Association of non-HDL cholesterol with plaque burden and composition of culprit lesion in acute coronary syndrome. An intravascular ultrasound-virtual histology study.

OBJECTIVE: Lipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS). METHODS: A total of 601 patients divided into two groups: normal non-HDL-C≤130 mg/dl (n=410) and high non-HDL cholesterol >130 mg/dl (n=191). IVUS performed before coronary intervention. RESULTS: Mean age 53.18±12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59±9.98% vs. 81.61±5.39%; p=0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p=0.027), while necrotic core greater in high non-HDL-C group (p=0.033). Segmental analysis, necrotic core was significantly higher in percentage (p=0.006) and volumes (p=0.011) in normal versus high non-HDL-C groups. Total cholesterol (r=0.099, p=0.015), LDL-C (r=0.081,p=0.046), triglycerides (r=0.083, p=0.041),and non-HDL-C (r=0.099, p=0.015) positively correlated with plaque burden. Total cholesterol (r=0.115, p=0.005), LDL-C (r=0.107, p=0.009), and non-HDL-C (r=0.105, p=0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume. CONCLUSION: Non-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS.

A Case of Necrotizing Lymphadenitis Misdiagnosed as a Neck Abscess.

Histiocytic necrotizing lymphadenitis (HNL), also known as Kikuchi disease, is a relatively rare sub-acute necrotic localized lymphadenitis. This benign, self-limiting condition is characterized by fever, painful lymphadenopathy, skin rash, and other systemic symptoms. Due to its nonspecific presentation, unclear etiology, and pathogenesis, HNL has a low incidence rate in clinical practice. Insufficient awareness among clinicians and pathologists can easily lead to misdiagnosis. This article reported a 27-year-old female patient who was admitted to the hospital with fever, neck pain, and enlarged lymph nodes in the neck. There were no special medical or personal histories, and postoperative pathology confirmed tissue necrotizing lymphadenitis. After treatment with steroids and symptomatic therapy, she recovered and was discharged from the hospital. Follow-up to date has shown no recurrence.

Evaluating performance, intestinal lesions, and immunity related genes in heritage and modern broiler breeds during a necrotic enteritis challenge.

In this comparative study, the differential responses of heritage (ACRB; Athens Canadian Random Bred) and modern (Cobb) broilers to a necrotic enteritis (NE) challenge were evaluated. The design was a 2×2 factorial with breed (ACRB and Cobb) and challenge (non-challenged and NE-challenged) as main factors. On day (d) of hatch, 96 male chicks (48 ACRB and 48 Cobb) were allocated to 4 experimental groups with 8 replicate cages and 3 birds/cage. On d 14, birds in the NE-challenged groups were orally gavaged with 3,000 Eimeria maxima sporulated oocysts followed by 2 doses of ∼1×108 CFU of Clostridium perfringens on d 19 and 20. On d 21, 2 birds/cage were necropsied to score NE lesions, and spleen and cecal tonsils (CT) samples were collected from 1 bird/cage for assessing mRNA abundance. Challenged ACRB birds exhibited reduced growth performance and relative growth performance compared to challenged Cobb birds. There was no significant interaction between breed and challenge during the challenge period (d 14-21) for mortality. However, there was a challenge main effect (P ≤ 0.05) on mortality as manifested by greater NE-associated mortality compared to non-challenged birds. No significant breed × challenge interaction or breed main effect on lesion scores were observed in the duodenum, jejunum, and ileum. NE-challenged Cobb birds exhibited greater mRNA abundance of IL-18, TNFα, TLR1.2, TLR2.1, CCR5, CCR6, CCL20, and AvBD1 in CT compared to NE challenged ACRB birds. There was a significant breed × challenge interaction effect on mRNA abundance of IL-10, AvBD13, NK-Lysin, and LEAP2 in the spleen. Moreover, a main effect of breed was observed in IL-1ß, IL-18, TNFα, TLR2.1, CCR5, CCL20, and NK-Lysin where ACRB birds had higher mRNA abundance than Cobb birds (P ≤ 0.05). The observed differences in performance, pathology, and mRNA abundance between ACRB and Cobb broilers during the NE challenge highlight the distinct immune response profiles of heritage and modern breeds, emphasizing the need for breed-specific nutritional, managerial, and genetic selection programs for modulating immune responses during enteric disease challenges.

