Insects that ingest microbial pathogens are also exposed to their toxins. The sensitivity of insects to ingested toxins of human pathogens and the potential mechanism of toxin resistance has not been thoroughly studied. We tested the survival of Drosophila melanogaster orally fed with exotoxins and endotoxins of ten human bacterial pathogens. We discovered that only a few toxins adversely affect fly survival, and that most toxins either do not affect or paradoxically extend insect survival (hormetic effect) at the dosages tested. We found that in Drosophila, Jra, a homolog of stress response transcription factor Jun, mediates a broad-spectrum toxin response, since the survival of Jra mutants was shortened in the presence of most of the tested toxins. This study begins to uncover the mechanism of the response of insects to toxins. It describes how a toxin-induced Jun stress response system helps insects reduce their sensitivity to toxins of human pathogens. Keywords: toxin; sensitivity; resistance; survival; immunity; Drosophila melanogaster Abbreviations: Jun related antigen (Jra); immune deficiency (Imd); antimicrobial peptides (AMP); mitogen-activated protein kinase (MAPK); Bloomington Drosophila stock center (BDSC); wild type (WT); lipopolysaccharide (LPS); adenosine diphosphate (ADP); adenosine triphosphate (ATP); adenosine monophosphate (cAMP); Jun N-terminal Kinase (JNK); Nuclear Factor-κB (NF-κB); absorption, distribution, metabolism, and excretion (ADME); absorption, distribution, metabolism, excretion, and toxicity (ADMET); confidence interval (CI); soluble N-ethylmale-imide-sensitive factorattachment protein receptors (SNARE); basic leucine zipper (bZIP); deoxyribonucleic acid (DNA); eukaryotic elongation factor (eEF); programmed death-ligand (PD-L); cluster of differentiation (CD).
Flies naturally contain microbes in their intestines after eating microbe-rich food like decaying fruits. When ingesting microbes, insects are also exposed to their toxins. The sensitivity of insects to ingested microbial toxins and their mechanism of response to toxins has not been thoroughly studied. Transcriptional regulator c-Myc has been shown to regulate the response to some but not all microbial toxins in mammals. We tested the sensitivity of wild-type and Myc mutant Drosophila melanogaster strains to two exotoxins, Clostridium perfringens α-toxin and Vibrio cholerae toxin, and two endotoxins, lipopolysaccharides (LPS) of Salmonella minnesota and S. typhimurium. We observed that both sexes of wild-type flies were insensitive to tested toxins. Similarly, Myc mutant males were insensitive to the four toxins. In contrast, female Myc mutants were significantly more sensitive to all tested toxins than wild-type females. The median survival of female Myc mutants was shortened by at least 54 hours in the presence of bacterial toxins. The component of LPS, lipid A, shortened the median survival of Myc females by 104 hours, indicating that the toxicity of LPS is caused by lipid A. This study demonstrates a sex-specific mechanism of the response of insects to toxins and describes that Myc protects female fruit flies from the tested microbial toxins. Keywords: bacterial toxins; sensitivity; resistance; survival; immunity; Drosophila melanogaster Abbreviations: Immune deficiency (Imd); antimicrobial peptides (AMP); mitogen-activated protein kinase (MAPK); Bloomington Drosophila stock center (BDSC); wild type (WT); lipopolysaccharide (LPS); adenosine diphosphate (ADP); Jun N-terminal Kinase (JNK); Nuclear Factor-κB (NF-κB); absorption, distribution, metabolism, and excretion (ADME); absorption, distribution, metabolism, excretion, and toxicity (ADMET); confidence interval (CI); deoxyribonucleic acid (DNA); intestinal stem cells (ISCs); Janus kinases (JAK); signal transducer and activator of transcription (STAT); epidermal growth factor EGF; and Wingless (Wg).
