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The somatic chromosome number of Panax vietnamensis Ha et Grushv. was determined to be 2n = 24, based on the hypotonic shock method by potassium chloride solution. In this study, we investigated the effect of potassium chloride and colchicine solutions on chromosome dispersion of Panax vietnamensis at different concentrations. The treatment using 0.2% KCl solution in 45 minutes combined with 0.05% colchicine solution in 2 hours subsequently resulted in proper hypotonia. The result showed that chromosomes were evenly dispersed. The hypotonic shock method seemed to be effective in equally distributing chromosomes. The result can be applied in cell genetic studies and selective breeding programs for Panax vietnamensis.

Tru Long pummelo is an endemic plant of Quang Nam province with high economic value. However, many different diseases, especially brown spot disease caused by Alternaria fungus on pummelos, have affected the quality of pummelos. Pesticides are overused and misused for the environment and human health. Therefore, there is an urgent need to reduce the use of synthetic chemicals. Biological control offers an alternative to the use of pesticides. Eight yeast strains have been isolated from healthy leaves, pummelo fruits, and healthy mulberries. They were screened for biological activity against Alternaria sp. by the dual culture method. The inhibitory potency ranged from 10.46% to 59.86%. The strain with the highest percentage (59.86%) was identified as Candida tropicalis using sequence analysis of the ITS region.

Despite widespread use of antiretroviral therapy (ART), people with HIV (PWH) continue to suffer substantial morbidity and mortality from pulmonary diseases. We sought to evaluate the prevalence of pulmonary symptoms, evaluations, and diagnoses (both infectious and noninfectious) among PWH receiving care at one of the largest HIV clinics in the United States. All PWH seen at the Infectious Disease Program in Atlanta, Georgia, from July 2013 to June 2018 were included. Multivariable logistic regression was used to assess the odds of all-cause mortality. Among 8387 patients, median age was 48 years, 35% had documented smoking, 74% were male, and the 47% with ≥1 pulmonary symptom or diagnosis were older and had higher rates of smoking compared to those without any symptoms or diagnoses (p-values

Ag/SiO2 colloidal nanocomposites (NCs) were prepared through the semi-continuous chemical reduction of silver ions on a silica surface; NaBH4 was used as a primary reducing agent, while carboxymethyl cellulose (CMC) served as a secondary reductant and a stabilizer at low temperature. Silver nanoparticles (AgNPs) of an average diameter of 3.89±0.18 nm were uniformly and densely dispersed on the SiO2 surface, forming 218.6-nm-sized Ag/SiO2 NCs. The zeta potential of the Ag/SiO2 NCs (−92.6 mV) was more negative than that of silica (−24 mV), indicating their high long-term stability. Furthermore, their proposed formation mechanism was confirmed via Fourier transform infrared spectroscopy. Then, the bactericidal effect of the Ag/SiO2 was evaluated based on their minimal inhibitory concentration (MIC) against Ralstonia solanacearum 15 (R. solanacearum 15); it was 62.5 ppm, much lower than that of conventional AgNPs (500 ppm). Therefore, these highly stable Ag/SiO2 colloidal NCs with more effective antibacterial activity than conventional AgNPs are a promising nanopesticide in agriculture.

An angled twin-layer porous substrate photobioreactor (TL-PSBR) using LED light was designed to cultivate Nannochloropsis oculata. Flocculation and sedimentation by modification of pH to 11 were determined as the optimal method for harvesting the N. oculata inoculum. The following optimised parameters were found: tilt angle 15°, Kraft 220 g m

OBJECTIVE The aim of the study was to elucidate the risk factors underlying abnormal cytology-based cervical cancer screening (Pap testing) in justice-involved women (JIW) compared with non-JIW in an urban safety net hospital. METHODS Retrospective chart review of women with a history of correctional involvement who received care at Grady Health System between 2010 and 2018 and had a Pap test was performed (n = 191). An age-matched cohort of women with no correctional involvement and had a Pap test at Grady served as the control (n = 394). Variables of interest were age, HIV, smoking, race, mental health history, and history of incarceration. Outcomes of interests were rate of abnormal Pap tests and follow-up. χ2 and logistic regression models evaluated associations between the variables of interest and outcomes. RESULTS Rates of abnormal Pap tests were significantly higher in JIW (35.6%) than controls (18.5%, p < .0001). Compared with controls, JIW were significantly more likely to have high-grade cervical cytology (odds ratio [OR] = 3.89, p < .0005) and be lost to gynecologic follow-up (OR = 8.75, p < .0001) and a history of severe mental illness (29.5% vs 4.3%, p < .0001). Those with abnormal Pap tests were likely to be HIV-positive (OR = 20.7, p < .001) and have a history of incarceration (OR = 2.33, p < .001). Predictors of high-grade Pap test were smoking history (OR = 0.16, p = .014), HIV-positive (OR = 3.66, p = .025), and history of incarceration (OR = 3.96, p < .0005). CONCLUSIONS Justice-involved women represent a high-risk subpopulation with significantly increased rates of high-grade cytology and lost to follow-up. This underscores the need for attention to screening programs and follow-up interventions for JIW.

