Cervical Cancer in Mexico: From a Renowned Vaccination Program to Unfulfilled Needs in Treatment Access.

Mexico's national human papillomavirus (HPV) vaccination program was established in 2008, providing free access to HPV vaccines and quickly becoming an immense success story, achieving significant coverage among young Mexican females. However, despite these efforts and notable achievements, cervical cancer caused mainly by HPV remains a challenging issue among Mexican women aged 15 years or older. A critical obstacle faced by women in the country is a lack of early detection and screening resources, coupled with delays in diagnosis and treatment, exacerbated by the poor distribution of already insufficient healthcare resources. This situation creates adverse conditions for the female demographic in the country. Our editorial aims to draw attention to the urgent need to improve access to adequate prevention, screening, and treatment for cervical cancer patients in Mexico, advocating for a collective effort between the Mexican government, public health professionals, and civil society.

Enucleations, Eviscerations, and Exenterations at a Supratertiary-care Hospital in Puerto Rico: A Retrospective Study.

OBJECTIVE: To provide a descriptive analysis of the indications and the intraoperative and postoperative complications of eye enucleations and eviscerations, and orbital exenterations performed at the only academic institution in Puerto Rico providing supratertiary care. METHODS: A retrospective medical record review of patients who underwent enucleations, eviscerations, and exenterations from January 2015 through June 2020 was conducted. The data were analyzed to generate a descriptive profile of the demographic characteristics of the patients, their clinical indications and surgical complications, and a histopathological diagnosis per type of eye-removal procedure. RESULTS: A total of 118 eyes were removed via enucleation, evisceration, or exenteration over the 66-month study period. The average patient age was 64 (±17.5) years and 63.8% of the patients were male. The most frequently performed eye-removal procedure was enucleation (73.7%), followed by evisceration (18.6%) and exenteration (7.6%). The main clinical indications for enucleations and eviscerations were infectious processes, namely panophthalmitis, endophthalmitis, and/or perforated corneal ulcers, that failed medical management. In our sample, squamous cell carcinoma was the most common diagnosis (both clinically and histopathologically) leading to exenteration. Postoperative complications in our patient cohort were minimal. CONCLUSION: At our institution, enucleations predominate over eviscerations. Retrospective reviews published in recent years indicate that the rate of eviscerations at our institution is comparatively low. The results of this study, the first of its kind at our institution, may encourage a re-evaluation of the indications for evisceration versus enucleation in our patient population.

Requirement of respiratory support in acute bronchiolitis in infants is linked to endothelial and neutrophil activation.

BACKGROUND: Evidence shows that activation of pulmonary vascular endothelium and neutrophils are involved in the pathophysiology of acute bronchiolitis. We hypothesized that levels of markers of endothelial activation and leukocyte counts are associated with requirement and duration of respiratory support. METHODS: Thirty-four infants with bronchiolitis and eight controls were included. Nasopharyngeal swabs and blood samples were taken at admission. Serum levels of Angiopoietin (Ang)-1, Ang-2, sP-selectin, sE-selectin, vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1), and leukocyte counts were measured. For univariate analysis, bronchiolitis cases were grouped into two groups, namely those not requiring and those requiring any form of respiratory support. To control for known risk factors for poor outcome (i.e., age, prematurity, and congenital heart disease), and for days post symptom onset, linear regression analysis was performed with duration of any type of respiratory support in days. RESULTS: Ang-2 levels, Ang-2/Ang-1 ratios, sE-selectin levels, immature neutrophil count, and neutrophil/lymphocyte ratio (NLR) were higher in acute bronchiolitis versus controls. Ang-2, and NLR levels were significantly higher, and lymphocyte counts significantly lower, in infants that required respiratory support versus those that did not. Ang-2 levels (ß: .32, 95% confidence interval [CI]: 0.19-1.19) and NLR (ß: .68, 95% CI: 0.17-1.19) were positive predictors for the duration of respiratory support. CONCLUSIONS: Markers of endothelial and neutrophil activation are associated with respiratory support for acute bronchiolitis. Admission Ang-2 levels and NLR may be promising markers to determine requirement of respiratory support and deserve further study.

Viral causes of severe acute respiratory infection in hospitalized children and association with outcomes: A two-year prospective surveillance study in Suriname.

