Search

Purpose: To curtail the potential of donor corneal tissue disseminating fungi to the recipient's eye, we evaluated the addition of amphotericin B to McCarey-Kaufman (M-K)—corneal storage medium supplemented with colistin. Methods: Amphotericin B was examined for its ability to inhibit the growth of Candida albicans and Aspergillus flavus using a microbroth dilution test and checkerboard assay in combination with only gentamicin and a combination of colistin, gentamicin, and amphotericin B. The safety on epithelium and endothelium was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The minimal inhibitory concentration of gentamicin was found to be >256 μg/ml against both C. albicans and A. flavus, whereas that of amphotericin B was found to be in a range of 0.25–0.5 and 1–2 μg/ml for C. albicans and A. flavus, respectively. According to the checkerboard assay, 80% (4/5) of C. albicans isolates and 100% (5/5) of A. flavus isolates responded synergistically to the combination of amphotericin B and gentamicin, but only 20% (1/5) of C. albicans isolates showed an additive effect. None of the tested isolates displayed antagonism. The combined effect of the three drugs also did not display any antagonistic effect. Additionally, the MTT assay reveals no toxic effect of the antimicrobials used on corneal epithelial and endothelial cells. Conclusion: In vitro experiments demonstrate that amphotericin B is not toxic to either epithelium or endothelium and is a promising additive to the M-K medium supplemented with colistin.

Abstract Background Previous research exploring the role of race on prostate cancer (PCa) outcomes has demonstrated greater rates of disease progression and poorer overall survival for African American (AA) compared to Caucasian American (CA) men. The current study examines self‐reported race as a predictor of long‐term PCa outcomes in patients with low and favorable‐intermediate risk disease treated with external beam radiation therapy (EBRT). Methods This retrospective cohort study examined patients who were consented to enrollment in the Center for Prostate Disease Research Multicenter National Database between January 01, 1990 and December 31, 2017. Men self‐reporting as AA or CA who underwent EBRT for newly diagnosed National Comprehensive Cancer Network‐defined low or favorable‐intermediate risk PCa were included. Dependent study outcomes included: biochemical recurrence‐free survival, (ii) distant metastasis‐free survival, and (iii) overall survival. Each outcome was modeled as a time‐to‐event endpoint using race‐stratified Kaplan–Meier estimation curves and multivariable Cox proportional hazards analysis. Results Of 840 men included in this study, 268 (32%) were AA and 572 (68%) were CA. The frequency of biochemical recurrence, distant metastasis, and deaths from any cause was 151 (18.7%), 29 (3.5%), and 333 (39.6%), respectively. AA men had a significantly younger median age at time of EBRT and slightly higher biopsy Gleason scores. Multivariable Cox proportional hazards analyses demonstrated no racial differences in any of the study endpoints. Conclusions These findings reveal no racial disparity in PCa outcomes for AA compared to CA men, in a long‐standing, longitudinal cohort of patients with comparable access to cancer care.

Purpose: To assess the efficacy of the addition of polymyxin E (colistin) in the McCarey-Kaufman (MK) corneal storage solution against multi-drug resistant strains of Enterobacteriaceae, Staphylococcus aureus, and Candida spp. Methods: A standard micro broth dilution test and a checkerboard assay were performed for five multi-drug resistant (MDR) clinical strains of P. aeruginosa and five clinical strains of methicillin-resistant S. aureus (MRSA) and C. albicans against colistin and gentamicin alone and in combination. The minimum inhibitory concentration (MIC) and the fractional inhibitory concentration index (FICI) were calculated to assess the efficacy of each combination. Results: The MIC of colistin was in the range of 1–2 μg/mL for P. aeruginosa, whereas it was 256–1024 μg/mL against S. aureus. In comparison, the MIC of gentamicin was found to be 0.5–512 μg/mL and 0.5–8 μg/mL against P. aeruginosa and S. aureus, respectively. All five isolates of C. albicans did not exhibit any susceptibility to either colistin or gentamicin even at a concentration of ≥ 512 μg/mL each. The checkerboard assay was performed to evaluate the nature of the interaction of the combination of colistin and gentamicin. Based on the FICI, it was observed that the colistin and gentamicin combination has a maximum synergistic effect (FIC 0.5–4) was 100% (5/5) for P. aeruginosa and the minimum additive effect was 20% (1/5) for S. aureus isolates. Antagonism (FIC ≥ 4) was not observed in any combination between the strains used in the study. Both colistin and gentamicin alone or in combination were, however, ineffective against Candida spp. Conclusion: The addition of colistin has an inhibitory effect on bacterial contamination that could be possibly caused by MDR strains and could potentially be considered as an additional additive in corneal storage media.

