Prominent Lesions Research Articles

Histological Alterations in Two Estuarine Fishes, (Mugil cephalus and Sillago sihama) from Ennore Creek, South East Coast, India

Background: Two fish species namely the flathead grey mullet, Mugil cephalus and Silver sillago, Sillago sihama were selected for the histological studies to assess the impact of pollution on the vital organs of fishes. Methods: The gill, liver and kidney tissues of Mugil cephalus and Sillago sihama of Ennore Creek and unpolluted reference site, Arambakkam were collected.Histological sections of tissues collected from the UPRS, Arambakkam showed normal histoarchitecture. However, there were several histological alterations in the above-mentioned organs of these two species collected from Ennore Creek due to high pollution in Ennore Creek. Result: The present study showed that the fishes are exposed to pollution-induced stress at Ennore Creek, making the fishes anaemic, weak and vulnerable to diseases. The Ennore Creek is a coastal wetland affected by a major oil spill and other anthropogenic pollution sources. Histological analysis revealed the occurrence of prominent gill and liver lesions, especially in the tissues of M. Cephalus. This study provides scientific evidence for the biological impacts on the resident fishes in the Ennore creek and calls for further research on the impacts of coastal water pollution and potential management strategies.

Novel Mastadenovirus Infection as Cause of Pneumonia in Imported Black-and-White Colobuses (Colobus guereza), Thailand.

We identified a novel mastadenovirus, herein referred to as colobus adenovirus (CoAdV), as the likely cause of fatal respiratory and enteric diseases in multiple black-and-white colobuses (Colobus guereza) imported into Thailand in 2022. Among 9 affected colobuses, 4 died. Viral antigen was abundant in respiratory and enteric tissues, where prominent lesions and clinical signs were observed. We successfully cultivated CoAdV in Vero cells and characterized the complete viral genome, which indicated the virus is genetically distinct from other simian adenoviruses. We also conducted a retrospective study of archival samples from 7 other unrelated colobuses that had respiratory distress or diarrhea and found similar viral strains in 4 of those colobuses. Although we could not determine the potential harm to humans or other nonhuman primates from current information, the zoonotic and spillover potential of this virus to other related hosts should not be neglected. Veterinarians should consider CoAdV when pneumonia is diagnosed in colobuses.

A human high-fidelity DNA polymerase holoenzyme has a wide range of lesion bypass activities.

During replication, lagging strand lesions are initially encountered by high-fidelity DNA polymerase (pol) holoenzymes comprised of pol δ and the PCNA sliding clamp. To proceed unhindered, pol δ holoenzymes must bypass lesions without stalling. This entails dNMP incorporation opposite the lesion (insertion) and the 5' template nucleotide (extension). Historically, it was viewed that high-fidelity pol holoenzymes stall upon encountering lesions, activating DNA damage tolerance pathways that are ultimately responsible for lesion bypass. Our recent study of 4 prominent lesions revealed that human pol δ holoenzymes support insertion and/or bypass for multiple lesions and the extents of these activities depends on the lesion and pol δ proofreading. In the present study, we expand these analyses to other prominent lesions. Collectively, analyses of 10 lesions from both studies reveal that the insertion and bypass efficiencies of pol δ holoenzymes each span a complete range (0 - 100%). Consequently, the fates of pol δ holoenzymes upon encountering lesions are quite diverse. Furthermore, pol δ proofreading promoted holoenzyme progression at 7 of the 10 lesions and did not deter progression at any. Altogether, the results significantly alter our understanding of the replicative capacity of high-fidelity pol holoenzymes and their functional role(s) in lesion bypass.

