Outcome Of Infectious Diseases Research Articles

The impact of the cost-of-living crisis on population health in the UK: rapid evidence review

BackgroundIn the UK, unique and unforeseen factors, including COVID-19, Brexit, and Ukraine-Russia war, have resulted in an unprecedented cost of living crisis, creating a second health emergency. We present, one of the first rapid reviews with the aim of examining the impact of this current crisis, at a population level. We reviewed published literature, as well as grey literature, examining a broad range of physical and mental impacts on health in the short, mid, and long term, identifying those most at risk, impacts on system partners, including emergency services and the third sector, as well as mitigation strategies.MethodsWe conducted a rapid review by searching PubMed, Embase, MEDLINE, and HMIC (2020 to 2023). We searched for grey literature on Google and hand-searched the reports of relevant public health organisations. We included interventional and observational studies that reported outcomes of interventions aimed at mitigating against the impacts of cost of living at a population level.ResultsWe found that the strongest evidence was for the impact of cold and mouldy homes on respiratory-related infections and respiratory conditions. Those at an increased risk were young children (0–4 years), the elderly (aged 75 and over), as well as those already vulnerable, including those with long-term multimorbidity. Further short-term impacts include an increased risk of physical pain including musculoskeletal and chest pain, and increased risk of enteric infections and malnutrition. In the mid-term, we could see increases in hypertension, transient ischaemic attacks, and myocardial infarctions, and respiratory illnesses. In the long term we could see an increase in mortality and morbidity rates from respiratory and cardiovascular disease, as well as increase rates of suicide and self-harm and infectious disease outcomes. Changes in behaviour are likely particularly around changes in food buying patterns and the ability to heat a home. System partners are also impacted, with voluntary sectors seeing fewer volunteers, an increase in petty crime and theft, alternative heating appliances causing fires, and an increase in burns and burn-related admissions. To mitigate against these impacts, support should be provided, to the most vulnerable, to help increase disposable income, reduce energy bills, and encourage home improvements linked with energy efficiency. Stronger links to bridge voluntary, community, charity and faith groups are needed to help provide additional aid and support.ConclusionAlthough the CoL crisis affects the entire population, the impacts are exacerbated in those that are most vulnerable, particularly young children, single parents, multigenerational families. More can be done at a community and societal level to support the most vulnerable, and those living with long-term multimorbidity. This review consolidates the current evidence on the impacts of the cost of living crisis and may enable decision makers to target limited resources more effectively.

Omega-3 long-chain polyunsaturated fatty acids and their bioactive lipids: A strategy to improve resistance to respiratory tract infectious diseases in the elderly?

Age-related changes in organ function, immune dysregulation, and the effects of senescence explain in large part the high prevalence of infections, including respiratory tract infections in older persons. Poor nutritional status in many older persons increases susceptibility to infection and worsens prognosis. Interestingly, there is an association between the amount of saturated fats in the diet and the rate of community-acquired pneumonia. Polyunsaturated fatty acids, particularly omega-3 long chain polyunsaturated fatty acids (ω-3 LC-PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have well-known anti-inflammatory, immunomodulatory, and antimicrobial effects, which may, in theory, be largely induced by PUFAs-derived lipids such as specialized pro-resolving mediators (SPMs). In adults, preliminary results of studies show that ω-3 LC-PUFAs supplementation can lead to SPM generation. SPMs have a crucial role in the resolution of inflammation, a factor relevant to survival from infection independent of the pathogen’s virulence. Moreover, the immune system of older adults appears to be more sensitive to ω-3 PUFAs. This review explores the effects of ω-3 LC-PUFAs, and PUFA bioactive lipid-derived SPMs in respiratory tract infections and the possible relevance of these data to infectious disease outcomes in the older population. The hypothesis that PUFAs have beneficial effects via SPM generation will need to be confirmed by animal experiments and patient-derived data.

Prioritizing Equity in Antimicrobial Stewardship Efforts (EASE): a framework for infectious diseases clinicians.