oronavirus (COVID-19) has caused marked impact on graduate medical education for all medical specialties. Radiation Oncology and the American Board of Radiology have also had to rapidly adapt to converting education and examinations to virtual platforms. We describe our small pilot experience in transitioning our in-person mock oral examinations to a virtual platform. Survey-based assessment revealed excellent feedback regarding ease of use and educational usefulness. Our mock oral examinations pilot experience adds to evidence that virtual mock oral examinations are an important considerationfor Radiation Oncology education and a feasible alternative to an in-person oral examination.

Purpose: The aim of this study is to quantify and describe the feasibility, clinical outcomes, and patient-reported outcomes of reduced planning target volume (PTV) margins for prostate cancer treatment using real-time, continuous, intrafraction monitoring with implanted radiation frequency transponder beacons. Methods and materials: For this prospective, nonrandomized trial, the Calypso localization system was used for intrafraction target localization in 31 patients with a PTV margin reduced to 2 mm in all directions. A total of 1333 fractions were analyzed with respect to movement of the prostate, pauses and interruptions, and dosimetric data. Pre- and posttreatment quality-of-life scores were tracked at baseline, during treatment, and up to 24 months after treatment. Results: The mean time of daily treatment was 10 minutes, with 96.1% of all treatments falling within a 20-minute treatment window standard. On average, beacon motion exceeded 3 mm during active treatment only 1.76% of the time. The average length of treatment interruption was 34.2 seconds, with an average of 1 interruption every 3.39 fractions. The displacement or excursion of the prostate was the greatest in the superior or inferior dimension (0.11 mm and 0.09 mm, respectively) and anterior or posterior dimension (0.07 mm and 0.13 mm, respectively), followed by the left or right dimension (0.05 mm and 0.06 mm, respectively). At 6 months, patients demonstrated a smaller change in Expanded Prostate Cancer Index Composite scores than the ProtecT comparator group (decreased short-term morbidity). However, in the Bowel and Urinary domains at 12 and 24 months, there was no significant difference. Conclusions: Our data confirm and support that the use of Calypso tracking with intensity modulated radiation therapy reliably provides minimal disruption to daily treatments and overall time of treatment, with the PTV only moving outside of a 3-mm margin < 2% of the time. The use of a 3-mm PTV margin provides adequate dosimetric coverage while minimizing genitourinary and gastrointestinal toxicity.

Fagonia arabica (FA) possesses a thrombolytic property which has been earlier reported in our laboratory. Current study was undertaken to investigate the effect of aqueous extract of FA on thrombin-induced tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) release from cultured human umbilical vein endothelial cell line (HUVE) for studying its clot lytic activity. For this, establishment of cell line model has been done by isolating the cells from human umbilical cord. Cell toxicity was evaluated using XTT assay. Estimation of t-PA and PAI-1 t-PA complex were done using ELISA technique. Thrombin treatment induces the t-PA and PAI-1 release from HUVE cell line, and FA treatment was found to antagonize the thrombin induced t-PA and PAI-1 release. Our preliminary results suggest that FA may be used as an alternative to thrombolytic drug. However, study demands further experiments using animal model of thrombosis to establish the role of FA as a novel thrombolytic drug.

