Academic response to storm-related natural disasters—lessons learned

On 30 October 2017, selected faculty and administrators from Research Centers in Minority Institutions (RCMI) grantee institutions gathered to share first-hand accounts of the devastating impact of Hurricanes Harvey, Irma, and Maria, which had interrupted academic activities, including research, education, and training in Puerto Rico, Florida, and Texas. The presenters reviewed emergency response measures taken by their institutions to maintain community health care access and delivery, the storm-related impact on clinical and research infrastructure, and strategies to retain locally grown clinical expertise and translational science research talent in the aftermath of natural disasters. A longer-term perspective was provided through a comparative review of lessons learned by one New Orleans-based institution (now more than a decade post-storm) in the aftermath of Hurricane Katrina. Caring for the internal and external communities associated with each institution and addressing the health disparities exacerbated by storm-related events is one key strategy that will pay long-term dividends in the survival of the academic institutions and the communities they serve

Walnuts, Long-Chain Polyunsaturated Fatty Acids, and Adolescent Brain Development: Protocol for the Walnuts Smart Snack Dietary Intervention Trial

Background: Adolescence, when the most complex behaviors are refined to adult sophistication, represents a major window of opportunity and vulnerability for neuropsychological development. To support and protect this complex and active brain growth, different nutritional components considered essential need to be acquired from the diet. For instance, omega-3 fatty acids are mainly obtained from seafood, seeds, and walnuts. Known for their rich lipid profile, walnuts contain sizable amounts of an essential fatty acid, alpha-linolenic acid (ALA), the vegetable omega-3 fatty acid that is the precursor of two longer-chain omega-3 polyunsaturated fatty acids (omega-3 PUFA): docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids. While there is growing evidence of neuropsychological improvements in the young developing brain associated with omega-3 PUFA intake, few studies have examined whether consuming walnuts during adolescence entails similar beneficial effects. There is a need to further explore the ways in which walnuts influence youthful brain function, particularly for the long-term. Thus, we designed the WALNUTs study (WSS), a population-based randomized controlled trial conducted in adolescents in Barcelona, Spain. We hypothesize that walnut intake will increase omega-3 PUFA tissue availability (particularly ALA) to a level that enhances the neuropsychological development during adolescence. Methodology/Design: We conducted a 6-month population-based randomized controlled trial in teenagers (n = 800) and we aimed to determine the effectiveness of the intervention (four walnuts per day, or 30 kernel g, ~1.5g of ALA) in enhancing brain neuropsychological and socio-emotional development compared to a control group with no walnut intervention. Before randomization, different neuropsychological tests were recorded for all participants, and blood samples (in a subsample of participants) were collected to measure omega-3 PUFA levels at baseline, and all again, after randomization and the intervention. The data is now collected and we will conduct linear regression models to assess the effect of the intervention. Discussion: The WALNUTs (WSS) study results will allow us to better understand the role of plant-based omega-3 PUFA intake from regular walnut consumption on neuropsychological development during adolescence. Results could be translated into nutritional public health recommendations targeting teenagers. Trial Registration: ClinicalTrials.gov, U.S. National Library of Medicine, National Institutes of Health # NCT02590848. Retrospectively registered 29/10/2015

Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population

The human cervicovaginal microbiota resides at an interface between the host and the environment and may affect susceptibility to disease. Puerto Rican women have high human papillomavirus (HPV) infection and cervical cancer rates. We hypothesized that the population structure of the cervicovaginal bacterial and fungal biota changed with cervical squamous intraepithelial lesions and HPV infections. DNA was extracted from cervix, introitus, and anal sites of 62 patients attending high-risk San Juan clinics. The 16S rRNA V4 region and ITS-2 fungal regions were amplified and sequenced using Illumina technology. HPV genotyping was determined by reverse hybridization with the HPV SPF10-LiPA25 kit. HPV prevalence was 84% of which ∼44% subjects were infected with high-risk HPV, ∼35% were co-infected with as many as 9 HPV types and ∼5% were infected with exclusively low-risk HPV types. HPV diversity did not change with cervical dysplasia. Cervical bacteria were more diverse in patients with CIN3 pre-cancerous lesions. We found enrichment of Atopobium vaginae and Gardnerella vaginalis in patients with CIN3 lesions. We found no significant bacterial biomarkers associated with HPV infections. Fungal diversity was significantly higher in cervical samples with high-risk HPV and introitus samples of patients with Atypical Squamous Cells of Undetermined Significance (ASCUS). Fungal biomarker signatures for vagina and cervix include Sporidiobolaceae and Sacharomyces for ASCUS, and Malassezia for high-risk HPV infections. Our combined data suggests that specific cervicovaginal bacterial and fungal populations are related to the host epithelial microenvironment, and could play roles in cervical dysplasia

Cervicovaginal Microbiome and Urine Metabolome Paired Analysis Reveals Niche Partitioning of the Microbiota in Patients with Human Papilloma Virus Infections