Health equity gaps persist across minoritized groups due to systems of oppression affecting health-related social needs such as access to transportation, education and literacy, or food and housing security. Consequently, disparities in the prevalence of multidrug-resistant infections, infectious disease outcomes, and inappropriate antimicrobial use have been reported across minoritized populations. The Joint Commission and Centers for Medicare and Medicaid Services (CMS) have formally acknowledged the importance of integrating health equity-focused initiatives into existing hospital quality improvement (QI) programs. Here, we review documented disparities in antimicrobial stewardship and offer a framework, derived from components of existing health equity and QI tools, to guide clinicians in prioritizing equity in antimicrobial stewardship efforts (EASE).

Endogenous Retroviruses Unveiled: A Comprehensive Review of Inflammatory Signaling/Senescence-Related Pathways and Therapeutic Strategies.

Endogenous retroviruses (ERVs), a subset of genomic transposable elements (TEs) in a broader sense, have remained latent within mammalian genomes for tens of millions of years. These genetic elements are typically in a silenced state due to stringent regulatory mechanisms. However, under specific conditions, they can become activated, triggering inflammatory responses through diverse mechanisms. This activation has been shown to play a potential role in various neurological disorders, tumors, and cellular senescence. Consequently, the regulation of ERV expression through various methods holds promise for clinical applications in disease treatment. ERVs also engage in interactions with a variety of exogenous viruses, thereby influencing the outcomes of viral infectious diseases. This article comprehensively reviews the pathogenic cascade of ERVs, encompassing activation, inflammation, associated diseases, senescence, and interplay with viruses. Additionally, it outlines therapeutic strategies targeting ERVs with the aim of offering novel research directions for understanding the relationship between ERVs and diseases, along with corresponding treatment modalities.

Исход COVID-19 тяжелого течения у ребенка с морбидным ожирением

Obesity is one of the most essential medical and social problems. When it was noted that obese children had higher risks of disease, complications and mortality, the overweight effect on the course and outcome of infectious respiratory diseases became particularly important during the flu pandemic. According to numerous studies, obesity has been considered as a predictor of the adverse and even fatal outcome of COVID-19, participating in the formation of multisystem inflammatory syndrome in children (MIS-C). This article demonstrates a case study of severe COVID-19 complicated by MIS-C, multiple thrombosis, and multiple organ dysfunction syndrome in a 9-year-old child with morbid obesity. The article describes the patient management and the complex of diagnostic and therapeutic measures conducted. The main pathogenetic mechanisms of the inflammatory process explaining the association between obesity and the SARS-CoV-2 coronavirus damaging effects are also considered. The need for timely diagnosis and treatment of both obesity itself and comorbid pathology is shown to prevent potentially life-threatening conditions. KEYWORDS: children, obesity, new coronavirus infection, COVID-19, SARS-CoV-2, multisystem inflammatory syndrome, premorbid history, thrombosis, multiple organ dysfunction syndrome. FOR CITATION: Kartashova D.A., Bokova T.A., Razheva I.V., Bevz A.S., Vorontsova S.V. Severe COVID-19 course outcome in a child with morbid obesity. Russian Journal of Woman and Child Health. 2024;7(1):79–85 (in Russ.). DOI: 10.32364/2618-8430-2024-7-1-12.

Pathogen-driven nucleotide overload triggers mitochondria-centered cell death in phagocytes.

Staphylococcus aureus is a dangerous pathogen that evolved refined immuno-evasive strategies to antagonize host immune responses. This involves the biogenesis of death-effector deoxyribonucleosides, which kill infectious foci-penetrating macrophages. However, the exact mechanisms whereby staphylococcal death-effector deoxyribonucleosides and coupled imbalances of intracellular deoxyribonucleotide species provoke immune cell death remain elusive. Here, we report that S. aureus systematically promotes an overload of deoxyribonucleotides to trigger mitochondrial rupture in macrophages, a fatal event that induces assembly of the caspase-9-processing apoptosome and subsequent activation of the intrinsic pathway of apoptosis. Remarkably, genetic disruption of this cascade not only helps macrophages coping with death-effector deoxyribonucleoside-mediated cytotoxicity but also enhances their infiltration into abscesses thereby ameliorating pathogen control and infectious disease outcomes in laboratory animals. Combined with the discovery of protective alleles in human CASP9, these data highlight the role of mitochondria-centered apoptosis during S. aureus infection and suggest that gene polymorphisms may shape human susceptibility toward a predominant pathogen.

