Smell loss associated with SARS-CoV-2 is not clinically different from other viruses: a multicenter cohort study.

BACKGROUND: Although the COVID-19 pandemic has increased the prevalence of cases with olfactory loss, other respiratory viruses can also cause this condition. We aimed to compare the prevalence of acute SARS-CoV-2 infection and other respiratory viruses in patients with sudden smell loss, and to assess the impact of SARS-CoV-2 viral load and co-infection on olfactory symptoms. METHODS: Patients with sudden smell loss were recruited in a multicenter prospective cohort study in 15 hospitals in Brazil. Clinical questionnaire, Connecticut Chemosensory Clinical Research Center (CCCRC) olfactory test and nasopharyngeal swab to perform a PCR-based respiratory viral panel were collected at first visit (day 0) and 30 and 60 days after recruitment. RESULTS: 188 of 213 patients presented positive test result for SARS-CoV-2, among which 65 were co-infected with other respiratory viruses (e.g., rhinovirus, enterovirus, and parainfluenza). 25 had negative test results for SARS-CoV-2. Patients in both SARSCoV-2 and non-SARS-CoV-2 groups had objective anosmia (less than 2 points according to the psychophysical olfactory CCCRC) at day 0, with no significant difference between them. Both groups had significant smell scores improvement after 30 and 60 days, with no difference between them. Co-infection with other respiratory viruses, and SARS-CoV-2 viral load did not impact olfactory scores. CONCLUSION: Patients with sudden smell loss associated with SARS-CoV-2 and other respiratory viruses had similar presentation, with most participants initiating with anosmia, and total or near total recovery after 60 days. SARS-CoV-2 viral load and co-infections with other respiratory viruses were not associated with poorer olfactory outcomes.

The Tumor Microenvironment: An Introduction to the Development of Microfluidic Devices.

The tumor microenvironment (TME) is like the Referee of a soccer match who has constant eyes on the activity of all players, such as cells, acellular stroma components, and signaling molecules for the successful completion of the game, that is, tumorigenesis. The cooperation among all the "team members" determines the characteristics of tumor, such as the hypoxic and acidic niche, stiffer mechanical properties, or dilated vasculature. Like in soccer, each TME is different. This heterogeneity makes it challenging to fully understand the intratumor dynamics, particularly among different tumor subpopulations and their role in therapeutic response or resistance. Further, during metastasis, tumor cells can disseminate to a secondary organ, a critical event responsible for approximately 90% of the deaths in cancer patients. The recapitulation of the rapidly changing TME in the laboratory is crucial to improve patients' prognosis for unraveling key mechanisms of tumorigenesis and developing better drugs. Hence, in this chapter, we provide an overview of the characteristic features of the TME and how to model them, followed by a brief description of the limitations of existing in vitro platforms. Finally, various attempts at simulating the TME using microfluidic platforms are highlighted. The chapter ends with the concerns that need to be addressed for designing more realistic and predictive tumor-on-a-chip platforms.

Quantitative Viral Outgrowth Assay to Measure the Functional SIV Reservoir in Myeloid Cells.

The role of CD4+ T cells in HIV infection and the latent reservoir, that is, latently infected cells that harbor replication competent virus, has been rigorously assessed. We have previously reported a quantitative viral outgrowth assay (QVOA) for SIV that demonstrated the frequency of latently infected CD4+ T cells is approximately 1 in a million cells, similar to that of HIV infected individuals on ART. However, the frequency of productively infected monocytes in blood and macrophages in tissues has not been similarly studied. Myeloid cells are infected during acute HIV and SIV infection; however, unlike lymphocytes, they are resistant to the cytopathic effects of the virus. Moreover, tissue-resident macrophages have the ability to self-renew and persist in the body for months to years. Thus, tissue macrophages, once infected, have the characteristics of a stable viral reservoir. A better understanding of the number of productively infected macrophages is critical to understanding the role of infected myeloid cells as a viral reservoir. In order to assess the functional latent reservoir. we have developed specific QVOAs for monocytes in blood, and macrophages in spleen, BAL and brain, which are described in detail in this chapter.

