Displaying publications 21 - 40 of 244 in total

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  1. Nieland L, van Solinge TS, Cheah PS, Morsett LM, El Khoury J, Rissman JI, et al.
    Mol Ther Oncolytics, 2022 Jun 16;25:121-136.
    PMID: 35572197 DOI: 10.1016/j.omto.2022.04.001
    Non-coding RNAs, including microRNAs (miRNAs), support the progression of glioma. miR-21 is a small, non-coding transcript involved in regulating gene expression in multiple cellular pathways, including the regulation of proliferation. High expression of miR-21 has been shown to be a major driver of glioma growth. Manipulating the expression of miRNAs is a novel strategy in the development of therapeutics in cancer. In this study we aimed to target miR-21. Using CRISPR genome-editing technology, we disrupted the miR-21 coding sequences in glioma cells. Depletion of this miRNA resulted in the upregulation of many downstream miR-21 target mRNAs involved in proliferation. Phenotypically, CRISPR-edited glioma cells showed reduced migration, invasion, and proliferation in vitro. In immunocompetent mouse models, miR-21 knockout tumors showed reduced growth resulting in an increased overall survival. In summary, we show that by knocking out a key miRNA in glioma, these cells have decreased proliferation capacity both in vitro and in vivo. Overall, we identified miR-21 as a potential target for CRISPR-based therapeutics in glioma.
  2. Kraft TS, Cummings DK, Venkataraman VV, Alami S, Beheim B, Hooper P, et al.
    Philos Trans R Soc Lond B Biol Sci, 2023 Jan 16;378(1868):20210431.
    PMID: 36440571 DOI: 10.1098/rstb.2021.0431
    Cooperation in food acquisition is a hallmark of the human species. Given that costs and benefits of cooperation vary among production regimes and work activities, the transition from hunting-and-gathering to agriculture is likely to have reshaped the structure of cooperative subsistence networks. Hunter-gatherers often forage in groups and are generally more interdependent and experience higher short-term food acquisition risk than horticulturalists, suggesting that cooperative labour should be more widespread and frequent for hunter-gatherers. Here we compare female cooperative labour networks of Batek hunter-gatherers of Peninsular Malaysia and Tsimane forager-horticulturalists of Bolivia. We find that Batek foraging results in high daily variation in labour partnerships, facilitating frequent cooperation in diffuse networks comprised of kin and non-kin. By contrast, Tsimane horticulture involves more restricted giving and receiving of labour, confined mostly to spouses and primary or distant kin. Tsimane women also interact with few individuals in the context of hunting/fishing activities and forage mainly with spouses and primary kin. These differences give rise to camp- or village-level networks that are more modular (have more substructure when partitioned) among Tsimane horticulturalists. Our findings suggest that subsistence activities shape the formation and extent of female social networks, particularly with respect to connections with other women and non-kin. We discuss the implications of restricted female labour networks in the context of gender relations, power dynamics and the adoption of farming in humans. This article is part of the theme issue 'Cooperation among women: evolutionary and cross-cultural perspectives'.
  3. Barman M, Mahmood S, Augustine R, Hasan A, Thomas S, Ghosal K
    Int J Biol Macromol, 2020 Nov 01;162:1849-1861.
    PMID: 32781129 DOI: 10.1016/j.ijbiomac.2020.08.060
    Applying nanotechnology to deliver drug could result in several benefits such as prolong duration of action, enhancement in overall bioavailability, targeting to specific site, low initial loading dose require, systemic stability enhancement etc. Halloysite is one of those clay minerals showing maximum effectiveness when consider as a nano drug carriers for different kind applications. Here, we have used norfloxacin as the model drug for loading into halloysite nanotube (HNT) for its anti-bacterial activity. Norfloxacin was loaded into halloysites by vacuum operation and sonication. The nanotubes were evaluated using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), scanning electron microscopy (SEM), optical microscopy, water absorption studies, cytotoxicity studies, antimicrobial studies and in vitro diffusion studies. SEM, FT-IR and XRD analysis data showed that the norfloxacin was successfully loaded into nanotubes. TEM analysis confirmed loading of norfloxacin in halloysites' lumen. The halloysite/chitosan nanocomposites were prepared by solvent casting and freeze-drying method. SEM analysis revealed compact and rugged surface of nanocomposites due to existing norfloxacin loaded halloysite. FTIR and XRD confirmed formation of nanocomposite. The nanocomposites showed good antimicrobial effect and good biocompatibility in cytotoxicity study. The in-vitro release studies revealed that halloysite/chitosan nanocomposites were able to sustain the drug release. Also, the nanocomposites were stable in various humidity conditions. Therefore, all the outcomes suggest that the prepared nanocomposites can provide enhanced therapeutic benefits and they can be very potential nano vehicle for sustaining drug delivery.
  4. Shah PK, Duncan HF, Abdullah D, Tomson PL, Murray G, Friend TM, et al.
    Int Endod J, 2020 Nov;53(11):1569-1580.
    PMID: 32748456 DOI: 10.1111/iej.13377
    AIM: To compare the educational benefits and user friendliness of two anonymized endodontic case difficulty assessment (CDA) methods.

