Severe Systemic Infection Research Articles

Gas-forming renal abscesses in critically ill patients: ultrasound-guided drainage.

This study aimed to describe and evaluate a real-time ultrasound-guided (US-guided) drainage technique for effective and safe drainage of gas-forming renal abscesses (GRA) in an intensive care unit(ICU). This retrospective study included four patients with GRA who were admitted to the ICU of a tertiary care center between September 2021 and September 2023. The patients were all comorbid with severe systemic infections and required drainage of abscesses for infection control. This study describes in detail the process of rapid and precise US-guided drainage of GRA by an ultrasound interventionist through certain maneuvers and techniques. Six US-guided drainage procedures were completed in four patients, and seven catheters were placed accurately in the abscesses with a 100% success rate. No intraoperative or postoperative complications such as bleeding and peripheral organ damage were observed, and the median time with catheters was 13 days (8-46 days). The technique of real-time US-guided drainage of GRA can be performed safely in the ICU without the need to leave the ICU, greatly reducing risk.

Cytolysin A is an intracellularly induced and secreted cytotoxin of typhoidal Salmonella

Typhoidal Salmonella enterica serovars, such as Typhi and Paratyphi A, cause severe systemic infections, thereby posing a significant threat as human-adapted pathogens. This study focuses on cytolysin A (ClyA), a virulence factor essential for bacterial dissemination within the human body. We show that ClyA is exclusively expressed by intracellular S. Paratyphi A within the Salmonella-containing vacuole (SCV), regulated by the PhoP/Q system and SlyA. ClyA localizes in the bacterial periplasm, suggesting potential secretion. Deletion of TtsA, an essential Type 10 Secretion System component, completely abolishes intracellular ClyA detection and its presence in host cell supernatants. Host cells infected with wild-type S. Paratyphi A contain substantial ClyA, with supernatants capable of lysing neighboring cells. Notably, ClyA selectively lyses macrophages and erythrocytes while sparing epithelial cells. These findings identify ClyA as an intracellularly induced cytolysin, dependent on the SCV environment and secreted via a Type 10 Secretion System, with specific cytolytic activity.

Infection route influence the consequences of Nocardia farcinica infection in BALB/c mice

BackgroundNocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue.MethodsBALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested.ResultsIntraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes.ConclusionThe study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Synergistic cross-kingdom host cell damage between Candida albicans and Enterococcus faecalis.

The fungus Candida albicans and the Gram-positive bacterium Enterococcus faecalis share mucosal niches in the human body. As opportunistic pathogens, both are found to expand population size during dysbiosis, and can cause severe systemic infections in susceptible individuals. Here, we show that the presence of C. albicans results in increased host cell damage by E. faecalis . Furthermore, E. faecalis aggravates oropharyngeal candidiasis in mice. Increased damage is mediated by enterococcal cytolysin, and involves both physical interaction and altered glucose availability. Physical interaction promotes accumulation of bacteria on host cells, facilitating contact of cytolysin with host cells. Glucose depletion by the metabolic activity of the fungus sensitized host cells to cytolysin. This work illustrates how a complex interplay between fungi and bacteria can result in detrimental consequences for the host.

Development of a Simple and Rapid DNA Extraction Method for Aspergillus flavus

Abstract Aspergillus species are known to be very important in human and domestic animal health. Aspergillus species commonly cause severe systemic and skin infections, as well as allergic lung diseases. With the development of PCR techniques, these methods are used to identify and diagnose fungi. DNA extraction from Aspergillus species is difficult because the fungal cell wall structure is very durable and complex. Fungal DNA extraction methods containing proteinase K and liquid nitrogen are widely used to break down the cell wall. However, these methods cause DNA loss during the extraction in Aspergillus species. In this study, on the contrary, the commonly used DNA extraction by means of ammonium hydroxide, which is generally used to break down chitin in DNA extraction of ticks and plants, is used. The efficiency of the cell wall lysis method from A. flavus with ammonium hydroxide was compared with methods containing proteinase K and liquid nitrogen. For this purpose, DNA extraction of A. flavus was tried using three different methods. As a result, the cell wall of A. flavus was lysed using ammonium hydroxide in this study. The obtained DNA’s quality, concentration, and PCR performance were sufficient. This method has been evaluated as a faster, more straightforward, and more economical alternative.

Prevention and Management of Infectious Complications in Retrograde Intrarenal Surgery: A Comprehensive Review.

