ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection.

Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent of Coronavirus Disease 2019 (COVID-19). Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchoalveolar lavage fluid (BALF) from critically ill COVID-19 patients was associated with reduced intensive care unit (ICU) and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.

Use of Blockchain Technology in the Domain of Physical Exercise, Physical Activity, Sport, and Active Ageing: A Systematic Review.

Blockchain technology provides a distributed support for information storage and traceability. Recently, it has been booming in a wide variety of domains: finance, food, energy, and health. In the field of physical activity, physical exercise, sport, and active ageing, this technology could also originate some interesting services introducing support for reliable repository of results, for gamification, or for secure data interchange. This systematic review explores the use of blockchain in this context. The objective is to determine to which extent this technology has fulfilled the potential of blockchain to bring these new added-value services. The authors explored 5 repositories in search of papers describing solutions applied to the above-mentioned frame. 17 papers were selected for full-text analysis, and they displayed diverse applications of blockchain, such as Fitness and healthcare, Sport, and Active ageing. A detailed analysis shows that the solutions found do not leverage all the possibilities of blockchain technology. Most of the solutions analyzed use blockchain for managing, sharing, and controlling access to data and do not exploit the possibilities of Smart Contracts or oracles. Additionally, the advantages of the blockchain model have not been fully exploited to engage users using approaches such as gamification.

ACE2-containing defensosomes serve as decoys to inhibit SARS-CoV-2 infection.

Extracellular vesicles of endosomal origin, exosomes, mediate intercellular communication by transporting substrates with a variety of functions related to tissue homeostasis and disease. Their diagnostic and therapeutic potential has been recognized for diseases such as cancer in which signaling defects are prominent. However, it is unclear to what extent exosomes and their cargo inform the progression of infectious diseases. We recently defined a subset of exosomes termed defensosomes that are mobilized during bacterial infection in a manner dependent on autophagy proteins. Through incorporating protein receptors on their surface, defensosomes mediated host defense by binding and inhibiting pore-forming toxins secreted by bacterial pathogens. Given this capacity to serve as decoys that interfere with surface protein interactions, we investigated the role of defensosomes during infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of COVID-19. Consistent with a protective function, exosomes containing high levels of the viral receptor ACE2 in bronchioalveolar lavage fluid from critically ill COVID-19 patients was associated with reduced ICU and hospitalization times. We found ACE2+ exosomes were induced by SARS-CoV-2 infection and activation of viral sensors in cell culture, which required the autophagy protein ATG16L1, defining these as defensosomes. We further demonstrate that ACE2+ defensosomes directly bind and block viral entry. These findings suggest that defensosomes may contribute to the antiviral response against SARS-CoV-2 and expand our knowledge on the regulation and effects of extracellular vesicles during infection.

Adherence to triage among women with HPV-positive self-collection: a study in a middle-low income population in Argentina.

INTRODUCTION: Screening for cervical cancer (CC) prevention has substantially changed with the introduction of human papillomavirus (HPV) tests. This technology compared to cytology has increased the detection of pre-malignant and malignant cervical lesions in real-world programmes in different settings. Very importantly, through self-collection, HPV testing can reduce barriers to screening and increase coverage. However, when using HPV self-collection, triage tests are a key step in the CC prevention process, and high adherence to triage has been difficult to obtain in low-middle income settings. The aim of this study was to measure adherence to triage among women with HPV+ self-collection and analysed factors associated with this adherence in a middle-low resource setting in Argentina. We also evaluated key indicators related to the implementation of the HPV self-collection strategy. METHODS: We analysed data on screening/triage/diagnosis/treatment from women aged 30+ who performed self-collection between 2015 and 2017 (n = 15,763), in the public health system in Tucuman, Argentina. We analysed secondary data from the national screening information system. The primary outcomes were: 1) adherence to cytology triage within the recommended timeframe (120 days) and 2) overall adherence to cytology triage including data at 18 months after screening. Multivariable regression was used to examine the association between age group, year of the screening test, record of the previous Pap-based screening and health insurance status with adherence to triage test as a primary outcome. We reported odds ratios, 95% confidence intervals and p-value of 0.05, which was considered the threshold for p-values). RESULTS: We analysed data of 2,389 HPV+ women. The overall adherence to triage at 18 months was 42.9%. The percentage of women completing cytology triage within the recommended timeframe of 120 days was lower (25.2%). Women with the record of a previous Pap-based screening had 1.86 times the odds of having a triage compared to women without a record of a previous Pap-based screening (95% CI: 1.64-2.64, p <0.001). Furthermore, the probability of having triage at the recommended timeframe was higher among women who were older and women with public health insurance. CONCLUSIONS: Our results showed that adherence to triage in the recommended timeframe was low. In addition, the probability of having triage at the recommended timeframe was higher among women with a record of a previous Pap-based screening, a proxy of the use of health services. Our results showed that adherence to triage in the context of the HPV-self-collection strategy is challenging. The implementation of alternative approaches that might facilitate adherence to triage should be further investigated.

