Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.

Maintenance of stemness is tightly linked to cell cycle regulation through protein phosphorylation by cyclin-dependent kinases (CDKs). However, how this process is reversed during differentiation is unknown. We report here that exit from stemness and differentiation of pluripotent cells along the neural lineage are controlled by CDC14, a CDK-counteracting phosphatase whose function in mammals remains obscure. Lack of the two CDC14 family members, CDC14A and CDC14B, results in deficient development of the neural system in the mouse and impairs neural differentiation from embryonic stem cells (ESCs). Mechanistically, CDC14 directly dephosphorylates specific proline-directed Ser/Thr residues of undifferentiated embryonic transcription Factor 1 (UTF1) during the exit from stemness, triggering its proteasome-dependent degradation. Multiomic single-cell analysis of transcription and chromatin accessibility in differentiating ESCs suggests that increased UTF1 levels in the absence of CDC14 prevent the proper firing of bivalent promoters required for differentiation. CDC14 phosphatases are dispensable for mitotic exit, suggesting that CDC14 phosphatases have evolved to control stemness rather than cell cycle exit and establish the CDK-CDC14 axis as a critical molecular switch for linking cell cycle regulation and self-renewal.

Periostin in the relation between periodontal disease and atherosclerotic coronary artery disease: A pilot randomized clinical study.

OBJECTIVE: The aim of this study was to analyze the effects of periodontal treatment on markers of atherosclerotic coronary artery disease and circulating levels of periostin. BACKGROUND: Periostin is necessary for periodontal stability, but it is highly present in atherosclerotic plaques. Treatment of periodontal disease, with low levels of local periostin, is thought to reduce systemic levels of periostin. Thus, this may contribute to cardiovascular health. METHODS: A pilot randomized controlled clinical trial was designed to include patients with severe periodontal disease and history of atherosclerotic coronary artery disease. Samples of gingival crevicular fluid (GCF) and serum were collected before and after periodontal treatment by periodontal surgery or non-surgical therapy. The levels of several markers of inflammation and cardiovascular damage were evaluated including CRP, IFN-γ, IL-1ß, IL-10, MIP-1α, periostin, and TNF-α in GCF and CRP, Fibrinogen, IFN-γ, IL-1ß, IL-6, IL-10, L-Selectin, MIP-1α, Periostin, TNF-α, and vWF in serum. RESULTS: A total of 22 patients with an average of 56 years old were recruited for participating in this study. Twenty of them were male. Most of them (82%) had suffered an acute myocardial event and underwent surgery for placing 1, 2, or 3 stents in the coronary arteries more than 6 months ago but less than 1 year. The treatment of periodontal disease resulted in an overall improvement of all periodontal parameters. Regarding the evaluation of GCF and serum, a significant increase of periostin in the GCF was observed after periodontal surgery. In contrast, although other markers in GCF and serum improved, no significant correlations were found. CONCLUSION: Treatment of periodontal disease through periodontal surgery induces a local and transient increase in the levels of periostin in the gingival crevicular fluid. The effects on systemic markers of inflammation and cardiovascular function have not been confirmed.

The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes.

In-depth analysis of the transcriptomes of several model organisms has revealed that genomes are pervasively transcribed, giving rise to an abundance of non-canonical and mainly antisense RNA polymerase II-derived transcripts that are produced from almost any genomic context. Pervasive RNAs are degraded by surveillance mechanisms, but the repertoire of proteins that control the fate of these non-productive transcripts is still incomplete. Trypanosomes are single-celled eukaryotes that show constitutive RNA polymerase II transcription and in which initiation and termination of transcription occur at a limited number of sites per chromosome. It is not known whether pervasive transcription exists in organisms with unregulated RNA polymerase II activity, and which factors could be involved in the process. We show here that depletion of RBP33 results in overexpression of ∼40% of all annotated genes in the genome, with a marked accumulation of sense and antisense transcripts derived from silenced regions. RBP33 loss does not result in a significant increase in chromatin accessibility. Finally, we have found that transcripts that increase in abundance upon RBP33 knockdown are significantly more stable in RBP33-depleted trypanosomes, and that the exosome complex is responsible for their degradation. Our results provide strong evidence that RBP33 dampens non-productive transcription in trypanosomes.

