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1.
Curr Pharm Des ; 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32003666

RESUMO

Parkinson's disease is one of the most severe progressive neurodegenerative diseases which have a mortifying effect on the health of almost hundreds of millions of people around the globe. The neural cells producing dopamine in the substantia nigra of the brain die out which leads to symptoms like hypokinesia, rigidity, bradykinesia and rest tremor.Parkinsonism cannot be cured but the symptoms can be reduced with the intervention of medicinal drugs, surgical treatments and physical therapies. Delivering drugs to the brain for treating Parkinson's disease is very challenging, the blood brain barrier act as a highly selective semi permeable barrier which refrains the drug from reaching the brain. Conventional drug delivery systems used for Parkinson's disease does not easily cross the blood barrier and further leads to a number of side effects. Recent advancements in drug delivery technologies have facilitated the drug delivery to the brain without flooding the blood stream and by directly targeting the neurons.In the era of Nanotherapeutics, liposomes can be an efficient drug delivery option for brain targeting.Liposomes can facilitate the passage of drugs across the blood brain barrier, enhances the efficacy of the drugs and minimises the side effects related to it. The review aims at providing a broad updated view of the liposomes, which can be used for targetingParkinson's disease.

2.
Sci Adv ; 6(4): eaay8514, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-32010790

RESUMO

Poor transport of neuropharmaceutics through central nervous system (CNS) barriers limits the development of effective treatments for CNS disorders. We present the facile synthesis of a novel neuroinflammation-targeting polyethylene glycol-based dendrimer (PEGOL-60) using an efficient click chemistry approach. PEGOL-60 reduces synthetic burden by achieving high hydroxyl surface density at low generation, which plays a key role in brain penetration and glia targeting of dendrimers in CNS disorders. Systemically administered PEGOL-60 crosses impaired CNS barriers and specifically targets activated microglia/macrophages at the injured site in diverse animal models for cerebral palsy, glioblastoma, and age-related macular degeneration, demonstrating its potential to overcome impaired blood-brain, blood-tumor-brain, and blood-retinal barriers and target key cells in the CNS. PEGOL-60 also exhibits powerful intrinsic anti-oxidant and anti-inflammatory effects in inflamed microglia in vitro. Therefore, PEGOL-60 is an effective vehicle to specifically deliver therapies to sites of CNS injury for enhanced therapeutic outcomes in a range of neuroinflammatory diseases.

3.
J Int AIDS Soc ; 23(2): e25431, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32064766

RESUMO

INTRODUCTION: Accurate costing is key for programme planning and policy implementation. Since 2011, there have been major changes in eligibility criteria and treatment regimens with price reductions in ART drugs, programmatic changes resulting in clinical task-shifting and decentralization of ART delivery to peripheral health centres making existing evidence on ART care costs in Zambia out-of-date. As decision makers consider further changes in ART service delivery, it is important to understand the current drivers of costs for ART care. This study provides updates on costs of ART services for HIV-positive patients in Zambia. METHODS: We evaluated costs, assessed from the health systems perspective and expressed in 2016 USD, based on an activity-based costing framework using both top-down and bottom-up methods with an assessment of process and capacity. We collected primary site-level costs and resource utilization data from government documents, patient chart reviews and time-and-motion studies conducted in 10 purposively selected ART clinics. RESULTS: The cost of providing ART varied considerably among the ten clinics. The average per-patient annual cost of ART service was $116.69 (range: $59.38 to $145.62) using a bottom-up method and $130.32 (range: $94.02 to $162.64) using a top-down method. ART drug costs were the main cost driver (67% to 7% of all costs) and are highly sensitive to the types of patient included in the analysis (long-term vs. all ART patients, including those recently initiated) and the data sources used (facility vs. patient level). Missing capacity costs made up 57% of the total difference between the top-down and bottom-up estimates. Variability in cost across the ten clinics was associated with operational characteristics. CONCLUSIONS: Real-world costs of current routine ART services in Zambia are considerably lower than previously reported estimates and sensitive to operational factors and methods used. We recommend collection and monitoring of resource use and capacity data to periodically update cost estimates.