    METHODOLOGY: A cohort (n = 206) of fourth-year undergraduate dental students were recruited from four different Dental Schools and divided randomly into two groups (Group A and B). The participants assessed six test endodontic cases using anonymized versions of the American Association of Endodontists (AAE) case difficulty assessment form (AAE Endodontic Case Difficulty Assessment Form and Guidelines, 2006) and EndoApp, a web-based CDA tool. Group A (n = 107) used the AAE form for assessment of the first three cases, followed by EndoApp for the latter. Group B (n = 99) used EndoApp for the initial three cases and switched to the AAE form for the remainder. Data were collected online and analysed to assess participants' knowledge reinforcement and agreement with the recommendation generated. Statistical analysis was performed using the two-way mixed model anova, Cohen's Kappa (κ) and independent t-tests, with the levels of significance set at P 

  5. Pal A, Roy S, Kumar A, Mahmood S, Khodapanah N, Thomas S, et al.
    ACS Omega, 2020 Aug 18;5(32):19968-19977.
    PMID: 32832751 DOI: 10.1021/acsomega.0c01228
    This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepiride-Captisol complexes of different mass ratios (1:1, 1:2, and 1:3 w/w) by a physical mixing or freeze-drying technique, and found that complexation with Captisol enhanced the water solubility of glimepiride. Molecular docking and dynamic simulation predicted complex formation; at the same time, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscope indicated molecular interactions that support complexation. We also found that an inclusion complex was better than a physical mixture in enhancing the complexation of glimepiride with Captisol and enhancing water solubility. Phase solubility study of the glimepiride-Captisol complex showed an AL-type profile, implying the formation of a 1:1 inclusion complex. The study also revealed that pH influenced the stability of the complex because the stability constant of the glimepiride-Captisol complex was higher in distilled water of pH ∼6.0 than in phosphate buffer of pH 7.2.
  6. Ghosal K, Das A, Das SK, Mahmood S, Ramadan MAM, Thomas S
    Int J Biol Macromol, 2019 Jun 01;130:645-654.
    PMID: 30797807 DOI: 10.1016/j.ijbiomac.2019.02.117
    This study aimed to develop and characterize the calcium alginate films loaded with diclofenac sodium and other hydrophilic polymers with different degrees of cross-linking obtained by external gelation process. To the formed films different physicochemical evaluation were performed which showed an initial character of the films. The films produced by this external gelation process were found thicker (0.031-0.038 mm) and stronger (51.9-52.9 MPa) but less elastic (2.3%) than those non-cross-linked films (0.029 mm; 39.7 MPa; 4.4%). The lower water vapor permeability (WVP) values of the films were obtained where maximum level of crosslinking occurs. Composite films can be cross-linked in presence of external crosslinking agent to improve the quality of the produced matrices for various uses. The characterization of the film was performed using Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared Spectroscopy (FT-IR) analysis. The Scanning Electron Microscopy (SEM) study showed the morphology of treated composite films. The kinetic release studies showed a sustained release of the drug from the formulated films as it can be prolonged in composite film. The prepared biodegradable Ca-Alginate bio-composite film may be of clinical importance for its therapeutic benefit.
  7. Alli YA, Ejeromedoghene O, Oladipo A, Adewuyi S, Amolegbe SA, Anuar H, et al.
    ACS Appl Bio Mater, 2022 Nov 21;5(11):5240-5254.
    PMID: 36270024 DOI: 10.1021/acsabm.2c00670
    Quaternary Trimethyl Chitosan (QTMC) and QTMC-Silver Nanoparticles (QTMC-AgNPs) have been synthesized, characterized, and tested as antibacterial agents against Staphylococcus aureus, Escherichia coli, and two plant fungi (Sclerotium rolfsil and Fusarium oxysporum). The as-prepared water-soluble QTMC was in situ reacted with silver nitrate in the presence of clean compressed hydrogen gas (3 bar) as a reducing agent to produce QTMC-AgNPs. UV-vis, ATR-FTIR, HR-TEM/SEM, XPS, DLS, XRD, and TGA/DTG were employed to assess the optical response, morphology/size, surface chemistry, particle size distribution, crystal nature, and thermal stability of the synthesized QTMC-AgNPs, respectively. The as-prepared QTMC-AgNPs were quasi-spherical in shape with an