From the discovery of a novel arepavirus in diseased arecanut palms (Areca catechu L.) in India to the identification of known and novel arepaviruses in bee and plant transcriptomes through data-mining.

Arecanut palm is a commercially important plantation crop valued for its nut. In this investigation, we report the discovery of a putative novel arepavirus, named areca palm necrotic ringspot virus 2 (ANRSV2), in necrotic ringspot diseased areca palms in Bantwal, Dakshina Kannada, Karnataka, India through RNA-sequencing and transmission electron microscopy. Further, the presence of ANRSV2 in the diseased samples was confirmed through reverse transcriptase-polymerase chain reaction assays. In addition, by mining public domain transcriptome data for arepaviral sequences, we identified a putative novel arepavirus in Psychotria rubra, a non-palm host. We recovered the genome sequences of the areca palm necrotic ringspot virus in honey bees, tomato, Onobrychis viciifolia, and Rhamnus heterophylla. These findings broaden our comprehension of arepaviral diversity and host range, and suggest an intriguing possibility of pollen-mediated arepaviral transmission that necessitates empirical validation. Further studies are needed to understand the biology of identified putative novel arepaviruses.

LAMTOR1/mTORC1 promotes CD276 to induce immunosuppression via PI3K/Akt/MMP signaling pathway in Clostridium perfringens-induced necrotic enteritis of laying hens.

Clostridium perfringens (C. perfringens) causes avian necrotic enteritis, leading to huge economic losses to the poultry industry. This pathogen induces host immunosuppression; however, the molecular mechanism is still unclear. Thus, we established a laying hen infection model to explore this mechanism. We randomly divided 20 one-old-day laying hens into the control and infection groups. The infection group was infected intragastrically with 1 × 109 colony-forming units of C. perfringens in 1 mL of sterile phosphate-buffered saline (PBS) once a day from d 17 to 20; the control group received the same volume of PBS without the bacterium. Twenty-four hours after the last challenge, we sacrificed the laying hens and collected the jejunum for analysis. The infection group presented alterations in blood biochemical parameters and necrotic lesion scores as well as damage to the jejunum. Proteomics revealed 427 upregulated and 291 downregulated proteins in the infection group. In the infection group, CD3, CD4, and CD8 messenger RNA expression (mRNA) expression was decreased; LAMTOR1 and mTORC1 mRNA expression was increased; CD276 protein expression was enhanced; and the PI3K/Akt/MMP pathway was activated in jejunum of laying hens. This is the first study to report CD276 expression in the jejunum related to immunosuppression in a laying hen model of necrotic enteritis. It provides some new key targets to potentially control avian necrotic enteritis.

Research Note: Effects of on-farm and hatchery hatching on broiler performance, intestinal lesions, and immune response during a subclinical necrotic enteritis challenge.