Testosterone affects type I/type II interferon response of neutrophils during hepatic amebiasis.

Differences in immune response between men and women may influence the outcome of infectious diseases. Intestinal infection with Entamoeba histolytica leads to hepatic amebiasis, which is more common in males. Previously, we reported that innate immune cells contribute to liver damage in males in the murine model for hepatic amebiasis. Here, we focused on the influences of sex and androgens on neutrophils in particular. Infection associated with neutrophil accumulation in the liver was higher in male than in female mice and further increased after testosterone treatment in both sexes. Compared with female neutrophils, male neutrophils exhibit a more immature and less activated status, as evidenced by a lower proinflammatory N1-like phenotype and deconvolution, decreased gene expression of type I and type II interferon stimulated genes (ISGs) as well as downregulation of signaling pathways related to neutrophil activation. Neutrophils from females showed higher protein expression of the type I ISG viperin/RSAD2 during infection, which decreased by testosterone substitution. Moreover, ex vivo stimulation of human neutrophils revealed lower production of RSAD2 in neutrophils from men compared with women. These findings indicate that sex-specific effects on neutrophil physiology associated with maturation and type I IFN responsiveness might be important in the outcome of hepatic amebiasis.

Effect of Vitamin D3 Levels on Varicella-Zoster Virus Infection and IFN-Gamma Expression in Children: A Cross-Sectional Study in Iraq

Background: This study aimed to explore the correlation between Vitamin D3 levels and IFN-Gamma expression in children residing in the southern and central provinces of Iraq. Vitamin D3 plays a pivotal role in immune function, and IFN-Gamma is a crucial cytokine involved in antiviral defense. Investigating the connection between Vitamin D3 and IFN-Gamma offers valuable insights into immune responses and potential implications for infectious diseases.Methods: A case-control study was conducted, involving children from various schools and kindergartens in the southern and central provinces of Iraq. The study assessed Vitamin D3 levels and measured IFN-Gamma expression. Statistical analyses were performed to determine the relationship between these variables.Results: The outcomes revealed a significant positive correlation between Vitamin D3 levels and IFN-Gamma expression within the study population (p < 0.05). Children with higher Vitamin D3 levels exhibited elevated IFN-Gamma expression, suggesting a possible immunomodulatory impact of Vitamin D3 on IFN-Gamma production.Conclusion:These findings underscore the importance of maintaining adequate Vitamin D3 levels to support immune function, particularly in relation to IFN-Gamma expression. Improving Vitamin D3 status could potentially bolster antiviral defense mechanisms and reduce susceptibility to viral infections among children in the southern and central provinces of Iraq. Further investigation is warranted to delve into the underlying mechanisms and potential clinical ramifications of this significant association. Additionally, exploring the long-term effects of maintaining optimal Vitamin D3 levels on immune function and the outcomes of infectious diseases in this population would offer valuable insights for preventive and therapeutic strategies.

Crosstalk of ferroptosis and oxidative stress in infectious diseases.

Ferroptosis is a type of programmed cell death that pathogens can leverage to enhance their replication, transmission, and pathogenicity. Hosts typically combat pathogenic infections by utilizing oxidative stress as a defense mechanism. Nonetheless, some pathogens can trigger considerable oxidative stress while infecting, inducing an intense inflammatory response in the host's immune system and activating cell death. The process of ferroptosis is closely linked to oxidative stress, with their interaction exerting a substantial impact on the outcome of infectious diseases. This article presents an overview of the interrelated mechanisms of both Ferroptosis and oxidative stress in infectious diseases, identifying potential targets for treating such diseases in the context of their interaction.

