Publications by authors named "Daniel Simon"

334 Publications

ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery".

Sex Med 2021 Dec 28;10(1):100471. Epub 2021 Dec 28.

Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium.

Introduction: Much has been published on the surgical and functional results following Gender Affirming Surgery ('GAS') in trans individuals. Comprehensive results regarding sexual wellbeing following GAS, however, are generally lacking.

Aim: To review the impact of various GAS on sexual wellbeing in treatment seeking trans individuals, and provide a comprehensive list of clinical recommendations regarding the various surgical options of GAS on behalf of the European Society for Sexual Medicine.

Methods: The Medline, Cochrane Library and Embase databases were reviewed on the results of sexual wellbeing after GAS.

Main Outcomes Measure: The task force established consensus statements regarding the somatic and general requirements before GAS and of GAS: orchiectomy-only, vaginoplasty, breast augmentation, vocal feminization surgery, facial feminization surgery, mastectomy, removal of the female sexual organs, metaidoioplasty, and phalloplasty. Outcomes pertaining to sexual wellbeing- sexual satisfaction, sexual relationship, sexual response, sexual activity, enacted sexual script, sexuality, sexual function, genital function, quality of sex life and sexual pleasure- are provided for each statement separately.

Results: The present position paper provides clinicians with statements and recommendations for clinical practice, regarding GAS and their effects on sexual wellbeing in trans individuals. These data, are limited and may not be sufficient to make evidence-based recommendations for every surgical option. Findings regarding sexual wellbeing following GAS were mainly positive. There was no data on sexual wellbeing following orchiectomy-only, vocal feminization surgery, facial feminization surgery or the removal of the female sexual organs. The choice for GAS is dependent on patient preference, anatomy and health status, and the surgeon's skills. Trans individuals may benefit from studies focusing exclusively on the effects of GAS on sexual wellbeing.

Conclusion: The available evidence suggests positive results regarding sexual wellbeing following GAS. We advise more studies that underline the evidence regarding sexual wellbeing following GAS. This position statement may aid both clinicians and patients in decision-making process regarding the choice for GAS. Müjde Özer, Sahaand Poor Toulabi, Alessandra D. Fisher, et al. ESSM Position Statement "Sexual Wellbeing After Gender Affirming Surgery". Sex Med 2021;XX:XXXXXX.
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http://dx.doi.org/10.1016/j.esxm.2021.100471DOI Listing
December 2021

Facial Gender Surgery: Systematic Review and Evidence-Based Consensus Guidelines from the International Facial Gender Symposium.

Plast Reconstr Surg 2022 Jan;149(1):212-224

From the Departments of Plastic and Reconstructive Surgery and Psychiatry, Johns Hopkins University School of Medicine; Johns Hopkins Center for Transgender Health, Johns Hopkins Hospital; Division of Plastic and Reconstructive Surgery, Oregon Health & Science University; Division of Plastic and Reconstructive Surgery, Louisiana State University Medical Center and Children's Hospital of New Orleans; The Meltzer Clinic PC; James Vogel Plastic Surgery; Align Surgical Associates, Inc.; Division of Plastic Surgery, Department of Surgery, University of Washington School of Medicine; and The Facialteam Group, HC Marbella International Hospital.

Background: Increasing societal acceptance of transgender people has led to broader availability of gender surgery and rapid growth in transition-related operations. Facial gender surgery aims to modify patients' facial features to be more congruent with their physical expression of gender, reducing gender dysphoria and improving quality of life. Growth in research and technique evolution has not kept pace with growth in clinical volume. Therefore, the first International Facial Gender Symposium was held at Johns Hopkins University in 2019, convening surgeons who perform facial gender surgery to share ideas and assess the state of clinical evidence.

Methods: To review the literature on facial gender surgery, the authors developed a search strategy for seven electronic databases (PubMed, PsycINFO, Embase, CINAHL, Web of Science, Cochrane, and Gender Studies) through May of 2019, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review guidelines.

