Publications by authors named "Haider Ali"

188 Publications

Reduced Fluoroscopy Time With Physician-Controlled Fluoroscopy During Endoscopic Retrograde Cholangiopancreatography: A Community Hospital Experience.

Cureus 2021 Mar 8;13(3):e13771. Epub 2021 Mar 8.

Department of Medicine, Division of Gastroenterology, Advocate Lutheran General Hospital, Park Ridge, USA.

Background and objective Fluoroscopy during endoscopic retrograde cholangiopancreatography (ERCP) is associated with radiation exposure and related health risks. Either the physician or the radiology technologist can activate fluoroscopy during ERCP. The aim of this study was to determine if physician-controlled fluoroscopy is associated with decreased fluoroscopy time, which may correspond to less radiation exposure to patients and staff.  Methods We conducted a single-center, retrospective study; data were collected on ERCP performed using physician-controlled and technologist-controlled fluoroscopy. Fluoroscopy time, procedure complexity level, and Stanford Fluoroscopy Score were compared between the two groups. Results The median fluoroscopy time significantly differed between the two groups with 108 seconds for physician-controlled and 146 seconds for technologist-controlled procedures (p=0.004). The ratio of median fluoroscopy time to procedure complexity level was significantly lower in the physician-controlled group at 73.0 seconds compared to 97.0 seconds in the technologist-controlled group (p=0.002). The ratio of median fluoroscopy time to Stanford Fluoroscopy Score was 25.5 seconds in the physician-controlled group compared to 39.3 seconds in the technologist-controlled group, which was also statistically significant (p<0.001). A subgroup analysis of physicians with advanced training in ERCP also showed a significantly reduced median fluoroscopy time to Stanford Fluoroscopy Complexity Score ratio: 25.5 seconds for physician-controlled versus 35.0 seconds for technologist-controlled (p=0.001). Conclusion The ERCP technique with physician-controlled fluoroscopy may be associated with shorter fluoroscopy time. This may correspond to decreased radiation exposure to patients compared to radiology technologist-controlled fluoroscopy. Further investigations with larger, prospective studies are warranted.
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http://dx.doi.org/10.7759/cureus.13771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026404PMC
March 2021

Anti-aging natural compounds and their role in the regulation of metabolic pathways leading to longevity.

Mini Rev Med Chem 2021 Apr 5. Epub 2021 Apr 5.

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad. Pakistan.

Aging is an unavoidable process, leads to cell senescence due to physiochemical changes in an organism. Anti-aging remedies have always been of great interest since ancient times. The purpose of anti-aging activities is to increase the life span and the quality of life. Anti-aging activities are primarily involved in the therapies of age-related disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), cardiovascular diseases, cancer and chronic obstructive pulmonary diseases. These diseases are triggered by multiple factors that are involved in numerous molecular pathways including telomere shortening, NF-κB pathway, adiponectin receptor pathway, insulin and IGF signaling pathway, AMPK, mTOR and mitochondria dysfunction. Natural products are known as effective molecules to delay the aging process through influencing metabolic pathways and thus ensure an extended lifespan. These natural compounds are being utilized in drug design and development through computational and high throughput techniques for effective pro-longevity drugs. A comprehensive study of natural compounds demonstrated with their anti-aging activities along with databases of natural products for drug designing was executed and summarized in this review article.
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http://dx.doi.org/10.2174/1389557521666210405162006DOI Listing
April 2021

Impacting Water Droplets Can Alleviate Dust from Slanted Hydrophobic Surfaces.

Langmuir 2021 Apr 31;37(14):4355-4369. Epub 2021 Mar 31.

Mechanical Engineering Department, KFUPM, Dhahran 31261, Saudi Arabia.

Water droplet impacting on a slanted dusty hydrophobic surface is examined in relation to dust mitigation from surfaces. Impacting droplet characteristics including droplet spreading/retraction rates, slipping length, and rebound heights are analyzed via high-speed recording and a tracker program. The environmental dust characteristics in terms of size, shape, elemental composition, and surface free energy are evaluated by adopting the analytical methods. The findings reveal that the dynamic characteristics of the impacting droplet on the slanted hydrophobic surface are significantly influenced by the dust particles. The maximum droplet spreading over the dusty surface becomes smaller than that of the nondusty surface. The presence of the dust particles on the slanted hydrophobic surface increases energy dissipation, and the water droplet slipping length over the surface becomes less than that corresponding to the nondusty surface. Impacting droplet fluid infuses over the dust particle surface, which enables mitigation of dust from the surface to the droplet fluid. A dust-mitigated area on the slanted surface is larger than that corresponding to the horizontal surface; in which case, the area ratio becomes almost six-fold, which slightly reduces with increasing Weber number. The optical transmittance of the dust-mitigated surface by the impacting droplet remains high.
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http://dx.doi.org/10.1021/acs.langmuir.1c00436DOI Listing
April 2021

Immunoinformatics and Molecular Docking Studies Predicted Potential Multiepitope-Based Peptide Vaccine and Novel Compounds against Novel SARS-CoV-2 through Virtual Screening.

Biomed Res Int 2021 26;2021:1596834. Epub 2021 Feb 26.

Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, Pakistan.

Background: Coronaviruses (CoVs) are enveloped positive-strand RNA viruses which have club-like spikes at the surface with a unique replication process. Coronaviruses are categorized as major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Nowadays, a new strain of coronaviruses is identified and named as SARS-CoV-2. Multiple cases of SARS-CoV-2 attacks are being reported all over the world. SARS-CoV-2 showed high death rate; however, no specific treatment is available against SARS-CoV-2.

Methods: In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against SARS-CoV-2 for the development of the coronavirus vaccine. Cytotoxic T-lymphocyte and B-cell epitopes were predicted for SARS-CoV-2 coronavirus protein. Multiple sequence alignment of three genomes (SARS-CoV, MERS-CoV, and SARS-CoV-2) was used to conserved binding domain analysis.

Results: The docking complexes of 4 CTL epitopes with antigenic sites were analyzed followed by binding affinity and binding interaction analyses of top-ranked predicted peptides with MHC-I HLA molecule. The molecular docking (Food and Drug Regulatory Authority library) was performed, and four compounds exhibiting least binding energy were identified. The designed epitopes lead to the molecular docking against MHC-I, and interactional analyses of the selected docked complexes were investigated. In conclusion, four CTL epitopes (GTDLEGNFY, TVNVLAWLY, GSVGFNIDY, and QTFSVLACY) and four FDA-scrutinized compounds exhibited potential targets as peptide vaccines and potential biomolecules against deadly SARS-CoV-2, respectively. A multiepitope vaccine was also designed from different epitopes of coronavirus proteins joined by linkers and led by an adjuvant.