Knowledge of Medical Students Regarding Antimicrobial Resistance

The discovery of antibiotics has enhanced the treatment outcomes of infectious diseases. Nevertheless, the injudicious use of antibiotics has triggered a global public health crisis and caused a worldwide spread of antimicrobial-resistant microorganisms. Antimicrobial resistance is slowly becoming a major health problem all around the world, especially in our country, and this might be due to the incorrect, unwise prescription of antimicrobial agents among some doctors, which gives rise to this problem. The present study aimed to estimate the knowledge of medical students in Baghdad regarding antimicrobial usage and resistance and to find the association of sociodemographic factors with knowledge scores. A descriptive cross-sectional study was conducted in six medical colleges in Baghdad. An online- based questionnaire was published and used in collecting the data. The data were reviewed and entered to be statistically analyzed in SPSS using the Chi-square test and were presented as frequencies, percentages, graphs and tables. The results showed that 44.1% of the studied sample had a fair knowledge of antimicrobial resistance. There was a statistical significance between gender and knowledge about antimicrobial resistance as the P-value was 0.006. In addition, there was a statistically significant association between the stage and the knowledge about antimicrobial resistance, where the P-value was (0.000). It was concluded that most of the participants had fair to good knowledge regarding antimicrobial resistance that was significantly associated with gender and stage.

Social inequalities and the COVID-19 pandemic

Social inequality has been identified as an important determinant of the outcome of infectious diseases and the recent SARS-CoV-2 pandemic has vividly reminded us that there are no “equal opportunity infectors”. In a recent article, Chakrabarty et al. (2023) reported the finding of a cross-country comparison of COVID-19 cases and social deprivation, using up-to-date statistical modelling. These results add to the extensive evidence showing that vulnerable populations are consistently at higher risk of contracting the infection and to suffer from more severe symptoms, whatever the spatial scale used (from the country to the neighborhood). Spatial clustering of socially deprived groups, preexisting pathologies and hotspots of COVID-19 cases and deaths indicate that the SARS-CoV-2 should be seen as a syndemic, where both the infection dynamics and the outcome of the disease strongly depend on the three-way interaction between the virus, preexisting pathologies, and the socioeconomic environment.

319. Infectious disease healthcare utilization and outcomes of patients discharged to skilled nursing facilities on parenteral antibiotic therapy

Abstract Background Hospitalized patients are frequently discharged to a skilled nursing facility (SNF) for parenteral antibiotic therapy (PAT). While there are studies describing the healthcare utilization and outcomes of individuals receiving post-hospital PAT in non-institutional settings, characterization of the PAT experience among SNF patients remains limited. To address this gap in knowledge, we conducted a retrospective cohort study of hospitalized patients discharged to a SNF on antimicrobial therapy. Methods Health records of patients (age ≥18 years) hospitalized in a single hospital who were discharged on systemic antibiotics to a SNF from 1/1/2016 - 12/31/2018 were reviewed. Subjects who received an inpatient ID consultation and were discharged on PAT were included. Information captured included patient demographics, diagnoses, discharge antibiotic regimen and timing, post-discharge encounters, 90-day hospital readmissions, and losses to follow-up. This study was approved by the Institutional Review Board with a waiver for informed consent. Results 155 patients meeting the inclusion criteria were identified. Post-discharge follow-up with the ID Service was not recommended for 19 patients (12.3%). Patients who followed-up post-discharge had a total of 264 sub-specialty provider (mean: 2.8/patient; range: 0-13) and 170 ID provider (mean: 1.7/patient; range: 0-5) face-to-face encounters within 90 days of discharge. Average time to ID clinic follow-up was 3.2 weeks (range: 1-6 weeks). ID clinic nursing staff conducted 1373 telephone encounters (mean: 13.9/patient; range, 3-40) with SNF nursing staff within 90 days of discharge. The 90-day hospital readmission rate was 37% (36/101 patients) and 47% of readmissions were ID-related. The 90-day mortality rate was 9%; 2 patients died before and 7 after outpatient follow-up was established. Conclusion ID clinic follow-up of patients discharged to a SNF on PAT was infrequent, but their care entailed a higher volume of telephone care coordination, and they experienced higher readmission rates relative to patients receiving PAT in ambulatory settings. Further studies to better understand if these findings are driven by patient factors or issues related to SNF care practices are needed. Disclosures All Authors: No reported disclosures

Advances in the regulation of inflammasome activation by GBP family in infectious diseases.

