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IntroductionChronic critically ill patients (CCI) in pediatric intensive care unit (PICU) are at risk of negative health outcomes, and account for a considerable amount of ICU resources. This study aimed to (a) describe the prevalence of CCI children, (b) compare their clinical characteristics and ICU resources use with non-CCI children, and (c) identify associated risk factors of CCI.MethodsA retrospective national registry study including 2015–2017 data from the eight Swiss PICUs of five tertiary and three regional hospitals, admitting a broad case-mix of medical and surgical patients, including pre- and full-term infants. CCI patients were identified using an adapted definition: PICU length of stay (LOS) ≥8 days and dependence on ≥1 PICU technology.ResultsOut of the 12,375 PICU admissions, 982 (8%) were CCI children and compared to non-CCI children, they were younger (2.8 vs. 6.7 months), had more cardiac conditions (24% vs. 12%), and higher mortality rate (7% vs. 2%) (p

Cervical cancer has killed millions of women over the past decade. In 2019 the World Health Organization launched the Cervical Cancer Elimination Strategy, which included ambitious targets for vaccination, screening, and treatment. The COVID-19 pandemic disrupted progress on the strategy, but lessons learned during the pandemic – especially in vaccination, self-administered testing, and coordinated mobilization on a global scale – may help with efforts to achieve its targets. However, we must also learn from the failure of the COVID-19 response to include adequate representation of global voices. Efforts to eliminate cervical cancer will only succeed if those countries most affected are involved from the very start of planning. In this article we summarize innovations and highlight missed opportunities in the COVID response, and make recommendations to leverage the COVID experience to accelerate the elimination of cervical cancer globally.

Analyses of disciplines encompassing futures studies reveal a prevailing tendency to perceive time as a linear sequence of projections. However, this perspective is not applicable to the current context of social transformation in the age of globalization and digitization, such as sustainable development. Preliminary investigations into time-based design and futures studies have shown the potential of time-based paradigms for predicting reliable future scenarios and redesigning current forms of spaces, relationships, and services in response to these desired futures. In this paper, we describe a project of an Ephemeral and Temporary Space Design Laboratory, which has been a pedagogical experiment for 3 years to date in the School of Design at the Politecnico di Milano. The objective of this project is to systematically design an area of the city by reflecting on the relationship between design systems and social change, using participatory design methods such as field research and interviews with local residents to systematically redesign the urban space of the Lodi/Corvetto area in the city of Milan. This research aims to investigate the systematic influence of time factors on the spatial design of urban communities through futuristic and time/space-based design perspectives. The findings demonstrate that the utilization of time-based paradigms and tools can effectively enhance the time-based design approach, resulting in its increased integration within the design process. This integration plays a pivotal role in the construction of systems that have the capability to interact with and catalyze social transformation within the broader public and shared community.

BackgroundTest-seeking is associated with HIV in Brazilian blood donors. This study sought to investigate the frequency with which three different donor groups: deferred donors, accepted donors who tested HIV positive [HIV (+)], and accepted donors who tested infectious disease markers negative [IDM (-)], came to the blood bank at the suggestion of a health care professional.Study design and methodsDonors deferred for reporting high-risk behaviors and participants in an HIV risk factor case-control study completed a confidential audio computer-assisted self-interview (ACASI) that included two questions related to health care professionals and test-seeking.ResultsOf 4013 enrolled deferred donors, 468 (11.8%) reported a health care professional suggested donation as a way to be tested for infection. Of 341 HIV (+) and 791 IDM (-) participants, 43 (12.6%) and 11 (1.4%), respectively, reported a health care professional suggested donation as a way to be tested for infection. Physicians were the most frequently reported source of referral: [(61.5% of deferred, 69.1% of HIV (+), and 9.1% of IDM (-) donors)].ConclusionHIV (+) donors and deferred donors were 10 times more likely to report test-seeking behavior by suggestion of health care professional than IDM (-) donors. If true, efforts should be made to educate health care professionals and blood donors on how to safeguard the blood supply, emphasizing that HIV testing should be done at volunteer testing centers rather than at the blood centers.