BACKGROUND: Early palliative care addresses biopsychosocial needs for people living with HIV in an outpatient setting. We sought to describe patients referred to a palliative care program and compare the medical outcomes of emergency department (ED) visits, hospitalizations, primary care visits, and viral load suppression among patients enrolled in the program, to patients who did not enroll (no-show group). SETTING: We completed a retrospective cohort study at an urban, academically- affiliated HIV primary care clinic. METHODS: Data were collected from electronic medical records. Descriptive statistics characterized patient demographics at baseline, comorbidities, and reasons for referral to palliative care. Viral load suppression, rates of ED visits, hospitalizations, primary care visits, and retention in care were compared between the palliative and no-show groups. RESULTS: The most common reasons for referral were chronic pain management and medication/appointment adherence. Median percent of viral load measurements suppressed increased over time, but did not differ statistically between groups (Pre: 28.6% and 15.5%, post: 70.8% and 50.0%, palliative and no-show groups respectively). Median rates of ED visits and hospitalizations were low and were not impacted by palliative care. Rates of primary care visit attendance remained stable in the palliative group (4.6/year) but declined in the no-show group (3.5/year), p

Purpose The purpose of this study is to assess the factors that motivate young people’s intention to undergo cosmetic surgery in Vietnam. Design/methodology/approach This study applies Ajzen’s theory of planned behavior as a research model. The study is based on a quantitative method that applied exploratory factor analysis. Findings In total, 412 valid responses are used for the statistical analysis. The results confirm that subjective norm (SN), attitude toward cosmetic surgery and perceived behavioral control (PBC) are the main factors that motivate young people’s intention to undergo cosmetic surgery. Originality/value The results show the positive relationship between attitude toward cosmetic surgery, SN, PBC and intention to undergo cosmetic surgery in Vietnam.

In this study, samples from 429 dog individuals across three main regions of Vietnam (Southern Vietnam (SVN), Central Vietnam (CVN), and Northern Vietnam (NVN)) were collected to analyze the 582 bp region mtDNA HVI, so as to study the genetic diversity and to screen the rare haplotype E in the Vietnamese village dog population. Nine new haplotypes A, two new haplotypes B, and three haplotypes C were unique to Vietnam dogs, in which the new haplotypes An3, An7, Cn1, and Cn3 concerned mutations at new polymorphism sites (15,517, 15,505, 15,479, and 15,933, respectively) which have not been previously reported. The detection of haplotypes A9 and A29, and the appearance of haplotype A200 in the two individual dogs sampled support that the Southeast Asian dog is the ancestor of today’s Australian dingo and Polynesian dog. The two rare haplotypes E (E1 and E4) were reconfirmed in Vietnamese dogs and discussed. This study also contributes to strengthening the theory of domestication of dogs to the south of the Yangtze River and the Southeast Asian origin of the dingo.

Low health literacy and poor retention in care may contribute to HIV health disparities among African Americans, but causal pathways have not been examined. We utilized an adapted health literacy model to examine the role of health literacy on racial disparities in retention in care. Retention in care for 699 participants was assessed 24-months post survey and operationalized as 100% visit adherence versus less than 100% visit adherence. Most participants were African American (60%) and virally suppressed (93%). Results from a path analysis revealed that non-African American race was related to greater health literacy (p = .023) and to 100% visit adherence (p = .024). Greater health literacy was associated with 100% visit adherence (p = .008), which was in turn related to viral suppression (p

As national HIV prevention goals aim to increase the proportion of persons living with HIV, determining existing disparities in retention in care will allow for targeted intervention. The purpose of this systematic review was to identify existing disparities in retention in care. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) 2015 guided this systematic review. Electronic databases, including PubMed/MEDLINE, CINAHL, Sociological Collection, PsychInfo, and Cab Direct/Global Health, were systematically searched and twenty studies were included. This review identified disparities in retention in care that have been documented by race, gender, age, HIV exposure, incarceration history, place of birth, and U.S. geographic location. Research is necessary to further identify existing disparities in retention in care and to better understand determinants of health disparities. Additionally, interventions must be tailored to meet the needs of health disparate populations and should be assessed to determine their effectiveness in reducing health disparities.

Progressive multifocal leukoencephalopathy (PML) and PML immune reconstitution inflammatory syndrome (PML-IRIS) can be devastating neurological processes associated with HIV, but limited knowledge of their characteristics in the established antiretroviral therapy (ART) era is available. We conducted a case series to evaluate the clinical course of PML and PML-IRIS at our urban safety-net hospital in Atlanta, GA. All HIV-positive individuals with a positive John Cunningham virus DNA polymerase chain reaction in the spinal fluid between May 1, 2013 to June 1, 2017 were identified from the electronic health records (EHRs) using the HIV Disease Registry. Demographics, symptom presentation, laboratory data, imaging results, treatment, and outcomes were abstracted from the EHR. PML and PML-IRIS were defined using the American Association of Neurology criteria. Of the 32 individuals identified, 6 (19%) were felt to have asymptomatic positive results. Of the remainder, 15 (58%) HIV-positive patients had PML and 11 (42%) PML-IRIS (2 with an unmasking presentation and 9 with a paradoxical presentation). The most common presenting symptoms were motor weakness (18, 69%), cognitive deficits (15, 58%), and dysarthria (11, 42%). Corticosteroids were used in 12 patients and maraviroc in 3 patients. Outcomes were dismal with 7 (47%) patients with PML and 9 (82%) with PML-IRIS dying or being referred to hospice, with median survival times of 266 days in the PML group and 109 days in the PML-IRIS group. Despite widespread access to ART, patients with PML continue to have poor outcomes, particularly among those who develop PML-IRIS. More research is needed to understand the risks for and prevention of PML-IRIS.

BACKGROUND: The incidence of anal cancer in HIV positive women is a growing public health concern where they have a 7.8 fold increased risk for anal cancer than women in the general population. We examined knowledge of anal cancer, anal cancer screening and HPV in HIV positive women and high-risk HIV negative women. METHODS: Women were recruited from the Women’s Interagency HIV Study and completed an adapted Knowledge of Anal Cancer and HPV Scale. Correlations among anal cancer knowledge and sociodemographic and risk factors were assessed using Pearson’s or Spearman Rho r test. Student’s t test or Chi –square tests identified significant differences between groups by HIV-status or risk factors. RESULTS: Among 155 women, 72% (n=113) correctly identified the purpose of an anal Pap test. However, only 42% (n=65) identified HIV as a risk factor for anal cancer. HIV positive women were more knowledgeable about anal cancer than HIV negative women (t=2.104, p=.037). Women with a history of an abnormal cervical Pap test (t=2.137, p=.034), younger age (t= 3.716, p= .000), reported history of anal sex (t= 3.284, p= .001), some college education or higher (t= −2.005, p=.047), and non-smokers (t=2.425, p=.016) were significantly more knowledgeable about HPV. CONCLUSIONS: Although most women were knowledgeable about anal cancer, many women could not identify important risk factors for anal cancer, such as HIV infection. Patient educational interventions tailored to HIV positive women are warranted to improve knowledge and awareness of risk for anal cancer.