average particle size of 12.5 nm, as determined by ImageJ software utilizing HR-TEM images and further validated by DLS analysis. The development of crystalline nanoparticles was confirmed by the presence of distinct and consistent lattice fringes with an approximate interplanar d-spacing of 2.04 nm in QTMC-AgNPs. The QTMC-AgNPs exhibited significant antibacterial activity with a clear zone of inhibition of 30 mm and 26 mm around the disks against E. coli and S. aureus, respectively. In addition, QTMC-AgNPs showed highly efficient antifungal activity with 100% and 76.67% growth inhibition against two plant pathogens, S. rolfsii and F. oxysporum, respectively, whereas QTMC revealed no impact. Overall, QTMC-AgNPs showed a promising therapeutic potential and,thus, can be considered for drug design rationale.
  8. Chatterjee S, Mahmood S, Hilles AR, Thomas S, Roy S, Provaznik V, et al.
    Int J Biol Macromol, 2023 Sep 01;248:125757.
    PMID: 37429342 DOI: 10.1016/j.ijbiomac.2023.125757
    Research and development in health care industry is in persistence progression. To make it more patient-friendly or to get maximum benefits from it, special attention to different advanced drug delivery system (ADDS) is employed that delivers the drug at the target site and will be able to sustain/control release of drugs. ADDS should be non-toxic, biodegradable, biocompatible along with desirable showing physicochemical and functional properties. These drug delivery systems can be totally based on polymers, either with natural or synthetic polymers. The molecular weight of polymer can be tuned and different groups of polymers can be modified or substituted with other functional groups. Degree of substitution is also tailored. Cationic starch in recent years is exploited in drug delivery, tissue engineering and biomedicine. Due to their abundant availability, low cost, easy chemical modification, low toxicity, biodegradability and biocompatibility, extensive research is now being carried out. Our present discussion will shed light on the usage of cationic starch in health care system.
  9. Ninan N, Muthiah M, Bt Yahaya NA, Park IK, Elain A, Wong TW, et al.
    Colloids Surf B Biointerfaces, 2014 Mar 1;115:244-52.
    PMID: 24362063 DOI: 10.1016/j.colsurfb.2013.11.048
    In this article, gelatin/copper activated faujasites (CAF) composite scaffolds were fabricated by lyophilisation technique for promoting partial thickness wound healing. The optimised scaffold with 0.5% (w/w) of CAF, G (0.5%), demonstrated pore size in the range of 10-350 μm. Agar disc diffusion tests verified the antibacterial role of G (0.5%) and further supported that bacterial lysis was due to copper released from the core of CAF embedded in the gelatin matrix. The change in morphology of bacteria as a function of CAF content in gelatin scaffold was studied using SEM analysis. The confocal images revealed the increase in mortality rate of bacteria with increase in concentration of incorporated CAF in gelatin matrix. Proficient oxygen supply to needy cells is a continuing hurdle faced by tissue engineering scaffolds. The dissolved oxygen measurements revealed that CAF embedded in the scaffold were capable of increasing oxygen supply and thereby promote cell proliferation. Also, G (0.5%) exhibited highest cell viability on NIH 3T3 fibroblast cells which was mainly attributed to the highly porous architecture and its ability to enhance oxygen supply to cells. In vivo studies conducted on Sprague Dawley rats revealed the ability of G (0.5%) to promote skin regeneration in 20 days. Thus, the obtained data suggest that G (0.5%) is an ideal candidate for wound healing applications.
  10. M H, Chong EWN, Jafarzadeh S, Paridah MT, Gopakumar DA, Tajarudin HA, et al.
    Polymers (Basel), 2019 Jan 26;11(2).
    PMID: 30960194 DOI: 10.3390/polym11020210