BACKGROUND: Viruses are the most frequent cause of severe acute respiratory infection (SARI) in children. It is currently unknown whether presence of a virus, the number of viruses, or type of virus, are associated with clinical outcomes of pediatric SARI in developing countries. METHODS: Between 2012 and 2014 nasopharyngeal swabs and demographic and clinical variables were prospectively collected for surveillance of viral causes of SARI in Surinamese children within 48 hours after hospitalization. These swabs were tested for 18 respiratory viruses using a multiplex polymerase chain reaction (PCR) panel to identify the specific viral causes of SARI, unknown to the treating physicians. In post hoc analyses we evaluated if the PCR results, and demographic and clinical characteristics, were associated with course of disease, duration of respiratory support, and length of stay (LOS). RESULTS: Of a total of 316 analyzed children, 290 (92%) had one or more viruses. Rhinovirus/enterovirus (43%) and respiratory syncytial virus (34%) were most prevalent. Course of disease was mild in 234 (74%), moderate in 68 (22%), and severe in 14 (4%) children. Neither presence of a single virus, multiple viruses, or the type of virus, were different between groups. Prematurity and lower weight-for-age-z-score were independent predictors of a severe course of disease, longer duration of respiratory support, and longer LOS. CONCLUSIONS: Viruses are common causes of pediatric SARI in Suriname, yet not necessarily associated with clinical outcomes. In developing countries, demographic and clinical variables can help to identify children at-risk for worse outcome, while PCR testing may be reserved to identify specific viruses, such as influenza, in specific patient groups or during outbreaks.

Characteristics, Upon Presentation, of a Cohort of Patients with Vogt-Koyanagi-Harada Disease in Puerto Rico.

OBJECTIVE: To describe the clinical features, upon initial presentation, of a cohort of patients with Vogt-Koyanagi-Harada (VKH) disease who live in Puerto Rico. METHODS: A retrospective medical record review of patients with VKH was performed. The demographic and clinical characteristics were analyzed. RESULTS: Twenty-two patients who met the diagnostic criteria for VKH were identified and included in the analysis. The median age at presentation was 41 years; 68.2% were female, and all patients were Hispanics. Bilateral disease was present in 90.9% of patients, and 59.1% of patients were categorized as having probable VKH. A headache was reported in 54.5% of patients and was the most common complaint at the time of presentation; the second most common complaint was tinnitus, which was present in 22.7% of patients. Vitiligo, alopecia, and meningismus were each preset in 9.1% of patients while hearing loss and aseptic meningitis were each reported in 4.5% of patients. Seventy-seven percent of patients had either topical or systemic corticosteroid use prior to the initial encounter. CONCLUSION: Our study suggests that in Puerto Rico, patients with Vogt-Koyanagi-Harada disease may have a distinctive prevalence of characteristics at the presentation when compared to other ethnic groups, including other Hispanic cohorts.

Epidemiology and Mortality of Early-Onset Neonatal Sepsis in Suriname: A 2-Year Surveillance Study.

We conducted a nationwide surveillance study to produce reliable national estimates on incidence, etiology, and mortality of early-onset neonatal sepsis (EONS) in Suriname. The estimated national population incidence rate of EONS was 1.37 (95% CI: 0.90-1.99) per 1000 live births and in-hospital mortality was 25.9%.

Photobleaching Efficiency Parallels the Enhancement of Membrane Damage for Porphyrazine Photosensitizers.

Photostability is considered a key asset for photosensitizers (PS) used in medical applications as well as for those used in energy conversion devices. In light-mediated medical treatments, which are based on PS-induced harm to diseased tissues, the photoinduced cycle of singlet oxygen generation has always been considered to correlate with PS efficiency. However, recent evidence points to the fundamental role of contact-dependent reactions, which usually cause PS photobleaching. Therefore, it seems reasonable to challenge the paradigm of photostability versus PS efficiency in medical applications. We have prepared a series of Mg(II) porphyrazines (MgPzs) having similar singlet oxygen quantum yields and side groups with different electron-withdrawing strengths that fine-tune their redox properties. A detailed investigation of the photobleaching mechanism of these porphyrazines revealed that it is independent of singlet oxygen, occurring mainly via photoinduced electron abstraction of surrounding electron rich molecules (solvents or lipids), as revealed by the formation of an air-stable radical anion intermediate. When incorporated into phospholipid membranes, photobleaching of MgPzs correlates with the degree of lipid unsaturation, indicating that it is caused by an electron abstraction from the lipid double bond. Interestingly, upon comparing the efficiency of membrane photodamage between two of these MgPzs (with the highest and the lowest photobleaching efficiencies), we found that the higher the rate of PS photobleaching the faster the leakage induced in the membranes. Our results therefore indicate that photobleaching is a necessary step toward inflicting irreversible biological damage. We propose that the design of more efficient PS for medical applications should contemplate contact-dependent reactions as well as strategies for PS regeneration.