Making the Best Use of Resources in Global Cancer Care.

Inequitable access to high-quality cancer control and care remains one of the greatest public health challenges in countries at all resource levels. Core issues include the limited oncology health care workforce and equitable access to affordable (essential) cancer diagnostics, medicines, surgery, systemic therapies, and radiotherapy, compounded by existing social inequalities. To reduce cancer health disparities globally and subnationally, countries can enhance their capabilities to deliver high-quality, affordable care closer to where most people live. Decentralization and integration of health services can be part of the solution, offloading the strained capacity of tertiary facilities where possible and expanding cadres of trained providers to support some aspects of cancer prevention and control that require a lesser degree of specialization. The strategy to eliminate cervical cancer provides a salient example of a data-driven effort that optimizes resources to dramatically reduce one of the greatest cancer health disparities globally. Here, we highlight two responses to meet the challenge through greater engagement of the primary care workforce and by adoption of universal health care coverage to ensure access to cancer prevention.

Psycho-social impact of positive human papillomavirus testing in Jujuy, Argentina results from the Psycho-Estampa study.

Human papillomavirus (HPV) testing can have a negative impact on women's lives which might also result in abandoning the follow-up and treatment process. This study measured the psycho-social impact of HPV-positivity among HPV-tested women from Jujuy, Argentina, a middle-low income setting. In this cross-sectional study (2015-2016), the psycho-social impact of HPV-positivity was measured using the Psycho-Estampa Scale, specifically designed and validated to be used in screening contexts. We measured mean scores for each of the five scale domains, and the Overall Impact score (Values from 1: No impact to 4: Heavy impact). We compared scores according to cytology triage diagnosis using ordinal logistic regression. A total of 163 HPV-positive women were recruited at the Centro Carlos Alvarado hospital and included in the study sample; of these, 124 (76.1%) had normal triage cytologies. The overall Impact score was between low and moderate (mean:2.56, SD:0.65). The highest psycho-social impact was measured in the Worries about cancer and treatment domain (mean score:3.60, SD:0.60), followed by Sexuality domain (mean:2.50; SD:1.00). The Uncertainty about information provided by health providers domain had the lowest mean score (mean:2.14, SD:0.73). Compared to women with normal cytologies (n = 124), women with abnormal cytologies (n = 39) had a higher likelihood of greater overall Psycho-social Impact (OR: 2.91; p = 0.0036). No statistically significant differences were found in scores of specific domains according to cytology results. It is important to devise specific counseling interventions to reduce the psycho-social impact of HPV-Testing as primary screening and its potential effect on completion of the diagnosis/ treatment process.

Adherencia al triaje en contexto de tamizaje con autotoma del test de virus del papiloma humano en la provincia de Jujuy / riage of Women with Human Papillomavirus Self-Collection in Jujuy Province

INTRODUCCIÓN: Es reconocida la efectividad del test del virus del papiloma humano (VPH) para prevenir el cáncer cervicouterino (CC), así como su potencial para reducir barreras de acceso al tamizaje a través de su modalidad autotoma (ATVPH). Uno de los principales desafíos consiste en garantizar el acceso a la citología de triaje de las mujeres con AT-VPH positivas (VPH+). El objetivo de este estudio fue analizar la magnitud y los determinantes sociales de la adherencia al triaje (realización de citología posterior a un resultado de test de VPH+) en mujeres de 30 años o más con AT-VPH+ dentro del sistema público de salud de la provincia de Jujuy. MÉTODOS: Se efectuó un estudio descriptivo transversal con análisis del Sistema de Información para el Tamizaje (SITAM) y encuestas domiciliarias a mujeres de 30 años o más con autotomas positivas en Jujuy durante 2015-2016, sin registro de triaje. RESULTADOS: El porcentaje estimado de adherencia al triaje fue de entre 96% y 81%. Estos porcentajes son menores a los 60 y 120 días de realizada la AT (18% y 35%, respectivamente). Las mujeres con cobertura de obra social/privada y sin condición de hacinamiento poseen mayor probabilidad de adherir al triaje. El principal motivo de no adherencia fueron los problemas con la entrega de resultados. CONCLUSIONES: Pese a los altos niveles de adherencia al triaje, es necesario incorporar intervenciones que mejoren la entrega de resultados y ayuden a enfrentar las barreras socioestructurales

Programmatic human papillomavirus testing in cervical cancer prevention in the Jujuy Demonstration Project in Argentina: a population-based, before-and-after retrospective cohort study.

