Publications by authors named "Naresh Kumar"

629 Publications

Outcomes of Patients With Spinal Metastases From Prostate Cancer Treated With Conventionally-Fractionated External Beam Radiation Therapy.

Global Spine J 2021 Mar 2:2192568221994798. Epub 2021 Mar 2.

Department of Radiation Oncology, National University Cancer Institute, National University Hospital, National University Health System, National University of Singapore, Singapore, Singapore.

Study Design: Retrospective cohort study.

Objective: To evaluate the outcomes of conventionally-fractionated external beam radiation therapy (cEBRT) in the treatment of prostate cancer spinal metastases (PCSM).

Methods: Patients who received palliative cEBRT for PCSM in our institution between 2008 and 2018 were included. Our outcomes were local progression-free survival (LPFS), overall survival (OS), pain response and toxicities graded using CTCAE version 4.03. Univariable and multivariable Cox proportional hazard regressions were performed to identify predictors for LPFS and OS.

Results: A total of 100 patients with 132 sites of PCSM were identified, with a median follow-up of 54 months. Fourteen-percent of patients underwent surgical intervention before receiving cEBRT. Eighteen spinal segments (13.6%) had local progression, with a median time to local progression of 8 months. The median LPFS and OS were 7.8 and 9.0 months, respectively. The complete and partial pain response rates were 57% and 39% respectively. The incidence of grade ≥3 acute toxicities was 11%. Better ECOG performance status (0 to 1), castration-sensitive disease, spinal surgery and use of novel antiandrogen agent were identified as significant predictors for improved OS on multivariable analysis.

Conclusions: In our prostate cancer cohort, cEBRT is an effective treatment modality for local palliation of spinal metastases. More aggressive treatment approach should be considered for patients with excellent performance status and castration-sensitive disease in light of their expected longer survival. Further studies are warranted to identify the predictors for radiotherapy response in this population.
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http://dx.doi.org/10.1177/2192568221994798DOI Listing
March 2021

Physical plasma-derived oxidants sensitize pancreatic cancer cells to ferroptotic cell death.

Free Radic Biol Med 2021 Feb 23. Epub 2021 Feb 23.

Research Group PLASMANT, Department of Chemistry, University of Antwerp, Antwerp, 2610, Belgium. Electronic address:

Despite modern therapeutic advances, the survival prospects of pancreatic cancer patients remain poor, due to chemoresistance and dysregulated oncogenic kinase signalling networks. We applied a novel kinome activity-mapping approach using biological peptide targets as phospho-sensors to identify vulnerable kinase dependencies for therapy sensitisation by physical plasma. Ser/Thr-kinome specific activity changes were mapped upon induction of ferroptotic cell death in pancreatic tumor cells exposed to reactive oxygen and nitrogen species of plasma-treated water (PTW). This revealed a broad kinome activity response involving the CAMK, the AGC and CMGC family of kinases. This systems-level kinome network response supports stress adaptive switches between chemoresistant anti-oxidant responses of Kelch-like ECH-associated protein 1 (KEAP1)/Heme Oxygenase 1 (HMOX1) and ferroptotic cell death sensitisation upon suppression of Nuclear factor (erythroid derived 2)-like 2 (NRF2) and Glutathione peroxidase 4 (GPX4). This is further supported by ex vivo experiments in the chicken chorioallantoic membrane assay, showing decreased GPX4 and Glutathione (GSH) expression as well as increased lipid peroxidation, along with suppressed BxPC-3 tumor growth in response to PTW. Taken all together, we demonstrate that plasma treated water-derived oxidants sensitize pancreatic cancer cells to ferroptotic cell death by targeting a NRF2-HMOX1-GPX4 specific kinase signaling network.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.02.026DOI Listing
February 2021

Prevalence of Irritable Bowel Syndrome and Frequency of Symptoms in the General Population of Pakistan.

Cureus 2021 Jan 6;13(1):e12541. Epub 2021 Jan 6.

Family Medicine, Jinnah Post Graduate Medical Center, Karachi, PAK.

Introduction: Irritable bowel syndrome (IBS) is a chronic and debilitating functional gastrointestinal disorder. Risk factors include infective enteritis, female sex, antibiotic exposure, anxiety, and depression. The aim of this study is to find out the prevalence of IBS in healthy population and determine the characteristics of symptoms.

Material And Methods: A cross-section study was conducted in the internal medicine unit of a tertiary care hospital in multiple cities of Pakistan. Eight hundred (800) healthy peoples were selected for study from June 2019 to August 2019. Diagnosis of IBS was made by using Rome III criteria.

Results: The prevalence of irritable bowel syndrome (IBS) in general population in our study was 33.2%. IBS was more common in females compared to males (57.7% vs. 42.2%; p value = 0.009). IBS was more common in age group between 20 and 29 years (45.5%). Among patient diagnosed with IBS in this study, the most common was bloating (74.7%) followed by increased stool frequency (54.4%).

Conclusion: IBS is very prevalent in Pakistan, yet there is very little data and awareness related to it. Any change in stool frequency or consistency in young adults, especially women, shall be evaluated for IBS after ruling out other diseases. Early diagnosis and treatment of IBS will assist in improving the patient's quality of life.
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http://dx.doi.org/10.7759/cureus.12541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863025PMC
January 2021

Pulmonary Health Effects of Indoor Volatile Organic Compounds-A Meta-Analysis.

Int J Environ Res Public Health 2021 Feb 7;18(4). Epub 2021 Feb 7.

Department of Public Health Sciences, Division of Environmental Health, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.