Preparing healthcare facilities in sub-Saharan Africa for future outbreaks: insights from a multi-country digital self-assessment of COVID-19 preparedness.

BACKGROUND: Despite previous experience with epidemics, African healthcare systems were inadequately prepared and substantially impacted by the coronavirus disease 2019 (COVID-19) pandemic. Limited information about the level of COVID-19 preparedness of healthcare facilities in Africa hampers policy decision-making to fight future outbreaks in the region, while maintaining essential healthcare services running. METHODS: Between May-November 2020, we performed a survey study with SafeCare4Covid - a free digital self-assessment application - to evaluate the COVID-19 preparedness of healthcare facilities in Africa following World Health Organization guidelines. The tool assessed (i) COVID-19-related capabilities with 31 questions; and (ii) availability of essential medical supplies with a 23-supplies checklist. Tailored quality improvement plans were provided after assessments. Information about facilities' location, type, and ownership was also collected. RESULTS: Four hundred seventy-one facilities in 11 African countries completed the capability assessment; 412 also completed the supplies checklist. The average capability score on a scale of 0-100 (n=471) was 58.0 (interquartile range 40.0-76.0), and the average supplies score (n=412) was 61.6 (39.0-83.0). Both scores were significantly lower in rural (capability score, mean 53.6 [95%CI:50.3-57.0]/supplies score, 59.1 [55.5-62.8]) versus urban facilities (capability score, 65.2 [61.7-68.7]/supplies score, 70.7 [67.2-74.1]) (P<0.0001 for both comparisons). Likewise, lower scores were found for public versus private clinics, and for primary healthcare centres versus hospitals. Guidelines for triage and isolation, clinical management of COVID-19, staff mental support, and contact tracing forms were largely missing. Handwashing stations were partially equipped in 33% of facilities. The most missing medical supply was COVID-19 specimen collection material (71%), while 43% of facilities did not have N95/FFP2 respirators and 19% lacked medical masks. CONCLUSIONS: A large proportion of public and private African facilities providing basic healthcare in rural areas, lacked fundamental COVID-19-related capabilities and life-saving personal protective equipment. Decentralization of epidemic preparedness efforts in these settings is warranted to protect healthcare workers and patients alike in future epidemics. Digital tools are of great value to timely measure and improve epidemic preparedness of healthcare facilities, inform decision-making, create a more stakeholder-broad approach and increase health-system resilience for future disease outbreaks.

Dysphagia and stenosis secondary to intramural esophageal pseudodiverticulosis.

We present the case of a patient with smoking, alcoholism, cirrhosis and HIV who was endoscopically diagnosed with esophageal candidiasis due to an episode of dysphagia. After treatment with antifungals and PPIs, the patient remained asymptomatic for almost 3 years. He presented an event of food impaction that was resolved by an upper endoscopy in which an esophageal stenosis and multiple esophageal pseudodiverticulosis were visualized. The biopsies only showed chronic nonspecific esophagitis. The stenosis was dilated with a balloon and PPIs were continued, with good response. Esophageal intramural pseudodiverticulosis is rare and can lead to motor disorders and strictures. It has a doubtful association with HIV and a clearer relationship with alcoholism, smoking, diabetes, reflux and candidiasis. The endoscopic diagnosis can be difficult so in order to make an accurate diagnosis is necessary an esophagram or CT. Treatment is based on controlling risk factors and dilating stenosis. The prognosis is usually favorable.

Estimating ambient air pollution mortality and disease burden and its economic cost in Barcelona.