Conclusion: Our investigations predicted epitopes and the reported molecules that may have the potential to inhibit the SARS-CoV-2 virus. These findings can be a step towards the development of a peptide-based vaccine or natural compound drug target against SARS-CoV-2.
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http://dx.doi.org/10.1155/2021/1596834DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910514PMC
March 2021

Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection.

Drug Dev Res 2021 Mar 9. Epub 2021 Mar 9.

School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India.

Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
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http://dx.doi.org/10.1002/ddr.21810DOI Listing
March 2021

Coronavirus and its terrifying inning around the globe: The pharmaceutical cares at the main frontline.

Chemosphere 2021 Feb 16;275:129968. Epub 2021 Feb 16.

Department of Agronomy, University of Haripur, Khyber Pakhtunkhwa, Pakistan. Electronic address:

A novel coronavirus (2019-nCoV) is an acute life-threatening disease, emerged in China, which imposed a potentially immense toll in terms of public health emergency due to high infection rate and has a devastating economic impact that attracts the world's attention. After that, on January 30, 2020, it was officially declared as a global pandemic by World Health Organization (WHO). The International Committee on Taxonomy of Viruses (ICTV) recognized it as a Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and the disease named Coronavirus Disease-19 (COVID-19). Several studies have been ameliorated the active role of COVID-19 transmission, etiology, pathogenicity, and mortality rate as serious impact on human life. The symptoms of this disease may include fever, fatigue, cough and some peoples are severely prone to gastrointestinal infection. The elderly and seriously affected peoples are likely concerned with serious outcomes. In this review, we mainly aimed to provide a benchmark summary of the silent characteristics and findings of some candidates for antiviral drugs and immunotherapies such as plasma therapy, cytokine therapy, antibodies, intravenous immunoglobulin, and pharmaceutical health concerns that are related to this disease.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129968DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884917PMC
February 2021

Towards advancing scientific knowledge of climate change impacts on short-duration rainfall extremes.

Philos Trans A Math Phys Eng Sci 2021 Apr 1;379(2195):20190542. Epub 2021 Mar 1.

School of Engineering, Newcastle University, Newcastle upon Tyne, UK.

A large number of recent studies have aimed at understanding short-duration rainfall extremes, due to their impacts on flash floods, landslides and debris flows and potential for these to worsen with global warming. This has been led in a concerted international effort by the INTENSE Crosscutting Project of the GEWEX (Global Energy and Water Exchanges) Hydroclimatology Panel. Here, we summarize the main findings so far and suggest future directions for research, including: the benefits of convection-permitting climate modelling; towards understanding mechanisms of change; the usefulness of temperature-scaling relations; towards detecting and attributing extreme rainfall change; and the need for international coordination and collaboration. Evidence suggests that the intensity of long-duration (1 day+) heavy precipitation increases with climate warming close to the Clausius-Clapeyron (CC) rate (6-7% K), although large-scale circulation changes affect this response regionally. However, rare events can scale at higher rates, and localized heavy short-duration (hourly and sub-hourly) intensities can respond more strongly (e.g. 2 × CC instead of CC). Day-to-day scaling of short-duration intensities supports a higher scaling, with mechanisms proposed for this related to local-scale dynamics of convective storms, but its relevance to climate change is not clear. Uncertainty in changes to precipitation extremes remains and is influenced by many factors, including large-scale circulation, convective storm dynamics andstratification. Despite this, recent research has increased confidence in both the detectability and understanding of changes in various aspects of intense short-duration rainfall. To make further progress, the international coordination of datasets, model experiments and evaluations will be required, with consistent and standardized comparison methods and metrics, and recommendations are made for these frameworks. This article is part of a discussion meeting issue 'Intensification of short-duration rainfall extremes and implications for flash flood risks'.
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http://dx.doi.org/10.1098/rsta.2019.0542DOI Listing
April 2021

Synthesis, structure, electrochemistry and magnetism of cobalt-, nickel- and zinc-containing [M(OH)(HO)(α-SiWO)] (M = Co, Ni, and Zn).

Dalton Trans 2021 Mar 26;50(11):3923-3930. Epub 2021 Feb 26.

Jacobs University, Department of Life Sciences and Chemistry, Campus Ring 1, 28759 Bremen, Germany.

Interaction of the trilacunary 9-tungstosilicate [A-α-SiWO] with cobalt(ii), nickel(ii) and zinc(ii) ions in pH 9 aqueous medium at room temperature led to the formation of the respective M-containing heteropolytungstates [M(OH)(HO)(α-SiWO)] (M = Co (1), Ni (2), and Zn (3)). Polyanions 1-3 were characterized in the solid state by single-crystal XRD, FT-IR spectroscopy, and thermogravimetric and elemental analyses. Electrochemical studies showed that the Co ions in 1 can be oxidized to Co and the CVs of the W centers of the polyanions feature well-defined and chemically reversible reduction waves. Magnetic measurements on 1 and 2 showed paramagnetism with complex ferromagnetic and antiferromagnetic interactions. A model was presented for extracting the exchange constants for the magnetic exchange interaction.
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http://dx.doi.org/10.1039/d0dt03392hDOI Listing
March 2021

Complete Blood-count-based Inflammatory Score (CBCS) of COVID-19 Patients at Tertiary Care Center.

Altern Ther Health Med 2021 Feb 20. Epub 2021 Feb 20.

Context: Inflammation is a significant factor driving the rise of multiple cases of viral pneumonia, including COVID-19 infection. Peripheral white blood cells (WBCs), the neutrophil (NEU)-to-lymphocyte (LYM) ratio (NLR), the platelet-to-lymphocyte (PLR) ratio, and hemoglobin (Hb) are markers of systematic inflammatory reaction and often predict disease severity.

Objective: The current study intended to examine the prognostic importance of hemoglobin (Hb), total leukocyte count (TLC), absolute neutrophile count (ANC), absolute lymphocyte count (ALC), NLR, d-NLR [derived NLR = ANC/(WBC-ANC)], absolute platelet count (APC), and PLR, based on complete blood counts (CBCs) for COVID-19 patients.

Design: The research team designed a retrospective that was conducted between March 27 and June 5, 2020, after the first COVID-19 case was reported in Ajmer, Rajasthan, India on March 27.

Setting: The study took place at Jawaharlal Nehru (JLN) Medical College in Ajmer, Rajasthan, India.

Participants: The study included 364 participants who were all COVID-positive patients who came to the hospital during the study's period, including patients from various age groups and of both genders.

