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Background: To understand T-cell responses to SARS-CoV-2, it is essential to define the contribution of infection versus immunization to virus-specific hybrid immunity. Here, we characterized the breadth and magnitude of T-cell responses to the entire SARS-CoV2 proteome over a 2-year follow-up period in infected and vaccinated (CoV2+Vac+) and vaccinated and infected (Vac+CoV2+) individuals. Method(s): We selected samples from 38 (19 CoV2+ and 19 CoV2-, time1, T1) ProHEpiC-19 cohort participants, a prospective, longitudinal study starting in March 2020 involving 7,776 healthcare workers in Spain. Longitudinal samples were available from 10 of them after a 3-dose mRNA vaccination, including 5 CoV2+Vac+ and 5 Vac+CoV2+, at 824.5 and 250.5 days from symptoms onset (DfSO, time 2, T2). We measured the breadth and magnitude of IFN-y T-cell responses by ELISpot assay in cryopreserved PBMCs, using a 15-mer overlapping peptide (OLP) library of 2,790 SARS-CoV-2 peptides in 100 pools. Result(s): We identified immunodominant T-cell responses in S1, S2, nsp3, Env, NC, and M proteins across the SARS-CoV2 proteome. We observed an increased breadth of T-cell responses (responding pools over the entire region) to S1 (44 - 30%) and S2 (31 - 40%) in CoV2+Vac+ and Vac+CoV2+, respectively. In addition, CoV2+Vac+ had an exclusive and sustained response to M. We found significantly stronger responses in CoV2+Vac+ (P=0.0313). Particularly the total magnitude was greater in CoV2+Vac+ vs. Vac+CoV2+ in S1 (4476.88 vs. 1498.53), Env (457.34 vs. 250.50), and M (455.13 vs. 0.00) but not in S2 and nsp3. The total number of peptides for deconvolution was higher in CoV2+Vac+ (32 peptides) than in Vac+CoV2+ (3 peptides) during the follow-up. Seventy-five percent of the responses targeted S, and 25% M, ORF1a, and Env. Conclusion(s): These results profile immunodominant T-cell responses in S1, S2, nsp3, Env, NC, and M proteins across the entire SARS-CoV2 proteome. The data delineate differences in the number of T-cell responses primed hybrid immunity by infection previous to vaccination (CoV2+Vac+), being broader and of higher magnitude and underlining an exclusive T-cell response to the M region. Overall, these findings identify differences in long-term T-cell hybrid immunity primed by infection or vaccination, which may have implications in protection from re-infection and vaccine design.
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Background: Transgender women (TGW) are among the population most affected by the HIV epidemic in Argentina, despite a progressive legal framework. TransCITAR is a trans-specific cohort in Argentina that aims to assess physical and mental health among transgender and non-binary people (TGNBP). We present baseline characteristics of TGW. Method(s): TGW attending a trans-friendly clinic to receive HIV/STIs prevention/ treatment, mental health care and/or gender-affirming hormone therapy (GHT) were invited to participate. Semiannual visits including clinical assessments, laboratory tests, and psychosocial interviews were performed. Oral PrEP was offered as part of a combined prevention strategy since September 2021. Result(s): Between September/2019 and August/2022, 500 TGNBP were enrolled, 416 were TGW (median age: 30 years, IQR 25-37). High social vulnerability was observed (Table 1). Regarding trans-specific characteristics, 49.8% reported industrial silicone injections and 36.8% were receiving GHT. 76.9% were sex workers. Baseline STIs prevalence were: HIV 42.3% (10.2% diagnosed at enrolment), syphilis 40% (defined as positive nontreponemal test VDRL with titers of at least 1/8), past HBV 18.5%, chronic HBV 3.8%, HCV antibody positive 2.6%. Only 57% presented HBV protective antibodies titers (HBVsAb>=10UI/ml), 8 TGW were on PreP. For those with HIV, median CD4+ cell count was 602 cells/mm3 (IQR 378-933), 66.5% were on ART at enrolment (53.6% were virally suppressed) and 14.8% initiated at baseline. During 36 months of follow up, 4 TGW died (one AIDS-related and one COVID-19-related). Bivariate analyses showed that a positive HIV diagnosis was independently associated with migration, low level of education, unstable housing, silicone injecion and sex work, while was negatively associated with being on GHT. In multivariable logistic regression, only sociodemographic variables remain associated: migrant (aOR=.487, 95% CI=.304-.768);incomplete high school (aOR=.463, 95% CI=.300=.714);unstable housing (aOR=.614, 95% CI=.401- .940);and sex work (aOR=.324, 95% CI=.177-.593). Conclusion(s): TGW from TransCITAR presented poor health outcomes: high prevalence of HIV/syphilis, high proportion with incomplete/no HBV vaccine and high levels of depression and violence. A comprehensive approach to care and addressing social determinants of health is pivotal to reduce HIV burden in this population.