In this study, we evaluate the association between vaginal and cervical human papillomavirus infections high-risk types (HPV+H), negative controls (HPV−), the bacterial biota, and urinary metabolites via integration of metagenomics, metabolomics, and bioinformatics analysis. We recently proposed that testing urine as a biofluid could be a non-invasive method for the detection of cervical HPV+H infections by evaluating the association between cervical HPV types and a total of 24 urinary metabolites identified in the samples. As a follow-up study, we expanded the analysis by pairing the urine metabolome data with vaginal and cervical microbiota in selected samples from 19 Puerto Rican women diagnosed with HPV+H infections and HPV− controls, using a novel comprehensive framework, Model-based Integration of Metabolite Observations and Species Abundances 2 (MIMOSA2). This approach enabled us to estimate the functional activities of the cervicovaginal microbiome associated with HPV+H infections. Our results suggest that HPV+H infections could induce changes in physicochemical properties of the genital tract through which niche partitioning may occur. As a result, Lactobacillus sp. enrichment coincided with the depletion of L. iners and Shuttleworthia, which dominate under normal physiological conditions. Changes in the diversity of microbial species in HPV+H groups influence the capacity of new community members to produce or consume metabolites. In particular, the functionalities of four metabolic enzymes were predicted to be associated with the microbiota, including acylphosphatase, prolyl aminopeptidase, prolyl-tRNA synthetase, and threonyl-tRNA synthetase. Such metabolic changes may influence systemic health effects in women at risk of developing cervical cancer. Overall, even assuming the limitation of the power due to the small sample number, our study adds to current knowledge by suggesting how microbial taxonomic and metabolic shifts induced by HPV infections may influence the maintenance of microbial homeostasis and indicate that HPV+H infections may alter the ecological balance of the cervicovaginal microbiota, resulting in higher bacterial diversity

Discriminating high-risk cervical Human Papilloma Virus infections with urinary biomarkers via non-targeted GC-MS-based metabolomics.

Genital human papillomavirus (HPV) is the world's most commonly diagnosed sexually transmitted infection, and high-risk HPV types are strongly linked to cervical dysplasia and carcinoma. Puerto Ricans are among the US citizens with higher HPV prevalence and lower screening rates and access to treatment. This bleak statistic was as a motivation to detect biomarkers for early diagnosis of HPV in this population. We collected both urine and cervical swabs from 43 patients attending San Juan Clinics. Cervical swabs were used for genomic DNA extractions and HPV genotyping with the HPV SPF10-LiPA25 kit, and gas chromatography-mass spectrometry (GC-MS) was employed on the urine-derived products for metabolomics analyses. We aimed at discriminating between patients with different HPV categories: HPV negative (HPV-), HPV positive with simultaneous low and high-risk infections (HPV+B) and HPV positive exclusively high-risk (HPV+H). We found that the metabolome of HPV+B is closer to HPV- than to HPV+H supporting evidence that suggests HPV co-infections may be antagonistic due to viral interference leading to a lower propensity for cervical cancer development. In contrast, metabolites of patients with HPV+H were significantly different from those that were HPV-. We identified three urinary metabolites 5-Oxoprolinate, Erythronic acid and N-Acetylaspartic acid that discriminate HPV+H cases from negative controls. These metabolites are known to be involved in a variety of biochemical processes related to energy and metabolism and may likely be biomarkers for HPV high-risk cervical infection. However, further validation should follow using a larger patient cohort and diverse populations to confirm our finding

Cervical human papillomavirus infection in a sample of Hispanic women living in Puerto Rico: comparison with cervical cytology reports.

ObjectivePersistent infection with high-risk (HR) HPV is a necessary risk factor for the development of cervical cancer. Information on HPV infection is limited in Puerto Rico. This study determined the distribution of HPV types and the association of HR-HPV types with cervical pathology in a clinic-based sample of women in PR.MethodsData from 92 female participants aged 18 to 34 years and recruited from the University of Puerto Rico-Gynecology Clinic, were analyzed. Cervical cytology was performed. HPV testing was performed using L1 consensus primer PCR with MY09/ MY11 primers and typed by dot-blot hybridization. Logistic regression modeling was used to determine the crude and covariate adjusted association between HR-HPV and cervical pathology.ResultsTwenty percent (n = 18) of the patients had abnormal cytology, 45.7% (n = 42) were HPV positive, and 30.4% (n = 28) were HR HPV-positive. Women infected with HR-risk HPV types were 7.9 (95% CI = 2.5-25.5) times more likely to have abnormal cytology as compared to women without HR infection when adjusted by age and age at first sexual intercourse.ConclusionThe burden of HPV infection was high, and, as expected, HR HPVs were strongly associated with dysplasia. A population-based study is needed to estimate HPV prevalence and its association with related malignancies in our population. This will be of great value in determining disease burden and will increase awareness of the HPV vaccination in our population

Inflammatory cytokines and a diverse cervicovaginal microbiota associate with cervical dysplasia in a cohort of Hispanics living in Puerto Rico.