Outcome Measures: Using the results of the CBC, the research team measured: (1) Hb in g/dl, (2) ANC, (3) ALC, and (4) APC. The neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) were calculated from measurements of the levels of the circulating biomarkers, as cells × 103/μl.

Result: For participants who were severely symptomatic, the mean age was 57.86 ± 8.92. Males were more likely to experience severe symptoms. Participants' Hb values were significantly different between groups, and TLC, ANC, NLR, d-NLR, and PLR were highest in the severely symptomatic group and lowest in the asymptomatic group. NLR was positively associated with a risk of COVID-19 pneumonia, while Hb was negatively associated with development of pneumonia.

Conclusions: Disease severity and age are independent predictors of poor outcomes. The NLR should be used as a routine blood test that can help in the diagnosis of disease severity in COVID-19. NLR is very simple tool that can be used as a fast and low-cost test that is easily available, even in small centers where the facilities for other tests, such as tests of LDH, CRP, and IL-6, and high resolution CT scans aren't available. Thus, NLR can be used as single independent predictor of COVID-19 disease severity.
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February 2021

Photocatalytic, Bactericidal and Molecular Docking Analysis of Annealed Tin Oxide Nanostructures.

Nanoscale Res Lett 2021 Feb 10;16(1):33. Epub 2021 Feb 10.

Physics Department, Lahore Garrison University, Lahore, 54000, Pakistan.

Nanosized tin oxide was fabricated with a simple and cost-effective precipitation technique and was analyzed by performing x-ray powder diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, high-resolution transmission electron (HR-TEM) microscopy, energy-dispersive x-ray (EDX) and UV-Vis spectroscopy. The XRD results revealed that tin oxide particles possessed typical orthorhombic structure and exhibited improved crystallinity with annealing. Calcination at 250 °C produced predominantly orthorhombic SnO which transformed to SnO at higher temperatures of 500 and 750 °C. HRTEM and FESEM images showed existence of agglomeration within the particles of tin oxide. The absorption was found to increase up to a certain annealing temperature followed by a decrease, which was recorded via UV-Vis spectroscopy. The effect of annealing temperature on dye decomposition behavior of synthesized photocatalysts was studied. It was noted that annealing temperature affects the size of synthesized particles, band gap width and photoactivity of tin oxide. The sample prepared at 500 °C followed first-order kinetics and exhibited maximum photocatalytic reactivity toward methylene blue. The experimental results obtained from the present study indicate that SnO is a promising and beneficial catalyst to remove contaminants from wastewater and environment. The antimicrobial evaluation of SnO annealed at 500 °C against selected targets such as E. coli and S. aureus depicted significant inhibition zones in comparison with 250 and 750 °C samples. Furthermore, molecular docking predictions of SnO nanoparticles (NPs) were performed against active pocket of β-lactamase and DNA gyrase enzyme belonging to cell wall and nucleic acid biosynthetic pathway, respectively. The fabricated NPs showed good binding score against β-lactamase of both E. coli (- 5.71 kcal/mol) and S. aureus (- 11.83 kcal/mol) alongside DNA gyrase (- 9.57 kcal/mol; E. coli and - 8.61 kcal/mol; S. aureus). These in silico predictions suggested SnO NPs as potential inhibitors for selected protein targets and will facilitate to have a clear understanding of their mechanism of action that may contribute toward new antibiotics discovery.
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http://dx.doi.org/10.1186/s11671-021-03495-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876220PMC
February 2021

Silver Decorated 2D Nanosheets of GO and MoS2 serve as Nanocatalyst for Water Treatment and Antimicrobial Applications as ascertained with Molecular Docking Evaluation.

Nanotechnology 2021 Feb 8. Epub 2021 Feb 8.

Physics, Government College University Lahore, Katchery Road, Lahore, Punjab, 54000, PAKISTAN.

Two-dimensional (2D) nanosheets doped with silver nanoparticles (AgNPs) have found significant antibacterial applications in industry. In this work, synthesis of graphene oxide (GO) and reduced graphene oxide (rGO) was realized through a modified Hummers route. Different concentrations (5 & 10 wt.%) of Ag were doped in MoS2 and rGO using a hydrothermal approach. Synthesized Ag-MoS2 and Ag-rGO were evaluated through XRD that confirmed the hexagonal structure of MoS2 along with the transformation of GO to Ag-rGO as indicated by a shift in XRD peaks. FTIR confirmed the presence of Mo-O bonding vibrations, and S=O functional groups present in the prepared samples. Morphological information of GO and formation of MoS2 nanopetals were verified through FESEM, while spherical morphology, interlayer spacing, and homogeneous distribution of AgNPs were scrutinized through HR-TEM. Raman analysis was employed to probe any evidence regarding defect densities of GO. Optical properties of GO, MoS2, Ag-rGO, and Ag-MoS2 were visualized through UV-Vis & PL spectroscopy. Prepared products were employed as nanocatalysts to purify industrial wastewater, while degradation of undoped and doped samples was inspected using UV-Vis spectroscopy. Experimental results revealed that the photocatalytic response of Ag-rGO and Ag-MoS2 enhanced upon doping. Besides, the nanocatalyst (Ag-MoS2 & Ag-rGO) exhibited an excellent antibacterial activity towards S. aureus gram positive (G+) and E. coli gram negative (G-). To rationalize biocidal mechanism of Ag-doped MoS2 NPs and Ag-rGO, in silico molecular docking study was employed for two enzymes (i.e. β-lactamase & ddlB) from cell wall biosynthetic pathway and FabI from fatty acid biosynthetic pathway belonging to S. aureus. The present study provides evidence for the development of cost-effective and environmental-friendly products that could receive favorable recommendation for use in industrial and biomedical applications.
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http://dx.doi.org/10.1088/1361-6528/abe43cDOI Listing
February 2021

A retrospective review of the use of oxymorphone immediate release for long term pain control in cancer patients with gastrostomy tubes.

Ann Palliat Med 2021 Mar 27;10(3):2662-2667. Epub 2021 Jan 27.

Department of Palliative, Rehabilitation, and Integrative Medicine, UT MD Anderson Cancer Center, Houston, TX, USA.

Background: Cancer patients often require feeding or venting gastrostomy-tubes (G-tubes) for enteral nutrition or symptom palliation. The administration of most extended-release (ER) opioids via the G-tube or orally followed by clamping of the venting G-tube is contraindicated. Oxymorphone immediate release (IR) may be useful because of its longer half-life compared to other IR opioids. We examined the use of oxymorphone IR administered every 8 hours in patients with G-tubes.