BACKGROUND: Human papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys. METHODS: This is a prospective, single-arm, open-label, non-randomized, Phase IIa trial among 9-11 year-old girls and boys to determine the immunogenicity after a single dose of the nonavalent HPV vaccine (GARDASIL® 9) over 24 months, with a deferred booster dose at 24 months and an optional booster at 30 months after the first dose. Participants provide blood specimens at 6, 12, 18, 24, and 30 months after the first dose. Serologic geometric mean titers (GMT) of the nine vaccine types (HPV 16/18/ 6/11/31/33/45/52/58) will be measured at each time point. The primary objective is to determine the stability of type-specific serologic GMT of HPV16 and HPV18 between the 6- vs. 12-month, 12- vs. 18-month, and 18- vs. 24-month visits. Secondary objectives are to determine the stability of type-specific serologic GMT of the other HPV types (HPV 6/11/31/33/45/52/58) between the visits and to assess safety and reactogenicity after each vaccine dose. DISCUSSION: Single dose HPV vaccination could simplify the logistics and reduce costs of HPV vaccination in the US and across the world. This study will contribute important immunogenicity data on the stability and kinetics of type-specific antibody titers and inform feasibility of the single dose HPV vaccination paradigm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02568566 . Registered on October 6, 2015.

Toll-like receptors (TLRs) are innate immune defenders thought to be critical for the clearance of human papillomavirus (HPV) infections hence preventing the development of HPV-associated high-grade cervical intra-epithelial neoplasia (CIN2 or 3), a potential cervical cancer precursor. However, the role of TLRs in the regression of established cervical lesions, such as CIN2, is hindered by a lack of prospective design studies. Using SYBR green real-time PCR assays, we have examined the gene expression of TLR2, TLR3, TLR7, TLR8 and TLR9, in cytobrush collected endocervical cells of 63 women diagnosed with CIN2 at study entry (baseline) and followed over a 3-year period. Wilcoxon rank-sum test was used to examine the association between TLR expression levels, measured at baseline, and CIN2 outcome (regression vs. persistence/progression) over time. HPV genotyping was performed using Roche Linear Array Assay detecting 37 HPV types. Women with CIN2 regression showed significantly higher baseline levels of TLR2 (p = 0.006) and TLR7 (p = 0.007), as well as a non-significant trend for a higher TLR8 expression (p = 0.053) compared to women with CIN2 persistence/progression. Six women with CIN2 regression, who presented with an HR-HPV DNA-negative CIN2 lesion at study entry, had significantly higher baseline levels of TLR2 (p = 0.005), TLR7 (p = 0.013) and TLR8 (p = 0.012), compared to women with CIN2 persistence/progression, suggesting their role in clearance of HPV prior to clearance of the lesion. Our results confirm a key role of TLRs in regression of CIN2 and support the potential use of TLR-agonists for treatment of these lesions.

ObjectivesThis study explores the association between combination antiretroviral therapy (cART) and oral health outcomes (dental and periodontal) among perinatally HIV-infected (PHIV) youth.MethodsWe conducted a cross-sectional study of oral health among PHIV youth participating in the Oral Health substudy of the Pediatric HIV/AIDS Cohort Study (PHACS). Dentists at research sites were trained/calibrated on how to perform a standardized oral mucosal, dental and periodontal examination. They assessed the decayed-missing-filled-surfaces and teeth index (DMFS/T). The number of decayed surfaces and teeth and the number of teeth with gingival bleeding on probing for each participant were derived from the examination. Data for analysis included lifetime measurements of CD4 cell count and viral load, sociodemographic information and current/past history of ART.ResultsAmong 209 PHIV youth, 95% were on ART at the time of enrolment. Among 143 PHIV youth on the same cART for at least 1 year, we found that the mean decayed teeth score of those receiving cART containing an integrase inhibitor was 86% higher than that of those on cART without an integrase inhibitor after adjusting for age, lifetime proportion of unsuppressed viral load and CD4 cell count nadir. Initiating protease inhibitors before age 6 years was associated with a significantly lower DMFT score than participants who initiated at age 6 years and older.ConclusionOur study revealed that PHIV youth who received cART containing an integrase inhibitor had a significantly higher number of untreated active caries than those on cART without an integrase inhibitor. This may warrant closer dental surveillance of those receiving an integrase inhibitor.

