Exsanguinated to death by a perforated duodenal ulcer: Masquerader apprehended on autopsy.

ABSTRACT: Gastroduodenal perforation commonly due to spontaneous perforation of a pre-existing peptic ulcer is a surgical emergency. On laparotomy, approximately 60%-70% perforations are duodenal and 15%-20% gastric. The most prevalent etiology are Helicobacter pylori infection in 65%-70% and non-steroidal anti-inflammatory drugs (NSAIDS) abuse in 30%-50% cases depending on the prevalence of H. pylori infection. We report here the autopsy findings in a 29-year-old male who collapsed suddenly in the emergency room of our hospital after a bout of massive hematemesis.

Brolucizumab in age-related macular neovascularization (BRAIN study): Efficacy, optical coherence tomography biomarkers, and safety profile.

BACKGROUND: Brolucizumab is a new anti-vascular endothelial growth factor (anti-VEGF) in the treatment of neovascular age-related macular degeneration (nAMD) and idiopathic polypoidal choroidal vasculopathy (IPCV). MATERIALS AND METHODS: A retrospective, consecutive, interventional study was conducted from a tertiary eye hospital, in which treatment-naïve and treatment-switch patients were included. They underwent an intravitreal injection of brolucizumab. The decision to reinject was made based on the presence of fluid on spectral domain optical coherence tomography (SD-OCT) or worsening of vision at follow-up. Outcome measures were changes in best-corrected visual acuity (BCVA), central subfield thickness (CST), fluid (subretinal/intraretinal/sub-retinal pigment epithelium fluid) levels, and OCT biomarkers and safety analysis. RESULTS: A total of 59 eyes of 50 patients with a total of 132 intravitreal injections were included. There was a statistically significant improvement (P < 0.05) in BCVA from baseline in logMAR treatment-naïve patients (mean BCVA at baseline 0.6 ± 0.41 and 0.37 ± 0.56). The mean baseline CST of all patients significantly reduced from 582.92 ± 233.11 µm at baseline to 474.06 ± 252.89 µm at the final treatment visit. Thirty-eight percent of patients showed complete resolution of SHRM after a single injection. The interval between each subsequent injection increased from a mean of 67 to 96 days in treatment-switch patients and from 47 to 151 days in treatment-naïve patients. CONCLUSION: Brolucizumab promises reduced number of injections with longer treatment intervals.

Successful Implementation of Image-Guided Pencil-Beam Scanning Proton Therapy in Medulloblastomas.

Medulloblastoma is the most common malignant brain tumour in children, while much rarer in adults. Although the prognosis and outcomes have greatly improved in the era of modern multidisciplinary management, long-term treatment-induced toxicities are common. Craniospinal irradiation followed by a boost to the primary and metastatic tumour sites forms the backbone of treatment. Proton therapy has been endorsed over conventional photon-based radiotherapy due to its superior dosimetric advantages and subsequently lower incidence and severity of toxicities. We report here our experience from South-East Asia's first proton therapy centre of treating 40 patients with medulloblastoma (38 children and adolescents, 2 adults) who received image-guided, intensity-modulated proton therapy with pencil-beam scanning between 2019 and 2023, with a focus on dosimetry, acute toxicities, and early survival outcomes. All patients could complete the planned course of proton therapy, with mostly mild acute toxicities that were manageable on an outpatient basis. Haematological toxicity was not dose-limiting and did not prolong the overall treatment time. Preliminary data on early outcomes including overall survival and disease-free survival are encouraging, although a longer follow-up and data on long-term toxicities are needed.

Photocatalytic degradation of fluoroquinolone antibiotics using chitosan biopolymer functionalized copper oxide nanoparticles prepared by facile sonochemical method.

Photocatalytic degradation is an excellent method for removing pharmaceutical residues due to their simplicity, ecological benignity, high efficiency, and exceptional stability. Herein, we demonstrate the sonochemically synthesised chitosan biopolymer functionalized copper oxide nanoparticles as an efficient photocatalyst for the degradation of fluoroquinolone-based antibiotics. The X-ray diffraction Rietveld refinement revealed the formation of single-phase copper oxide (CuO) with a monoclinic structure. The presence of biopolymer functionalization was corroborated by Fourier Transform Infrared spectroscopy by observing the -NH2 and -OH functional groups. The high-resolution transmission electron microscopic images inferred that Chitosan functionalized copper oxide (C-CuO) particles are nano-sized with a smooth texture and aggregation-free particles. The strong absorbance and the broad photoluminescence emission in the ultraviolet-visible region confirm the suitability of CuO and C-CuO nanoparticles for photocatalytic applications. The catalytic activity was studied against fluoroquinolone-based antibiotics such as ciprofloxacin and norfloxacin under direct sunlight illumination. Interestingly, the C-CuO catalyst demonstrated 71.07 % (@140 min.) and 71.9 % (@60 min.) of degradation for ciprofloxacin and norfloxacin, respectively. The obtained photocatalytic activity of the prepared CuO and C-CuO catalysts was superior to the CuO particles prepared by the coprecipitation method (CC-CuO).