A weighted and cumulative point system for accurate scoring of intestinal pathology in a piglet model of necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a serious condition in premature infants, in which a portion of the intestine undergoes inflammation and necrosis. The preterm pig develops NEC spontaneously, making it a suitable model for exploring novel NEC treatments. We aimed to revise the intestinal scoring system to more accurately describe the diversity of NEC lesions in the preterm piglet model. We included 333 preterm piglets from four experiments, each delivered via cesarean section. The piglets were fed either a gently processed (GP) or harshly processed (HP) milk formula for 96 h before euthanasia. At necropsy, the gastrointestinal tract was assessed with 1) an established 6-grade score and 2) a descriptive approach focusing on the distribution and severity of hyperemia, hemorrhage, pneumatosis intestinalis (intramural gas), and necrosis. Subsequently, the descriptive registrations were converted into a weighted and cumulative point (WCP) score. Compared to the 6-grade score, the WCP score enabled a greater segregation of severity levels, especially among organs with more prominent NEC lesions. IL-1β in small intestinal lesions and both IL-8 and IL-1β in colon lesions correlated positively with the WCP scale. A histopathological grade system (0–8) was established and revealed mucosal pathology in lesion biopsies, which were not recognized macroscopically. Finally, the WCP score showed a higher NEC-promoting effect of the HP formula compared to the GP formula. The descriptive registrations and extended score range of this revised intestinal scoring system enhance the accuracy of describing NEC lesions in preterm pigs. This approach may increase the efficiency of preclinical NEC experiments.

Further Insights into The Pathogenic Mechanisms of Haemotropic Mycoplasma ovis.

In this study, we examined the effects of experimental intraperitoneal infection with haemotropic Mycoplasma ovis (0.5 mL of blood containing 80% parasitaemia) on selected serum biomarkers and cellular pathology in mice. After infection, M. ovis cells appeared in the blood films within one week. A dose-dependent peak of parasitemia was observed during the 3rd-week post-infection (pi), with a significant decrease in mean PCV between treatment versus control group at week 3 (t 14 = -3.693, P < 0.02), week 5 (t 14 = -2.096, P = 0.055), and week 7 (t 14 = -4.329, P = 0.001). There was a significantly (t 8 = -2.330, P = 0.048) lower serum oestrogen in treatment (10.38 ± 5.07) than control (17.43 ± 4.48), while serum progesterone was significantly (t 8 = 5.415, P = 0.001) increased in treatment (27.37 ± 2.17) than control (15.92 ± 4.20). Serum haptoglobin was significantly (t 8 = 8.525, P < 0.01) lower in treatment (8.72 ± 1.49) than control (18.16 ± 1.98) while the SAA was significantly (t 8 = 3.362, P = 0.01) higher in treatment (16.79 ± 2.71) than control (11.59 ± 2.15). Prominent lesions observed in the ovary include degeneration, necrosis, vacuolation, and hypertrophy of the lutein cells in corpora lutea. In the lymph nodes, diffused cellular hyperplasia of the lymphoid tissue in the cortex. In the liver, degeneration and necrosis accompanied by leucocytic cellular infiltration and Kupffer cell proliferation within the sinusoids. There were diffused leucocytic infiltrations and proliferative lesions in the glomerulus of the kidneys. The disturbance in progesterone and ovarian pathology highlights the potential role of haemotropic M. ovis in reproductive disorders. The observed changes in biomarkers and cellular reactions following M. ovis infection in the mouse may be further advanced in sheep and goats.

18 F FDG PET/CT versus 99m Tc MDP Bone scintigraphy in imaging of metastatic osseous disease in breast cancer patients; Solving the discrepancies in light of serum markers.

