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BACKGROUNDNovel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respiratory infections.METHODSWe applied a highly sensitive non-depletion tandem mass spectrometry discovery approach to investigate plasma protein expression in pulmonary TB cases compared to healthy controls in South African and Peruvian cohorts. Bioinformatic analysis using linear modeling and network correlation analyses identified 118 differentially expressed proteins, significant through 3 complementary analytical pipelines. Candidate biomarkers were subsequently analyzed in 2 validation cohorts of differing ethnicity using antibody-based proximity extension assays.RESULTSTB-specific host biomarkers were confirmed. A 6-protein diagnostic panel, comprising FETUB, FCGR3B, LRG1, SELL, CD14, and ADA2, differentiated patients with pulmonary TB from healthy controls and patients with other respiratory infections with high sensitivity and specificity in both cohorts.CONCLUSIONThis biomarker panel exceeds the World Health Organization Target Product Profile specificity criteria for a triage test for TB. The new biomarkers have potential for further development as near-patient TB screening assays, thereby helping to close the case-detection gap that fuels the global pandemic.FUNDINGMedical Research Council (MRC) (MR/R001065/1, MR/S024220/1, MR/P023754/1, and MR/W025728/1); the MRC and the UK Foreign Commonwealth and Development Office; the UK National Institute for Health Research (NIHR); the Wellcome Trust (094000, 203135, and CC2112); Starter Grant for Clinical Lecturers (Academy of Medical Sciences UK); the British Infection Association; the Program for Advanced Research Capacities for AIDS in Peru at Universidad Peruana Cayetano Heredia (D43TW00976301) from the Fogarty International Center at the US NIH; the UK Technology Strategy Board/Innovate UK (101556); the Francis Crick Institute, which receives funding from UKRI-MRC (CC2112); Cancer Research UK (CC2112); and the NIHR Biomedical Research Centre of Imperial College NHS.
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Biomarcadores , Proteômica , Tuberculose Pulmonar , Humanos , Biomarcadores/sangue , Proteômica/métodos , Masculino , Feminino , Adulto , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/sangue , Mycobacterium tuberculosis , Pessoa de Meia-Idade , Peru/epidemiologia , África do Sul/epidemiologia , Estudos de Casos e Controles , Sensibilidade e EspecificidadeRESUMO
Background: The prevalence of post-COVID-19 Syndrome (PCS) is estimated to be between 10% and 20%. The main reported symptoms are fatigue, memory alterations, dyspnea, sleep disorders, arthralgia, anxiety, taste alterations, coughing and depression. This study aims to determine the prevalence of post-COVID-19 symptoms in a group of Colombian patients who were recruited during their outpatient appointments. Methodology: This cross-sectional study was conducted between December 2021 to May 2022. It included patients from outpatient facilities located in five main cities in Colombia who were positive for SARS-CoV-2 infection detected by reverse transcription-polymerase chain reaction (RT-PCR) testing and reported PCS in the following 12 weeks after their COVID-19 diagnosis. Results: A total of 1047 individuals >18 years old met the inclusion criteria and were included in the study. The median age was 46 years old. 68.2% of the participants were female, 41.5% of the patients reported having a pre-existent condition (hypertension, anxiety disorder, diabetes, hyperthyroidism, obesity and asthma). Only 22% had received at least one dose of COVID-19 vaccine prior to the COVID-19 episode registered. The more prevalent symptoms within our group are described as follows: fatigue (53.3%), dyspnea (40.3%), arthralgia and/or myalgia (43%), cephalea (40.5%), sleep disorders (35.7%) and coughing (31.3%). 72% of the patients presented four or more post-COVID 19 symptoms, 9% two symptoms, and 10% only one symptom. Conclusion: The findings of this study are consistent with international literature publicly available. The distribution and prevalence of post-COVID symptoms highlight the importance of further research to improve understanding and its potential consequences and implications in terms of quality of life and health care planning services.
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Considering an entropy-based division of energy transferred into heat and work, we develop an alternative theoretical framework for the thermodynamic analysis of two-level systems. When comparing these results with those obtained using the standard definitions of these quantities, we observe the appearance of a different term of work, which represents the energy cost of rotating the Bloch vector in the presence of the external field that defines the local Hamiltonian. Additionally, we obtain explicit expressions for the temperature, the heat capacity, and the internal entropy production of the system in both paradigms. In order to illustrate our findings we study, from both perspectives, matter-radiation interaction processes for two different systems.