Retrograde intrarenal surgery (RIRS) is a minimally invasive procedure increasingly used to treat renal stones and other intrarenal pathologies due to its reduced risk of complications, shorter recovery time, and lower postoperative pain compared to more invasive surgical techniques. However, despite its advantages, RIRS is associated with a significant risk of infectious complications, ranging from simple urinary tract infections (UTIs) to severe systemic infections such as urosepsis, which can lead to increased morbidity, prolonged hospitalization, and, in severe cases, mortality. This review aims to summarize the current knowledge on preventing and managing infectious complications associated with RIRS. By exploring the pathophysiology of these infections, identifying patient and procedural risk factors, and evaluating evidence-based strategies for prevention and management, this review provides comprehensive insights into minimizing infection risks in RIRS. A thorough literature review was conducted, examining studies and clinical trials that address the incidence, risk factors, prevention strategies, and management protocols for infections in RIRS. This review also assesses current guidelines from professional organizations and recent infection control technologies and practices advancements. The review identifies multiple risk factors contributing to infections in RIRS, including patient-specific factors such as comorbidities and procedural factors like the duration of surgery and use of instrumentation. Effective prevention strategies include preoperative antibiotic prophylaxis, stringent aseptic techniques during surgery, and careful postoperative monitoring. The review also highlights the importance of a multidisciplinary approach involving urologists, infectious disease specialists, and microbiologists in managing complex cases of infection. Infectious complications remain a significant concern in RIRS, necessitating a comprehensive approach to prevention and management. By adhering to evidence-based guidelines and utilizing a multidisciplinary strategy, healthcare professionals can significantly reduce the incidence of infections, thereby improving patient outcomes and the overall safety of RIRS. Future research should focus on advancing infection control technologies and developing novel prophylactic and therapeutic approaches to further enhance the safety and effectiveness of RIRS.

Deterioration of neuroimmune homeostasis in Alzheimer’s Disease patients who survive a COVID-19 infection

Growing evidence has implicated systemic infection as a significant risk factor for the development and advancement of Alzheimer’s disease (AD). With the emergence of SARS-CoV-2 (COVID-19) and the resultant pandemic, many individuals from the same aging population vulnerable to AD suffered a severe systemic infection with potentially unidentified long-term consequences for survivors. To study the impact of COVID-19 survival on the brain’s intrinsic immune system in a population also suffering from AD, we profiled post-mortem brain tissue from patients in the UF Neuromedicine Human Brain and Tissue Bank with a diagnosis of AD who survived a COVID-19 infection (COVID-AD) and contrasted our findings with AD patients who did not experience a COVID-19 infection, including a group of brain donors who passed away before arrival of SARS-CoV-2 in the United States. We assessed disease-relevant protein pathology and microglial and astrocytic markers by quantitative immunohistochemistry and supplemented these data with whole tissue gene expression analysis performed on the NanoString nCounter® platform. COVID-AD patients showed slightly elevated Aβ burden in the entorhinal, fusiform, and inferior temporal cortices compared to non-COVID-AD patients, while tau pathology burden did not differ between groups. Analysis of microglia revealed a significant loss of microglial homeostasis as well as exacerbated microgliosis in COVID-AD patients compared to non-COVID-AD patients in a brain region-dependent manner. Furthermore, COVID-AD patients showed reduced cortical astrocyte numbers, independent of functional subtype. Transcriptomic analysis supported these histological findings and, in addition, identified a dysregulation of oligodendrocyte and myelination pathways in the hippocampus of COVID-AD patients. In summary, our data demonstrate a profound impact of COVID-19 infection on neuroimmune and glial pathways in AD patients persisting for months post-infection, highlighting the importance of peripheral to central neuroimmune crosstalk in neurodegenerative diseases.

Decreased Tongue-Lip Motor Function in Japanese Population with Low Taste Sensitivity: A Cross-Sectional Study.