The effects of traditional and on-farm hatching systems on broiler performance and health under a subclinical necrotic enteritis (NE) challenge were evaluated in this study. A 2×2 factorial study explored the effects of place of hatch (on-farm hatched [OFH] vs. hatchery hatched [HH]) and NE challenge (nonchallenged vs. challenged) on broilers. Cobb 500 eggs (∼E19) were acquired from a commercial hatchery; 840 eggs were placed in pens on clean shavings in prewarmed floor pens and allowed to hatch out, while 927 eggs were placed in a hatcher set under standard practices. On day (d) of hatch, all chicks were weighed and randomly distributed to 4 treatments (8 replicate pens each and 30 birds/pen). The OFH birds were placed immediately after sorting while HH birds were placed back in the hatcher overnight to simulate commercial hatchery procedures. After placing HH birds, feed and litter in the challenge group pens were sprayed with a live oocyst coccidia vaccine as a predisposing factor to NE. The small intestines of 3 male chicks per pen were scored for NE lesions (n = 24) on d 8 (peak NE challenge) and jejunal samples were collected from 1 bird per pen for RNA extraction and qPCR on d 8 and d 14. Data were analyzed using JMP Pro17 and significance between treatments was identified by LSD (P ≤ 0.05). Regardless of the hatching system, the subclinical NE challenge caused a significant reduction in average daily gain (ADG) and average daily feed intake (ADFI), and increased feed conversion ratio (FCR) until d 28 (P ≤ 0.05). Moreover, OFH birds exhibited significantly better growth (P ≤ 0.05) through d 28 but had similar performance to HH birds by d 42. There were no significant differences in NE lesion scores between HH and OFH groups. In conclusion, OFH system resulted in better broiler performance compared to HH system under both no-challenge and challenge conditions during the starter and grower periods. This practice may hold potential for further exploration by the industry as an alternative to traditional hatching, aiming to improve the welfare and productivity of broilers.

In vivo overexpression of the avian interleukin-17 in a necrotic enteritis disease model modulates the expression of antimicrobial peptides in the small intestine of broilers.

In humans and mice, the induction of interleukin (IL)-17 expression enhances epithelial barrier integrity through the secretion of antimicrobial peptides (AMP), thereby improving antibacterial defense. However, it is unclear whether IL-17 has similar antibacterial effects in chickens by modulating the expression of AMPs, such as avian beta-defensins (also known as gallinacins) and cathelicidins. This study evaluated the in vivo effects of inoculating 20-day-old broiler chickens with two doses of a plasmid encoding chicken IL-17 (pCDNA3.1/rchIL-17-V5-HIS TOPO plasmid [pCDNA3.1-IL-17]; 5 or 10 µg/bird). On day 23 of age, all broilers, except those in the negative control group, were orally challenged with a virulent Clostridium perfringens strain for three days. To investigate IL-17-mediated effects against C. perfringens infection, the expression of avian beta-defensin 1 (avBD1), avBD2, avBD4, avBD6, cathelicidins, and inducible nitric oxide synthase (iNOS) genes were quantified, and gross necrotic enteritis (NE) lesion scores were assessed in the small intestine. The results showed that broilers receiving the higher dose of pCDNA3.1-IL-17 (10 µg) had significantly lower NE lesion scores compared to those receiving the lower dose (5 µg), the vector control, and the positive control groups. Furthermore, the expression of all avian beta-defensins and cathelicidin genes was detectable across all groups, regardless of treatment and time points. IL-17 treatment led to significantly higher expression of avBD1, avBD2, avBD4, avBD6, cathelicidin, and iNOS in the duodenum, jejunum, and ileum compared to control chickens. In C. perfringens-infected chickens, the expression of avBD1, avBD2, avBD4, cathelicidin, and iNOS in the ileum was significantly higher than in control chickens. Pre-treatment with the higher dose of pCDNA3.1-IL-17 (10 µg) in infected chickens was associated with reduced NE lesion severity and increased expression of avBD1, avBD2, cathelicidin, and iNOS in the ileum, but not avBD4 and avBD6. These findings provide new insights into the potential effect of IL-17 and reduction in NE lesion severity by modulating AMP expression which may be involved in mediating protective immunity against intestinal infection with C. perfringens.

Electrochemical impedance spectroscopy unmasks high-risk atherosclerotic features in human coronary artery disease.

