Pathogenic Features Research Articles

Real-world utilization of ceftazidime/avibactam among inpatients in the national Veterans Affairs Healthcare System.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Multidrug-resistant (MDR) infections are challenging to treat due to underlying patient conditions, pathogen characteristics, and high antibiotic resistance rates. As newer antibiotic therapies come to market, limited data exist about their real-world utilization. This was a national retrospective cohort study of ceftazidime/avibactam (approved in 2015) utilization among inpatients from the Veterans Affairs (VA) Healthcare System, from 2015 through 2021. Joinpoint regression was used to estimate time trends in utilization. Ceftazidime/avibactam use increased by 52.3% each year (days of therapy per 1,000 bed days; 95% confidence interval, 12.4%-106.4%). We identified 1,048 unique predominantly male (98.3%) and white (66.2%; Black, 27.7%) patients treated with ceftazidime/avibactam, with a mean (SD) age of 71.5 (11.9) years. The most commonly isolated organisms were Pseudomonas aeruginosa (36.3%; carbapenem resistant, 80.6%; MDR, 65.0%) and Klebsiella species (34.1%; carbapenem resistant, 78.4%; extended-spectrum cephalosporin resistant, 90.7%). Common comorbid conditions included hypertension (74.8%), nervous system disorders (60.2%), diabetes mellitus (48.7%), and cancer (45.1%). Median time to ceftazidime/avibactam initiation from admission was 6 days, with a median of 3 changes in therapy before ceftazidime/avibactam initiation and a subsequent median length of inpatient stay of 14 days (median of 8 days of ceftazidime/avibactam therapy). Treatment heterogeneity was high, both before ceftazidime/avibactam initiation (89.6%) and during ceftazidime/avibactam treatment (85.6%), and common concomitant antibiotics included vancomycin (41.4%), meropenem (24.1%), cefepime (15.2%), and piperacillin/tazobactam (15.2%). The inpatient mortality rate was 23.6%, and 20.8% of patients had a subsequent admission with ceftazidime/avibactam treatment. Utilization of ceftazidime/avibactam increased from 2015 to 2021 in the national VA Healthcare System. Ceftazidime/avibactam was utilized in complex, difficult-to-treat patients, with substantial treatment heterogeneity and variation in the causative organism and culture site.

The non-bacterial pathogenic and clinical characteristics of acute respiratory tract infection in children in a hospital of pediatric in Sichuan Province from 2019 to 2021

Objective: To explore the non-bacterial pathogen distribution, epidemiological characteristics, and clinical features of acute respiratory infections in children in Sichuan Province. Methods: Using a retrospective cohort study method, this study selected hospitalized children diagnosed with acute respiratory infections at West China Second Hospital of Sichuan University from February 2019 to January 2021, and tested 13 pathogens using polymerase chain reaction (PCR)-fragment analysis. The children were divided into infant group (<1 year old), toddler group (1 year old ≤ age <3 years old), preschool group (3 years old ≤ age <6 years old) and school-age group (6 years old ≤ age <18 years old). The distribution of pathogen positive rates, seasonal epidemic characteristics, clinical characteristics, and some laboratory test indicators were analyzed in children. Statistical analysis was performed on the results using SPSS 22.0 software, with count data expressed as percentages and inter group comparisons using SPSS 22.0 software χ2 Inspection. Results: A total of 2 922 pediatric patients were included in this study, with 1 748 (59.8%) positive for pathogens detected. Among them, 1 391 (79.6%) were detected as a single pathogen, and 357 (20.4%) were detected as a mixture of two or more pathogens. The most commonly detected pathogens were rhinovirus (HRV) (39.7%), syncytial virus (RSV) (22.8%), and parainfluenza virus (PIV) (12.5%). Pathogen positivity is more common in children under 6 years old (χ2=146.59, P<0.001), with a slightly higher positivity rate in male children (61.3%, 1 047/1 707) than in female children (57.7%, 701/1 215) (χ2=3.91, P=0.048), and compared with pathogen negative children, positive children are more prone to symptoms such as cough, wheezing, and shortness of breath (χ2=259.15, 366.06, 12.48, P<0.001). The distribution of different pathogens varies among children of different age groups, and HRV is more common in children aged 1-3 and 3-6 years old (χ2=9.74, P<0.001), while RSV is more common in children under 1 year old (χ2=178.63, P<0.001), while mycoplasma pneumoniae (MP) and influenza virus (InfA/B) are less common in children under 1 year old (χ2=92.54, 12.90,22.21, P<0.01). The prevalence of multiple pathogens showed seasonal changes. HRV showed a high prevalence trend in spring and autumn, while the prevalence of RSV infection was mainly seen in autumn and winter festivals. The positive rate of different pathogens after the outbreak of novel coronavirus pneumonia was significantly lower than that before the outbreak (χ2=252.68, P<0.001). Conclusion: The detection rate of non-bacterial respiratory pathogens in children in Sichuan Province from 2019 to 2021 is high, which is prone to symptoms such as cough, wheezing, and shortness of breath, with HRV and RSV being the main types. The positive rate of respiratory pathogens varies among different age groups, genders, and seasons.