BACKGROUND: The new WHO air quality guidelines indicate that the air pollution disease burden is greater than previously reported. We aimed to estimate the air pollution disease burden and its economic cost in Barcelona to inform local action. METHODS: We used a quantitative health impact assessment to estimate the non-accidental mortality and incidence of childhood asthma and lung cancer attributable to long-term air pollution exposure in the city of Barcelona (Spain) in 2018-2019. We used the population weighted mean of PM2.5 and NO2 assigned at the geocoded address during the study period and the 2021 WHO air quality guidelines as counterfactual scenario to estimate new annual cases attributable to each pollutant separately and combined. We estimated the social cost of attributable deaths and the health care cost of childhood asthma and lung cancer attributable cases. We also estimated attributable mortality by city district and the mortality avoidable by achieving the WHO air quality interim targets. RESULTS: Mean exposure was 17 µg/m3 for PM2.5 and 39 µg/m3 for NO2. Total combined air pollution attributable mortality was 13% (95%CI = 9%-17%), corresponding to 1,886 deaths (95%CI = 1,296-2,571) and a social cost of €1,292 million (95%CI = 888-1,762) annually. Fifty-one percent (95%CI = 21%-71%) and 17% (95%CI = 7%-29%) of new cases of childhood asthma and lung cancer were attributable to air pollution with a health care cost of €4.3 and €2.7 million, respectively. Achieving the first unmet WHO air quality interim targets for PM2.5 and for NO2 would avoid 410 deaths and €281 million annually. CONCLUSION: Air pollution in Barcelona represents a huge disease and economic burden, which is greater than previous estimates. Much stronger measures to reduce PM2.5 and NO2 levels are urgently needed. Until the WHO air quality guidelines are met in the city, achieving each WHO air quality interim targets would avoid hundreds of deaths each year.

An RNA-binding protein complex regulates the purine-dependent expression of a nucleobase transporter in trypanosomes.

Post-transcriptional regulation of gene expression is particularly important in trypanosomatid protozoa. RNA-binding proteins (RBPs) regulate mRNA stability and translation, yet information about how RBPs are able to link environmental cues to post-transcriptional control is scarce. In Trypanosoma brucei, we have previously characterized a short RNA stem-loop cis-element (PuRE, Purine Responsive Element) within the 3'-UTR of the NT8 nucleobase transporter mRNA that is necessary and sufficient to confer a strong repression of gene expression in response to purines. In this study, we have identified a protein complex composed of two RNA-binding proteins (PuREBP1 and PuREBP2) that binds to the PuRE in vitro and to NT8 mRNA in vivo. Depletion of PuREBP1 by RNA interference results in the upregulation of just NT8 and the mRNAs encoding the amino acid transporter AATP6 paralogues. Moreover, we found that the PuREBP1/2 complex is associated with only a handful of mRNAs, and that it is responsible for the observed purine-dependent regulation of NT8 expression.

Community outbreak of COVID-19 among people who use drugs attending a harm reduction centre in Barcelona, Spain.

BACKGROUND: The COVID-19 pandemic particularly affected the health of vulnerable population, such as people who use drugs. Due to compromised baseline health status, certain drug uses and settings and socioeconomic deprivation related to poverty and homelessness, drug users faced higher risk of COVID-19 infection. They had difficulty in adhering to the public health measures (i.e. physical distancing, hand hygiene and mask use). Also, the struggle to implement non-pharmaceutical actions (i.e. test-trace-isolate-quarantine strategy) among SARS-COV-2-infected drug users and their close contacts challenged the public health response. Therefore, this study aimed to describe a community COVID-19 outbreak and its approach among drug users of a harm reduction programme in an outpatient drug treatment centre in Barcelona, Spain. METHODS: We conducted an observational descriptive study of an outbreak of COVID-19 among people who use drugs attending the harm reduction programme of an outpatient drug treatment centre in the city of Barcelona, between July and October 2021 (n = 440). A passive search for cases was carried out with rapid antigens tests targeting symptomatic users who attended the facilities. RESULTS: Nineteen positive COVID-19 cases were identified among symptomatic drug users, between July and October 2021, with an attack rate of 4.3%. Specific measures were taken to control the outbreak, such as offering accommodation to self-isolate in a low-threshold residential resource to homeless drug users who tested positive and intensifying the vaccination strategy. The management of the outbreak was carried out in close collaboration between the outpatient centre and the main public health stakeholders in the city of Barcelona. CONCLUSIONS: This study shows the complexity of managing and investigating COVID-19 outbreaks in vulnerable population groups. Epidemiological control measures, such as the test-trace-isolate-quarantine strategy, were challenging to implement due to technology-related barriers and socioeconomic vulnerabilities, especially homelessness. Community-based interventions, cooperation among stakeholders and housing-related policies were helpful in tackling outbreaks among people who use drugs. When addressing vulnerable and hidden populations, the perspective of inequalities should be included in epidemiological surveillance and outbreak control strategies.