Methods: This was a retrospective chart review of 40 consecutive cancer patients with G-tubes who underwent opioid rotation (OR) to oxymorphone. Demographics, symptoms, morphine equivalent daily dose (MEDD), and oxymorphone dose were collected. Successful OR was defined as a 2-point or 30% reduction in pain score and continued use of oxymorphone at follow-up in outpatient setting, or discharge in inpatient setting. Opioid rotation ration (ORR) between MEDD and oxymorphone in patients with successful OR was calculated as MEDD before the OR divided by total oxymorphone dose/day at follow-up or discharge.

Results: The median age was 56 years, 57.5% were white, 68% male, 47.5% (n=19) had head and neck cancer, 90% had advanced disease, 67.5% (n=27) were inpatient, and 15% (n=6) had venting G-tubes. 25/40 (62.5%) patients had successful OR to oxymorphone. The median ORR from MEDD to oxymorphone was 3.5 (IQR, 3.1-4). There were no independent predictors for successful OR, and ORR did not significantly differ among various groups.

Conclusions: Oxymorphone IR can be used successfully in cancer patients with G-tubes using an ORR of 3.5 to calculate dose from MEDD.
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http://dx.doi.org/10.21037/apm-20-969DOI Listing
March 2021

Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans.

Am J Hum Genet 2021 02 27;108(2):324-336. Epub 2021 Jan 27.

Division of Reproduction and Genetics, First Affiliated Hospital of USTC, Hefei National Laboratory for Physical Sciences at Microscale, the CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Basic Medical Sciences, Division of Life Sciences and Medicine, CAS Center for Excellence in Molecular Cell Science, Collaborative Innovation Center of Genetics and Development, University of Science and Technology of China, Hefei 230027, China. Electronic address:

Human infertility is a multifactorial disease that affects 8%-12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs2]) from a consanguineous Pakistani family with two males suffering from non-obstructive azoospermia (NOA) and one female diagnosed with premature ovarian insufficiency (POI) as well as a nonsense mutation (c.958G>T [p.Glu320]) and a splicing mutation (c.1180-3C>G) in two unrelated Chinese men (individual P3907 and individual P6032, respectively) with meiotic arrest. Mutations in C14orf39 resulted in truncated proteins that retained SYCE1 binding but exhibited impaired polycomplex formation between C14ORF39 and SYCE1. Further cytological analyses of meiosis in germ cells revealed that the affected familial males with the C14orf39 frameshift mutation displayed complete asynapsis between homologous chromosomes, while the affected Chinese men carrying the nonsense or splicing mutation showed incomplete synapsis. The phenotypes of NOA and POI in affected individuals were well recapitulated by Six6os1 mutant mice carrying an analogous mutation. Collectively, our findings in humans and mice highlight the conserved role of C14ORF39/SIX6OS1 in SC assembly and indicate that the homozygous mutations in C14orf39/SIX6OS1 described here are responsible for infertility of these affected individuals, thus expanding our understanding of the genetic basis of human infertility.
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http://dx.doi.org/10.1016/j.ajhg.2021.01.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895996PMC
February 2021

Evaluating the Role of Anesthesia on Intraoperative Blood Loss and Visibility during Endoscopic Sinus Surgery: A Meta-analysis.

Am J Rhinol Allergy 2021 Jan 21:1945892421989155. Epub 2021 Jan 21.

Head and Neck Institute, Cleveland Clinic, Cleveland, Ohio.

Background: Previous studies and meta analyses have led to incongruent and incomplete results respectively when total intravenous anesthesia (TIVA) and inhalational anesthesia (IA) are compared in endoscopic sinus surgeries in regards to intraoperative bleeding and visibility.

Objective: To perform a more comprehensive meta-analysis on randomized controlled trial (RCTs) comparing TIVA with IA in endoscopic sinus surgery to evaluate their effects on intraoperative bleeding and visibility.

Methods: A systematic review and meta-analysis of studies comparing TIVA and IA in endoscopic sinus surgery for chronic rhinosinusitis was completed in May 2020. Utilizing databases, articles were systematically screened for analysis and 19 studies met our inclusion criteria. The primary outcome included intraoperative visibility scores combining Boezaart, Wormald and Visual Analogue Scale (VAS). Secondary outcomes included rate of blood loss (mL/kg/min), estimated total blood loss (mL), Boezaart, Wormald scores, VAS, heart rate, and mean arterial pressure (MAP).

Results: 19 RCTs with 1,010 patients were analyzed. TIVA had a significantly lower intraoperative bleeding score indicating better endoscopic visibility (Boezaart, VAS, and Wormald) than IA (-0.514, p = 0.020). IA had a significantly higher average rate of blood loss than TIVA by 0.563 mL/kg/min (p = 0.016). Estimated total blood loss was significantly lower in TIVA than IA (-0.853 mL, p = 0.002). There were no significant differences between TIVA and IA in the mean heart rate (-0.225, p = 0.63) and MAP values (-0.126, p = 0.634). The subgroup analyses revealed no significant difference between TIVA and IA when remifentanil was not utilized and whenever desflurane was the IA agent.

Conclusion: TIVA seemed to have superior intraoperative visibility scores and blood loss during endoscopic sinus surgery when compared to IA. However, the results are not consistent when stratifying the results based on the use of remifentanil and different inhaled anesthetics. Therefore, the conclusion cannot be made that one approach is superior to the other.
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http://dx.doi.org/10.1177/1945892421989155DOI Listing
January 2021

Microwave Ablation as a Treatment for Spinal Metastatic Tumors: A Systematic Review.

World Neurosurg 2021 Apr 8;148:15-23. Epub 2021 Jan 8.

Department of Neurological Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Background: Microwave ablation (MWA) is a novel technique that offers several potential advantages over existing ablation systems, which include production of larger ablation zones, shorter procedural times, and more effective heating through high impedance tissues such as bone.

Methods: A systematic review was performed using inclusion criteria defined as follows: 1) metastatic spinal tumors treated with open or percutaneous MWA alone or in combination with other treatments, 2) available data on pain palliation and/or local tumor control, and 3) retrospective or prospective studies with at least 1 patient.

Results: A total of 156 patients harboring 196 spinal lesions underwent MWA in the 8 included studies. Most studies employed the use of additional interventions, which included minimally invasive open surgery with pedicle screw fixation, traditional open surgical intervention, and cement augmentation. Despite the variability in time intervals for pain assessment, postoperative pain scores decreased considerably in both percutaneous and open MWA studies. No evidence of tumor progression was additionally seen in >80% of patients at the last follow-up across 5 studies. Complications were reported in 6.5% of all patients who underwent percutaneous MWA and in 12.2% of patients who underwent open MWA.