4.
Curr Top Med Chem ; 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32108008

RESUMO

Alzheimer disease (AD) is the most prevalent and severe neurodegenerative disease affecting more than 0.024 billion people globally, more common in women as compared to men. Senile plaques and amyloid deposition is one of the main causes of AD, amyloid deposition isconsidered as a central event which induces the link between the production of ß amyloid and vascular changes. Presence of numerous biomarkers such as Cerebral amyloid angiopathy, Microvascular changes, Senile plaques, changes in white matter, Granulovascular degeneration specifies the manifestation of AD while as an aggregation of tau protein is considered as a primary marker of AD. Likewise microvascular changes, activation of microglia (immune defense system of CNS), amyloid beta aggregation, senile plaque and many more biomarkers is nearly found in all Alzheimer patients. It was seen that 70% of Alzheimer cases occur due to genetic factors. It has been reported in various studies that apolipoprotein E(APOE) mainly APOE4 is one of the major risk factor for the later onset of AD. Several pathological changes also occur in the white matter which includes dilation of the perivascular space, loss of axons, reactive astrocytosis, oligodendrocytes and failure to drain interstitial fluid. In this review we are aiming to highlight about the various biological signatures associated with the AD which may further help in discovering multitargeting drug therapy.

5.
J Acquir Immune Defic Syndr ; 83(3): 301-309, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31913989

RESUMO

OBJECTIVE: To determine whether domain-specific neurocognitive (NC) impairments predict falls in HIV+ compared with HIV- women. DESIGN: Cross-sectional data analysis from 825 HIV+ and 392 HIV- women in the Women's Interagency HIV Study with NC testing within 2 years before falls surveys. METHODS: NC impairment (T score <40) was assessed in 7 domains: executive function, psychomotor speed, attention, learning, memory, fluency, and fine motor function. For domains associated with any fall within 6 months in simple logistic regression (P < 0.05), hierarchical regression models evaluated associations between NC impairment and odds of falling, adjusting for: (1) study site and HIV, (2) demographics, (3) comorbid conditions, (4) substance use/central nervous system active medications, and HIV-specific factors. RESULTS: Median age was higher in HIV+ than HIV- women (51 vs. 48 yrs); prevalence of falls was similar (19% HIV+, 16% HIV-). Overall, executive function [OR (odds ratio) = 1.82, 95% CI (confidence interval): 1.21 to 2.74; P = 0.004], psychomotor speed (OR = 1.59, 95% CI: 1.05 to 2.42, P = 0.03), and fine motor (OR 1.70, 95% CI: 1.11 to 2.61, P = 0.02) impairments were associated with greater odds of falls in fully adjusted models. In fully adjusted models, associations of executive function, psychomotor speed, and fine motor were nonsignificant among HIV+ women; conversely, among HIV- women, associations with impaired executive and fine motor functions were strengthened and remained significant. CONCLUSIONS: Cognitive impairment was associated with falls among middle-aged HIV- but not HIV+ women. Additional studies should elucidate mechanisms by which domain-specific NC impairment impacts fall risk among older HIV+ and HIV- women and how different factors modify relationships between cognition and falls.

6.
Res Theory Nurs Pract ; 34(1): 49-64, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31937636

RESUMO

Decreased cognitive function is related to undesirable psychological outcomes such as greater emotional distress and lower quality of life, particularly among women living with HIV who experience cognitive impairment (WLWH-CI). Yet, few studies have examined the psychosocial resources that may attenuate these negative emotional outcomes. The current study sought to identify the interrelated contributions of social relationships and psychological resources in 399 WLWH-CI by applying Socio-Emotional Adaptation (SEA) theory using data from the Women's Interagency HIV Study (WIHS). Cognitive impairment (CI) was defined as impairment on two or more cognitive domains. Logistic regression models were used to estimate the odds of experiencing specific emotions due to a combination of four psychosocial resources. Emotions (i.e., depression, apathy, fear, anger, and acceptance) were related to a combination of binary (positive/negative) psychosocial resources including relationship with an informal support partner, relationship with a formal caregiver, coping, and perceived control. Understanding the conditions that may influence emotions in WLWH-CI is important for identifying and appropriately addressing the needs of this population. As CI increases, these individuals experience increasing challenges with articulating their care needs and having their needs met. As such, it becomes increasingly important to identify possible triggers for emotional responses to best address these underlying challenges.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31933016