Coronary plaque rupture remains the prominent mechanism of myocardial infarction. Accurate identification of rupture-prone plaque may improve clinical management. This study assessed the discriminatory performance of electrochemical impedance spectroscopy (EIS) in human cardiac explants to detect high-risk atherosclerotic features that portend rupture risk. In this single-center, prospective study, n = 26 cardiac explants were collected for EIS interrogation of the three major coronary arteries. Vessels in which advancement of the EIS catheter without iatrogenic plaque disruption was rendered impossible were not assessed. N = 61 vessels underwent EIS measurement and histological analyses. Plaques were dichotomized according to previously established high rupture-risk parameter thresholds. Diagnostic performance was determined via receiver operating characteristic areas-under-the-curve (AUC). Necrotic cores were identified in n = 19 vessels (median area 1.53 mm2) with a median fibrous cap thickness of 62 µm. Impedance was significantly greater in plaques with necrotic core area ≥1.75 mm2 versus <1.75 mm2 (19.8 ± 4.4 kΩ vs. 7.2 ± 1.0 kΩ, p = .019), fibrous cap thickness ≤65 µm versus >65 µm (19.1 ± 3.5 kΩ vs. 6.5 ± 0.9 kΩ, p = .004), and ≥20 macrophages per 0.3 mm-diameter high-power field (HPF) versus <20 macrophages per HPF (19.8 ± 4.1 kΩ vs. 10.2 ± 0.9 kΩ, p = .002). Impedance identified necrotic core area ≥1.75 mm2, fibrous cap thickness ≤65 µm, and ≥20 macrophages per HPF with AUCs of 0.889 (95% CI: 0.716-1.000) (p = .013), 0.852 (0.646-1.000) (p = .025), and 0.835 (0.577-1.000) (p = .028), respectively. Further, phase delay discriminated severe stenosis (≥70%) with an AUC of 0.767 (0.573-0.962) (p = .035). EIS discriminates high-risk atherosclerotic features that portend plaque rupture in human coronary artery disease and may serve as a complementary modality for angiography-guided atherosclerosis evaluation.

Polygonum hydropiper Compound Extract Inhibits Clostridium perfringens-Induced Intestinal Inflammatory Response and Injury in Broiler Chickens by Modulating NLRP3 Inflammasome Signaling.

Necrotic enteritis (NE) is a critical disease affecting broiler health, with Clostridium perfringens as its primary pathogen. Polygonum hydropiper compound extract (PHCE), formulated based on traditional Chinese veterinary principles, contains primarily flavonoids with antibacterial, anti-inflammatory, and antioxidant properties. However, PHCE's efficacy against Clostridium perfringens-induced NE and its underlying mechanism remain unclear. This study employed network pharmacology and molecular docking to predict PHCE's potential mechanisms in treating NE, followed by determining its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against Clostridium perfringens (C. perf). Subsequently, the effects of various PHCE doses on intestinal damage, antioxidant capacity, and inflammatory factors in C. perf-infected broilers were assessed. Network pharmacology and molecular docking suggested that PHCE's therapeutic mechanism for NE involves the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway, with flavonoids such as quercetin, kaempferol, and isorhamnetin as key active components. PHCE exhibited an MIC of 3.13 mg/mL and an MBC of 12.5 mg/mL against C. perf. High PHCE doses effectively reduced intestinal damage scores in both the jejunum and ileum, accompanied by attenuated intestinal pathological changes. Additionally, the high dose significantly increased superoxide dismutase (SOD) levels while decreasing malondialdehyde (MDA), hydrogen peroxide (H2O2), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6) in the jejunum and ileum (p < 0.01 or p < 0.05). PHCE also modulated the expression of caspase-1, IL-1ß, gasdermin D (GSDMD), and NLRP3 mRNA, key components of the NLRP3 inflammasome signaling pathway, in both intestinal segments. These findings collectively indicate that PHCE protects against C. perf-induced oxidative stress and inflammatory damage in NE. By enhancing antioxidant capacity, PHCE likely reduces oxidative stress and inflammatory responses, subsequently modulating NLRP3 inflammasome signaling pathway key factor expression. Overall, this research provides valuable insights into the protective mechanism of the herbal compound PHCE and its potential benefits for avian health.

Rapid detection of Impatiens necrotic spot virus from thrips vectors using reverse transcription-recombinase polymerase amplification.

