Preformulation and stability in biological fluids of the retrocyclin RC-101, a potential anti-HIV topical microbicide

<p>Abstract</p> <p>Background</p> <p>RC-101, a cationic peptide retrocyclin analog, has <it>in vitro </it>activity against HIV-1. Peptide drugs are commonly prone to conformational changes, oxidation and hydrolysis when exposed to excipients in a formulation or biological fluids in the body, this can affect product efficacy. We aimed to investigate RC-101 stability under several conditions including the presence of human vaginal fluids (HVF), enabling the efficient design of a safe and effective microbicide product. Stability studies (temperature, pH, and oxidation) were performed by HPLC, Circular Dichroism, and Mass Spectrometry (LC-MS/MS). Additionally, the effect of HVF on formulated RC-101 was evaluated with fluids collected from healthy volunteers, or from subjects with bacterial vaginosis (BV). RC-101 was monitored by LC-MS/MS for up to 72 h.</p> <p>Results</p> <p>RC-101 was stable at pH 3, 4, and 7, at 25 and 37°C. High concentrations of hydrogen peroxide resulted in less than 10% RC-101 reduction over 24 h. RC-101 was detected 48 h after incubation with normal HVF; however, not following incubation with HVF from BV subjects.</p> <p>Conclusions</p> <p>Our results emphasize the importance of preformulation evaluations and highlight the impact of HVF on microbicide product stability and efficacy. RC-101 was stable in normal HVF for at least 48 h, indicating that it is a promising candidate for microbicide product development. However, RC-101 stability appears compromised in individuals with BV, requiring more advanced formulation strategies for stabilization in this environment.</p

The Iowa Homemaker vol.26, no.7

Five-Pound Party Planning, Ruth Hackett, page 2 Homemaking Under the Round Roof, Shirliann Fortmann, page 3 Home Economists Look to New Horizons, Katherine Goeppinger, page 4 Graduate Studies Solve Research Questions, Marjorie Clampitt, page 5 Headlines Challenge Home Economists, Eloise Davison, page 6 Both Sides of the Pacific, Margaret Waterland, page 7 Wardrobe Accompaniments Chase Winter Blues, Jean Bunge, page 8 Home Economics Journeys from Iowa State to China, Jean Ory, page 9 What’s New, Marjorie Clampitt, page 10 Shoe Care Means Longer Wear, Charlene Stettler, page 11 Counselling Homemakers is Fun, Sue Marie Schreiber, page 12 Glamour is Her Business, Mary Margaret Ryan, page 13 Notions for Campus and Home, Margaret Buswell, page 14 ’46 Graduate Combines College and Career, Beverly Seig, page 15 Keeping Up With Today, Joyce Edgar, page 1

Relation Representations in Analogical Reasoning and Recognition Memory

Many computational models of reasoning rely on explicit relation representations to account for human cognitive capacities such as analogical reasoning. Relational luring, a phenomenon observed in recognition memory, has been interpreted as evidence that explicit relation representations also impact episodic memory; however, this assumption has not been rigorously assessed by computational modeling. We implemented an established model of recognition memory, the Generalized Context Model (GCM), as a framework for simulating human performance on an old/new recognition task that elicits relational luring. Within this basic theoretical framework, we compared representations based on explicit relations, lexical semantics (i.e., individual word meanings), and a combination of the two. We compared the same alternative representations as predictors of accuracy in solving explicit verbal analogies. In accord with previous work, we found that explicit relation representations are necessary for modeling analogical reasoning. In contrast, preliminary simulations incorporating model parameters optimized to fit human data reproduce relational luring using any of the alternative representations, including one based on non-relational lexical semantics. Further work on model comparisons is needed to examine the contributions of lexical semantics and relations on the luring effect in recognition memory

Relational and lexical similarity in analogical reasoning and recognition memory: Behavioral evidence and computational evaluation.

We examined the role of different types of similarity in both analogical reasoning and recognition memory. On recognition tasks, people more often falsely report having seen a recombined word pair (e.g., flower: garden) if it instantiates the same semantic relation (e.g., is a part of) as a studied word pair (e.g., house: town). This phenomenon, termed relational luring, has been interpreted as evidence that explicit relation representations-known to play a central role in analogical reasoning-also impact episodic memory. We replicate and extend previous studies, showing that relation-based false alarms in recognition memory occur after participants encode word pairs either by making relatedness judgments about individual words presented sequentially, or by evaluating analogies between pairs of word pairs. To test alternative explanations of relational luring, we implemented an established model of recognition memory, the Generalized Context Model (GCM). Within this basic framework, we compared representations of word pairs based on similarities derived either from explicit relations or from lexical semantics (i.e., individual word meanings). In two experiments on recognition memory, best-fitting values of GCM parameters enabled both similarity models (even the model based solely on lexical semantics) to predict relational luring with comparable accuracy. However, the model based on explicit relations proved more robust to parameter variations than that based on lexical similarity. We found this same pattern of modeling results when applying GCM to an independent set of data reported by Popov, Hristova, and Anders (2017). In accord with previous work, we also found that explicit relation representations are necessary for modeling analogical reasoning. Our findings support the possibility that explicit relations, which are central to analogical reasoning, also play an important role in episodic memory