The Pathogenicity Test, Cultural and Morphological Characterization of Anthracnose (Colletotrichum lindemuthianum) of Green Gram (Vigna radiata L. Wilczek)

Aims: The objective of this study was to identify the appropriate anthracnose fungus of green gram using symptomatology, identification, pathogenicity test and characterization of samples.&#x0D; Study Design: Pathogenicity test, cultural and morphological characterization.&#x0D; Place and Duration of Study: The laboratory studies were conducted in the Department of Plant Pathology, N. M. College of Agriculture, Navsari Agricultural University, Navsari, Gujarat during rabi 2020-21.&#x0D; Methodology: The sample was collected and subjected to isolation, purification and identification of pathogen. Four different pathogenecity tests were conducted to verify the pathogen causing anthracnose of green gram. On the other hand, the cultural and morphological characteristics of pathogen were studied. &#x0D; Results: The pathogenecity test confirmed that the pathogen as Colletotrichum lindemuthianum in all four tests. Spraying inoculum after needle pricking and carborandum powder producing 100% infection in inoculated plants while 96% in spraying spore suspension without any abrasion. The less per cent of infection was observed in seed inoculated plants. The cultural studies of C. lindemuthianium shown sub-aerial whitish-to-pink cottony growth and pinkish-to-brown pigmentation under the culture plate. The morphological study of C. lindemuthianium observed as single-celled, hyaline, cylindrical, and smooth with oil globules. The acervuli were blackish brown and measure 181.3 × 254.6 µm. The setae were visible through the conidial mass with 1-3 septations.&#x0D; Conclusion: A study on green gram anthracnose confirmed C. lindemuthianum as pathogen in all four pathogenicity test with needle pricking and carborandum powder producing 100% infection in inoculated plants while 96% in spraying spore suspension without any abrasion. Cultural studies revealed whitish-pink cottony growth and pinkish-brown pigmentation. C. lindemuthianium was morphologically observed as single-celled, hyaline, cylindrical, smooth, with oil globules, blackish brown acervuli, and visible setae through conidial mass with 1-3 septations. Therefore, these findings are important for identifying the anthracnose disease of green gram.

Prognostic risk factors of catheter-related bloodstream infection in patients with maintenance hemodialysis

To analyze the pathogen distribution and prognostic risk factors of catheter-related bloodstream infection (CRBSI) in patients with maintenance hemodialysis (MHD) during non-hospitalization. A retrospective comparative study was conducted. Thirty-four patients of MHD with semi-permanent catheter admitted to the department of nephrology of Gansu Provincial Hospital from January 2020 to May 2023 due to CRBSI during non-hospitalization were enrolled. The distribution characteristics of pathogens causing CRBSI in MHD patients during non-hospital period were analyzed. All patients were actively given anti-infection treatment after admission. The general data, laboratory indicators and prognosis during hospitalization were collected through the electronic medical record system. Patients were divided into poor prognosis group (14 cases) and good prognosis group (20 cases) according to the treatment results during hospitalization. Univariate and binary Logistic regression were used to analyze the risk factors affecting the prognosis of patients, and receiver operator characteristic curve (ROC curve) was drawn to evaluate its predictive value for prognosis. A total of 28 pathogenic bacteria were isolated from 34 patients, of which 25 were Gram-positive, Staphylococcus was the most common pathogen, accounting for 82.15% of the total, and 16 strains of Staphylococcus aureus (57.15%), including 6 methicillin-resistant Staphylococcus aureus (MRSA, 21.43%). There were 7 strains of Staphylococcus epidermidis (25.00%), including 3 strains of methicillin-resistant Staphylococcus epidermidis (MRSE, 10.71%). There were 3 strains of Gram-negative bacteria, 1 strain each of Pseudomonas aeruginosa, Escherichia coli and Acinetobacter baumannii. Univariate analysis showed that the fever duration of MHD patients with CRBSI in the poor prognosis group was significantly longer than that in the good prognosis group [days: 8.50 (3.75, 45.00) vs. 2.50 (1.00, 4.75), P < 0.01], serum erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and random blood glucose (GLU) were significantly higher than those in the good prognosis group [ESR (mm/1 h): 82.36±24.98 vs. 56.95±35.65, CRP (mg/L): 123.45±74.10 vs. 67.35±55.22, GLU (mmol/L): 8.74±3.66 vs. 6.42±1.95, all P < 0.05]. Binary Logistic regression analysis showed that serum CRP was an independent risk factor for poor prognosis in MHD patients with CRBSI [odds ratio (OR) = 1.020, 95% confidence interval (95%CI) was 1.002-1.038, P = 0.025]. ROC curve analysis showed that the area under the curve (AUC) of serum CRP in predicting poor prognosis of MHD patients with CRBSI was 0.711; when the optimal cut-off value was 104.65 mg/L, the sensitivity was 64.3% and the specificity was 85.0%, indicating that it has good predictive value. Gram-positive bacteria are the main pathogens of CRBSI in MHD patients during non-hospital period. The poor prognosis is mainly related to the high level of serum CRP. Serum CRP level can effectively screen the high-risk group of MHD patients with CRBSI with poor prognosis.