RESUMO

Antiretroviral therapy (ART) is inconsistently associated with depression. These associations may depend on factors such as biological sex, age, and health status. Identifying such factors may help optimize treatment of HIV and depression. We implemented a novel approach to examine interindividual variability in the association between ART agents and depressive symptoms. 3434 women living with HIV (WLWH) from the Women's Interagency HIV Study (WIHS) were computationally divided into subgroups based on sociodemographic (e.g., age) and longitudinal (from 1995 to 2016) behavioral and clinical profiles (e.g., substance use, HIV RNA, CD4 counts). Five subgroups (n's ranged from 482 to 802) were identified and characterized as those with: controlled HIV/vascular comorbidities; profound HIV legacy effects; younger women [<45 years of age] with hepatitis C; primarily 35-55 year olds; and poorly controlled HIV/substance use. Within each subgroup, we examined associations between ART agents used over the past 6 months and item-level depressive symptoms on the Center for Epidemiologic Studies Depression Scale. Tenofovir (4 of 5 subgroups) followed by efavirenz, emtricitabine, stavudine, lopinavir, etravirine, nelfinavir, ritonavir, and maraviroc were the most common agents associated with depressive symptoms, although the pattern and directionality varied by subgroup. For example, lopinavir was associated with fewer symptoms among the subgroup with a legacy HIV effect but more symptoms among the subgroup with well-controlled HIV/vascular comorbidities. Unexpectedly, dolutegravir and raltegravir were not associated with depressive symptoms among any subgroup. Findings underscore marked interindividual variability in ART agents on depression in WLWH. Sociodemographic, clinical, and behavioral factors are important determinants of the relationship between ART agents and depressive symptoms in WLWH. Graphical Abstract Are antiretroviral agents a risk factor for depressive symptoms in women with HIV? We examined associations between ART-agents and depressive symptoms among similar subgroups of women with HIV from the Women's Interagency HIV Study. The patterns of associations depended on sociodemographic, clinical, and behavioral characteristics of women.

8.
AIDS Res Hum Retroviruses ; 36(2): 131-133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31709815

RESUMO

Diabetes mellitus (DM) is associated with expansion of proinflammatory lymphocyte subsets. We investigated the relationship of total white blood cell (WBC) count and lymphocyte subsets with incident DM in the Women's Interagency HIV Study (WIHS). Higher CD4 and CD8 T cell counts, lymphocyte count, and total WBC count were associated with incident DM among both women with and without HIV, although the association of CD8 was not statistically significant among women without HIV.

9.
J Med Econ ; 23(2): 184-192, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31547724

RESUMO

Introduction: Primary immune thrombocytopenia (ITP), an autoimmune disorder characterized by low platelet count, can lead to serious bleeding events. Little is known about the current epidemiology of ITP in the US, and even less is known about the current healthcare burden of ITP, especially in the 12-month period following ITP diagnosis.Method: We used a retrospective cohort design and data from two US private healthcare claims databases (2010-2016) to identify persons with evidence of newly diagnosed ITP. We weighted estimates of the annual incidence of ITP by age and sex to reflect the US population, and summarized healthcare utilization and expenditures (2016 US$) during the first 12 months after ITP diagnosis ("follow-up period").Results: Annual incidence of ITP in the US was 6.1 per 100,000 persons, higher among females versus males (6.7 vs. 5.5), and highest among children aged 0-4 years (8.1) and adults aged ≥65 years (13.7). Patients with ITP averaged 0.33 (95% CI: 0.32-0.35) hospitalizations and 15.3 (15.1-15.6) ambulatory encounters during the follow-up period; mean total healthcare expenditures during this period were $21,290 (20,502-22,031). Hospitalizations were more common during the first 3 months following diagnosis, and were twice as frequent among children versus adults; expenditures for ambulatory encounters were substantially higher for adults versus children aged 0-4 years.Conclusions: Our findings suggest that nearly 20,000 children and adults are newly diagnosed with ITP each year in the US, substantially higher than previously reported. Among patients requiring formal medical care, the economic burden during the first 12 months following diagnosis is high, with estimated US expenditures totaling over $400 million.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31857212