Traumatic esophageal perforation in Puerto Rico Trauma Hospital: A case-series.

BACKGROUND: Esophageal injuries are rare, life-threatening, events with an overall reported incidence of less than 3%. In rare cases, trauma due to blunt or penetrating injuries cause esophageal perforations, which account for less than 15% of all esophageal injuries. MATERIALS AND METHODS: A case-series study was conducted to describe the outcomes and management of all the traumatic esophageal injuries at the Puerto Rico Trauma Hospital (PRTH) from 2000 through 2017. These cases were evaluated in terms of etiology of perforation, mechanism of injury and esophageal level. RESULTS: Sixteen patients were treated for esophageal injuries at the PRTH between 2000 and 2017. Of these patients, 15 (93.7%) were males with a median age of 24.5 years (16, 49). Regarding the etiology of the esophageal perforation, 2 (12.5%) patients suffered blunt esophageal trauma, and 14 (87.5%) patients had penetrating trauma to the esophagus. The most common mechanism of perforation was gunshot wound 10 (62.4%), followed by stab wound 4 (25.0%), and the least common were motor vehicle collision 1 (6.3%) and pedestrian injured by traffic 1 (6.3%). Regarding esophageal location, 9 (56.3%) patients presented cervical, 6 (37.5%) thoracic, and 1 (6.3%) abdominal injuries. Most patients 13 (81.3%) had a prompt diagnosis of traumatic esophageal perforation, while 3 (18.7%) patients had a delayed diagnosis. Only 2 (12.5%) deaths occurred among our 16 patients, including 1 (6.3%) in delayed diagnosed subjects. CONCLUSION: Esophageal perforation is a life-threatening condition and should be treated urgently. An early diagnosis and prompt surgical treatment completed in the first 24-h is fundamental for a good outcome.

Triplet Excited States and Singlet Oxygen Production by Analogs of Red Wine Pyranoanthocyanins.

During the maturation of red wines, the anthocyanins of grapes are transformed into pyranoanthocyanins, which possess a pyranoflavylium cation as their basic chromophore. Photophysical properties of the singlet and triplet excited states of a series of synthetic pyranoflavylium cations were determined at room temperature in acetonitrile solution acidified with 0.10 mol dm-3 trifluoroacetic acid (TFA, to inhibit competitive excited state proton transfer) and at 77 K in a rigid TFA-acidified isopropanol glass. In solution, the triplet states of these pyranoflavylium cations are efficiently quenched by molecular oxygen, resulting in sensitized formation of singlet oxygen, as confirmed by direct detection of the triplet-state decay by laser flash photolysis and of singlet oxygen monomol emission in the near infrared. The strong visible light absorption, the relatively small singlet-triplet energy differences, the excited state redox potentials and the reasonably long lifetimes of pyranoflavylium triplet states in the absence of molecular oxygen suggest that they might be useful as triplet sensitizers and/or as cationic redox initiators in polar aprotic solvents like acetonitrile.

Predictability of BRCA1/2 mutation status in patients with ovarian cancer: How to select women for genetic testing in middle-income countries.

OBJECTIVES: To evaluate the accuracy of algorithms for predicting BRCA1/2 germ-line mutation carrier probability, and to identify factors that could improve their performance among Brazilian women with ovarian cancer (OC). STUDY DESIGN: In this cross-sectional study, we enrolled patients (unselected for family history of cancer) undergoing treatment or follow-up for OC in a single centre in Brazil. Clinical and demographic data, including family history of cancer, were obtained. Blood samples were collected for genetic testing. MAIN OUTCOME MEASURES: The entire coding sequence of BRCA1 and BRCA2 was evaluated for mutations. Mutation carrier probability was calculated using BOADICEA, BRCAPRO, Myriad and the Manchester score. Sensitivity, specificity, positive and negative predictive values, and area under the receiver operating characteristic curves (AUC) were calculated for each algorithm. Logistic regression was used to detect additional factors associated with BRCA1/2 status, and these were added to the algorithms before recalculating the AUCs. RESULTS: BRCA1/2 mutations were identified in 19 of the 100 included patients. BOADICEA outperformed other algorithms (sensitivity, 73.7%; specificity, 87.7%; AUC, 0.87, with a threshold of a 10% risk of mutation). Later menarche was associated with the presence of a BRCA1/2 mutation. Although adding age at menarche resulted in a larger AUC for all models, this increase was significant only for the Myriad algorithm. CONCLUSION: A BOADICEA risk evaluation of 10% or more most accurately predicted BRCA1/2 status, and the inclusion of age at menarche tended to improve the performance of all algorithms. Using these tools could reduce the number of tests, but at the expense of missing a significant proportion of mutation carriers.