Robinetin Alleviates Metabolic Failure in Liver through Suppression of p300-CD38 Axis.

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

Immunotherapy Strategy for Systemic Autoimmune Diseases: Betting on CAR-T Cells and Antibodies.

Systemic autoimmune diseases (SAIDs), such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and rheumatoid arthritis (RA), are fully related to the unregulated innate and adaptive immune systems involved in their pathogenesis. They have similar pathogenic characteristics, including the interferon signature, loss of tolerance to self-nuclear antigens, and enhanced tissue damage like necrosis and fibrosis. Glucocorticoids and immunosuppressants, which have limited specificity and are prone to tolerance, are used as the first-line therapy. A plethora of novel immunotherapies have been developed, including monoclonal and bispecific antibodies, and other biological agents to target cellular and soluble factors involved in disease pathogenesis, such as B cells, co-stimulatory molecules, cytokines or their receptors, and signaling molecules. Many of these have shown encouraging results in clinical trials. CAR-T cell therapy is considered the most promising technique for curing autoimmune diseases, with recent successes in the treatment of SLE and SSc. Here, we overview novel therapeutic approaches based on CAR-T cells and antibodies for targeting systemic autoimmune diseases.

Adenovirus and Mycoplasma pneumoniae co-infection as a risk factor for severe community-acquired pneumonia in children.

To investigate the pathogenic characteristics and risk factors of pediatric severe community-acquired pneumonia (CAP). We retrospectively analyzed the clinical data of hospitalized children with severe CAP from April 2014 to June 2019 in China. Data of age, sex and pathogenic results were collected: bacterial and fungal cultures, respiratory viruses from sputum or bronchoalveolar lavage fluid (BALF), serum Mycoplasma pneumoniae (MP)-IgM and Chlamydia Pneumoniae-IgM, and BALF or blood (1-3)-β-D-glucan/galactomannan test. A total of 679 children with severe CAP were included in the analysis. The number of cases infected with MP was higher in males than in females. There were significant differences between the ≤1-year and >1-year groups in terms of pathogen. The top three bacteria cultured were Haemophilus influenzae (57/679, 8.4%), Streptococcus pneumoniae (50/679, 7.4%), and Pseudomonas aeruginosa (25/679, 3.7%). The top three viruses detected were adenovirus (AdV, 124/679, 18.3%), respiratory syncytial virus (24/679, 3.5%), and parainfluenza virus (21/679, 3.1%). AdV and MP were the leading pathogens, detected in 18.3% and 32.6% cases, respectively. MP infection increased the risk of AdV infection (OR 3.77, p < 0.0001). MP infection was a risk factor for severe AdV-infected pneumonia, while sex, age, bacteria, Chlamydia Pneumoniae, fungal, and AdV infections were risk factors for severe MP-infected pneumonia. AdV and MP were dominant pathogens in children with severe CAP. AdV and MP infection predisposed each other to develop severe illness. AdV-MP co-infection may lead to severe pneumonia.

Etiological characteristics of wound infection in severe trauma patients and logistic regression analysis of influencing factors of infection