Background/Objectives: Taste disorders have a negative impact on meal enjoyment, which is essential for maintaining adequate nutrition and quality of life. Japan is a rapidly aging society with an increasing number of individuals with taste disorders. However, despite the increasing prevalence of taste disorders, the correlation between oral frailty and taste sensitivity remains largely unknown. The objective of this study was to assess the relationship between oral health status and taste sensitivity among the Japanese population. Methods: Participants were recruited from Kanagawa Dental University Hospital Medical-Dental Collaboration Center between 2018 and 2021. The exclusion criteria were severe systemic infections, pregnancy, or lactation. Clinical examinations, oral function assessments, and taste tests were conducted using tap water and 1% sweet, 0.3% salty, 0.03% umami, and 0.1% umami tastants. The relationships between oral function, systemic indicators, and taste sensitivity were statistically evaluated. Results: Of the 169 participants included in this cross-sectional study, 39.6% were male and 60.4% were female (median age, 68 years). Participants with low taste sensitivity showed a decline in tongue-lip motor function, independent of age, sex, or smoking status. A multiple logistic regression analysis conducted using two age categories-younger than 65 years and older than 65 years-revealed an association between tongue-lip motor function and taste sensitivity among participants younger than 65 years. Conclusions: Decreased taste sensitivity is associated with tongue-lip motor function. Therefore, the early maintenance of oral function and taste sensitivity may be beneficial for optimal tongue-lip motor function.

Anti-fungal efficacy of Carvacrol against Candida glabrata clinical isolates of vulvovaginal candidiasis

Fungal infections affect over 1 billion people worldwide each year, including superficial infections like athlete's foot and more severe systemic infections. Fungal diseases are responsible for an estimated 1.5 million deaths annually, a figure comparable to or exceeding the mortality rate of diseases like malaria or tuberculosis. The limited arsenal of available antifungal drugs, coupled with the emergence of drug-resistant fungal strains, has increased this concern. Therefore, there is a significant need to explore alternative therapeutics to overcome fungal pathogens. Carvacrol, phenolic monoterpenoids, is present in essential oils of many plants and is known for its biological and pharmacological properties. In the present study, the efficacy of carvacrol was investigated against four Candida glabrata strains isolated from patients of vulvovaginal candidiasis, which have shown varying extents of susceptibility against fluconazole. Carvacrol, a phytoactive monoterpene phenol, has shown a minimum inhibitory concentration (MIC50) ranging from 75 to 125 µg/mL and minimum fungicidal concentration of 150 and 175 µg/mL for all clinical isolates, including wild-type strains. Carvacrol, in combination with fluconazole, has shown a strong synergism against wild type C. glabrata with a FIC index value of 0.156. Preliminary mechanistic investigations unveiled that exposure to carvacrol significantly reduced cell surface hydrophobicity and ergosterol content in all strains. In conclusion, carvacrol holds promising potential as an effective antifungal agent against C. glabrata, which is categorized as high priority in the first fungal pathogen priority list of the World Health Organisation released in 2022 for highlighting priority areas for action, including the development of effective therapeutic solution.

Dietary L-arabinose-induced gut dysbiosis exacerbates Salmonella infection outcome.

The gut microbiota is essential for providing colonization resistance against pathogens. Dietary sugars markedly shift the composition of the intestinal microbiota and alter host susceptibility to enteric infections. Here, we demonstrate the effect of L-arabinose on bacterial infection by using a mouse infection model with Salmonella enterica serovar Typhimurium (S. Tm). In the presence of microbiota, L-arabinose induces a dramatic expansion of Enterobacteriaceae, thereby decreasing the microbiota diversity and causing more severe systemic infection. However, L-arabinose supplementation does not alter the disease progression of Salmonella infection in a microbiota-depleted mouse model. More importantly, short-term supplementation of L-arabinose fails to exert anti-diabetic effects in Salmonella-infected hyperglycemia mice and still promotes infection. Overall, our work reveals that a high intake of dietary L-arabinose supports a bloom of Enterobacteriaceae in Salmonella-infected gut, further accelerating the process of systemic infection.IMPORTANCEL-arabinose is a promising natural sweetener and food additive for the regulation of hyperglycemia. Since diabetic subjects are more susceptible to infections, the safety of dietary L-arabinose in diabetic patients experiencing infection remains a concern. Our findings reveal that L-arabinose exacerbates Salmonella infection outcome by inducing gut microbiota dysbiosis in mice. High dietary intake of L-arabinose may be deleterious for diabetic individuals undergoing infection.

