Type-Specific Identification of Genital Human Papillomavirus Infection in Women with Cytological Abnormality

Objectives: To estimate the frequency of human papillomavirus (HPV) infection and the genotype distribution of HPV among women with a Pap smear showing atypical squamous cells of undetermined significance (ASC-US) attending the Program for the Detection and Control of Cervical Cancer in Bogotá, Colombia. Study Design: Cervical samples from 200 women with an ASC-US Pap smear were analyzed for the presence of HPV DNA and genotype distribution using a commercial molecular technique (Linear Array®; Roche Molecular Systems, USA). Results: HPV infection was found in 140 women (70%). High-risk HPV types were present in 46.4% of the samples; 16.4% showed a low-risk HPV type, and 37.1% showed both. Of the positive samples, 42.9% were infected with a single viral genotype, whereas 57.1% exhibited multiple HPV infections. The most common HPV genotypes were HPV 16, 53, and 52 with a prevalence of 26.4, 16.4, and 13.6%, respectively. Conclusion: The epidemiological characterization of HPV infections described in this study might guide actions for epidemiological surveillance to strengthen the program in Bogotá and to develop appropriate HPV vaccination programs.Instituto de Genética Veterinari

Type-Specific Identification of Genital Human Papillomavirus Infection in Women with Cytological Abnormality

Objectives: To estimate the frequency of human papillomavirus (HPV) infection and the genotype distribution of HPV among women with a Pap smear showing atypical squamous cells of undetermined significance (ASC-US) attending the Program for the Detection and Control of Cervical Cancer in Bogotá, Colombia. Study Design: Cervical samples from 200 women with an ASC-US Pap smear were analyzed for the presence of HPV DNA and genotype distribution using a commercial molecular technique (Linear Array®; Roche Molecular Systems, USA). Results: HPV infection was found in 140 women (70%). High-risk HPV types were present in 46.4% of the samples; 16.4% showed a low-risk HPV type, and 37.1% showed both. Of the positive samples, 42.9% were infected with a single viral genotype, whereas 57.1% exhibited multiple HPV infections. The most common HPV genotypes were HPV 16, 53, and 52 with a prevalence of 26.4, 16.4, and 13.6%, respectively. Conclusion: The epidemiological characterization of HPV infections described in this study might guide actions for epidemiological surveillance to strengthen the program in Bogotá and to develop appropriate HPV vaccination programs.Instituto de Genética Veterinari

2-Deoxy-D-Glucose Treatment Induces Ketogenesis, Sustains Mitochondrial Function, and Reduces Pathology in Female Mouse Model of Alzheimer's Disease

Previously, we demonstrated that mitochondrial bioenergetic deficits preceded Alzheimer's disease (AD) pathology in the female triple-transgenic AD (3xTgAD) mouse model. In parallel, 3xTgAD mice exhibited elevated expression of ketogenic markers, indicating a compensatory mechanism for energy production in brain. This compensatory response to generate an alternative fuel source was temporary and diminished with disease progression. To determine whether this compensatory alternative fuel system could be sustained, we investigated the impact of 2-deoxy-D-glucose (2-DG), a compound known to induce ketogenesis, on bioenergetic function and AD pathology burden in brain. 6-month-old female 3xTgAD mice were fed either a regular diet (AIN-93G) or a diet containing 0.04% 2-DG for 7 weeks. 2-DG diet significantly increased serum ketone body level and brain expression of enzymes required for ketone body metabolism. The 2-DG-induced maintenance of mitochondrial bioenergetics was paralleled by simultaneous reduction in oxidative stress. Further, 2-DG treated mice exhibited a significant reduction of both amyloid precursor protein (APP) and amyloid beta (Aβ) oligomers, which was paralleled by significantly increased α-secretase and decreased γ-secretase expression, indicating that 2-DG induced a shift towards a non-amyloidogenic pathway. In addition, 2-DG increased expression of genes involved in Aβ clearance pathways, degradation, sequestering, and transport. Concomitant with increased bioenergetic capacity and reduced β-amyloid burden, 2-DG significantly increased expression of neurotrophic growth factors, BDNF and NGF. Results of these analyses demonstrate that dietary 2-DG treatment increased ketogenesis and ketone metabolism, enhanced mitochondrial bioenergetic capacity, reduced β-amyloid generation and increased mechanisms of β-amyloid clearance. Further, these data link bioenergetic capacity with β-amyloid generation and demonstrate that β-amyloid burden was dynamic and reversible, as 2-DG reduced activation of the amyloidogenic pathway and increased mechanisms of β-amyloid clearance. Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated β-amyloid burden

An inclusive Research and Education Community (iREC) model to facilitate undergraduate science education reform