The plant virus, Impatiens necrotic spot virus (INSV), is an economically important pathogen of vegetables, fruits, and ornamental crops. INSV is vectored by the western flower thrips, Frankliniella occidentalis, a small insect pest that is globally distributed. In recent years, INSV outbreaks have reached epidemic levels in the Salinas Valley of California-an agriculturally rich region where most of the lettuce (Lactuca sativa) is produced in the United States. Due to the obligate nature in which virus transmission occurs, new tools that could rapidly detect INSV from thrips vectors would enhance our ability to predict where virus outbreaks may occur. Here, we report on the development of a reverse transcription-recombinase polymerase amplification (RT-RPA) assay that can detect INSV from individual thrips. The assay uses crude extraction methods, is performed at a single temperature of 42 °C, can be completed in 25 min, and provides sensitivity levels that are comparable to other available detection methods. When the assay was used on field populations of thrips, INSV was successfully identified and quantified from individual larvae and adults. The work provides a new cost-effective surveillance tool that can rapidly detect INSV from its insect vector and from plants.

Investigation and Confirmation of PYCARD as a Potential Biomarker for the Management of Psoriasis Disease.

Purpose: Psoriasis is not yet completely curable, and its etiology and pathogenesis are unclear. Necroptosis, also known as programmed necrosis, is a regulated mode of necrotic cell death. The interaction between inflammatory diseases and necrotic apoptosis has recently attracted significant attention. We explored the molecular mechanisms of necrotic apoptosis-related genes in psoriasis using bioinformatics methods to identify potential biomarkers for psoriasis. Patients and Methods: In this study, we screened psoriasis differentially expressed genes from the datasets GSE13355 and GSE14905 and took intersections with necrotic apoptosis-related genes for the next analysis. We used multiple machine learning algorithms to screen key genes and perform enrichment analysis. In addition, we performed an immune infiltration analysis. Transcription factors were predicted by the R package "RcisTarget". We also observed the cellular clustering of key genes in different cell types at the single-cell sequencing level. We used real-time fluorescence-based quantitative-polymerase chain reaction, Western blot, and immunohistochemistry to analyze gene expression in clinical samples. We constructed an imiquimod-induced psoriasis-like dermatitis model in mice for further validation. Results: Seven key genes were screened as follows: AIM2, CARD6, HPSE, MYD88, PYCARD, RAI14, and TNFSF10. Enrichment analysis showed that the key genes were mainly involved in inflammatory pathways. Immune infiltration analysis showed significantly higher levels of CD8 T cells, CD4 initial T cells, and CD4 memory-activated T cells in the disease group's samples than in the normal patients' samples. The key gene expression in single cells analyzed showed that PYCARD was significantly expressed in keratinocytes. PYCARD was selected for gene expression analysis; the results showed that its expression was significantly elevated in the skin lesion tissues of patients with psoriasis. We also verified that PYCARD might play a vital role in the development of psoriasis skin lesions using animal experiments. Conclusion: PYCARD plays a vital role in psoriasis development and is a potential biomarker for psoriasis.

Optimal parameters for the efficient microwave ablation of liver tumor from the 3D-IRCADb-01 database.

Purpose: Microwave ablation is a minimally invasive thermal modality for cancer treatment with high survival and low recurrence rates. Despite the unquestionable benefits of microwave ablation, the interaction between the medical instruments and the tissue may cause damage to the healthy tissue around the tumor. Such damages can be removed by clarifying the conditions for their development. In addition to clinical methods, computer simulations have become very effective tools for optimizing microwave ablation performance. Methods: The study was focused on the determination of the optimal input power for complete microwave tumor ablation with an ade-quate safety margin avoiding injury to the surrounding healthy tissue. In three-dimensional simulations, the liver tumor model was based on a real tumor (1.74 cm × 2.40 cm × 1.43 cm) from the 3D-IRCADb-01 database. Calculations were performed for a 10-slot antenna proven to achieve a higher degree of ablation zone localization than a standard single-slot antenna. The temperature-dependent dielectric and thermal properties of healthy and tumoral liver tissue, blood perfusion, and water content were included in the model. Results: The obtained simulation results revealed that the proper choice of input power ensures that necrotic tissue is mainly located in the tumor with minimal damage to the surrounding healthy tissue. Conclusions: This study may represent a step forward in the planning of individual microwave ablation treatment for each patient.