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Chronic kidney disease (CKD) constitutes a major health problem and one of the leading causes of death worldwide. Patients with CKD have impaired immune functions that predispose them to an increased risk of infections, as well as virus-associated cancers and a diminished vaccine response. In this study, we aimed to identify clinical and laboratory parameters associated with in-hospital mortality in patients evaluated in the department of emergency (ER) and admitted with the diagnosis of severe acute respiratory syndrome (SARS) caused by coronavirus disease 2019 (COVID-19) at the Baptist Hospital of Nicaragua (BHN). There were 37 patients with CKD, mean age 58.3 ± 14.1 years, admitted to BHN due to COVID-19, and among them, 24 (65.7%) were males (p = 0.016). During hospitalization, 23 patients with CKD (62.1%) died of complications associated with COVID-19 disease, which was a higher proportion (odds ratio (OR) 5.6, confidence interval (CI) 2.1-15.7, p = 0.001) compared to a group of 70 patients (64.8% males, mean age 57.5 ± 13.7 years) without CKD admitted during the same period in whom 28.5% died of COVID-19. In the entire cohort, the majority of patients presented with bilateral pneumonia, and the most common symptoms at admission were dyspnea, cough, and fever. Serum levels of D-dimer, ferritin and procalcitonin were significantly higher in patients with CKD compared with those without CKD. Multivariate analysis revealed that CKD, age (>60 years), and hypoxia measured in the ER were factors associated with increased in-hospital mortality. Among patients with CKD but not in those without CKD (OR 36.8, CI 1.5-88.3, p = 0.026), an increased monocytes-to-lymphocyte ratio (MLR) was associated with higher mortality and remained statistically significant after adjusting for confounders. The MLR measured in the ER may be useful for predicting in-hospital mortality in patients with CKD and COVID-19 and could contribute to early risk stratification in this group.
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Resumen (analítico) En este artículo de investigación cualitativa, la tecnología fotográfica y la memoria visual se convierten en plataformas para producir expresiones artísticas de reconciliación. En tal sentido, la creación fotográfica se usó como medio para exteriorizar significados e interpretaciones visuales sobre un territorio. Estudiantes de una institución educativa rural participaron en talleres de creación fotográfica y laboratorios de fundamentación sobre memoria y reconciliación. Este trabajo empírico permitió aplicar instrumentos de observación participante, explorando el acto creativo a través de una guía de elementos que potenciaron posturas críticas de los jóvenes hacia el territorio. Los resultados de un modelo de acciones creativas, aplicado a procesos de pensamiento crítico, permitieron comprobar que el autorretrato fotográfico se convierte en un artefacto comunicativo autorreferenciado socialmente.
Abstract (analytical) In this qualitative research article, photographic technology and visual memory are used in platforms to produce artistic expressions of reconciliation. Photographic creation was used to express meanings and visual interpretations of a territory. Students from a rural school participated in photographic creation workshops and activities focused on memory and reconciliation. This empirical work facilitated the application of participant observation instruments, exploring the act of creation through a handbook that promoted critical thinking for young people regarding the territory. The results of a creative action model applied to critical thought processes verified that the photographic self-portrait becomes a socially self-referenced communicative artifact.
Resumo (analítico) Neste artigo de pesquisa qualitativa, a tecnologia fotográfica e memória visual tornam-se plataformas para produzir expressões artísticas de reconciliação. Nesse sentido, a criação fotográfica foi utilizada como um meio de externalizar significados visuais e interpretações de um território. Os alunos da instituição educacional rural Giovanni Montini participam de oficinas de criação fotográfica e de laboratórios de fundamentação em memória e reconciliação. Este trabalho empírico permitiu a aplicação de instrumentos de observação participante, explorando o ato criativo por meio de um guia de elementos (estruturação, navegação, programação e representação) que impulsionaram as posições críticas dos jovens em relação ao território. Os resultados de um modelo de ações criativas, aplicadas aos processos de pensamento crítico, permitiram verificar que o autoretrato fotográfico torna-se um dispositivo comunicativo socialmente auto-referenciado.
