Desenlaces clínicos de los pacientes con diabetes e hiperglucemia de estrés que presentaron infección por SARS-CoV-2

Introduction. Diabetes and stress hyperglycemia (SH) have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease.Objective. To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and stress hyperglycemia [SH]) with SARS-CoV-2 infection.Materials and methods. A retrospective cohort study was conducted in Cali-Colombia. Patients aged ≥18 years with a diagnosis of SARS-CoV-2 infection managed in the emergency room, hospitalization or intensive care unit (ICU) between March 2020 and December 2021 were included. Immunocompromised patients and pregnant women were excluded. Patients were classified in three groups: without diabetes, with diabetes and SH. A comparison between the groups was performed. Results. A total of 945 patients were included (59.6% without diabetes, 27% with diabetes and 13.4% with SH). Fifty-five-point three percent required ICU management, with a higher need in patients with SH (89.8%) and diabetes (67.1%), with no difference between these groups (p=0.249). A higher chance of death was seen in SH vs. without diabetes (adjOR= 8.12, 95% CI 5.12-12.88, p<0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, the need for de novo renal replacement therapy and mortality was higher in patients with metabolic alterations (diabetes and SH). Conclusions. Diabetes and SH are associated to worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered as high risk at moment of COVID-19 diagnosis that allow to mitigate adverse outcomes.Introducción. La diabetes y la hiperglucemia de estrés (HE) se han relacionado con peores desenlaces clínicos en pacientes infectados por SARS-CoV-2 y con riesgo de enfermedad grave. Objetivo. Evaluar los resultados clínicos en tres grupos de pacientes (con diabetes, sin diabetes e hiperglucemia de estrés [SH]) con infección por SARS-CoV-2.Materiales y métodos. Se realizó un estudio de cohorte retrospectivo en Cali-Colombia. Se incluyeron pacientes ≥18 años con diagnóstico de infección por SARS-CoV-2 atendidos en urgencias, hospitalización o unidad de cuidados intensivos (UCI) entre marzo de 2020 y diciembre de 2021. Se excluyeron pacientes inmunocomprometidos y mujeres embarazadas. Los pacientes fueron clasificados en tres grupos: sin diabetes, con diabetes e HE. Se realizó una comparación entre los grupos.Resultados. Se incluyeron un total de 945 pacientes (59,6% sin diabetes, 27% con diabetes y 13,4% con HE). El 55,3% requirió manejo en UCI, con mayor necesidad en pacientes con HE (89,8%) y diabetes (67,1%), sin diferencia entre estos grupos (p=0,249). Se observó una mayor probabilidad de muerte en HE vs. sin diabetes (adjOR= 8,12, 95% IC 5,12-12,88, p<0,01). La frecuencia de síndrome de distrés respiratorio agudo, necesidad de ventilación mecánica invasiva, uso de vasopresores e inotrópicos, necesidad de terapia de reemplazo renal de novo y la mortalidad fue mayor en pacientes con alteraciones metabólicas (diabetes e HE).Conclusiones. La diabetes y la HE se asociaron a peores resultados clínicos y mortalidad en pacientes con COVID-19. Estos pacientes deben ser identificados tempranamente y considerados de alto riesgo al momento del diagnóstico de COVID-19 que permitan mitigar los desenlaces adversos

Enabling Responsible Online Gambling by Real-time Persuasive Technologies

Online gambling, unlike other offline addiction forms, provides unprecedented opportunities for monitoring users’ behaviour in real-time, along with the ability to adapt persuasive interactions and messages that would match the gamblers usage and personal context. Online gambling industry usually offers Application Programming Interfaces (APIs) that are mainly intended to allow third-party applications to interact with their services and enhance user’s experience. In this paper, we claim that such API’s can also be utilised to retrieve gamblers’ online data, such as browsing and betting history and other available offers, and use it to build more proactive and intelligent responsible gambling systems. We report on our experience in this field and make the argument that the available data for persuasive marketing and usability should, under certain usage conditions, also be made available for responsible online gambling services. We discuss the psychological foundations of our proposed approach and the risks and challenges typically resulted when building such a software-assisted intervention, persuasion and emotion regulation technology. We also explain the potential impact of corporate social responsibility and data protection prospects. Furthermore, we explore the required principles that should be followed by the gambling industry for enabling responsible online gambling. We finally propose a conceptual architecture to show our vision and explain how it can be implemented. In the broader context, the paper is intended to provide insights on building behavioural awareness and regulation information systems related to problematic digital media usage. Keywords: Persuasive technologies, responsible online gambling, gambling data availability, corporate social responsibility

Comparison of the diagnostic accuracy of commercial NS1-based diagnostic tests for early dengue infection

