Comparing patient-reported outcomes and lifestyle factors before and after the COVID-19 pandemic among Black and Hispanic breast cancer survivors in New Jersey.

PURPOSE: The impact of the COVID-19 pandemic restrictions in the US since March 2020 on cancer survivorship among Black and Hispanic breast cancer (BC) survivors remains largely unknown. We aimed to evaluate associations of the pandemic with participant characteristics, patient-reported outcomes (PROs), and lifestyle factors among Black and Hispanic BC survivors in the Women's Circle of Health Follow-Up Study and the New Jersey BC Survivors Study. METHODS: We included 447 Black (npre = 364 and npost = 83) and 182 Hispanic (npre = 102 and npost = 80) BC survivors who completed a home interview approximately 24 months post-diagnosis between 2017 and 2023. The onset of the pandemic was defined as March 2020. The association of the pandemic with binary outcomes was estimated using robust Poisson regression models. RESULTS: Hispanic and Black BC survivors recruited after the onset of the pandemic reported higher socioeconomic status and fewer comorbidities. Black women in the post-pandemic group reported a higher prevalence of clinically significant sleep disturbance (prevalence ratio (PR) 1.43, 95% CI 1.23, 1.68), lower sleep efficiency, and lower functional well-being, compared to the pre-pandemic group. Hispanic women were less likely to report low health-related quality of life (vs. high; PR 0.62, 95% CI 0.45, 0.85) after the onset of the pandemic. CONCLUSIONS: Ongoing research is crucial to untangle the impact of the pandemic on racial and ethnic minorities participating in cancer survivorship research, as well as PROs and lifestyle factors. IMPLICATIONS FOR CANCER SURVIVORS: This study highlights the importance of considering the impact of the pandemic in all aspects of research, including the interpretation of findings.

Breast and Colorectal Cancer Screening Utilization after Hurricane María and the COVID-19 Pandemic in Puerto Rico.

Puerto Rico (PR) has faced environmental and public health challenges that could have significantly affected cancer screening access. Using administrative claims data from PR's Medicaid population, this study assessed trends in colorectal and breast cancer screening from 2016 to 2021, the impact of disasters in screening, and the absolute deficit in screening due to the pandemic. The monthly rates of claims were analyzed using Poisson regression. Significant reductions in breast and colorectal cancer screening utilization were observed. The colorectal cancer screening rate in 2017 was 77% lower a month after Hurricanes Irma and María [RRadj: 0.23; 95% CI: 0.20, 0.25] compared to the same time period in 2016. Breast cancer screening dropped 50% in November 2017 compared to November 2016 [RRadj: 0.50; 95% CI: 0.47, 0.54]. Prospectively, a recovery in utilization has been observed only for breast cancer screening. The results revealed that cancer screening utilization substantially declined after environmental disasters and the pandemic. These findings have potentially severe long-term implications for cancer health disparities and mortality in PR.

Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers.

Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation. Dendrimers with 50% functionalization exhibited negligible internalization capacities at all incubation times. Molecular dynamics simulations revealed that the solvent accessibility of the cationic surface charges is a key factor affecting cell internalization, unlike the total charge, functionality or size of surface-modified PAMAM dendrimers. These findings provide valuable insights to assist the design of PAMAM-based systems for drug delivery applications.

Rational Discovery of Microtubule-Stabilizing Peptides.

Microtubule (MT) stabilization is an attractive pharmacological strategy to hamper the progress of neurodegenerative diseases. In this regard, seeking peptides with MT-stabilizing properties has awoken great interest. This work reports the rational discovery of two structurally related MT-stabilizing octapeptides using a combination of protein-peptide docking, conventional molecular dynamics, Gaussian accelerated molecular dynamics (GaMD), and tubulin polymerization assays. FASTA sequences for ∼1000 peptides were crafted from single and double mutants of davunetide (NAP) and docked against the Taxol (TX) site on an octameric MT model representing a portion of the MT wall. Docked peptides were rescored after MM minimization and binding free energy refinement through single-point MM/GBSA calculations. The 60 best-ranked peptides were subjected to 50 ns MD simulations on peptide-MT complexes at the terminal TX site in the octameric Tau-MT model resulting in 11 complexes with occupancies greater than 99% and peptide-protein binding free energies less than -40 kcal/mol. Selected peptides were then examined through 300 ns GaMD simulations in complexes containing two identical ligands at the terminal and intermediate TX sites in the Tau-MT model to account for the differential association of MT-binding peptides to different regions of the MT structure. Six candidates showed a favorable MT-binding potential based on the analysis of interaction frequencies and relative mobilities of the complex components, suggesting a pivotal role of Arg278, Gln281, and Arg369 residues for peptides recognition. Four candidates were predicted to preserve an adequate balance of longitudinal and lateral interactions between tubulin dimers in peptide-MT complexes such that MT-stabilizing effects could be expected. MT polymerization experiments confirmed that four peptides (HAPVSIHQ, NYPVSIHQ, NWPVSIWQ, HAPVSIIQ) exhibit MT-stabilizing activity in vitro with NWPVSIWQ (P43) and HAPVSIIQ (P52) being the most active. Tryptophan quenching assays verified that P43 and P52 bind to nonpolymeric tubulin, whereas viability experiments on HEK cells confirmed their safety to pursue future pharmacological studies. The results herein presented are valuable to making progress in the rational design of MT-stabilizing peptides.