Guanylate-binding proteins (GBPs) are a subfamily of interferon-inducible proteins that undertake distinct roles in the the context of bacteria, virus, chlamydia and parasites infections. These proteins exert a notable influence on the progression and outcomes of infectious diseases. Within the realm of host cell-autonomous immunity against pathogens, GBPs have been identified as the regulators of pyroptosis through canonical and noncanonical inflammasome activation pathways. In this review, we summarize the structure and evolution of GBP family members, the canonical and noncanonical inflammasome activation pathways, the roles of GBPs in regulating inflammasome activation, and the mechanisms of GBPs affecting infections induced by different pathogens. We hope to provide new basic research clues for the pathogenesis and diagnosis and treatment of infectious diseases.

Endogenous bacteriophages in intensive care patients with bacteremia and sepsis

Aim. To study the effect of endogenous bacteriophages on the outcome of infectious and inflammatory diseases in intensive care patients.Materials and methods. 30 patients with positive hemoculture were examined for the presence of bacteriophages. The detection of endogenous bacteriophages in the blood of patients was made using traditional virological methods. Statistical analysis was performed using the Statistica 10 program.Results. The bacteriophages were found in the blood of 11 patients, 5 of them were examined in dynamics15 strains of microorganisms were isolated. The mortality rate of patients in the phagopositive group was 18.2 %. 19 patients had no endogenous bacteriophages. In this group, the mortality rate was 68.4 %, that is significantly higher than in patients with endogenous phages. K. pneumonia was are the main causative agent of bacteremia and sepsis (12 strains out of 36).Conclusions. Fatal outcomes were more often detected in patients whose endogenous bacteriophages were not detected in the blood. The most serious complications with frequent fatal outcomes were observed in patients with bacteremia caused by K. pneumonia.

Molecular and phenotypic distinctions of macrophages in tolerant and susceptible to hypoxia rats.

Individual hypoxia tolerance is a major influence on the course and outcome of infectious and inflammatory diseases. Macrophages, which play central roles in systemic inflammatory response and other immunity reactions, are subject to functional activation orchestrated by several transcription factors including hypoxia inducible factors (HIFs). HIF-1 expression levels and the lipopolysaccharide (LPS)-induced systemic inflammatory response severity have been shown to correlate with hypoxia tolerance. Molecular and functional features of macrophages, depending on the organisms resistance to hypoxia, can determine the severity of the course of infectious and inflammatory diseases, including the systemic inflammatory response. The purpose is the comparative molecular and functional characterization of non-activated and LPS-activated bone marrow-derived macrophages under normoxia in rats with different tolerance to oxygen deprivation. Hypoxia resistance was assessed by gasping time measurement in an 11,500 m altitude-equivalent hypobaric decompression chamber. Based on the outcome, the animals were assigned to three groups termed 'tolerant to hypoxia' (n=12), 'normal', and 'susceptible to hypoxia' (n=13). The 'normal' group was excluded from subsequent experiments. One month after hypoxia resistance test, the blood was collected from the tail vein to isolate monocytes. Non-activated and LPS-activated macrophage cultures were investigated by PCR, flow cytometry and Western blot methods. Gene expression patterns of non-activated cultured macrophages from tolerant and susceptible to hypoxia animals differed. We observed higher expression of VEGF and CD11b and lower expression of Tnfa, Il1b and Epas1 in non-activated cultures obtained from tolerant to hypoxia animals, whereas HIF-1α mRNA and protein expression levels were similar. LPS-activated macrophage cultures derived from susceptible to hypoxia animals expressed higher levels of Hif1a and CCR7 than the tolerant group; in addition, the activation was associated with increased content of HIF-1α in cell culture medium. The observed differences indicate a specific propensity toward pro-inflammatory macrophage polarization in susceptible to hypoxia rats.

Pre-Existing Interstitial Lung Abnormalities in Patients with Head and Neck Squamous Cell Carcinoma and Their Follow Up after Therapy.