<p>Abstract</p> <p>Background</p> <p>We compared the diagnostic accuracy and reproducibility of commercially available NS1-based dengue tests and explored factors influencing their sensitivities.</p> <p>Methods</p> <p>Paired analysis of 310 samples previously characterized as positive (n = 218) and negative (n = 92) for viral isolation and/or RT-PCR and/or IgM seroconversion. Masked samples were tested by two observers with Platelia™ Dengue NS1 Ag, second generation Pan-E™ Dengue Early ELISA, SD Dengue NS1 Ag ELISA, Dengue NS1 Ag STRIP™, and SD BIOLINE™ Dengue Duo (NS1/IgM/IgG).</p> <p>Results</p> <p>SD BIOLINE™ NS1/IgM/IgG had the highest sensitivity (80.7% 95%CI 75-85.7) with likelihood ratios of 7.4 (95%CI 4.1-13.8) and 0.21 (95%CI 0.16-0.28). The ELISA-format tests showed comparable sensitivities; all below 75%. STRIP™ and SD NS1 had even lower sensitivities (<65%). The sensitivities significantly decreased in samples taken after 3 days of fever onset, in secondary infections, viral serotypes 2 and 4, and severe dengue. Adding IgM or IgG to SD NS1 increased its sensitivity in all these situations.</p> <p>Conclusions</p> <p>The simultaneous detection of NS1/IgM/IgG would be potentially useful for dengue diagnosis in both endemic and non endemic areas. A negative result does not rule out dengue. Further studies are required to assess the performance and impact of early laboratory diagnosis of dengue in the routine clinical setting.</p

Plasmodium falciparum CS C-terminal fragment: preclinical evaluation and phase I clinical studies

Preclinical evaluation of synthetic peptides corresponding to the C-terminal regions of the circumsporozoite (CS) protein in various Plasmodia showed that these preparations were immunogenic and safe upon injection in various animal models. Additionally, the corresponding peptide from Plasmodium falciparum was widely recognized by sera and PBL obtained from semi-immune adults living in malaria endemic areas. Moreover, the CS C-terminal peptide derived from P. berghei conferred protection upon challenge with live sporozoites in mice. A GLP preparation of the synthetic peptide corresponding to residues 282-383 of the Pf CS, NF-54 strain is currently evaluated in a open, non-randomized, Phase I human trial. Data obtained after the second antigen injection show that the malaria vaccine Pf CS 282-383 is safe, well tolerated and gives rise to high antibody titre, CD4+ and CD8+ lymphocyte responses

A synthetic malaria vaccine elicits a potent CD8(+) and CD4(+) T lymphocyte immune response in humans. Implications for vaccination strategies

We report the first synthetic peptide vaccine eliciting strong CD8(+) and CD4(+) T lymphocyte responses in humans. The vaccine, representing the C-terminal region of the circumsporozoite protein of Plasmodium falciparum (amino acids 282-383) was well tolerated and strong sporozoite-specific antibodies were elicited. In addition, robust lymphocyte proliferation responses were equally elicited with concomitant in vitro production of IFN-gamma, crucial in the elimination of the parasite. Most importantly, we also observed the development of CD8(+) T lymphocyte responses decisive in the immunity to malaria. The latter finding opens new, possibly safer, avenues for vaccination strategies when a CD8(+) T cell response is needed

Phase I trial of a P.vivax CS protein derived synthetic vaccinecandidate

IP 1106-05-063-97G. Corradin, J.A. Lopez, S. Herrera. -- En: Annals of TropicalMedicine yParasitology. -- Vol. 92, no. 5;(1998) ; p. 539-551. -- Plamodium vivax malaria vaccine development / Myriam Arevalo, Socrates Herrera. -- En:;circumsporozoite protein in individuals naturally exposedto malaria / Myriam Arevalo, Anais Zully Valencia,;Molecular Immunology. -- Vol. 38 (2001) ; p. 443-455. -- Variants of the plasmodium vivax circumsporozoite;protein (VK210 and VK247) in colombian isolates. -- En: MemoriasInst Oswaldo Cruz,Rio de Janeiro. -- Vol. 96,;no. 5 (jul 2001) ; p. 709-712. -- Identification of HLA-A2restricted CD8+T-limphosyte to plasmodium vivax;circumsporozoite protein by immunized Aotus monkeys / Myriam Arevalo, M.A.Roggero, J.M. Gonzalez, J. Vergara,;ARTICULO(S) EN REVISTA: Mapping and comparison of the B-cellepitopes recognized on the plasmodium vivax;Juana Vergara. -- En: Parasity immunology. -- Vol. 24, no.3 (mar 2002) ;p. 161-169

HLA-A*0201 restricted CD8+ T-lymphocyte responses to malaria: identification of new Plasmodium falciparum epitopes by IFN-gamma ELISPOT