The Alaskan Layered Pollution and Chemical Analysis (ALPACA) field campaign included deployment of a suite of atmospheric measurements in January–February 2022 with the goal of better understanding atmospheric processes and pollution under cold and dark conditions in Fairbanks, Alaska. We report on measurements of particle composition, particle size, ice nucleating particle (INP) composition, and INP size during an ice fog period (29 January–3 February). During this period, coarse particulate matter (PM10) concentrations increased by 150% in association with a decrease in air temperature, a stronger temperature inversion, and relatively stagnant conditions. Results also show a 18%–78% decrease in INPs during the ice fog period, indicating that particles had activated into the ice fog via nucleation. Peroxide and heat treatments performed on INPs indicated that, on average, the largest contributions to the INP population were heat‐labile (potentially biological, 63%), organic (31%), then inorganic (likely dust, 6%). Measurements of levoglucosan and bulk and single‐particle composition corroborate the presence of dust and aerosols from combustion sources. Heat‐labile and organic INPs decreased during the peak period of the ice fog, indicating those were preferentially activated, while inorganic INPs increased, suggesting they remained as interstitial INPs. In general, INP concentrations were unexpectedly high in Fairbanks compared to other locations in the Arctic during winter. The fact that these INPs likely facilitated ice fog formation in Fairbanks has implications for other high latitude locations subject to the hazards associated with ice fog. Plain Language Summary: The Alaskan Layered Pollution and Chemical Analysis field campaign occurred January–February 2022 with the goal of better understanding the atmosphere and atmospheric pollution during the winter in Fairbanks, Alaska. We studied a rare subset of atmospheric particles called ice nucleating particles which facilitate the formation of ice fog by allowing water to freeze at temperatures above −38°C. During our study, there was an ice fog event that coincided with a pollution event. During this event, there was a significant increase in coarse particulate matter associated with a decrease in temperature and calm winds. Ice nucleating particle concentration in the air decreased during the ice fog event indicating that the INPs had activated into the ice fog and were not able to be captured. We determined that most INPs were heat‐labile (potentially biological), followed by organic. Very few INPs were inorganic. Inorganic INPs increased during the ice fog period while heat‐labile and organic INPs decreased indicating that they were being selectively activated into the fog. Overall, INP concentrations in Fairbanks were quite high compared to other Arctic locations and carries implications for ice fog formation in other high‐latitude locations. Key Points: Fairbanks had higher wintertime ice nucleating particle (INP) concentrations than other high‐latitude locationsINP concentrations in Fairbanks decreased during the ice fog period, indicating that INPs were activated into the fogINP composition in Fairbanks was dominated by heat‐labile INPs [ABSTRACT FROM AUTHOR]

The lack of optimal models to evaluate novel agents is delaying the development of effective immunotherapies against human breast cancer (BC). In this prospective open label study, we applied neoadjuvant intratumoral immunotherapy with empty cowpea mosaic virus-like particles (eCPMV) to 11 companion dogs diagnosed with canine mammary cancer (CMC), a spontaneous tumor resembling human BC. We found that two neoadjuvant intratumoral eCPMV injections resulted in tumor reduction in injected tumors in all patients and in noninjected tumors located in the ipsilateral and contralateral mammary chains of injected dogs. Tumor reduction was independent of clinical stage, tumor size, histopathologic grade, and tumor molecular subtype. RNA-seq-based analysis of injected tumors indicated a decrease in DNA replication activity and an increase in activated dendritic cell infiltration in the tumor microenvironment. Immunohistochemistry analysis demonstrated significant intratumoral increases in neutrophils, T and B lymphocytes, and plasma cells. eCPMV intratumoral immunotherapy demonstrated antitumor efficacy without any adverse effects. This novel immunotherapy has the potential for improving outcomes for human BC patients.

ObjectiveGuidelines recommend 3-year cervical cancer screening intervals to avoid unnecessary invasive procedures; however, regular testing remains critical. We evaluated trends in cervical cancer screening among low-income women receiving family planning-related services and their association with patient and provider characteristics.Materials and methodsUsing claims and enrollment data from California's publicly funded family planning program, we identified 540,026 women with a clinician visit at 216 sites between 2011 and 2015. We calculated guideline adherent cervical cancer testing rates for 6-month periods among women aged 21 to 24, 25 to 29, and 30 to 64 years. We also calculated guideline adherent chlamydia testing for women aged 21 to 24 years.ResultsHaving a 3-year cervical cancer screening test declined for all age groups. The odds of cervical cancer screening declined for women aged 21 to 24 years by an estimated 11% every 6 months (odds ratio [OR] = 0.90, 95% confidence interval [CI] = 0.89-0.90), a significantly greater decline than for the other age groups. Among women aged 21 to 29 years, the decrease was significantly larger for Latina (ratio of ORs = 0.95, 95% CI = 0.95-0.96) and Spanish-speaking (ratio of ORs = 0.95, 95% CI = 0.95-0.96) women compared with non-Latina and non-Spanish-speaking women. A smaller decline was seen for chlamydia screening.ConclusionsChanges in screening interval guidelines are associated with overall decreased screening. This trend was strongest among women aged 21 to 24 years, even as they continued to be screened appropriately for chlamydia, suggesting many missed opportunities. Efforts to reduce unnecessary cervical cancer screening should be monitored to maintain appropriate screening rates to avoid advanced-stage diagnoses and higher health care costs.

BACKGROUND:Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth. RESULTS:Species richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus. CONCLUSIONS:The microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer "health"-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis.