Three atypical lethal cases associated with acute Zika virus infection in Suriname.

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks.

Three atypical lethal cases associated with acute Zika virus infection in Suriname

Acute Zika virus infection usually presents with a self-limiting triad of fever, rash and arthritis. There is limited information on severe or lethal cases. We report three cases of lethal acute Zika infection, confirmed with polymerase chain reaction, in adult patients with some co-morbidities. The patients showed rapid clinical deterioration with hemorrhagic and septic shock, and exaggerated acute and innate inflammatory responses with pronounced coagulopathy, and died soon after admission to the hospital. It remains unclear whether the fatal outcomes were due to acute Zika virus infection alone or to the combination with exacerbated underlying prior disease or co-infection. Nonetheless, the severity of these cases implies that increased awareness for atypical presentations of Zika virus infection, and careful clinical assessment of patients with symptoms of Zika, is warranted during current and future outbreaks...(AU)

Dengue seroprevalence and risk factors for past and recent viral transmission in Venezuela: a comprehensive community-based study.

Dengue transmission in Venezuela has become perennial and a major public health problem. The increase in frequency and magnitude of recent epidemics prompted a comprehensive community-based cross-sectional study of 2,014 individuals in high-incidence neighborhoods of Maracay, Venezuela. We found a high seroprevalence (77.4%), with 10% of people experiencing recent infections. Multivariate logistic regression analysis showed that poverty-related socioeconomic factors (place and duration of residence, crowding, household size, and living in a shack) and factors/constraints related to intradomiciliary potential mosquito breeding sites (storing water and used tires) were linked with a greater risk of acquiring a dengue infection. Our results also suggest that transmission occurs mainly at home. The combination of increasingly crowded living conditions, growing population density, precarious homes, and water storage issues caused by enduring problems in public services in Maracay are the most likely factors that determine the permanent dengue transmission and the failure of vector control programs.

Molecular and serological characterization of species B2 adenovirus strains isolated from children hospitalized with acute respiratory disease in Buenos Aires, Argentina.

BACKGROUND: Between September 2000 and November 2005, approximately 10% of the retrospectively examined human adenovirus (HAdV)-positive pediatric cases of acute respiratory disease (ARD) requiring hospitalization at the Hospital Nacional de Pediatria Juan P. Garrahan in Buenos Aires, Argentina, were found to have a HAdV-B2 infection. OBJECTIVE: To characterize genetically and antigenically the HAdV-B2 virus isolates. STUDY DESIGN: Restriction enzyme analysis (REA), hexon and fiber gene sequencing and virus neutralization assays (VN) were carried out on 8 HAdV-B2 respiratory virus isolates. RESULTS: REA showed that the 8 examined HAdV-B2 virus isolates were HAdV11, belonging to two genomic variants: HAdV11a and a BclI variant of HAdV11c which we designated 11c4. Molecular analysis of the hexon genes showed that both REA variants had a HAdV11-like hexon gene. Confirming previous reports, the 7 HAdV11a virus isolates were found to have HAdV14-like fiber genes and therefore are HAdV H11/F14. The fiber gene of the HAdV11c4 virus isolates most closely resembled that of various strains of HAdV7. In VN assays, the 4 tested HAdV11a strains were serotyped as HAdV11-14. The HAdV11c4 strain was serotyped as HAdV11 but also showed a weak but significant reactivity with antiserum to HAdV7. Compared with the other HAdV-positive cases in our study, infection with HAdV11 caused a similarly severe disease. CONCLUSIONS: Our results provide evidence to the long term world-wide circulation of HAdV H11/F14 as a causative agent of ARD. Combined, our molecular and serology data support the rationale to base the molecular typing and designation of recombinant viruses on the sequences of the hexon and fiber genes.

Prenatal exposure to nicotine and impaired reading performance.