Volatile organic compounds (VOCs) are commonly found in consumer products, including furniture, sealants and paints. Thus, indoor VOCs have become a public health concern, especially in high-income countries (HICs), where people spend most of their time indoors, and indoor and outdoor air exchange is minimal due to a lack of ventilation. VOCs produce high levels of reaction with the airway epithelium and mucosa membrane and is linked with pulmonary diseases. This paper takes a stock of the literature to assess the strength of association (measured by effect size) between VOCs and pulmonary diseases with the focus on asthma and its related symptoms by conducting a meta-analysis. The literature was searched using the PubMed database. A total of 49 studies that measured VOCs or VOC types and pulmonary health outcomes were included in the analysis. The results of these studies were tabulated, and standard effect size of each study was computed. Most studies were conducted in high-income countries, including France ( = 7), Japan ( = 7) and the United States ( = 6). Our analysis suggests that VOCs have a medium-sized effect on pulmonary diseases, including the onset of asthma (effect size (or Cohen's d) ~0.37; 95% confidence interval (CI) = 0.25-0.49; = 23) and wheezing (effective size ~0.26; 95% CI = 0.10-0.42; = 10). The effect size also varied by country, age and disease type. Multiple stakeholders must be engaged in strategies to mitigate and manage VOC exposure and its associated pulmonary disease burden.
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http://dx.doi.org/10.3390/ijerph18041578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914726PMC
February 2021

Physiological response of diverse halophytes to high salinity through ionic accumulation and ROS scavenging.

Int J Phytoremediation 2021 Feb 2:1-11. Epub 2021 Feb 2.

ICAR - Central Soil Salinity Research Institute, Karnal, India.

Salt stress induced modulations in different ionic ratios and ROS system were studied in ten halophytic species, namely at salinity level of ECe ∼ 30 dSm (≈300 mM NaCl) to explore their possible role in salt tolerance ability of these halophytes. These halophytes were categorized for their salt tolerance levels based on the ratios of Na/K, Na/Ca, Na/Cl and Na + Cl/K + Ca. Variable responses were observed among all halophytes where had lowest leaf Na/K (0.44) which is one of the best indicator of salt tolerance, had lowest Na/Ca and Na/Cl (0.97 and 0.18), whereas had lowest Na + Cl/K + Ca (0.79). Specific enzymes activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), catalase (CAT) and peroxidase (POX) were also assessed to get better comprehension of the ROS scavenging system under salinity in these halophytes. showed highest APX and SOD activity followed by . Most efficient enzyme in degrading hydrogen peroxide i.e. CAT showed highest activity in followed by and , whereas and showed higher POX activity. Significant variability in HO and MDA content was also observed. These results possibly suggest higher inbuilt genetic potential of these halophytes to combat high salinity induced oxidative stress via higher antioxidant activities. : Halophytic plant adopt different strategies to cope up with the toxic ions and our studies show that the induction of antioxidant defense system to scavenge ROS, alongwith structural modifications in terms of lipid peroxidation and compartmentalization of toxic ions are the main strategies for tighter control of ion fluxes in the studied halophytes.
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http://dx.doi.org/10.1080/15226514.2021.1874289DOI Listing
February 2021

Biopolymer production using volatile fatty acids as resource: Effect of feast-famine strategy and lignin reinforcement.

Bioresour Technol 2021 Apr 20;326:124736. Epub 2021 Jan 20.

School of Civil and Environmental Engineering, Yonsei University, Seoul 03722, Republic of Korea. Electronic address:

The present study aimed to investigate the biopolymer production using VFA's as carbon source through feast and famine strategy in a sequencing batch reactor. Famine condition with nutrients and oxygen limitation resulted in high polyhydroxybutyrate yield (PHB: 2.65 ± 0.012 g/L; 0.36 ± 0.015 gPHB/gVFA) than feast mode (0.26 ± 0.02 g/L; 0.034 ± 0.013 gPHB/gVFA). Repeated batch operations induced substrate consumption, wherein acetate utilization was high in both the conditions (feast: 83%, famine 74%) followed by butyrate (feast: 74%, famine 72%). Besides, high biomass concentration was also observed in feast condition (3.45 ± 0.14 g/L VSS), while oxygen and nutrients limitation in famine mode regulated the carbon use for biomass growth (2.46 ± 0.15 g/L VSS). Further, PHB grafting with lignin (3% and 5%) exhibited increased thermal stability than pristine PHB. Biopolymer production using VFA's as carbon source and utilization of lignin as functional filler for strengthening PHB offer lignin valorization also wider its applications specifically in the biomedical field.
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http://dx.doi.org/10.1016/j.biortech.2021.124736DOI Listing
April 2021

Spices and herbs: Potential antiviral preventives and immunity boosters during COVID-19.

Phytother Res 2021 Jan 29. Epub 2021 Jan 29.

Dairy Microbiology Division, National Dairy Research Institute, ICAR, Karnal, India.

A severe acute respiratory syndrome is an unusual type of contagious pneumonia that is caused by SARS coronavirus. At present, the whole world is trying to combat this coronavirus disease and scientific communities are putting rigorous efforts to develop vaccines. However, there are only a few specific medical treatments for SARS-CoV-2. Apart from other public health measures taken to prevent this virus, we can boost our immunity with natural products. In this article, we have highlighted the potential of common spices and herbs as antiviral agents and immunity boosters. A questionnaire-based online survey has been conducted on home remedies during COVID-19 among a wide range of peoples (n-531) of different age groups (13-68 years) from various countries. According to the survey, 71.8% of people are taking kadha for combating infection and boosting immunity. Most people (86.1%) think that there is no side effect of kadha while 13.9% think vice versa. A total of 93.6% of people think that spices are helpful in curing coronavirus or other viral infection as well as boosting immunity. Most people are using tulsi drops, vitamin C, and chyawanprash for boosting their immunity. Therefore, we conclude from the survey and available literature that spices and herbs play a significant role against viral infections.
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http://dx.doi.org/10.1002/ptr.7019DOI Listing
January 2021

Can Polyether Ether Ketone Dethrone Titanium as the Choice Implant Material for Metastatic Spine Tumor Surgery?

World Neurosurg 2021 Jan 26;148:94-109. Epub 2021 Jan 26.

Department of Radiation Oncology, National University Health System, Singapore.