A rare endoscopic finding: primary esophageal melanoma.

We report a case of a patient accidentally diagnosed with an esophageal lesion compatible (histologically and immunohistochemically) with epithelioid melanoma. The skin examination did not reveal any evidence of melanoma and the patient was diagnosed with primary malignant melanoma of the esophagus. It's a very rare tumour. The majority of melanocytic lesions of the gastrointestinal tract are presumably secondary to a cutaneous melanoma and in order to discard this, a thorough skin examination is needed. Diagnosis is based on endoscopic image, histological data and especially on immunohistochemical evaluation. Primary malignant melanoma has a very poor prognosis as it usually presents distant metastasis when diagnosed. Surgery (with or without associated immunotherapy) remains the base of treatment in absence of advanced disease.

Esophageal stent placement for endoscopic treatment failure.

Up until approximately 10 years ago, the treatment for acute refractory esophageal variceal bleeding was balloon tamponading. Esophageal fully covered self-expanding stents are considered as effective as balloons and also much safer. They are kept in situ for longer periods, what eases the access to more definitive treatments with a low complication rate. We present 6 cases of patients with cirrhosis and massive bleeding due to esophageal varices refractory to conventional treatment, successfully treated with an esophageal fully covered self-expanding stent. There were no major complications, achieving an effective bleeding control in all cases.

National Institute on Aging Butler-Williams Scholars Program: The first 30 years.

The development of a skilled research workforce in aging is fundamental to understanding conditions associated with growing older and extending healthy, active years of life. The National Institutes of Health (NIH) supports the training of health scientists, and its National Institute on Aging (NIA) prioritizes the professional development of investigators with an interest in aging. Since 1987, NIA's Summer Institute on Aging Research, renamed the Butler-Williams (B-W) Scholars Program in 2013, has offered an intensive one-week experience on issues, opportunities, and challenges of research on aging, with emphasis on disparities and health equity. The first 30 years of the Program are described in this report, including its history, selected curriculum highlights, Scholar outcomes, and qualitative data from faculty, and the program's impact on the training, growth, and development of scientists in aging research. Questions raised over a decade ago by the Committee on the Future Health Care Workforce for Older Americans Board on Health Care Services are revisited, and recommendations for the future are provided. This important Program remains an exemplar for the training and development of health scientists for careers that advance biomedical research and emphasize an equitable understanding of factors related to extending healthy years of life.

Tackling health inequalities in a public health organization: the case of the Barcelona Public Health Agency.