Ability of final PET/CT to predict response to first-line treatment in real patients with classical Hodgkin lymphoma.

Up to 25% of patients with classical Hodgkin lymphoma (cHL) and a negative interim PET/CT will progress. Unfortunately, there are few published studies on the predictive value of PET/CT performed after finishing treatment. The objective of our study was to assess the role of the final PET/CT (fPET/CT) in predicting progression in a retrospective series of patients treated in the last 10 years with a homogeneous protocol (ABVD + / - radiotherapy). We reviewed a cohort of 227 patients with newly diagnosed cHL. fPET/CT was performed on 212 patients (93%). In patients with a positive fPET, progression-free survival at 60 months was 17% (94% if fPET was negative, p = 0.000). The positive and negative predictive values for the fPET were 76% and 94%, respectively (Fisher's exact test, p = 0.000). In the subgroup of patients with advanced-stage cHL, progression-free survival at 60 months was 91% with negative fPET and 0% with positive fPET (p = 0.000). However, fPET was negative in 19 of the 29 patients with a positive interim PET/CT (only 2 showed progression). In conclusion, fPET is a useful tool to predict treatment failure in patients with newly diagnosed cHL, especially advanced-stage disease.

Comparing Different Interventions' Effects on Latinas' Screening Mammography Attainment and Participant-Driven Information Diffusion.

Evaluation of multiple community-based approaches to improve Latinas' breast cancer (BC) screening utilization has resulted in inconsistent findings. Factors contributing to this variation include heterogeneity in approaches (e.g., types of conceptual frameworks) and study quality (e.g., lack of measurement of spillover effects). This pilot study sought to clarify which approach may be most effective by evaluating the relative efficacy of two conceptual approaches using an area-level design with 145 Latinas nonadherent to U.S. Preventive Services Taskforce (USPSTF) BC screening guidelines. Each study arm included identical intervention format and duration (e.g., three group-based sessions, logistic assistance (LA) via five monthly calls and referral to free/low-cost screening programs). However, study content differed. While educate+LA addressed participants' BC prevention and screening behavior, empower+LA addressed participants' and their social networks' BC screening. After adjusting for age, insurance status, and baseline mammography intention, when compared with educate+LA participants, empower+LA participants were more likely to report obtaining mammograms, engaging more individuals about BC, initiating BC conversations in public settings, and discussing mammography specifically. Our study has important implications regarding the utility of evaluating behavioral interventions overall in terms of behavioral and spillover network effects.

Polyamidoamine-based nanovector for the efficient delivery of methotrexate to U87 glioma cells.

The purpose of this study was to design a polyamidoamine (PAMAM)-based nanovector for the efficient delivery of methotrexate to U87 glioma cells. To this end, 0-100% acetylated PAMAM dendrimers of the fourth generation were synthesized and evaluated using drug encapsulation measurements, molecular dynamics simulations, neurotoxicity assays and neuronal internalization experiments. The best system was tested as a nanovector for methotrexate delivery to U87 glioma cells. The authors found that 25% acetylated PAMAM dendrimers of the fourth-generation combine low intrinsic toxicity, large drug complexation capacity and efficient internalization into hippocampal neurons. Nanovector complexation enhances the cytotoxic response of methotrexate against U87 glioma cells compared with free drug solutions. In conclusion, 25% acetylated PAMAM dendrimers of the fourth-generation increase drug uptake by glioma cells and thereby act as efficient nanovectors for methotrexate delivery.