Conclusions: This review showed that MWA can be effective in achieving analgesia for up to 6 months in select cases, although most procedures were performed in combination with augmentation and/or open surgery. Local tumor control was additionally successful in most patients, suggestive of a potential curative role for MWA.
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http://dx.doi.org/10.1016/j.wneu.2020.12.162DOI Listing
April 2021

Unravelling the reactivity of metastable molybdenum carbide nanoclusters in the C-H bond activation of methane, ethane and ethylene.

Nanoscale 2021 Feb 6;13(8):4451-4466. Epub 2021 Jan 6.

Renewable Energy and Chemicals Lab, Department of Chemical Engineering, Indian Institute of Technology Delhi, Hauz Khas, New Delhi, India.

C-H bond activation steps in non-oxidative methane dehydroaromatization (MDA), constitute a key functionalization of the reactant and adsorbed species to form aromatics. Previous studies have focused on studying the energetics of these steps at the most stable active sites involving molybdenum carbide species. Herein, a different paradigm is presented via studying the reactivity of a metastable molybdenum carbide (MoC) nanocluster for the C-H bond activation of methane, ethane, and ethylene and comparing it with the reactivity of the lowest energy MoC nanocluster. Interestingly, the metastable nanocluster is observed to result in a consistent reduction (by half) in the C-H bond activation barrier of the respective alkane and alkene molecules compared to the global minimum isomer. This specific metastable form of the nanocluster is identified from a cascade genetic algorithm search, which facilitated a rigorous scan of the potential energy surface. We attribute this significant lowering of the C-H bond activation barrier to unique co-planar orbital overlap between the reactant molecule and active centers on the metastable nanocluster. Based on geometrical and orbital analysis of the transition states arising during the C-H bond activation of methane, ethane, and ethylene, a proton-coupled electron transfer mechanism is proposed that facilitated C-H bond cleavage. Motivated by the high reactivity for C-H bond activation observed on the metastable species, a contrasting framework to analyze the elementary-step rate contributions is presented. This is based on the statistical ensemble analysis of nanocluster isomers, where the calculated rates on respective isomers are normalized with respect to the Boltzmann probability distribution. From this framework, the metastable isomer is observed to provide significant contributions to the ensemble average representations of the rate constants calculated for C-H bond activation during the MDA reaction.
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http://dx.doi.org/10.1039/d0nr07044kDOI Listing
February 2021

An Integrated Approach to Selecting a Prepared Medical Decision-Maker.

J Pain Symptom Manage 2020 Dec 24. Epub 2020 Dec 24.

Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Background: We implemented a systematic multidisciplinary process to engage new outpatients with cancer in selecting and preparing a medical decision-maker.

Measures: Templated advance care planning notes and medical power of attorney documents were used in the electronic health record by the third office visit.

Intervention: Patients were coached to meet with social work from a "culture of yes," viewed a video about the importance of selecting a prepared medical a decision-maker in English or in Spanish, and referenced cards containing simple explanations of advance directives when responding to advance directive questions.

Outcomes: A total of 351 patients were evaluated. By visit 3, there was no increase in documented social work advance care planning notes in intervention or scanned medical power of attorney documents in the electronic health record.

Conclusions/lessons Learned: This systematic multidisciplinary approach did not engage new outpatients with cancer in preparing a medical decision-maker. More active physician involvement and varied ways of engagement are needed.
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http://dx.doi.org/10.1016/j.jpainsymman.2020.12.006DOI Listing
December 2020

Improving Lithium-Ion Half-/Full-Cell Performance of WO -Protected SnO Core-Shell Nanoarchitectures.

ChemSusChem 2021 Feb 9;14(3):917-928. Epub 2020 Dec 9.

Nanoscience and Technology Department, National Centre for Physics, Quaid-e-Azam University Campus, 45320-, Islamabad, Pakistan.

Anodes derived from SnO offer a greater specific capacity comparative to graphitic carbon in lithium-ion batteries (LIBs); hence, it is imperative to find a simple but effective approach for the fabrication of SnO . The intelligent surfacing of transition metal oxides is one of the favorite strategies to dramatically boost cycling efficiency, and currently most work is primarily aimed at coating and/or compositing with carbon-based materials. Such coating materials, however, face major challenges, including tedious processing and low capacity. This study successfully reports a new and simple WO coating to produce a core-shell structure on the surface of SnO . The empty space permitted natural expansion for the SnO nanostructures, retaining a higher specific capacity for over 100 cycles that did not appear in the pristine SnO without WO shell. Using WO -protected SnO nanoparticles as anode, a coin half-cell battery was designed with Li-foil as counter-electrode. Furthermore, the anode was paired with commercial LiFePO as cathode for a coin-type full cell and tested for lithium storage performance. The WO shell proved to be an effective and strong enhancer for both current rate and specific capacity of SnO nanoarchitectures; additionally, an enhancement of cyclic stability was achieved. The findings demonstrate that the WO can be used for the improvement of cyclic characteristics of other metal oxide materials as a new coating material.
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http://dx.doi.org/10.1002/cssc.202002408DOI Listing
February 2021

Random urine drug testing among patients receiving opioid therapy for cancer pain.

Cancer 2021 Mar 24;127(6):968-975. Epub 2020 Nov 24.

Department of Palliative, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: There is limited information regarding the true frequency of nonmedical opioid use (NMOU) among patients receiving opioid therapy for cancer pain. Data to guide patient selection for urine drug testing (UDT) as well as the timing and frequency of ordering UDT are insufficient. This study examined the frequency of abnormal UDT among patients with cancer who underwent random UDT and their characteristics.

Methods: Demographic and clinical information for patients with cancer who underwent random UDT were retrospectively reviewed and compared with a historical cohort that underwent targeted UDT. Random UDT was ordered regardless of a patient's risk potential for NMOU. Targeted UDT was ordered on the basis of a physician's estimation of a patient's risk for NMOU.

Results: In all, 552 of 573 eligible patients (96%) underwent random UDT. Among these patients, 130 (24%) had 1 or more abnormal results; 38 of the 88 patients (43%) who underwent targeted UDT had 1 or more abnormal results. When marijuana was excluded, 15% of the random group and 37% of the targeted group had abnormal UDT findings (P < .001). It took a shorter time from the initial consultation to detect 1 or more abnormalities with the random test than the targeted test (median, 130 vs 274 days; P = .02). Abnormal random UDT was independently associated with younger age (P < .0001), male sex (P = .03), Cut Down, Annoyed, Guilty, and Eye Opener-Adapted to Include Drugs positivity (P = .001), and higher Edmonton Symptom Assessment System anxiety (P = .01).