Instrumentation during metastatic spine tumor surgery (MSTS) provides stability to the spinal column in patients with pathologic fracture or iatrogenic instability produced while undergoing extensive decompression. Titanium is the current implant material of choice in MSTS. However, it hinders radiotherapy planning and generates artifacts, with magnetic resonance imaging and computed tomography scans used for postoperative evaluation of tumor recurrence and/or complications. The high modulus of elasticity of titanium (110 GPa) results in stress shielding, which may lead to construct failure at the bone-implant interface. Polyether ether ketone (PEEK), a thermoplastic polymer, is an emerging alternative to titanium for use in MSTS. The modulus of elasticity of PEEK (3.6 GPa) is close to that of cortical bone (17-21 GPa), resulting in minimal stress shielding. Its radiolucent and nonmetallic properties cause minimal interference with magnetic resonance imaging and computed tomography scans. PEEK also causes low-dose perturbation for radiotherapy planning. However, PEEK has reduced bioactivity with bone and lacks sufficient rigidity to be used as rods in MSTS. The reduced bioactivity of PEEK may be addressed by 1) surface modification (introducing porosity or bioactive coating with hydroxyapatite [HA] or titanium) and 2) forming composites with HA/titanium. The mechanical properties of PEEK may be improved by forming composites with HA or carbon fiber. Despite these modifications, all PEEK and PEEK-based implants are difficult to handle and contour intraoperatively. Our review provides a comprehensive overview of PEEK and modified PEEK implants, with a description of their properties and limitations, potentially serving as a basis for their future development and use in MSTS.
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http://dx.doi.org/10.1016/j.wneu.2021.01.059DOI Listing
January 2021

Cesium lead bromide quantum dots induced effects on performance of copper phthalocyanine based organic field-effect transistors.

Nanotechnology 2021 Jan 27. Epub 2021 Jan 27.

Physics Department Science Faculty, University of Allahabad Faculty of Science, Allahabad, Uttar Pradesh, INDIA.

Highly luminescent all-inorganic Cesium Lead Bromide (CsPbBr3) perovskite quantum dots (QDs) have been intensively used as photo sensitizer in optoelectronic devices, moreover, p-type small organic molecule copper phthalocyanine (CuPc) also widely used as a photoactive material in solar cells, organic field effect transistors (OFETs), etc. Herein, the CsPbBr3-QDs/CuPc heterostructure has been prepared to study the effect of CsPbBr3-QDs on CuPc. The optical properties of both CuPc and QDs/CuPc heterostructure have been compared and contrasted using UV-vis absorbance and photoluminescence (PL) measurements. Further, to study electronic and charge transfer features, we have fabricated field effect transistors (FETs) on both pristine CuPc and QDs/CuPc heterostructure thin films and studied their photo-responsive electrical characteristics. Both pristine and QDs/CuPc based FETs show enhancement in current and mobility under illumination. The enhancement in current and mobility of QDs/CuPc based FETs is due to a large number of photoexcited charge carriers. We also observed that the current and mobility in QDs/CuPc heterostructure based FET are lower than that of pristine CuPc based FET. This can be explained by the n-type doping effect of CsPbBr3 QDs on CuPc which reduces the accumulation of holes in the active p-channel near the insulating layer and charges are transferred from QDs to CuPc. Thus, we have observed the charge transfer effect for CsPbBr3 QDs/CuPc heterostructure which can be used in optoelectronic devices.
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http://dx.doi.org/10.1088/1361-6528/abe070DOI Listing
January 2021

Prevalence and Symptom Characteristics of Irritable Bowel Syndrome Among Bronchial Asthma Patients in Pakistan.

Cureus 2020 Dec 22;12(12):e12231. Epub 2020 Dec 22.

Internal Medicine, Jinnah Postgraduate Medical Centre, Karachi, PAK.

Introduction: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that leads to a variety of symptoms including abdominal discomfort and change in stool frequency and consistency. Asthma is a common disease of the airway. Some studies have suggested that a relationship between IBS and asthma exist, while others have contradicted the claim. This study aims to determine the prevalence of IBS in asthmatic patients and compare their symptoms with symptoms of IBS patients in non-asthmatic patients.

Methodology: In this case-control study, 100 known and documented asthmatic patients were included as cases, and 100 non-asthmatic healthy patients were included as controls from July to August 2019. These patients were given a questionnaire based on ROME II criteria for the diagnosis of IBS. Prevalence and symptoms of IBS were compared between cases and controls. A probability level,  < 0.05 was considered significant.  Result: IBS was found in 41 out of 100 asthma patients (41%) and 18 out of 100 controls (18%) with a P-value of 0.0005 and was more common in females in both asthmatic (63.41%) and non-asthmatic patients (66.66%). Symptoms such as abdominal pain/distress (63.41% vs. 11.11%, P-value: 0.0013) and bloating (82.92% vs. 33.33%, P-value: 0.0005) were significantly higher in asthmatic patient with IBS compared to non-asthmatic patient with IBS.

Conclusion: Prevalence of IBS among asthma patients was significantly higher as compared to non-asthmatics. Routine screening of asthma patients and further studies to understand the pathogenesis underlying association between IBS and asthma should be conducted to detect and manage such patients effectively.
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http://dx.doi.org/10.7759/cureus.12231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819454PMC
December 2020

Impact of poor evidence management on DNA profiling in sexual assault and homicide: A case report.

Med Leg J 2021 Mar 21;89(1):58-60. Epub 2021 Jan 21.

Forensic Science Laboratory, Home Department, Government of NCT of Delhi, Delhi, India.

Increasing numbers of female victims of violent sexual assaults are being murdered with the aim of concealing the identity of the perpetrator. Proper handling and analysis of evidence is very important in gaining a conviction in many criminal cases. After evidence is collected, due precautions must be taken to ensure that the integrity of the sample is maintained, and chances of contamination are minimised. This paper presents a case study where improper handling of biological evidence led to loss of evidentiary value, and the semen could not be located on the vaginal swabs and victim's garments due to improper preservation of samples. However, the DNA from the nail of a decomposed finger helped identify the victim, and the suspect was apprehended based on the clues given by her family.
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http://dx.doi.org/10.1177/0025817220966487DOI Listing
March 2021

Analysis of unplanned hospital readmissions up to 2-years after metastatic spine tumour surgery.

Eur Spine J 2021 Jan 18. Epub 2021 Jan 18.