The role of antigen specific CD8+ T-lymphocytes in mediating protection against sporozoite-induced malaria has been well established in murine models. In humans, indirect evidence has accumulated suggesting a similar protective role for antigen-specific CD8+ T-lymphocytes. Nevertheless, the low frequency of circulating specific cells together with the lack of sensitive methods to quantify them has hampered the direct assessment of their function. Using a combination of short-term cell culture and IFN-gamma ELISPOT, we studied CD8+ T-lymphocyte responses to a panel of HLA-A*0201 binding peptides. In addition to confirming the response to already described epitopes, we also identified five new CD8+ T-lymphocyte epitopes. These epitopes are presented in pre-erythrocytic stages gene products of Plasmodium falciparum 7G8 strain and correspond to the following protein segments: circumsporozoite (CS) 64-72, 104-113, 299-308 and 403-411; liver stage antigen (LSA-1) repeat region; sporozoite surface protein 2 or thrombospondin related anonymous protein (SSP2/TRAP) 78-88 and 504-513. Four of these peptides are conserved amongst all published sequences of P. falciparum strains. We conclude that the modified IFN-gamma ELISPOT assay is a sensitive technique to monitor antigen-specific CD8+ T-lymphocyte responses in human malaria which may help in the improvement and assessment of the efficacy of malaria subunit vaccines

Clinical indicators of fatal dengue in two endemic areas of Colombia: a hospital-based case-control study

According to the World Health Organization, 98% of fatal dengue cases can be prevented; however, endemic countries such as Colombia have recorded higher case fatality rates during recent epidemics. We aimed to identify the predictors of mortality that allow risk stratification and timely intervention in patients with dengue. We conducted a hospital-based, case-control (1:2) study in two endemic areas of Colombia (2009-2015). Fatal cases were defined as having either 1) positive serological test (IgM or NS1), 2) positive virological test (RT-PCR or viral isolation), or 3) autopsy findings compatible with death from dengue. Controls (matched by state and year) were hospitalized nonfatal patients and had a positive serological or virological dengue test. Exposure data were extracted from medical records by trained staff. We used conditional logistic regression (adjusting for age, gender, disease's duration, and health-care provider) in the context of multiple imputation to estimate exposure to case-control associations.Weevaluated 110 cases and 217 controls (mean age: 35.0 versus 18.9; disease's duration pre-admission: 4.9 versus 5.0 days). In multivariable analysis, retro-ocular pain (odds ratios [OR] = 0.23), nausea (OR = 0.29), and diarrhea (OR = 0.19) were less prevalent among fatal than nonfatal cases, whereas increased age (OR = 2.46 per 10 years), respiratory distress (OR = 16.3), impaired consciousness (OR = 15.9), jaundice (OR = 32.2), and increased heart rate (OR = 2.01 per 10 beats per minute) increased the likelihood of death (AUC: 0.97, 95% confidence interval: 0.96, 0.99). These results provide evidence that features of severe dengue are associated with higher mortality, which strengthens the recommendations related to triaging patients in dengue-endemic areas

Safety and elicitation of humoral and cellular responses in colombian malaria-naive volunteers by a Plasmodium vivax circumsporozoite protein-derived synthetic vaccine

Substantial experimental evidence indicates that the Plasmodium circumsporozoite (CS) protein has great potential as a vaccine candidate. We tested the safety and immunogenicity of vaccines composed of P. vivax CS-derived synthetic peptides. Sixty-nine healthy, malaria-naive volunteers were randomized to receive three injections of placebo or synthetic proteins N, R, or C (10, 30, or 100 microg/dose) in a double-blinded fashion. Vaccines were well tolerated and no serious adverse events were observed. Peptides N and R elicited humoral responses at all doses; peptide C elicicted these responses only at doses of 30 and 100 microg. The N peptide at a dose of 100 microg elicited the greatest antibody response. Antibodies to the three peptides recognized P. vivax sporozoites in an immunofluorescent antibody test. Peripheral blood mononuclear cells from most immunized volunteers also produced interferon-gamma upon peptide in vitro stimulation. These vaccines appear safe, well tolerated, and immunogenic in malaria-naive volunteers. Further optimization and development of this vaccine is being attempted to conduct phase II clinical trials

Generation and characterization of malaria-specific human CD8(+) lymphocyte clones: effect of natural polymorphism on T cell recognition and endogenous cognate antigen presentationby liver cells

CD8(+) cytolytic T lymphocytes (CTL) play a fundamental role in the clearance of malaria parasites from the liver in mouse models. In humans, however, only low levels of parasite-specific CD8(+) T lymphocytes have been observed in individuals living in endemic areas. In the present study, we identified high levels of circulating CD8(+) T lymphocytes specific for a previously described HLA-A2-restricted CTL epitope of the circumsporozoite (CS) protein of Plasmodium falciparum in an adult living in Burkina Faso, as evidenced by IFN-gamma ELISPOT assay and MHC-tetramer technology. After cloning by limiting dilution culture, T cell recognition of natural CS variants of P. falciparum was studied. The results demonstrate that naturally occurring variations drastically affect residues critical for T cell recognition as only two out of nine sequences analyzed were efficiently recognized by the CTL clones. These clones were also used to analyze T cell recognition of the endogenously presented cognate antigen. We observed efficient antigen recognition of both HLA-A*0201-transfected murine antigen presenting cells and liver cells from HLA-A*0201/K(b)-transgenic mice upon infection with recombinant vaccinia virus encoding the CS protein (WR-CS). More importantly, we demonstrate for the first time efficient recognition of WR-CS-infected human liver cells