Conclusions: Approximately 1 in 4 patients receiving opioids for cancer pain at a supportive care clinic who underwent random UDT had 1 or more abnormalities. Random UDT detected abnormalities earlier than the targeted test. These findings suggest that random UDT is justified among patients with cancer pain.
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http://dx.doi.org/10.1002/cncr.33326DOI Listing
March 2021

Management challenges at end-of-life in a patient with agitated delirium and benzodiazepine withdrawal at comprehensive cancer care center.

Ann Palliat Med 2020 Nov 19. Epub 2020 Nov 19.

Department of Palliative Care, Rehabilitation, and Integrative Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Most people have some idea of how they want to live their life; however, an estimated twothirds of Americans have not completed their advance directives. This becomes an issue when up to 90% of patients develop delirium during their final days of life, at which point we depend on advance directives or surrogate decision-makers. Here, we present a case of terminal delirium in a patient with advanced cancer and a history of alprazolam abuse who had not discussed his end-of-life wishes with the medical team or with his estranged family. Treatment was provided to address reversible causes of delirium, including correcting electrolyte imbalances, urinary retention, and administered antibiotics for purulent otitis media. Hyperactive delirium was managed aggressively with intravenous neuroleptics and benzodiazepine, while keeping a balance between somnolence and control of agitative symptoms. Without knowing the patient's wishes, the family continued to struggle with decision making. However, with multidisciplinary team approach patients and caregivers' symptoms were better managed. Family then requested us to transfer him to a local hospice facility. The patient eventually passed away peacefully surrounded by his family members. This case highlights the importance of advance care planning, addressing emotional distress in estranged family members regarding symptom burden, and developing the appropriate treatment regimen for a delirious patient with a history of benzodiazepine abuse. Our case serves as a reminder of the support, guidance, and impact that inpatient palliative care teams can offer to both the patient and caregivers.
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http://dx.doi.org/10.21037/apm-20-495DOI Listing
November 2020

Determine the Potential Epitope Based Peptide Vaccine Against Novel SARS-CoV-2 Targeting Structural Proteins Using Immunoinformatics Approaches.

Front Mol Biosci 2020 15;7:227. Epub 2020 Oct 15.

Department of Bioinformatics and Biotechnology, Government College University Faisalabad, Faisalabad, Pakistan.

Coronaviruses (CoVs) belong to the Coronaviridae-family. The genus Beta-coronaviruses, are enveloped positive strand RNA viruses with club-like spikes at the surface with a unique replication process and a large RNA genome (∼25 kb). CoVs are known as one of the major pathogenic viruses causing a variety of diseases in birds and mammals including humans (lethal respiratory dysfunctions). Recently, a new strain of coronavirus has been identified and named as SARS-CoV-2. A large number of COVID-19 (disease caused by SARS-CoV-2) cases are being diagnosed all over the World especially in China (Wuhan). COVID-19 showed high mortality rate exponentially, however, not even a single effective cure is being introduced yet against COVID-19. In the current study, immunoinformatics approaches were employed to predict the antigenic epitopes against COVID-19 for the development of a coronavirus peptide vaccine. Cytotoxic T-lymphocyte (CTL) and B-cell epitopes were predicted for SARS-CoV-2 coronavirus structural proteins (Spikes, Membrane, Envelope, and Nucleocapsid). The docking complexes of the top 10 epitopes having antigenic sites were analyzed led by binding affinity and binding interactional analyses of top ranked predicted peptides with the MHC-I HLA molecule. The predicted peptides may have potential to be used as peptide vaccine against COVID-19.
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http://dx.doi.org/10.3389/fmolb.2020.00227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593713PMC
October 2020

Biochemical interaction of salt sensitivity: a key player for the development of essential hypertension.

Mol Cell Biochem 2021 Feb 18;476(2):767-773. Epub 2020 Oct 18.

Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Worldwide, more than 1 billion people have elevated blood pressure, with up to 45% of adults affected by the disease. In 2016 the global health study report on patients from 67 countries was released in Lancet, which identified hypertension as the world's leading cause for death and disability-adjusted years since 1990. This paper aims to analyze the pathophysiological connection between hemodynamic inflammatory reactions through sodium balance, salt sensitivity, and potential pathophysiological reactions. Besides, we explore how sodium consumption enhances the expression of transient receptor potential channel 3 (TrpC3) mRNA and facilitates the release of calcium inside immune cell groups, together with elevated blood pressure in essential hypertensive patients.
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http://dx.doi.org/10.1007/s11010-020-03942-0DOI Listing
February 2021

Lumbar Facet Joint Cyst Treated With Decompression and Interlaminar Stabilization.

Cureus 2020 Jul 25;12(7):e9391. Epub 2020 Jul 25.

Neurosurgery, Texas A&M University College of Medicine, Houston, USA.

Spinal facet joint cysts (FJCs) are an increasingly reported cause of lower back pain, radiculopathy, and neurological deficits owing to their proximity to adjacent nerve roots. The etiology of these cysts has not yet been fully elucidated, although they appear to be related to degenerative changes in the facet joints themselves. Conservative management strategies including physical therapy and oral analgesics rarely result in spontaneous regression of an FJC, often providing only short-term relief. The current treatment modalities reported for FJCs generally range from percutaneous cyst aspiration to decompression surgery with or without instrumented spinal fusion. However, instrumented fusion often results in a higher rate of complications such as pseudoarthrosis and adjacent segment disease. The Coflex (Paradigm Spine, LLC, New York, NY) interlaminar stabilization (ILS) implant is a novel titanium, U-shaped device which acts as a motion-preserving stabilizer and has proven to be a viable alternative to instrumental fusion. Here, we discuss a case of an FJC treated with both decompression and placement of a Coflex ILS device.
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http://dx.doi.org/10.7759/cureus.9391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445097PMC
July 2020

Machine Learning in Laryngoscopy Analysis: A Proof of Concept Observational Study for the Identification of Post-Extubation Ulcerations and Granulomas.

Ann Otol Rhinol Laryngol 2021 Mar 14;130(3):286-291. Epub 2020 Aug 14.

Department of Computer Science, Johns Hopkins University, Baltimore, MD, USA.

Objective: Computer-aided analysis of laryngoscopy images has potential to add objectivity to subjective evaluations. Automated classification of biomedical images is extremely challenging due to the precision required and the limited amount of annotated data available for training. Convolutional neural networks (CNNs) have the potential to improve image analysis and have demonstrated good performance in many settings. This study applied machine-learning technologies to laryngoscopy to determine the accuracy of computer recognition of known laryngeal lesions found in patients post-extubation.

Methods: This is a proof of concept study that used a convenience sample of transnasal, flexible, distal-chip laryngoscopy images from patients post-extubation in the intensive care unit. After manually annotating images at the pixel-level, we applied a CNN-based method for analysis of granulomas and ulcerations to test potential machine-learning approaches for laryngoscopy analysis.