Production of indole-3-acetic acid (IAA) is well documented in various studies for the bacteria that inhabit the rhizosphere of plants, but with roots of wet rice, the outstandings have been not yet elucidated. This study began with the isolation of bacteria type strain Azospirillum sp. and developed the investigation to a screening of their ability in IAA production. This screening conducted a selection of only bacteria that was capable of the production of IAA with its content of over 25 µg. mL

The aim of the research “Some common difficulties in listening of English majored freshmen at Tay Do University" is to figure out some major factors causing difficulties for students in listening to English. The research is carried out within 12 weeks. Participants of this study are 100 English majored freshmen course 13, chosen randomly (including students in class 13A, 13B, and 13C) at Tay Do University. During the research time, participants are given questionnaires and paper interviews to show their ideas. The questionnaire and paper interview are two main instruments of this study, which are used to gather information about students' problems facing in listening. As a result, the research through the expected outcome will show some difficulties in listening of English majored freshmen at Tay Do University that related to linguistics like vocabulary, grammar, pronunciation, accents and intonation, and background knowledge and unfamiliar topics, psychological obstacle, and the length and speed rate of speech. Article visualizations

Supplemental Digital Content is available in the text, HIV-associated periodontal diseases (PD) could serve as a source of chronic inflammation. Here, we sought to characterize the oral microbial signatures of HIV+ and HIV– individuals at different levels of PD severity. This cross-sectional study included both HIV+ and HIV– patients with varying degrees of PD. Two tooth, 2 cheek, and 1 saliva samples were obtained for microbiome analysis. Mothur/SILVADB were used to classify sequences. R/Bioconductor (Vegan, PhyloSeq, and DESeq2) was employed to assess overall microbiome structure differences and differential abundance of bacterial genera between groups. Polychromatic flow cytometry was used to assess immune activation in CD4 and CD8 cell populations. Around 250 cheek, tooth, and saliva samples from 50 participants (40 HIV+ and 10 HIV–) were included. Severity of PD was classified clinically as None/Mild (N), Moderate (M), and Severe (S) with 18 (36%), 16 (32%), and 16 (32%) participants in each category, respectively. Globally, ordination analysis demonstrated clustering by anatomic site (R2 = 0.25, P

Among the many factors that increase students’ achievement in the mastery of foreign languages, including English, are motivation and use of language learning strategies. Previous studies by a range of researchers have identified these two elements as the most important in obtaining success in language learning. This study carried out on 152 university students, roughly equal in gender, studying at a university in Can Tho, Vietnam, sought to discover the relationships between these two factors within the Vietnamese language learning context. In particular, the study sought to 1) discover which of two types of motivation, intrinsic and extrinsic, is most prevalent among the students studied; 2) their use of language learning strategies; 3) reveals the relationship between students' motivation and use of language learning strategies; and 4) describe the differences in their use of language learning strategies based on whether their motivation was high, medium or low. Research instruments included Schmidt et al.'s Questionnaire on Motivation in Learning English, and Oxford's Strategy Inventory for Language Learning (both modified for the Vietnamese language learning context and translated into Vietnamese), plus an interview with 18 of the students to gain greater insight into the answers they gave on the questionnaires. Results were obtained using standard deviations and t-tests. They showed that Vietnamese university students are mainly extrinsically motivated; that all strategies were used at least at a medium level, amidst other fluctuations; and that those metacognitive strategies are most prevalent among medium and high motivated students but affective strategies are most common among low motivation students. Recommendations flowing from these results are that teachers should prioritize the formal teaching of learning strategies and should attempt to increase intrinsic motivation by putting greater emphasis on making language learning fun and relevant to the students' interests and passions. Article visualizations

While human immunodeficiency virus (HIV) infection has become a treatable disease with the development of combination antiretroviral therapy (cART), chronic inflammation that affects the central nervous system and other organs is still common. Reliable methods are needed to study HIV-associated inflammatory biomarkers. In this study involving both plasma and cerebrospinal fluid (CSF), we compared multiplex bead array (MBA) to a relatively new technology based on microfluidics and glass nanoreactor (GNR) technology for the measurement of three commonly studied markers from HIV-infected individuals. We found that results correlated between the two platforms for MCP-1 in both fluids as well as for plasma TNFα (all p

In the 21st century, the development of many modern entertainment facilities makes people rarely focus on reading books. So, the reading culture gradually fell into oblivion. In reality, when teachers ask students about their reading habit, students often say “we seldom read books”, they mostly read books because of teacher requests or school assignments. Therefore, the research “The reading culture of English majored students at Tay Do University” was conducted with the purpose of helping English linguistic students to acknowledge the importance of reading books. Thanks to this, they can find their own situations and spend more time reading books. The participants of this study were 100 English majored students of four classes including English Linguistic 10B, 11A, 12C and 13A at Tay Do University that were chosen randomly. The instrument used in this thesis was the questionnaire. The data from questionnaires were statistically analyzed by SPSS English version 20.0 package. Based on research results, the researcher found out some common students’ thoughts on reading culture as well as solutions to develop their reading culture in the future.