Establishment of an LMBV-infection model in zebrafish larvae and its application in studying virus-host interactions

Largemouth bass virus (LMBV) causes high transmission efficiency and mortality in freshwater aquaculture industry. However, the host responses to LMBV infection, particularly the molecular mechanisms involved in vivo, remain largely uncertain. Zebrafish has been developed as a powerful model organism for the study of host inflammation and immune response upon pathogen infections. Here, we evaluated the susceptibility of LMBV to zebrafish larvae and investigated the host response upon virus infection using transcriptomic analysis. LMBV replicated well in larvae by inoculation with LMBV via the brain and the duct of Cuvier, but the later showed more severe systemic infection, evidenced by the cumulative mortality, the increased transcriptions of viral core genes, and the presence of mcp positive signal in infected larvae. After inoculation with LMBV via the duct of Cuvier, we observed numerous viral particles in the head and tail regions of infected larvae. Moreover, ROS and TUNEL positive signaling also significantly increased in LMBV infected larvae. Of note, a great deal of neutrophils migrated towards the virus infected sites during LMBV infection. Transcriptomic analysis showed that a total of 1263 genes were up-regulated and 1039 genes were down-regulated in response to LMBV infection. Enrichment analysis indicated that the majority of the enriched KEGG pathways were associated with metabolism, cell death and immune regulation, such as fatty acid metabolism, steroid hormone biosynthesis, PPAR signaling, apoptosis, necroptosis, phagosome, cytokine-cytokine receptor pathway, NOD-like receptor signaling, and toll-like receptor pathway. For instance, cell death related signaling molecules including casp9,fas,tnfα and sqstm1 were significantly up-regulated, while camk2a,sept4b and akt1 were down-regulated in response to LMBV infection. Thus, our data firstly established LMBV-infected model in zebrafish larvae which could provide an alternative means for investigation of LMBV-host interaction in vivo, and application for high throughput drug screening in the future.

Salmonella pathogenicity island-14 is a critical virulence factor responsible for systemic infection in chickens caused by Salmonella gallinarum

Salmonella enterica serovar Gallinarum (S. gallinarum) is an important host-specific pathogen that causes fowl typhoid, a severe systemic, septicemic, and fatal infection, in chickens. S. gallinarum causes high morbidity and mortality in chickens and poses a significant burden and economic losses to the poultry industry in many developing countries. However, the virulence factors and mechanisms of S. gallinarum-induced systemic infection in chickens remain poorly understood. In this study, we constructed a Salmonella pathogenicity island-14 (SPI-14) mutant strain (mSPI-14) of S. gallinarum and evaluated the pathogenicity of mSPI-14 in the chicken systemic infection model. The mSPI-14 exhibited the same level of bacterial growth and morphological characteristics but significantly reduced resistance to bile acids compared with the wild-type (WT) strain in vitro. The virulence of mSPI-14 was significantly attenuated in the chicken oral infection model in vivo. Chickens infected with WT showed typical clinical symptoms of fowl typhoid, with all birds succumbing to the infection within 6 to 9 days post-inoculation, and substantial increases in bacterial counts and significant pathological changes in the liver and spleen were observed. In contrast, all mSPI-14-infected chickens survived, the bacterial counts in the organs were significantly lower, and no significant pathological changes were observed in the liver and spleen. The expression of interleukin (IL)-1β, IL-12, CXCLi1, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in the liver of mSPI-14-infected chickens were significantly lower than those in the WT-infected chickens. These results indicate that SPI-14 is a crucial virulence factor in systemic infection of chickens, and avirulent mSPI-14 could be used to develop a new attenuated live vaccine to prevent S. gallinarum infection in chickens.

Targeted rescue of synaptic plasticity improves cognitive decline in sepsis-associated encephalopathy

Sepsis-associated encephalopathy (SAE) is a frequent complication of severe systemic infection resulting in delirium, premature death, and long-term cognitive impairment. We closely mimicked SAE in a murine peritoneal contamination and infection (PCI) model. We found long-lasting synaptic pathology in the hippocampus including defective long-term synaptic plasticity, reduction of mature neuronal dendritic spines, and severely affected excitatory neurotransmission. Genes related to synaptic signaling, including the gene for activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and members of the transcription-regulatory EGR gene family, were downregulated. At the protein level, ARC expression and mitogen-activated protein kinase signaling in the brain were affected. For targeted rescue we used adeno-associated virus-mediated overexpression of ARC in the hippocampus invivo. This recovered defective synaptic plasticity and improved memory dysfunction. Using the enriched environment paradigm as a non-invasive rescue intervention, we found improvement of defective long-term potentiation, memory, and anxiety. The beneficial effects of an enriched environment were accompanied by an increase in brain-derived neurotrophic factor (BDNF) and ARC expression in the hippocampus, suggesting that activation of the BDNF-TrkB pathway leads to restoration of the PCI-induced reduction of ARC. Collectively, our findings identify synaptic pathomechanisms underlying SAE and provide a conceptual approach to target SAE-induced synaptic dysfunction with potential therapeutic applications to patients with SAE.