AbstractTo investigate the etiological characteristics of wound infection in severe trauma patients and logistic regression analysis of the influencing factors of infection. The 116 patients with severe trauma who were intervened in our hospital from 22 October 2017 to 9 September 2019 were selected as the subjects of this retrospective study and divided into a control group and an observation group according to whether they were infected or not, 58 cases each. Observe and compare the pathogenic characteristics (pathogen distribution and drug resistance) of the two groups of patients and logistic regression analysis of the influencing factors of infection. The gram‐positive bacteria in the observation group were mainly Staphylococcus aureus, accounting for 17.20%; the fungi were mainly Candida tropicalis, accounting for 17.20%; and the gram‐negative bacteria were mainly Acinetobacter baumannii, accounting for 20.39%; the control group was gram‐positive. The main bacteria are S. aureus, accounting for 8.60%; the fungi are mainly Candida albicans, accounting for 4.3%; and the gram‐negative bacteria, which are mainly Pseudomonas aeruginosa, accounting for 14.56%. Gram‐positive bacteria Enterococcus faecium, S. aureus, Enterococcus faecalis, Staphylococcus epidermidis. The highest drug resistance of other gram‐positive bacteria is penicillin and erythromycin at 85.00% and above. Fungi C. tropicalis, Candida parapsilosis, C. albicans, fluconazole and amphotericin B have the highest resistance to 80.00% and above. Gram‐negative bacteria A. baumannii, Ps. aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, Enterobacter cloacae and other gram‐negative bacteria are the most resistant to ampicillin, and Piperacillin was 70.00% and above. The combined primary diseases of the two groups of patients, ventilator use ≧3 days, long‐term use of glucocorticoids, catheter use days ≧5 days, fever days ≧3 days and long‐term use of broad‐spectrum antimicrobial drugs, the difference is statistically significant academic significance (p &lt; 0.05). Logistic analysis showed that combined with underlying diseases, fever days ≥3 days, long‐term use of glucocorticoids and catheter use days ≥5 days are the influencing factors for the occurrence of wound infections in patients with severe trauma. Trauma patients are prone to wound infections, and there are many influencing factors. Close observation of patients should be strengthened. Effective prevention and control measures should be taken for related influencing factors to reduce the incidence of infection.

Understanding of Eosinophilic Esophagitis in Children - A Comprehensive Study on Epidemiology, Clinical Manifestations, Diagnosis and Innovative Treatment Modalities

Introduction:&#x0D; In the late 1960s, probable cases of eosinophilic esophagitis (EoE) emerged, initially linked to esophageal rings and congenital causes or gastroesophageal reflux disease (GERD). Doubts about the GERD association arose due to poor responses to antisecretory therapy. EoE is now a significant pediatric health concern, impacting 1 to 7 cases per 10,000 children.&#x0D; Purpose of the Study:&#x0D; This study aims to comprehensively explore EoE's epidemiology, etiology, subtypes, clinical manifestations, diagnostic methods, and treatment modalities.&#x0D; Materials and Methods:&#x0D; The study employs a cross-sectional analysis of pediatric EoE patients, utilizing endoscopic evaluation and histological assessment. Three distinct EoE subtypes are identified based on pathogenic characteristics. Clinical manifestations, diagnostic methods, and treatments, including endoscopy, are examined.&#x0D; Results:&#x0D; Clinical manifestations span a broad spectrum in the pediatric population. Diagnostic methods include endoscopy, esophageal manometry, impedance-pH monitoring, capsule endoscopy, and string tests. Three distinct EoE subtypes are identified with unique characteristics. Treatment modalities involve dietary management, proton pump inhibitors, topical corticosteroids, biologic therapies, allergen immunotherapy, and endoscopic interventions.&#x0D; Conclusion:&#x0D; Formerly associated with GERD, EoE is now a significant pediatric health concern. The study underscores the importance of comprehensive diagnostic approaches and diverse treatment modalities, including promising biologic therapies and allergen immunotherapy. Understanding these aspects is crucial for effective management and improved outcomes in patients.

Potentially pathogenic multidrug-resistant &lt;i&gt;Vibrio&lt;/i&gt; sp. isolated from dumpsites in Rivers State, Nigeria

Vibrio sp. is associated with several disease conditions. An assessment of the pathogenic potential of such strains is key in assessing the risk these organisms could pose to human health. This study therefore was aimed at analyzing the pathogenic potential of MDR Vibrio sp. isolated from select dumpsites in Port Harcourt, Rivers State. Two dumpsites in Port Harcourt, Rivers State were assessed for the presence of Vibrio sp. using standard microbiological techniques involving a pre-enrichment using alkaline peptone water, culture on Thiosulfate-citrate-bile salts-sucrose and biochemical characterisation. Following antimicrobial susceptibility testing using the standard Kirby Bauer disc diffusion method, pathogenic potential was assessed based on haemolytic activity and biofilm forming potential. Results showed that the highest rates of resistance were against cefuroxime (68.8%) while the lowest resistance rates (3.2%) were against the quinolone antibiotics (ofloxacin and ciprofloxacin). In total, 38 antibiograms were observed among the 93 isolates with AUG-CAZ-CRX-CXM noted as the most commonly occurring antibiogram. Only 31.2% (29/93) of isolates were multidrug resistant. A total of 47.3% of the test isolates exhibited pathogenic potential (either haemolytic ability or biofilm forming potential), with more (37.6%) exhibiting biofilm forming potential. A co-occurrence of both pathogenic characteristics was observed in only 6 (13.6%) isolates. Of the 93 isolates, a co-occurrence of MDR and pathogenic potential was observed in 16.1% of isolates (15/93). This study shows a moderate association between potentially pathogenic multidrug resistance Vibrio sp. and the sampled dumpsites indicating a low potential public health risk because of the non-pathogenic nature of strains isolated.