Lung cancer is one of the quickest and most fatal diseases and is divided into two types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). Approximately 50% of NSCLC patients harbour mutations in the epidermal growth factor receptor(EGFR) gene, spanning from exon 18 to exon 21, which are responsible for the tyrosine kinase domain of the EGFR protein. Currently, gefitinib and erlotinib are two drugs inhibiting EGFR which are used in the treatment of lung cancer. The indication for use of these drugs depends on the mutation status of EGFR. Resistance to treatment with these two drugs has been found with mutations in exon 20; however, mutations in exon 18, 19, 21 benefited from the same treatment. Therefore, we built a molecular protocol for detecting mutations in exon 21 of EGFR in NSCLC patients in Vietnam which, in this study, is based on the real-time polymerase chain reaction high resolution melting (PCR HRM) technique. We successfully designed pairs of primers for the real-time PCR HRM technique to detect mutations in exon 21 and for the Sanger sequencing method to confirm the real-time PCR HRM results. We also investigated the optimal concentration of MgCl2 for the real-time PCR HRM protocol. Performance characteristics of the real-time PCR HRM protocol were evaluated in terms of specificity, limit of detection, repeatability, and it showed good results. Finally, we applied the molecular protocol to 172 clinical samples and compared these with the Sanger nucleotide sequencing method and the peptide nucleic acid (PNA) clamping method. The results of the comparison demonstrate that the molecular protocol constructed for detection of exon 21 mutations can be used in the treatment of NSCLC patients.

BACKGROUND Human immunodeficiency virus–infected individuals (HIVIIs) have a higher incidence of head and neck squamous cell carcinoma (HNSCC), and clinical and histopathological differences have been observed in their tumors in comparison with those of HNSCC patients without a human immunodeficiency virus (HIV) infection. The reasons for these differences are not clear, and molecular differences between HIV-related HNSCC and non–HIV-related HNSCC may exist. This study compared the mutational patterns of HIV-related HNSCC and non–HIV-related HNSCC. METHODS The DNA of 20 samples of HIV-related HNSCCs and 32 samples of non–HIV-related HNSCCs was sequenced. DNA libraries covering exons of 18 genes frequently mutated in HNSCC (AJUBA, CASP8, CCND1, CDKN2A, EGFR, FAT1, FBXW7, HLA-A, HRAS, KEAP1, NFE2L2, NOTCH1, NOTCH2, NSD1, PIK3CA, TGFBR2, TP53, and TP63) were prepared and sequenced on an Ion Personal Genome Machine sequencer. DNA sequencing data were analyzed with Ion Reporter software. The human papillomavirus (HPV) status of the tumor samples was assessed with in situ hybridization, the MassARRAY HPV multiplex polymerase chain reaction assay, and p16 immunostaining. Mutation calls were compared among the studied groups. RESULTS HIV-related HNSCC revealed a distinct pattern of mutations in comparison with non–HIV-related HNSCC. TP53 mutation frequencies were significantly lower in HIV-related HNSCC. Mutations in HIV+ patients tended to be TpC>T nucleotide changes for all mutated genes but especially for TP53. CONCLUSIONS HNSCC in HIVIIs presents a distinct pattern of genetic mutations, particularly in the TP53 gene. HIV-related HNSCC may have a distinct biology, and an effect of the HIV virus on the pathogenesis of these tumors should not be ruled out. Cancer 2017. © 2017 American Cancer Society.

