Background. We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical ...intraepithelial neoplasia grade 3 (CIN3) and cancer. Methods. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. Results. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95–1.8-fold) and 1.7-fold (95% CI, 1.1–2.6-fold) increased risk for CIN3 or cancer, respectively (Ptrend=.008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (Ptrend=.009). Conclusions. Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.
WHO has recommended HPV testing for cervical screening where it is practical and affordable. If used, it is important to both clarify and implement the clinical management of positive results. We ...estimated the performance in Lusaka, Zambia of a novel screening/triage approach combining HPV typing with visual assessment assisted by a deep-learning approach called automated visual evaluation (AVE).
In this well-established cervical cancer screening program nested inside public sector primary care health facilities, experienced nurses examined women with high-quality digital cameras; the magnified illuminated images permit inspection of the surface morphology of the cervix and expert telemedicine quality assurance. Emphasizing sensitive criteria to avoid missing precancer/cancer, ~ 25% of women screen positive, reflecting partly the high HIV prevalence. Visual screen-positive women are treated in the same visit by trained nurses using either ablation (~ 60%) or LLETZ excision, or referred for LLETZ or more extensive surgery as needed. We added research elements (which did not influence clinical care) including collection of HPV specimens for testing and typing with BD Onclarity™ with a five channel output (HPV16, HPV18/45, HPV31/33/52/58, HPV35/39/51/56/59/66/68, human DNA control), and collection of triplicate cervical images with a Samsung Galaxy J8 smartphone camera™ that were analyzed using AVE, an AI-based algorithm pre-trained on a large NCI cervical image archive. The four HPV groups and three AVE classes were crossed to create a 12-level risk scale, ranking participants in order of predicted risk of precancer. We evaluated the risk scale and assessed how well it predicted the observed diagnosis of precancer/cancer.
HPV type, AVE classification, and the 12-level risk scale all were strongly associated with degree of histologic outcome. The AVE classification showed good reproducibility between replicates, and added finer predictive accuracy to each HPV type group. Women living with HIV had higher prevalence of precancer/cancer; the HPV-AVE risk categories strongly predicted diagnostic findings in these women as well.
These results support the theoretical efficacy of HPV-AVE-based risk estimation for cervical screening. If HPV testing can be made affordable, cost-effective and point of care, this risk-based approach could be one management option for HPV-positive women.
Background. Little is known about the epidemiology of oral human papillomavirus (HPV) in Latin America. Methods. Women (N = 5838) aged 22-29 in the control and vaccine arms of an HPV-16/18 vaccine ...trial in Costa Rica had oral, cervical, and anal specimens collected. Samples were tested for alpha mucosal HPV types (SPF₁₀/LiPA₂₅ version 1); a subset of oral samples (n = 500) was tested for cutaneous HPV types in the genera alpha, beta, gamma, mu, and nu. Results. In the control arm (n = 2926), 1.9% of women had an oral alpha mucosal HPV detected, 1.3% had carcinogenic HPV, and 0.4% had HPV-16; similar patterns for non-16/18 HPV types were observed in the vaccine arm. Independent risk factors for any oral alpha mucosal HPV among women in the control arm included marital status (adjusted odds ratio AOR, 3.2; 95% confidence interval CI, 1.8-5.7 for single compared to married/living as married), number of sexual partners (AOR, 2.4; 95% CI, 1.0-6.1 for ≥4 partners compared to 0-1 partners), chronic sinusitis (AOR, 3.1; 95% CI, 1.5-6.7), and cervical HPV infection (AOR, 2.6; 95% CI, 1.4-4.6). Detection of beta HPV was common (18.6%) and not associated with sexual activity. Conclusions. Unlike cutaneous HPV types, alpha mucosal HPV types were uncommon in the oral region and were predominately associated with sexual behavior. Clinical Trials Registration. NCT00128661.
