Proteomic Analysis of a Noninvasive Human Model of Acute Inflammation and Its Resolution: The Twenty-one Day Gingivitis Model

The 21-day experimental gingivitis model, an established noninvasive model of inflammation in response to increasing bacterial accumulation in humans, is designed to enable the study of both the induction and resolution of inflammation. Here, we have analyzed gingival crevicular fluid, an oral fluid comprising a serum transudate and tissue exudates, by LC−MS/MS using Fourier transform ion cyclotron resonance mass spectrometry and iTRAQ isobaric mass tags, to establish meta-proteomic profiles of inflammation-induced changes in proteins in healthy young volunteers. Across the course of experimentally induced gingivitis, we identified 16 bacterial and 186 human proteins. Although abundances of the bacterial proteins identified did not vary temporally, Fusobacterium outer membrane proteins were detected. Fusobacterium species have previously been associated with periodontal health or disease. The human proteins identified spanned a wide range of compartments (both extracellular and intracellular) and functions, including serum proteins, proteins displaying antibacterial properties, and proteins with functions associated with cellular transcription, DNA binding, the cytoskeleton, cell adhesion, and cilia. PolySNAP3 clustering software was used in a multilayered analytical approach. Clusters of proteins that associated with changes to the clinical parameters included neuronal and synapse associated proteins

Investigation of CXCR4 Chemokine Receptor Involvement in the Uptake and Penetration of siRNA Nanoparticles in Pancreatic Cancer Cell Lines and 3D Tumor Spheroids

With the urgency of developing novel therapies for pancreatic cancer, the Oupický lab designed a polymer, PAMD-Toc, that incorporates AMD3100, an antagonist of the most widely expressed chemokine receptor in cancer cells, CXCR4. This study seeks to determine if the CXCR4 receptor is involved in the uptake and penetration of siRNA-carrying PAMD-Toc nanoparticles into pancreatic cancer cells and tumors. Findings suggest that the presence of CXCR4 increases the efficacy of PAMD-Toc nanoparticle uptake and tumor penetration, which makes PAMD-Toc nanoparticles a promising siRNA delivery vector for pancreatic cancer gene therapy.https://digitalcommons.unmc.edu/surp2022/1027/thumbnail.jp

Usability Challenges with Insulin Pump Devices in Diabetes Care: What Trainers Observe with First-time Pump Users

Insulin pumps are designed for the self-management of diabetes mellitus in patients and are known for their complexity of use. Pump manufacturers engage trainers to help patients use the devices correctly to control the symptoms of their disease. Usability research related to insulin pumps and other infusion pumps has centered on the relationship between user interface design and the effectiveness of task completion by a single evaluator perspective, namely first-time users. From a different perspective, there is a lack of insight into the experiences of insulin pump trainers during learning sessions with first-time users. The focus of the study is to present the lived experiences and shared impressions of the insulin pump trainers. Their narratives will be used to conduct an interpretive examination of the phenomena uncovered and to provide the essence of their lived experiences

Discriminative Speaker Representation via Contrastive Learning with Class-Aware Attention in Angular Space

The challenges in applying contrastive learning to speaker verification (SV) are that the softmax-based contrastive loss lacks discriminative power and that the hard negative pairs can easily influence learning. To overcome the first challenge, we propose a contrastive learning SV framework incorporating an additive angular margin into the supervised contrastive loss in which the margin improves the speaker representation's discrimination ability. For the second challenge, we introduce a class-aware attention mechanism through which hard negative samples contribute less significantly to the supervised contrastive loss. We also employed gradient-based multi-objective optimization to balance the classification and contrastive loss. Experimental results on CN-Celeb and Voxceleb1 show that this new learning objective can cause the encoder to find an embedding space that exhibits great speaker discrimination across languages.Comment: Accepted by ICASSP 2023, 5 pages, 2 figure

Genetic variants in ARID5B and CEBPE are childhood ALL susceptibility loci in Hispanics.

Recent genome-wide studies conducted in European Whites have identified novel susceptibility genes for childhood acute lymphoblastic leukemia (ALL). We sought to examine whether these loci are susceptibility genes among Hispanics, whose reported incidence of childhood ALL is the highest of all ethnic groups in California, and whether their effects differ between Hispanics and non-Hispanic Whites (NHWs). We genotyped 13 variants in these genes among 706 Hispanic (300 cases, 406 controls) and 594 NHW (225 cases, 369 controls) participants in a matched population-based case-control study in California. We found significant associations for the five studied ARID5B variants in both Hispanics (p values of 1.0 × 10(-9) to 0.004) and NHWs (p values of 2.2 × 10(-6) to 0.018). Risk estimates were in the same direction in both groups (ORs of 1.53-1.99 and 1.37-1.84, respectively) and strengthened when restricted to B-cell precursor high-hyperdiploid ALL (>50 chromosomes; ORs of 2.21-3.22 and 1.67-2.71, respectively). Similar results were observed for the single CEBPE variant. Hispanics and NHWs exhibited different susceptibility loci at CDKN2A. Although IKZF1 loci showed significant susceptibility effects among NHWs (p < 1 × 10(-5)), their effects among Hispanics were in the same direction but nonsignificant, despite similar minor allele frequencies. Future studies should examine whether the observed effects vary by environmental, immunological, or lifestyle factors

Pro-tobacco marketing and anti-tobacco campaigns aimed at vulnerable populations: A review of the literature.