Xylazine-Induced Necrotic Skin Ulcers in a Fentanyl-Injecting Individual in South Florida, United States: A Case Report.

Xylazine, commonly referred to as "Tranq," is an alpha-2-adrenergic receptor agonist that is FDA-approved only as a sedative and tranquilizer for veterinary use. However, its use as an adulterant in various illicit drugs, including fentanyl, has been on the rise, leading to its street name, "Tranq-Dope." Intravenous injection use of xylazine produces distinctive skin ulceration with accompanying necrosis, which can be considered virtually pathognomonic. A 41-year-old male with polysubstance abuse disorder presented to the emergency department with severe skin ulcerations on the right forearm and left calf with associated pain and erythema at injection sites. The concern for complicated skin tissue infection was acknowledged and the patient was admitted. The initial urine toxicology report was positive for cocaine, cannabinoids, benzodiazepines, and fentanyl. Upon detailed history-taking, the patient attested to recent changes in the sedative and euphoric effects of fentanyl use, which increased the index of suspicion for xylazine exposure. Immunoassay-based xylazine test strips were positive. Initially, he was administered broad-spectrum intravenous antibiotics, then switched to oral antibiotics at discharge. He was compliant with starting buprenorphine and buprenorphine-naloxone following discharge for management of his severe opioid use disorder. Xylazine's alpha-2-adrenergic agonistic properties in the periphery are thought to initiate a cascade of effects starting with vasoconstriction causing impaired blood perfusion hindering wound healing and increasing vulnerability to secondary infections. This case report aims to alert the medical community about the alarming occurrence of xylazine as an adulterant in illicit drugs and to describe the characteristic skin lesions associated with xylazine injections. Awareness of xylazine use should be considered in patients who develop necrotic skin ulcerations at injection sites along with alterations in typical effects of drug use.

Skin, Heart, and CNS Involvement in Granulomatosis With Polyangiitis: A Case Report.

We discuss the case of a 60-year-old male who presented with ankle pain, a necrotic rash, and progressive weakness in both lower limbs and the right upper limb. An infectious workup of the skin lesions came back negative. Additionally, his kidney function tests indicated an acute kidney injury. This prompted investigations for vasculitis etiologies, which revealed a positive cytoplasmic antineutrophil cytoplasmic autoantibody (c-ANCA). His neurological deficits were also investigated, and imaging suggested embolic infarcts. Cardiac imaging showed valve vegetations and blood culture showed a lack of growth suggestive of a noninfective nature of these lesions. Based on all these findings, a kidney biopsy was obtained and demonstrated pauci-immune segmental vasculitis consistent with ANCA-associated glomerulonephritis. As such, the patient showed improvement with heavy pulse steroid and immunomodulator therapy. Although skin, heart, and CNS involvement have been previously reported with ANCA-associated vasculitis, it is rare, especially together, and can prove a diagnostic challenge. Therefore, it is important to consider vasculitis etiology in patients presenting similarly. In addition, this case highlights the overlapping clinical picture between infective endocarditis and vasculitis with valvular involvement, making differentiation between the two challenging.

Metal Oxide Nanoparticles Exhibit Anti-Acanthamoeba castellanii Properties by Inducing Necrotic Cell Death.