    This study aimed to compare the performance of fabricated microbially induced precipitated calcium carbonate⁻ (MB⁻CaCO₃) based red seaweed (Kappaphycus alvarezii) bio-polymer film and commercial calcium carbonate⁻ (C⁻CaCO₃) based red seaweed bio-film with the conventional biodegradable mulch film. To the best of our knowledge, there has been limited research on the application of commercial CaCO₃ (C⁻CaCO₃) and microbially induced CaCO₃ (MB⁻CaCO₃) as fillers for the preparation of films from seaweed bio-polymer and comparison with biodegradable commercial plasticulture packaging. The results revealed that the mechanical, contact angle, and biodegradability properties of the polymer composite films incorporated with C⁻CaCO₃ and MB⁻CaCO₃ fillers were comparable or even superior than the conventional biodegradable mulch film. The seaweed polymer film incorporated with MB⁻CaCO₃ showed the highest contact angle of 100.94°, whereas conventional biodegradable mulch film showed a contact angle of 90.25°. The enhanced contact angle of MB⁻CaCO₃ resulted in high barrier properties, which is highly desired in the current scenario for plasticulture packaging application. The water vapor permeability of MB⁻CaCO₃ based seaweed films was low (2.05 ± 1.06 g·m/m²·s·Pa) when compared to conventional mulch film (2.68 ± 0.35 g·m/m²·s·Pa), which makes the fabricated film an ideal candidate for plasticulture application. The highest tensile strength (TS) was achieved by seaweed-based film filled with commercial CaCO₃ (84.92% higher than conventional mulch film). SEM images of the fractured surfaces of the fabricated films revealed the strong interaction between seaweed and fillers. Furthermore, composite films incorporated with MB⁻CaCO₃ promote brighter film, better water barrier, hydrophobicity, and biodegradability compared to C⁻CaCO₃ based seaweed polymer film and conventional mulch film. From this demonstrated work, it can be concluded that the fabricated MB⁻CaCO₃ based seaweed biopolymer film will be a promising candidate for plasticulture and agricultural application.
  11. Atiqah MSN, Gopakumar DA, F A T O, Pottathara YB, Rizal S, Aprilia NAS, et al.
    Polymers (Basel), 2019 Nov 05;11(11).
    PMID: 31694184 DOI: 10.3390/polym11111813
    The conventional isolation of cellulose nanofibers (CNFs) process involves high energy input which leads to compromising the pulp fiber's physical and chemical properties, in addition to the issue of elemental chlorine-based bleaching, which is associated with serious environmental issues. This study investigates the characteristic functional properties of CNFs extracted via total chlorine-free (TCF) bleached kenaf fiber followed by an eco-friendly supercritical carbon dioxide (SC-CO2) treatment process. The Fourier transmission infra-red FTIR spectra result gave remarkable effective delignification of the kenaf fiber as the treatment progressed. TEM images showed that the extracted CNFs have a diameter in the range of 10-15 nm and length of up to several micrometers, and thereby proved that the supercritical carbon dioxide pretreatment followed by mild acid hydrolysis is an efficient technique to extract CNFs from the plant biomass. XRD analysis revealed that crystallinity of the fiber was enhanced after each treatment and the obtained crystallinity index of the raw fiber, alkali treated fiber, bleached fiber, and cellulose nanofiber were 33.2%, 54.6%, 88.4%, and 92.8% respectively. SEM images showed that amorphous portions like hemicellulose and lignin were removed completely after the alkali and bleaching treatment, respectively. Moreover, we fabricated a series of cellulose nanopapers using the extracted CNFs suspension via a simple vacuum filtration technique. The fabricated cellulose nanopaper exhibited a good tensile strength of 75.7 MPa at 2.45% strain.
  12. Fadilah NIM, Riha SM, Mazlan Z, Wen APY, Hao LQ, Joseph B, et al.
    Front Bioeng Biotechnol, 2023;11:1160577.
    PMID: 37292094 DOI: 10.3389/fbioe.2023.1160577
    Skin tissue engineering possesses great promise in providing successful wound injury and tissue loss treatments that current methods cannot treat or achieve a satisfactory clinical outcome. A major field direction is exploring bioscaffolds with multifunctional properties to enhance biological performance and expedite complex skin tissue regeneration. Multifunctional bioscaffolds are three-dimensional (3D) constructs manufactured from natural and synthetic biomaterials using cutting-edge tissue fabrication techniques incorporated with cells, growth factors, secretomes, antibacterial compounds, and bioactive molecules. It offers a physical, chemical, and biological environment with a biomimetic framework to direct cells toward higher-order tissue regeneration during wound healing. Multifunctional bioscaffolds are a promising possibility for skin regeneration because of the variety of structures they provide and the capacity to customise the chemistry of their surfaces, which allows for the regulated distribution of bioactive chemicals or cells. Meanwhile, the current gap is through advanced fabrication techniques such as computational designing, electrospinning, and 