BACKGROUND: Human papillomavirus (HPV) testing for cervical cancer prevention was introduced in Argentina through the Jujuy Demonstration Project (2011-14). The programme tested women aged 30 years and older attending the public health system with clinician-collected HPV tests. HPV self-collection was introduced as a programmatic strategy in 2014. We aimed to evaluate the effectiveness of programmatic HPV testing to detect cervical intraepithelial neoplasia (CIN) of grade 2 or worse (CIN2+) in comparison with cytology-based screening. METHODS: We did a population-based, before-and-after retrospective cohort study using data from the National Cervical Cancer Prevention Program for the Jujuy province in northwest Argentina. We obtained data for the cytology-based screening period from Jan 1, 2010, until Dec 31, 2011, and for the HPV-based screening period from Jan 1, 2012, until Dec 31, 2014. The primary outcome was detection of histologically diagnosed CIN2+ among women aged 30 years and older. To assess the outcomes in all individuals included in the study, we used multivariable logistic regression and propensity score matching. The reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) framework was used for the before-and-after analysis of programmatic dimensions. FINDINGS: Of the 29 631 women who underwent cytology-based screening in 2010-11, CIN2+ was detected in 236 (0·8%) individuals. Of the 49 565 women HPV tested in 2012-14 (clinician-collected tests, n=44 700; self-collection tests, n=4865), 693 (1·4%; 658 clinician-collected tests; 35 self-collection tests) were found to have CIN2+ after the first round of screening. Compared with cytology-based screening, the odds ratio of being diagnosed with a CIN2+ lesion was 2·34 (95% CI 2·01-2·73; p<0·0010) with clinician-collected tests, and 1·08 (0·74-1·52; p=0·68) when screened with self-collection tests, after controlling for age and health insurance status. Screening coverage was similar in both periods (52·7% vs 53·2%); improvements of programmatic indicators were observed in the HPV testing period in relation to laboratory centralisation, lower overscreening (6·6% vs 0·0%), higher adherance to age recommendations (79·3% vs 98·8%), and a decrease of inadequate samples (3·6% vs 0·2%). INTERPRETATION: HPV testing in middle-income settings increases detection of CIN2+ lesions and allows for improvement of programmatic indicators. Evidence suggests that the introduction of HPV testing will accelerate the reduction of cervical cancer burden. FUNDING: Argentinian National Cancer Institute and National Council of Scientific and Technologic Research.

Factors associated with low adherence to cervical cancer follow-up retest among HPV+/ cytology negative women: a study in programmatic context in a low-income population in Argentina.

BACKGROUND: Cervical Cancer is still a major public health challenge in low and middle-income countries. HPV testing has been an innovative approach, which was introduced in Argentina for women aged 30+ through the Jujuy Demonstration Project (JDP) carried out between 2012 and 2014. After a positive HPV-test, cytology is used as triage method. Under this protocol, the group of women with HPV+ and normal cytology are recommended to repeat the test within 12-18 months. Studies have shown that this group has increased risk of CIN2+, however, assuring high levels of repeating test among these women is difficult to achieve. We analyze those factors associated with lower re-test attendance among HPV+/ cytology negative women at a programmatic level in low-middle income settings. METHODS: We used data of women aged 30+ HPV-tested in the JDP and followed until 2018 (n = 49,565). We performed a set of different adjusted logistic regression models. Primary outcomes were re-test attendance and re-test attendance within recommended timeframe. We assessed as covariates age, health insurance status, year of HPV-testing, Pap testing in the past 3 years, HPV-testing modality (clinician-collected (CC) tests/self-collected (SC) tests), and span between HPV-test collection and report of results. RESULTS: Forty nine thousand five hundred sixty five women were HPV-tested and 6742 had a positive HPV-test. Among HPV+ women, a total of 4522 were HPV+/Cytology negative (67.1%). In total, 3172 HPV+/Cytology negative women (70.1%) had a record of a second HPV test as of March 2018. Only 1196 women (26%) completed the second test within the timeframe. Women with no record of a previous Pap (OR: 0.46, 95% CI: 0.4-0.53, p < 0.001), aged 64+ (OR: 0.46, 95% CI: 0.31-0.68, p < 0.001) were less likely to be retested; while women with clinician-collected samples had higher odds of being re-tested (OR: 1.42, 95% CI: 1.06-1.91, p < 0.001). CONCLUSIONS: Low re-test rates were found in HPV +/ normal cytology women. Tailored interventions are needed to increase the effectiveness of the screening in this group, especially for those women with characteristics associated to lower attendance.