Modulation of inflammation by anti-TNF α mAb-dendrimer nanoparticles loaded in tyramine-modified gellan gum hydrogels in a cartilage-on-a-chip model.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease characterized by joint inflammation. Since the inflammatory condition plays an important role in the disease process, it is important to develop and test new therapeutic approaches that specifically target and treat joint inflammation. In this study, a human 3D inflammatory cartilage-on-a-chip model was established to test the therapeutic efficacy of anti-TNFα mAb-CS/PAMAM dendrimer NPs loaded-Tyramine-Gellan Gum in the treatment of inflammation. The results showed that the proposed therapeutic approach applied to the human monocyte cell line (THP-1) and human chondrogenic primary cells (hCH) cell-based inflammation system revealed an anti-inflammatory capacity that increased over 14 days. It was also possible to observe that Coll type II was highly expressed by inflamed hCH upon the culture with anti-TNF α mAb-CS/PAMAM dendrimer NPs, indicating that the hCH cells were able maintain their biological function. The developed preclinical model allowed us to provide more robust data on the potential therapeutic effect of anti-TNF α mAb-CS/PAMAM dendrimer NPs loaded-Ty-GG hydrogel in a physiologically relevant model.

Exploring the use of residual variance for uniformity of body weight in meat quail lines using Bayesian inference.

1. Uniformity in animal products is an important aspect of the production system. Several studies have reported estimates of genetics on residual variance in different species, indicating that it could be exploited to improve uniformity by selection. Nevertheless, there are no reports about the possibilities of such a selection strategy in meat quail.2. Records of hatching weight (HW) and body weight at 42 days (W42) of female and male birds from two meat quail lines (UFV1 and UFV2) were analysed. A three-step genetic evaluation was used to investigate the effect of genetic variation on residual variance of HW and W42 in both lines. In Step 1, a single-trait model was fitted to the data. In Step 2, log-transformed squared estimated residuals (ln(ê2)) were evaluated for these traits. In Step 3, a multi-trait analysis was performed to estimate the genetic correlation between the additive genetic effects for HW, W42, and their respective ln(ê2).3. The heritability estimates ranged from 0.12 to 0.23 for HW and from 0.22 to 0.35 for W42. The estimated heritabilities for the residual part were low and ranged from 0.0003 to 0.02 for both traits, and the genetic coefficient of variation residual variance estimates ranged from 0.31 to 0.42 for HW and from 0.09 to 0.25 for W42. Genetic correlations between the means (HW and W42) and ln(ê2) values were both positive and did not differ from zero, indicating no association between mean and ln(ê2).4. In conclusion, the uniformity of HW and W42 could be improved by selecting for lower residual variance in both meat quail lines, but the accuracy of selection may be low due to low heritability for uniformity, mainly for W42.

Systolic dysfunction by two-dimensional speckle tracking echocardiography in dogs with parvoviral enteritis.

INTRODUCTION/OBJECTIVES: Parvoviral enteritis (PVE) can cause either primary or secondary myocardial injury; the latter is associated with systemic inflammatory response syndrome and sepsis. Strain (St) and strain rate (SR) are relatively new speckle tracking echocardiographic (STE) variables used to assess myocardial function and are less influenced by preload and volume status than are conventional variables. The aim of this study was to evaluate systolic function in dogs with PVE using two-dimensional STE. ANIMALS: Forty-five client-owned dogs were included. MATERIALS AND METHODS: Dogs were classified into four groups: healthy (n = 9), PVE-mild (n = 15), PVE-severe (n = 13) and PVE-died (n = 8). Left ventricular global and segmental myocardial St and SR were assessed in radial, circumferential and longitudinal axes in the right parasternal transverse and apical 4-chamber views. In the circumferential and longitudinal axes, the value of each segment was determined separately at the endocardial and epicardial levels. RESULTS: Compared to healthy animals, all dogs with PVE showed significantly impaired St and SR values, mainly for PVE-severe and PVE-died groups. Moreover, the lowest SR value was observed in the circumferential axis at the mid-septal epicardial segment in the PVE-died group. For this variable, a cut-off value of 0.95 s-1 demonstrated 100% sensitivity and specificity for distinguishing between PVE-severe and PVE-died groups. CONCLUSIONS: In the present study, all dogs with PVE developed systolic dysfunction, which was more severe in non-survivors. Assessment of St and SR in dogs with PVE might be clinically useful for evaluating haemodynamic status and developing suitable therapeutic strategies to improve prognosis.