Subtractive Proteomics and Reverse-Vaccinology Approaches for Novel Drug Target Identification and Chimeric Vaccine Development against Bartonella henselae Strain Houston-1.

Bartonella henselae is a Gram-negative bacterium causing a variety of clinical symptoms, ranging from cat-scratch disease to severe systemic infections, and it is primarily transmitted by infected fleas. Its status as an emerging zoonotic pathogen and its capacity to persist within host erythrocytes and endothelial cells emphasize its clinical significance. Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to the B. henselae strain Houston-1. Exploring these aspects is crucial for targeted therapeutic strategies against this versatile pathogen. Using reverse-vaccinology-based subtractive proteomics, this research aimed to identify the most antigenic proteins for formulating a multi-epitope vaccine against the B. henselae strain Houston-1. One crucial virulent and antigenic protein, the PAS domain-containing sensor histidine kinase protein, was identified. Subsequently, the identification of B-cell and T-cell epitopes for the specified protein was carried out and the evaluated epitopes were checked for their antigenicity, allergenicity, solubility, MHC binding capability, and toxicity. The filtered epitopes were merged using linkers and an adjuvant to create a multi-epitope vaccine construct. The structure was then refined, with 92.3% of amino acids falling within the allowed regions. Docking of the human receptor (TLR4) with the vaccine construct was performed and demonstrated a binding energy of -1047.2 Kcal/mol with more interactions. Molecular dynamic simulations confirmed the stability of this docked complex, emphasizing the conformation and interactions between the molecules. Further experimental validation is necessary to evaluate its effectiveness against B. henselae.

Essential oils as promising treatments for treating Candida albicans infections: research progress, mechanisms, and clinical applications.

Candida albicans: (C. albicans) is a prevalent opportunistic pathogen that can cause severe mucosal and systemic fungal infections, leading to high morbidity and mortality rates. Traditional chemical drug treatments for C. albicans infection have limitations, including the potential for the development of drug resistance. Essential oils, which are secondary metabolites extracted from plants, have gained significant attention due to their antibacterial activity and intestinal regulatory effects. It makes them an ideal focus for eco-friendly antifungal research. This review was aimed to comprehensively evaluate the research progress, mechanisms, and clinical application prospects of essential oils in treating C. albicans infections through their antibacterial and intestinal regulatory effects. We delve into how essential oils exert antibacterial effects against C. albicans infections through these effects and provide a comprehensive analysis of related experimental studies and clinical trials. Additionally, we offer insights into the future application prospects of essential oils in antifungal therapy, aiming to provide new ideas and methods for the development of safer and more effective antifungal drugs. Through a systematic literature review and data analysis, we hope to provide insights supporting the application of essential oils in antifungal therapy while also contributing to the research and development of natural medicines. In the face of increasingly severe fungal infections, essential oils might emerge as a potent method in our arsenal, aiding in the effective protection of human and animal health.

Isolation of Vibrio cholerae and Vibrio vulnificus from Estuarine Waters, and Genotyping of V. vulnificus Isolates Using Loop-Mediated Isothermal Amplification.

Bacteria in the genus Vibrio are ubiquitous in estuarine and coastal waters. Some species (including Vibrio cholerae and Vibrio vulnificus) are known human pathogens causing ailments like cholera, diarrhea, or septicemia. Notably, V. vulnificus can also cause a severe systemic infection (known as vibriosis) in eels raised in aquaculture facilities. Water samples were periodically collected from the estuary of the Asahi River, located in the southern part of Okayama City, Japan. These samples were directly plated onto CHROMagar Vibrio plates, and colonies displaying turquoise-blue coloration were selected. Thereafter, polymerase chain reaction was used to identify V. cholerae and V. vulnificus. A total of 30 V. cholerae strains and 194 V. vulnificus strains were isolated during the warm season when the water temperature (WT) was higher than 20 °C. Concurrently, an increase in coliforms was observed during this period. Notably, V. vulnificus has two genotypes, designated as genotype 1 and genotype 2. Genotype 1 is pathogenic to humans, while genotype 2 is pathogenic to both humans and eels. The loop-mediated isothermal amplification method was developed to rapidly determine genotypes at a low cost. Of the 194 strains isolated, 80 (41.2%) were identified as genotype 1 strains. Among the 41 strains isolated when the WTs were higher than 28 °C, 25 strains (61.0%) belonged to genotype 1. In contrast, of the 32 strains isolated when the WTs were lower than 24 °C, 27 strains (84.4%) belonged to genotype 2. These results suggest that the distribution of the two genotypes was influenced by WT.

