted to be representative of the race/ethnicity and sex distribution of clients in the Ryan White HIV/AIDS Program. RESULTS: Eighty-four percent of participants were fully vaccinated with a primary vaccine series; stratified by race/ethnicity, the percentages were 88.9% of Hispanic, 72.0% of black/African American, and 67.5% of Haitian participants. Fully vaccinated participants were less likely to be black/African American than Hispanic (aOR = 0.18; 95% CI: 0.05 to 0.67) and more likely to not endorse any misconceptions about COVID-19 vaccines (aOR = 8.26; 95% CI: 1.38 to 49.64), to report encouragement to get vaccinated from sources of information (aOR = 20.82; 95% CI: 5.84 to 74.14), and to perceive that more than 50% of their social network was vaccinated (aOR = 3.35; 95% CI: 1.04 to 10.71). Experiences of health care discrimination, structural barriers to access vaccines, and recommendations from HIV providers were not associated with full vaccination. CONCLUSIONS: These findings highlight the importance of delivering accurate and positive messages about vaccines and engaging social networks to promote COVID-19 vaccination among people with HIV. This information can be leveraged to promote uptake of subsequent boosters and other recommended vaccines.


Subject(s)
Acquired Immunodeficiency Syndrome , COVID-19 , HIV Infections , Adult , Humans , United States , Ethnicity , Florida/epidemiology , COVID-19 Vaccines , Ethnic and Racial Minorities , Cross-Sectional Studies , Haiti , COVID-19/epidemiology , COVID-19/prevention & control , Minority Groups , HIV Infections/epidemiology , HIV Infections/prevention & control , Vaccination , White
14.
J Int Assoc Provid AIDS Care ; 23: 23259582241244684, 2024.
Article in English | MEDLINE | ID: mdl-38651291

ABSTRACT

Background: Patient-centered care (PCC) improves HIV adherence and retention, though lack of consensus on its conceptualization and understanding how it is interpreted has hindered implementation. Methods: We recruited 20 HIV providers at Ryan White Programs in FL for in-depth interviews. Thematic analysis identified core consistencies pertaining to: 1) provider perceptions, 2) current practices promoting PCC. Results: Provider perceptions of PCC emerged under four domains: 1) holistic, 2) individualized care, 3) respect for comfort and security, and 4) patient engagement and partnership. PCC practices occurred at multiple levels: 1) individual psychosocial and logistical support, 2) interpersonal support within patient-provider relationships through respectful communication and active engagement, and 3) institutional practices including feedback mechanisms, service integration, patient convenience, and diverse staffing. Conclusions: Our findings highlight the central tenets of PCC as respectful, holistic, individualized, and engaging care. We offer an HIV-adapted framework of PCC as a multilevel construct to guide future intervention.


Patient-centered care perspectives among HIV care providersThis study explores HIV care provider perceptions of patient-centered care (PCC) by analyzing common themes that arose in interviews. We found that providers perceived PCC to be holistic, individualized care focused on respecting patient comfort and security and actively engaging them as partners in care. Providers discussed a variety of ways in which they practiced PCC at the individual service level through psychosocial and logistical support, through their interpersonal relationships with respectful communication and trust, and through more structured facility level policies and activities such as greater service integration and employing a diverse staff. PCC is rapidly becoming the new standard of care and this study hopes to offer insight into provider perceptions of PCC and examples of practice in the HIV care field.


Subject(s)
Attitude of Health Personnel , HIV Infections , Patient-Centered Care , Qualitative Research , Adult , Female , Humans , Male , Middle Aged , Florida , Health Personnel/psychology , HIV Infections/psychology , Interviews as Topic , Perception
15.
Angiogenesis ; 16(1): 29-44, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22945845

