TOXOCARIASIS IN PUPPY - MORPHOLOGICAL DESCRIPTION AND CLINICAL MANAGEMENT

A 34-day-old, male Bully pup was presented in veterinary clinics with an uncertain anamnestic history of anorexia, lethargy, abdominal pain, and discomfort. On clinical examination, the pup had pale conjunctiva with a pot-bellied appearance and expelled cream-colored roundworms in feces. Blood and fecal samples were collected and analyzed. Hemoglobin and PCV values were lower, depicting anemia. A qualitative and quantitative examination of the fecal sample was carried out and results showed infection with Toxocara canis with fecal egg count (FEC) of 3200/gram of feces. Gross and light microscopic examination revealed the presence of adults of Toxocara canis with distinctive morphological features. Apropos, the pup was treated with a combination of pyrantel pamoate and fenbendazole orally @10mg/kg body weight, repeated after 14 days. The pup recovered successfully, as evidenced by decreased FECs, increased weight gain, and a high hematocrit score

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Oral myiasis in brain hemorrhage

Myiasis is a rare condition which arises from the invasion of body tissues or cavities of living animals or humans by maggots or larvae of certain species of flies. Oral myiasis is seen especially in individuals with neurologic deficit, secondary to oral wounds, suppurative lesions, and extraction wounds. The halitosis and neglected oral hygiene attracts flies to lay eggs in oral wounds which results in oral myiasis. We present a case of oral myiasis in a 63-year-old female patient who was medically compromised since 6 months

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part 10: Identification of inhibitors for the liver microsomal acetoxycoumarin: protein transacetylase

The quantitative structure-activity relationship (QSAR) studies conducted by us earlier revealed the cardinal role of the pyran ring carbonyl group in the acetoxy polyphenolic compounds for the acetoxy polyphenol: protein transacetylase (TAase) activity. Hence, an attempt was made to examine whether such substrate analogues of benzopyran acetates which lack in the pyran ring carbonyl group, such as 7-acetoxy-2,3-dihydro-2,2-dimethylbenzopyran (BPA), cetachin pentaacetate (CPA) and hematoxylin pentaacetate (HPA) could inhibit the 7,8-diacetoxy-4-methylcoumarin (DAMC):protein (glutathione-S-transferase) transacetylase activity. These compounds were indeed found to remarkably inhibit the TAase activity in a concentration dependent manner and exerted their inhibitory action very rapidly. Further BPA, CPA and HPA were found to abolish the TAase mediated activation of NADPH cytochrome C reductase as well as the inhibition of liver microsome catalyzed aflatoxin B, (AFB(1))-DNA binding by DAMC very effectively. These results strongly suggest that the acetoxybenzopyrans merit as potent inhibitors of TAase. (C) 2002 Elsevier Science Ltd. All rights reserved

Abstract 3476: Mechanistic evaluation of VS-6766 (dual RAF/MEK inhibitor) and defactinib (FAK inhibitor) in low-grade serous ovarian cancer models with correlations to clinical response