Cuscuta chinensis Lam. Flavonoids (CCLF) alleviate the symptoms of sepsis-associated encephalopathy via PI3K/Nrf2 pathway

Sepsis-associated encephalopathy (SAE) frequently encounters patients who are in intensive care units and ∼70% of patients with severe systemic infection. However, due to the unclear pathological mechanisms of SAE, the desease-modifying drug is still lack. Here, we aimed to explore whether the flavonoid components extracted from CCL (CCLF) seeds possess protective effects on SAE animals, and systematically evaluate the transcriptomic alteration (in the hippocampus) after CCLF treatment on SAE animals employing RNA sequencing. We observed that CCLF improved the brain’s learning and memory abilities and the structural integrity of BBB using cecal ligation and puncture (CLP)-induced SAE animal models, evaluated by behavioral test and tissue examination of animals respectively. RNA sequencing results showed that CCLF treatment reverses SAE-induced transcriptomic alteration in the hippocampus. Moreover, CCLF also dramatically relieved inflammatory (such as TNF-α, IL-2, and IL-6) and oxidative (MDA and SOD activity) stresses, and inhibited SAE-induced neuron apoptosis in brain tissues. More importantly, CCLF restored the PI3K/AKT signaling pathway and then induced the Nrf2 nuclear translocation to drive HO-1 expression both in vitro and in vivo. LY294002, an inhibitor of PI3K, obviously blocked CCLF’s functions on anti-apoptosis, anti-inflammation, and anti-oxidation in vivo, demonstrating that CCLF achieves its bioactivities in a PI3K/AKT signaling dependent manner. Altogether, CCLF exhibits remarkable neuro-protective function and may be a promising candidate for further clinical trials for SAE treatment.

Tumor necrosis factor-α inhibitor for successful treatment of toxic epidermal necrolysis with severe infection: a case series.

Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients' skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.

Occurrence of Salmonella in Fresh Foods Sold in the City of Nampula, Northern Mozambique

Salmonellosis, an infectious disease caused by the Salmonella species, encompasses a broad spectrum of clinical manifestations, ranging from mild self‐limiting gastroenteritis to severe systemic infections. It affects millions of people annually, causing immense morbidity and economic losses worldwide. This study aims to evaluate the occurrence of Salmonella in water and raw foods, focusing on meat, fish, shellfish, and vegetables consumed in the city of Nampula, north of Mozambique. A total of 81 samples of meat, fish and shellfish, vegetables, and water were collected from nine of the ten municipal markets in Nampula City. Salmonella detections were performed according to ISO 6579‐1. A chi‐square test was performed in the Python programming language to detect associations between positive samples and market localization. The results showed a high frequency of Salmonella. From the total sample, 38.5% were Salmonella positive. Fresh vegetables were the most contaminated samples, followed by fish, shellfish, raw meat, and water. The outcomes of this study did not find an association between the sample collection location and the test results for Salmonella. In this study, serovars of Salmonella were not identified which hinders the association of Salmonella occurrence with diseases. Consequently, we propose that the next study should focus on detecting the serotypes of Salmonella strains.

Tinjauan Vibrio Vulnificus sebagai Ancaman Emerging Foodborne Disease pada Makanan Laut Segar

Vibrio vulnificus is a crucial foodborne opportunistic pathogen that can cause wound infections, septicemia, and gastroenteritis with a 50% fatality rate. This bacteria occurs in estuaries and coastal waters and is found in large quantities in oysters and other mollusc shells. The increasing number of foodborne diseases worldwide is suspected to have occurred due to the expansion of the international food trade. Consumption of raw seafood, especially oysters containing Vibrio vulnificus bacteria, can result in acute, severe systemic infections and is responsible for 95% of deaths from seafood consumption in the United States. The diagnosis of Vibrio vulnificus infection is confirmed by the growth of the bacteria in culture media from wounds, feces or blood. This article discusses the characteristics of the bacteria, host, environment, transmission, pathogenesis, clinical symptoms, diagnostic techniques and geographical distribution of V. vulnificus.