Guidelines for safe handling of hazardous drugs: A systematic review.

OBJECTIVE: To review the scientific literature related to the safe handling of hazardous drugs (HDs). METHOD: Critical analysis of works retrieved from MEDLINE, the Cochrane Library, Scopus, CINHAL, Web of Science and LILACS using the terms "Hazardous Substances", "Antineoplastic Agents" and "Cytostatic Agents", applying "Humans" and "Guidelines" as filters. Date of search: January 2017. RESULTS: In total, 1100 references were retrieved, and from those, 61 documents were selected based on the inclusion and exclusion criteria: 24 (39.3%) documents related to recommendations about HDs; 27 (44.3%) about antineoplastic agents, and 10 (33.3%) about other types of substances (monoclonal antibodies, gene medicine and other chemical and biological agents). In 14 (23.3%) guides, all the stages in the manipulation process involving a risk due to exposure were considered. Only one guide addressed all stages of the handling process of HDs (including stages with and without the risk of exposure). The most described stages were drug preparation (41 guides, 67.2%), staff training and/or patient education (38 guides, 62.3%), and administration (37 guides, 60.7%). No standardized informatics system was found that ensured quality management, traceability and minimization of the risks associated with these drugs. CONCLUSIONS: Most of the analysed guidelines limit their recommendations to the manipulation of antineoplastics. The most frequently described activities were preparation, training, and administration. It would be convenient to apply ICTs (Information and Communications Technologies) to manage processes involving HDs in a more complete and simpler fashion.

Plataforma de e-servicios para educación e higiene nutricionales, orientada a la población infantil / E-services platform for child-oriented nutritional education and health

Una buena alimentación es uno de los pilares básicos para el correcto desarrollo tanto físico como intelectual de los niños. En una sociedad en la que cada vez la edad de escolarización de los pequeños es más temprana, la coordinación entre familia y escuela adquiere un rol vital para garantizar una correcta alimentación y cuidado del niño. Este artículo presenta los fundamentos de una plataforma web multidispositivo que favorece la colaboración y formación nutricional de los diferentes agentes involucrados en los procesos de cuidado y educación de los niños (padres, educadores, especialistas), haciendo uso de los últimos avances producidos en el campo de las tecnologías semánticas para mejorar la precisión y adecuación de las recomendaciones realizadas automáticamente por el sistema.

A good diet is one of the pillars for ensuring the proper physical and intellectual development of children. In a society in which schooling is initiated at increasingly early ages, the coordination between school and family acquires a vital role in assuring proper child nourishment and care. This article presents the foundations of a multi-device web platform that fosters the collaboration and nutritional training of the different actors (parents, educators, specialists) involved in the processes of care and education of children. The platform uses the latest advances in the field of semantic technologies to improve the accuracy of the recommendations made automatically by the system.

Functional evidence of des-Arg10-kallidin enzymatic inactivating pathway in isolated human umbilical vein.

It has been known for many years that plasma and tissues contain a variety of enzymes capable of metabolizing kinins. The aim of the present study was to evaluate, by means of functional studies in a capacitance vessel such as the human umbilical vein (HUV), the possible role played by the metallopeptidases angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP), and aminopeptidase M (APM) as an inactivating pathway of the B(1) receptor endogenous agonist des-Arg(10)-kallidin (DAKD). In HUV rings with and without endothelium, concentration-response curves (CRCs) to DAKD were determined after a 300-min incubation period, and enzymatic inhibitors were added to the organ baths 30 min before construction of the CRC. Presence of endothelial layer was confirmed by histological studies. There was a significant leftward shift observed in control HUV rings devoid of endothelium compared with intact tissues. Exposure to 1 microM captopril (ACE inhibitor) potentiated DAKD-elicited vasoconstrictor responses in HUV rings with endothelium while no such effect was observed in tissues devoid of endothelium. Application of 10 microM amastatin (APM inhibitor) induced a leftward shift of DAKD-elicited contractile responses in HUV with and without endothelium. On the other hand, 10 microM phosphoramidon (NEP inhibitor) showed no potentiating effect in HUV rings either with or without endothelium. However, under concurrent inhibition of ACE, NEP and APM, there was a higher potentiation of DAKD-elicited contractile responses compared with the effect observed with combined inhibition of ACE and APM. Moreover, when we evaluated contractile responses induced by Sar(0)-D-Phe(8)-des-Arg(9)-BK (a metabolically protected B(1) receptor agonist), no potentiating effect was observed under triple enzymatic inhibition. In conclusion, in the present study for the first time, we demonstrated in a capacitance vessel, HUV, that metallopeptidases ACE, NEP and APM represent a relevant functional inactivation pathway of DAKD.