Department of Orthopaedic Surgery, National University Health System, Level 11 Tower Block, 1E, Lower Kent Ridge Road, Singapore, 119228, Singapore.

Purpose: The aim of this study was to investigate rates, causes, and risk factors of unplanned hospital readmissions (UHR) within 30 days, 90 days, 1 year and 2 years after metastatic spine tumour surgery (MSTS) to augment multi-disciplinary treatment planning and improve patient education.

Methods: We retrospectively reviewed 272-patients who underwent MSTS between 2005 and 2016. Hospital records were utilised to obtain demographics, oncological, procedural details, and postoperative outcomes. All UHR within 2 years were reviewed. Primary outcomes were rates, causes, and risk factors of UHR. Risk factors for UHR were evaluated utilising multivariate logistic regression analysis.

Results: Thirty-day, 90 day, 1 year, and 2 year UHR-rates after MSTS were 17.2%, 31.1%, 46.2%, and 52.7%, respectively. Lung cancer primaries had the highest UHR-events (24.7%) whilst renal/thyroid displayed the least (6.6%). Disease-related causes (16.2%) were the most common reason for readmissions across all timeframes, followed by respiratory (13.7%) and progression of metastatic spine disease (12.7%). Urological conditions accounted for majority of readmissions within 30-days; disease-related causes, symptomatic spinal metastases, and respiratory conditions represented the most common causes at 30-90 days, 90 days-1 year, and 1-2 years, respectively. An ECOG >1 (p = 0.057), CCI >7 (p = 0.01), and primary lung tumour (p = 0.02) significantly increased UHR-risk on multivariate analysis.

Conclusion: Seventy-four percent of patients had at least one UHR within 2 years of MSTS and majority were secondary to disease-related causes. Majority of first UHR occurred between 30 and 90 days post-surgery. Local disease progression and overall disease progression account for the highest UHR-events at 90 days-1 year and 1-2 year timeframes, respectively. We define UHR in specific timeframes, thus enabling better surveillance and reducing unnecessary morbidity.
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http://dx.doi.org/10.1007/s00586-021-06723-5DOI Listing
January 2021

Issues in cyanobacterial taxonomy: comprehensive case study of unbranched, false branched and true branched heterocytous cyanobacteria.

FEMS Microbiol Lett 2021 Jan 16. Epub 2021 Jan 16.

Department of Botany, Institute of Science, Banaras Hindu University, Varanasi - 221005, India.

The order Nostocales is represented by morphologically diverse forms with respect to the branching patterns and polarity of the filaments. With growing understanding of taxonomy and systematics, members of the order Nostocales have also undergone multiple taxonomic revisions. The last decade has seen a surge in the description of new genera and families within the order Nostocales. In this study, we discuss the taxonomic status of all the newly described and reclassified taxa of some of the prominent morphological forms within the order Nostocales by constructing comprehensive phylogenetic trees. Further, we propose certain strategies that would contribute to resolving the taxonomic complexities arising due to inadequate taxon sampling.
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http://dx.doi.org/10.1093/femsle/fnab005DOI Listing
January 2021

Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region.

Indian J Crit Care Med 2020 Dec;24(12):1180-1184

Department of Biochemistry, Maulana Azad Medical College, New Delhi, India.

Aims And Objectives: Serum adrenomedullin (ADM) as a prognostic biomarker to study the gender-related differences in mortality pattern and its correlation with the sequential organ failure assessment (SOFA) and acute physiologic assessment and chronic health evaluation II (APACHE II) scores in patients of sepsis.

Measurements And Main Results: Eighty patients of sepsis of which 36 were males and 44 were females, were taken in the study as per sepsis III guidelines. They were followed up for a period of 28 days. Serum ADM was measured on day 1 and day 5. The endpoint was mortality or survival at day 28 after admission. The death rate among males was higher, with 23 of the total 36 (63.89%) patients having died when compared with females in which 25 patients out of 44 (56.82%) had died. The observed mortality rates correlated well with average APACHE II scores. The average APACHE II score was slightly higher in males (29 ± 8.97) when compared with females (27.02 ± 8.69). Similarly, day 1 SOFA and mean SOFA values were higher in males (10.22 ± 5.36) and (10.73 ± 6.01) when compared with females (8.27 ± 4.79) and (8.89 ± 5.6), respectively. Males despite having higher mortality rates, higher APACHE II, SOFA, and mean SOFA values were still having less mean levels of serum ADM (454.40 ± 81.13 pg/mL) when compared with females (479.62 ± 126.97 pg/mL).

Conclusion: Adrenomedullin is a protective neurohormone with antibacterial and anti-inflammatory properties. It is elevated in all patients with sepsis but the rise is more so in the female when compared with males. Higher ADM levels in females may suggest the protective effect of ADM as a part of the general protective neurohormonal stress response, which may explain the low death rate in females in sepsis.

How To Cite This Article: Daga MK, Kumar L, Mawari G, Kumar N, Singh S, Mishra TK. Adrenomedullin and Its Possible Role in Improved Survival in Female Patients with Sepsis: A Study in the South East Asian Region. Indian J Crit Care Med 2020;24(12):1180-1184.
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http://dx.doi.org/10.5005/jp-journals-10071-23672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775928PMC
December 2020

Thioether-linked dihydropyrrol-2-one analogues as PqsR antagonists against antibiotic resistant Pseudomonas aeruginosa.

Bioorg Med Chem 2021 Feb 1;31:115967. Epub 2021 Jan 1.

School of Chemistry, The University of New South Wales, NSW 2052 Sydney, Australia. Electronic address:

The Pseudomonas quinolone system (pqs) is one of the key quorum sensing systems in antibiotic-resistant P. aeruginosa and is responsible for the production of virulence factors and biofilm formation. Thus, synthetic small molecules that can target the PqsR (MvfR) receptor can be utilized as quorum sensing inhibitors to treat P. aeruginosa infections. In this study, we report the synthesis of novel thioether-linked dihydropyrrol-2-one (DHP) analogues as PqsR antagonists. Compound 7g containing a 2-mercaptopyridyl linkage effectively inhibited the pqs system with an IC of 32 µM in P. aeruginosa PAO1. Additionally, these inhibitors significantly reduced bacterial aggregation and biofilm formation without affecting planktonic growth. The molecular docking study suggest that these inhibitors bind with the ligand binding domain of the MvfR as a competitive antagonist.
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http://dx.doi.org/10.1016/j.bmc.2020.115967DOI Listing
February 2021

Highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives and interaction analysis with putative target lactate dehydrogenase.