OBJECTIVE: To investigate whether prenatal exposure to nicotine has an impact on several reading skill outcomes in school age children. STUDY DESIGN: Using a longitudinal sample of 5119 school age children in the Avon Longitudinal Study of Parents and Children, this study investigated specific reading skill outcomes in the area of speed, fluency, accuracy, spelling, and comprehension in relation to prenatal nicotine exposure, after adjusting for potential mediators and confounders. Prenatal nicotine exposure was divided into 3 categories: high (>17 mg per day), low (≤17 mg per day), and no exposure. RESULTS: We found that prenatal nicotine exposure was associated with increased risk of underperformance in specific reading skill outcomes after adjusting for potential mediators and confounders (P = .006). The effect of poor performance in decoding single words was most pronounced among children with prenatal exposure to high levels of nicotine in conjunction with a phonological deficit. Overall, the results showed that maternal smoking has moderate to large associations with delayed or decreased reading skills of children in the Longitudinal Study of Parents and Children. CONCLUSIONS: High prenatal nicotine exposure has a negative association with reading performance in school age children. In addition, modeling showed that environmental factors significantly moderated the interaction between prenatal nicotine exposure and reading skill outcomes.

Nanoaggregates of micropurified lipopolysaccharide identified using dynamic light scattering, zeta potential measurement, and TLR4 signaling activity.

Nanoaggregates composed of selected glycoforms from Escherichia coli 055:B5 lipopolysaccharide (LPS) were prepared by combining sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, zinc-imidazole reverse staining, zinc chelation after cutting gel slices, elution with either 0.5% triethylamine (TEA) or 0.4% to 0.5% surfactant (SDS or deoxycholate [DOC]) from extrusion-generated gel microparticles, and centrifugal diafiltration after appropriate surfactant dilution. Dynamic light scattering allows detecting these aggregates, giving a size distribution from 10 to 100nm in diameter. The formation of the aggregates prepared with selected DOC-eluted LPS glycoforms was notably improved over those prepared with TEA-eluted glycoforms. As the O-side chain length increased in the composition of the former aggregates, there was a gradual decrease in the electrophoretic mobility (from -1.2 to 0.0110(-8)m(2)/Vs), giving a calculated zeta potential from -15 to 0.1mV at pH6.8. These aggregates were further characterized for their abilities to elicit agonistic effects on human Toll-like receptor 4, as shown by in vitro activation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) in engineered HEK293 cells.

Leishmanicidal activity of Himatanthus sucuuba latex against Leishmania amazonensis.

Himatanthus sucuuba (HsL) latex exhibited a potent leishmanicidal activity against intracellular amastigotes of Leishmania amazonensis, a causative agent of cutaneous leishmaniasis. HsL inhibited intracellular amastigote growth in a dose-dependent manner (IC(50)=15.7microg/mL). Moreover, HsL increased nitric oxide (NO) and Tumor Nuclear Factor-alpha (TNF-alpha) and decreased Transforming Growth Factor-beta (TGF-beta) production in macrophages. As assessed by plasma membrane integrity and mitochondrial activity, HsL showed low toxicity for host macrophages. HsL in vivo was active by the oral route, reducing the parasite load in established footpad lesions after only five doses. In summary, these findings support HsL as an interesting candidate for further evaluations regarding its potential application as a therapeutical agent against Leishmania.

The global circulation of seasonal influenza A (H3N2) viruses.

Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.

Vitamin D status of wild Ricord's iguanas (Cyclura ricordii) and captive and wild rhinoceros iguanas (Cyclura cornuta cornuta) in the Dominican Republic.

Calcidiol (25-hydroxyvitamin D) values are reported for 22 wild Ricord's iguanas (Cyclura ricordii) and seven wild rhinoceros iguanas (Cyclura cornuta cornuta). Calcitriol (1,25-hydroxyvitamin D) values are reported for 12 wild Ricord's iguanas and seven wild rhinoceros iguanas. These animals were captured as part of a larger health assessment study being conducted on Ricord's iguanas in Isla Cabritos National Park, Dominican Republic. A total of 13 captive rhinoceros iguanas held outdoors at Parque Zoológico Nacional were also sampled for comparison. Mean concentrations of 25-hydroxyvitamin D were 554 nmol/L (222 ng/ml) with a range of 250-1,118 nmol/L (100-448 ng/ml) for wild Ricord's iguanas, 332 nmol/L (133 ng/ml) with a range of 260-369 nmol/L (104-148 ng/ml) for wild rhinoceros iguanas, and 317 nmol/L (127 ng/ml) with a range of 220-519 nmol/L (88-208 ng/ml) for captive rhinoceros iguanas. On the basis of these results, serum concentrations of at least 325 nmol/L (130 ng/ml) for 25-hydroxyvitamin D should be considered normal for healthy Ricord's and rhinoceros iguanas.