OBJECTIVES/GOALS: Cervical cancer is the fourth most common cancer among women worldwide, with approximately 570,000 newly diagnosed cases and 311,000 related deaths among women in 2018.In the United States, approximately 13,000 new cases of cervical cancer are diagnosed annually with approximately 4,000 women dying each year from cervical cancer. Nearly all cervical cancer is caused by oncogenic strains of the human papillomavirus (HPV). Prevention strategies to reduce cervical cancer after HPV exposure entail treatment of cervical dysplasia at the premalignant state, specifically low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL), along with the eventual clearance of HPV.The most common treatment for persistent LSIL or HSIL is the loop electrical excisional procedure (LEEP). This procedure is unfortunately not widely available in resource-limited countries and is associated with potential significant morbidities, including decreased fertility, preterm birth, premature rupture of membranes and cervical incompetence. Despite undergoing standard of care treatment, in certain high-risk populations, specifically HIV-infected women, there is a higher rate of premalignant HPV-related cervical disease persistence, progression and recurrence.There is a paramount need for novel nonsurgical treatments to stabilize or treat precancerous lesions of the cervix and to decrease the persistence of HPV infection. Medical treatment with the natural herb curcumin may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Curcumin is a major active component extracted from turmeric with anti-inflammatory, anti-infectious, and anti-cancer properties.Topical intravaginal curcumin has the promise of delivering this drug directly to the site of disease, ensuring adequate concentrations at the site of disease while avoiding systemic side effects. This proposed study will determine if there are higher rates of HPV clearance after curcumin administration among women with and without HIV who have premalignant HPV-related cervical disease, specifically LSIL or recently treated (with a LEEP) HSIL. METHODS/STUDY POPULATION: We are proposing a prospective double-blind randomized control trial to investigate the utility of topical intra-vaginal curcumin in increasing rates of HPV clearance and mitigating the high rates of disease recurrence in women with and without HIV. A sample of approximately 200 women with and without HIV who have biopsy-proven LSIL or recently treated HSIL will be randomized to one of two arms: 2000 mg of curcumin powder in capsules or placebo inserted intravaginally at bedtime once weekly for 20 weeks (excluding the time of menses). Cervical cytology and HPV testing will be performed at baseline and 6 months post-randomization. If a participant has abnormal cytology or a positive high-risk HPV test 6 months post-randomization, they will be scheduled to undergo a colposcopy with biopsies of all suspicious cervical lesions. If biopsy results are HSIL or greater, subjects will be referred back to routine clinical treatment, which may include a LEEP. Clinicians performing the colposcopies and the study participants will be blinded since the placebo has the same appearance as the curcumin capsules. At the end of the study, study participants will be offered the opportunity to participate in 2-3 hour focus groups to discuss acceptability of the product as a treatment for premalignant HPV-related cervical disease until data saturation is achieved. Power and sample size calculations are based on the primary outcome of interest, which is clearance of HPV at 6 months. Basu et al (2013) documented HPV clearance in as many as 80% of subjects with topical curcumin. To account for an expected lower success rate in HIV-infected women, who will also be included in the study, we intend to power our study to determine a more conservative 20% improvement in clearance rate at 6 months with curcumin treatment, assuming an expected clearance rate of HPV in HIV-infected women of 25%. In order to detect a 20% difference of HPV clearance among those treated with intravaginal curcumin vs. placebo at 6 months, about 80 patients per arm would achieve 80% power at the 5% significance level. To account for up to 20% loss to follow-up or discontinuation, the total sample size in each arm would be 100 subjects with a total of approximately 200 subjects enrolled in both arms. RESULTS/ANTICIPATED RESULTS: We are currently in the process of collecting data for this study. We hypothesize that intravaginal curcumin will have a 20% higher rate of HPV clearance at 6 months as compared to placebo. Primary outcome measures will include clearance of HPV at 6 months in curcumin vs. placebo. Secondary outcomes measures will include recurrence of disease by either cytologic or histologic abnormality requiring further surveillance or treatment at 6 months. We also hypothesize that intravaginal curcumin administered once weekly at bedtime for 20 weeks will be safe, acceptable, and well tolerated. This is based off of previous findings from the Phase 1 trial of intravaginal curcumin that we performed. During this Phase 1 trial, we explored daily intravaginal administration of 2000 mg of curcumin to further understand curcumin’s tolerability. Our focus group participants displayed an overwhelming consensus that daily administration affected quality of life, specifically due to the yellow-colored vaginal discharge from the medication. Study participants expressed that once or twice weekly administration was more tolerable and feasible. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. The primary outcome measure will be the proportion of study participants who discontinue treatment for any reason (acceptability) and the proportion of study participants who discontinue treatment due to adverse effects (tolerability). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-surgical treatments that decrease the morbidity and risk of progression of premalignant HPV-related cervical disease are greatly needed, especially in low-resource settings and among women experiencing barriers to care and/or at high risk for disease progression. Medical treatment with the natural herb curcumin is an emerging strategy that may allow subjects to receive treatment of cervical lesions without undergoing a surgical procedure.Several preclinical and clinical studies have shown curcumin’s ability to reduce tumors and precancerous lesions in animal and human cancer cells. Curcumin can suppress the activation of transcription factor NF-κB and the expression and activity of VEGF and p16INK4a, biomarkers known to be elevated in premalignant HPV-related cervical disease.Studies have also shown that curcumin alters HPV-associated molecular pathways in cancer cells, suppressing cervical cancer growth by inhibiting the transcription of oncoproteins HPV16 and HPV18 (designated as E6 and E7) and restoring p53 and retinoblastoma function. Our proposed study would therefore test the tolerability and effects of weekly curcumin administration and its ability to clear HPV infection. Our results will generate novel data as to what is an acceptable and well-tolerated dosing regimen of intravaginal curcumin, which would be crucial in designing further curcumin intervention studies. The results of our proposal will explore the effect of intravaginal curcumin as a standalone and adjuvant therapy to a LEEP among women with premalignant HPV-related cervical disease. The potential to not just excise diseased tissue, but to directly augment the clearance of the causative agent HPV, would have profound long-term ramifications in resource-limited settings and among women experiencing barriers to care and/or at high risk for disease progression.

In a high-volume clinic in the Southeastern United States, pregnant women living with human immunodeficiency virus (HIV) had improved HIV outcomes up to 6 months after delivery following the introduction of a multidisciplinary perinatal care coordination team., Women living with HIV are at high risk for loss to follow-up after delivery. In this study, viral suppression at delivery, timely attendance of an HIV care visit after delivery, and viral suppression 6 months postpartum all significantly increased among women living with HIV after utilization of a multidisciplinary perinatal care coordination team in a large HIV clinic in Atlanta, Georgia.

Introduction Human papillomavirus (HPV) and anal carcinoma are prevalent in high-risk patients including human immunodeficiency virus (HIV)-positive patients. There are currently no clear guidelines for screening, however. We assessed anal cytology specimens and HPV testing at an inner-city hospital by correlating anal cytology with anal biopsy (bx), and evaluated if results differed with traditional proctoscopy (TP) or high-resolution anoscopy (HRA). Materials and methods 209 anal cytology and subsequent biopsies taken during the period 2003-2014 from 152 male patients were reviewed. Demographic data for age, sex, HIV, HPV, cytology, histology, and the method of biopsy were analyzed. Results All specimens were followed by a biopsy within a period of 6 months. Ninety-seven percent of patients were HIV-positive and 43% had AIDS. Lesions most diagnosed on cytology were low-grade squamous intraepithelial lesion (LSIL) (52%) and atypical squamous cells of undetermined significance (ASC-US) (21.5%). Lesions most diagnosed on bx were anal intraepithelial neoplasia (AIN) grade 2-3 (52%) and AIN grade 1 (37%). Almost all ASC-US cases tested for HPV were positive (97%). There was cytology histology correlation in 48% of LSIL and 83% of high-grade squamous intraepithelial lesions. Anal cytology had 97% sensitivity in detecting AIN and carcinoma and a positive predictive value of 96%. There was no difference in rate of detection of AIN 1and AIN 2-3 on bx using TP versus HRA. Conclusion Screening in high-risk patients detected almost all high- and low-grade squamous intraepithelial lesions, however, anal cytology alone could not predict the degree of dysplasia. It may be prudent to perform anal bx in all atypical anal cytology. Clear guidelines are needed for screening of a high risk population.