Risk factors and outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. PATIENTS AND METHODS: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. RESULTS: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p < 0.0001); ECOG 3-4 (OR, 2.56, 95% CI 1.4-4.7, p = 0.003); neutropenia (< 0.5 × 109/L) (OR 2.8, 95% CI 1.3-6.1, p = 0.01); and a C-reactive protein (CRP) > 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). CONCLUSIONS: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19.

Cytotoxicity and in vivo plasma kinetic behavior of surface-functionalized PAMAM dendrimers.

Understanding the molecular features responsible for the plasma kinetics of surface-modified polyamido amine (PAMAM) dendrimers is critical to explore novel biomedical applications for these nanomaterials. In this report, polyethylene glycol (PEG) and folic acid (FA) were employed to obtain partially-substituted PAMAM dendrimers as model biocompatible nanomaterials with different size, charge and surface functionality. Cytotoxicity assays on HEK cells at 1-500 µM concentration confirmed that PEG and FA incorporation increased the cell viability of PAMAM-based nanomaterials. Measurements of plasma kinetics in vivo revealed that PEG-PAMAM has an extended circulation time in mice blood (71.7 min) over native PAMAM (53.3 min) and FA-PAMAM (41.8 min). Molecular dynamics simulations revealed a direct relationship between circulation time and dendrimer size, thus providing valuable evidence to increase understanding about the modulation of functional properties of PAMAM-based systems through surface modification, and to guide future efforts on the rational design of novel biomedical nanomaterials.

The "Empowering Latinas to Obtain Breast Cancer Screenings" study: Rationale and design.

BACKGROUND: Latinas suffer disproportionately from breast cancer (BC) in part due to lower guideline-concordant screening. Multiple intervention approaches have been developed to promote screening through direct patient education and empowerment approaches (i.e., training community members to share BC information). This study compares the relative effects of these approaches on: 1) women's BC screening; and, 2) women's dissemination of BC information within their social networks. DESIGN/METHODS: Our quasi-experimental trial is being implemented in community venues in two predominantly Latino neighborhoods in South and West Chicago. Eligible participants: 1) are female; 2) are 52-74 years old; 3) have not obtained a mammogram in the past 2 years; and, 4) have not previously participated in health-related volunteerism. Based on their geographic location, participants are assigned to one of two group-based interventions. Both interventions consist of three two-hour sessions, which includes BC early detection education. The education intervention sessions also covers BC prevention (diet, physical activity), whereas the empowerment intervention covers sharing information with family/friends, and health volunteerism. Navigation is provided for all women who wish to obtain mammograms. Primary outcomes include: 1) receipt of BC screening; and, 2) participants' dissemination of BC information. Secondary outcomes include positive changes in 1) participants' self-reported psychosocial facilitators; and, 2) social network members' BC behaviors. DISCUSSION: The design of our program allows for a preliminary comparison of the effectiveness of these two approaches. This work will inform larger comparativeness trials and offers a new approach to intervention evaluation via social network analysis.

Partially PEGylated PAMAM dendrimers as solubility enhancers of Silybin.

PEGylated PAMAM-G4 dendrimers with substitution percentages of 50% and intermediate size PEG chains (0.55 and 2.0 kDa) were synthesized and evaluated as solubility enhancers and potential supramolecular carriers for the poorly soluble drug Silybin (SIL). Aqueous solubility profiles revealed that the PEGylated system with 2.0 kDa chains induced a five-fold solubility increase for SIL and the largest drug-loading capacity within the systems under study with an average complex stoichiometry of 71:1 according to the Higuchi-Connors formulation for multiple binding sites. The supramolecular interaction between SIL and PEGylated PAMAM-G4 dendrimers was confirmed by 2D-NOESY experiments, which evidenced the simultaneous complexation of the drug in both PAMAM-G4 branches and outermost PEG chains. In vitro release studies showed that 2.0 kDa PEG chains induced a more extended release time compared with 0.5 kDa PEG chains. This result was attributed to the enhancement of PEG assistance to SIL complexation in systems with longer PEG chains, which are able to self-penetrate into dendrimer cavities and cooperate in the stabilization of SIL complexes, thus delaying the release of SIL from the supramolecular host. These results are valuable for the future design and development of novel PAMAM-based systems for SIL complexation and delivery.

Original title: HIV infection and unawareness among men who have sex with men in Puerto Rico: data from The National HIV behavioral surveillance system 2011-2014.