J Biomol Struct Dyn 2021 Jan 8:1-16. Epub 2021 Jan 8.

Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India.

Malaria infection caused by is majorly responsible for millions of deaths in humans every year. Moreover, a rapid increase in resistance to existing drugs has posed an urgent need for new anti-malarials. Herein, we report the highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives, inspired from naturally occurring dependensin against chloroquine (CQ) sensitive and resistant strains. Chemically synthesized, four dependensin analogs exhibited growth inhibition at nanomolar concentrations ranging from 63.96 to 725.8 nM by blocking the parasite development at the ring and early trophozoite stages. The growth inhibitory activity of dependensin analogs was correlated with their anti-plasmodial lactate dehydrogenase activity by computational analysis. Molecular docking, 50 ns simulation and a 2D-Quantitative Structure-Activity Relationship (2D-QSAR) modelling revealed the interaction with their putative target lactate dehydrogenase (PfLDH). Here, developing the predictive 2D descriptors such as thermodynamic, spatial, electronic, and topological with multiple linear regression analysis (MLRA), the structural requirements for potent and selective PfLDH inhibitory activity has been identified. The strong binding of compound to the catalytic Nicotinamide adenine dinucleotide (NADH) binding pocket of the PfLDH further supported the PfLDH targeting potential of dependensin analogs. Overall, this study revealed a highly potent anti-malarial activity of benzopyrano(4,3-b)benzopyran derivatives with their putative anti-PfLDH activity. Communicated by Ramaswamy H. Sarma.
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http://dx.doi.org/10.1080/07391102.2020.1868336DOI Listing
January 2021

Electro-fermentation for biofuels and biochemicals production: Current status and future directions.

Bioresour Technol 2021 Mar 23;323:124598. Epub 2020 Dec 23.

School of Civil and Environmental Engineering, Yonsei University, Seoul 03722, Republic of Korea. Electronic address:

Electro-fermentation is an emerging bioporcess that could regulate the metabolism of electrochemically active microorganisms. The provision of electrodes for the fermentation process that functions as an electron acceptor and supports the formation and transportation of electrons and protons, consequently producing bioelectricity and value-added chemicals. The traditional method of fermentation has several limitations in usability and economic feasibility. Subsequently, a series of metabolic processes occurring in conventional fermentation processes are most often redox misaligned. In this regard, electro-fermentation emerged as a hybrid technology which can regulate a series of metabolic processes occurring in a bioreactor by regulating the redox instabilities and boosting the overall metabolic process towards high biomass yield and enhanced product formation. The present article deals with microorganisms-electrode interactions, various types of electro-fermentation systems, comparative evaluation of pure and mixed culture electro-fermentation application, and value-added fuels and chemical synthesis.
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http://dx.doi.org/10.1016/j.biortech.2020.124598DOI Listing
March 2021

Readmission-Free Survival Analysis in Metastatic Spine Tumour Surgical Patients: A Novel Concept.

Ann Surg Oncol 2021 Jan 3. Epub 2021 Jan 3.

Department of Radiation Oncology, National University Health System, Singapore, Singapore.

Background: Outcomes commonly used to ascertain success of metastatic spine tumour surgery (MSTS) are 30-day complications/mortality and overall/disease-free survival. We believe a new, effective outcome indicator after MSTS would be the absence of unplanned hospital readmission (UHR) after index discharge. We introduce the concept of readmission-free survival (ReAFS), defined as 'the time duration between hospital discharge after index operation and first UHR or death'. The aim of this study is to identify factors influencing ReAFS in MSTS patients.

Patients And Methods: We retrospectively analysed 266 consecutive patients who underwent MSTS between 2005 and 2016. Demographics, oncological characteristics, procedural, preoperative and postoperative details were collected. ReAFS of patients within 2 years or until death was reviewed. Perioperative factors predictive of reduced ReAFS were evaluated using multivariate regression analysis.

Results: Of 266 patients, 230 met criteria for analysis. A total of 201 had UHR, whilst 1 in 8 (29/230) had no UHR. Multivariate analysis revealed that haemoglobin ≥ 12 g/dL, ECOG score of ≤ 2, primary prostate, breast and haematological cancers, comorbidities ≤ 3, absence of preoperative radiotherapy and shorter postoperative length of stay significantly prolonged the time to first UHR.

Conclusions: Readmission-free survival is a novel concept in MSTS, which relies on patients' general condition, appropriateness of interventional procedures and underlying disease burden. Additionally, it may indicate the successful combination of a multi-disciplinary treatment approach. This information will allow oncologists and surgeons to identify patients who may benefit from increased surveillance following discharge to increase ReAFS. We envisage that ReAFS is a concept that can be extended to other surgical oncological fields.
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http://dx.doi.org/10.1245/s10434-020-09404-7DOI Listing
January 2021

A novel hospital capacity versus clinical justification triage score (CCTS) for prioritization of spinal surgeries in the "new normal state" of the COVID-19 pandemic.

Eur Spine J 2021 Jan 2. Epub 2021 Jan 2.

Department of Orthopaedic Surgery, University Spine Centre, National University Hospital, National University Health System, 1E Kent Ridge Road, Singapore, 119228, Singapore.

Introduction: During the Coronavirus disease 2019 outbreak, while healthcare systems and hospitals are diverting their resources to combat the pandemic, patients who require spinal surgeries continue to accumulate. The aim of this study is to describe a novel hospital capacity versus clinical justification triage score (CCTS) to prioritize patients who require surgery during the "new normal state" of the COVID-19 pandemic.