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Tecnologia , Observação , Pesquisa Qualitativa , Memória , Instituições Acadêmicas , Estudantes , ArtefatosRESUMO
BACKGROUNDTuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma.METHODSWe applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatographic separation combined with high-resolution mass spectrometry to study nondepleted plasma of 11 patients with active TB compared with 10 healthy controls. Prioritized candidates were verified in independent UK (n = 118) and South African cohorts (n = 203).RESULTSWe generated the most comprehensive TB plasma proteome to date, profiling 5022 proteins spanning 11 orders-of-magnitude concentration range with diverse biochemical and molecular properties. We analyzed the predominantly low-molecular weight subproteome, identifying 46 proteins with significantly increased and 90 with decreased abundance (peptide FDR ≤ 1%, q ≤ 0.05). Verification was performed for novel candidate biomarkers (CFHR5, ILF2) in 2 independent cohorts. Receiver operating characteristics analyses using a 5-protein panel (CFHR5, LRG1, CRP, LBP, and SAA1) exhibited discriminatory power in distinguishing TB from other respiratory diseases (AUC = 0.81).CONCLUSIONWe report the most comprehensive TB plasma proteome to date, identifying novel markers with verification in 2 independent cohorts, leading to a 5-protein biosignature with potential to improve TB diagnosis. With further development, these biomarkers have potential as a diagnostic triage test.FUNDINGColciencias, Medical Research Council, Innovate UK, NIHR, Academy of Medical Sciences, Program for Advanced Research Capacities for AIDS, Wellcome Centre for Infectious Diseases Research.
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Biomarcadores/sangue , Mycobacterium tuberculosis/metabolismo , Proteoma/análise , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/epidemiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Redes Reguladoras de Genes , Humanos , Masculino , Peru/epidemiologia , Estudos Prospectivos , Proteoma/metabolismo , Curva ROC , África do Sul/epidemiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
An explicit expression for the temperature of an open two-level quantum system is obtained as a function of local properties under the hypothesis of weak interaction with the environment. This temperature is defined for both equilibrium and out-of-equilibrium states and coincides with the environment temperature if the system reaches thermal equilibrium with a heat reservoir. Additionally, we show that within this theoretical framework the total entropy production can be partitioned into two contributions: one due to heat transfer and another, associated to internal irreversibilities, related to the loss of internal coherence by the qubit. The positiveness of the heat capacity is established, as well as its consistency with the well-known results at thermal equilibrium. We apply these concepts to two different systems and show that they behave in analogous ways as their classical counterparts.
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BACKGROUND: Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods. METHODS/PRINCIPAL FINDINGS: A descriptive study that combines active (ACD), passive (PCD), and reactive (RCD) case detection was performed in urban and peri-urban neighborhoods of Quibdó, Colombia. Heads of households were interviewed and epidemiological surveys were conducted to assess malaria prevalence and identify potential risk factors. Sixteen primary cases, eight by ACD and eight by PCD were recruited for RCD. Using the RCD strategy, prevalence of 1% by microscopy (6/604) and 9% by quantitative polymerase chain reaction (qPCR) (52/604) were found. A total of 73 houses and 289 volunteers were screened leading to 41 secondary cases, all of them in peri-urban settings (14% prevalence). Most secondary cases were genetically distinct from primary cases indicating that there were independent occurrences. Plasmodium vivax was the predominant species (76.3%, 71/93), most of them being asymptomatic (46/71). Urban and peri-urban neighborhoods had significant sociodemographic differences. Twenty-four potential breeding sites were identified, all in peri-urban areas. The predominant vectors for 1,305 adults were Anopheles nuneztovari (56,2%) and An. Darlingi (42,5%). One An. nuneztovari specimen was confirmed naturally infected with P. falciparum by ELISA. CONCLUSIONS: This study found no evidence supporting the existence of urban malaria transmission in Quibdó. RCD strategy was more efficient for identifying malaria cases than ACD alone in areas where malaria transmission is variable and unstable. Incorporating parasite genotyping allows discovering hidden patterns of malaria transmission that cannot be detected otherwise. We propose to use the term "focal case" for those primary cases that lead to discovery of secondary but genetically unrelated malaria cases indicating undetected malaria transmission.