Background Italy was the first country in Europe to report a SARS-CoV-2 case. Since then, the country has suffered a large number of COVID-19 infections both in adults and children. This disease has been shown to lead to different outcomes in these two groups, which often present varying symptoms and comorbidities. Aim Therefore, we aimed to evaluate the symptoms, comorbidities and laboratory values in adults and children. Methods We present the characteristics of 1,324 adults and 563 pediatric COVID-19 Italian patients. The data was retrieved from studies published in Italy and found via PubMed and Google Scholar. Results The virus appeared to affect adults more than children and men more than women, and to result in more severe outcomes in patients with abnormal laboratory values and a higher number of comorbidities. Adults are at higher risk for complications and death, and they usually present with fever, respiratory symptoms, cough, fatigue, diarrhea, myalgia, and/or loss of taste, smell, or appetite. Children usually have a milder disease progression and usually present with fever, cough, rhinorrhea, pharyngitis, sore throat, pneumonia, GI symptoms (diarrhea, vomiting, abdominal pain), fatigue, and dyspnea. Conclusion Our findings support early reports that showed that SARS-CoV-2 is associated with more common asymptomatic cases and milder clinical outcome in children than in adults. Acute respiratory distress syndrome and Multisystem inflammatory syndrome in children (systemic vasculitis) are the most severe disease progressions for adults and children, respectively.
Coronavirus disease (COVID-19) pandemic continues to pose challenges.Patients with Chronic Lymphocytic Leukemia (CLL) have many risk factors that predispose them to a severe course of COVID-19– related illness, including co-morbidities, older age, and higher prevalence of immunodeficiency from leukemia. Case presentation: A 70-year-old man had a 2-day history of nonproductive cough, dysnoea and shortness of breath, myalgias/ arthralgias, and headache. He explained that had 6-7 day that not felt well: fatigue, fever over 38.0°C, renching and night sweats. He has been healthy till now. His finger oxygen saturation on air room was 80%. Chest tomography showed bilateral ground glass opacities with basal pulmonary consolidation and bilateral pleural effusions. The complete blood count showed a high leucocytosis and a rise of absolute lymphocyte count. TR-PCR of swab nasopharyngeal for Sars-Cov-2 resulted negative. Antibody anti-Sars-CoV-2 IgM and IgG resulted negative on admission and positive on discharged day. Conclusions: There are limited cases available regarding the presentation of COVID-19 in CLL patients. For these reasons this patient group is of particular concern. Our aim is to describe a patient diagnosed with COVID-19 induced hyperleucocytosisand newly diagnosed CLL. Keywords: COVID-19; Chronic lymphocytic leukemia; Leucocytosis; Lymphocytosis
Background India has the second highest number of confirmed Coronavirus cases in the world after the USA with 29.3 million cases reported so far. We aimed to perform a systematic review and meta-analysis of the clinical characteristics, comorbidities, and outcomes of SARS-CoV-2 positive patients with special emphasis on Gastrointestinal (GI) manifestations. Methods In this meta-analysis, we conducted a systematic review of high-quality articles on confirmed COVID-19 cases in India published in PubMed and Google Scholar between February 2020 and March 2021. Statistical descriptive analysis and correlation analyses of symptoms, comorbidities and outcomes were performed. Results The mean age of the patients was 46.16 years. Of these, 67.53% were males. Overall, 6.4% patients died. Cough (37.79%) was the most common presenting symptom followed by fever (35.5%), nasal congestion, and rhinorrhea (23.60%) but, these symptoms were unrelated to outcome. Patients with shortness of breath (r = 0.69, p = 0.03) and fatigue/weakness (r = 0.95, p = 0.04) had high mortality. Hypertension and Diabetes Mellitus were the most common comorbidities but were not associated with negative outcome. Preexisting chronic kidney disease (r = 0.80, p = 0.01), mechanical ventilation (r = 0.895, p = 0.003) and ICU admission (r = 0.845, p = 0.008) correlated with poor outcome. GI symptoms were reported in 12.05% of the patients. Nausea and vomiting were the most prevalent GI symptoms, but diarrhea (r = 0.95, p = 0.004) was associated with significant mortality. Conclusion Overall, COVID-19 patients in India present with cough, fever, shortness of breath and fatigue as the main symptoms. Among GI symptoms, diarrhea was associated with fatal outcomes. However, more high-quality studies are needed for better understanding of the GI manifestations and their outcomes in the Indian population.