Background: Low-grade serous ovarian cancer (LGSOC) constitutes up to 10% of all ovarian cancer and has clinical and molecular characteristics (resistance to chemotherapy, presence of RAS/RAF mutations, lack of TP53 mutations) distinct from high-grade serous ovarian cancer. Here, we characterized the effects of the dual RAF/MEK inhibitor VS-6766 and the FAK inhibitor defactinib on signal transduction and viability in LGSOC cell lines and patient-derived organoids. To correlate molecular characteristics with clinical response, we characterized genomic alterations in archival tumor samples from patients with LGSOC treated with the combination of VS-6766 and defactinib on a clinical trial (FRAME).Material and Methods: We exposed 5 LGSOC cell lines to clinical Cmax concentrations adjusted for protein binding of VS-6766 and defactinib. We quantified phospho- and total proteins (n=66) with an antibody-bead based assay normalized to GAPDH. We also studied growth inhibitory effects of the combination on KRAS mutant (mt) LGSOC patient-derived organoids. We performed next generation sequencing on archival samples from LGSOC patients treated with VS-6766 in combination with defactinib.Results: Signal transduction changes at 1 hr included reduction of p-FAK in 5/5 cell lines in response to defactinib. Cells exposed to VS-6766 showed a reduction in p-ERK and p-p90-RSK in 4/5 cell lines. Additionally, VS-6766 decreased p-cJUN and increased p-IκB in 4/5 cell lines, changes correlated with apoptosis. At 24 hrs, p-ERK and p-p90-RSK inhibition were maintained in 3/5 cell lines. Both drugs increased cleaved PARP in 4/5 cell lines and VS-6766 increased p-SMAD3 and BIM levels, indicating an increase in cell death/apoptosis. The combination of VS-6766 + defactinib showed synergistic growth inhibition in a KRAS mt LGSOC organoid model (combination index 0.51). The clinical combination of VS-6766 and defactinib (September 2021 cut-off) has shown an objective response rate (ORR) of 11/24 (46%) across all patients with LGSOC, and an ORR of 64% (7/11) for patients with KRAS mt LGSOC (n=11). In addition to mutations in KRAS, emerging data may suggest a correlation of U2AF1 and MED12 mutations with response.Conclusions: VS-6766, the dual RAF/MEK inhibitor, induces significant inhibition of ERK pathway signaling in addition to perturbations in TNF/NFκB signaling. Both defactinib and VS-6766 induce apoptosis in LGSOC models. The results provide mechanistic insights into the encouraging response rates observed in patients with LGSOC treated with VS-6766 and defactinib (NCT03875820). These data support the ongoing randomized phase II ENGOTov60/GOG3052/RAMP201 study (NCT04625270).Citation Format: Adam R. Stewart, Lisa Pickard, Ekta Paranjape, Victoria Sanchez Perez, Sanjib Chowdhury, Stephanie Lustgarten, Silvia Coma, Jonathan A. Pachter, Mark S. Carey, Gabriel DiMattia, Hannah C. Badham, Toby Prout, Mona Parmar, Muneeb Mahmud, Christina Yap, Matthew G. Krebs, Susana Banerjee, Udai Banerji. Mechanistic evaluation of VS-6766 (dual RAF/MEK inhibitor) and defactinib (FAK inhibitor) in low-grade serous ovarian cancer models with correlations to clinical response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3476

The competence of 7,8-diacetoxy-4-methylcoumarin and other polyphenolic acetates in mitigating the oxidative stress and their role in angiogenesis

The potential role of polyphenolic acetate (PA) in causing diverse biological and pharmacological actions has been well studied in our laboratory. Our investigations, for the first time, established the role of calreticulin transacetylase (CRTAase) in catalyzing the acetylation of nitric oxide synthase (NOS) by Pas leading to robust activation of NOS. 7, 8-Diacetoxy-4-methylcoumarin (DAMC) and other acetoxycoumarins augmented the expression of thioredoxin (TRX) and vascular endothelial growth factor (VEGF) in human peripheral blood mononuclear cells (PBMCs). These findings substantiated our earlier observations that DAMC was a superb inducer of angiogenesis. The enhanced expression of thioredoxin reductase (TRXR) and diminished expression of thioredoxin interacting protein (TRXIP) leading to increased expression and activity of TRX in PBMCs due to the action of DAMC was revealed by real time RT-PCR analysis. The possible activation of TRX due to acetylation was confirmed by the fact that TRX activity of PBMCs was enhanced by variousacetoxycoumarins in tune with their affinities to CRTAase as substrates. DAMC caused enhanced production of NO by way of acetylation of NOS as mentioned above and thereby acted as an inducer of VEGF. Real time RT-PCR and VEGF ELISA results also revealed the overexpression of TRX. DAMC and other PAs were found to reduce the oxidative stress in cells as proved by significant reduction of intracellular ROS levels. Thus, the crucial role of TRX in DAMC-induced angiogenesis with the involvement of VEGF was established