BACKGROUND: Unawareness of HIV infection is a public health challenge that needs to be addressed, particularly in the case of men who have sex with men (MSM), since recent data are reporting increasing rates of HIV in this population in Puerto Rico. OBJECTIVES: We examined differences in the prevalence of HIV infection and unawareness among MSM in 2011 and 2014 using data from the National HIV Behavioral Surveillance System, 2011 and 2014. METHODS: Bivariate analyses was used to compare demographical and behavioral characteristics in both cycles (2011 and 2014). Prevalence ratio (PR) was assessed with Poisson regression models to determine changes in HIV prevalence and unawareness across cycles, using the 2011 NHBS-MSM cycle as reference group. RESULTS: A stable rate in HIV prevalence was observed in 2011 and 2014. There was a higher prevalence in 2014 than in 2011 in multiple behavioral characteristics such as age at sexual initiation, the number of sexual partners in the 12 months prior to being interviewed, HIV testing in the year prior to being interview, and the disclosure of sexual orientation to a healthcare provider. A significant decrease in HIV unawareness was reported (76.67%, 2011; 46.51%, 2014). Age-adjusted regression models showed a marginal reduction of 55% in HIV unawareness for men who disclosed their sexual orientation to their healthcare providers. CONCLUSION: Behavioral surveillance systems in groups such as MSM in on the island will aid to monitor prospectively the effectiveness of HIV testing outreach and engagement, as well as capacity capacity-building strategies targeted towards health care providers, aimed to increase HIV testing and awareness among this group.

Prevention of Synaptic Alterations and Neurotoxic Effects of PAMAM Dendrimers by Surface Functionalization.

One of the most studied nanocarriers for drug delivery are polyamidoamine (PAMAM) dendrimers. However, the alterations produced by PAMAM dendrimers in neuronal function have not been thoroughly investigated, and important aspects such as effects on synaptic transmission remain unexplored. We focused on the neuronal activity disruption induced by dendrimers and the possibility to prevent these effects by surface chemical modifications. Therefore, we studied the effects of fourth generation PAMAM with unmodified positively charged surface (G4) in hippocampal neurons, and compared the results with dendrimers functionalized in 25% of their surface groups with folate (PFO25) and polyethylene glycol (PPEG25). G4 dendrimers significantly reduced cell viability at 1 µM, which was attenuated by both chemical modifications, PPEG25 being the less cytotoxic. Patch clamp recordings demonstrated that G4 induced a 7.5-fold increment in capacitive currents as a measure of membrane permeability. Moreover, treatment with this dendrimer increased intracellular Ca2+ by 8-fold with a complete disruption of transients pattern, having as consequence that G4 treatment increased the synaptic vesicle release and frequency of synaptic events by 2.4- and 3-fold, respectively. PFO25 and PPEG25 treatments did not alter membrane permeability, total Ca2+ intake, synaptic vesicle release or synaptic activity frequency. These results demonstrate that cationic G4 dendrimers have neurotoxic effects and induce alterations in normal synaptic activity, which are generated by the augmentation of membrane permeability and a subsequent intracellular Ca2+ increase. Interestingly, these toxic effects and synaptic alterations are prevented by the modification of 25% of PAMAM surface with either folate or polyethylene glycol.

Mechanism of PAMAM Dendrimers Internalization in Hippocampal Neurons.

Polyamidoamine (PAMAM) dendrimers are hyperbranched macromolecules which have been described as one of the most promising drug nanocarrier systems. A key process to understand is their cellular internalization mechanism because of its direct influence on their intracellular distribution, association with organelles, entry kinetics, and cargo release. Despite that internalization mechanisms of dendrimers have been studied in different cell types, in the case of neurons they are not completely described. Considering the relevance of central nervous system (CNS) diseases and neuropharmacology, the aim of this report is to describe the molecular internalization mechanism of different PAMAM-based dendrimer systems in hippocampal neurons. Four dendrimers based on fourth generation PAMAM with different surface properties were studied: unmodified G4, with a positively charged surface; PP50, with a substitution of the 50% of amino surface groups with polyethylene glycol neutral groups; PAc, with a substitution of the 30% of amino surface groups with acrylate anionic groups; and PFO, decorated with folic acid groups in a 25% of total terminal groups. Confocal images show that both G4 and PFO are able to enter the neurons, but not PP50 and PAc. Colocalization study with specific endocytosis markers and specific endocytosis inhibitor assay demonstrate that clathrin-mediated endocytosis would be the main internalization mechanism for G4, whereas clathrin- and caveolae-mediated endocytosis would be implicated in PFO internalization. These results show the existence of different internalization mechanisms for PAMAM dendrimers in neurons and the possibility to control their internalization properties with specific chemical modifications.