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In recent years, the economic, technological, and sociocultural environments have been in constant change. Customers are more demanding and aware of market trends. Companies innovate their processes through the implementation of technologies that allow them to optimize operations and facilitate business-client interaction. However, many companies, especially small and medium-sized enterprises, face difficulties in adapting to new business models. There are even companies that are not willing to change the traditional way they carry out their daily business operations, which can present more challenges in today's market. The digital transformation has caused companies to restructure their business models in recent years. Currently, with the arrival of COVID-19, many businesses have been affected due to the lack of digitization in the processes. Small and medium-sized companies were forced to embark on E-Commerce in order to reach their customers and survive the competition. Still, not all companies have managed to properly implement a digital transformation strategy to redesign their structures and operations. In Panama there are still no studies focused on the degree of digitalization of small and medium-sized companies. This research aims to describe the degree of digitalization of local companies in the province of Chiriqui-Panama © 2022 IEEE.
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We present a low-cost Remote Laboratory platform developed to support the practices of the Vehicle Electronics course during the COVID-19 pandemic. The platform, which emerged as an emergency solution, has become a significant teaching resource. Although the platform was designed primarily for microcontroller (or FPGA) based practices, it could be extended to Analogue Electronics practices. From a hardware perspective, low-cost devices such as a Raspberry Pi, a camera or a old PC box have been used, while the software interface has been developed using Node-RED. © 2022 IEEE.
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Background & Aim: Due to its immunomodulatory potential, therapy based on the transfer of regulatory T cells (Tregs) has acquired great interest in the treatment of diseases in which it is necessary to restore immune homeostasis. Until now, autologous Treg cell therapy has proven to be safe, but the employment of blood as the source of Treg presents several limitations in terms of Treg recovery and the quality of the employed Tregs. Our group has developed a new technology to produce massive amounts of GMP Treg derived from the pediatric thymic tissue discarded in pediatric cardiac surgeries (thyTreg) that could overcome the main obstacles. Indeed, we are employing thyTreg cells with success in a clinical trial as autologous cell therapy in transplanted children. Given the large amounts of thyTreg that can be obtained from a single thymus, the main objective of this work is to evaluate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible the allogeneic use of this cellular therapy in order to treat a range of immune diseases and patients. Methods, Results & Conclusion: The thyTreg obtained in the laboratory using the protocol developed by our group exhibit high viability (>90%) and high purity (>80%) in terms of CD25+FoxP3+ expression. ThyTreg have been observed to express low levels of immunogenicity markers (CD40L, CD80, CD86) by flow cytometry. Moreover, in vitro models of thyTreg co-culture with allogeneic peripheral blood mononuclear cells (PBMC) from healthy donors have been performed to i) determine if thyTreg generate an immunogenic response on PBMC, and ii) evaluate the capacity of thyTreg to suppress the proliferation of allogeneic PBMC. Even that the HLA disparity in the allogeneic cocultures between thyTreg and PBMC was high (13 of the 21 typed pairs had HLA <4/12 concordance), thyTreg did not induce the expression of activation markers (CD25, CD69) nor the proliferation or the production of pro-inflammatory cytokines (IFN-g) by allogeneic PBMCs. Moreover, thyTreg greatly inhibit the proliferation of allogeneic CD4 and CD8 T cells, reaching levels of around 70% inhibition of proliferation at a 1: 1 ratio. The results suggest that allogenic thyTreg are not immunogenic and are capable of exerting their suppressive function in an allogeneic context, indicating their possible off-the-shelf use as a treatment for transplant rejection, graft-versus- host disease, autoimmune diseases or the cytokine release syndrome characteristic of severe COVID-19 patients.