Cervical cancer (CC) is women's fourth most common cancer worldwide. A worrying increase in CC rates in Hispanics suggests that besides Human papillomavirus infections, there may be other cofactors included in the epithelial microenvironment that could play a role in promoting the disease. We hypothesized that the cervical microbiome and the epithelial microenvironment favoring inflammation is conducive to disease progression in a group of Hispanics attending gynecology clinics in Puerto Rico. Few studies have focused on the joint microbiota and cytokine profile response in Hispanics outside the US, especially regarding the development of precancerous lesions. We aimed to investigate the relationship between the cervicovaginal microbiome and inflammation in Hispanic women living in PR while considering cervical dysplasia and HPV genotype risk. Cervical samples collected from 91 participants coming to gynecology clinics in San Juan, underwent 16S rRNA genes (V4 region) profiling, and cytokines were measured using Luminex MAGPIX technology. Cytokines were grouped as inflammatory (IL-1β, TNFα, IFNγ, IL-6), anti-inflammatory (IL- 4, IL-10, TGFβ1), and traffic-associated (IL-8, MIP1a, MCP1, IP10). They were related to microbes via an inflammation scoring index based on the quartile and tercile distribution of the cytokine's concentration. We found significant differences in the diversity and composition of the microbiota according to HPV type according to carcinogenic risk, cervical disease, and cytokine abundance. Community State Types (CSTs) represents a profile of microbial communities observed within the vaginal microbiome ecological niche, and Lactobacillus-depleted CST IV had ~ 90% dominance in participants with high-grade squamous intraepithelial lesions and high-risk HPV. The increasing concentration of pro-inflammatory cytokines was associated with a decrease in L. crispatus. In contrast, dysbiosis-associated bacteria such as Gardnerella, Prevotella, Atopobium concomitantly increased with pro-inflammatory cytokines. Our study highlights that the cervical microbiota of Hispanics living in Puerto Rico is composed mostly of diverse CST profiles with decreased Lactobacillus and is associated with a higher pro-inflammatory environment. The joint host-microbe interaction analyses via cytokine and microbiota profiling have very good translational potential

Acceptability of cervical and anal HPV self-sampling in a sample of Hispanic women in Puerto Rico.

Self-sampling techniques have been shown to be reliable in determining human papillomavirus (HPV) infection, although the acceptability of this method of sampling has not been studied in Puerto Rico (PR). The objective of this study was to determine the acceptability of cervicovaginal and anal self-sampling for HPV DNA testing among women in PR. One hundred women aged 18-34 years old and undergoing routine Pap smears in an OBGYN clinic in PR were recruited. Interviewer-administered and computer-based questionnaires were used to collect information on relevant risk factors. To assess acceptability, four-item acceptability Likert scales were used that measured comfort, pain, privacy, and embarrassment. Overall acceptability indexes were calculated as the sum of the Likert scores. Clinician-collected and self-collected cervicovaginal and anal samples for HPV-DNA testing were obtained from the participating women. Although the acceptability of both sampling methods was high, it was higher for self- rather than clinician-sampling of the cervix (difference in mean score = -0.71, p<0.05); contrarily, it was higher for clinician-sampling of the anus (difference in mean score = 0.64). When analyzing individual items within the scale, less embarrassment was observed with respect to the self-collection of cervical and anal samples. Nevertheless, most women reported that they preferred having a clinician collect cervical and anal samples (67% and 61%, respectively); and most of these women (86% for cervical samples and 92% for anal samples) felt more confident that this sample would be properly taken. Despite this, in this population, the high level of acceptability with regard to self-collected samples and the previously documented concordance between self- and clinician-collected samples support the use of cervical and anal HPV DNA self-sampling techniques in future HPV-related population-based studies and screening programs in PR

Academic response to storm-related natural disasters—lessons learned

On 30 October 2017, selected faculty and administrators from Research Centers in Minority Institutions (RCMI) grantee institutions gathered to share first-hand accounts of the devastating impact of Hurricanes Harvey, Irma, and Maria, which had interrupted academic activities, including research, education, and training in Puerto Rico, Florida, and Texas. The presenters reviewed emergency response measures taken by their institutions to maintain community health care access and delivery, the storm-related impact on clinical and research infrastructure, and strategies to retain locally grown clinical expertise and translational science research talent in the aftermath of natural disasters. A longer-term perspective was provided through a comparative review of lessons learned by one New Orleans-based institution (now more than a decade post-storm) in the aftermath of Hurricane Katrina. Caring for the internal and external communities associated with each institution and addressing the health disparities exacerbated by storm-related events is one key strategy that will pay long-term dividends in the survival of the academic institutions and the communities they serve