Funding: This work was supported by Howard Hughes Medical Institute grants to DIH is GT12052 and MJG is GT15338.Over the last two decades, there have been numerous initiatives to improve undergraduate student outcomes in STEM. One model for scalable reform is the inclusive Research Education Community (iREC). In an iREC, STEM faculty from colleges and universities across the nation are supported to adopt and sustainably implement course-based research – a form of science pedagogy that enhances student learning and persistence in science. In this study, we used pathway modeling to develop a qualitative description that explicates the HHMI Science Education Alliance (SEA) iREC as a model for facilitating the successful adoption and continued advancement of new curricular content and pedagogy. In particular, outcomes that faculty realize through their participation in the SEA iREC were identified, organized by time, and functionally linked. The resulting pathway model was then revised and refined based on several rounds of feedback from over 100 faculty members in the SEA iREC who participated in the study. Our results show that in an iREC, STEM faculty organized as a long-standing community of practice leverage one another, outside expertise, and data to adopt, implement, and iteratively advance their pedagogy. The opportunity to collaborate in this manner and, additionally, to be recognized for pedagogical contributions sustainably engages STEM faculty in the advancement of their pedagogy. Here, we present a detailed pathway model of SEA that, together with underpinning features of an iREC identified in this study, offers a framework to facilitate transformations in undergraduate science education.Peer reviewe

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Clustering COVID-19 ARDS patients through the first days of ICU admission. An analysis of the CIBERESUCICOVID Cohort

Background Acute respiratory distress syndrome (ARDS) can be classified into sub-phenotypes according to different inflammatory/clinical status. Prognostic enrichment was achieved by grouping patients into hypoinflammatory or hyperinflammatory sub-phenotypes, even though the time of analysis may change the classification according to treatment response or disease evolution. We aimed to evaluate when patients can be clustered in more than 1 group, and how they may change the clustering of patients using data of baseline or day 3, and the prognosis of patients according to their evolution by changing or not the cluster.Methods Multicenter, observational prospective, and retrospective study of patients admitted due to ARDS related to COVID-19 infection in Spain. Patients were grouped according to a clustering mixed-type data algorithm (k-prototypes) using continuous and categorical readily available variables at baseline and day 3.Results Of 6205 patients, 3743 (60%) were included in the study. According to silhouette analysis, patients were grouped in two clusters. At baseline, 1402 (37%) patients were included in cluster 1 and 2341(63%) in cluster 2. On day 3, 1557(42%) patients were included in cluster 1 and 2086 (57%) in cluster 2. The patients included in cluster 2 were older and more frequently hypertensive and had a higher prevalence of shock, organ dysfunction, inflammatory biomarkers, and worst respiratory indexes at both time points. The 90-day mortality was higher in cluster 2 at both clustering processes (43.8% [n = 1025] versus 27.3% [n = 383] at baseline, and 49% [n = 1023] versus 20.6% [n = 321] on day 3). Four hundred and fifty-eight (33%) patients clustered in the first group were clustered in the second group on day 3. In contrast, 638 (27%) patients clustered in the second group were clustered in the first group on day 3.Conclusions During the first days, patients can be clustered into two groups and the process of clustering patients may change as they continue to evolve. This means that despite a vast majority of patients remaining in the same cluster, a minority reaching 33% of patients analyzed may be re-categorized into different clusters based on their progress. Such changes can significantly impact their prognosis

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Asymptomatic bacteriuria and inflammatory response to urinary tract infection of elderly ambulatory women in nursing homes

Background. Bacteriuria ? 105 CFU/ml is evidence of urinary tract infection in the absence of associated signs or symptoms. The presence of pyuria with asymptomatic bacteriuria established the response of elderly women against microorganisms capable of causing invasiveness or tissue injury of the urinary tract. Methods. The association between bacteriuria and pyuria was determined in 178 elderly, ambulatory women without symptoms of urinary tract infection in seven nursing homes. Urine culture results were subsequently analyzed in conjunction with absolute leukocyte count in urine. In this cross-sectional study, asymptomatic bacteriuria in elderly women was classified with and without pyuria. Results. The prevalence of asymptomatic bacteriuria was found in 44 (24.7%) elderly women. The presence of pyuria had a sensitivity of 63.6% for bacteriuria and a specificity of 91%. The positive predictive value for the presence of pyuria predicting those with bacteriuria was 70%, and the negative predictive value for the absence of pyuria predicting those without bacteriuria was 88.4%. Escherichia coli was the most common organism isolated in 81.8% of the women. Conclusions. Bacteriuria ? 105 CFU/ml associated with pyuria was detected in 77% of elderly women with asymptomatic urinary tract infections. Bacteriuria of < 105 CFU/ml with pyuria proves less sensitive as an indicator of urinary tract infection. Elderly women with pyuria but without bacteriuria should be studied for other causes of urinary tract inflammation