INTRODUCTION:We reviewed research literature on pro-tobacco marketing and anti-tobacco campaigns targeting eight vulnerable populations to determine key findings and research gaps. Results can inform tobacco policy and control efforts and the design of public education campaigns for these groups. METHODS:Five journal databases in medicine, communication, and science, were used to identify 8875 peer-reviewed, original articles in English, published in the period 2004-2018. There were 144 articles that met inclusion criteria on pro-tobacco marketing or anti-tobacco campaigns aimed at eight US groups: women of reproductive age, racial/ethnic minority groups (African American, Hispanic/Latino, Asian/Pacific Islander and American Indian/Alaska Native), Lesbian/Gay/Bisexual/Transgender (LGBT) populations, groups with low socioeconomic status, rural/inner city residents, military/veterans, and people with mental health or medical co-morbidities. We summarized the number of articles for each population, type of tobacco, and pro-tobacco or anti-tobacco focus. Narrative summaries were organized by population and by pro-tobacco or anti-tobacco focus, with key strategies and gaps by group. RESULTS:There were more studies on pro-tobacco marketing rather than anti-tobacco campaigns, and on cigarettes rather than other tobacco products. Major gaps included studies on Asian Americans, American Indian/Alaska Natives, pregnant women, LGBT populations, and those with mental health or medical co-morbidities. Gaps related to tobacco products were found for hookah, snus, and pipe/roll-your-own tobacco in the pro-tobacco studies, and for all products except cigarettes in anti-tobacco studies. Common tobacco industry methods used were tailoring of product and package design and messages that were used to reach and appeal to different sociodemographic groups. Studies varied by research design making it difficult to compare results. CONCLUSIONS:We found major research gaps for specific groups and tobacco products. Public education campaigns need a stronger foundation in empirical studies focused on these populations. Research and practice would benefit from studies that permit comparisons across studies

Solubilização micelar do ibuprofeno: influência do grupo polar dos tensoativos no grau de solubilização

An important property of micelles with particular significance in pharmacy is their ability to increase the solubility of poorly soluble drugs in water, thus increasing their bioavailability. In this work, the solubilization of ibuprofen (IBU) was studied in micellar solutions of three surfactants possessing the same hydrocarbon tail but different hydrophilic head groups, namely sodium dodecyl sulphate (SDS), dodecyltrimethylammonium bromide (DTAB), and n-dodecyl octa(ethylene oxide) (C12EO8). The results showed that, irrespective of the surfactant type, the solubility of IBU increased linearly with increasing surfactant concentration, as a consequence of the association between the drug and the micelles. The 80 mM DTAB and the 80 mM C12EO8 micellar solutions resulted in a 16-fold increase in solubility of IBU when compared to the buffer solution, whereas the 80 mM SDS micellar solution resulted in a 5.5-fold increase in IBU solubility. The highest value of molar solubilization capacity (chi) was obtained with DTAB, chi = 0.97, followed by C12EO8 ,chi = 0.72, and finally SDS, chi = 0.23. However, due to the stronger tendency of the nonionic surfactant in forming micelles in solution, at the same surfactant concentration, we obtained the same solubility of IBU in both DTAB and C12EO8.Uma propriedade importante das micelas, do ponto de vista farmacêutico, refere-se ao potencial destas em solubilizar fármacos pouco solúveis em água, aumentando sua biodisponibilidade. No presente trabalho, estudou-se a solubilização de ibuprofeno (IBU) em soluções micelares constituídas de três tensoativos apresentando a mesma cauda apolar, porém diferentes grupos hidrofílicos. Os tensoativos estudados foram dodecil sulfato de sódio (SDS), brometo de dodeciltrimetilamônio (DTAB) e óxido de n-dodecil octaetileno (C12EO8). De acordo com os resultados obtidos, a solubilidade do IBU aumentou linearmente com o aumento da concentração de todos os tensoativos estudados, devido às interações entre as micelas e o fármaco. O fármaco IBU apresentou um aumento de 16 vezes em sua solubilidade na presença de DTAB 80 mM e de C12EO8 80 mM. Por outro lado, na presença de SDS 80 mM a solubilidade do IBU aumentou apenas 5,5 vezes. O maior valor para o parâmetro capacidade molar de solubilização (chi) foi observado com o tensoativo DTAB, chi = 0,97, seguido pelo C12EO8, chi = 0,72 e, finalmente, o SDS, chi = 0,23. Entretanto, devido à grande tendência do C12EO8 em formar micelas, o perfil de solubilidade do IBU foi semelhante em DTAB e C12EO8