Beyond Cell Penetrating Peptides: Designed Molecular Transporters

Inspired originally by peptides that traverse biological barriers, research on molecular transporters has since identified the key structural requirements that govern cellular entry, leading to new, significantly more effective and more readily available agents. These new drug delivery systems enable or enhance cellular and tissue uptake, can be targeted and provide numerous additional advantages of significance in imaging, diagnostics and therapy

Impact of postmenopausal vaginal discomfort on sex and relationships in Brazil: the CLOSER survey.

The CLOSER (CLarifying Vaginal Atrophy's Impact On SEx and Relationships) survey investigated how postmenopausal vaginal atrophy (VA) affects relationships between Brazilian women and male partners.Postmenopausal women (age 55-65 years) with VA, and male partners of women with the condition, completed an online survey on the impact of VA and local estrogen treatment on intimacy and relationships.A total of 360 women and 352 men from Brazil were included. Women (83%) and men (91%) reported that they were comfortable discussing VA with their partners. Women's key source of information on VA was health-care providers (HCPs), but 44% felt that not enough information is available. VA caused 70% of women to avoid sexual intimacy and resulted in less satisfying sex. VA had a negative impact on women's feelings and self-esteem. Women (76%) and men (70%) both reported that treatment with vaginal estrogen improved their sexual relationship, primarily by alleviating women's pain during sex. Women (56%) and men (59%) felt closer to each other after treatment.VA had a negative impact on sexual relationships for both women and men in Brazil, and reduced women's self-confidence. Vaginal hormone therapy improved couples' sexual relationships. A proactive attitude of HCPs is essential to educate women on VA and the potential benefits of treatment

Probe molecule studies: Active species in alcohol synthesis

The goal of this research is to develop a better understanding of the mechanisms of formation of alcohols and other oxygenates from syngas over supported catalysts. Probe molecules are added in situ during the reaction to help delineate reaction pathways and identify reaction intermediate species. The key of our study is to investigate how the species generated by these probe molecules interact with surface species present during oxygenate formation. The catalysts chosen for tills investigation is Co/Cu/ZnO/Al[sub 2]O[sub 3]. Detailed motivations for studying this system as well as using CH[sub 3]NO[sub 2] as the probe molecule were given in a previous report. (A) Pretreatment of a Co(O%)/Cu/ZnO/Al[sub 2]O[sub 3] to be used as a base catalyst was carried out. (B) XRD experiments were carried out with the calcined and reduced samples of the O%-Co, 5%-Co and 10%-Co catalysts. (C) Temperature programmed reduction was performed with the O%-Co, 5%-Co and 10%-Co catalysts. (D) CO hydrogenation under the same conditions used for the 5%-Co and 10%-Co catalysts was conducted over the Co(O%)/Cu/ZnO/Al[sub 2]O[sub 3] catalyst. (E) CH[sub 3]NO[sub 2] addition to the steady state reaction of CO hydrogenation was conducted over both the O%-Co and the 10%-Co catalysts

Probe molecule studies: Active species in alcohol synthesis. Eighth quarterly report, July 1992--September 1992

Goal is to understand the mechanisms of formation of alcohols and other oxygenates from syngas over supported catalysts. Work during this period: BET surface areas and XRD patterns of Cu/ZnO/Al{sub 2}O{sub 3} and Co(5%)/Cu/ZnO/Al{sub 2}O{sub 3} suggest that Co did not change the structure. CO was hydrogenated over 10% Co catalyst. C{sub 2}H{sub 4} additions increased the isopropanol and decreased the methanol production. Blank runs with H{sub 2}/He/CH{sub 3}OH/C{sub 2}H{sub 4} showed that C{sub 2}H{sub 4} does not react with CH{sub 3}OH

Designed Guanidinium-Rich Amphipathic Oligocarbonate Molecular Transporters Complex, Deliver and Release siRNA in Cells

The polyanionic nature of oligonucleotides and their enzymatic degradation present challenges for the use of siRNA in research and therapy; among the most notable of these is clinically relevant delivery into cells. To address this problem, we designed and synthesized the first members of a new class of guanidinium-rich amphipathic oligocarbonates that noncovalently complex, deliver, and release siRNA in cells, resulting in robust knockdown of target protein synthesis in vitro as determined using a dual-reporter system. The organocatalytic oligomerization used to synthesize these co-oligomers is step-economical and broadly tunable, affording an exceptionally quick strategy to explore chemical space for optimal siRNA delivery in varied applications. The speed and versatility of this approach and the biodegradability of the designed agents make this an attractive strategy for biological tool development, imaging, diagnostics, and therapeutic applications

The Weak Relationship between Vitamin D Compounds and Glucose Homeostasis Measures in Pregnant Women with Obesity : An Exploratory Sub-Analysis of the DALI Study

Altres ajuts: Netherlands Organization for Health Research and Development (ZonMw, 200310013); Polish Ministry of Science (2203/7, PR/2011/2); Odense University Free Research Fund; NIHR Clinical Research Network: Eastern; In Spain (CAIBER 1527-B-226); Spanish Diabetes Society (SED) XI Grant for clinical research projects in diabetes.Studies on the relationship between vitamin D (VitD) and glucose homeostasis usually consider either total VitD or 25OHD3 but not 25OHD2 and epimers. We aimed to evaluate the cross-sectional association of VitD compounds with glucose homeostasis measurements in pregnant women with overweight/obesity participating in the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention study. Methods: The analysis included 912 women. Inclusion criteria: <20 weeks gestation, body mass index ≥29 kg/m and information on exposure and outcome variables at baseline. Measurements: A 75 g OGTT at <20, 24-28 and 35-37 weeks gestation (except if previous diabetes diagnosis). Exposure variables: 25OHD2, 25OHD3 and C3-epimer. Outcome variables: fasting and post-challenge insulin sensitivity and secretion indices, corresponding disposition indices (DI), plasma glucose at fasting and 1 and 2 h, hyperglycemia in pregnancy (HiP). Statistics: Multivariate regression analyses with adjustment. Results: Baseline VitD sufficiency was 66.3%. Overall, VitD compounds did not show strong associations with any glucose homeostasis measures. 25OHD3 showed direct significant associations with: FPG at <20 and 24-28 weeks (standardized β coefficient (β) 0.124, p = 0.030 and 0.111, p = 0.026 respectively), 2 h plasma glucose at 24-28 weeks (β 0.120, p = 0.018), and insulin sensitivity (1/HOMA-IR, β 0.127, p = 0.027) at 35-37 weeks; it showed an inverse association with fasting DI (QUCKI*HOMA-β) at <20 and 24-28 weeks (β −0.124, p = 0.045 and β −0.148, p = 0.004 respectively). 25OHD2 showed direct associations with post-challenge insulin sensitivity (Matsuda, β 0.149, p = 0.048) at 24-28 weeks) and post-challenge DI (Matsuda*Stumvoll phase 1) at 24-28 and 35-37 weeks (β 0.168, p = 0.030, β 0.239, p = 0.006). No significant association with C3-epimer was observed at any time period. Conclusions: In these women with average baseline VitD in sufficiency range, VitD compounds did not show clear beneficial associations with glucose homeostasis measures

Correction to: Reldesemtiv in Patients with Spinal Muscular Atrophy: a Phase 2 Hypothesis-Generating Study (Neurotherapeutics, (2021), 18, 2, (1127-1136), 10.1007/s13311-020-01004-3)

This article has been updated to add the author Richard S. Finkel. The original article has been corrected