P186 Comparative Analysis of Clinical Phenotypes and Pathogenic Features between Late-Onset and Infantile-Onset Monogenic Inflammatory Bowel Disease

Abstract Background Previous research on monogenic IBD (m-IBD) has mainly focused on very-early-onset IBD (VEO-IBD) and Montreal classification A1 type IBD patients. In non-A1 type (age &amp;gt; 16y) late-onset IBD patients, some individuals also exhibit IBD manifestations due to monogenic mutations. Here we systematically review the literature, using infantile-onset monogenic IBD patients as a control, to explore the genetic characteristics, clinical presentations, and treatment strategies of late-onset monogenic IBD. Methods Based on the onset age of IBD, m-IBD was categorized into infantile-onset (IO, &amp;lt;2 years) and late-onset (LO, &amp;gt;16 years as non-A1 type based on Montreal classification) groups. A systematic review was conducted to analyze the gastrointestinal (GI) clinical features of detailed cases published from January 1990 to June 2023 and to summarize the correlation between genetic pathogenesis and onset ages. Results 512 m-IBD cases (398 IO and 114 LO) associated with 87 genes were included. Of these genes, 25 out of 87 genes were found to cause both IO and LO conditions. Crohn’s disease (CD) was the predominant type of IBD, account for 42.2% of IO and 44.7% of LO cases. Difficult-to-treat IBD patients showed similar rates (17.4% for IO and 13.0% for LO). However, infantile-onset cases were predominantly associated with complex perianal disease (13.5%), while late-onset cases were linked to postoperative recurrence following surgical resections (10.6%). Anti-inflammatory medicine and biologics were the main strategies, but in infantile-onset (IO) cases, immunosuppressants (57.9%), parenteral nutrition (26.8%), gastroenterostomy (20.2%), and HSCT (24.6%) were more frequently utilized compared to late-onset (LO) cases, where intestinal resection (37.8%) was more prevalent. Homozygosity was the predominant zygosity type (39.9% in IO and 39.3% in LO), while heterozygosity was more prevalent in LO cases (28.9%) compared to IO cases (13.3%) (p&amp;lt;0.05). Most of the genes associated with median onset ages of IBD before 2 years were causative genes for primary immunodeficiency (PID), whereas significantly lower rate of PID genes mutation was found in LO cases (26/27, 96.3% vs. 6/11, 54.5%, p= 0.005). Conclusion m-IBD patients predominantly present with CD, ulceration and atypical pathology, colon involvement, and difficult to treat regardless of onset ages, but vary in terms of family history, GI symptoms, location of the lesion, polyps and villous atrophy, type of complications, treatment options, and type of Difficult-to- treat IBD.

Abundance and Diversity of Several Bacterial Genera in the Mariculture Environment

Although there have been some studies on pathogenic bacteria and their pathogenicity in animals, few studies have assessed the effects of aquaculture on the diversity of potentially pathogenic bacteria. This study used Illumina sequencing and quantitative PCR to explore the diversity of several bacterial genera containing pathogenic bacteria in the mariculture environment and the intestines of different cultured animals. These bacterial genera can be divided into two categories: The first category (14 genera) had high abundances and a low coefficient of variation among similar samples were significantly correlated with the total number of bacteria (r2 &gt; 0.7, p ≈ 0). The other category (7 genera) with low abundances and a high coefficient of variation had no significant relationship with bacterial abundance. These results indicated that these bacterial genera had different responses and adaptation mechanisms to the aquaculture environment. Principal component analysis (PCA) showed that a high abundance of genera was closely related to the pond environment. The abundance of these bacterial genera in the animals’ intestines was much higher than source water, especially for Mycoplasma, Pseudoalteromonas, Vibrio, and Enterococcus, suggesting the aquaculture promoted the high abundance of these bacteria. This study provides a theoretical basis for sediment-associated pathogens acting as a potential pathogen source in the aquaculture environment. This study provides a strategy for disease prevention and control according to the characteristics of potential pathogens in the cultural process.