Inflammatory Bowel Disease Management During the COVID-19 Outbreak: The Ten Do's and Don'ts from the ECCO-COVID Taskforce.

Our knowledge of COVID-19 is changing and evolving rapidly, with novel insights and recommendations, almost on a daily basis. It behooves the medical community to provide updated information on a regular basis, on best practice to facilitate optimal care of infected patients and on appropriate advice for the general population. This is particularly important in the case of patients with chronic conditions, such as inflammatory bowel disease [IBD]. In this review, we have compiled existing evidence on the impact of COVID-19 in IBD patients and provide guidance on the most appropriate care to adopt during the pandemic. Our review highlights that IBD, per se, is not a risk factor for COVID-19. However, all IBD patients with symptoms should be tested for SARS-CoV-2 and the procedures for disease management should be carefully adapted: [i] in SARS-CoV-2-positive IBD patients, medical treatments should be re-evaluated [with a particular focus on corticosteroids] always with the purpose of treating active disease and maintaining remission; [ii] non-urgent surgeries and endoscopic procedures should be postponed for all patients; [iii] online consultancy should be implemented; and [iv] hospitalization and surgery should be limited to life-threatening situations.

¿Cuándo empieza la diabetes? Detección e intervención tempranas en diabetes mellitus tipo 2 / When does diabetes start? Early detection and intervention in type2 diabetes mellitus

La diabetes mellitus tipo2 (DM2) es una enfermedad progresiva cuyos cambios fisiopatológicos se producen varios años antes de su detección. Un abordaje basado en el desarrollo fisiopatológico de la DM2 y sus complicaciones enfatiza la importancia de una intervención temprana e intensiva, no solo para prevenir la disfunción de las células beta, sino también para actuar sobre los posibles factores de riesgo cardiovascular asociados antes de alcanzar los umbrales glucémicos fijados actualmente para el diagnóstico de la DM2. En el terreno de la DM2 de reciente diagnóstico, el estudio VERIFY ha mostrado que el tratamiento precoz combinado con metformina-vildagliptina proporciona mejoras relevantes en el control glucémico a largo plazo y puede influir positivamente en la evolución de la enfermedad

Type 2 diabetes mellitus (DM2) is a progressive disease whose pathophysiological changes occur several years before its detection. An approach based on the pathophysiological development of DM2 and its complications emphasises the importance of early and intensive intervention, not only to prevent beta-cell dysfunction but also to act on the potential associated cardiovascular risk factors before reaching the blood glucose thresholds currently set for diagnosing DM2. In the field of recently diagnosed DM2, the VERIFY study has shown that early treatment combined with metformin-vildagliptin provides relevant improvements in long-term glycaemic control and can positively affect the disease's progression

Avaliação da deformação miocárdica pela ecocardiografia feature tracking em gatos com defeito perimembranoso do septo ventricular / Evaluation of myocardial deformation by the ecocardiography feature tracking in cats with perimembranosous defect of the septo ventricular

O desenvolvimento de novas ferramentas, como a ecocardiografia bidimensional feature tracking (2D-FTI), permite diagnosticar, de forma precoce, se há disfunção miocárdica em doenças cardíacas, inclusive as congênitas. O defeito septal ventricular (DSV) é a alteração congênita mais observada em felinos, no entanto pouco se sabe sobre a disfunção cardíaca nessa cardiopatia, especialmente em animais assintomáticos. O objetivo deste estudo foi avaliar, por meio do 2D-FTI, a deformação miocárdica ventricular esquerda pela mensuração dos índices ecocardiográficos strain (St) e strain rate (StR) radial, circunferencial e longitudinal, em gatos saudáveis e com DSV. Foram avaliados 12 gatos saudáveis e seis gatos com DSV para obtenção de St e StR em diversos segmentos miocárdicos. No sentido longitudinal, houve diferença estatística (P<0,05) para os segmentos septal basal, mediano e apical epicárdicos (P=0,0017; P<0,0001; P=0,0288), lateral mediano epicárdico (P=0,0327), septal mediano endocárdico (P=0,0035), lateral mediano endocárdico (P=0,0461), St epicárdico (P=0,0250) e St global (P=0,0382). Também houve diferença no segmento lateral mediano circunferencial endocárdico (P=0,0248), lateral mediano radial (St: P=0,0409; StR: P=0,0166) e posterior mediano radial (P=0,0369). O estudo evidenciou que, mesmo em animais assintomáticos com DSV, há redução na deformação miocárdica ventricular principalmente no sentido longitudinal, demonstrando maior vulnerabilidade dessas fibras.(AU)