To assess the performance of 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) versus 99m Tc MDP bone scan in assessment of metastatic osseous disease in breast cancer patients in relation to serum markers. We reviewed PET/CT studies and bone scans for 37 patients (mean age of 55.38 ± 13.08 years) with metastatic breast cancer to bone. To assess metastatic osseous burden, we used semiquantitative scores derived from PET/CT (PMS) and bone scans (BMS). We used McNemar test to compare lesion detection between both modalities and receiver operator characteristic analysis to define the cutoff value of serum CA 15-3 that best predicts additional value for PET/CT over bone scan. In 13 patients (35.1%), more lesions or higher-intensity lesions were detected on PET/CT, while only 4 patients (10.8%) had more prominent lesions on bone scans ( P = 0.049). Additional lesions seen on PET/CT are predominantly osteolytic or medullary (early phase). Most lesions with higher uptake on bone scans appear sclerotic (late phase). CA 15-3 was positively correlated to PMS ( r = 0.386; P = 0.018) but not to BMS ( r = -0.027; P = 0.874). However, serum alkaline phosphatase was positively correlated to both PMS ( r = 0.389; P = 0.017) and BMS ( r = 0.363; P = 0.027). CA 15-3 value of >47 U/ml best predicted additional findings on PET/CT compared to bone scans (area under the curve = 0.708; P = 0.0261). FDG PET/CT detects metastatic osseous lesions during an earlier phase. A higher CA 15-3 predicts a higher metastatic burden on PET/CT but not on bone scan. Bone scans are less specific, likely by missing early lesions and detecting persistent uptake in healing sclerotic lesions.

Lead toxicity in African catfish: Promising role of magnetite nanogel against etho-neurological alterations, antioxidant suppression, gene toxicity, and histopathological/ immunohistochemical disruptions

Recently, toxicity with heavy metals has been a major health issue because of its detrimental impact on fish and fish consumers. Different from previous studies, here we are the first trial to assess the impending effect of the watery solution of magnetite (Fe3O4) nano gel (MG) against toxicity of lead (Pb) in African catfish (Clarias gariepinus). The evaluation included recording ethology, brain function, antioxidant traits, gene expression plus histopathological/and immunohistochemical assessment and residues in the brain tissues. Fish (n = 160; Bwt: 100.00 ± 7.39 g) were randomly allotted into four groups (40/group; 10 fish per replicate; four replicates/group). The first group (control) was not exposed to MG or lead chloride (PbCl2 as a source of Pb). The second (MG) group was exposed to 1.2 mg/L of MG. The third group (Pb) was subjected to PbCl2 (69.30 mg/L) toxicity. Meanwhile, the fourth group (MG + Pb) was subjected to PbCl2 toxicity (69.30 mg/L) and at the same time, treated with 1.2 mg/L of MG. The trial lasted for 45 days. The exposure to Pb resulted in notable ethological alterations (unusual swimming, surfacing, loss of equilibrium, laterality, and spiral movement). A clear decline in serum antioxidant parameters (catalase, reduced glutathione content, and total antioxidant capacity) and brain neurotransmitter (acetylcholine esterase) was observed in the Pb-exposed fish. An up-regulation of the myeloid differentiation factor 88 (MyD88), heat shock protein 70 (HSP70), and toll-like receptor (TLR-1 and TLR-5) genes of the brain plus higher residual Pb deposition in brain tissues were induced by Pb exposure. Additionally, prominent histopathological lesions including neuronal degeneration and vacuolation as well as a strong caspase-3 and a weak B-cell lymphoma 2 (bcl-2) immune expression were obvious in the brain. Remarkably, the addition of MG in water induced an improvement in these biomarkers and retrieved the histopathological changes. Considering these outcomes, MG is a promising candidate and an innovative approach as antitoxic against the toxicity of Pb for sustaining the performance and health of African catfish.

Clinical descriptive and long-term outcome of melanocytic uveal lesions in young dogs: 40 cases (45 eyes) including 13 cases of sector iridectomy.