3D bioprinting to fabricate multifunctional scaffolds with long-term safety. This review stipulates the wound healing processes used by commercially available engineered skin replacements (ESS), highlighting the demand for a multifunctional, and next-generation ESS replacement as the goals and significance study in tissue engineering and regenerative medicine (TERM). This work also scrutinise the use of multifunctional bioscaffolds in wound healing applications, demonstrating successful biological performance in the in vitro and in vivo animal models. Further, we also provided a comprehensive review in requiring new viewpoints and technological innovations for the clinical application of multifunctional bioscaffolds for wound healing that have been found in the literature in the last 5 years.
  13. Duncan CJ, Mohamad SM, Young DF, Skelton AJ, Leahy TR, Munday DC, et al.
    Sci Transl Med, 2015 Sep 30;7(307):307ra154.
    PMID: 26424569 DOI: 10.1126/scitranslmed.aac4227
    Type I interferon (IFN-α/β) is a fundamental antiviral defense mechanism. Mouse models have been pivotal to understanding the role of IFN-α/β in immunity, although validation of these findings in humans has been limited. We investigated a previously healthy child with fatal encephalitis after inoculation of the live attenuated measles, mumps, and rubella (MMR) vaccine. By targeted resequencing, we identified a homozygous mutation in the high-affinity IFN-α/β receptor (IFNAR2) in the proband, as well as a newborn sibling, that rendered cells unresponsive to IFN-α/β. Reconstitution of the proband's cells with wild-type IFNAR2 restored IFN-α/β responsiveness and control of IFN-attenuated viruses. Despite the severe outcome of systemic live vaccine challenge, the proband had previously shown no evidence of heightened susceptibility to respiratory viral pathogens. The phenotype of IFNAR2 deficiency, together with similar findings in STAT2-deficient patients, supports an essential but narrow role for IFN-α/β in human antiviral immunity.
  14. Lea AJ, Clark AG, Dahl AW, Devinsky O, Garcia AR, Golden CD, et al.
    PLoS Biol, 2023 Sep;21(9):e3002311.
    PMID: 37695771 DOI: 10.1371/journal.pbio.3002311
    Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of "lifestyle" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be "mismatched" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions, with different health effects in "ancestral" versus "modern" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the "matched" to "mismatched" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.
  15. Lea AJ, Clark AG, Dahl AW, Devinsky O, Garcia AR, Golden CD, et al.
    ArXiv, 2023 Feb 13.
    PMID: 36713247
    Globally, we are witnessing the rise of complex, non-communicable diseases (NCDs) related to changes in our daily environments. Obesity, asthma, cardiovascular disease, and type 2 diabetes are part of a long list of "lifestyle" diseases that were rare throughout human history but are now common. A key idea from anthropology and evolutionary biology-the evolutionary mismatch hypothesis-seeks to explain this phenomenon. It posits that humans evolved in environments that radically differ from the ones experienced by most people today, and thus traits that were advantageous in past environments may now be "mismatched" and disease-causing. This hypothesis is, at its core, a genetic one: it predicts that loci with a history of selection will exhibit "genotype by environment" (GxE) interactions and have differential health effects in ancestral versus modern environments. Here, we discuss how this concept could be leveraged to uncover the genetic architecture of NCDs in a principled way. Specifically, we advocate for partnering with small-scale, subsistence-level groups that are currently transitioning from environments that are arguably more "matched" with their recent evolutionary history to those that are more "mismatched". These populations provide diverse genetic backgrounds as well as the needed levels and types of environmental variation necessary for mapping GxE interactions in an explicit mismatch framework. Such work would make important contributions to our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and sociocultural contexts.
  16. Corbel V, Kont MD, Ahumada ML, Andréo L, Bayili B, Bayili K, et al.
    Parasit Vectors, 2023 Jan 20;16(1):21.
    PMID: 36670470 DOI: 10.1186/s13071-022-05554-7
    BACKGROUND: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both.

