Assessing the effectiveness and safety of transbronchial lung cryobiopsy utilizing a flexible bronchoscope with an endobronchial blocker in diffuse parenchymal lung lesions.

Transbronchial lung cryobiopsy (TBLC) with flexible bronchoscope represents an encouraging modality to obtain a larger size specimen without crush artifact, and a higher diagnostic yield in patients with diffuse parenchymal lung lesions/diseases as compared to conventional transbronchial lung biopsy, and fewer complications as opposed to surgical lung biopsy. Artificial airway is preferred as it provides better airway protection in cases of severe bleeding. Although various researchers have published data on different modalities, the data is not sufficient to standardize a single technique. This study describes the procedural technique, safety, and yield of TBLC using a flexible bronchoscope with an endobronchial blocker. We performed a retrospective analysis of 100 consecutive patients who underwent TBLC using flexible bronchoscopy from May 2018 to June 2022. TBLC samples were obtained under moderate sedation without the use of artificial airway or fluoroscopy. Among the 100 patients, the majority were male (63%). The mean age of the enrolled patients was 44.43±15.92 years. The predominant diagnoses in our study were hypersensitivity pneumonitis (27%), followed by sarcoidosis (12%) and tuberculosis (10%). We obtained alveolated lung tissue in 90 out of 100 cases with a median biopsy size of 5 mm (in greatest dimension, interquartile range 5-4 mm), resulting in a specific histopathological diagnosis in 82 cases. The most frequent complications were bleeding and pneumothorax (13%). Mild bleeding occurred in 58% of the patients, and moderate bleeding occurred in 20% of the patients. There was no episode of severe/life-threatening bleeding. None of the patients required intensive care unit admission or endotracheal intubation. In conclusion, the use of TBLC through flexible bronchoscopy with an endobronchial blocker emerges as a minimally invasive, secure, time-efficient, and readily reproducible technique. Significantly, this procedure can be seamlessly executed in the bronchoscopy suite, eliminating the requirement for an artificial airway or general anesthesia.

7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.

Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation1,2. Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation3, we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.

Therapeutic Approaches in Pancreatic Cancer: Recent Updates.

Cancer is a significant challenge for effective treatment due to its complex mechanism, different progressing stages, and lack of adequate procedures for screening and identification. Pancreatic cancer is typically identified in its advanced progression phase with a low survival of ~5 years. Among cancers, pancreatic cancer is also considered a high mortality-causing casualty over other accidental or disease-based mortality, and it is ranked seventh among all mortality-associated cancers globally. Henceforth, developing diagnostic procedures for its early detection, understanding pancreatic cancer-linked mechanisms, and various therapeutic strategies are crucial. This review describes the recent development in pancreatic cancer progression, mechanisms, and therapeutic approaches, including molecular techniques and biomedicines for effectively treating cancer.

High-frequency imagery to capture coral tissue (Montipora capricornis) response to environmental stress, a pilot study.

Environment stress is a major threat to the existence of coral reefs and has generated a lot of interest in the coral research community. Under the environmental stress, corals can experience tissue loss and/or the breakdown of symbiosis between the cnidarian host and its symbiotic algae causing the coral tissue to appear white as the skeleton can be seen by transparency. Image analysis is a common method used to assess tissue response under the environmental stress. However, the traditional approach is limited by the dynamic nature of the coral-algae symbiosis. Here, we observed coral tissue response in the scleractinian coral, Montipora capricornis, using high frequency image analysis throughout the experiment, as opposed to the typical start/end point assessment method. Color analysis reveals that the process can be divided into five stages with two critical stages according to coral tissue morphology and color ratio. We further explore changes to the morphology of individual polyps by means of the Pearson correlation coefficient and recurrence plots, where the quasi-periodic and nonstationary dynamics can be identified. The recurrence quantification analysis also allows the comparison between the different polyps. Our research provides a detailed visual and mathematical analysis of coral tissue response to environmental stress, which potentially shows universal applicability. Moreover, our approach provides a robust quantitative advancement for improving our insight into a suite of biotic responses in the perspective of coral health evaluation and fate prediction.

Revisiting the therapeutic potential of gingerols against different pharmacological activities.

The rhizomes of ginger have been in use in many forms of traditional and alternative medicines. Besides being employed as condiment and flavoring agent, it is used in the treatment of nausea, osteoarthritis, muscle pain, menstrual pain, chronic indigestion, Alzheimer's disease, and cancer. Ginger rhizome contains volatile oils, phenolic compounds and resins, and characterization studies showed that [6]-gingerol, [6]-shogaol, and [6]-paradol are reported to be the pharmacologically active components. Gingerol is a major chemical constituent found as volatile oil in the rhizomes of ginger. It has several medicinal benefits and used for the treatment of rheumatoid arthritis, nausea, cancer, and diabetes. Many studies have been carried out in various parts of the world to isolate and standardize gingerol for their use as a complementary medicine. The present review summarizes wide range of research studies on gingerol and its pharmacological roles in various metabolic diseases.