Results: Based on the English language literature and clinical experience, the authors suggest guidelines for screening, management, and appropriate surgical technique for patients undergoing facial gender surgery. They highlight facial gender surgery as a medically necessary intervention and identify shortcomings in current guidelines.

Conclusions: Facial gender surgery represents a complex array of craniofacial and soft-tissue procedures that require application of advanced skills and decision-making. Facial gender operations are not cosmetic, are medically necessary, and require development of new CPT codes specific to facial gender surgery. It is imperative to create educational programs and methods to define sufficient training for facial gender surgery surgeons. Research priorities include better procedural outcomes data, more quality-of-life studies, and insight into variation in both patient and procedural subgroups.
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http://dx.doi.org/10.1097/PRS.0000000000008668DOI Listing
January 2022

Immediate mobilization of distal radius fractures stabilized by volar locking plate results in a better short-term outcome than a five week immobilization: A prospective randomized trial.

Clin Rehabil 2021 Dec 1:2692155211036674. Epub 2021 Dec 1.

AUVA Trauma Hospital Lorenz Böhler - European Hand Trauma Center, Vienna, Austria.

Objective: To evaluate the impact of immediate (first day after surgery) mobilization compared to standard five weeks cast immobilization on the functional outcome after volar locking plate fixation of distal radius fractures.

Design: Prospective randomized parallel group comparative trial.

Setting: Trauma Hospital, Austria.

Participants: Patients with isolated unstable distal radius fractures, stabilized with volar angular stable locking plate.

Interventions: The immediate mobilization group received a removable forearm splint for one week and active supervised group physiotherapy and home exercises for the shoulder, elbow, wrist, and fingers from the first postoperative day. The cast immobilization group received a non-removable cast for five weeks. In the first five weeks supervised group physiotherapy and home exercises were performed for shoulder, elbow, and fingers. Thereafter additional supervised and home exercises for the wrist were started.

Main Measures: At regular intervals of six and nine weeks, three and six months, and one year post surgery range of motion, grip strength, and x-rays were evaluated. Additionally, the shortened disabilities of the arm, shoulder and hand (DASH) score, Patient-rated Wrist Evaluation, Mayo Wrist score, and pain according to the Visual Analog Scale score were analyzed.

Results: One hundred and sixteen patients were prospectively randomized into two study groups. At the one-year follow-up, patients in the immediate mobilization group showed a significantly higher range of motion in extension/flexion (mean difference 10.2°, 99% confidence interval 0.6-19.8), grip strength (mean difference 5.1 kg, 99% confidence interval -0.5 to 10.7), and Mayo Wrist score (mean difference 7.9 points, 99% confidence interval 2.3-13.5) than the cast immobilization group. Range of motion in supination/pronation (mean difference 13.4°, 99% confidence interval 1.5-25.3) and in radial/ulnar deviation (mean difference 6.3°, 99% confidence interval 0.9-11.7) differed significantly up to nine weeks favoring the immediate mobilization group. The Patient-rated Wrist Evaluation revealed significantly better scores after three months (mean difference 9.3 points, 99% confidence interval 0.5-18.1) and DASH after six months (mean difference 7.3 points, 99% confidence interval 0.3-14.3) in the immediate mobilization group. All other subsequent follow-up examinations indicated no significant differences in respect of pain, range of motion, and patient-reported outcome measurements between the study groups. There were no significant differences in respect of radiological loss of reduction and complications between the groups.

Conclusions: Immediate mobilization in combination with supervised physiotherapy of the wrist after volar locking plate fixation of unstable distal radius fractures results in a significantly improved range of motion and grip strength after one year compared to cast immobilization. No increased risk for loss of reduction and other complications was observed.
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http://dx.doi.org/10.1177/02692155211036674DOI Listing
December 2021

Biostack: Nontoxic Metabolite Detection from Live Tissue.

Adv Sci (Weinh) 2022 Jan 5;9(2):e2101711. Epub 2021 Nov 5.

Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK, USA.

There is increasing demand for direct in situ metabolite monitoring from cell cultures and in vivo using implantable devices. Electrochemical biosensors are commonly preferred due to their low-cost, high sensitivity, and low complexity. Metabolite detection, however, in cultured cells or sensitive tissue is rarely shown. Commonly, glucose sensing occurs indirectly by measuring the concentration of hydrogen peroxide, which is a by-product of the conversion of glucose by glucose oxidase. However, continuous production of hydrogen peroxide in cell media with high glucose is toxic to adjacent cells or tissue. This challenge is overcome through a novel, stacked enzyme configuration. A primary enzyme is used to provide analyte sensitivity, along with a secondary enzyme which converts H O back to O . The secondary enzyme is functionalized as the outermost layer of the device. Thus, production of H O remains local to the sensor and its concentration in the extracellular environment does not increase. This "biostack" is integrated with organic electrochemical transistors to demonstrate sensors that monitor glucose concentration in cell cultures in situ. The "biostack" renders the sensors nontoxic for cells and provides highly sensitive and stable detection of metabolites.
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http://dx.doi.org/10.1002/advs.202101711DOI Listing
January 2022

Hospitalization for Heart Failure in the United States, UK, Taiwan, and Japan: An International Comparison of Administrative Health Records on 413,385 Individual Patients.

J Card Fail 2021 Oct 8. Epub 2021 Oct 8.

Department of Population Science and Gene Health, National Heart & Lung Institute, Imperial College London, London, UK; The Department of Medicine, Louis Stokes Veteran Affairs Medical Center, Cleveland, Ohio.

Background: Registries show international variations in the characteristics and outcome of patients with heart failure (HF), but national samples are rarely large, and case selection may be biased owing to enrolment in academic centers. National administrative datasets provide large samples with a low risk of bias. In this study, we compared the characteristics, health care resource use (HRU) and outcomes of patients with primary HF hospitalizations (HFH) using electronic health records (EHR) from 4 high-income countries (United States, UK, Taiwan, Japan) on 3 continents.

Methods And Results: We used electronic health record to identify unplanned HFH between 2012 and 2014. We identified 231,512, 10,991, 36,900, and 133,982 patients with a primary HFH from the United States, the UK, Taiwan, and Japan, respectively. HFH per 100,000 population was highest in the United States and lowest in Taiwan. Fewer patients in Taiwan and Japan were obese or had chronic kidney disease. The length of hospital stay was shortest in the United States (median 4 days) and longer in the UK, Taiwan, and Japan (medians of 7, 9, and 17 days, respectively). HRU during hospitalization was highest in Japan and lowest in UK. Crude and direct standardized in-hospital mortality was lowest in the United States (direct standardized rates 1.8, 95% confidence interval 1.7%-1.9%) and progressively higher in Taiwan (direct standardized rates 3.9, 95% CI 3.8%-4.1%), the UK (direct standardized rates 6.4, 95% CI 6.1%-6.7%), and Japan (direct standardized rates 6.7, 95% CI 6.6%-6.8%). The 30-day all-cause (25.8%) and HF (7.2%) readmissions were highest in the United States and lowest in Japan (11.9% and 5.1%, respectively).

Conclusions: Marked international variations in patient characteristics, HRU, and clinical outcomes exist; understanding them might inform health care policy and international trial design.
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http://dx.doi.org/10.1016/j.cardfail.2021.08.024DOI Listing
October 2021

Evaluation of the genetic toxicity of sofosbuvir and simeprevir with and without ribavirin in a human-derived liver cell line.

An Acad Bras Cienc 2021 24;93(4):e20200632. Epub 2021 Sep 24.

Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA), PPG Biologia Celular e Molecular Aplicada à Saúde, Av. Farroupilha, 8001, Prédio 22, 4° andar, 92425-900 Canoas, RS, Brazil.