To describe the clinical features surgical technique, early and long-term outcome with or without surgery, and histopathological findings of melanocytic anterior uveal lesions in young dogs. Medical records of dogs at a guide dog facility removed from training due to a pigmented iris lesion were reviewed from 2014 to 2021. Selected dogs had surgical iridectomies performed. Iridal melanocytic lesions were characterized as well-delineated, pigmented, and flat (nevus) or raised (mass) lesions of the iris. Forty dogs (18 Labrador retrievers, 18 German shepherd dogs, 1 Golden retriever, 3 Labrador/Golden mixes) ranging from 0.5 to 3.1 years of age were affected unilaterally (n = 35) or bilaterally (n = 5). Sector iridectomy was performed in 13 dogs with prominent and well-isolated mass lesion and enucleation was carried out in 2 dogs with extensive lesions, while all other cases were monitored without surgical intervention. Postoperative complications included dyscoria (13/13), focal posterior synechia (9/13) and focal nonprogressive cataract (8/13). All eyes remained visual and comfortable up to 6.2 years post-iridectomy with no clinically identifiable local recurrence. Histopathology was consistent with uveal melanocytoma in all samples obtained surgically. All cases that did not undergo surgery remained free of complications up to 4.5 year post diagnosis. Melanocytic anterior uveal lesions may be overrepresented in certain lineages of breeds and be present at a young age. While none of the eyes developed complications when monitored without surgery, early surgical excision of the mass by sector iridectomy yields noteworthy functional outcome and retention of a comfortable globe.

Successful Treatment of Refractory Discoid Lupus Erythematosus with Deucravacitinib

Discoid lupus erythematosus (DLE) is the most common subtype of chronic cutaneous lupus erythematosus (CLE) that may present with or without systemic lupus erythematosus (SLE). Treatment for DLE remains limited, as there are no medications specifically approved to treat DLE. Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, is currently being studied for adults with moderate-to-severe discoid and/or subacute CLE. We report a case of successful treatment of refractory DLE with deucravacitinib. A 65-year-old female with a longstanding history of systemic lupus erythematosus presented with prominent discoid lesions involving the nose, cheeks, and mid upper cutaneous lip. Having tried topical medications, multiple courses of systemic steroids were attempted, but the patient flared shortly after the tapers. Despite the patient experiencing some improvement on mycophenolate mofetil and prednisone, the decision to switch to deucravacitinib was made due to the patient developing multiple infections while on the former regimen. Three months after starting deucravacitinib, the patient returned with their skin completely clear. A better understanding of the molecular pathogenesis of CLE is informing the development of more targeted therapeutic strategies. TYK2 and Janus Kinases (JAKs) both mediate the signaling of cytokines, some of which play a role in the pathogenesis of SLE. Deucravacitinib binds to TYK2 at the regulatory domain, which is unique to its respective kinase unlike conventional Janus Kinase (JAK) inhibitors that bind to the active domain conserved across all JAKs. Deucravacitinib offers more targeted inhibition with a potentially improved safety profile compared to conventional JAK inhibitors.

Imaging and clinical characteristics of incidental abnormal thyroid uptake on PSMA PET/CT.