    METHODS: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC50 and LC99, respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI50 and OI99), to measure mortality and the sterilizing effect, respectively.

    RESULTS: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC50/LC99 or OI50/OI99 values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were

  17. Thomas S, Borges F, Bhandari M, De Beer J, Urrútia Cuchí G, Adili A, et al.
    J Bone Joint Surg Am, 2020 May 20;102(10):880-888.
    PMID: 32118652 DOI: 10.2106/JBJS.18.01305
    BACKGROUND: Myocardial injury after noncardiac surgery (MINS) is common and of prognostic importance. Little is known about MINS in orthopaedic surgery. The diagnostic criterion for MINS was a level of ≥0.03 ng/mL on a non-high-sensitivity troponin T (TnT) assay due to myocardial ischemia.

    METHODS: We undertook an international, prospective study of 15,103 patients ≥45 years of age who had inpatient noncardiac surgery; 3,092 underwent orthopaedic surgery. Non-high-sensitivity TnT assays were performed on postoperative days 0, 1, 2, and 3. Among orthopaedic patients, we determined (1) the prognostic relevance of the MINS diagnostic criteria, (2) the 30-day mortality rate for those with and without MINS, and (3) the probable proportion of MINS cases that would go undetected without troponin monitoring because of a lack of an ischemic symptom.