ALKS 4230, an engineered cytokine designed for selective binding to the intermediate affinity interleukin-2 receptor (IL-2R), is being evaluated as a monotherapy and in combination with pembrolizumab in patients with advanced solid tumors. The selectivity of ALKS 4230 is achieved through stable fusion of circularly permuted IL-2 to IL-2Rα, with the goal of driving antitumor responses via selective activation of CD8+ T cells and NK cells, while avoiding activation of regulatory T cells (Tregs), which express the high affinity IL-2R. High levels of vascular endothelial growth factor (VEGF) are associated with an immunosuppressive tumor microenvironment and diminished response to high-dose IL-2. Lucitanib is an anti-angiogenic, multi-tyrosine kinase inhibitor targeting VEGFR1-3, PDGFRα/β, and FGFR1-3. We evaluated the antitumor efficacy and mechanism of the combination of RDB 1462, the mouse ortholog of ALKS 4230, and lucitanib in the MC38 mouse syngeneic tumor model. C57BL/6 mice were subcutaneously implanted with MC38 cells and treated with RDB 1462 (1.5 mg/kg and 3 mg/kg once every 3 days for 3 weeks), lucitanib (10 mg/kg daily for 28 days), or the combination of both molecules. After 11 days of treatment, lucitanib monotherapy resulted in 100% tumor growth inhibition (TGI), while 1.5 mg/kg and 3 mg/kg RDB 1462 monotherapy resulted in 25% and 51% TGI, respectively. Lucitanib monotherapy extended survival, with a mean survival time (MST) of 39 days compared to 15 days for vehicle, with no complete tumor regressions. MSTs were 18-22 days for RDB 1462 monotherapy groups, 60 days for the lower dose combination arm, and >60 days for the higher dose combination. Durable complete tumor regressions were observed in 1/20 mice treated with either dose of RDB 1462 monotherapy and 5/10 mice treated with the lower dose of RDB 1462 in combination with lucitanib. 10/10 mice treated with the higher dose of RDB 1462 in combination with lucitanib exhibited complete responses on Day 60. Flow cytometric analyses revealed that RDB 1462 treatment induced significant peripheral CD8+ T cell expansion compared to vehicle (p The combination of an intermediate affinity IL-2R-selective cytokine and an angiogenesis inhibitor resulted in durable dose-dependent antitumor efficacy in the MC38 mouse tumor model. Citation Format: Jared E. Lopes, Rachel L. Dusek, Liliane Robillard, Minh Nguyen, Bruce Roth, Bryan Vought, Arthur Liberzon, Raymond J. Winquist, Heather C. Losey. The combination of a mouse ortholog of ALKS 4230, a selective agonist of the intermediate affinity IL-2 receptor, and the angiogenesis inhibitor lucitanib enhances antitumor activity [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2202.

OBJECTIVE: The PARP inhibitors rucaparib, niraparib, olaparib, and veliparib have shown remarkable antitumor activity against various cancer types. We evaluated the brain penetration of PARP inhibitors in mice and the anti-tumor effects of selected PARP inhibitors in orthotopic and intracranial BRCA1-mutant triple-negative breast cancer (TNBC) MDA-MB-436 mouse models. PK/PD models were used to characterize the systemic/brain PK and tumor growth inhibition. METHODS: In non-tumor-bearing NOD-SCID female mice, plasma concentrations were determined at selected time points following an oral dose of 2, 5, 15, 50, or 150 mg rucaparib. The antitumor efficacy of rucaparib (2, 5, 15, 50, or 150 mg BID for 28 days) was evaluated in the MDA-MB-436 orthotopic model. In addition, a single dose of rucaparib (150 mg), niraparib (50 mg), olaparib (150 mg), or veliparib (150 mg) was given to male CD-1 mice; plasma, brain, and cerebrospinal fluid (CSF) concentrations of these compounds were determined at various time points. Intracranial efficacy was evaluated in luciferase-expressing MDA-MB-436 tumors following treatment of rucaparib (150 mg BID) or niraparib (50 mg QD) for 57 days. Tumor burden was evaluated using bioluminescence measurements. Semi-mechanistic PK and tumor growth inhibition models were developed to evaluate systemic, brain, and CSF concentration-time profiles for all 4 PARP inhibitors, and to evaluate tumor inhibition for rucaparib and niraparib using NONMEM software. RESULTS: All of the PARP inhibitors showed limited brain penetration in mice with an intact blood-brain barrier. However, rucaparib and niraparib demonstrated antitumor efficacy in a BRCA1-mutant, intracranial, TNBC mouse model. Brain and CSF concentrations were modeled as separate physiologically relevant compartments with PARP inhibitors being able to distribute to both brain and CSF compartments from the systemic compartment following oral administration. The model characterized plasma, brain, and CSF drug concentrations simultaneously. A modified Simeoni model with a 1st-order tumor growth rate adequately described the dose-dependent tumor inhibition at different doses of rucaparib in the orthotopic tumor model. The effects of brain tumor inhibition by rucaparib and niraparib were sufficiently described by a simpler model with a 1st-order tumor growth rate and a 2nd-order tumor inhibition rate that was proportional to brain drug concentrations. CONCLUSIONS: Systemic and brain concentrations, as well as orthotopic and intracranial tumor inhibition data, following oral administration in mice, were adequately described using semi-mechanistic models. Further studies are warranted to understand the intracranial distribution and antitumor activity of PARP inhibitors. Citation Format: Michelle Liao, Feng Jin, Minh Nguyen, Liliane Robillard, Andrew D. Simmons, Thomas C. Harding, Jim J. Xiao. Evaluation of brain pharmacokinetics (PK) and tumor growth inhibition of PARP inhibitors in mouse xenograft models using semi-mechanistic PK/pharmacodynamic (PD) modeling [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3026.