BACKGROUND: Municipalities are important actors in the implementation of policies to tackle health inequalities, which requires political will, the availability of financial support, and technical and human resources. With the aim of aligning with local government political priorities, in 2017 the Barcelona Public Health Agency (Agència de Salut Pública de Barcelona, henceforth ASPB), which is responsible for the public health functions of the city, launched a strategy to improve the approach to tackling health inequalities in all its services. The objectives of this study were to show how social health inequalities were addressed in the ASPB from 2017 to 19 and to describe which actions were proposed after a participatory process aiming to create a plan to systematically incorporate health inequalities in ASPB actions. METHODS: The ASPB has 304 workers, 8 directors and 20 services or departments. Participatory methodologies were carried out: 1) semi-structured interviews with department heads (N = 12, 60%); 2) world cafe workshops open to a group of workers (N = 63, 37%); 3) a Quick and Colorful voting session open to a group of workers (N = 108, 63%); and 4) Hanlon matrix with 19 actions to be prioritized (N = 12 services, 60%). RESULTS: Semi-structured interviews and world cafe workshops provided 40 potential actions. After a step by step process of participatory prioritization, seven lines of action emerged: 1) to make progress in collaborative networking; 2) to promote policy evaluation; 3) to increase the ability of the ASPB to evaluate policies to reduce health inequalities; 4) to incorporate the axes of inequalities in all ASPB products; 5) to improve information on vulnerable groups; 6) to incorporate the gender perspective; and 7) to participate in an internal training plan to address health inequalities. CONCLUSIONS: The participation of ASPB public health professionals and staff allowed the organization to design a shared plan of actions to address health inequalities. This experience could be useful for other municipalities whose political agendas include tackling inequalities in health.

Multi-level policy responses to tackle socioeconomic inequalities in the incidence of COVID-19 in a European urban area.

BACKGROUND: Spain has been hit hard by COVID-19 since March 2020, especially in its metropolitan areas. We share experiences from Barcelona in measuring socioeconomic inequalities in the incidence of COVID-19 in the different waves, and in implementing coordinated and equity-oriented public health policy responses. METHODS: We collected daily data on confirmed COVID-19 cases, geocoded the address of residence to assign each case to one of the 73 neighborhoods and 1068 census tracts, and calculated the cumulative incidence of COVID-19 by neighborhood and five income groups (quintiles of census tracts) by sex across four waves of the pandemic. We adjusted hierarchical Bayesian spatial models to obtain the relative risk (RR) of cumulative incidences in each quintile compared with the richest areas. A variety of public health policies implemented to tackle the pandemic and especially these inequalities in COVID-19 incidence and vaccination are selected and described. RESULTS: Area-level income inequalities in the incidence of COVID-19 were present at different degree in all four waves. In the second wave (10/1/2020 to 12/6/2020), RR for the poorest income quintile census tracts compared with the richest was 1.43 (95% credible interval-CI-: 1.22-1.67) for men and 1.58 (95% CI: 1.35-1.83) for women. Later, inequalities in vaccination coverage also arose. Equity-oriented policy responses included: "health hotels" or home delivery of basic products for individuals with COVID-19 and without adequate conditions for isolation; new emergency facilities for homeless people, including those with active drug use; mass screening in high incidence areas; contingency plans for nursing homes and schools; adapting community health programs for their early reactivation; digital self-appointment support points and community vaccination days. CONCLUSION: COVID-19 hit Barcelona neighborhoods unequally, with variations between waves. The rapid availability of geolocalized data and by socioeconomic level helped public authorities to implement targeted policies and collaborative interventions for the most vulnerable populations. Further studies would be needed to evaluate their impact.

Prevalence of sexual harassment among young Spaniards before, during, and after the COVID-19 lockdown period in Spain.

BACKGROUND: Sexual harassment is a type of coercion, including social pressure, intimidation, physical force, and verbal acts, in addition to other forms such as cyber-harassment, recognized as a major important public health problem. METHODS: This cross-sectional study, based on a survey administered online to men and women aged 18 to 35 years and living in Spain throughout 15th and 28th October 2020, aims to analyze the prevalence and factors associated with sexual harassment among young people in Spain within the last 12 months, particularly according to the COVID-19 lockdown period. It has been conducted by bivariate analysis and robust Poisson regression models. The final sample includes 2.515 participants. RESULTS: The results indicate that women were almost twice as likely as men to experience sexual harassment (49% vs 22.2%). Also, among heterosexual men and women, the estimated prevalence was lower concerning that observed among bisexuals, gays, and lesbians (31.5% vs 53, 39.2, and 34.6% respectively). The prevalence percentage in the 18-24 age group was twice high as that observed in the 30-35 age group. Finally, during the lockdown period, the harassment through electronic channels increased (32.6% vs 16.5 and 17.8% before and after this period, respectively) and decreased on public roads (22.9% vs 63.4 and 54.4% pre-lockdown and post-lockdown periods, respectively). CONCLUSION: These findings highlight that sexual harassment presents a high prevalence among young people, especially cyber-harassment, and workplace harassment and it is important to be aware that young women are more likely to suffer harassment and even more if they do not have a partner or have LGB orientation. During the lockdown sexual harassment has moved from public spaces to the social network.