    RESULTS: Three hundred and sixty-seven orthopaedic patients (11.9%) had MINS. MINS was associated independently with 30-day mortality including among those who had had orthopaedic surgery. Orthopaedic patients without and with MINS had a 30-day mortality rate of 1.0% and 9.8%, respectively (odds ratio [OR], 11.28; 95% confidence interval [CI], 6.72 to 18.92). The 30-day mortality rate was increased for patients with MINS who had an ischemic feature (i.e., symptoms, or evidence of ischemia on electrocardiography or imaging) (OR, 18.25; 95% CI, 10.06 to 33.10) and for those who did not have an ischemic feature (OR, 7.35; 95% CI, 3.37 to 16.01). The proportion of orthopaedic patients with MINS who were asymptomatic and in whom the myocardial injury would have probably gone undetected without TnT monitoring was 81.3% (95% CI, 76.3% to 85.4%).

    CONCLUSIONS: One in 8 orthopaedic patients in our study had MINS, and MINS was associated with a higher mortality rate regardless of symptoms. Troponin levels should be measured after surgery in at-risk patients because most MINS cases (>80%) are asymptomatic and would go undetected without routine measurements.

    LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

  18. Dias A, Brook MN, Bancroft EK, Page EC, Chamberlain A, Saya S, et al.
    BJUI Compass, 2023 May;4(3):361-373.
    PMID: 37025481 DOI: 10.1002/bco2.156
    OBJECTIVES: The relation of serum androgens and the development of prostate cancer (PCa) is subject of debate. Lower total testosterone (TT) levels have been associated with increased PCa detection and worse pathological features after treatment. However, data from the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) and Prostate Cancer Prevention (PCPT) trial groups indicate no association. The aim of this study is to investigate the association of serum androgen levels and PCa detection in a prospective screening study of men at higher genetic risk of aggressive PCa due to BRCA1/2 pathogenic variants (PVs), the IMPACT study.

    METHODS: Men enrolled in the IMPACT study provided serum samples during regular visits. Hormonal levels were calculated using immunoassays. Free testosterone (FT) was calculated from TT and sex hormone binding globulin (SHBG) using the Sodergard mass equation. Age, body mass index (BMI), prostate-specific antigen (PSA) and hormonal concentrations were compared between genetic cohorts. We also explored associations between age and TT, SHBG, FT and PCa, in the whole subset and stratified by BRCA1/2 PVs status.

    RESULTS: A total of 777 participants in the IMPACT study had TT and SHBG measurements in serum samples at annual visits, giving 3940 prospective androgen levels, from 266 BRCA1 PVs carriers, 313 BRCA2 PVs carriers and 198 non-carriers. The median number of visits per patient was 5. There was no difference in TT, SHBG and FT between carriers and non-carriers. In a univariate analysis, androgen levels were not associated with PCa. In the analysis stratified by carrier status, no significant association was found between hormonal levels and PCa in non-carriers, BRCA1 or BRCA2 PVs carriers.

    CONCLUSIONS: Male BRCA1/2 PVs carriers have a similar androgen profile to non-carriers. Hormonal levels were not associated with PCa in men with and without BRCA1/2 PVs. Mechanisms related to the particularly aggressive phenotype of PCa in BRCA2 PVs carriers may therefore not be linked with circulating hormonal levels.