Background Anal cancer rates have increased, particularly in human immunodeficiency virus (HIV)–infected (HIV+) women. We assessed factors associated with anal precancer in HIV+ and at-risk HIV-negative women from the Atlanta Women’s Interagency HIV Study cohort. Methods All participants underwent high-resolution anoscopy and anal cytology and had anal and cervical samples collected. Specimens were tested for 37 human papillomavirus (HPV) types and for FAM19A4 and microRNA124-2 promoter methylation. Binary logistic regression and multivariate analysis were conducted with histologic anal high-grade squamous intraepithelial lesion (A-HSIL) as the dependent variable. Results Seventy-five women were enrolled: 52 (69%) were HIV+ with three-fourths having undetectable viral load; 64 (86%) were black; mean age was 49 ± 8 years. Forty-nine (65%) anal cytology samples were abnormal, and 38 (51%) of anal samples were positive for at least 1 of 13 high-risk HPV (hrHPV) types. Thirteen (18%) anal biopsies identified A-HSIL. Hypermethylation of FAM19A4 and/or microRNA124-2 was found in 69 (95%) anal samples and 19 (26%) cervical samples. In multivariate analyses, the odds of having A-HSIL were >6 times higher in women with anal hrHPV (adjusted odds ratio [aOR], 6.08 [95% confidence interval {CI}, 1.27–29.18], P = .02) and with positive cervical methylation (aOR, 6.49 [95% CI, 1.66–25.35], P = .007), but not significantly higher in women with positive anal methylation. Conclusions Anal hrHPV and promoter hypermethylation in the cervix show promise as biomarkers for anal cancer screening in HIV+ and at-risk HIV-negative women. Greater understanding of gene silencing by promoter hypermethylation in anal carcinogenesis is needed.

The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a retrospective chart review of HIV-infected men at the Grady Ponce de Leon Center HIV Clinic (Atlanta, GA) referred for high-resolution anoscopy (HRA), a procedure where anal tissue is examined under magnification and abnormal areas are biopsied. Between December 2013 and September 2015, 147 men underwent HRA: 72% were black, and 94% were men who have sex with men. CD4 count closest to time of HRA was a median 325 cells/mm(3) (interquartile range 203–473), and 69% had an undetectable HIV viral load. Ninety-four percent had abnormal anal cytology [80% atypical squamous cells of undetermined significance/low-grade squamous intraepithelial lesion (LSIL) and 20% atypical squamous cells, cannot exclude HSIL/HSIL], and 97% had abnormal histology (35% LSIL, 65% HSIL). Statistically significant variables associated with HSIL included number of biopsies [odds ratio (OR) 1.55, 95% confidence interval (CI) 1.13–2.14] and having ≥1 high-grade anal cytology in the last 12 months (OR 3.76, 95% CI 1.38–10.23). No significant association was found between HSIL and CD4, HIV viral load, or recent sexually transmitted infection. In this population, the burden of anal HSIL was extremely high, regardless of most recent anal cytology result. In newly diagnosed HIV-infected men with no history of anal cancer screening, performing HRA as primary anal cancer screening instead of cytology appears to be a viable option.

Background Rapid entry programs (REPs) improve time to antiretroviral therapy (ART) initiation (TAI) and time to viral suppression (TVS). We assessed the feasibility and effectiveness of a REP in a large HIV clinic in Atlanta, Georgia, serving a predominately un- or underinsured population. Methods The Rapid Entry and ART in Clinic for HIV (REACH) program was implemented on May 16, 2016. We performed a retrospective cohort study with the main independent variable being period of enrollment: January 1, 2016, through May 15, 2016 (pre-REACH); May 16, 2016, through July 31, 2016 (post-REACH). Included individuals were HIV-infected and new to the clinic with detectable HIV-1 RNA. Six-month follow-up data were collected for each participant. Survival analyses were conducted for TVS. Logistic and linear regression analyses were used to evaluate secondary outcomes: attendance at first clinic visit, viral suppression, TAI, and time to first attended provider visit. Results There were 117 pre-REACH and 90 post-REACH individuals. Median age (interquartile range [IQR]) was 35 (25–45) years, 80% were male, 91% black, 60% men who have sex with men, 57% uninsured, and 44% active substance users. TVS decreased from 77 (62–96) to 57 (41–70) days (P < .0022). Time to first attended provider visit decreased from 17 to 5 days, and TAI from 21 to 7 days (P < .0001), each remaining significant in adjusted models. Conclusions This is the largest rapid entry cohort described in the United States and suggests that rapid entry is feasible and could have a positive impact on HIV transmission at the population level.

Diabetes is one of the most frequently diagnosed comorbidities in individuals living with HIV. Dual control of both conditions is essential because both diseases negatively impact the immune and vascular systems. The purpose of this retrospective study was to assess the factors associated with dual control of HIV and diabetes. Patients from a large urban Ryan White-funded HIV clinic with a diagnosis of diabetes were identified; inclusion criteria comprised age over 25 years, use of antiretroviral therapy for at least 6 months, and a diagnosis of diabetes. Optimal control was described as a non-detectable viral load (i.e. log10 HIV1-viral load

Background We examined the prognostic value of a panel of biomarkers in patients with squamous cell carcinoma of the head and neck (SCCHN) who were human immunodeficiency virus (HIV) positive (HIV-positive head and neck cancer) and HIV negative (HIV-negative head and neck cancer). Methods Tissue microarrays (TMAs) were constructed using tumors from 41 disease site-matched and age-matched HIV-positive head and neck cancer cases and 44 HIV-negative head and neck cancer controls. Expression of tumor biomarkers was assessed by immunohistochemistry (IHC) and correlations examined with clinical variables. Results Expression levels of the studied oncogenic and inflammatory tumor biomarkers were not differentially regulated by HIV status. Among patients with HIV-positive head and neck cancer, laryngeal disease site (P = .003) and Clavien-Dindo classification IV (CD4) counts