Involvement of the PI3K/AKT Intracellular Signaling Pathway in the AntiCancer Activity of Hydroxytyrosol, a Polyphenol from Olea europaea, in Hematological Cells and Implication of HSP60 Levels in Its Anti-Inflammatory Activity.

Hydroxytyrosol (HT), the main representative of polyphenols of olive oil, has been described as one of the most powerful natural antioxidants, also showing anti-inflammatory, antimicrobial, cardioprotective and anticancer activity in different type of cancers, but has been little studied in hematological neoplasms. The objective of this work was to evaluate the anticancer potential of HT in acute human leukemia T cells (Jurkat and HL60) and the anti-inflammatory potential in murine macrophages (Raw264.7). For this, cytotoxicity tests were performed for HT, showing IC50 values, at 24 h, for Jurkat, HL60 and Raw264.7 cells, of 27.3 µg·mL-1, 109.8 µg·mL-1 and 45.7 µg·mL-1, respectively. At the same time, HT caused cell arrest in G0/G1 phase in both Jurkat and HL60 cells by increasing G0/G1 phase and significantly decreasing S phase. Apoptosis and cell cycle assays revealed an antiproliferative effect of HT, decreasing the percentage of dividing cells and increasing apoptosis. Furthermore, HT inhibited the PI3K signaling pathway and, consequently, the MAPK pathway was activated. Inflammation tests revealed that HT acts as an anti-inflammatory agent, reducing NO levels in Raw264.7 cells previously stimulated by lipopolysaccharide (LPS). These processes were confirmed by the changes in the expression of the main markers of inflammation and cancer. In conclusion, HT has an anticancer and anti-inflammatory effect in the cell lines studied, which were Raw264.7, Jurkat, and HL60, and could be used as a natural drug in the treatment of liquid cancers, leukemias, myelomas and lymphomas.

Fused Cells between Human-Adipose-Derived Mesenchymal Stem Cells and Monocytes Keep Stemness Properties and Acquire High Mobility.

Human-adipose-derived mesenchymal stem cells (hADMSCs) are multipotent stem cells which have become of great interest in stem-cell therapy due to their less invasive isolation. However, they have limited migration and short lifespans. Therefore, understanding the mechanisms by which these cells could migrate is of critical importance for regenerative medicine. Methods: Looking for novel alternatives, herein, hADMSCs were isolated from adipose tissue and co-cultured with human monocytes ex vivo. Results: A new fused hybrid entity, a foam hybrid cell (FHC), which was CD90+CD14+, resulted from this co-culture and was observed to have enhanced motility, proliferation, immunomodulation properties, and maintained stemness features. Conclusions: Our study demonstrates the generation of a new hybrid cellular population that could provide migration advantages to MSCs, while at the same time maintaining stemness properties.

Performance and Implementation Evaluation of the Abbott BinaxNOW Rapid Antigen Test in a High-Throughput Drive-Through Community Testing Site in Massachusetts.

