Interference of reversible redox compounds in enzyme catalysed assays - Electrochemical limitations.

BACKGROUND: Several commercial assay kits exist with limited explanation of the kit components and reagent constituents, which greatly increases potential incompatibility issues resulting in the loss of samples, time, and data. Herein we explore such issues via the redox ion [Fe(CN)6]3/4- in two commercial l-lactate and pyruvate assay kits. RESULTS: We clearly demonstrate significant interference from redox compounds with the l-lactate and pyruvate assays; a significance in signal inhibition/mechanism restriction, and false/mechanism exhaustion, respectively. Potential mechanisms are explored to explain interference. CONCLUSION: The need for transparency is crucial for consistency of assay kit performance from lab to lab. There is a need for suppliers to list the components of kits and/or list the potential for interference from specific agents to ensure that results obtained from these kits are reliable and reproducible.

Differential Cytokine Responses and the Clinical Severity of Adult and Pediatric Nephropathia Epidemica.

Nephropathia epidemica (NE), caused by the hantavirus infection, is endemic in Tatarstan Russia. The majority of patients are adults, with infection rarely diagnosed in children. This limited number of pediatric NE cases means there is an inadequate understanding of disease pathogenesis in this age category. Here, we have analyzed clinical and laboratory data in adults and children with NE to establish whether and how the disease severity differs between the two age groups. Serum cytokines were analyzed in samples collected from 11 children and 129 adult NE patients during an outbreak in 2019. A kidney toxicity panel was also used to analyze urine samples from these patients. Additionally, serum and urine samples were analyzed from 11 control children and 26 control adults. Analysis of clinical and laboratory data revealed that NE was milder in children than in adults. A variation in serum cytokine activation could explain the differences in clinical presentation. Cytokines associated with activation of Th1 lymphocytes were prominent in adults, while they were obscured in sera from pediatric NE patients. In addition, a prolonged activation of kidney injury markers was found in adults with NE, whilst only a short-lasting activation of these markers was observed in children with NE. These findings support previous observations of age differences in NE severity, which should be considered when diagnosing the disease in children.

Rosuvastatin as a Supplemental Treatment for the Clinical Symptoms of Nephropathia Epidemica: A Pilot Clinical Study.

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1ß and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases.

Lost in translation. Homer in English; the patient's story in medicine.

In a series of previous articles, we have considered how we might reconceptualise central themes in medicine and medical education through 'thinking with Homer'. This has involved using textual approaches, scenes and characters from the Iliad and Odyssey for rethinking what is a 'communication skill', and what do we mean by 'empathy' in medical practice; in what sense is medical practice formulaic, like a Homeric 'song'; and what is lyrical about medical practice. Our approach is not to historicise medicine and medical education, but to use thinking with Homer as a medium and metaphor for questioning the habitual and the taken-for-granted in contemporary practice. In this article, we tackle the complex theme of 'translation'. We use the lens of translation studies to examine the process of turning the patient's story into medical language. We address the questions: what makes a 'good' translation? What are the consequences of mistranslation and poor translation? And, while things are inevitably lost in translation, does this matter?

The embodiment of lyricism in medicine and Homer.

Improving the quality of communication between doctors and their patients and colleagues is of vital importance. Poor communication, especially within and across clinical teams working around patients in pathways of care, leads to avoidable medical error, where an unacceptable number of patients are severely harmed or die each year. The figures from such iatrogenesis have now reached epidemic proportions, constituting one of the major killers of patients worldwide. Despite 30 years' worth of explicit attention to teaching communication skills at undergraduate level, communication in medicine is failing to improve at an acceptable rate. The authors suggest a rather unusual approach to this dilemma of 'communication hypocompetence'­thinking medicine lyrically­as an extension of thinking with Homer's little-discussed lyrical aesthetic. A key part of the problem of communication hypocompetence is the well-researched phenomenon of 'empathy decline' in students, where 'hardening' and cynicism occur as over-determined ego defences. Empathy decline may be a symptom of the repression of the lyrical genre in medicine, where the epic, tragic and dark comic genres dominate. The lyrical genre emphasises coming to know the patient as a person and an individual. Importantly, central to performing the lyric genre is the heightened use of the senses in taking a history, physical examination and diagnostic work. Framing medicine as lyrical work challenges undue emphasis on 'cure' at the expense of humane 'care'.