e18077 Background: To investigate the incidence, features, and clinical characteristics of unexpected prostate-specific membrane antigen (PSMA) uptake within the thyroid gland of patients with prostate cancer (PCa) who underwent F-18 DCFPyL PSMA PET/CT. Methods: We retrospectively reviewed a cohort of 1148 PCa patients who underwent PSMA PET/CT at our institution between 11/2021 - 09/2023. Scans with abnormal thyroid uptake were identified. Clinical data included patient demographics, PCa history, Gleason score, prostate specific antigen (PSA), ultrasonography (US), fine needle aspirate (FNA) / thyroidectomy, histopathology, and history of neck radiation or prior malignancy. Each scan was further analyzed with lesion-specific iso-contour method (42% cutoff) to obtain PET parameters (most prominent nodule SUVmax, SUVmean, PSMA volume, tumor lesion PSMA, contralateral gland SUVmax, SUVmax-nodule / SUVmax-contralateral gland ratio, most prominent PCa lesion SUVmax), PCa tumor distribution, and tumor volume. CT-related variables (nodule number, dominant nodule size, short/long axis ratio, CT-HU, integral total value) were also collected. Pearson's chi-square testing and Kruskal-Wallis testing was performed for categorical and nonparametric data respectively. Receiver operating characteristic (ROC) curves with area under curve (AUC) value were determined using IBM SPSS (version 29.0). Results: Of the 1148 PSMA PET/CTs, 60 (5.2%) had abnormal thyroid uptake (nodular: 58, diffuse: 2). Diffuse uptake was found to represent thyroiditis in both patients. 43 (56.7%) had an US, 20 (33%) were biopsied (11 benign, 5 indeterminate, 4 malignant), and 5 (8.3%) pursued thyroidectomy (3 malignant, 2 benign). 22 patients (36.7%) had histopathology data and 5 malignancies (2 PCa, 1 CLL, 2 primary thyroid) were identified. Nodule size was larger in those who had an US relative to those who did not. Among those with US data, no significant differences in clinical or histopathological parameters were seen. SUVmax (p: 0.01; AUC: 0.876, 95%CI: 0.731-1.0) and SUVmean (p:0.01; AUC: 0.871, 95%CI: 0.722-1.0) were higher in the malignant group. Nodule SUVmax/contralateral gland SUVmax ratio showed borderline significance (p = 0.05). Conclusions: Incidental PSMA PET uptake in the thyroid gland is seen in approximately 5% of patients. Focal uptake should prompt consideration of US and FNA due to the possibility of prostate cancer metastasis and thyroid cancer. SUVmax/mean is higher in malignant lesions.

Identification of Elsinoë phaseoli causing bean scab in Kenya and evaluation of sporulation using five adapted techniques

AbstractThis research addresses the presence of Elsinoë phaseoli in Kenya, where information on the biology of this pathogen remains scarce. Employing a multifaceted approach, the study demonstrates the steps taken to isolate, identify, and characterize E. phaseoli as the pathogen responsible for scab on common bean. Field observations confirmed scab symptoms, particularly the prominent pod lesions. Elsinoë phaseoli was isolated from common bean using a targeted streaking method on older acervulus‐bearing lesions. Morphological examinations revealed a notable diversity within E. phaseoli colonies, consistent with the characteristics of the genus. Molecular identification through ITS‐rDNA sequencing confirmed isolate AscoSK1 obtained in this study as belonging to E. phaseoli, offering a robust species differentiation method. Assessing conidium production required the implementation of five different culture methods. An adaptation of the Scheper et al. (2013) method yielded the highest quantity of conidia from 25 colonies spaced at 1 cm apart, with a conidial yield of 5.0 × 106 conidia per 9‐cm‐diameter Petri dish. A higher conidial yield was attained after the colonies were pre‐incubated on potato dextrose agar in the dark at room temperature for 28 days, followed by a transfer to corn meal agar for an additional 2 days at 20°C. This emphasizes the pivotal influence of incubation duration and pre‐culture conditions on the process. This research provides insights into the biology of E. phaseoli and introduces an improved method for enhancing in vitro sporulation of the pathogen, setting groundwork for future research and handling.

Analysis of Response and Progression Patterns of Tyrosine Kinase Inhibitors in Recurrent or Metastatic Adenoid Cystic Carcinoma: A Post Hoc Analysis of Two KCSG Phase II Trials.

In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed. In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor. Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Homonymous hemianopia due to cerebral venous thrombosis: A case report