Effects of intrinsic characteristics of Salmonella enterica strains isolated from foods and humans, and their interaction with food matrices during simulated gastric conditions

The stomach's acidic pH is a crucial barrier against foodborne pathogens such as Salmonella enterica. This study investigated the survival of S. enterica under simulated oral and gastric conditions (SGC; pH 2 for 120 min) as a function of intrinsic pathogen characteristics and food matrix. Fifty-seven S. enterica strains isolated from food and human infections (previously characterized by serotype, virulotype, multi-drug resistance, isolation source, and isolation season) were subjected to SGC using water as a vehicle. Population reduction among the 57 isolates ranged from 2.7 to 4.7 log CFU, revealing that human isolates were inactivated less than food isolates (p = 0.0008). Among food strains, strains isolated during the cold season (food sampled from December to February) displayed the highest reduction (p = 0.00002). Six representatives of the 57 S. enterica strains were selected according to their virulotype and antimicrobial profile. They were further used to evaluate their survival under SGC in four food matrices (water, mango, tomato, and chicken), measuring S. enterica at 30 min intervals. The strains in chicken showed the lowest reduction and inactivation rate (1.42 ± 0.35 log CFU; 0.03 ± 0.005 min−1), followed by tomato (3.75 ± 0.57 log CFU; 0.15 ± 0.02 min−1), water (4.23 ± 0.27 log CFU; 0.17 ± 0.02 min−1), and mango (4.49 ± 0.39 log CFU; 0.17 ± 0.03 min−1). These data suggest that not all S. enterica strains have the same ability to survive under SGC, influencing the probability of arriving into the small intestine.

Pathogenic Characteristics of an Infection with Canine Influenza Virus and Streptococcus equi subsp. zooepidemicus Alone or in Combination in Mice

Both Streptococcus equi subsp. zooepidemicus (SEZ) and canine influenza virus (CIV) are two important pathogens causing infectious respiratory disease in dogs and are frequently codetected in respiratory secretions. However, the clinical significance of viral/bacterial coinfection remains unknown. This study investigated the pathogenic characteristics of infection with CIV and SEZ alone or in combination in mice. Our data indicated that the severity of the disease is related to the challenge order of CIV and SEZ. Coinfection of CIV and SEZ induced higher weight loss in mice than single infection, except for the VB group (viral followed by secondary bacterial infection). Compared with the concurrent or sequential infection groups of CIV and SEZ, mice in the CIV–SEZ preincubation group exhibited more obvious weight loss, higher mortality, and significantly enhanced burden of SEZ and CIV in tissues. Interestingly, viral and bacterial preincubation before coinfection caused typical pulmonary fibrosis in mice. Correspondingly, transforming growth factor (TGF)-β was upregulated, and its canonical small mother against decapentaplegic (Smad) 2/3 signaling was noticeably induced. Further investigation indicated that the activity of the viral neuraminidase (NA) enzyme upon sialic acid was considerably increased due to the direct interaction of CIV with SEZ, which may be related to the activation of the TGF-β signaling pathway. These findings implicate an unexpected contribution of the direct interaction between CIV and SEZ to synergistic pathogenicity.

Pathogenic characteristics and influence factors of bloodstream infection-induced severe sepsis in pediatric intensive care unit

Objective: To summarize the pathogenic characteristics of bloodstream infection (BSI)-induced severe sepsis and analyze the influence factors in pediatric intensive care unit (PICU). Methods: Pediatric patients who were diagnosed with severe sepsis caused by BSI in the PICU of Children's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from January 2016 to December 2021 were retrospectively selected and divided into survival group and death group according to their discharge outcomes. Clinical characteristics, laboratory parameters, pathogenic characteristics and drug resistance of the patients were collected. The characteristics of pathogens, clinical and laboratory indicators were summarized, and the influencing factors of death in children with severe sepsis caused by BSI were analyzed based on binary multivariate logistic regression. Results: A total of 132 patients, aged [M (Q1, Q3)] 36 (10, 119) months, with BSI-induced severe sepsis were enrolled in this study, including 81 males and 51 females. There were 38 cases aged 36 (15, 120) months in the death group, including 23 males and 15 females. There were 94 cases, aged 36 (8, 108) months, in the survival group, including 58 males and 36 females. A total of 132 strains of pathogens were isolated, including 87 strains (65.9%) of Gram-negative bacteria. The top 5 pathogens were Klebsiella pneumoniae (24 cases, 18.2%), Escherichia coli (17 cases, 12.9%), Acinetobacter baumannii (13 cases, 9.8%), Pseudomonas aeruginosa (10 cases, 7.6%) and Staphylococcus aureus (10 cases, 7.6%). The proportion of multi-drug resistant bacteria in hospital-acquired BSI was higher than that in community-acquired BSI [52.9% (36/68) vs 15.6% (10/64), P=0.001]. The proportions of community-acquired infection were 58.5% (55/94) and 23.7% (9/38) in the survival and death groups, respectively, the difference was statistically significant (P<0.001). The proportion of central venous catheter insertion before bloodstream infection in the death group was higher than that in the survival group [63.2% (24/38) vs 42.6% (40/94), P=0.034]. According to the binary multivariate logistic regression analysis, hospital-acquired infection (OR=4.80, 95%CI: 1.825-12.621, P=0.001), absolute neutrophil count (ANC) (OR=0.93, 95%CI: 0.863-0.993, P=0.030) and decreased albumin (OR=0.89, 95%CI: 0.817-0.977, P=0.014) were risk factors for death. Conclusions: The common pathogen of BSI-induced severe sepsis in PICU is Gram-negative bacteria. The proportion of multi-drug resistant organisms of BSI obtained in hospitals is high. Children with severe sepsis due to BSI with nosocomial acquired infection, ANC and decreased albumin have a high risk of death.