Inhibition of Arenavirus Entry and Replication by the Cell-Intrinsic Restriction Factor ZMPSTE24 Is Enhanced by IFITM Antiviral Activity.

In the absence of effective vaccines and treatments, annual outbreaks of severe human haemorrhagic fever caused by arenaviruses, such as Lassa virus, continue to pose a significant human health threat. Understanding the balance of cellular factors that inhibit or promote arenavirus infection may have important implications for the development of effective antiviral strategies. Here, we identified the cell-intrinsic zinc transmembrane metalloprotease, ZMPSTE24, as a restriction factor against arenaviruses. Notably, CRISPR-Cas9-mediated knockout of ZMPSTE24 in human alveolar epithelial A549 cells increased arenavirus glycoprotein-mediated viral entry in pseudoparticle assays and live virus infection models. As a barrier to viral entry and replication, ZMPSTE24 may act as a downstream effector of interferon-induced transmembrane protein (IFITM) antiviral function; though through a yet poorly understood mechanism. Overexpression of IFITM1, IFITM2, and IFITM3 proteins did not restrict the entry of pseudoparticles carrying arenavirus envelope glycoproteins and live virus infection. Furthermore, gain-of-function studies revealed that IFITMs augment the antiviral activity of ZMPSTE24 against arenaviruses, suggesting a cooperative effect of viral restriction. We show that ZMPSTE24 and IFITMs affect the kinetics of cellular endocytosis, suggesting that perturbation of membrane structure and stability is likely the mechanism of ZMPSTE24-mediated restriction and cooperative ZMPSTE24-IFITM antiviral activity. Collectively, our findings define the role of ZMPSTE24 host restriction activity in the early stages of arenavirus infection. Moreover, we provide insight into the importance of cellular membrane integrity for productive fusion of arenaviruses and highlight a novel avenue for therapeutic development.

Antibody and T Cell Immune Responses to SARS-CoV-2 Peptides in COVID-19 Convalescent Patients.

Identifying immunogenic targets of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical to advance diagnostic and disease control strategies. We analyzed humoral (ELISA) and T-cell (ELISpot) immune responses to spike (S) and nucleocapsid (N) SARS-CoV-2 proteins as well as to human endemic coronavirus (eCoV) peptides in serum from convalescent coronavirus disease 2019 (COVID-19) patients from Tatarstan, Russia. We identified multiple SARS-CoV-2 peptides that were reactive with serum antibodies and T cells from convalescent COVID-19. In addition, age and gender associated differences in the reactivity to S and N protein peptides were identified. Moreover, several SARS-CoV-2 peptides tested negatively correlated with disease severity and lung damage. Cross-reactivity to eCoV peptides was analyzed and found to be lower in COVID-19 compared to controls. In this study, we demonstrate the changing pattern of immunogenic peptide reactivity in COVID-19 serum based on age, gender and previous exposure to eCoVs. These data highlight how humoral immune responses and cytotoxic T cell responses to some of these peptides could contribute to SARS-CoV-2 pathogenesis.

Immunogenic SARS-CoV-2 S and N Protein Peptide and Cytokine Combinations as Biomarkers for Early Prediction of Fatal COVID-19.