Methodology: A consensus study using the Delphi technique was carried out among clinicians from the Orthopaedic Surgery, Neurosurgery, and Anaesthesia departments. Three rounds of consensus were carried out via survey and Webinar discussions.

Results: A 50-points score system consisting of 4 domains with 4 subdomains was formed. The CCTS were categorized into the hospital capacity, patient factors, disease severity, and surgery complexity domains. A score between 30 and 50 points indicated that the proposed operation should proceed without delay. A score of less than 20 indicates that the proposed operation should be postponed. A score between 20 and 29 indicates that the surgery falls within a grey area where further discussion should be undertaken to make a joint justification for approval of surgery.

Conclusion: This study is a proof of concept for the novel CCTS scoring system to prioritize surgeries to meet the rapidly changing demands of the COVID-19 pandemic. It offers a simple and objective method to stratify patients who require surgery and allows these complex and difficult decisions to be unbiased and made transparently among surgeons and hospital administrators.
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http://dx.doi.org/10.1007/s00586-020-06679-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778399PMC
January 2021

An overview of the tumors affecting the spine-inside to out.

Neurooncol Pract 2020 Nov 18;7(Suppl 1):i10-i17. Epub 2020 Nov 18.

Department of Radiation Oncology, National University Health System, Singapore.

Spine tumors may arise within or surrounding the spinal cord and/or vertebral column. Spinal tumors can be benign or malignant. Based on their epicenter, they may be classified as intradural-intramedullary, intradural-extramedullary, or extradural. Of these, extradural lesions are the most common, and are typically metastatic. Primary bone tumors of the spinal column comprise 5% of all primary skeletal tumors. The majority of primary spinal column tumors are benign, with malignant tumors comprising only 20%. Overall, spine metastases are the most common malignant spine tumor, and these usually arise from primaries such as lung, breast, and prostate cancers. The advent of improved systemic therapies leading to improved survival and the frequent use of imaging has positioned metastatic spine disease as the new epidemic in oncology. For spine tumors, establishing the correct diagnosis is heavily reliant on magnetic resonance imaging and histological confirmation. In this review, we will provide an overview of the epidemiology, radiological and histopathological features, and the natural history of key primary (benign and malignant) spinal cord and column tumors and metastatic spine tumors. Treatment principles for primary spinal cord or column tumors are aimed toward curative resection, whereas palliative resection forms the treatment principle for most metastatic tumors.
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http://dx.doi.org/10.1093/nop/npaa049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705529PMC
November 2020

The "Spinal Metastasis Invasiveness Index": A Novel Scoring System to Assess Surgical Invasiveness.

Spine (Phila Pa 1976) 2020 Dec 1. Epub 2020 Dec 1.

Department of Orthopaedics, Spine Surgery, Sonnenhof Spital, Buchserstrasse 30, 3006 Bern, Switzerland.

Study Design: Retrospective review.

Objective: The aim of this study was to develop a surgical invasiveness index for metastatic spine tumor surgery (MSTS) that can serve as a standardized tool in predicting intraoperative blood loss and surgical duration; for the purpose of ascertaining resource requirements and aiding in patient education.

Summary Of Background Data: Magnitude of surgery is important in the metastatic spine disease (MSD) population since these patients have a continuing postoperative oncological process; a consideration that must be taken into account to maintain or improve quality of life. Surgical invasiveness indices have been established for general spine surgery, adult deformity, and cervical deformity, but not yet for spinal metastasis.

Methods: Demographic, oncological, and procedural data were collected from consecutive patients that underwent MSTS. Binary logistic regression, using median values for surgical duration and intraoperative estimated blood loss (EBL), was used to determine statistical significance of variables to be included in the "spinal metastasis invasiveness index" (SMII). The corresponding weightage of each of these variables was agreed upon by experienced spine surgeons. Multivariable regression analysis was used to predict operative time and EBL while controlling for demographical, procedural, and oncological characteristics.

Results: Two hundred and sixty-one MSD patients were included with a mean age of 59.7-years and near equal sex distribution. The SMII strongly predicted extended surgical duration (R = 0.28, P < 0.001) and high intraoperative blood loss (R = 0.18, P < 0.001). When compared to a previously established surgical invasiveness index, the SMII accounted for more variability in the outcomes. For every unit increase in score, there was a 42-mL increase in mean blood loss (P < 0.001) and 5-minute increase in mean operative time (P < 0.001).

Conclusion: Long surgical duration and high blood loss were strongly predicted by the newly developed SMII. The use of the SMII may aid in preoperative risk assessment with the goal of improving patient outcomes and quality of life.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000003823DOI Listing
December 2020

River water treatment using electrocoagulation for removal of acetaminophen and natural organic matter.

Chemosphere 2020 Oct 9:128571. Epub 2020 Oct 9.

Department of Civil and Environmental Engineering, Birla Institute of Technology, Mesra, Ranchi, 835215, Jharkhand, India. Electronic address:

Electrocoagulation (EC) was assessed for removal of acetaminophen and natural organic matter (measured as UV) from river water. Process was assessed for time, electrode materials, inter electrode distance, and voltage. Best conditions for removal of acetaminophen and UV absorbance were 60 min reaction time, aluminum-aluminum electrodes, 2 cm inter electrode distance, and 9 V. Acetaminophen tested at 1, 2, 5, 10, and 20 mg L showed that treatment efficiency decreased as the concentration increased. The main mechanism for removal of acetaminophen was H bonding with Al(OH) flocs; this was confirmed by XRD and FT-IR spectrum. Pseudo-second order kinetics model exhibited a good fit on experimental data for acetaminophen removal at different concentrations. Univariate ANOVA indicated statistically significant difference between treatments for acetaminophen removal (F = 136, P = <0.001). A significant linear correlation was found between UV absorbance and acetaminophen removal at different concentrations. Preliminary analysis suggest that EC will cost US$ 0.22/m for river water treatment. The lab-scale EC process was compared with a full-scale water treatment plant for removal of natural organic matter. Water treatment plant after multiple levels of purification was not able to fully remove UV absorbance whereas EC treatment showed good efficiency.
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http://dx.doi.org/10.1016/j.chemosphere.2020.128571DOI Listing
October 2020

ASO Author Reflections: Readmission-Free Survival: A Novel Clinical and Quality Outcome Measure for Metastatic Spine Tumor Surgical Patients.