This work presents a new on-line adaptive filter, which is based on a similarity analysis between standard electrode locations, in order to reduce artifacts and common interferences throughout ...electroencephalography (EEG) signals, but preserving the useful information. Standard deviation and Concordance Correlation Coefficient (CCC) between target electrodes and its correspondent neighbor electrodes are analyzed on sliding windows to select those neighbors that are highly correlated. Afterwards, a model based on CCC is applied to provide higher values of weight to those correlated electrodes with lower similarity to the target electrode. The approach was applied to brain computer-interfaces (BCIs) based on Canonical Correlation Analysis (CCA) to recognize 40 targets of steady-state visual evoked potential (SSVEP), providing an accuracy (ACC) of 86.44 ± 2.81%. In addition, also using this approach, features of low frequency were selected in the pre-processing stage of another BCI to recognize gait planning. In this case, the recognition was significantly ( p < 0.01 ) improved for most of the subjects ( A C C ≥ 74.79 % ) , when compared with other BCIs based on Common Spatial Pattern, Filter Bank-Common Spatial Pattern, and Riemannian Geometry.
The impact of human papillomavirus (HPV) vaccination on cervical screening, colposcopy, and treatment is incompletely understood. In 2004-2005, investigators in the Costa Rica Vaccine Trial ...randomized 7,466 women aged 18-25 years, 1:1, to receive HPV vaccination or hepatitis A vaccination. The worst-ever cytology diagnosis and the 4-year cumulative proportions of colposcopy referral and treatment by vaccination arm were compared for 2 cohorts. The total vaccinated cohort included 6,844 women who provided cervical samples. The naive cohort included 2,284 women with no evidence of previous HPV exposure. In the total vaccinated cohort, HPV-vaccinated women had a significant (P = 0.01) reduction in cytological abnormalities: 12.4% for high-grade lesions and 5.9% for minor lesions. Colposcopy referral was reduced by 7.9% (P = 0.03) and treatment by 11.3% (P = 0.24). Greater relative reductions in abnormal cytology (P < 0.001) were observed for HPV-vaccinated women in the naive cohort: 49.2% for high-grade lesions and 18.1% for minor lesions. Colposcopy referral and treatment were reduced by 21.3% (P = 0.01) and 45.6% (P = 0.08), respectively, in the naive cohort. The overall impact on health services will be modest in the first years after vaccine introduction among young adult women, even in regions with high coverage.
The HPV-automated visual evaluation (PAVE) Study is an extensive, multinational initiative designed to advance cervical cancer prevention in resource-constrained regions. Cervical cancer ...disproportionally affects regions with limited access to preventive measures. PAVE aims to assess a novel screening-triage-treatment strategy integrating self-sampled HPV testing, deep-learning-based automated visual evaluation (AVE), and targeted therapies.
Phase 1 efficacy involves screening up to 100,000 women aged 25-49 across nine countries, using self-collected vaginal samples for hierarchical HPV evaluation: HPV16, else HPV18/45, else HPV31/33/35/52/58, else HPV39/51/56/59/68 else negative. HPV-positive individuals undergo further evaluation, including pelvic exams, cervical imaging, and biopsies. AVE algorithms analyze images, assigning risk scores for precancer, validated against histologic high-grade precancer. Phase 1, however, does not integrate AVE results into patient management, contrasting them with local standard care.Phase 2 effectiveness focuses on deploying AVE software and HPV genotype data in real-time clinical decision-making, evaluating feasibility, acceptability, cost-effectiveness, and health communication of the PAVE strategy in practice.
Currently, sites have commenced fieldwork, and conclusive results are pending.
The study aspires to validate a screen-triage-treat protocol utilizing innovative biomarkers to deliver an accurate, feasible, and cost-effective strategy for cervical cancer prevention in resource-limited areas. Should the study validate PAVE, its broader implementation could be recommended, potentially expanding cervical cancer prevention worldwide.
The consortial sites are responsible for their own study costs. Research equipment and supplies, and the NCI-affiliated staff are funded by the National Cancer Institute Intramural Research Program including supplemental funding from the Cancer Cures Moonshot Initiative. No commercial support was obtained. Brian Befano was supported by NCI/ NIH under Grant T32CA09168.
Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence ...to cervical precancer and cancer.
We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P(trend)<0.0001), and RPS19 rs2305809 (P(trend)=0.0007), respectively. Both SNPs were also associated with progression.
These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.
Breast cancer incidence is increasing rapidly in Latin America, with a higher proportion of cases among young women than in developed countries. Studies have linked inflammation to breast cancer ...development, but data is limited in premenopausal women, especially in Latin America.