Rapid diagnostic tests (RDTs) for SARS-CoV-2 antigens (Ag) that can be performed at point of care (POC) can supplement molecular testing and help mitigate the COVID-19 pandemic. Deployment of an Ag RDT requires an understanding of its operational and performance characteristics under real-world conditions and in relevant subpopulations. We evaluated the Abbott BinaxNOW COVID-19 Ag card in a high-throughput, drive-through, free community testing site in Massachusetts using anterior nasal (AN) swab reverse transcriptase PCR (RT-PCR) for clinical testing. Individuals presenting for molecular testing in two of seven lanes were offered the opportunity to also receive BinaxNOW testing. Dual AN swabs were collected from symptomatic and asymptomatic children (≤18 years of age) and adults. BinaxNOW testing was performed in a testing pod with temperature/humidity monitoring. One individual performed testing and official result reporting for each test, but most tests had a second independent reading to assess interoperator agreement. Positive BinaxNOW results were scored as faint, medium, or strong. Positive BinaxNOW results were reported to patients by phone, and they were instructed to isolate pending RT-PCR results. The paired RT-PCR result was the reference for sensitivity and specificity calculations. Of 2,482 participants, 1,380 adults and 928 children had paired RT-PCR/BinaxNOW results and complete symptom data. In this study, 974/1,380 (71%) adults and 829/928 (89%) children were asymptomatic. BinaxNOW had 96.5% (95% confidence interval [CI], 90.0 to 99.3) sensitivity and 100% (95% CI, 98.6 to 100.0) specificity in adults within 7 days of symptoms and 84.6% (95% CI, 65.1 to 95.6) sensitivity and 100% (95% CI, 94.5 to 100.0) specificity in children within 7 days of symptoms. Sensitivity and specificity in asymptomatic adults were 70.2% (95% CI, 56.6 to 81.6) and 99.6% (95% CI, 98.9 to 99.9), respectively, and in asymptomatic children, they were 65.4% (95% CI, 55.6 to 74.4) and 99.0% (95% CI, 98.0 to 99.6), respectively. By cycle threshold (CT ) value cutoff, sensitivity in all subgroups combined (n = 292 RT-PCR-positive individuals) was 99.3% with CT values of ≤25, 95.8% with CT values of ≤30, and 81.2% with CT values of ≤35. Twelve false-positive BinaxNOW results (out of 2,308 tests) were observed; in all 12, the test bands were faint but otherwise normal and were noted by both readers. One invalid BinaxNOW result was identified. Interoperator agreement (positive versus negative BinaxNOW result) was 100% (n = 2,230/2,230 double reads). Each operator was able to process 20 RDTs per hour. In a separate set of 30 specimens (from individuals with symptoms ≤7 days) run at temperatures below the manufacturer's recommended range (46 to 58.5°F), sensitivity was 66.7% and specificity 95.2%. BinaxNOW had very high specificity in both adults and children and very high sensitivity in newly symptomatic adults. Overall, 95.8% sensitivity was observed with CT values of ≤30. These data support public health recommendations for use of the BinaxNOW test in adults with symptoms for ≤7 days without RT-PCR confirmation. Excellent interoperator agreement indicates that an individual can perform and read the BinaxNOW test alone. A skilled laboratorian can perform and read 20 tests per hour. Careful attention to temperature is critical.

Impact of a community contraceptive counselling intervention on adolescent fertility rates: a quasi-experimental study.

BACKGROUND: From 2000 to 2008, in urban areas in Spain, adolescent fertility and abortion rates underwent unprecedented increases, consecutive to intensive immigration from developing countries. To address unmet needs for contraception information and services, a community-based, gender-sensitive and culturally adapted brief counselling intervention (SIRIAN program) was launched in some deprived neighbourhoods with a high proportion of immigrants in Barcelona. Once a randomized controlled trial demonstrated its effectiveness in increasing the use of contraceptives, we aim to examine its population impact on adolescent fertility rates. METHODS: Quasi-experimental study with comparison group, using population data from 2005 to 2016. Five neighbourhoods in the lowest tercile of Disposable Household Income were intervened in 2011-13. The comparison group included the three neighbourhoods which were in the same municipal district and in the lowest Disposable Household Income tercile, and displayed the highest adolescent fertility rates. Generalized linear models were fitted to assess absolute adolescent fertility rates and adjusted by immigrant population between pre-intervention (2005-10) and post-intervention periods (2011-16); Difference in Differences and relative pre-post changes analysis were performed. RESULTS: In 2005-10 the intervention group adolescent fertility rate was 27.90 (per 1000 women 15-19) and 21.84 in the comparison group. In 2011-16 intervention areas experienced great declines (adolescent fertility rate change: - 12.30 (- 12.45 to - 12.21); p < 0.001), while comparison neighbourhoods remained unchanged (adolescent fertility rate change: 1.91 (- 2.25 to 6.07); p = 0.368). A reduction of - 10.97 points (- 13.91 to - 8.03); p < 0.001) is associated to the intervention. CONCLUSION: Adolescent fertility rate significantly declined in the intervention group but remained stable in the comparison group. This quasi-experimental study provide evidence that, in a country with universal health coverage, a community counselling intervention that increases access to contraception, knowledge and sexual health care in hard-to-reach segments of the population can contribute to substantially reduce adolescent fertility rates. Reducing adolescent fertility rates could become a feasible goal in cities with similar conditions.