Rationale: Diagnosing cerebral venous thrombosis (CVT) can be difficult because of nonspecific symptoms, such as headache and homonymous hemianopia (HH). Herein, we present a case of delayed CVT diagnosis due to nonspecific neurological symptoms and nonprominent lesions in a patient with HH. Patient concern: A 65-year-old woman presented with a sudden onset headache accompanied by right HH that lasted for 1 day. Brain computed tomography and magnetic resonance imaging were initially performed due to suspicion of ischemic lesions or hemorrhage in the left postchiasmal visual pathway; however, no remarkable acute brain lesions were detected. Ophthalmological examinations revealed no notable findings, except for a definite field defect in the Humphrey visual field test. The headaches then waxed and waned but recurred 3 days after the initial symptom. A repeat brain magnetic resonance imaging was performed, which revealed left sectoral gyral swelling and vascular enhancement in the occipital lobe. To further evaluate venous drainage, additional 3-dimensional cerebral computed tomography angiography and 4-vessel angiography were conducted, revealing a partial filling defect in the left transverse sinus and superior venous drainage impairment. These findings suggested the presence of venous thrombosis in the left transverse sinus. Diagnosis: The patient was diagnosed with thrombosis of the left transverse sinus, which subsequently caused the right HH. Intervention: Anticoagulation therapy with parenteral heparin was started as soon as the diagnosis of CVT was confirmed. Eventually, the patient was solely managed with oral warfarin administration. Outcomes: Following 3 days of treatment, her headache resolved, and a subsequent visual field testing conducted 2 weeks later revealed a definite improvement in the field defect. Lessons: Despite its favorable prognosis, CVT can be challenging to diagnose. CVT should be considered as a differential diagnosis when diagnosing patients who present with headaches accompanied by HH without prominent brain lesions.

Displasia mesenquimal placentaria

Placental mesenchymal dysplasia is a rare entity, confused with ultrasound and macroscopy with partial mole due to vesicular lesions and the presence of a fetus. Microscopy reveals hydropic trunk villi with great mesenchymal hyperplasia and prominent vascular lesions but without hyperplasia of the trophoblastic epithelium. The fetus, usually female, may be normal or present malformations, tumors or chromosomopathies. We present the study of four cases of placental mesenchymal dysplasia; three first-pregnancies, aged 39 and 20, and a second-pregnancy, aged 26. The oldest in the third trimester presented with preeclampsia and a female stillbirth with pulmonary and splenic anomalies, the other two presented vaginal bleeding and pelvic pain and one case was a finding in prenatal control at 8 weeks of gestation. In three cases, fetus and embryo were observed, two of them had a necropsy.