Authors:
Naresh Kumar

Ann Surg Oncol 2020 Dec 1. Epub 2020 Dec 1.

Department of Orthopaedic Surgery, National University Health System, Level 11 Tower Block, 1E, Lower Kent Ridge Road, Singapore, 119228, Singapore.

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http://dx.doi.org/10.1245/s10434-020-09420-7DOI Listing
December 2020

In situ differentiation of human-induced pluripotent stem cells into functional cardiomyocytes on a coaxial PCL-gelatin nanofibrous scaffold.

Mater Sci Eng C Mater Biol Appl 2021 Jan 11;118:111354. Epub 2020 Aug 11.

Department of Emergency Medicine, Wexner Medical Center, The Ohio State University, Columbus, OH, USA; Department of Physiology and Cell Biology, Wexner Medical Center, The Ohio State University, Columbus, OH, USA; Dorothy M. Davis Heart & Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, USA. Electronic address:

Human-induced pluripotent stem cells (hiPSCs) derived cardiomyocytes (hiPSC-CMs) have been explored for cardiac regeneration and repair as well as for the development of in vitro 3D cardiac tissue models. Existing protocols for cardiac differentiation of hiPSCs utilize a 2D culture system. However, the efficiency of hiPSC differentiation to cardiomyocytes in 3D culture systems has not been extensively explored. In the present study, we investigated the efficiency of cardiac differentiation of hiPSCs to functional cardiomyocytes on 3D nanofibrous scaffolds. Coaxial polycaprolactone (PCL)-gelatin fibrous scaffolds were fabricated by electrospinning and characterized using scanning electron microscopy (SEM) and fourier transform infrared (FTIR) spectroscopy. hiPSCs were cultured and differentiated into functional cardiomyocytes on the nanofibrous scaffold and compared with 2D cultures. To assess the relative efficiencies of both the systems, SEM, immunofluorescence staining and gene expression analyses were performed. Contractions of differentiated cardiomyocytes were observed in 2D cultures after 2 weeks and in 3D cultures after 4 weeks. SEM analysis showed no significant differences in the morphology of cells differentiated on 2D versus 3D cultures. However, gene expression data showed significantly increased expression of cardiac progenitor genes (ISL-1, SIRPA) in 3D cultures and cardiomyocytes markers (TNNT, MHC6) in 2D cultures. In contrast, immunofluorescence staining showed no substantial differences in the expression of NKX-2.5 and α-sarcomeric actinin. Furthermore, uniform migration and distribution of the in situ differentiated cardiomyocytes was observed in the 3D fibrous scaffold. Overall, our study demonstrates that coaxial PCL-gelatin nanofibrous scaffolds can be used as a 3D culture platform for efficient differentiation of hiPSCs to functional cardiomyocytes.
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http://dx.doi.org/10.1016/j.msec.2020.111354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708677PMC
January 2021

Impact of Air Pollution and Weather on Dry Eye.

J Clin Med 2020 Nov 20;9(11). Epub 2020 Nov 20.

Bascom Palmer Eye Institute, University of Miami, Miami, FL 33136, USA.

Air pollution has broad effects on human health involving many organ systems. The ocular surface is an excellent model with which to study the effects of air pollution on human health as it is in constant contact with the environment, and it is directly accessible, facilitating disease monitoring. Effects of air pollutants on the ocular surface typically manifest as dry eye (DE) symptoms and signs. In this review, we break down air pollution into particulate matter (organic and inorganic) and gaseous compounds and summarize the literature regarding effects of various exposures on DE. Additionally, we examine the effects of weather (relative humidity, temperature) on DE symptoms and signs. To do so, we conducted a PubMed search using key terms to summarize the existing literature on the effects of air pollution and weather on DE. While we tried to focus on the effect of specific exposures on specific aspects of DE, environmental conditions are often studied concomitantly, and thus, there are unavoidable interactions between our variables of interest. Overall, we found that air pollution and weather conditions have differential adverse effects on DE symptoms and signs. We discuss these findings and potential mitigation strategies, such as air purifiers, air humidifiers, and plants, that may be instituted as treatments at an individual level to address environmental contributors to DE.
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http://dx.doi.org/10.3390/jcm9113740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699870PMC
November 2020

Validity of Sequential Organ Failure Assessment and Quick Sequential Organ Failure Assessment in Assessing Mortality Rate in the Intensive Care Unit With or Without Sepsis.

Cureus 2020 Oct 20;12(10):e11071. Epub 2020 Oct 20.

Surgery, Civil Hospital Karachi, Dow University of Health Sciences, Karachi, PAK.

Introduction Sepsis and septic shock (sepsis-induced hypotension not improved by adequate fluid resuscitation) are among the most common reasons for admission to an intensive care unit (ICU) and display high mortality rates. Different scoring systems are used to diagnose and predict the mortality of patients having sepsis. This study aims to validate the prognostic accuracy of Sequential Organ Failure Assessment (SOFA) and Quick Sequential Organ Failure Assessment (qSOFA) in determining the mortality of both septic and non-septic patients. Materials and methods This retrospective cohort study was conducted in May 2018 in the Surgical Intensive Care Unit (SICU) of a tertiary care hospital in Karachi, Pakistan. Past 200 patient records, from January 2018 to April 2018, were examined, and 20 records were discarded due to insufficient data. Sufficient observational data were collected, which was used to assess the validity of the SOFA and qSOFA in determining the mortality rate of sepsis. A comparison of the two modalities was made. Results Out of the 200 patients, 180 were enrolled. Data from their entire ICU stay were used to calculate their initial, highest, and mean SOFA and qSOFA. Mean SOFA score up to nine correlated with a mortality rate of up to <79%, while scores 10 and above predicted a 100% mortality rate. A mean qSOFA score of three predicted a 67% mortality rate. Univariate logistic analysis performed with odds ratio showed that the mean qSOFA score was in comparison more closely able to predict mortality, followed by mean SOFA score (p values < 0.01). Conclusions This study concluded that both SOFA and qSOFA scores are good predictors of mortality. However, qSOFA is more closely accurate in predicting mortality than SOFA. But further analysis with larger sample size for a longer duration as well as the application of these scores in the emergency departments and general wards can prove the precision of this study.
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http://dx.doi.org/10.7759/cureus.11071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676951PMC
October 2020

Effect of e-learning methods on Dental education: An observational study.