Poor dietary intake or unhealthy lifestyle contributes to various health disorders, including postprandial hyperglycemia, leading to type-2 diabetes mellitus (T2DM). Reduction of postprandial glucose levels through diet is a key strategy for preventing and managing T2DM. Thus, it is essential to understand how dietary components affect glycemic regulation. Dietary polyphenols (DPs), such as anthocyanins and other phenolics found in various fruits and vegetables, are often recommended for their potential health benefits, though their systemic effectiveness is subject to ongoing debate. Therefore, this review assesses the current and historical evidence of DPs bioactivities, which regulate crucial metabolic markers to lower postprandial hyperglycemia. Significant bioactivities such as modulation of glucose transporters, activation of 5' adenosine monophosphate-activated protein kinase (AMPK), and regulation of incretins are discussed, along with prospects for diet-induced therapeutics to prevent the onset of T2DM. STATEMENT OF SIGNIFICANCE: This review uniquely synthesizes both current and historical data on the metabolic bioactivities of dietary polyphenols (DPs), particularly focusing on their mechanisms; such as modulation of glucose transporters, AMPK activation, and incretin regulation that may help lower postprandial hyperglycemia, offering a more integrated understanding of diet-induced strategies for T2DM prevention., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Leptospira borgpetersenii commonly causes human leptospirosis, including severe disease. The first published analysis of L. borgpetersenii , performed on two strains of serovar Hardjo (L550 and JB197), concluded that the L. borgpetersenii genome is in the process of genome decay with functional consequences leading to a more obligately host-dependent life cycle. Yet whole genome analysis has only been carried out on few strains of L. borgpetersenii , with limited closed genomes and comprehensive analysis. Herein we report the complete, circularized genomes of seven non-Hardjo Leptospira borgpetersenii isolates from human leptospirosis patients in Sri Lanka. These isolates (all ST144) were found to be nearly identical by whole genome analysis; serotyping showed they are a novel serovar. We show that the L. borgpetersenii isolated from humans in Sri Lanka are less genomically decayed than previously reported isolates: fewer pseudogenes (N=141) and Insertion Sequence (IS) elements (N=46) compared to N=248, N=270, and N=400 pseudogenes, and N=121 and N=116 IS elements in published L. borgpetersenii Hardjo genomes (L550, JB197 and TC112). Compared to previously published L. borgpetersenii whole genome analyses showing two to three VM proteins in L. borgpetersenii isolates from cattle, rats and humans, we found that all of the human L. borgpetersenii isolates from Sri Lanka, including previously reported serovar Piyasena, have 4 encoded VM proteins, one ortholog of L. interrogans Copenhageni LIC12339 and 3 orthologs of LIC12844. Our findings of fewer pseudogenes, IS elements and expansion of the LIC12844 homologs of the PF07598 family in these human isolates suggests that this newly identified L. borgpetersenii serovar from Sri Lanka has unique pathogenicity. Comparative genome analysis and experimental studies of these L. borgpetersenii isolates will enable deeper insights into the molecular and cellular mechanisms of leptospirosis pathogenesis., Competing Interests: Declaration of Competing Interest Some of work reported here has been filed in patent applications from Yale University. JMV and spouse have an equity interest in Luna Bioscience, Inc, which may have a future interest in licensing this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Tuberculosis is a serious life-threatening disease among the top global health challenges and rapid and effective diagnostic biomarkers are vital for early diagnosis especially given the increasing prevalence of multidrug resistance., Methods: Two human whole blood microarray datasets, GSE42826 and GSE42830 were retrieved from publicly available gene expression omnibus (GEO) database. Deregulated genes (DEGs) were identified using GEO2R online tool and Gene Ontology (GO), protein-protein interaction (PPI) network analysis was performed using Metascape and STRING databases. Significant genes (n = 8) were identified using T-test/ANOVA and Molecular Complex Detection (MCODE) score ≥10, which was validated in GSE34608 dataset. The diagnostic potential of three biomarkers was assessed using Area Under Curve (AUC) of Receiver Operating Characteristic (ROC) plot. The transcriptional levels of these genes were also examined in a separate dataset GSE31348, to monitor the patterns of variation during tuberculosis treatment., Results: A total of 62 common DEGs (57 upregulated, 7 downregulated genes) were identified in two discovery datasets. GO functions and pathway enrichment analysis shed light on the functional roles of these DEGs in immune response and type-II interferon signaling. The genes in Module-1 (n = 18) were linked to innate immune response, interferon-gamma signaling. The common genes (n = 8) were validated in GSE34608 dataset, that corroborates the results obtained from discovery sets. The gene expression levels demonstrated responsiveness to Mtb infection during anti-TB therapy in GSE31348 dataset. In GSE34608 dataset, the expression levels of three specific genes, GBP5, IFITM3, and EPSTI1, emerged as potential diagnostic makers. In combination, these genes scored remarkable diagnostic performance with 100% sensitivity and 89% specificity, resulting in an impressive Area Under Curve (AUC) of 0.958. However, GBP5 alone showed the highest AUC of 0.986 with 100% sensitivity and 89% specificity., Conclusions: The study presents valuable insights into the critical gene network perturbed during tuberculosis. These genes are determinants for assessing the effectiveness of an anti-TB response and distinguishing between active TB and healthy individuals. GBP5, IFITM3 and EPSTI1 emerged as candidate core genes in TB and holds potential as novel molecular targets for the development of interventions in the treatment of TB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Arya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Acute trauma resuscitation is challenging and disorganized in low- and middle-income countries as there is lack of evidence-based transfusion practices with respect to ratio, volume, trigger, cutoff points for various triggers. This study aims to study the patterns of blood use in various mechanisms of injury, by interfacility transfer status and define triggers for transfusion of various blood components. Prospective observational study, emergency department of level 1 trauma center (August 2017-August 2018)., Methods: Demographic, injury, clinical, laboratory, transfusion characteristics, and patient outcomes were collected from electronic hospital records and transfusion service records. We used multivariate logistic regression to identify triggers of transfusion of red blood cells, plasma, platelets (PLTs), cryoprecipitate, and mortality predictors., Results: Among 986 severely injured patients 80% were males, 92% had blunt injuries and commonest trauma was Head. The median length of intensive care unit stay and hospital stay were more in a referred group. Patients brought to center directly received more massive transfusions (56, 13.05% vs. 48, 8.62%). Railway track injuries received the most total median packed red blood cells (PRBCs) units in both groups. The triggers for various blood product transfusions include: Hematocrit < 32.08 for PRBC, PT >16.9 s for plasma, PLT count <130 lakhs for platelets, MAP <89.7 mmHg and PT >18.2 s for cryoprecipitate., Conclusion: Railway track injuries with inferior extremity injuries required maximum transfusion requirements and were a trigger for PRBC, plasma, PLTs, and cryoprecipitate. Smartphone-based apps and transfusion prediction models can be framed based on the triggers and cut points., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Emergencies, Trauma, and Shock.)