Interstitial lung abnormalities (ILAs) are incidentally found nondependent parenchymal abnormalities affecting more than 5% of any lung zone and are potentially related to interstitial lung disease and worsening post-treatment outcomes in malignancies and infectious diseases. The aim of this study was to determine the prevalence and type of ILA changes in patients with head and neck squamous cell carcinoma (HNSCC) and their change in the follow-up period. This retrospective single-center study included 113 patients with newly diagnosed HNSCC who underwent lung MSCT prior to treatment. ILAs were reported in 13.3% of patients on pretreatment MSCT. Patients with ILAs were significantly older (median 75 vs. 67 years). ILAs were most prevalent in lower zones (73.3%) (p = 0.0045). The most reported ILA subtype was subpleural non-fibrotic (60%) (p = 0.0354). Reticulations were the most frequently described pattern (93.3%) (p < 0.0001). Progression of ILAs was reported in almost 30% of patients after receiving therapy. Patients with pre-existing ILAs were more likely to develop radiation-induced lung fibrosis after adjuvant radiotherapy (p = 0.0464). In conclusion, ILA's incidence, distribution and presentation were similar to previous research conducted in other special cohorts. Our research suggests a possible association of more frequent radiation pneumonitis with ILA changes in patients with HNSCC, which should be further investigated.

Sex differences in neurologic presentation and outcome of SARS-CoV-2, especially cerebrovascular manifestations

Neurological manifestations of COVID-19 and their impact have not been well characterized. Neurological involvement may be caused directly by the effects of the virus infecting the brain or indirectly by the local and systemic immune responses against the virus. Acute cerebrovascular disease, particularly ischemic stroke, has emerged as a serious complication of infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The arrival of COVID-19 represented a unique occasion to study sex difference, and accentuated the need for further study to elucidate the mechanisms that differentiate clinical outcomes among male and female patients. Recent pandemics has a clear sex disparity in clinical outcomes, and morbidity and mortality from COVID-19 are higher among men. Interestingly, the previous decade, there was sparse literature evaluating the impact of sex differences on outcomes in infectious diseases, especially on neurologic complications. Ongoing advances in scientific research have demonstrated sex differences in the neurological complications of neuroinfectious diseases, and sex and disparities in health care are frequently encountered. The evidence for potential sex differences and gender inequalities, including socioeconomic status and occupational exposure in the COVID-19 pandemic is continuing to emerge. In summary, sex is increasingly recognized as a critical determinant of health and disease, particularly relevant to the topical COVID-19 pandemic. Morbidity and mortality from COVID-19 are greater for males, however, the mechanisms for this difference are unclear. Understanding the differences in outcomes between males and females improve the effectiveness of health interventions. However, outcomes of the neurologic complications of infectious disease may be partially explained by sex differences in immune responses. With this narrative, we intend to provide the reader with a comprehensive coverage of where we currently stand regarding sex differences specific, especially on outcomes critical neurologic manifestations of the SARS-CoV-2 infection.

Relationship between zinc levels, anthropometric parameters and socio-demographic status among primary school pupils in a semi-urban community in Nigeria

Background: Zinc plays important roles in many biological processes in the body such as acting as a catalyst for numerous enzymes involved in nucleic acid metabolism cellular replication tissue repair and the growth of tissues hence, the study was aimed to determine the relationship between zinc levels, anthropometric parameters and socio-demographic status among primary school pupils. Methods: The study was a cross-sectional descriptive design carried out among four hundred primary school pupils between the ages 6-12 years in Ogbomoso. Questionnaires were distributed to obtain socio-demographic information from pupils and blood was collected for serum zinc analysis using ELISA technique. The data obtained were analyzed using Statistical Package for Social Sciences (SPSS) version 21 Results: The level of serum zinc deficiency in the study population was 9.5%. Serum zinc levels are significantly higher among younger age groups compared to older age groups (F=6.913, p value=0.001). The family size and socio-economic class are significantly associated with zinc levels. Zinc level was significantly lower in underweight children (0.389±0.25) compared to normal weight (0.819±0.39), overweight (0.991±0.62) and obese children (0.654±0.41), F=7.264, p=0.001 Conclusions: Zinc deficiency is an important component of nutritionally related morbidity worldwide. Zinc supplementation or food fortification among school children will have beneficial effects on the incidence and outcome of serious childhood infectious diseases.