Results: A total of 127 images from 25 patients were manually annotated for presence and shape of these lesions-100 for training, 27 for evaluating the system. There were 193 ulcerations (148 in the training set; 45 in the evaluation set) and 272 granulomas (208 in the training set; 64 in the evaluation set) identified. Time to annotate each image was approximately 3 minutes. Machine-based analysis demonstrated per-pixel sensitivity of 82.0% and 62.8% for granulomas and ulcerations respectively; specificity was 99.0% and 99.6%.

Conclusion: This work demonstrates the feasibility of machine learning via CNN-based methods to add objectivity to laryngoscopy analysis, suggesting that CNN may aid in laryngoscopy analysis for other conditions in the future.
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http://dx.doi.org/10.1177/0003489420950364DOI Listing
March 2021

Contending charcoal rot disease of mungbean by employing biocontrol and zinc.

Physiol Mol Biol Plants 2020 Jul 14;26(7):1385-1397. Epub 2020 May 14.

Institute of Agricultural Sciences, University of the Punjab, Lahore, Pakistan.

Role of rhizobacteria and zinc (Zn) was investigated in the management of charcoal rot disease in mungbean [ (L.) Wilczek] caused by (Tassi) Goid. In vitro, screening tests with eight rhizobacteria [ (FCBP-0324), (FCBP-0189), (FCBP-0450), (FCBP-0025), (FCBP-0022), (FCBP-0099), (FCBP-0083) and (FCBP-0727)] were conducted against and FCBP-0727 were found as the most effective biocontrol agent. Molecular analyses of 16S rDNA combined with cultural and biochemical analyses confirmed FCBP-0727 identification (GeneBank Accession No. LC415039). Cell-free culture filtrate (CFCF) and cell culture of were separated and antifungal trials of both substrates indicated inhibition in mycelial growth and suppression in sclerotia formation, although the CFCF appeared to be more destructive against the pathogen. Ethyl-acetate and chloroform extracts of bacterial secondary metabolites completely halted the growth of . The GC-MS analysis of CFCF of chloroform extract proved to be rich sources of bioactive fungicide like phthalates, adipic acid, propanoic acid, and linoleic acid. Likewise, CFCF of ethyl acetate also exhibited important organic compounds like phthalates, diisopropylglycol and octasiloxan. Pot experiment revealed that soil inoculation with in combination with Zn (2.5 mg/kg) protected mungbean plants against through improving photosynthetic pigment, total protein content and activities of antioxidant enzymes (catalase, peroxidase and polyphenol oxidase). The present study will open new vistas for biological management of charcoal rot disease of mungbean using a combination of rhizobacteria and Zn.
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http://dx.doi.org/10.1007/s12298-020-00817-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326837PMC
July 2020

Photocatalytic, dye degradation, and bactericidal behavior of Cu-doped ZnO nanorods and their molecular docking analysis.

Dalton Trans 2020 Jun;49(24):8314-8330

Solar Cell Applications Research Lab, Department of Physics, Government College University Lahore, 54000, Punjab, Pakistan.

Nanostructures of Cu-doped ZnO (Cu:ZnO) were prepared with the chemical precipitation technique with an aim to enhance the photocatalytic and antibacterial properties of ZnO. Phase constitution, the presence of functional groups, optical properties, elemental composition, surface morphology and microstructure were evaluated using an X-ray diffractometer (XRD), Fourier transform infrared spectroscopy (FTIR), UV-Vis spectrophotometer, energy dispersive X-ray spectroscopy (EDS), field emission scanning electron microscope (FESEM) and high resolution transmission electron microscope (HR-TEM), respectively. Emission spectra were obtained with a photoluminescence (PL) spectroscope whereas interlayer d-spacing was estimated through HR-TEM. ZnO consisted of a hexagonal wurtzite structure. The crystallinity of the sample was observed to increase with increasing doping concentration. The addition of Cu to ZnO served to transform nanoclusters into nanorods as revealed during SEM analysis. Catalytic activity enhanced due to the formation of nanorods, and UV-Vis absorption spectra showed that methylene blue (MB) degraded more efficiently with ZnO nanoclusters compared to the NaBH4 reagent. In addition, the doped NPs showed enhanced bacterial efficiency for G +ve. Finally, a molecular docking study was undertaken to highlight the importance of the binding interactions of the Cu-doped ZnO nanorods with β-lactamase and beta-ketoacyl-acyl carrier protein synthase III (FabH) as possible enzyme targets. This research indicates that Cu-doped Zn nanorods are a highly efficient photocatalyst and can be aptly employed for wastewater treatment and antibacterial applications.
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http://dx.doi.org/10.1039/d0dt01397hDOI Listing
June 2020

Frequency of Concomitant Use of Gabapentinoids and Opioids among Patients with Cancer-Related Pain at an Outpatient Palliative Care Clinic.

J Palliat Med 2021 01 2;24(1):91-96. Epub 2020 Jun 2.

M.D. Anderson Cancer Center, University of Texas, Houston, Texas, USA.

Patients with cancer-related pain use opioids for nociceptive pain, while gabapentinoids are common to treat neuropathic pain. The simultaneous use of opioids with gabapentinoids has been associated with an increased risk of opioid-related death. Determine the frequency of combined use of gabapentinoids among patients receiving opioids for cancer-related pain. We also examined if concomitant use of opioids and gabapentinoids together was associated with increased scores of fatigue and drowsiness on the Edmonton Symptom Assessment Scale (ESAS) compared to patients on opioids. Retrospective study of patients on opioids and opioids plus gabapentinoids at their third visit to the outpatient Supportive Care Center. We found that 48% (508/1059) of patients were on opioids. Of these patients, 51% (257/508) were on opioids only, and 49% (251/508) were on opioids plus gabapentinoids. The median (interquartile range [IQR]) morphine equivalent daily dose for patients on opioids was 75 (45, 138) mg, and opioids plus gabapentinoids was 68 (38, 150) mg ( = 0.94). The median (IQR) gabapentinoid equivalent daily dose was 900 (300, 1200) mg. The median (IQR) for ESAS-fatigue in patients on opioids was 5 (3, 7), and opioids plus gabapentinoids was 5 (3, 7) ( = 0.27). The median (IQR) for ESAS-drowsiness in patients on opioids was 3 (0, 5), and opioids plus gabapentinoids was 3 (0, 6) ( = 0.11). Almost 50% of advanced cancer patients receiving opioids for pain were exposed to gabapentinoids. Maximal efforts should be made to minimize potential complications from the concomitant use of opioids with gabapentinoids.
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http://dx.doi.org/10.1089/jpm.2019.0614DOI Listing
January 2021

Neuroleptic strategies for terminal agitation in patients with cancer and delirium at an acute palliative care unit: a single-centre, double-blind, parallel-group, randomised trial.