Hemophagocytic Lymphohistiocytosis in Erythema Nodosum Leprosum: Case Report of an Unusual Conundrum.

Hemophagocytic lymphohistiocytosis (HLH) and erythema nodosum leprosum (ENL) result from a complex agent-host interaction and form a continuum of the same spectrum. A 30-year-old multi-gravida presented at 36 weeks gestation with fever and erythematous raised lesions over the face and upper and lower limbs after defaulting treatment for borderline lepromatous leprosy. Skin biopsy confirmed ENL, hence multi-drug therapy (MDT) and oral steroids were restarted. However, her condition worsened and she developed icterus, periorbital puffiness, pleural effusion, ascites and splenomegaly. Laboratory investigations showed pancytopenia, conjugated hyperbilirubinemia, transaminitis, elevated lactate dehydrogenase, hypertriglyceridemia, hyperferritinemia and hypofibrinogenemia. Dapsone was stopped on the suspicion of dapsone hypersensitivity but hyperbilirubinemia progressed. Diagnosis of HLH was clinched after bone marrow aspirate showed florid hemophagocytosis and subsequently, intravenous immunoglobulin (2 g/kg) over 5 days and dexamethasone were administered. The patient improved gradually with normalization of laboratory parameters and restarted MDT. This case depicts a rare and potentially catastrophic complication of ENL and emphasizes a vigil for HLH syndrome in such cases.

Topical Gentamicin 0.1% Promotes Collagen 7 Expression in Recessive Dystrophic Epidermolysis Bullosa.

Background: Currently, there is no cure for epidermolysis bullosa (EB) but few studies have explored the role of aminoglycosides in promoting collagen 7 expression in recessive dystrophic EB (RDEB). Materials and Methods: Consecutive patients aged >1 year with a confirmed diagnosis of dystrophic EB (DEB) were advised to apply 0.1% w/w gentamicin cream in a collagen base (Derbriment G™) twice daily on a representative area on right lower limb (RLL) and paraffin gauze dressings on the corresponding opposite side on the left lower limb (LLL). Skin lesions were evaluated clinically during the 12-week treatment period at the end of which a repeat skin biopsy was sent for immunofluorescence antigen mapping (IFM). Results: Twelve patients with DEB were recruited but only eight completed the study and were analyzed. The mean fluorescence intensity (MFI) of the study cohort increased from 2765 ± 1732.07 (263-4845) at baseline to 5412.75 ± 3937.64 (2100-13536) at 12 weeks; a 95.75% (range 5.34%-775.14%) increase in the MFI of collagen 7 from baseline (P = 0.06). Among patients with a known termination codon mutation (n = 3), the percentage increase in MFI was greater among patients with known premature termination codon (PTC) mutations compared to those with unknown mutations. The clinical severity did not change significantly in terms of the mean number of blisters, erosions, and scarring during the study period. None of the parents reported any adverse effect. Conclusions: Topical gentamicin 0.1% w/w is a safe and effective way to promote the expression of COL7A1 in DEB patients, especially those carrying PTC mutations.

A Breakthrough in the Era of Calcium Silicate-Based Cements: A Critical Review.

Calcium silicate-based cements (CSCs) or mineral trioxide aggregate (MTA) lookalike materials are blocks of cement or root canal sealers produced from calcium (Ca) and silicate. They have superior sealing ability, bioactivity, and marginal adaptability, making them appropriate for various dental treatment applications. Mineral trioxide aggregate is widely used in numerous endodontic repair techniques. The capacity of this cement to promote tissue regeneration and stimulate mineralization accounts for its widespread usage in pulp capping, apexification, apical surgeries, and revascularization. Several studies have been conducted to investigate changes in the components of MTA-based types of cement directed to improve their presentation clinically. To improve flowability, new Ca silicate-based formulations have been introduced commercially. In these new formulations, essential features such as adequate radiopacity and setting time, color stability, alkaline pH, and calcium ion release and biocompatibility must be considered. Owing to an increased range of indications of CSCs, including some for restorative dentistry, and with the emergence of novel silicate calcium-based materials with considerable changes in their compositions, it is necessary to examine the available scientific literature that evaluates their usage in these applications. Therefore, this review paper aims to assess the existing knowledge of CSCs, emphasizing their potential uses in restorative and endodontic dentistry. This report strives to update doctors' understanding of CSCs, allowing for a better therapeutic approach.

Langerhans cell sarcoma with BRAF-V600E mutation and hemophagocytosis: An autopsy report.

Langerhans cell sarcoma (LCS) is a rare high-grade neoplasm of langerhans cell phenotype having unambiguous malignant cytological features. We report such a rare case in a 20-year-old man who presented with dyspnea and high-grade fever. On evaluation, he had generalized lymphadenopathy, hepatosplenomegaly, and a large anterior mediastinal mass. Fine needle aspiration from the mediastinal mass and bone marrow aspirate showed numerous atypical cells, many of which showed grooved nuclei. In addition, the bone marrow showed prominent hemophagocytosis. The patient had a stormy hospital stay and succumbed to the illness. The autopsy revealed a rare multisystem involvement by LCS involving the lymph nodes, liver, spleen, lungs, and intestine, which harbored a BRAFV600E mutation and was associated with hemophagocytosis.