Social Inequalities in Fertility in Women Residing in Urban Neighbourhoods in Spain: A Multilevel Approach.

BACKGROUND: Reproductive health inequalities tend to be more marked in large cities because they include neighbourhoods with unequal social and community networks, resources and opportunities. The aim was to describe social inequalities in fertility patterns among women who gave birth between 2007 and 2016 in the city of Barcelona (Spain) by jointly evaluating the effect of individual and socioeconomic neighbourhood characteristics. METHODS: We conducted a multilevel study of women's individual characteristics (age, educational attainment, and country of origin) and neighbourhood characteristics (disposable household income, percentage of unemployment and percentage of foreigners). RESULTS: Multilevel modelling revealed significant variability in fertility across neighbourhoods after adjustment for individual explanatory variables. The fertility rate (FR) was higher in better educated women (adjusted relative risk: aRR 2.76), those aged 30-39 years (aRR 2.13), and in those born in Spain in relation to their respective reference groups. The FR was lowest in women with upper to post-secondary, non-tertiary education (aRR 0.86) who were born in high income countries (aRR 0.57). Women living in neighbourhoods with a low income (aRR 1.46) and with a higher unemployment (aRR 1.33) were more likely to have children. In contrast, women living in neighbourhoods with a lower percentage of foreigners had the lowest FR (aRR 0.81). CONCLUSIONS: The neighbourhood's characteristics played an important role in fertility patterns, independently of women's individual characteristics. At the contextual level, the highest FR was found in the poorest settings, highlighting inequalities. At the individual level, the FR was highest among women with higher education and in their thirties.

Antiproliferative and Pro-Apoptotic Effect of Uvaol in Human Hepatocarcinoma HepG2 Cells by Affecting G0/G1 Cell Cycle Arrest, ROS Production and AKT/PI3K Signaling Pathway.

Natural products have a significant role in the development of new drugs, being relevant the pentacyclic triterpenes extracted from Olea europaea L. Anticancer effect of uvaol, a natural triterpene, has been scarcely studied. The aim of this study was to understand the anticancer mechanism of uvaol in the HepG2 cell line. Cytotoxicity results showed a selectivity effect of uvaol with higher influence in HepG2 than WRL68 cells used as control. Our results show that uvaol has a clear and selective anticancer activity in HepG2 cells supported by a significant anti-migratory capacity and a significant increase in the expression of HSP-60. Furthermore, the administration of this triterpene induces cell arrest in the G0/G1 phase, as well as an increase in the rate of cell apoptosis. These results are supported by a decrease in the expression of the anti-apoptotic protein Bcl2, an increase in the expression of the pro-apoptotic protein Bax, together with a down-regulation of the AKT/PI3K signaling pathway. A reduction in reactive oxygen species (ROS) levels in HepG2 cells was also observed. Altogether, results showed anti-proliferative and pro-apoptotic effect of uvaol on hepatocellular carcinoma, constituting an interesting challenge in the development of new treatments against this type of cancer.