Clinicopathological correlates in the frontotemporal lobar degeneration-motor neuron disease spectrum.

Amyotrophic lateral sclerosis (ALS) is a devastating motor neuron disease (MND) that shares a common clinical, genetic and pathologic spectrum with frontotemporal dementia (FTD). It is highly heterogeneous in its presentation and features. Up to 50% of patients with MND develop cognitive-behavioural symptoms during the course of the disease, meeting criteria for FTD in 10%-15% of cases. In the absence of a precise biomarker, neuropathology is still a valuable tool to understand disease nosology, reach a definite diagnostic confirmation and help define specific subgroups of patients with common phenotypic, genetic and biomarker profiles. However, few neuropathological series have been published, and the frequency of frontotemporal lobar degeneration (FTLD) in MND is difficult to estimate. In this work we describe a large clinicopathological series of MND patients, analysing the frequency of concurrent FTLD changes and trying to define specific subgroups of patients based on their clinical, genetic and pathological characteristics. We performed an observational, retrospective, multicentre case study. We included all cases meeting neuropathological criteria for MND from the Neurological Tissue Bank of the FRCB-IDIBAPS-Hospital Clínic Barcelona Biobank between 1994 and 2022, regardless of their last clinical diagnosis. While brain donation is encouraged in all patients, it is performed in very few, and representativeness of the cohort might not be precise for all patients with MND. We retrospectively reviewed clinical and neuropathological data and describe the main clinical, genetic and pathogenic features, comparing neuropathologic groups between MND with and without FTLD changes and aiming to define specific subgroups. We included brain samples from 124 patients, 44 of whom (35.5%) had FTLD neuropathologic features (i.e. FTLD-MND). Pathologic TDP-43 aggregates were present in 93.6% of the cohort and were more extensive (higher Brettschneider stage) in those with concurrent FTLD (P < 0.001). Motor symptom onset was more frequent in the bulbar region in FTLD-MND cases than in those with isolated MND (P = 0.023), with no differences in survival. We observed a better clinicopathological correlation in the MND group than in the FTLD-MND group (93.8% versus 61.4%; P < 0.001). Pathogenic genetic variants were more common in the FTLD-MND group, especially C9orf72. We describe a frequency of FTLD of 35.5% in our series of neuropathologically confirmed cases of MND. The FTLD-MND spectrum is highly heterogeneous in all aspects, especially in patients with FTLD, in whom it is particularly difficult to define specific subgroups. In the absence of definite biomarkers, neuropathology remains a valuable tool for a definite diagnosis, increasing our knowledge in disease nosology.

PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications.

Sepsis is a serious organ dysfunction caused by a dysregulated immune host reaction to a pathogen. The innate immunity is programmed to react immediately to conserved molecules, released by the pathogens (PAMPs), and the host (DAMPs). We aimed to review the molecular mechanisms of the early phases of sepsis, focusing on PAMPs, DAMPs, and their related pathways, to identify potential biomarkers. We included studies published in English and searched on PubMed® and Cochrane®. After a detailed discussion on the actual knowledge of PAMPs/DAMPs, we analyzed their role in the different organs affected by sepsis, trying to elucidate the molecular basis of some of the most-used prognostic scores for sepsis. Furthermore, we described a chronological trend for the release of PAMPs/DAMPs that may be useful to identify different subsets of septic patients, who may benefit from targeted therapies. These findings are preliminary since these pathways seem to be strongly influenced by the peculiar characteristics of different pathogens and host features. Due to these reasons, while initial findings are promising, additional studies are necessary to clarify the potential involvement of these molecular patterns in the natural evolution of sepsis and to facilitate their transition into the clinical setting.