Abstract Background Vaginal microbiota (VMB) composition is altered in women with cervical intra-epithelial neoplasia (CIN) compared to healthy controls and is associated with disease progression. However, the impact of CIN excision on the VMB and innate immunity is not known. This observational study aims to explore the impact of CIN excision on the VMB, antimicrobial peptides (AMP) and proinflammatory cytokines. Methods We sampled 103 non-pregnant, premenopausal women at the time of excisional treatment for CIN and at their 6-month follow-up visit. A further 39 untreated controls with normal cytology were also sampled. We used metataxonomics to group vaginal swab samples into community state types (CSTs) and ELISA to quantify cytokine and AMP levels in matched vaginal secretions. Analyses were performed to compare the bacterial composition and immune analyte levels before and after CIN excision and in healthy controls. Results Women with CIN had significantly higher rates of Lactobacillus species depletion pre-treatment compared to healthy controls (CST IV 21/103, 20% vs 1/39, 3%, p = 0.0081). Excision did not change the VMB composition, with CST IV remaining significantly more prevalent after excision compared to untreated, healthy controls (CST IV 19/103, 20% vs 1/39, 3%, p = 0.0142). Prevotella bivia and Sneathia amnii were significantly higher in samples before treatment compared to untreated controls, and Prevotella bivia remained significantly higher amongst the treated, with less Lactobacillus crispatus compared to untreated controls. IL-1β and IL-8 remained significantly elevated pre- (p < 0.0001 and p = 0.0014, respectively) and post-treatment (p < 0.0001 and p = 0.0035, respectively) compared to untreated controls. Levels of human beta-defensin-1 and secretory leukocyte protease inhibitor were both significantly reduced following CIN excision (p < 0.0001); however, their levels remained lower than controls post-treatment. Conclusions Women with CIN have an increased prevalence of Lactobacillus sp. depletion, high-diversity VMB composition, and higher levels of proinflammatory cytokines and AMPs compared to normal controls. Surgical excision of the disease reduces levels of vaginal AMPs but does not alter VMB composition or cytokine levels. These findings suggest that women with CIN have an inherent predisposition to a high-diversity proinflammatory environment that is not corrected by disease excision. The failure to re-establish a Lactobacillus-enriched CST may explain why women remain at high risk of pre-invasive and invasive disease recurrence.

ObjectivesThe American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology.MethodsA systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version.ResultsColposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression.ConclusionsA recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.

The American Society for Colposcopy and Cervical Pathology (ASCCP) Colposcopy Standards recommendations address the role of colposcopy and directed biopsy for cervical cancer prevention in the United States (US). The recommendations were developed by an expert working group appointed by ASCCP's Board of Directors. An extensive literature review was conducted and supplemented by a systematic review and meta-analysis of unpublished data. In addition, a survey of practicing colposcopists was conducted to assess current colposcopy practice in the US. Recommendations were approved by the working group members, and the final revisions were made based on comments received from the public. The recommendations cover terminology, risk-based colposcopy, colposcopy procedures, and colposcopy adjuncts. The ASCCP Colposcopy Standards recommendations are an important step toward raising the standard of colposcopy services delivered to women in the US. Because cervical cancer screening programs are currently undergoing important changes that may affect colposcopy performance, updates to some of the current recommendations may be necessary in the future.

ObjectivesThe American Society for Colposcopy and Cervical Pathology Colposcopy Standards address the role of and approach to colposcopy and biopsy for cervical cancer prevention in the United States. Working Group 1 was tasked with defining the role of colposcopy, describing benefits and potential harms, and developing an official terminology.MethodsA systematic literature review was performed. A national survey of American Society for Colposcopy and Cervical Pathology members provided input on current terminology use. The 2011 International Federation for Cervical Pathology and Colposcopy terminology was used as a template and modified to fit colposcopic practice in the United States. For areas without data, expert consensus guided the recommendation. Draft recommendations were posted online for public comment and presented at an open session of the 2017 International Federation for Cervical Pathology and Colposcopy World Congress for further comment. All comments were considered for the final version.ResultsColposcopy is used in the evaluation of abnormal or inconclusive cervical cancer screening tests. Colposcopy aids the identification of cervical precancers that can be treated, and it allows for conservative management of abnormalities unlikely to progress. The potential harms of colposcopy include pain, psychological distress, and adverse effects of the procedure. A comprehensive colposcopy examination should include documentation of cervix visibility, squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), lesion(s) visibility, size and location of lesions, vascular changes, other features of lesion(s), and colposcopic impression. Minimum criteria for reporting include squamocolumnar junction visibility, presence of acetowhitening, presence of a lesion(s), and colposcopic impression.ConclusionsA recommended terminology for use in US colposcopic practice was developed, with comprehensive and minimal criteria for reporting.