PAMAM-grafted TiO2 nanotubes as novel versatile materials for drug delivery applications.

PAMAM-grafted TiO2 nanotubes (PAMAM-TiO2NT) have been synthesized and evaluated as new drug nanocarriers, using curcumin (CUR), methotrexate (MTX), and silibinin (SIL) as model therapeutic compounds. TiO2NT were surface-modified using a silane coupling agent and subsequently conjugated with PAMAM dendrimer of the third generation. The characterization of PAMAM-TiO2NT nanomaterials was performed by FTIR, TEM, N2 adsorption-desorption isotherms, XRD, and TGA techniques, which accounted for a 2.6wt.% of PAMAM grafting in the prepared materials. The drug loading capacity, drug release properties, and cytotoxicity of PAMAM-TiO2NT showed a significant improvement compared to pristine TiO2NT, thus revealing the promising properties of these new materials for drug delivery purposes.

Demographic and High-Risk Behaviors associated with HPV and HPV Vaccine Awareness among Persons Aged 15-74 Years in Puerto Rico.

OBJECTIVE: Studies of human papillomavirus (HPV) awareness in Puerto Rico (PR) are limited and are of interest given low HPV vaccine uptake in this population. This cross-sectional study aimed to determine factors associated to HPV and HPV vaccine awareness among persons aged 15-74 years living in Puerto Rico. METHODS: We analysed data from a sub-sample of 1,476 men and women who participated in a 2008 population-based island-wide household survey and who completed an HPV module. Multivariate logistic regression models were used to examine factors associated with HPV and HPV vaccine awareness. RESULTS: Overall, 37.2% of participants had heard about HPV and 33.4% had heard of the vaccine. Multivariate logistic regression showed that women were more likely to have heard of HPV (OR adjusted: 4.54; 95% CI=3.45, 5.98) or of the HPV vaccine (OR adjusted: 6.15; 95% CI=4.50, 8.40) as compared to men. HPV awareness was also lower among older adults, persons with lower income and with lower educational attainment, those without children and smokers (p < 0.05). CONCLUSION: In 2008, two years after the introduction of the first HPV vaccine in PR and the US, public awareness about HPV infection and the HPV vaccine was lower in Hispanics in PR as compared to other populations. Identified high-risk populations should be targeted in preventive care strategies. Future efforts should increase HPV knowledge and vaccine use in this population in order to maximize the impact of vaccination programs.

[Eating disorders inventory scores among mothers of adolescents with and without eating disorders]. / Las madres de adolescentes y jóvenes chilenos con trastornos alimentarios.

BACKGROUND: Parents have a control role in the development and treatment of eating disorders among teenagers. AIM: To compare attitudes, beliefs and behaviors between mothers of patients with eating disorders and mothers of teenagers without these disorders. MATERIAL AND METHODS: Twenty one mother-sibling pairs of adolescents with eating disorders and 15 pairs of adolescents without this condition, but of similar age, were studied. The eating disorders inventory (EDI-2), a self administered questionnaire that includes 91 items, was applied. RESULTS: No differences in any of the subscales of EDI-2 were observed between mothers of teenagers with or without eating disorders. No differences in perfectionism, maturity fears, impulsivity and interpersonal distrust were observed between adolescents with and without eating disorders. The latter had a lesser drive for thinness and inefficacy. CONCLUSIONS: In this sample, no differences in behaviors, attitudes and beliefs about food, were observed between mothers of adolescents with and without eating disorders.

Las madres de adolescentes y jóvenes chilenos con trastornos alimentarios / Eating disorders inventory scores among mothers of adolescents with and without eating disorders

Background: Parents have a control role in the development and treatment of eating disorders among teenagers. Aim: To compare attitudes, beliefs and behaviors between mothers of patients with eating disorders and mothers of teenagers without these disorders. Material and methods: Twenty one mother-sibling pairs of adolescents with eating disorders and 15 pairs of adolescents without this condition, but of similar age, were studied. The eating disorders inventory (EDI-2), a self administered questionnaire that includes 91 items, was applied. Results: No differences in any of the subscales of EDI-2 were observed between mothers of teenagers with or without eating disorders. No differences in perfectionism, maturity fears, impulsivity and interpersonal distrust were observed between adolescents with and without eating disorders. The latter had a lesser drive for thinness and inefficacy. Conclusions: In this sample, no differences in behaviors, attitudes and beliefs about food, were observed between mothers of adolescents with and without eating disorders.