Lancet Oncol 2020 07 29;21(7):989-998. Epub 2020 May 29.

Department of Palliative Care, Rehabilitation and Integrative Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: The role of neuroleptics for terminal agitated delirium is controversial. We assessed the effect of three neuroleptic strategies on refractory agitation in patients with cancer with terminal delirium.

Methods: In this single-centre, double-blind, parallel-group, randomised trial, patients with advanced cancer, aged at least 18 years, admitted to the palliative and supportive care unit at the University of Texas MD Anderson Cancer Center (Houston, TX, USA), with refractory agitation, despite low-dose haloperidol, were randomly assigned to receive intravenous haloperidol dose escalation at 2 mg every 4 h, neuroleptic rotation with chlorpromazine at 25 mg every 4 h, or combined haloperidol at 1 mg and chlorpromazine at 12·5 mg every 4 h, until death or discharge. Rescue doses identical to the scheduled doses were administered at inception, and then hourly as needed. Permuted block randomisation (block size six; 1:1:1) was done, stratified by baseline Richmond Agitation Sedation Scale (RASS) scores. Research staff, clinicians, patients, and caregivers were masked to group assignment. The primary outcome was change in RASS score from time 0 to 24 h. Comparisons among group were done by modified intention-to-treat analysis. This completed study is registered with ClinicalTrials.gov, NCT03021486.

Findings: Between July 5, 2017, and July 1, 2019, 998 patients were screened for eligibility, with 68 being enrolled and randomly assigned to treatment; 45 received the masked study interventions (escalation n=15, rotation n=16, combination n=14). RASS score decreased significantly within 30 min and remained low at 24 h in the escalation group (n=10, mean RASS score change between 0 h and 24 h -3·6 [95% CI -5·0 to -2·2]), rotation group (n=11, -3·3 [-4·4 to -2·2]), and combination group (n=10, -3·0 [-4·6 to -1·4]), with no difference among groups (p=0·71). The most common serious toxicity was hypotension (escalation n=6 [40%], rotation n=5 [31%], combination n=3 [21%]); there were no treatment-related deaths.

Interpretation: Our data provide preliminary evidence that the three strategies of neuroleptics might reduce agitation in patients with terminal agitation. These findings are in the context of the single-centre design, small sample size, and lack of a placebo-only group.

Funding: National Institute of Nursing Research.
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http://dx.doi.org/10.1016/S1470-2045(20)30307-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433183PMC
July 2020

Surgical Management of Skull Base Osteoradionecrosis in the Cancer Population - Treatment Outcomes and Predictors of Recurrence: A Case Series.

Oper Neurosurg (Hagerstown) 2020 09;19(4):364-374

Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Skull base osteoradionecrosis (ORN) is a challenging treatment-related complication sometimes seen in patients with cancer. Although ORN management strategies for other anatomic sites have been reported, there is a paucity of data guiding the management of skull base ORN.

Objective: To report a single-center tertiary care series of skull base ORN and to better understand the factors affecting ORN recurrence after surgical management.

Methods: We conducted a retrospective cohort study of patients with skull base ORN treated at our center between 2003 and 2017. Univariate and multivariate binary logistic regressions were performed to identify predictors of recurrence.

Results: A total of 31 patients were included in this study. The median age at ORN diagnosis was 61.1 yr (range, 32.8-84.9 yr). Of these 31 patients, 15 (48.4%) patients were initially treated medically. All 31 patients underwent surgery. Three (14.3%) of 21 patients treated with a free flap and 4 (50.0%) of 8 patients who underwent primary closure experienced recurrence. Cox regression analysis revealed that reconstruction with local tissue closure (P = .044) and ongoing treatment for active primary cancer (P = .022) were significant predictors of recurrence. The median overall survival from index surgery for ORN treatment was 83.9 mo. At 12-mo follow-up, 78.5% of patients were alive.

Conclusion: In this study, we assess the outcomes of our treatment approach, surgical debridement with vascularized reconstruction, on recurrence-free survival in patients with skull base ORN. Further studies with larger cohorts are needed to assess current treatment paradigms.
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http://dx.doi.org/10.1093/ons/opaa082DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490162PMC
September 2020

Effect of Gibberellic Acid on Production of Biomass, Polyphenolics and Steviol Glycosides in Adventitious Root Cultures of (Bert.).

Plants (Basel) 2020 Mar 30;9(4). Epub 2020 Mar 30.

Department of Biotechnology, Quaid-i-Azam University Islamabad, Islamabad 45320, Pakistan.

In current study, the effect of gibberellic acid was tested for production of biomass, polyphenolics and Steviol glycosides in adventitious root cultures of . Adventitious cultures were induced from the roots of in vitro grown plantlets on Murashige and Skoog (MS) medium containing combination of gibberellic acid (GA; 0.5, 1.0, 1.5 and 2.0 mg/L) and naphthalene acetic acid (NAA; 0.5 mg/L). Initially, a known mass of inoculum roots were shifted into suspension media augmented with various GA concentrations. The growth behavior of adventitious roots was recorded every 3 days for a period of 30 days. Maximum biomass biosynthesis (13.12 g/flask) was noticed in exponential phase on 27th day in the suspension containing 2.0 mg/L of GA. Other GA concentrations also displayed optimum patterns of biomass accumulation as compared to the control. Adventitious roots were investigated for total phenolic content (TPC) and production (TPP), total flavonoid content (TFC) and production (TFP), and 1, 1-diphenyl-2-picrylhydrazyl (DPPH)-based antioxidant potential. Maximum phenolics (TPC 9.84 mg gallic acid equivalent (GAE)/g-dry weight (DW)) and TPP (147.6 mg/L), TFC (5.12 mg Quercitin equivalent (QE)/g-DW) and TFP (76.91 mg/L) were observed in 2.0 mg/L GA treated cultures. The same concentration of gibberellic acid enhanced antioxidant activity (77.2%). Furthermore, maximum stevioside (7.13 mg/g-DW), rebaudioside-A (0.27 mg/g-DW) and dulcoside-A (0.001 mg/g-DW) were observed in roots exposed to 2.0 mg/L GA. This is the first report on the application of GA on biomass accumulation and secondary metabolite production in . The current study will be helpful to scale up the adventitious root cultures in bioreactors for the production of biomass and pharmaceutically important secondary metabolites.
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http://dx.doi.org/10.3390/plants9040420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238111PMC
March 2020