Eculizumab suppresses zymosan-induced release of inflammatory cytokines IL-1α, IL-1β, IFN-γ and IL-2 in autologous serum-substituted PBMC cultures: Relevance to cytokine storm in Covid-19

Background and objectiveCytokine storm (CS) is a major contributor to the fatal outcome of severe infectious diseases, including Covid-19. Treatment with the complement (C) C5 inhibitor eculizumab was beneficial in end-stage Covid-19, however, the mechanism of this effect is unknown. To clarify this, we analyzed the relationship between C activation and production of pro-inflammatory cytokines in a PBMC model. MethodsHuman PBMC with or without 20 % autologous serum was incubated with C3a, C5a, zymosan or zymosan-pre-activated serum (ZAS) for 24 h with or without eculizumab or the C5a receptor antagonist, DF2593A. C activation (sC5b-9) and 9 inflammatory cytokines were measured by ELISA. ResultsIn serum-free unstimulated PBMC only IL-8 release could be measured during incubation. Addition of C5a increased IL-8 secretion only, ZAS induced both IL-2 and IL-8, while zymosan led to significant production of all cytokines, most abundantly IL-8. In the presence of serum the above effects were greatly enhanced, and the zymosan-induced rises of IL-1α, IL-1β IFN-γ and IL-2 were significantly attenuated by eculizumab but not by DF2593a. ConclusionsThese data highlight the complexity of interrelationships between C activation and cytokine secretion under different experimental conditions. The clinically relevant findings include the abundant formation of the chemokine IL-8, which was stimulated by C5a, and the suppression of numerous inflammatory cytokines by eculizumab, which explains its therapeutic efficacy in severe Covid-19. These data strengthen the clinical relevance of the applied PBMC model for drug screening against CS, enabling the separation of complex innate immune cross-talks.

Monsoon Floods: A Challenge To Pakistan's Already Fragile Healthcare Infrastructure.

Madam, This monsoon season's floods from mid-July 2022 onwards have proven to be the most catastrophic climate disaster in Pakistan's history, flooding a third of the country, killing more than 1290 people, and forcing a staggering 634,000 people to take refuge in relief camps [1]. Furthermore, of greater concern is the implications of the floods on already fragile healthcare infrastructure in a country with a weak economy and limited fund allocation for Health Services. In this regard, the World Health Organization has reported damage to 1460 health facilities; 432 are inoperable and 1,028 were partially destroyed [1]. Considering the deficit of healthcare centres, and medical professionals and the availability of medications in low-lying, agricultural, and rural setups of the major provinces, the transmission of infectious diseases is inevitable. Subsequently, there is a significant concern surrounding the feasibility of relief camps set up, where overcrowding of displaced individuals, lack of proper sanitation and sewage systems, and inadequate hygienic food further stimulate communicable disease spread. Notably, the stagnant water surface remaining after flood water recedes serves as an ideal reservoir for mosquito vector growth and hence transmission of infectious diseases such as malaria and dengue affecting vulnerable populations, primarily the refugees in congested camps lacking basic sanitation and insecticidal net beds to sleep under. Moreover, overcrowding and destruction of sewage systems causing water contamination could lead to the oral-faecal transfer of gastrointestinal pathogens, causative agents of diarrheal diseases [2]. Cholera is the most prevalent infectious disease outcome of the floods as evidenced by reports of 115 922 cases of acute diarrhoea in KPK in the aftermath of the summer 2010 floods [2]. In addition, one of the major concerns identified among the displaced population is the alarming number of pregnant women in dire need of proper medical and residential facilities to facilitate their infants. In this context, the United Nations Population Fund (UNFPA), released a startling estimate of 650,000 pregnant women affected by floods of which over 73,000 are expected to deliver within a month [3]. UNFPA has set a precedent by providing 8,311 dignity kits, 7,411 newborn baby kits, and 6,412 clean delivery kits. However, this would not be enough considering the magnitude of mass displacement [3]. ---Continue