We investigated the associations between serum biomarkers of chronic inflammation (interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), leptin, adiponectin) and risk of premenopausal breast cancer among 453 cases and 453 matched, population-based controls from Chile, Colombia, Costa Rica, and Mexico. Odds ratios (OR) were estimated using conditional logistic regression models. Analyses were stratified by size and hormonal receptor status of the tumors.
IL-6 (OR
= 1.33 (1.11-1.60)) and TNF-α (OR
= 1.32 (1.11-1.58)) were positively associated with breast cancer risk in fully adjusted models. Evidence of heterogeneity by estrogen receptor (ER) status was observed for IL-8 (P-homogeneity = 0.05), with a positive association in ER-negative tumors only. IL-8 (P-homogeneity = 0.06) and TNF-α (P-homogeneity = 0.003) were positively associated with risk in the largest tumors, while for leptin (P-homogeneity = 0.003) a positive association was observed for the smallest tumors only.
The results of this study support the implication of chronic inflammation in breast cancer risk in young women in Latin America. Largest studies of prospective design are needed to confirm these findings in premenopausal women.
The COVID-19 pandemic has stricken mental health worldwide. Marginalized populations in low- and middle-income countries have been the most affected, as they were already experiencing barriers to ...accessing mental health care prior to the pandemic and are unequally exposed to the stressors associated with the health emergency, such as economic ravages or increased risk of complicated disease outcomes.
The aim of this paper is to describe a comprehensive initiative resulting from a public-civil partnership to address the increased burden of mental health illness associated with the COVID-19 pandemic in rural Chiapas, Mexico.
To address the emerging health needs of the general population and health professionals resulting from the pandemic, Compañeros En Salud (CES), a non-profit civil society organization based in Chiapas, implemented a comprehensive strategy to compensate for the shortage of mental health services in the region in collaboration with the Chiapas Ministry of Health. The strategy included three components: capacity building in mental health care delivery, psychosocial support to the general population, and provision of mental health care to CES collaborating staff. In this capacity building article, implementers from CES and the government share descriptive information on the specific interventions carried out and their beneficiaries, as well as a critical discussion of the strategy followed.
Through this strategy, we have been successful in filling the gaps in the public health system to ensure that CES-served populations and CES-collaborating health professionals have access to mental health care. However, further studies to quantify the impact of this intervention in alleviating the burden of mental health illnesses associated with the pandemic are needed.
The current situation represents an opportunity to reimagine global mental health. Only through the promotion of community-based initiatives and the development of integrated approaches will we ensure the well-being of marginalized populations.
Reducing the energy requirements of buildings is imperative in the face of global warming and the imminent need to build low or zero-carbon housing in the following decades. This research proposes ...the design of a structural foundation to reduce heat transfer between the ground and the house to improve thermal comfort, thus reducing the incidence of low interior temperatures and lower energy requirements. The proposed foundation consists of a waffle slab system incorporating on-site cellular concrete fabrication for a residential home. The foundation proposal was evaluated over a year through simulation to quantify the heating demand reduction for four cities with temperate semi-arid and temperate sub-humid climates. The analysis shows that the prevalence of low temperatures is reduced when applying any of the proposed foundations. However, the benefits must be weighed for cities like Durango and Puebla since the reduction of hours with low temperatures is minimal, and they show an increase in energy for cooling. The city with the most significant benefit in reducing the incidence of low temperatures and the heating demand is Toluca, followed by Zacatecas, which are cities showing prevalent heating demands. Based on the results, it is observed that it is viable to apply foundations with a lower overall heat transfer coefficient, with the addition of lightened materials produced on-site. However, it is still necessary to conduct more experimental studies on these prefabricated systems applied to foundation slabs and care for their implementation in mixed climates.
•Load-bearing thermal foundations lessen heat transfer in residential buildings.•Foundation with on-site fabricated lightweight concrete enhance material circularity.•Low indoor temperatures are reduced through improved cellular concrete foundations.•House's energy use is reduced when improving foundations with cellular concretes.•Insulation benefits must be weighted for homes built on non-dominant cold regions.
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