Molecular Mechanisms and Applications of N-Acyl Homoserine Lactone-Mediated Quorum Sensing in Bacteria.

Microbial biodiversity includes biotic and abiotic components that support all life forms by adapting to environmental conditions. Climate change, pollution, human activity, and natural calamities affect microbial biodiversity. Microbes have diverse growth conditions, physiology, and metabolism. Bacteria use signaling systems such as quorum sensing (QS) to regulate cellular interactions via small chemical signaling molecules which also help with adaptation under undesirable survival conditions. Proteobacteria use acyl-homoserine lactone (AHL) molecules as autoinducers to sense population density and modulate gene expression. The LuxI-type enzymes synthesize AHL molecules, while the LuxR-type proteins (AHL transcriptional regulators) bind to AHLs to regulate QS-dependent gene expression. Diverse AHLs have been identified, and the diversity extends to AHL synthases and AHL receptors. This review comprehensively explains the molecular diversity of AHL signaling components of Pseudomonas aeruginosa, Chromobacterium violaceum, Agrobacterium tumefaciens, and Escherichia coli. The regulatory mechanism of AHL signaling is also highlighted in this review, which adds to the current understanding of AHL signaling in Gram-negative bacteria. We summarize molecular diversity among well-studied QS systems and recent advances in the role of QS proteins in bacterial cellular signaling pathways. This review describes AHL-dependent QS details in bacteria that can be employed to understand their features, improve environmental adaptation, and develop broad biomolecule-based biotechnological applications.

Applying model approaches in non-model systems: A review and case study on coral cell culture.

Model systems approaches search for commonality in patterns underlying biological diversity and complexity led by common evolutionary paths. The success of the approach does not rest on the species chosen but on the scalability of the model and methods used to develop the model and engage research. Fine-tuning approaches to improve coral cell cultures will provide a robust platform for studying symbiosis breakdown, the calcification mechanism and its disruption, protein interactions, micronutrient transport/exchange, and the toxicity of nanoparticles, among other key biological aspects, with the added advantage of minimizing the ethical conundrum of repeated testing on ecologically threatened organisms. The work presented here aimed to lay the foundation towards development of effective methods to sort and culture reef-building coral cells with the ultimate goal of obtaining immortal cell lines for the study of bleaching, disease and toxicity at the cellular and polyp levels. To achieve this objective, the team conducted a thorough review and tested the available methods (i.e. cell dissociation, isolation, sorting, attachment and proliferation). The most effective and reproducible techniques were combined to consolidate culture methods and generate uncontaminated coral cell cultures for ~7 days (10 days maximum). The tests were conducted on scleractinian corals Pocillopora acuta of the same genotype to harmonize results and reduce variation linked to genetic diversity. The development of cell separation and identification methods in conjunction with further investigations into coral cell-type specific metabolic requirements will allow us to tailor growth media for optimized monocultures as a tool for studying essential reef-building coral traits such as symbiosis, wound healing and calcification at multiple scales.

Extraanatomic Bypass to Supraceliac Abdominal Aorta for Complex Thoracic Aortic Obstruction.

BACKGROUND: The standard surgical treatment of coarctation of the aorta is through a left posterolateral thoracotomy. However, when a concomitant cardiac procedure is required or the conventional approach is not possible or is hazardous, extraanatomic bypass to the supraceliac abdominal aorta may be advantageous. We discuss our technique and report the long-term results. METHODS: Between January 1986 and January 2015, 25 patients (16 males, 9 females) underwent extraanatomic bypass to the supraceliac abdominal aorta for various lesions of the arch and the descending thoracic aorta. Extraanatomic bypass to the supraceliac abdominal aorta was performed for patients in whom balloon dilatation was not feasible due to associated arch hypoplasia (n = 9), long-segment thoracic aorta narrowing due to nonspecific aortoarteritis (n = 3), or isolated long-segment coarctation of the aorta (n = 3). Patients who needed concomitant cardiac procedures, such as aortic valve replacement (n = 4), ascending aortic aneurysm repair (n = 2), or coronary artery bypass grafting (n = 1), and in whom balloon dilatation had failed, also underwent extraanatomic bypass to the supraceliac abdominal aorta. Extraanatomic bypass was also performed in 3 patients with recurrent coarctation after surgical repair and in whom balloon dilation was not feasible or unsuccessful. RESULTS: There were no early or late deaths. The peak-to-peak gradients between the upper limb and the lower limb decreased from 59.3 ± 16.3 mm Hg to 2.0 ± 2.8 mm Hg (p < 0.0001). The mean follow-up was 96.6 ± 92.6 months (range, 1 to 240 months; median, 54 months). Doppler interrogation of the lower limb arterial system after a mean follow-up of 86.4 ± 85.2 months showed an unobstructed flow pattern. The ankle-brachial pressure index improved from a preoperative value of 0.60 ± 0.07 to 1.04 ± 0.11 (p < 0.0001). Systolic blood pressure decreased significantly compared with preoperative values (153.9 ± 18.9 vs 122.8 ± 10.2, p < 0.0001). Three patients continued to receive antihypertensive medication due to persistent mild hypertension. CONCLUSIONS: Extraanatomic bypass to the supraceliac abdominal aorta provides effective palliation for complex aortic obstructions. It is easy and quick to perform, avoids fatal complications, and is well tolerated in all age groups.