PURPOSE: The treatment of amoebic infections is often problematic, largely due to delayed diagnosis, amoebae transformation into resistant cyst form, and lack of availability of effective chemotherapeutic agents. Herein, we determined anti-Acanthamoeba castellanii properties of three metal oxide nanoparticles (TiO2, ZrO2, and Al2O3). METHODS: Amoebicidal assays were performed to determine whether metal oxide nanoparticles inhibit amoebae viability. Encystation assays were performed to test whether metal oxide nanoparticles inhibit cyst formation. By measuring lactate dehydrogenase release, cytotoxicity assays were performed to determine human cell damage. Hoechst 33342/PI staining was performed to determine programmed cell death (apoptosis) and necrosis in A. castellanii. RESULTS: TiO2-NPs significantly inhibited amoebae viability as observed through amoebicidal assays, as well as inhibited their phenotypic transformation as evident using encystation assays, and showed limited human cell damage as observed by measuring lactate dehydrogenase assays. Furthermore, TiO2-NPs altered parasite membranes and resulted in necrotic cell death as determined using double staining cell death assays with Hoechst33342/Propidium iodide (PI) observed through chromatin condensation. These findings suggest that TiO2-NPs offers a potential viable avenue in the rationale development of therapeutic interventions against Acanthamoeba infections.

Global trends in opioid use for pain management in acute pancreatitis: A multicentre prospective observational study.

BACKGROUND: Since there is no current international consensus on the optimal approach for pain management in acute pancreatitis (AP), analgesic practices may vary across different healthcare settings. OBJECTIVE: This study explored global disparities in analgesic use, in particular opioids, during admission and at discharge in hospitalised AP patients. METHODS: This was a post hoc analysis of the prospective PAINAP database, which included all admissions for AP between April and June 2022 with a 1-month follow-up. Demographic details, analgesic use, and clinical outcomes were recorded during admission and at discharge. Odds ratios (ORs) for opioid use during admission and at discharge were identified using multivariable regression analyses. RESULTS: Amongst the 1864 patients (52% males, median age 56 (interquartile range, 41-71)) across three different continents, simple analgesics were predominantly used as the primary analgesic (70%). Opioid use during admission was lowest in European centres (67%). Admission in Asian (OR, 2.53 (95% confidence interval (CI), 1.59-4.04), p < 0.001), and Australian (OR, 5.81 (95% CI, 3.19-10.56), p < 0.001) centres was associated with opioid administration during admission compared with European centres. Increased pain severity, longer pre-admission pain duration, organ failure, and longer length of admission increased opioid use during admission. At discharge, Asian (OR, 2.01 (95% CI, 1.40-2.88), p < 0.001) and Australian (OR, 1.91 (95% CI, 1.28-2.85), p = 0.002) centres were associated with opioid prescription compared with European centres. Increased pain severity, longer pre-admission pain duration, acute necrotic collections, and walled-off necrosis also increased the likelihood of opioid prescription at discharge. CONCLUSION: There are substantial intercontinental differences in opioid use for AP pain. Accordingly, there is a need for international guidelines on pain management in AP.

Clostridium perfringens antigens and challenges for development of vaccines against necrotic enteritis in poultry.

INTRODUCTION: Chickens with Necrotic Enteritis (NE), caused by Clostridium perfringens, exhibit acute and chronic symptoms that are difficult to diagnose, leading to significant economic losses. Vaccination is the best method for controlling and preventing NE. However, only two vaccines based on the CPA and NetB toxins have been commercialized, offering partial protection, highlighting the urgent need for more effective vaccines. OBJECTIVE: This review aimed to identify promising antigens for NE vaccine formulation and discuss factors affecting their effectiveness. METHODS: A systematic review using five scientific databases identified 30 eligible studies through the Rayyan tool, which were included for quality review. RESULTS: We identified 25 promising antigens, including CPA, NetB, FBA, ZMP, CnaA, FimA, and FimB, categorized by their role in disease pathogenesis. This review discusses the biochemical, physiological, and genetic traits of recombinant antigens used in vaccine prototypes, their expression systems, and immunization potential in chickens challenged with virulent C. perfringens strains. Market supply challenges, immunogenic potential, vaccine platforms, adjuvants, and factors related to vaccination schedules-such as administration routes, dosing intervals, and age at immunization-are also addressed. Additionally, the study notes that vaccine formulations tested under mild challenges may not offer adequate field-level protection due to issues replicating aggressive conditions, strain virulence loss, and varied methodologies. CONCLUSIONS: An ideal NE vaccine should incorporate multiple antigens, molecular adjuvants, and delivery systems via in ovo and oral routes. The review underscores the challenges in developing and validating NE vaccines and the urgent need for a standardized protocol to replicate aggressive challenges accurately.