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Stress index is a useful indicator in mechanical ventilation to assess improper ventilation settings. It can indicate tidal overdistension or tidal recruitment, which are two major mechanisms of ventilator-induced lung injury. However, it's implementation require dedicated hardware and software and is not a widespread parameter used in commercial ventilators. In this work, an alternative, simple way to visually inspect the concavity of the pressure-time curve during mechanical ventilation is presented, by calculating the pressure difference of the pressure-time curve. This proves useful when implemented in low-cost emergency devices, such as those designed to cope with the COVID-19 pandemic, because of the reduced computational load required to perform its calculation. The method was implemented in a low-cost emergency mechanical ventilator and tested with an artificial lung for a proof-of-concept. Results show that this alternative method can be effectively used to qualitatively assess the concavity of the pressure-time curve.
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Background: During the first months of coronavirus disease 2019 (COVID 19) pandemic there were several reports of myocardial involvement in recovered patients despite of symptoms presented during acute phase of the infection. That information led to a rising number of recomendations of screening for myocardial damage with different methods like electrocardiogram, echocardiography, cardiac magnetic resonance and biomarkers in the pursuit of a cardiac event free return to normal activities. Because of this and knowing the capability of strain imaging to detect subclinical myocardial damage we decided to evaluate values of left ventricular global longitudinal strain (GLS) and right ventricular free wall strain (RVFWS) in patients that were derived for echocardiographic evaluation after COVID 19 infection and their evolution. Methods: We enrolled prospectively patients derived to our laboratory for evaluation of Doppler echocardiography after confirmed COVID 19 infection if they were in the month after clinical discharge and did not have previous known structural cardiac alterations. We obtained demographic, symptoms and echocardiographic data and calculated GLS and RVFWS. Six months after the index examination we did phone calls to asess symptoms and events. Data is presented with mean and standard deviation and percentages. Results: of 68 patients included 38 (55,88%) were male, mean age was 42 years (+- 12,5) and half of them were sedentary. 52 had mild symptoms during infection, 15 moderate and 1 severe that required mechanical ventilation. At the time of examination 58 were asymptomatic (85,29%) and the other complaint of dyspnea (3), weakness (8) and palpitations (6). Regarding echocardiographic data, mean eyection fraction estimated by Simpson?s biplane method was 65,6% (+- 4,33) and left atrial indexed volume 25 ml/m2 (+- 5,98). 44 patients had normal left ventricular diastolic function, 21 grade 1 dysfunction and 2 had grade 2, with mean E/e? relation 8,52 (+-2,03). Mean pulmonary artery systolic pressure estimated was 27,4 mmHg (+- 4,1) and tricuspid anular plane systolic excursion was 23,81 mm (+-3,12). Mean GLS was - 21,52% (+- 1,91) and RVFWS was - 29,15% (+- 5,4), in 2 patients we could not measure RVFWS due to bad quality of images. Only 2 patients had GLS above - 18%, thta were the patient with severe symptoms and 1 with moderate symptoms;and 10 had RVFWS above - 23%, all of them with moderate symptoms. We could contact 60 patients (88,23%) after 6 months and none of them had cardiac events or persistence of symptoms. Conclusions: Calculation of GLS and RVFWS in this patients was feasible. We observed abnormalities in patients with severe and moderate symptoms at the time of infection, more frequently in RVFWS, but without relation to cardiac events or symptoms on follow up.