AMPK Controls Glycolytic Compensation in Gvhd-Causing T Cells

Background: The heightened metabolic requirements of alloreactive T cells following allogeneic stem cell transplantation represents a promising area for therapeutic intervention. We have shown that during the initiation of acute graft-versus-host-disease (aGVHD), murine T cells upregulate activity of AMP-activated protein kinase (AMPK), a cellular energy sensor that regulates oxidative and mitochondrial metabolism. Further, transfer of allogeneic T cells deficient in AMPK (AMPK KO) increased recipient survival and decreased disease severity while still preserving leukemia clearance. In the current studies, we demonstrate a novel role for AMPK in controlling glycolytic compensation, both in vitro and vivo, and provide a mechanism as to why cells lacking AMPK are unable to perform this vital function. Together, these data highlight the potential clinical utility in targeting metabolic decision-making to curtail T cell-mediated inflammatory responses, with significant therapeutic implications for the prevention and treatment of aGVHD. Methods: AMPK-deficient murine T cells from AMPKa1/a2 dKO C57BL/6J mice were transplanted into allogeneic B6D2F1 recipients and recovered on day 7 post-transplant. To delete AMPK in primary human T cells, T cells were isolated from healthy donors and electroporated with Cas 9 ribonucleoprotein complexes targeting the AMPKa1 locus. Glycolytic compensation was assessed by measuring extracellular acidification rates (ECAR) using the Agilent Seahorse analyzer and a mitochondrial stress kit. Intracellular cytokine expression for IFNgamma was assessed in day 7 murine T cells following re-stimulation with F1 splenocytes in the presence of Brefeldin A. Aldolase A and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) enzymatic assays were run on cell lysates with Biovision-Abcam kits according to manufacturer instructions. To measure GAPDH activity, T cells were positively selected for CD45.1 from day 7 recipient spleens, followed by cell lysis and detection of enzymatic activity. Results: AMPK KO murine T cells recovered on day 7 were unable to mediate a compensatory increase in glycolysis following inhibition of the electron transport chain (Figure 1A), (-6.499±5.156 vs 29.11±7.064, p&amp;lt;0.0001). Human T cells lacking AMPK gave similar results, with glycolytic compensation impaired both in vitro and following human T cell expansion in vivo in a xenogeneic model of GVHD. Immunoprecipitation of proteins from day 7 murine T cells, using an antibody specific to phosphorylated AMPK targets, recovered lower levels of multiple glycolytic enzymes including aldolase, enolase, pyruvate kinase M, and GAPDH (Figure 1B). Functionally, murine T cells lacking AMPK exhibited impaired aldolase activity following anti-CD3/CD28 stimulation and a decrease in GAPDH activity on day 7 post-transplant. Importantly, these changes in glycolysis correlated with an impaired ability of AMPK KO T cells to produce significant amounts of IFNγ upon antigenic re-stimulation with F1 splenocytes. Discussion: Our results demonstrate that in addition to influencing oxidative metabolism, AMPK also plays a role in glycolytic metabolism during GVHD in both murine and human T cells. Further, our data suggest that the more prominent lesion in human T cells post-transplant was in glycolysis , a result supported by the novel observation that a set of glycolysis-related proteins are immunoprecipitated together at much lower rates in the absence of AMPK. These findings suggest a model in which AMPK phosphorylation provides a nidus for important interactions among glycolytic enzymes and that in the absence of AMPK, these interactions are lessened, and glycolysis is consequently reduced. Important to our understanding of GVHD pathogenesis, rates of T cell glycolysis can be directly linked to IFNγ production, where reduced glycolytic activity frees GAPDH to sequester IFNγ transcripts and thereby limit IFNγ protein translation. Altogether, these results document a prominent role for AMPK in controlling T cell glycolytic activity during GVHD development and offer an additional mechanistic explanation for the decreased severity of GVHD seen following transplantation of AMPK KO T cells. Consistently similar results in human xenogeneic T cells provides a further strong rationale for development of AMPK inhibition as a clinically translatable strategy for GVHD prevention and treatment.

Evaluation of the Histopathological Changes Accompanied for the Toxic Effects of Diazinon on the Spleen of Mice

This study was carried out to determine the histopathological changes caused by diazinon in the spleen of Swiss albino mice. Experimental groups containing low dose (30 mg/kg), medium dose (60 mg/kg) and high dose (120 mg/kg) were exposed to diazinon through oral administration for 30 consecutive days. Separation and hemorrhage in the capsule, congestion, enlarged white pulp, amyloid formation, and karyolysis in some megakaryocytes were determined in the splenic parenchyma of the low dose group. An increase in the number of enlarged white pulps, hemorrhage within splenic parenchyma, accumulation of cells into dilated sinusoids and amyloid formation were examined in the medium dose group. Some cells passing from the splenic parenchyma into dilated sinusoids were also observed. Intensive congestion, necrotic areas within spleen tissue, an increase in the number of karyolytic megakaryocytes, fibrosis and some cells passing from the splenic parenchyma into enlarged sinusoids were prominent histological lesions in the high dose group. These results showed that diazinon caused severe dose-related histopathological damages and had the capacity to disrupt functions of the spleen.

Assessment of hematological indicators, histological alterations, and DNA damage in Danube sturgeon (Acipenser gueldenstaedtii) exposed to the organophosphate malathion