RESUMO

Hypokalemia is prevalent in patients resuscitated from out-of-hospital cardiac arrest and can contribute to polymorphic ventricular tachycardia (PMVT) by prolonging the QT interval. We present an interesting scenario of malignant ventricular arrythmia initially attributed to moderate hypokalemia that persisted after correction of potassium. Subsequent electrophysiological study showed two frequent PMVT-triggering PVCs mapped to the base of the antero-lateral papillary muscle and the para-Hisian region of the right side of the interventricular septum. The patient underwent catheter ablation to prevent further recurrences and dual chamber ICD implantation for secondary prevention.

11.
J Acquir Immune Defic Syndr ; 82 Suppl 3: S230-S243, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31764259

RESUMO

BACKGROUND: Evidence-based HIV interventions often fail to reach anticipated impact due to insufficient utilization in real-world health systems. Human-centered design (HCD) represents a novel approach in tailoring innovations to fit end-users, narrowing the gap between efficacious interventions and impact at scale. METHODS: We combined a narrative literature review of HCD in HIV programs with our experience using HCD to redesign an intervention promoting patient-centered care (PCC) practices among health care workers (HCW) in Zambia. We summarize the use and results of HCD in the global HIV response and share case study insights to advance conceptualization of HCD applications. RESULTS: The literature review identified 13 articles (representing 7 studies) on the use of HCD in HIV. All studies featured HCD hallmarks including empathy development, user-driven inquiry, ideation, and iterative refinement. HCD was applied to mHealth design, a management intervention and pre-exposure prophylaxis delivery. Our HCD application addressed a behavioral service delivery target: changing HCW patient-centered beliefs, attitudes, and practices. Through in-depth developer-user interaction, our HCD approach revealed specific HCW support for and resistance to PCC, suggesting intervention revisions to improve feasibility and acceptability and PCC considerations that could inform implementation in transferable settings. CONCLUSIONS: As both a research and implementation tool, HCD has potential to improve effective implementation of the HIV response, particularly for product development; new intervention introduction; and complex system interventions. Further research on HCD application strengths and limitations is needed. Those promoting PCC may improve implementation success by seeking out resonance and anticipating the challenges our HCD process identified.

12.
J Acquir Immune Defic Syndr ; 82 Suppl 2: S162-S169, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31658205

RESUMO

BACKGROUND: Despite marked gains in longevity attributable to antiretroviral therapy (ART), older women living with HIV (OWLH) experience substantial health challenges, and few studies addressed whether they can achieve successful aging (SA). This is among the first studies examining prevalence and psychosocial correlates of self-rated SA (SRSA) among OWLH and women at risk of HIV. METHODS: The sample included 386 OWLH and 137 HIV-seronegative women enrolled in the Women's Interagency HIV Study (WIHS) who were aged 50 years and older and participated in the "From Surviving to Thriving" (FROST) substudy. The FROST survey included measures of SRSA and positive psychosocial constructs. RESULTS: Participants were on average 57 years (SD = 5.3), 74% African American and 30% unemployed. Among OWLH, 94% were on ART and 73% were virally suppressed. Compared with OWLH, a higher proportion of HIV-seronegative women had an annual income ≤ $6000, no health insurance, and reported lower optimism and health-related quality of life. We found no differences in SRSA prevalence by HIV status: 84% of OWLH and 83% of HIV-seronegative women reported SRSA ≥7 (range = 2-10, higher scores signify better SRSA). Having SRSA ≥7 was associated with higher levels of positive psychosocial characteristics (eg, resilience and optimism) among both OWLH and HIV-seronegative women. CONCLUSIONS: SRSA is achievable among older women with and at risk of HIV despite health complications. Among disadvantaged women, factors other than HIV may be primary drivers of SRSA. Future research is needed to examine determinants of SRSA and to design public health interventions enhancing SA within this population.