The development of new tools, such as two-dimensional feature tracking (2D-FTI), allows early diagnosis of myocardial dysfunction in heart diseases including congenital heart disease. The ventricular septal defect (VSD) is the most frequently observed congenital abnormality in cats, however, little is known about cardiac dysfunction, especially in asymptomatic animals. The objective of this study was to evaluate the left ventricular myocardial deformation through 2D-FTI by the measurement of the radial, circumferential and longitudinal echocardiographic strain (St) and strain rate (StR) indices. Twelve healthy cats and six cats with VSD were evaluated to obtain St and StR in several myocardial segments. In the longitudinal direction, there was a statistical difference (P<0.05) for the epimyocardial basal septal, mid-septal, apical septal (P=0.0017; P<0.0001; P=0.0288), epimyocardial mid-lateral (P=0.0327), endomyocardial mid-septal (P=0.0035), endomyocardial mid-lateral (P=0.0461), St epimyocardial (P=0.0250) and St global (P=0.0382). There was also difference in the circumferential endomyocardial mid-lateral segment (P=0.0248), radial mid-lateral (St: P=0.0409; StR: P=0.0166) and radial mid-posterior (P=0.0369). The study showed that even in asymptomatic animals with VSD there is a reduction in ventricular myocardial deformation mainly in the longitudinal direction, demonstrating the fragility of these fibers.(AU)

When does diabetes start? Early detection and intervention in type2 diabetes mellitus. / ¿Cuándo empieza la diabetes? Detección e intervención tempranas en diabetes mellitus tipo 2.

Type 2 diabetes mellitus (DM2) is a progressive disease whose pathophysiological changes occur several years before its detection. An approach based on the pathophysiological development of DM2 and its complications emphasises the importance of early and intensive intervention, not only to prevent beta-cell dysfunction but also to act on the potential associated cardiovascular risk factors before reaching the blood glucose thresholds currently set for diagnosing DM2. In the field of recently diagnosed DM2, the VERIFY study has shown that early treatment combined with metformin-vildagliptin provides relevant improvements in long-term glycaemic control and can positively affect the disease's progression.

Atopic Dermatitis Host and Environment Model: Revisiting Therapeutic Options.

Summary: Atopic Dermatitis affects both children and adults and is a serious health concern in many countries. AD is a complex disease with host and environmental factors underlying its pathology. Its treatment is multidimensional reflecting the diverse nature of its triggers and includes emollients, topical steroids and calcineurin inhibitors among others. Immunological dysfunction can be addressed broadly with systemic immunosupressors and specifically with monoclonal antibodies. Dupilumab, which targets IL-4 and IL-13 was granted approval for treatment of moderate-to-severe AD. Biologics targeting IgE/Th2 pathways may have its role in patients with overlapping AD and asthma. Psychological distress can exacerbate symptoms and is associated with increased severity of AD. Environmental triggers, such as, allergens can be addressed in selected cases with allergic immunotherapy. In this paper, we discuss AD treatment and propose a new step-by-step approach aiming at maintaining disease control and improving quality of life.

Short and extended provocation tests have similar negative predictive value in non-immediate hypersensitivity to beta-lactams in children

Introduction and objectives: Drug provocation tests (DPTs) are the gold-standard method to diagnose non-immediate hypersensitivity reactions (NIHSR) to beta-lactam antibiotics (BL) in children. Our aim was to compare the negative predictive value (NPV) of one-day (short) DPT versus 3-7 days (extended) DPT for the diagnosis of NIHSR to BL in paediatric age. A secondary aim was to compare confidence on drug re-exposure after short and extended negative DPTs. Methods: The occurrence of HSR on drug re-exposure and drug refusal after negative diagnostic DPTs were evaluated in children/adolescents with a history of NIHSR to BL using a questionnaire performed six months to ten years after DPT. Patients were divided into two groups according to the protocol performed: short DPT vs. extended DPT. Results: We enrolled 212 children and adolescents (86 females, 126 males, mean age at DPT 5.52 years, p25 = 3 years, p75 = 7.25 years): 69 tested with short DPT, and 143 with extended DPT. The NPV of both types of DPT together was 95.2%. The NPV of short DPT was 97.5% and the NPV of extended DPT was 93.8% (p = 0.419). After negative DPT, beta-lactams were refused by carers in 14.75% of the children requiring subsequent treatment, 6.98% in the short DPT group and 18.99% in the extended DPT group (p = 0.074). Conclusions: In our paediatric sample, prolonging drug administration did not increase the NPV of diagnostic DPT for NIHSR to BL or reduce drug refusal. Altogether, the data here reported suggest that, however intuitive, prolonging DPT is not beneficial in the parameters analysed

No disponible

The Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing.