Effect of stimbiotic on growth performance, nutrient digestibility, oocyst shedding, blood profiles, and intestinal microbiota in necrotic enteritis-challenged broiler.

This experiment was conducted to investigate the effect of stimbiotic (STB) in broilers with necrotic enteritis (NE). A total of 180 one-day-old Arbor Acres (initial body weight of 34.81 ± 1.04 g) were used in this experiment for 32 days. All broilers were randomly allocated into six treatments, and each experimental group had 10 replicate cages with three broilers per cage. The experiment was conducted in a 2 × 3 factorial design consisting of two levels of challenge (challenge and non-challenge) and three levels of STB (0, 0.05, and 0.1%). The NE challenge significantly decreased (P < 0.05) growth performance, heterophil levels in blood, and intestinal lesion scores compared to the non-challenge group. Supplementation of 0.05% STB significantly decreased (P < 0.05) feed conversion ratio and the number of oocysts per gram of feces compared to the supplementation of 0 and 0.1% STB. At the genus level, the supplementation of 0.05% STB significantly decreased (P < 0.05) the abundance of Enterobacterales compared to the other groups on d 32. In conclusion, supplementation with 0.05% STB in a diet could positively regulate the fecal microflora and alleviate the decline in growth performance and nutrient digestibility caused by NE.

Necrotic enteritis in chickens: a comprehensive review of vaccine advancements over the last two decades.

Necrotic enteritis (NE) is a severe gastrointestinal disease that poses a significant threat to poultry, leading to progressive deterioration of the small intestine, reduced performance, and increased mortality rates, causing economic losses in the poultry industry. The elimination of antimicrobial agents from chicken feed has imposed a need to explore alternative approaches for NE control, with vaccination emerging as a promising strategy to counteract the detrimental consequences associated with NE. This comprehensive study presents an overview of the extensive efforts made in NE vaccination from 2004 to2023. The study focuses on the development and evaluation of vaccine candidates designed to combat NE. Rigorous evaluations were conducted in both laboratory animals and broiler chickens, the target population, to assess the vaccines' capacity to elicit an immune response and provide substantial protection against toxin challenges and experimental NE infections. The review encompasses the design of vaccine candidates, the antigens employed, in vivo immune responses, and the efficacy of these vaccines in protecting birds from experimental NE infection. This review contributes to the existing knowledge of NE vaccination strategies, offering valuable insights for future research and development in this field.

A comprehensive review of experimental models and induction protocols for avian necrotic enteritis over the past 2 decades.

Necrotic enteritis (NE) is a severe gastrointestinal disease that poses a significant threat to the poultry industry. It leads to progressive damage to the small intestine, reduced performance, increased mortality rates, and substantial economic losses. With the removal of antimicrobial agents from chicken feed, there is an urgent need to find alternative approaches for NE control. Various approaches, including vaccination, prebiotics, probiotics, and plant-derived products, have been utilized to address NE in poultry management. To evaluate the efficacy of these preventive measures against NE, successful induction of NE is crucial to observe effects of these approaches in related studies. This study presents a comprehensive overview of the methods and approaches utilized for NE reproduction in related studies from 2004 to 2023. These considerations are the careful selection of a virulent Clostridium perfringens strain, preparation of challenge inoculum, choice of time and the route for challenge inoculum administration, and utilization of one or more predisposing factors to increase the rate of NE occurrence in birds under experiment. We also reviewed the different systems used for lesion scoring of NE-challenged birds. By gaining clarity on these fundamental parameters, researchers can make informed decisions regarding the selection of the most appropriate NE experimental design in their respective studies.