13.
PLoS One ; 14(10): e0223573, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622394

RESUMO

Regular plasma HIV-RNA testing for persons living with HIV on antiretroviral therapy (ART) is now the global standard, but as many as 60% of persons in Africa today on ART do not have access to standard laboratory HIV-RNA assays. As a result, patients in Zambia often receive treatment without any means of determining true virologic failure, which poses a risk of premature switch of ART regimens and widespread HIV drug resistance. Dry blood spots (DBS) on the other hand require unskilled personnel and less complex storage supply chain so are ideal to capture viral-load results from HIV patients outside clinic settings. We assess collection of DBS in the community using non-medically trained personnel (NMP) and documented challenges. We trained 23 NMP to collect DBS from lost to follow-up (LTFU) patients in 4 rural and urban Zambian districts. We developed a phlebotomy box to transport DBS without contamination at ambient temperature and concomitant training and standard operating procedures. We evaluated this through field observations, bi-weekly meetings, reports, and staff meetings. The laboratory assessed DBS quality for testing validity. We attempted to collect DBS from 357 participants in the community. Though individual reasons for refusal from the remaining 37% were not collected, NMPs reported privacy concerns, awkward box-size which drew attention in the community and fears of undisclosed uses of samples related to witchcraft and circulating narratives about past research. Successful DBS collection was not associated with patient gender, age, time on ART, enrolment CD4, facility. DBS viral-load collection by NMP is feasible in Zambia. Our training approach and assessments of NMP not part of the health system can be extended to patients by giving them more responsibility to manage their own differentiated care groups. Concerted efforts that compare collection of DBS by NMP to those collected by skilled-medical personnel are needed.

14.
Behav Pharmacol ; 30(8): 642-652, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31625975

RESUMO

Neurodegenerative disorders have been considered as a growing health concern for decades. Increasing risk of neurodegenerative disorders creates a socioeconomic burden to both patients and care givers. Mitochondria are organelle that are involved in both neuroinflammation and neurodegeneration. There are few reports on the effect of mitochondrial metabolism on the progress of neurodegeneration and neuroinflammation. Therefore, the present review summarizes the potential contribution of mitochondrial metabolic pathways in the pathogenesis of neuroinflammation and neurodegeneration. Mitochondrial pyruvate metabolism plays a critical role in the pathogenesis of neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. However, there its potential contribution in other neurodegenerative disorders is as yet unproven. The mitochondrial pyruvate carrier and pyruvate dehydrogenase can modulate mitochondrial pyruvate metabolism to attenuate neuroinflammation and neurodegeneration. Further, it has been observed that the mitochondrial citric acid cycle can regulate the pathogenesis of neuroinflammation and neurodegeneration. Additional research should be undertaken to target tricarboxylic acid cycle enzymes to minimize the progress of neuroinflammation and neurodegeneration. It has also been observed that the mitochondrial urea cycle can potentially contribute to the progression of neurodegenerative disorders. Therefore, targeting this pathway may control the mitochondrial dysfunction-induced neuroinflammation and neurodegeneration. Furthermore, the mitochondrial malate-aspartate shuttle could be another target to control mitochondrial dysfunction-induced neuroinflammation and neurodegeneration in neurodegenerative disorders.