Insilico structure based drug design approach to find potential hits in ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

Tetraacyldisaccharide 4'-kinase (LpxK) is the prime enzyme responsible for the biosynthesis of lipid A. LpxK is a key antibacterial drug target, but it is less exploitation in Pseudomonas aeruginosa and other bacterial species limits its therapeutic use. Pseudomonas aeruginosa is responsible for severe infections like pneumonia and urinary tract infections. The precautionary measures of Pseudomonas aeruginosa infections are decisive as it results in extensive drug resistance, systemic bacteremia, and ventilator-associated pneumonia. The current rational approach highlights exploiting the use of computer-aided drug design approaches to counter Pseudomonas aeruginosa specific LpxK. The various approaches used were exploring the metabolic pathway database (Metacyc), drug target validation using DEG, protein modeling, ligand docking, e-pharmacophore assisted virtual screening, physicochemical and Toxicity profile prediction studies, and molecular simulations in spotting out novel potential hits compounds. The virtual hits which have highly ranked in the study were STOCK4S-16119, STOCK1S -60869, STOCK6S -43621, STOCK6S -3328, and STOCKS-39892 which can act as a scaffold for the establishment of new hits against LpxK and can result in control of Pseudomonas aeruginosa infectivity.

Effect of storage on plant biostimulant and bioactive properties of freeze-dried Chlorella vulgaris biomass.

Microalgae are potential plant biostimulants and biocontrol agents. A major hurdle towards their commercialization is the production of large volumes of biomass at the correct time of year. Secondary metabolites are unstable and the "shelf-life" of bioactive microalgal biomass needs to be investigated. The aim of the study was to investigate the effects of storage conditions on freeze-dried microalgae to determine how long the biomass retained its growth promoting and bioactive properties under various temperature and light conditions. Chlorella vulgaris biomass was stored in the dark at - 70 °C, 10 °C, and 25 °C and in the light at 25 °C. Samples were tested every 3-4 months for 15 months. Storage time significantly influenced the rate of change in the bioactivity in the C. vulgaris biomass with storage temperature also having some effect. Rooting activity decreased in the mungbean rooting assay over time up to 12 months and then increased slightly. Antimicrobial activity increased against Staphylococcus aureus and Escherichia coli for up to 12 months and then declined. Antioxidant activity measured in the DPPH assay remained relatively stable for up to 12 months and then significantly decreased with longer storage. The change in bioactivity over time was attributed to the gradual breakdown of the rigid cell wall of C. vulgaris, thereby improving extraction efficiency but exposing the secondary metabolites to oxygen, thus quickening their degradation. Biomass produced for commercial purposes requires preliminary validation as the results of the present study showed that bioactive compounds are susceptible to degradation over time. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10811-021-02596-9.

Interactive effects of plant growth-promoting rhizobacteria and a seaweed extract on the growth and physiology of Allium cepa L. (onion).

Detrimental effects caused by the overuse of synthetic agrochemicals have led to the development of natural biostimulants such as seaweed extracts and plant growth-promoting rhizobacteria (PGPR) being used as an alternative, environmentally-friendly technology to improve crop growth and increase agricultural yields. The present study aimed to investigate the interactions between PGPR and a commercial seaweed extract on the growth and biochemical composition of onion (Allium cepa). A pot trial was conducted under greenhouse conditions where onion plants were treated individually with the two PGPR, namely Bacillus licheniformis (BL) and Pseudomonas fluorescens (PF) and a seaweed extract Kelpak® (KEL) and combinations of KEL + BL and KEL + PF. Growth and yield parameters were measured after 12 weeks. KEL-treated plants showed the best growth response and overcame the inhibitory effects of BL treatment. KEL-treated plants also had the highest chlorophyll content. PGPR application improved the mineral nutrition of onion with these plants having the highest mineral content in the leaves and bulb. All biostimulant treatments increased the endogenous cytokinin and auxin content with the highest concentrations generally detected in the PF-treated plants. These results suggest that co-application of different biostimulant classes with different modes of action could further increase crop productivity with an improvement in both growth and nutrition content being achieved in onion with the co-application of a seaweed extract and PGPR.

Insights of tankyrases: A novel target for drug discovery.

Tankyrases are the group of enzymes belonging to a class of Poly (ADP-ribose) polymerase (PARP) recently named ADP-ribosyltransferase (ARTD). The two isoforms of tankyrase i.e. tankyrase1 (TNKS1) and tankyrase2 (TNKS2) were abundantly expressed in various biological functions in telomere regulation, Wnt/ß-catenin signaling pathway, viral replication, endogenous hormone regulation, glucose transport, cherubism disease, erectile dysfunction, and apoptosis. The structural analysis, mechanistic information, in vitro and in vivo studies led identification and development of several classes of tankyrase inhibitors under clinical phases. In the nutshell, this review will drive future research on tankyrase as it enlighten the structural and functional features of TNKS 1 and TNKS 2, different classes of inhibitors with their structure-activity relationship studies, molecular modeling studies, as well as past, current and future perspective of the different class of tankyrase inhibitors.