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We theoretically investigate the interaction of endogenous risk intolerance and monetary policy following a large recessionary shock. As asset prices dip, risk-tolerant agents' wealth share declines. This decline reduces the market's risk tolerance and triggers a downward loop in asset prices and aggregate demand when the interest rate policy is constrained. In this context, large-scale asset purchases are effective because they transfer unwanted risk to the government's balance sheet. These effects are sizable when the model is calibrated to match the estimates of aggregate asset demand inelasticity. The COVID-19 shock illustrates the environment we seek to capture.
ABSTRACT
In this paper we: (i) provide a model of the endogenous risk intolerance and severe asset price and aggregate demand contractions following an adverse real (non-financial) shock;and (ii) demonstrate the effectiveness of Large Scale Asset Purchases (LSAPs) in addressing these contractions. The key mechanism stems from heterogeneous risk tolerance: as a recessionary shock hits the economy and brings down asset prices, risk-tolerant agents' wealth share declines and their leverage rises endogenously. This reduces the market's risk tolerance and generates downward pressure on asset prices and aggregate demand. When monetary policy is unconstrained, it can offset the decline in risk tolerance with an interest rate cut that boosts the market's Sharpe ratio. However, if the interest rate policy is constrained, new contractionary feedbacks arise: recessionary shocks lead to further asset price and output drops, which feed the risk episode and trigger a downward loop. In this context, LSAPs improve asset prices and aggregate demand by transferring risk to the government's balance sheet, which reduces the market's required Sharpe ratio and reverses the contractionary feedbacks. Quantitatively, we show that aggregate shocks and LSAPs have large impacts on asset prices when the model is calibrated to fit the inelastic demand for aggregate assets uncovered in recent literature. We also show that heterogeneity in risk tolerance explains part of the demand inelasticity in normal times, and further reduces the elasticity after a recessionary shock. The Covid-19 shock and the large response by all major central banks provide a vivid illustration of the environment we seek to capture.
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The study focuses on the application of WhatsApp as a technological resource of vital importance for cognitive development through collaborative work, in the context of COVID-19. The experience has been developed with 2406 teachers of the UGEL of Utcubamba (Amazonas, Peru) and 30,842 schoolchildren of Regular Basic Education. The objective is to assess the usefulness of the WhatsApp application in the collaborative work of students in different contexts. The 2020 school year has been characterized by the role played by WhatsApp as a technological support, which was incorporated in a timely manner to take a relevant role in the monitoring and accompaniment of the educational process of schoolchildren. Collaborative work continues to be the fundamental characteristic of the formative process in any scenario, which has allowed interactivity associated with the synergy between the teacher and the students, as well as among them, as a response to autonomy. Remote learning and the teacher devoid of another resource made WhatsApp become the ideal resource for collaborative work on the axis of asynchrony, while highlighting the progressive development of autonomous learning. © 2020 by author(s) and Linguistica Antverpiensia.
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Background and importance Nutritional management in the intensive care unit (ICU) of patients with COVID-19 can influence their recovery. Several guides about nutritional support have appeared in the past few months Aim and objectives To assess the appropriateness of nutritional management for COVID-19 patients in the ICU requiring invasive mechanical ventilation (IMV) through compliance with the recommendations of the Spanish Society for Intensive Care (SEMICYUC), the European Society for Clinical Nutrition and Metabolism (ESPEN) and the American Society for Parenteral and Enteral Nutrition (ASPEN). Material and methods An observational retrospective study was conducted between 2 March and 13 May 2020. Patient data were taken from the clinical records. Demographic variables were age and sex;clinical variables were days until the start of artificial nutrition (AN), duration and type of enteral (EN) or parenteral nutrition (PN), body mass index (BMI), calorie intake/kg/day, protein/kg/day on the first and fifth days, increase in markers of hepatic cholestasis when duration of NP was >14 days, length of ICU stay and death. Results 41 patients were included, 75.6%(n=31) men, and average age was 59.6±12,2 years. Median time to start of AN was 1 (0-6) day. 34.1% (n=14) of patients were obese, of whom 21% (n=3) were morbidly obese (average BMI 44.86±6.4). Average total kcal/kg/day and protein/kg/day on the first and fifth days of nutrition were 21.9±7.5 kcal/kg/day and 1.35±0.6 g protein/kg/day and 23.5±9.8 kcal/kg/day and 1.9±3.2 g protein/kg/day, respectively. Only 17% (n=7) started AN with EN, which was hypercaloric/hyperproteic (n=3) and normocaloric/normoproteic (n=4). At any time during hospital stay, 97.5% of patients had PN with a median of 14.5 (2-52) days. 20 people had PN >14 days. Alkaline phosphatase remained increased for 11 of them with a median of 13 (3-38) days. Direct bilirubin was elevated in all patients. 34 patients died and 26 remained on PN until the day they died. Conclusion and relevance During the first day, AN accomplished the recommendations (20 kcal/kg/day and 1.2-1.3 g protein/kg/day). On the fifth day, total kilocalories did not achieve the recommended values (25 kcal/kg/day), although protein/kg/day was higher than the guidelines (1.5 kcal/kg/ day). The reason might be the increasing protein request of these patients. High doses of muscle relaxants could prevent proper functionality of digestive tube and low use of EN. It may be important to discuss the suitability of maintenance of AN for patients with a short life expectancy.