Tuberculosis (TB) remains a significant global health concern, necessitating accurate diagnosis and treatment monitoring. Extracellular vesicles (EVs), including exosomes, play crucial roles in disease progression, with their associated genes serving as potential biomarkers and therapeutic targets. Leveraging publicly available RNA-Seq datasets of TB patients and healthy controls (HCs), to identify differentially expressed genes (DEGs) and their associated protein-protein interaction networks and immune cell profiles, the common EV-related DEGs were identified and validated in the GSE42830 and GSE40553 datasets. We have identified nine common EV-related DEGs (SERPINA1, TNFAIP6, MAPK14, STAT1, ITGA2B, VAMP5, CTSL, CEACAM1, and PLAUR) upregulated in TB patients. Immune cell infiltration analysis revealed significant differences between TB patients and HCs, highlighting increased proportions of various immune cells in TB patients. These DEGs are involved in crucial cellular processes and pathways related to exocytosis and immune response regulation. Notably, VAMP5 exhibited excellent diagnostic performance (AUC-0.993, sensitivity-93.8%, specificity-100%), with potential as a novel biomarker for TB. The EV-related genes can serve as novel potential biomarkers that can distinguish between TB and HCs. VAMP5, which functions in exosome biogenesis and showed significant upregulation in TB, can be targeted for therapeutic interventions and treatment outcomes., Competing Interests: The authors declare no conflicts of interest.