Levels of Indicator Bacteria and Characteristics of Foodborne Pathogens from Carcasses of Cattle Slaughterhouses in Korea

The initial microbial contamination of carcasses during slaughtering adversely affects spoilage and shelf life and is of global concern for food safety and meat quality. This study evaluated the hygiene and quality using the prevalence of foodborne pathogens and the level of indicator bacteria on 200 carcasses, collecting 10 from each of 20 cattle slaughterhouses in Korea. The distribution of aerobic bacterial count in carcasses was significantly highest at 2.0–3.0 log10 CFU/cm2 (34.1%), whereas the Escherichia coli count was significantly highest at under 1.0 log10 CFU/cm2 (94.0%) (P < 0.05). Clostridium perfringens was most prevalent (60.0% of slaughterhouses; 17.5% of carcasses), followed by Yersinia enterocolitica (30.0% of slaughterhouses; 6.5% of carcasses), Staphylococcus aureus (15.0% of slaughterhouses; 4.0% of carcasses), Listeria monocytogenes 1/2a (5.0% of slaughterhouses; 1.0% of carcasses), Salmonella enterica subsp. enterica serovar Infantis (5.0% of slaughterhouses; 1.0% of carcasses), and Shiga toxin-producing E. coli O:66 (5.0% of slaughterhouses; 0.5% of carcasses). Although 28 C. perfringens isolates from 11 slaughterhouses were divided into 21 pulsotypes, all isolates showed the same toxinotype as type A and only carried the cpa. Interestingly, 83.3% of isolates from two slaughterhouses located in the same province showed resistance to tetracycline. Furthermore, 13 Y. enterocolitica isolates from six slaughterhouses were divided into seven pulsotypes that were divided into biotypes 1A and 2 and serotypes O:5 and O:8, except for isolates that could not be typed. Twelve (92.3%) isolates only carried ystB, but one (7.7%) isolate carried ail and ystA. Moreover, 46.2% of Y. enterocolitica isolates showed multidrug resistance against ampicillin, cefoxitin, and amoxicillin/clavulanic acid. This study supports the need for continuous monitoring of slaughterhouses and hygiene management to improve the microbiological safety of carcasses.

Features of the epidemiological surveillance system of rabies and monkeypox in the Republic of Cameroon

The prevention and control of zoonotic infections remain a problem in most countries. However, this problem has become particularly relevant in recent decades, when the occurrence and pandemic spread of zoonotic diseases have become more frequent. All spheres of the national economy that ensure the fight against infections of this group (healthcare systems, veterinary medicine, and ecology) are trying to jointly find appropriate solutions to ensure antiepidemic protection of the population by taking adequate measures to prevent and combat infectious zoonoses. According to the World Health Organization, the spread of zoonotic infections is observed on all continents, particularly in Asia and Africa. The epidemiological significance of zoonoses depends on their effects on the population (morbidity and mortality), their ability to overcome interspecific barriers, and the individual characteristics of pathogens. It is also influenced by factors such as geographical location, climate, population density, economic growth rates, and development level of private and industrial livestock and poultry farming. The epidemiological surveillance systems in Cameroon are compared with the surveillance system in Russia and with the standards set by international organizations such as the World Health Organization and the Food and Agriculture Organization of the United Nations. The emergence and spread of current zoonotic infections in the Republic of Cameroon are presented. The study showed the geographical, social, administrative, economic, and health characteristics of Cameroon, which may influence the emergence and spread of infectious zoonosis in the country. Zoonotic diseases have only begun to receive special attention in Cameroon’s health system in 2014–2016, following an outbreak of monkeypox (mpox) in Cameroon. Moreover, the study described the epidemiological surveillance system and a classification of epidemic events monitored by the Cameroon Disease, Epidemic and Pandemic Control Authority. In general, the surveillance system for human and animal zoonoses in Cameroon was designed to ensure a rapid response during an epidemic. However, some shortcomings exist, such as low data for some zoonotic diseases and insufficient or virtually nonexistent surveillance in some regions of the country. To intensify the fight against the epidemic spread of these zoonotic infections, the capacity of health workers and technical means for detection and monitoring must be improved. The update of the national vaccination schedule should consider diseases such as rabies, given its endemic nature in the country; this may be possible through the establishment of a service or office responsible for surveillance, detection, and response to infectious zoonotic diseases.

Advance of research on Hereditary spastic paraplegia type 4

Spastic paraplegia type 4 (SPG4) is the most common type of autosomally inherited spastic paraplegia. Its main clinical features include typical simple hereditary spastic paraplegia, with neurological impairments limited to lower limb spasticity, hypertonic bladder dysfunction, and mild weakening of lower limb vibration sensation, without accompanying features such as nerve atrophy, ataxia, cognitive impairment, seizures, and muscle tone disorders. SPAST is the main pathogenic gene underlying SPG4, and various pathogenic SPAST variants have been discovered. This disease has featured a high degree of clinical heterogeneity, and the same pathogenic variant can have different age of onset and severity among different patients and even within the same family. There is a lack of systematic research on the correlation between the genotype and phenotype of SPG4, and the pathogenic mechanism has remained controversial. This article has provided a review for the clinical characteristics, pathogenic gene characteristics, correlation between the genotype and phenotype, and pathogenic mechanism of this disease, with an aim to provide reference for its clinical diagnosis and treatment.