Total replacement of a lung by tuberculosis pneumatocele--an unusual post-tuberculosis sequel.

Total replacement of a lung by pneumatocele in pulmonary tuberculosis is rare. The formation of pneumatoceles in adult pulmonary tuberculosis can occur before, during or after anti-tuberculosis treatment. A case of pneumatocele formation in a 19-year young female following pulmonary tuberculosis is reported. The left lung was completely replaced by pneumatocele. Total replacement of a lung by pneumatocele inspite of successful chemotherapy of tuberculosis is rare and should be considered as one of the differential diagnosis for acquired cysts of the lung.

Structural alterations in Pseudomonas aeruginosa by zingerone contribute to enhanced susceptibility to antibiotics, serum and phagocytes.

AIMS: Excessive use of antibiotics has led to evolutionary adaptation resulting in emergence of multidrug resistance in P. aeruginosa. The aim of the present study was oriented towards exploiting zingerone (active component of ginger) in making P. aeruginosa more susceptible to killing with antibiotics, humoral/cellular defences and studying its underlying mechanism. MAIN METHOD: Effect of zingerone treatment on antibiotic susceptibility, serum, and phagocytic killing of P. aeruginosa was studied. The underlying mechanism was evaluated in terms of cell surface hydrophobicity, alginate and LPS production. TNF-α and MIP-2 cytokine production by mouse macrophages was also checked. Structural analysis was carried out using scanning electron microscopy (SEM) and liquid chromatography-mass spectrometry (LC-MS) analysis. KEY FINDINGS: Zingerone treated cells showed increased susceptibility to variety of antibiotics, serum as well as macrophages (p<0.05). Zingerone treatment significantly reduced cell surface hydrophobicity, alginate and LPS production (p<0.05). Zingerone treated cells showed significant decrease in TNF-α and MIP-2 cytokine production as compared to non-treated cells. Coupled with this, reduction in the production of extracellular protective matrix and modulation of chemical structure of LPS was also observed by scanning electron microscopy and liquid chromatography-mass spectrometric (LC-MS) respectively. Zingerone significantly influence surface structure of P. aeruginosa which contributes towards enhanced susceptibility to antibiotics and innate immune system. SIGNIFICANCE: Use of phytochemicals may prove to be a novel therapeutic approach by enhancing susceptibility of pathogenic microorganisms to antibiotics and immune system. Zingerone has proved to be one such agent which can be employed as a potential anti-virulent drug candidate against P. aeruginosa infections.

Unilateral and painless development of isoniazid induced gynecomastia during re-treatment of pulmonary tuberculosis.

A case of isoniazid induced gynecomastia is being reported in an 18-year old male, who received a re-treatment regimen for the relapse of pulmonary tuberculosis (TB). At the end of two months of the treatment, the patient developed a painless unilateral gynecomastia, which completely disappeared after a month of the cessation of isoniazid. A review of literature on isoniazid induced gynecomastia is discussed.

Multi-modality blood conservation strategy in open-heart surgery: an audit.

The objective of this study was to perform an audit of the use of homologous blood and blood products in patients undergoing open-heart surgery by a single surgical team that follows an in-house protocol for blood conservation. The hospital records of 310 consecutive patients (age >15 years) undergoing open-heart surgery over a period of 8 months were retrospectively reviewed to assess the comprehensive blood conservation protocol. Homologous blood and blood product usage during and after surgery, in the intensive care unit and up to hospital discharge was analyzed. Two hundred and fifty-six patients (82.6%) did not receive any blood or blood products. Only 54 patients (17.4%) received one or more units of allogenic transfusion either intraoperatively or postoperatively until discharge. Mean hemoglobin at discharge was 9.8 Grams% (8.9-12 Grams%). A standardized multidisciplinary approach to blood conservation in cardiac surgery decreases bleeding and transfusion requirements in a safe and cost effective manner.