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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: models/Detail_model.php
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Function: strpos
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Function: insertAPISummary
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Function: require_once
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Filename: helpers/my_audit_helper.php
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Function: str_replace
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Function: formatAIDetailSummary
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Filename: controllers/Detail.php
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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Filename: controllers/Detail.php
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causes most skin infections in humans, and the emergence of methicillin-resistant (MRSA) strains is a serious public health threat. There is an urgent clinical need for nonantibiotic immunotherapies to treat MRSA infections and prevent the spread of antibiotic resistance. Here, we investigated the pan-caspase inhibitor quinoline-valine-aspartic acid-difluorophenoxymethyl ketone (Q-VD-OPH) for efficacy against MRSA skin infection in mice. A single systemic dose of Q-VD-OPH decreased skin lesion sizes and reduced bacterial burden compared with vehicle-treated or untreated mice. Although Q-VD-OPH inhibited inflammasome-dependent apoptosis-associated speck-like protein containing caspase activation and recruitment domain (ASC) speck formation and caspase-1-mediated interleukin-1β (IL-1β) production, Q-VD-OPH maintained efficacy in mice deficient in IL-1β, ASC, caspase-1, caspase-11, or gasdermin D. Thus, Q-VD-OPH efficacy was independent of inflammasome-mediated pyroptosis. Rather, Q-VD-OPH reduced apoptosis of monocytes and neutrophils. Moreover, Q-VD-OPH enhanced necroptosis of macrophages with concomitant increases in serum TNF and TNF-producing neutrophils, monocytes/macrophages, and neutrophils in the infected skin. Consistent with this, Q-VD-OPH lacked efficacy in mice deficient in TNF (with associated reduced neutrophil influx and necroptosis), in mice deficient in TNF/IL-1R and anti-TNF antibody-treated WT mice. In vitro studies revealed that combined caspase-3, caspase-8, and caspase-9 inhibition reduced apoptosis, and combined caspase-1, caspase-8, and caspase-11 inhibition increased TNF, suggesting a mechanism for Q-VD-OPH efficacy in vivo. Last, Q-VD-OPH also had a therapeutic effect against and skin infections in mice. Collectively, pan-caspase inhibition represents a potential host-directed immunotherapy against MRSA and other bacterial skin infections.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8665304 | PMC |
http://dx.doi.org/10.1126/scitranslmed.abe9887 | DOI Listing |
Curr Microbiol
December 2024
Department of Medical Laboratory Technology, Dinabandhu Andrews Institute of Technology and Management, BaishnabghataPatuli Township, Block-S, 1/406A, Near Satyajit Ray Park, Patuli, Kolkata, West Bengal, 700094, India.
This review explores the bidirectional relationship between the human microbiome and SARS-CoV-2 infection, elucidating its implications for COVID-19 susceptibility, severity, and therapeutic strategies. Metagenomic analyses reveal notable alterations in microbiome composition associated with SARS-CoV-2 infection, impacting disease severity and clinical outcomes. Dysbiosis within the respiratory, gastrointestinal, oral, and skin microbiomes exacerbates COVID-19 pathology through immune dysregulation and inflammatory pathways.
View Article and Find Full Text PDFCureus
November 2024
Department of Infection Prevention and Control, King Abdulaziz Medical City, Riyadh, SAU.
is a group of bacteria commonly found in water sources. These bacteria are known to cause gastrointestinal and skin infections, while their association with urinary tract infections is relatively rare. Here, we present a case of epididymitis in a patient with a chronic neurogenic bladder managed with clean intermittent catheterization.
View Article and Find Full Text PDFCent Eur J Immunol
September 2024
This study presents a detailed clinical case of a 10-year-old boy with a history of prolonged cough, fever, and delayed diagnosis of bronchiectasis. Review of the case revealed that the child has had recurrent bronchitis, otitis media, skin allergies, and viral warts since early childhood, indicating persistent immune system abnormalities. Imaging studies, including pulmonary and sinus CT scans, show significant bronchiectasis accompanied by infections and sinusitis.
View Article and Find Full Text PDFEur J Med Res
December 2024
Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, No. 7 Weiwu, Zhengzhou, 450003, Henan, China.
Background: Nicastrin, a subunit of the γ-secretase complex, is encoded by the NCSTN gene and regulates notch signaling, it is involved in the pathogenesis of hidradenitis suppurativa (HS), Alzheimer disease (AD), and liver cancer. However, the animal models for studying HS are relatively scarce.
Methods: CRISPR/Cas-mediated genetic engineering was used to generate targeted knockout offspring mice (C57BL/6J).
J Med Case Rep
December 2024
Department of Gastroenterology, Shahid Mohammadi Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Background: Systemic lupus erythematosus is a multi-organ autoimmune disorder that is treated by immunosuppressive agents that weaken the immune defense against opportunistic pathogens and latent infections such as strongyloidiasis. Herein, we report the case of a 43-year-old woman known to have systemic lupus erythematosus who presented with gastrointestinal symptoms, edema, and bone pain 2 months after receiving immunosuppressive treatment.
Case Presentation: A 43-year-old Iranian female known to have systemic lupus erythematosus and antiphospholipid syndrome presented with abdominal pain, nausea, vomiting, and generalized edema.
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