ABSTRACT

Lymphedema is mainly caused by lymphatic obstruction and manifested as tissue swelling, often in the arms and legs. Lymphedema is one of the most common post-surgical complications in breast cancer patients and presents a painful and disfiguring chronic illness that has few treatment options. Here, we evaluated the therapeutic potential of interleukin (IL)-8 in lymphatic regeneration independent of its pro-inflammatory activity. We found that IL-8 promoted proliferation, tube formation, and migration of lymphatic endothelial cells (LECs) without activating the VEGF signaling. Additionally, IL-8 suppressed the major cell cycle inhibitor CDKN1C/p57(KIP2) by downregulating its positive regulator PROX1, which is known as the master regulator of LEC-differentiation. Animal-based studies such as matrigel plug and cornea micropocket assays demonstrated potent efficacy of IL-8 in activating lymphangiogenesis in vivo. Moreover, we have generated a novel transgenic mouse model (K14-hIL8) that expresses human IL-8 in the skin and then crossed with lymphatic-specific fluorescent (Prox1-GFP) mouse. The resulting double transgenic mice showed that a stable expression of IL-8 could promote embryonic lymphangiogenesis. Moreover, an immunodeficient IL-8-expressing mouse line that was established by crossing K14-hIL8 mice with athymic nude mice displayed an enhanced tumor-associated lymphangiogenesis. Finally, when experimental lymphedema was introduced, K14-hIL8 mice showed an improved amelioration of lymphedema with an increased lymphatic regeneration. Together, we report that IL-8 can activate lymphangiogenesis in vitro and in vivo with a therapeutic efficacy in post-surgical lymphedema.


Subject(s)
Interleukin-8/therapeutic use , Lymphatic Vessels/physiopathology , Lymphedema/drug therapy , Lymphedema/etiology , Postoperative Complications/drug therapy , Postoperative Complications/etiology , Regeneration , Animals , Cell Proliferation/drug effects , Cells, Cultured , Cyclin-Dependent Kinase Inhibitor p57/metabolism , Down-Regulation/drug effects , Embryonic Development/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Homeodomain Proteins/metabolism , Humans , Interleukin-8/metabolism , Interleukin-8/pharmacology , Lymphangiogenesis/drug effects , Lymphatic Vessels/drug effects , Lymphatic Vessels/pathology , Lymphedema/pathology , Lymphedema/physiopathology , Mice , Mice, Transgenic , Neovascularization, Physiologic/drug effects , Postoperative Complications/pathology , Postoperative Complications/physiopathology , Receptors, Interleukin-8/metabolism , Receptors, Interleukin-8A/metabolism , Receptors, Interleukin-8B/metabolism , Regeneration/drug effects , Tretinoin/pharmacology , Tumor Microenvironment/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Tumor Suppressor Proteins/metabolism
16.
Invest New Drugs ; 31(4): 845-57, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23299388

ABSTRACT

Despite compelling preclinical data in colorectal cancer (CRC), the efficacy of HDACIs has been disappointing in the clinic. The goal of this study was to evaluate the effectiveness of vorinostat and panobinostat in a dose- and exposure-dependent manner in order to better understand the dynamics of drug action and antitumor efficacy. In a standard 72 h drug exposure MTS assay, notable concentration-dependent antiproliferative effects were observed in the IC50 range of 1.2-2.8 µmol/L for vorinostat and 5.1-17.5 nmol/L for panobinostat. However, shorter clinically relevant exposures of 3 or 6 h failed to elicit any significant growth inhibition and in most cases a >24 h exposure to vorinostat or panobinostat was required to induce a sigmoidal dose-response. Similar results were observed in colony formation assays where ≥ 24 h of exposure was required to effectively reduce colony formation. Induction of acetyl-H3, acetyl-H4 and p21 by vorinostat were transient and rapidly reversed within 12 h of drug removal. In contrast, panobinostat-induced acetyl-H3, acetyl-H4, and p21 persisted for 48 h after an initial 3 h exposure. Treatment of HCT116 xenografts with panobinostat induced significant increases in acetyl-H3 and downregulation of thymidylate synthase after treatment. Although HDACIs exert both potent growth inhibition and cytotoxic effects when CRC cells were exposed to drug for ≥ 24 h, these cells demonstrate an inherent ability to survive HDACI concentrations and exposure times that exceed those clinically achievable. Continued efforts to develop novel HDACIs with improved pharmacokinetics/phamacodynamics, enhanced intratumoral delivery and class/isoform-specificity are needed to improve the therapeutic potential of HDACIs and HDACI-based combination regimens in solid tumors.