This study focused on organophosphate malathion toxicity in Danube sturgeon (Acipenser gueldenstaedtii) and its negative effects in sub-lethal concentration. In this context, the LC50 value of fish exposed to five different concentrations and two different sub-lethal concentrations depending on the LC50 value were considered. Accordingly, LC50 of malathion for 96 h was 3.24 mg L-1. In leukocyte (WBC) and hemoglobin (HGB) such as hematological indicators, significant differences were observed in sub-lethal concentration (One-eighth of the LC50 =0.4 mg L-1). In addition, serious histological alterations were observed in the gill and liver tissues after both acute (96 h) and chronic periods (28 days). While epithelial lifting and hyperplasia were the most prominent lesions in the gill, intense vacuolization were observed in the liver. In addition, circulatory disturbances, regressive changes, and progressive changes in the gill and circulatory disturbances and inflammation in the liver were significantly higher for the chronic period. Finally, significantly higher DNA damage was detected in fish exposed malathion in the chronic period compared to the control group. In conclusion, the present study has proven that malathion has a hematological, histological and genotoxic effect on the endangered species A. gueldenstaedtii. Thus, the current study will motivate for residue studies on A. gueldenstaedtii and trigger conservation strategies for local governments.

A prominent lesion overshadowing the real airway problem in an infant.

A prominent lesion overshadowing the real airway problem in an infant.

Kerion celsi: Clinical Features, Diagnosis and Therapeutic Approaches

Querion de Celso, also known as Celso abscess, is a rare and severe inflammatory condition that arises as a complication of folliculitis. It is characterized by the formation of a purulent and fluctuant abscess in the pilosebaceous region. This dermatological disorder is primarily associated with the invasion of pathogenic bacteria, most commonly Staphylococcus aureus, into the hair follicles and sebaceous glands. Clinically, kerion de Celso presents as a prominent, erythematous, warm, and fluctuant lesion, often accompanied by local pain, restricted movement, and potential systemic symptoms such as fever and malaise. The diagnosis of kerion de Celso relies on a comprehensive evaluation, including clinical assessment, histopathological findings, and microbiological analysis. These diagnostic modalities support the presence of an intense inflammatory response and aid in identifying the causative agent. Treatment of kerion de Celso necessitates a multidisciplinary approach. Systemic antibiotics are essential to eliminate the underlying bacterial infection, while analgesics and anti-inflammatory agents provide symptomatic relief. Surgical incision and drainage may be required in cases of extensive abscess formation. In more complex situations, immunosuppressive therapy may be considered to modulate the exaggerated inflammatory response. Adequate wound care and close follow-up are crucial to ensure successful resolution and prevent long-term complications. In summary, Celso's kerion is a rare but potentially severe condition that requires prompt recognition and appropriate management to minimize complications and promote healing. Understanding the clinical, etiological, and therapeutic aspects of this condition is essential for healthcare professionals to deliver optimal care and improve clinical outcomes.

Kerion of Celso: Clinical Features, Diagnosis and Therapeutic Approaches

Querion de Celso, also known as Celso abscess, is a rare and severe inflammatory condition that arises as a complication of folliculitis. It is characterized by the formation of a purulent and fluctuant abscess in the pilosebaceous region. This dermatological disorder is primarily associated with the invasion of pathogenic bacteria, most commonly Staphylococcus aureus, into the hair follicles and sebaceous glands. Clinically, kerion de Celso presents as a prominent, erythematous, warm, and fluctuant lesion, often accompanied by local pain, restricted movement, and potential systemic symptoms such as fever and malaise. The diagnosis of kerion de Celso relies on a comprehensive evaluation, including clinical assessment, histopathological findings, and microbiological analysis. These diagnostic modalities support the presence of an intense inflammatory response and aid in identifying the causative agent. Treatment of kerion de Celso necessitates a multidisciplinary approach. Systemic antibiotics are essential to eliminate the underlying bacterial infection, while analgesics and anti-inflammatory agents provide symptomatic relief. Surgical incision and drainage may be required in cases of extensive abscess formation. In more complex situations, immunosuppressive therapy may be considered to modulate the exaggerated inflammatory response. Adequate wound care and close follow-up are crucial to ensure successful resolution and prevent long-term complications. In summary, Celso's kerion is a rare but potentially severe condition that requires prompt recognition and appropriate management to minimize complications and promote healing. Understanding the clinical, etiological, and therapeutic aspects of this condition is essential for healthcare professionals to deliver optimal care and improve clinical outcomes.