15.
Clin Infect Dis ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31504324

RESUMO

BACKGROUND: Integrase strand-transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is recommended for HIV management. Although studies have suggested associations between INSTIs and weight gain, women living with HIV (WLHIV) are underrepresented. We evaluated the effect of switching or adding INSTIs among WLHIV. METHODS: Women enrolled in the Women's Interagency HIV Study (WIHS) from 2006-2017 who switched to or added an INSTI to ART (SWAD) were compared to women on non-INSTI ART (STAY). Body weight, body mass index (BMI), percentage body fat (PBF), and waist, hip, arm, and thigh circumferences, were measured 6-12 months before and 6-18 months after INSTI switch/add in SWAD with comparable time points in STAY. Linear regression models compared change over time by SWAD/STAY group, adjusted for age, race, WIHS site, education, income, smoking status, and baseline ART regimen. RESULTS: 1118 women (234 SWAD and 884 STAY) were followed for a mean 2.0 ([+/- 0.1 standard deviation (SD)] years; mean age 48.8 [+/- 8.8] years, and 61% were Black. On average, compared to the STAY group, the SWAD group experienced mean greater increases of 2.1 kg in body weight, 0.8 kg/m² in BMI, 1.4% in PBF, and 2.0, 1.9, 0.6, and 1.0 cm in waist, hip, arm, and thigh circumference, respectively (all p <0.05). No differences in magnitude of these changes were observed by INSTI type. CONCLUSION: In WLHIV, a switch to INSTI was associated with significant increases in body weight, body circumferences, and fat percentages compared to non-INSTI ART. The metabolic and other health effects of these changes deserve further investigation.

16.
J Chem Neuroanat ; 102: 101684, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31553920

RESUMO

With the rapid advances in technology, extensive use of mobile phones has increased the risk of health problems. This study was performed to find out the effect of mobile phone frequency on male Wistar rats. Animals were divided into two groups (n = 6 in each group). Group one was considered as control and group two (experimental group) was exposed to microwave radiation (2100 MHz) for 4 hours/day (5 days/week) for 3 months. Exposure of microwave radiation frequency showed significant alterations in cholinesterase activity, muscular strength, learning ability and anxiety. MWR exposure was also associated with significant alteration in the oxidative defense system and hippocampus degeneration. Histopathological observations clearly depicted the neural degeneration. Thus, it can be concluded that MWR significantly affects the central nervous system and may lead to many severe illnesses. This study may reveal a platform to understand its toxic effect and can further be used for amendment in current guidelines of mobile radiation.

17.
Leuk Lymphoma ; 60(14): 3529-3535, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31282240

RESUMO

Even though HIV is associated with worse prognosis in many malignancies, the clinical course of myelodysplastic syndrome (MDS) in HIV + patients has not been well studied. Determining the clinical presentation and outcomes of MDS in these patients would be important for future diagnostic strategies, as anemia and other cytopenias are commonly seen in HIV + patients. Unique data mining software was used to identify cases of MDS or AML in adult patients who were also HIV + at Albert Einstein/Montefiore Medical Center between 1 January 2003 and 1 January 2017. Using Chi-Square and Fisher's exact test, characteristics of the HIV + MDS patients were compared to 135 HIV - MDS patients from the same institution diagnosed between 1997 and 2011. Fourteen biopsy proven MDS patients were identified with concomitant HIV. HIV + MDS patients presented at a younger age (59 vs. 71 yrs, p = .001) had higher risk disease, faster progression to acute leukemia, and worse overall survival (median survival 11.2 vs. 69.1 mo, p < .001) compared to HIV - MDS controls. Additionally, there was a higher prevalence of clonal-hematopoiesis related mutations (ASXL1, DNMT3A) and a higher proportion of patients with high risk cytogenetics. Analysis of the largest single center cohort of HIV + MDS patients demonstrated that these individuals present at a significantly younger age and with higher risk disease than their HIV - counterparts.