Background: Lower limb trauma in emergency settings often leads to pain management challenges. Traditional methods, primarily non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, have limitations. This study explores the efficacy of epidural analgesia in emergency for lower limb trauma patients (ELETRA) as an alternative for managing pain in lower limb trauma patients upon arrival in emergency care., Objectives:  This study primarily focuses on determining ELETRA's effectiveness in reducing pain for patients with lower limb trauma upon arrival. It also aims to evaluate ELETRA's influence on decreasing stress and shortening hospital stays compared to traditional pain management approaches., Methods: This study was executed as a prospective, parallel-design, randomized controlled trial in the emergency department of a tertiary care teaching hospital. The interventions were performed in a dedicated induction room adjacent to the emergency operating theater. The trial was registered in the Clinical Trial Registry of India with registration number CTRI/2022/08/044699 dated 16/08/2022. Participants were 18- to 50-year-old patients with lower limb injuries, classified under American Society of Anesthesiologists (ASA) class 1 or 2. Participants were randomized into two groups: one receiving ELETRA and the other standard pain control treatment. The effectiveness of pain relief was measured through a visual analog scale (VAS), and hemodynamic parameters, adverse effects, levels of acute phase reactants, and stress hormones were also measured along with patient satisfaction., Results: The study enrolled 356 participants with lower limb injuries. After excluding participants lost following the intervention, data from 157 individuals in Group A and 160 in Group B were analyzed. Group A's success rate for analgesia (VAS < 2) was 92.35% (n = 145), significantly higher than Group B's 75.62% (n = 121) (p < 0.001). The commonest side effect was hypotension (5.73%) in Group A and nausea in Group B (7.5%). C-reactive protein (CRP) levels rose to 104.71 ± 8.99 mg/dL in Group A and 192.58 ± 9.23 mg/dL in Group B; the difference was statistically significant. Serum cortisol levels were also higher in Group B (67.18 ± 9.21) compared to Group A (44.72 ± 6.14) at one week. Group B had a longer hospital stay, averaging 12.24 ± 4.81 days, against Group A's 10.19 ± 4.91 days., Conclusion: ELETRA is a safe and effective alternative for pain management in lower limb trauma patients in emergency settings. It reduces pain, improves patient satisfaction, and has a favorable impact on stress responses., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Jain et al.)

Dopaminergic (DAergic) neurodegeneration in the substantia nigra pars compacta of the human brain is the pathological feature associated with Parkinson's disease (PD). Drosophila also exhibits mobility defects and diminished levels of brain dopamine on exposure to neurotoxicants mimicking PD. Our laboratory demonstrated in a Drosophila model of sporadic PD that there is no decrease in DAergic neuronal number; instead, there is a significant reduction in tyrosine hydroxylase (TH) fluorescence intensity (FI). Here, we present a sensitive assay based on the quantification of FI of the secondary antibody (ab). As the FI is directly proportional to the amount of TH synthesis, its reduction under PD conditions denotes the decrease in the TH synthesis, suggesting DAergic neuronal dysfunction. Therefore, FI quantification is a refined and sensitive method to understand the early stages of DAergic neurodegeneration. FI quantification is performed using the ZEN 2012 SP2 single-user software; a license must be acquired to utilize the imaging system to interactively control image acquisition, image processing, and analysis. This method will be of good use to biologists, as it can also be used with little modification to characterize the extent of degeneration and changes in the level of degeneration in response to drugs in different cell types. Unlike the expensive and cumbersome confocal microscopy, the present method will be an affordable option for fund-constrained neurobiology laboratories. Key features • Allows characterizing the incipient DAergic and other catecholaminergic neurodegeneration, even in the absence of loss of neuronal cell body. • Great alternative for the fund-constrained neurobiology laboratories in developing countries to utilize this method in different cell types and their response to drugs/nutraceuticals., Competing Interests: Competing interestsThe author declares no conflicts of interest., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

To compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. Head and neck malignancy grossly refers to squamous cell carcinomas of head and neck (HNSCC) have multiple treatment modalities and strategies, when opted in an appropriate manner renders tumours curable. The aim of this study is to compare and evaluation of surgical operability with and without induction chemotherapy in locally advanced head and neck squamous cell carcinoma. A prospective observational study involving 50 patients of histologically proven squamous cell carcinoma of head and neck region. Patients were categorized into two major groups, group-1 patients included resectable tumour stage and group-2 included unresectable tumour stage. Both groups were compared after appropriate chemotherapy and surgical intervention. There were a total of 78% males and 22% females with majority of patients in age group of 41-60 years. 54% patients had ulcerative type of growth pattern and most patients had primary site of lesion in oral cavity. 50% patients had moderately differentiated squamous cell carcinoma. Induction chemotherapy was considered in 70% of patients, while majority of patients were belonging to T4N2M0 stage. In this study, we recommend that the borderline category of patients who are initially in an unresectable tumour stage can undergo induction chemotherapy to downstage and shrink the tumour to a resectable stage following which the appropriate surgical intervention should be done with a close monitoring and sustained follow up to prevent recurrence., Competing Interests: Competing interestsThe authors have no competing interests to declare that are relevant to the content of this article. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript. The authors have no financial or proprietary interests in any material discussed in this article. Authors are responsible for correctness of the statements provided in the manuscript., (© Association of Otolaryngologists of India 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Coronavirus disease 2019 (COVID-19), is known for its variable severity and high infectivity. Though fewer than 15% of infected cases develop severe disease, a major proportion had prolonged stay in the intensive care unit (ICU). Prolonged ICU stay is known to have a long-term impact on behavior and quality of life. 8 Therefore, it is likely that patients discharged after severe COVID-19 have issues that persist for long term. The current study aimed to assess the long-term impact of severe COVID-19 on the Quality of life (QOL), sleep pattern, behavior, and workability., Methods: The current multicenter study adopted a cross-sectional design to analyze data from two tertiary care COVID-19 dedicated hospitals. All experimental procedures were approved by the ethics committee of the M.L.B Medical College. Participants were 20-60 age group who had been admitted to the ICU because of severe COVID-19 and had elapsed at least one and a half year since their discharge. After informed written consent the participants were assessed for: EUROHIS-QOL 8-item index; Workability Score; Quality of sleep; The major depression inventory (MDI) questionnaire; Generalized anxiety disorder 7 item scale (GAD-7); Current global health status score: an innovative subjective scale (1 -10) to determine the current global health status when 5 is the status before COVID-19., Findings: 491 participants were assessed, the median follow-up time after discharge from the hospital was 561·0 days (range, 548-580 days). The mean duration of ICU stay was 8.72 ± 2.85 days. There was significant reduction in the prevalence of obesity, diabetes, and hypertension as compared with discharge time. The mean of EUROHIS-QOL score, workability score, current global health status score was 3.28 ± 0.98, 6.87 ± 0.85, 4.53 ± 1.36 respectively. The mean MDI and anxiety scores were 4.12 ± 1.45 and 18.63 ± 3.28, respectively., Interpretation: Severe COVID-19 survivors have new-onset psychological disorders and sleep disturbances. Long term quality of life and work ability remains poor after prolong ICU admission secondary to severe COVID-19., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)