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Transmissão de Doença Infecciosa , Malária/epidemiologia , Malária/transmissão , Adolescente , Adulto , Animais , Anopheles/classificação , Anopheles/crescimento & desenvolvimento , Anopheles/parasitologia , Criança , Colômbia/epidemiologia , Estudos Transversais , Testes Diagnósticos de Rotina , Feminino , Variação Genética , Genótipo , Humanos , Entrevistas como Assunto , Malária/diagnóstico , Malária/parasitologia , Masculino , Microscopia , Pessoa de Meia-Idade , Epidemiologia Molecular , Mosquitos Vetores/classificação , Mosquitos Vetores/crescimento & desenvolvimento , Mosquitos Vetores/parasitologia , Plasmodium/classificação , Plasmodium/genética , Plasmodium/isolamento & purificação , Reação em Cadeia da Polimerase , Prevalência , Fatores de Risco , População Rural , População Urbana , Adulto JovemRESUMO
BACKGROUND: The recent scale-up in malaria control measures in Latin America has resulted in a significant decrease in the number of reported cases in several countries including Ecuador, where it presented a low malaria incidence in recent years (558 reported cases in 2015) with occasional outbreaks of both Plasmodium falciparum and Plasmodium vivax in the coastal and Amazonian regions. This success in malaria control in recent years has led Ecuador to transition its malaria policy from control to elimination. RESULTS: This study evaluated the general knowledge, attitude and practices (KAP) about malaria, as well as its prevalence in four communities of an endemic area in northwest Ecuador. A total of 258 interviews to assess KAP in the community indicated that most people in the study area have a basic knowledge about the disease but did not use to contribute to its control. Six hundred and forty-eight blood samples were collected and analysed by thick blood smear and real-time PCR. In addition, the distribution of the infections was mapped in the study communities. Although, no parasites were found by microscopy, by PCR the total malaria prevalence was 7.5% (6.9% P. vivax and 0.6% P. falciparum), much higher than expected and comparable to that reported in endemic areas of neighbouring countries with higher malaria transmission. Serology using ELISA and immunofluorescence indicated 27% respondents for P. vivax and 22% respondents for P. falciparum. CONCLUSIONS: Results suggest that despite a great malaria reduction in Ecuador, transition from control to elimination would demand further improvement in malaria diagnostics, including active case detection to identify and treat parasite asymptomatic carriers, as well as community participation in its elimination.
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Infecções Assintomáticas/epidemiologia , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Equador/epidemiologia , Humanos , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Pessoa de Meia-Idade , Plasmodium falciparum/fisiologia , Plasmodium vivax/fisiologia , Prevalência , Adulto JovemRESUMO
BACKGROUND: Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and protective efficacy of PvRAS immunization. METHODOLOGY/PRINCIPAL FINDINGS: A randomized, single-blinded trial was conducted. Duffy positive (Fy+; Pv susceptible) individuals were enrolled: 14 received bites from irradiated (150 ± 10 cGy) Pv-infected Anopheles mosquitoes (RAS) and 7 from non-irradiated non-infected mosquitoes (Ctl). An additional group of seven Fy- (Pv refractory) volunteers was immunized with bites from non-irradiated Pv-infected mosquitoes. A total of seven immunizations were carried out at mean intervals of nine weeks. Eight weeks after last immunization, a controlled human malaria infection (CHMI) with non-irradiated Pv-infected mosquitoes was performed. Nineteen volunteers completed seven immunizations (12 RAS, 2 Ctl, and 5 Fy-) and received a CHMI. Five of 12 (42%) RAS volunteers were protected (receiving a median of 434 infective bites) compared with 0/2 Ctl. None of the Fy- volunteers developed infection by the seventh immunization or after CHMI. All non-protected volunteers developed symptoms 8-13 days after CHMI with a mean pre-patent period of 12.8 days. No serious adverse events related to the immunizations were observed. Specific IgG1 anti-PvCS response was associated with protection. CONCLUSION: Immunization with PvRAS was safe, immunogenic, and induced sterile immunity in 42% of the Fy+ volunteers. Moreover, Fy- volunteers were refractory to Pv malaria. TRIAL REGISTRATION: Identifier: NCT01082341.