Subject(s)
Antineoplastic Agents/therapeutic use , Colorectal Neoplasms/drug therapy , Histone Deacetylase Inhibitors/therapeutic use , Hydroxamic Acids/therapeutic use , Indoles/therapeutic use , Acetylation/drug effects , Animals , Antineoplastic Agents/pharmacology , Blotting, Western , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Colorectal Neoplasms/pathology , DNA Mutational Analysis , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Histone Deacetylase Inhibitors/pharmacology , Humans , Hydroxamic Acids/pharmacology , Indoles/pharmacology , Male , Mice , Neoplasm Proteins/genetics , Panobinostat , Thymidylate Synthase/metabolism , Time Factors , Tumor Stem Cell Assay , Vorinostat , Xenograft Model Antitumor Assays
17.
Nucleic Acids Res ; 39(17): e112, 2011 Sep 01.
Article in English | MEDLINE | ID: mdl-21576234

ABSTRACT

Current methods for measuring deoxyribonucleoside triphosphates (dNTPs) employ reagent and labor-intensive assays utilizing radioisotopes in DNA polymerase-based assays and/or chromatography-based approaches. We have developed a rapid and sensitive 96-well fluorescence-based assay to quantify cellular dNTPs utilizing a standard real-time PCR thermocycler. This assay relies on the principle that incorporation of a limiting dNTP is required for primer-extension and Taq polymerase-mediated 5-3' exonuclease hydrolysis of a dual-quenched fluorophore-labeled probe resulting in fluorescence. The concentration of limiting dNTP is directly proportional to the fluorescence generated. The assay demonstrated excellent linearity (R(2) > 0.99) and can be modified to detect between ∼0.5 and 100 pmol of dNTP. The limits of detection (LOD) and quantification (LOQ) for all dNTPs were defined as <0.77 and <1.3 pmol, respectively. The intra-assay and inter-assay variation coefficients were determined to be <4.6% and <10%, respectively with an accuracy of 100 ± 15% for all dNTPs. The assay quantified intracellular dNTPs with similar results obtained from a validated LC-MS/MS approach and successfully measured quantitative differences in dNTP pools in human cancer cells treated with inhibitors of thymidylate metabolism. This assay has important application in research that investigates the influence of pathological conditions or pharmacological agents on dNTP biosynthesis and regulation.


Subject(s)
Deoxyribonucleotides/analysis , Nucleic Acid Hybridization/methods , DNA-Directed DNA Polymerase , Deoxyuracil Nucleotides/analysis , Fluorescence Resonance Energy Transfer , HCT116 Cells , Humans , Oligonucleotide Probes , Polymerase Chain Reaction , Ribonucleotides/chemistry , Templates, Genetic
18.
J Racial Ethn Health Disparities ; 10(1): 357-366, 2023 02.
Article in English | MEDLINE | ID: mdl-35099764

ABSTRACT

BACKGROUND: Identifying geographic locations most affected by the HIV epidemic is essential to addressing disparities that impact people living with HIV. This study sought to identify individual and neighborhood-level factors that are associated with residing in geographic hotspots of poor sustained HIV viral suppression. METHODS: Using data from the Miami-Dade County Ryan White HIV/AIDS program, spatial autocorrelation of poor sustained viral suppression (at least 1 laboratory test ≥ 200 copies/ml in 2017) was investigated using Global Moran's I followed by Local Moran's I and Getis Ord Gi* statistics by ZIP code tabulation areas (ZCTAs). Subsequently, multivariable logistic regression analysis was conducted to identify factors associated with residing in geographic hotspots of poor sustained viral suppression. RESULTS: Several ZCTAs in the northern part of the county, accounting for 1/3 of the Ryan White program clients, had significantly higher clustering of poor sustained viral suppression. Client-level sociodemographic characteristics such as race/ethnicity, age, and poverty, and neighborhood-level characteristics (socioeconomic disadvantage index, residential instability index, and racial/language homogeneity index) were significantly associated with living in a hotspot of poor sustained viral suppression. CONCLUSION: These findings highlight that spatial variation in sustained viral suppression exists within the county. Targeted strategies that address structural factors and the needs of people with HIV living in specified geographic areas may improve their HIV health outcomes and contribute towards local, regional, and national goals of ending the HIV epidemic.