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Background and importance From the beginning of the COVID-19 pandemic, tocilizumab has been positioned as an effective drug to treat cytokine release syndrome, which causes acute respiratory distress in patients with SARS-CoV2 pneumonia. Throughout these months, clinical protocols have been developed that improve the effectiveness, introducing it at the onset of symptoms. Aim and objectives To evaluate if the change in criteria for treatment with tocilizumab between the first and second waves of the COVID-19 pandemic, introducing it at the onset of symptoms, led to an improvement in its effectiveness. Material and methods A retrospective observational study was conducted between 3 March 2020 and 15 October 2020 in patients with COVID-19 confirmed by PCR, treated with tocilizumab in a first level hospital. Demographic, clinical and pharmacotherapeutic data were collected from electronic medical records. To compare the effectiveness of treatment between the first COVID-19 wave (3 March to 31 May 2020) and the second COVID-19 wave (31 May to 15 October), we collected for each patient: days from admission to tocilizumab administration, oxygen therapy requirement, ICU stay, hospital stay and survival. Differences between quantitative and qualitative variables were analysed, applying the Student's t test and the χ2 test (p≤0.005). Statistical analysis was performed with SPSS22.0. Results 167 patients (131 men), average age 58.9±12.6 years, were included. During the first wave, tocilizumab was administered to 100 patients. Days (average) until administration was 5±4.4. Length of hospital stay was 22.9±15.9 days. 39.0% of patients needed a stay in the ICU. Distribution of patients according to requirement for oxygen therapy: 48% high flow (HF) oxygen delivery systems, 19% low flow (LF) oxygen delivery systems and 31% with invasive mechanical ventilation. Two patients did not require oxygen therapy. The mortality rate was 28%. During the second wave, tocilizumab was administered to 67. Days (average) until administration was 2 ±2.2. Length (average) of hospital admission was 13.1±10.4 days. 10.1% of patients needed a stay in the ICU. Distribution of patients according to requirement for oxygen therapy: 11.6% HF and 88.4% LF. The mortality rate was 11.6%. We found statistically significant differences in length of hospital stay and mortality rate between the two groups. Conclusion and relevance The study showed that early administration of tocilizumab increased survival, decreased ICU income and shortened hospital stay. A limitation of our study was the lack of comparison between inflammatory parameters before and after administration. Further studies are needed.
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The sexual and reproductive rights of women, as well as the rights of their children, are being threatened due to the COVID-19 crisis. In these times of pandemic, both pregnant and postpartum women and their newborns have become victims of the consequences of the gyno-obstetric patriarchy paradigm. In this article, we analyze the negative consequences of coronavirus management in childbirth and abortion processes. Likewise, we defend that the crisis unleashed by COVID-19 can be an opportunity to make visible situations of sexual and reproductive injustice and bring about changes to guarantee the freedoms and rights of women and infants. © 2020 Universitat Autonoma de Barcelona and Universitat de Girona. All rights reserved.