The national incidence of epidemic Kaposi sarcoma (KS) has decreased dramatically since the availability of combined antiretroviral therapy. Despite national trends, we continue to see admissions for KS. Electronic medical records were queried to identify patients with HIV who were admitted with active KS between 2010 and 2013 and records were reviewed to determine patient characteristics and factors affecting survival. Data were collected from all hospital admissions until death or May 1, 2015. Kaplan-Meier survival analysis with log-rank tests were used to test for differences in survival and Cox proportional hazards models were used to assess the prognostic value of variables. Odds ratios were calculated to determine factors associated with death during hospital admissions. Forty-three patients were admitted 141 times, with 81 admissions specifically related to KS. The majority of patients were highly immunosuppressed when KS was diagnosed (median CD4 count: 11), and 68% had multiple organ involvement with KS. Comorbidities at diagnosis included hepatitis B (26%) and pneumocystis pneumonia (33%). Frequent reasons for admission included skin and soft tissue complaints (28.4%) and respiratory complaints (27.2%). The estimated median survival after KS diagnosis was 3.0 years. Lung involvement, liver involvement, poor performance status, and low CD4 T cell count (

Objective Assess whether a commitment contract informed by behavioral economics leads to persistent virologic suppression among HIV-positive patients with poor antiretroviral therapy (ART) adherence. Design Single-center pilot randomized clinical trial and a nonrandomized control group. Setting Publicly funded HIV clinic in Atlanta, Georgia, USA. Intervention The study involved three arms. First, participants in the provider visit incentive (PVI) arm received $30 after attending each scheduled provider visit. Second, participants in the incentive choice arm were given a choice between the above arrangement and a commitment contract that made the $30 payment conditional on both attending the provider visit and meeting an ART adherence threshold. Third, the passive control arm received routine care and no incentives. Participants A total of 110 HIV-infected adults with a recent plasma HIV-1 viral load more than 200 copies/ml despite ART. The sample sizes of the three groups were as follows: PVI, n = 21; incentive choice, n = 19; and passive control, n = 70. Main outcome measure Virologic suppression (plasma HIV-1 viral load ≤200 copies/ml) at the end of the incentive period and at an unanticipated postincentive study visit approximately 3 months later. Results The odds of suppression were higher in the incentive choice arm than in the passive control arm at the postincentive visit (adjusted odds ratio 3.93, 95% confidence interval 1.19-13.04, P = 0.025). The differences relative to the passive control arm at the end of the incentive period and relative to the PVI arm at both points in time were not statistically significant. Conclusion Commitment contracts can improve ART adherence and virologic suppression. Trial registration ClinicalTrials.gov identifier NCT01455740.

People living with HIV/AIDS (PLWHA) are at a higher risk of developing non-Hodgkin lymphoma (NHL). The influence of combined antiretrovirals (cART) on the presentation, treatment, and outcomes of HIV-associated NHL (HIV-NHL) warrants further investigation. We performed a retrospective analysis of PLWHA diagnosed with NHL who received care at the Infectious Diseases Ponce de Leon Center in Atlanta, Georgia, from January 1, 2004 to December 31, 2010. Thirty-five patients with HIV-NHL were identified. Among these patients, 7 had Burkitt lymphoma (BL), 20 had diffuse large B cell lymphoma (DLBCL), 7 had plasmablastic lymphoma (PL), and 1 had primary effusion lymphoma (PEL). The majority of patients (82.9%) presented with advanced disease, and 63% were not on ART at diagnosis. Despite having good performance status at presentation, the majority of patients presented with high International Prognostic Index (IPI) scores. There were differences between the histologic subtypes of NHL in regard to treatment, complications, and outcomes. The median CD4 lymphocyte count at diagnosis was 110 cells/mm(3) for patients with DLBCL [interquartile range (IQR): 66, 203], 165 cells/mm(3) for Burkitt lymphoma (IQR: 36, 199), and 98 cells/mm(3) for plasmablastic lymphoma (IQR: 34, 214). Overall, patients completed 67% of planned chemotherapy cycles. Common causes for chemotherapy termination were persistent myelosuppression (18.2%), social factors (22.7%), and disease progression (36.4%). Social factors included lack of transportation, substance abuse, unstable housing, and poor adherence. Two-year overall survival was 40% for all HIV-NHL. Half of the patients with DLBCL (n=10), 42% of patients with PL (n=3), and only 14.3% of patients with BL (n=1) were alive at 2 years. Among the overall survivors at 2 years, 85.7% had CD4200 cells/mm(3) and 78.6% had undetectable HIV viral loads (VL) at that time.

The microalga Haematococcus pluvialis is mainly cultivated in suspended systems for astaxanthin production. Immobilized cultivation on a Twin-Layer porous substrate photobioreactor (TL-PSBR) has recently shown promise as an alternative approach. In Vietnam, a TL-PSBR was constructed as a low-angle (15 &deg, ) horizontal system to study the cultivation of H. pluvialis for astaxanthin production. In this study, the biomass and astaxanthin productivities and astaxanthin content in the dry biomass were determined using different initial biomass (inoculum) densities (from 2.5 to 10 g dry weight m&minus, 2), different storage times of the initial biomass at 4 &deg, C (24, 72, 120 and 168 h) and different light intensities (300&ndash, 1000 &micro, mol photons m&minus, 2 s&minus, 1). The optimal initial biomass density at light intensities between 400&ndash, 600 &micro, mol photons&minus, 1 was 5&ndash, 7.5 g m&minus, 2. Algae stored for 24 h after harvest from suspension for immobilization on the TL-PSBR yielded the highest biomass and astaxanthin productivities, 8.7 g m&minus, 2 d&minus, 1 and 170 mg m&minus, 1, respectively, longer storage periods decreased productivity. Biomass and astaxanthin productivities were largely independent of light intensity between 300&ndash, 1 but the efficiency of light use per mole photons was highest between 300&ndash, 500 &micro, 1. The astaxanthin content in the dry biomass varied between 2&ndash, 3% (w/w). Efficient supply of CO2 to the culture medium remains a task for future improvements of angled TL-PSBRs.