The Iowa Homemaker vol.26, no.7

Five-Pound Party Planning, Ruth Hackett, page 2 Homemaking Under the Round Roof, Shirliann Fortmann, page 3 Home Economists Look to New Horizons, Katherine Goeppinger, page 4 Graduate Studies Solve Research Questions, Marjorie Clampitt, page 5 Headlines Challenge Home Economists, Eloise Davison, page 6 Both Sides of the Pacific, Margaret Waterland, page 7 Wardrobe Accompaniments Chase Winter Blues, Jean Bunge, page 8 Home Economics Journeys from Iowa State to China, Jean Ory, page 9 What’s New, Marjorie Clampitt, page 10 Shoe Care Means Longer Wear, Charlene Stettler, page 11 Counselling Homemakers is Fun, Sue Marie Schreiber, page 12 Glamour is Her Business, Mary Margaret Ryan, page 13 Notions for Campus and Home, Margaret Buswell, page 14 ’46 Graduate Combines College and Career, Beverly Seig, page 15 Keeping Up With Today, Joyce Edgar, page 16</p

Contraceptive Use and Pregnancy Incidence Among Women Participating in an HIV Prevention Trial

BackgroundRecent HIV prevention trials required use of effective contraceptive methods to fulfill eligibility for enrollment. We compared pregnancy rates in a subset of participants enrolled in the Microbicide Trials Network protocol (MTN-003), a randomized trial of chemoprophylaxis to prevent HIV acquisition among women aged 18-45 years who initiated depot medroxyprogesterone acetate (DMPA) or combined oral contraceptives (COCs) at enrollment, relative to those already using DMPA or COCs.MethodsData were analyzed from MTN-003 participants from Uganda. Before enrollment, information on contraceptive type and initiation date was obtained. Urine pregnancy tests were performed at monthly follow-up visits. Cox proportional hazards models were used to compare pregnancy incidence among new users (initiated ≤60 days before enrollment) and established users (initiated &gt;60 days before enrollment).ResultsOf 322 women enrolled, 296 were COC or DMPA users, 82 (28%) were new users, and 214 (72%) were established users. Pregnancy incidence was higher among new contraceptive users compared to established users (20.70% vs. 10.55%; adjusted hazard ratio [HR] = 1.66; 95% confidence interval [95% CI] 0.93-2.96). Among DMPA users, pregnancy incidence was 10.20% in new users versus 3.48% in established users (HR = 2.56; 95% CI 0.86-7.65). Among new COC users, pregnancy incidence was 42.67% in new users versus 23.67% in established COC users (adjusted HR = 1.74; 95% CI 0.87-3.48).ConclusionsNew contraceptive users, regardless of method, at the Uganda MTN-003 site had an increased pregnancy risk compared to established users, which may be due to contraceptive initiation primarily for trial eligibility. New users may benefit from intensive contraceptive counseling and additional contraceptive options, including longer acting reversible contraceptives

Assessing pregnancy and neonatal outcomes in Malawi, South Africa, Uganda, and Zimbabwe: Results from a systematic chart review.

A systematic chart review was performed to estimate the frequency of pregnancy outcomes, pregnancy complications and neonatal outcomes at facilities in Blantyre, Malawi; Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza and Harare, Zimbabwe to provide comparisons with estimates from an ongoing clinical trial evaluating the safety of two biomedical HIV prevention interventions in pregnancy. A multi-site, cross-sectional chart review was conducted at Maternal Obstetric Units and hospitals where women participating in the ongoing clinical trial would be expected to deliver. All individuals delivering at the designated facilities or admitted for postpartum care within seven days of a delivery elsewhere (home, health clinic, etc.) were included in the review. Data were abstracted for pregnancy outcomes, pregnancy complications, maternal and neonatal death, and congenital anomalies. Data from 10,138 records were abstracted across all four sites (Blantyre n = 2,384; Johannesburg n = 1,888; Kampala n = 3,708; Chitungwiza and Harare n = 2,158), which included 10,426 pregnancy outcomes. The prevalence of preterm birth was 13% (range across sites: 10.4-20.7) and 4.1% of deliveries resulted in stillbirth (range: 3.1-5.5). The most commonly noted pregnancy complication was gestational hypertension, reported among 4.4% of pregnancies. Among pregnancies resulting in a live birth, 15.5% were low birthweight (range: 13.8-17.4) and 2.0% resulted in neonatal death (range:1.2-3.2). Suspected congenital anomalies were noted in 1.2% of pregnancies. This study provides systematically collected data on background rates of pregnancy outcomes, pregnancy complications and neonatal outcomes that can be used as a reference in support of ongoing HIV prevention studies. In addition, estimates from this study provide important background data for future studies of investigational products evaluated in pregnancy in these urban settings