  19. Lesseur C, Diergaarde B, Olshan AF, Wünsch-Filho V, Ness AR, Liu G, et al.
    Nat Genet, 2016 Dec;48(12):1544-1550.
    PMID: 27749845 DOI: 10.1038/ng.3685
    We conducted a genome-wide association study of oral cavity and pharyngeal cancer in 6,034 cases and 6,585 controls from Europe, North America and South America. We detected eight significantly associated loci (P < 5 × 10-8), seven of which are new for these cancer sites. Oral and pharyngeal cancers combined were associated with loci at 6p21.32 (rs3828805, HLA-DQB1), 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2-TRIM5). Oral cancer was associated with two new regions, 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3), and with known cancer-related loci-9p21.3 (rs8181047, CDKN2B-AS1) and 5p15.33 (rs10462706, CLPTM1L). Oropharyngeal cancer associations were limited to the human leukocyte antigen (HLA) region, and classical HLA allele imputation showed a protective association with the class II haplotype HLA-DRB1*1301-HLA-DQA1*0103-HLA-DQB1*0603 (odds ratio (OR) = 0.59, P = 2.7 × 10-9). Stratified analyses on a subgroup of oropharyngeal cases with information available on human papillomavirus (HPV) status indicated that this association was considerably stronger in HPV-positive (OR = 0.23, P = 1.6 × 10-6) than in HPV-negative (OR = 0.75, P = 0.16) cancers.
  20. Jerome JTJ, Mercier F, Mudgal CS, Arenas-Prat J, Vinagre G, Goorens CK, et al.
    J Hand Microsurg, 2020 Dec;12(3):135-162.
    PMID: 33408440 DOI: 10.1055/s-0040-1713964
    With a lot of uncertainty, unclear, and frequently changing management protocols, COVID-19 has significantly impacted the orthopaedic surgical practice during this pandemic crisis. Surgeons around the world needed closed introspection, contemplation, and prospective consensual recommendations for safe surgical practice and prevention of viral contamination. One hundred orthopaedic surgeons from 50 countries were sent a Google online form with a questionnaire explicating protocols for admission, surgeries, discharge, follow-up, relevant information affecting their surgical practices, difficulties faced, and many more important issues that happened during and after the lockdown. Ten surgeons critically construed and interpreted the data to form rationale guidelines and recommendations. Of the total, hand and microsurgery surgeons (52%), trauma surgeons (32%), joint replacement surgeons (20%), and arthroscopy surgeons (14%) actively participated in the survey. Surgeons from national public health care/government college hospitals (44%) and private/semiprivate practitioners (54%) were involved in the study. Countries had lockdown started as early as January 3, 2020 with the implementation of partial or complete lifting of lockdown in few countries while writing this article. Surgeons (58%) did not stop their surgical practice or clinics but preferred only emergency cases during the lockdown. Most of the surgeons (49%) had three-fourths reduction in their total patients turn-up and the remaining cases were managed by conservative (54%) methods. There was a 50 to 75% reduction in the number of surgeries. Surgeons did perform emergency procedures without COVID-19 tests but preferred reverse transcription polymerase chain reaction (RT-PCR; 77%) and computed tomography (CT) scan chest (12%) tests for all elective surgical cases. Open fracture and emergency procedures (60%) and distal radius (55%) fractures were the most commonly performed surgeries. Surgeons preferred full personal protection equipment kits (69%) with a respirator (N95/FFP3), but in the case of unavailability, they used surgical masks and normal gowns. Regional/local anesthesia (70%) remained their choice for surgery to prevent the aerosolized risk of contaminations. Essential surgical follow-up with limited persons and visits was encouraged by 70% of the surgeons, whereas teleconsultation and telerehabilitation by 30% of the surgeons. Despite the protective equipment, one-third of the surgeons were afraid of getting infected and 56% feared of infecting their near and dear ones. Orthopaedic surgeons in private practice did face 50 to 75% financial loss and have to furlough 25% staff and 50% paramedical persons. Orthopaedics meetings were cancelled, and virtual meetings have become the preferred mode of sharing the knowledge and experiences avoiding human contacts. Staying at home, reading, and writing manuscripts became more interesting and an interesting lifestyle change is seen among the surgeons. Unanimously and without any doubt all accepted the fact that COVID-19 pandemic has reached an unprecedented level where personal hygiene, hand washing, social distancing, and safe surgical practices are the viable antidotes, and they have all slowly integrated these practices into their lives. Strict adherence to local authority recommendations and guidelines, uniform and standardized norms for admission, inpatient, and discharge, mandatory RT-PCR tests before surgery and in selective cases with CT scan chest, optimizing and regularizing the surgeries, avoiding and delaying nonemergency surgeries and follow-up protocols, use of teleconsultations cautiously, and working in close association with the World Health Organization and national health care systems will provide a conducive and safe working environment for orthopaedic surgeons and their fraternity and also will prevent the resurgence of COVID-19.
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