[Comparative analysis of various techniques for the repair of stress urinary incontinence in women. Review of our experience]. / Análisis comparativo de diferentes técnicas para la corrección de la incontinencia de stress en la mujer. Revisión de nuestra experiencia.

OBJECTIVE: We aim to expose our experience in the surgical correction of stress urinary incontinence (SUI) and to analyze the possible factors that could modify the outputs of this type of surgery. METHODS: We have studied 114 women who underwent surgery (60 Raz, 36 Burch, and 18 vaginal wall sling), with a mean follow-up time of 10.5 months. RESULTS: We have not succeeded in demonstrating that preoperative factors such as age, irritative voiding symptoms; history of prior hysterectomy or urethropexia, neurological disease, diabetes or recurrent urinary tract infections; the finding of cistocele, a positive Bonney-Marchetti test or bladder unstability, play any role in the outputs. The failure rate was 16.7% for vaginal wall sling procedure, 35% Raz, and 33.3% Burch. "Survival" analysis did not demonstrate differences related to the procedure or the surgeon. We discovered and important decrease of continence rate with time from the intervention. Higher incidence of postoperative pain, urinary retention and greater residual urine were detected with transvaginal procedures. There was no difference in the incidence of wound infection. CONCLUSIONS: We don't believe that the selection of candidates for this type of surgery should be carried out in base to the above mentioned preoperative factors. Also, we observed a consistent decrease of postoperative continence with time. Finally, we have detected a greater incidence of complications after transvaginal procedures.

[Limitations of ultrasonography in the clinical course monitoring of bladder tumors]. / Limitaciones de la ecografía en el control evolutivo de los tumores vesicales.

Ultrasonography is a fairly innocuous test in the follow-up of bladder tumours. Its results, however, can not be superposed to those of cystoscopy. This study aims to identify the risk factors for failure of transabdominal ultrasonography in the FU of bladder tumors. The influence of the primary tumour, sex and age of patients on the ability of ultrasonography to detect relapses was analyzed. Chi square and Student's t tests were used to associate the characteristics of primary tumours and patients to the results of ultrasonography. Student's t test was used to estimate the effect of diagnostic oversight in terms of annual recurrence rate and progression. The characteristics of primary tumours where relapse was detected or overlooked had no influence on the results of ultrasound follow-up as neither did age and sex. No differences were detected in recurrence rate of patients with anticipated (0.57) or overlooked (0.58) tumours. Although differences in progression rates (4.76% and 9% for overlooked and identified tumours, respectively) were substantial, they did not reach statistical significance. There are no features in the original tumour or the patient to anticipate the failure of ultrasound monitoring. Multiple and/or small relapses are overlooked more frequently that single and/or large ones, and tumours located in lateral walls, base and dome may be unnoticed. In spite of oversights, alternate ultrasound/cystoscopic monitoring does not compromise the outcome of the disease.

[A paratesticular myxoid liposarcoma as a simulator of a hernial process. A case report]. / Liposarcoma mixoide paratesticular como simulador de proceso herniario. Descripción de un caso.

OBJECTIVE: To describe a case of paratesticular liposarcoma in a 69-year-old male. The literature is briefly reviewed and the prognostic and therapeutic aspects are discussed. METHODS/RESULTS: The patient was submitted to surgery. Pathological analysis of the surgical specimen disclosed a myxoid liposarcoma with undifferentiated pleomorphic areas. Patient follow up has shown no recurrence or metastasis. CONCLUSIONS: This tumor type develops in scrotal soft tissue, slowly increasing scrotal size, and should be distinguished from inguinoscrotal hernia. Together with physical examination, ultrasonography is generally useful. Treatment is by radical orchiectomy through an inguinal approach; the role of adjuvant therapy remains unclear. It has a good prognosis, with frequent local relapses; metastatic spread is uncommon.