Early indications of the likelihood of severe coronavirus disease 2019 COVID-19 can influence treatments and could improve clinical outcomes. However, knowledge on the prediction markers of COVID-19 fatality risks remains limited. Here, we analyzed and quantified the reactivity of serum samples from acute (non-fatal and fatal) and convalescent COVID-19 patients with the spike surface glycoprotein (S protein) and nucleocapsid phosphoprotein (N protein) SARS-CoV-2 peptide libraries. Cytokine activation was also analyzed. We demonstrated that IgM from fatal COVID-19 serum reacted with several N protein peptides. In contrast, IgM from non-fatal serum reacted more with S protein peptides. Further, higher levels of pro-inflammatory cytokines were found in fatal COVID-19 serum compared to non-fatal. Many of these cytokines were pro-inflammatory and chemokines. Differences in IgG reactivity from fatal and non-fatal COVID-19 sera were also demonstrated. Additionally, the longitudinal analysis of IgG reactivity with SARS-CoV-2 S and N protein identified peptides with the highest longevity in humoral immune response. Finally, using IgM antibody reactivity with S and N SARS-CoV-2 peptides and selected cytokines, we have identified a panel of biomarkers specific to patients with a higher risk of fatal COVID-19 compared with that of patients who survive. This panel could be used for the early prediction of COVID-19 fatality risk.

Marketing social marketing: getting inside those "big dogs' heads" and other challenges.

Social marketing provides a powerful process for planning and implementing public health programs. Although often applied to the promotion of healthier lifestyles, social marketing can also be used to promote utilization of direct services or policy changes. Despite growing popularity among public health professionals, resistance by senior management, community advocates, policy makers, and others can create barriers to the use of the social marketing model. This article draws on the authors' observations, practice experiences, extensive training interactions, and qualitative studies with public health practitioners across the nation. It examines some of the key reasons that public health practitioners encounter resistance to using social marketing and discusses how a logic model can be used to market social marketing in organizations and communities.

Control of West Nile virus, Rhode Island, 2003.

Thanks largely to systematic larviciding by the State's 39 municipalities, and aided by the public's destruction of "backyard" mosquito habitats and adoption of personal protective measures (clothing, repellant), Rhode Island minimized the potential human burden of WNV during the 2003 mosquito season (six serious WNV cases, one death, and no reports of WNV-tainted blood donations). The potential burden of WNV on domestic animals was also reduced through immunization. Nonetheless, the State's first WNV death reminds us of the danger this disease poses for the very young, for elders, and for people of all ages who are immune-compromised. Similarly, the widespread location of birds positive for WNV signifies the ubiquity of risk. All mosquitoes must be avoided. Based on its experience with WNV control over the past few years, the State will continue and enhance its surveillance and control efforts in 2004. Once again, systematic larviciding by municipalities and continuing public education through multiple channels will form the backbone of control, supported by active surveillance for the virus in the wild, in domestic animals, and in humans. For the latter effort, the vigilance of the health care community is of signal importance to the protection of the public. Every human case is investigated thoroughly, to establish as accurately as possible the time and place of exposure. DEM and HEALTH use this information to assess potential weaknesses in WNV control efforts, and to take corrective action, as necessary. Health care providers also play an essential role in public education, reminding patients (all patients, but especially the very young, elders, and the immune-compromised) to avoid mosquito bites. Discussing the avoidance of mosquito bites with patients who engage in regular outdoor activity is especially important. School physicians and the medical directors of nursing homes are well-positioned to keep mosquito control and avoidance on the agenda of their respective institutions. Together, we can control the burden of this disease among domestic animals and humans, if we continue to pursue mosquito control and personal protection aggressively. If we don't, the potential for tragedy is tremendous, as evidenced by the recent experience of other regions of the country.

Public health response to bioterrorism with Bacillus anthracis: coordinating public health laboratory, communication, and law enforcement.

In October 2001, public health departments across the United States were part of an intensive response to a bioterrorism event using anthrax spores delivered by mail. It is useful to examine this experience as an unscripted exercise of bioterrorism response capacity, more realistic than scenarios of planned exercises. The event particularly challenged public health laboratory and communications capacity, but it also tested surveillance and training capacity. The bioterrorism response demonstrated the importance of strong partnerships between the public health laboratory and emergency response agencies as well as medical providers and the usefulness of open, flexible communication strategies.