18.
AIDS ; 33(13): 2025-2033, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335806

RESUMO

OBJECTIVES: HIV and hepatitis C virus (HCV) have been associated with cardiovascular disease (CVD), but it is unclear whether HIV and HCV are also associated with peripheral artery disease (PAD). We examined the association of HIV, HCV, and traditional CVD risk factors with PAD in the Women's Interagency HIV Study, a multicenter US cohort. METHODS: In this cross-sectional study, ankle-brachial index was estimated using Doppler ultrasound and manual sphygmomanometer in 1899 participants aged more than 40 years with HIV/HCV coinfection, HCV or HIV monoinfection, or neither infection. Multivariable logistic regression was used to estimate the odds of PAD (ankle-brachial index ≤0.9) after controlling for demographic, behavioral, and CVD risk factors. RESULTS: Over two-thirds were African-American, median age was 50 years, and PAD prevalence was 7.7% with little difference by infection status. After multivariable adjustment, neither HIV nor HCV infection was associated with greater odds of PAD. Factors associated with PAD included older age [adjusted odds ratio (aOR): 2.01 for age 61-70 vs. 40-50 years; 95% confidence interval (CI): 1.04, 3.87], Black race (aOR: 2.30; 95% CI: 1.15, 4.63), smoking (aOR: 1.27 per 10-pack-year increment; 95% CI: 1.09, 1.48), and higher SBP (aOR: 1.14 per 10 mmHg; 95% CI: 1.01, 1.28). CONCLUSION: The high PAD prevalence in this nationally representative cohort of women with or at risk for HIV is on par with general population studies in individuals a decade older than our study's median age. HIV and HCV infection are not associated with greater PAD risk relative to uninfected women with similar risk factors. Modifiable traditional CVD risk factors may be important early intervention targets in women with and at risk for HIV.

19.
Br J Cancer ; 121(5): 417-420, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31353364

RESUMO

Talimogene laherparepvec (T-VEC) has demonstrated efficacy for unresectable melanoma. We explored response patterns from a phase 2 study evaluating patients with unresectable stage IIIB-IVM1c malignant melanoma who received T-VEC plus ipilimumab or ipilimumab alone. Patients with objective response per modified irRC were evaluated for pseudo-progression (single ≥25% increase in tumour burden before response). Patients without pseudo-progression were classified by whether they responded within or after 6 months of treatment start; those with pseudo-progression were classified by whether pseudo-progression was due to increase in existing lesions or development of new lesions. Overall, 39% (n = 38/98) in the combination arm and 18% (n = 18/100) in the ipilimumab arm had an objective response. Eight responders (combination, n = 7 [18.4%]; ipilimumab, n = 1 [5.6%]) had pseudo-progression; most occurred by week 12 and were caused by an increase in existing lesions. These data reinforce use of T-VEC through initial progression when combined with checkpoint inhibitors.Trial Registration NCT01740297 (ClinicalTrials.gov; date of registration, December 4, 2012); 2012-000307-32 (ClinicalTrialsRegister.eu; date of registration, May 13, 2014).

20.
Langmuir ; 35(34): 11132-11140, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31356088

RESUMO

We investigate dynamic director field variations in shells of the nematic liquid crystal (LC) compound, 4-cyano-4'-pentylbiphenyl, suspended in and containing immiscible aqueous phases. The outer and inner shell interfaces are stabilized by the cationic surfactant, cetyl trimethyl ammonium bromide (CTAB), and by the water soluble polymer, poly(vinyl alcohol) (PVA), respectively. PVA and surfactant solutions normally promote tangential and orthogonal alignments, respectively, of the LC director. The rather high Krafft temperature of CTAB, TK ≈ 25 °C, means that its solubility in water is below the critical micelle concentration at room temperature in most labs. Here, we study the effect of cooling/heating past TK on the LC shell director configuration. Within a certain concentration range, CTAB in the outer aqueous phase (and PVA in the inner) switches the LC director field from hybrid to uniformly orthogonal upon cooling below TK. We argue that the effect is related to the migration of the surfactant through the fluid LC membrane into the initially surfactant-free aqueous PVA solution, triggered by the drastically reduced water solubility of CTAB at T < TK. The results suggest that LC shells can detect solutes in the continuous phase, provided there is sufficient probability that the solute migrates through the LC into the inner aqueous phase.

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