Seventy four Reference Sites of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) have been recognised by the European Commission in 2016 for their commitment to excellence in investing and scaling up innovative solutions for active and healthy ageing. The Reference Site Collaborative Network (RSCN) brings together the EIP on AHA Reference Sites awarded by the European Commission, and Candidate Reference Sites into a single forum. The overarching goals are to promote cooperation, share and transfer good practice and solutions in the development and scaling up of health and care strategies, policies and service delivery models, while at the same time supporting the action groups in their work. The RSCN aspires to be recognized by the EU Commission as the principal forum and authority representing all EIP on AHA Reference Sites. The RSCN will contribute to achieve the goals of the EIP on AHA by improving health and care outcomes for citizens across Europe, and the development of sustainable economic growth and the creation of jobs.

Acidosis láctica asociada a metformina, ¿un fantasma o un asesino? / Metformin-associated lactic acidosis, a ghost or a murderer?

No disponible

Direct monitoring of breast and endometrial cancer cell epigenetic response to DNA methyltransferase and histone deacetylase inhibitors.

DNA methylation and histone deacetylation are key epigenetic processes involved in normal cellular function and tumorigenesis. Therapeutic strategies based on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors are currently in use and under development for the treatment of cancers. Genome-wide DNA methylation profiling has been proposed for use in disease diagnosis, and histone modification profiling for disease stratification will follow suit. However, whether epigenome sequencing technologies will be feasible for rapid clinic diagnosis and patient treatment monitoring remains to be seen, and alternative detection technologies will almost certainly be needed. Here we used electrochemical impedance spectroscopy (EIS) employing a graphene-based screen-printed electrode system to directly measure global DNA methylation and histone H3 acetylation to compare non-cancer and breast cancer cell lines. We demonstrated that whilst global methylation was not useful as a differential marker in the cellular systems tested, histone H3 acetylation was effective at higher chromatin levels. Using breast and endometrial cancer cell models, EIS was then used to monitor cellular responses to the DNMT and HDAC inhibitors 5-Aza-2'-deoxycytidine and suberoylanilide hydroxamic acid in vitro, and proved very effective at detecting global cellular responses to either treatment, indicating that this approach could be useful in following treatment response to epigenetic drugs. Moreover, this work reports the first combined analysis of two epigenetic markers using a unified graphene-based biosensor platform, demonstrating the potential for multiplex analysis of both methylation and acetylation on the same sample.

Small-scale environmental enrichment and exercise enhance learning and spatial memory of Carassius auratus, and increase cell proliferation in the telencephalon: an exploratory study.

Carassius auratus is a teleost fish that has been largely used in behavioral studies. However, little is known about potential environmental influences on its performance of learning and memory tasks. Here, we investigated this question in C. auratus, and searched for potential correlation between exercise and visuospatial enrichment with the total number of telencephalic glia and neurons. To that end, males and females were housed for 183 days in either an enriched (EE) or impoverished environment (IE) aquarium. EE contained toys, natural plants, and a 12-hour/day water stream for voluntary exercise, whereas the IE had none of the above. A third plus-maze aquarium was used for spatial and object recognition tests. Different visual clues in 2 of its 4 arms were used to guide fish to reach the criteria to complete the task. The test consisted of 30 sessions and was concluded when each animal performed three consecutive correct choices or seven alternated, each ten trials. Learning rates revealed significant differences between EE and IE fish. The optical fractionator was used to estimate the total number of telencephalic cells that were stained with cresyl violet. On average, the total number of cells in the subjects from EE was higher than those from subjects maintained in IE (P=0.0202). We suggest that environmental enrichment significantly influenced goldfish spatial learning and memory abilities, and this may be associated with an increase in the total number of telencephalic cells.