Subject(s)
HIV Infections , Humans , Florida/epidemiology , HIV Infections/epidemiology , Sustained Virologic Response , Ethnicity , Residence Characteristics
19.
J Racial Ethn Health Disparities ; 10(2): 930-941, 2023 04.
Article in English | MEDLINE | ID: mdl-35426056

ABSTRACT

Low-income, minority women living with HIV often experience multiple barriers in care that contribute to suboptimal care outcomes. Medical case managers (MCM) and medical providers are key players involved in care coordination and aid women along the HIV care continuum. The objective of this study was to identify current and potential patient-centered practices that facilitate adherence to medication and retention in care, from the perspective of racially and ethnically diverse women living with HIV. We implemented a qualitative study using semi-structured interviews with 75 African American, Hispanic/Latina, and Haitian women who were enrolled in the Ryan White HIV/AIDS Program in South Florida in 2019. We organized domains of exploration using a patient-centered care framework to identify practices in which providers acknowledged, respected, and responded to clients' preferences, needs, and values. Interviews were analyzed using consensual thematic analysis approach. Findings reflect women valued MCMs who were proactive and directive in care, provided motivation, and aided with navigation of shame, fear, and stigma. Women valued medical providers who upheld simple educational communication. Moreover, women reported that providers who reviewed medical results with clients, incorporated questions about families, and inquired about multiple physical and clinical needs beyond HIV created opportunities for women to feel respected, valued, and in turn, enhanced their involvement in their care. Findings identify specific interpersonal practices that can enhance the ability to better meet the needs of diverse groups of women, specifically those from racial/ethnic minority groups who face multiple sociocultural barriers while in care.


Subject(s)
HIV Infections , Humans , Female , HIV Infections/drug therapy , Florida , Ethnicity , Haiti , Minority Groups
20.
AIDS Patient Care STDS ; 37(7): 361-372, 2023 07.
Article in English | MEDLINE | ID: mdl-37432309

ABSTRACT

Women with HIV in the United States are more negatively affected by adverse social determinants such as low education and poverty than men, and thus, especially need a supportive health care system. This cross-sectional study assessed the role of the patient-provider relationship on antiretroviral therapy (ART) adherence and durable viral suppression among women with HIV (WHIV) in Miami-Dade County, Florida. Patient-provider relationship was measured, in part, using the Health Care Relationship Trust Scale and Consumer Assessment of Health Care Providers and Systems. The survey was administered by telephone to women in the Ryan White Program June 2021-March 2022. Adherence was defined as 90% adherent on the average of three self-reported items. Lack of durable viral suppression was defined by at least one viral load ≥200 copies/mL among all tests conducted in a year. Logistic regression models were generated using backward stepwise modeling. Of 560 cis-gender women, 401 (71.6%) were adherent, and 450 (80.4%) had durable viral suppression. In the regression model, adherence was associated with higher patient-provider trust and provider communication as well as excellent perceived health, lack of significant depressive symptoms, no alcohol use within the last 30 days, and lack of transportation problems. In the regression model using provider as a random effect, durable viral suppression was associated with older age, Hispanic ethnicity, and lack of illegal drug use. While the results show that a strong patient-provider relationship facilitates ART adherence in WHIV, there was no association with durable viral suppression.


Subject(s)
HIV Infections , Male , Female , Humans , Florida/epidemiology , Cross-Sectional Studies , HIV Infections/drug therapy , HIV Infections/epidemiology , Professional-Patient Relations , Anti-Retroviral Agents
SELECTION OF CITATIONS
SEARCH DETAIL