J Educ Health Promot 2020 28;9:235. Epub 2020 Sep 28.

Department of Periodontics, Vishnu Dental College, Bhimavaram, Andhra Pradesh, India.

Background: The progress in the usage of technology in hardware, software, and cost-effective Internet connectivity enable the availability of science-related information and its usage in all the developing countries. Hence, in this practical world, there should be a need to implement effective and affordable dental education strategies to attain oral health for all in the coming years.

Objective: The aim of this study is to reduce the need to teach theory-based, on-site classes, e-learning came into existence. E-learning for dental education may alleviate the burden of severe health worker shortages and deliver affordable access to high-quality dental education.

Methodology: Evaluation and assessment methods were done to know the effectiveness of e-learning in dental education by conducting continuing dental education on newer materials and methods, assignments/formative assessments and by open discussions of case descriptions and their treatment modalities through Edmodo app in our dental institute. Effect on knowledge, skills, attitudes, and satisfaction levels of dental students compared to other traditional methods.

Results: Dental e-learning has the capacity to develop into a leading-edge to strengthen clinical training skills among dental students by conducting continuing dental education, assignments, formative assessments, case descriptions, and their treatment modalities through e-learning are the best ways to improve quantity and quality in dental education.

Conclusion: The probable prospective of e-learning could be innovative or revolutionary because this helps in both theoretical-related and clinical-related advancements, and it is possible only with e-learning in developing countries to meet the quality in education.
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http://dx.doi.org/10.4103/jehp.jehp_209_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652085PMC
September 2020

Nanoscale characterization of plasma functionalized graphitic flakes using tip-enhanced Raman spectroscopy.

J Chem Phys 2020 Nov;153(18):184708

National Physical Laboratory, Hampton Road, Teddington TW11 0LW, United Kingdom.

The chemical functionalization of graphene nanomaterials allows for the enhancement of their properties for novel functional applications. However, a better understanding of the functionalization process by determining the amount and location of functional groups within individual graphene nanoplatelets remains challenging. In this work, we demonstrate the capability of tip-enhanced Raman spectroscopy (TERS) to investigate the degree and spatial variability of the appearance of disorder in graphitic nanomaterials on the nanoscale with three different levels of nitrogen functionalization. TERS results are in excellent agreement with those of confocal Raman spectroscopy and chemical analysis, determined using x-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry, of the functionalized materials. This work paves the way for a better understanding of the functionalization of graphene and graphitic nanomaterials at the nano-scale, micro-scale, and macro-scale and the relationship between the techniques and how they relate to the changes in material properties of industrial importance.
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http://dx.doi.org/10.1063/5.0024370DOI Listing
November 2020

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

Ann Am Thorac Soc 2020 Nov 9. Epub 2020 Nov 9.

University of Utah School of Medicine, 12348, Study Design and Biostatistics Center and Division of Epidemiology, Salt Lake City, Utah, United States.

Rationale: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates.

Objective: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19.

Methods: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective.

Results: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury.

Conclusions: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation.

Clinical Trial Registration: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.
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http://dx.doi.org/10.1513/AnnalsATS.202008-940OCDOI Listing
November 2020

Interaction of the surface bound antimicrobial peptides melimine and Mel4 with .

Biofouling 2020 10 8;36(9):1019-1030. Epub 2020 Nov 8.

School of Optometry and Vision Science, University of New South Wales, Sydney, Australia.

Melimine and Mel4 are cationic antimicrobial peptides which can resist biofilm development once bound to biomaterials. The aim of the current study was to determine the mode of action of bound melimine and Mel4 against The peptides were covalently attached to glass using an azidobenzoic acid linker. The amount of attached peptides was confirmed by XPS and amino acid analysis and their covalent attachment by SDS extraction. The release of autolysins after interaction of with immobilized peptides was determined in cell free supernatants. The interaction of immobilized peptides with lipoteichoic acid was confirmed by ELISA. Membrane damage by surface bound peptides was assessed using DiSC(3)-5 (membrane potential sensitive), Syto-9 (membrane permeable) and PI (membrane impermeable) dyes with fluorescence microscopy. Release of ATP and nucleic acids (DNA/RNA) was measured in the surrounding fluid. Attachment of the peptides resulted in increased N% for melimine (5.4 ± 1.8%) and for Mel4 (4.8 ± 1.8%). The concentrations of immobilised amino acids were 0.297 nmole for melimine and 0.358 nmole for Mel4. SDS extraction released < 15% of peptides from the glass. The immobilized peptides bound ≥ 4 times more LTA than control surfaces. More autolysins (8 ± 2%;  = 0.026) were released from Mel4 than melimine or control surfaces. Membrane depolarization occurred at 15 min and was associated with a reduction in bacterial viability ≥ 37% for both peptides ( < 0.001). Disruption of the membrane potential resulted in loss of ATP from melimine (0.9 ± 0.4 nM) or Mel4 (0.6 ± 0.3 nM) coated surfaces compared to control ( < 0.001). Melimine coatings yielded 27 ± 11% ( = 0.026) and Mel4 gave 17 ± 12% ( = 0.150) PI stained cells after 4 h. DNA/RNA was released only by melimine coatings (2.1 ± 0.1 times;  = 0.011) compared to process control at 6 h. Both bound peptides resulted in the release of ATP, but only melimine released DNA/RNA while Mel4-coating resulted in the release of autolysins. Since the mode of action of melimine and Mel4 relate to the cell surface, they have potential for the development of infection-resistant implants.
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http://dx.doi.org/10.1080/08927014.2020.1843638DOI Listing
October 2020