Direct-acting antivirals have revolutionized the treatment of chronic hepatitis C. Sofosbuvir and simeprevir are prescribed worldwide. However, there is a scarcity of information regarding their genotoxicity. Therefore, the present study assessed the cytotoxic and genotoxic effects of sofosbuvir and simeprevir, alone and combined with ribavirin. HepG2 cells were analyzed using the in vitro cytokinesis-block micronucleus cytome assay. Cells were treated for 24 h with sofosbuvir (0.011-1.511 mM), simeprevir (0.156-5.0 µM), and their combinations with ribavirin (0.250-4.0 mM). No significant differences were observed in the nuclear division cytotoxicity index, reflecting the absence of cytotoxic effects associated to sofosbuvir. However, the highest concentration of simeprevir showed a significant difference for the nuclear division cytotoxicity index. Moreover, significant results were observed for nuclear division cytotoxicity index in two combinations of sofosbuvir plus ribavirin and only in the highest combination of simeprevir plus ribavirin. Additionally, our results showed that sofosbuvir did not increase the frequency of chromosomal damage, but simeprevir significantly increased the frequency of micronuclei at the highest concentrations. The combination index demonstrated that both sofosbuvir and simeprevir produced antagonism to the genotoxic effects of ribavirin. In conclusion, our results showed that simeprevir, but not sofosbuvir, has genotoxic effects in HepG2 cells.
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http://dx.doi.org/10.1590/0001-3765202120200632DOI Listing
October 2021

Clinical outcomes according to lesion complexity in high bleeding risk patients treated with 1-month dual antiplatelet therapy following PCI: Analysis from the Onyx ONE clear study.

Catheter Cardiovasc Interv 2021 Sep 3. Epub 2021 Sep 3.

The Cardiovascular Research Foundation, New York, New York, USA.

Objectives: To compare clinical outcomes in high bleeding risk (HBR) patients with and without complex percutaneous coronary intervention (PCI) treated with Resolute Onyx zotarolimus-eluting stents (ZES) after 1-month dual antiplatelet therapy (DAPT).

Background: PCI with 1-month DAPT has been demonstrated to be safe in HBR patients treated with Resolute Onyx ZES. Whether these outcomes are consistent in patients with complex lesions is uncertain.

Methods: Among HBR patients who were event-free 1 month after PCI with ZES and treated thereafter with single antiplatelet therapy (SAPT), the clinical outcomes between 1 month and 1 year were compared after complex PCI (3 vessels treated, ≥ 3 lesions treated, total stent length > 60 mm, bifurcation with ≥ 2 stents implanted, atherectomy, or left main, surgical bypass graft or chronic total occlusion PCI) versus noncomplex PCI. Propensity score adjustment was performed to adjust for baseline differences among complex and noncomplex patients.

Results: Complex patients (N = 401, 26.6% of total) had a higher prevalence of hyperlipidemia, diabetes mellitus and previous myocardial infarction (MI). Between 1 month and 1 year, rates of MI (7.1% vs. 4.0%, p = 0.02) and cardiac death/MI (9.3% vs. 6.1%, p = 0.04) were higher among complex versus noncomplex patients, although stent thrombosis rates were similar. After adjustment for baseline characteristics, differences in outcomes were no longer significant between groups.

Conclusions: Higher rates of ischemic outcomes in complex PCI patients were largely explained by baseline clinical differences, rather than lesion complexity, among HBR patients treated with 1-month DAPT following PCI with Resolute Onyx ZES.
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http://dx.doi.org/10.1002/ccd.29939DOI Listing
September 2021

Aim32 is a dual-localized 2Fe-2S mitochondrial protein that functions in redox quality control.

J Biol Chem 2021 10 28;297(4):101135. Epub 2021 Aug 28.

Department of Biology, Loyola Marymount University, Los Angeles, California, USA. Electronic address:

Yeast is a facultative anaerobe and uses diverse electron acceptors to maintain redox-regulated import of cysteine-rich precursors via the mitochondrial intermembrane space assembly (MIA) pathway. With the growing diversity of substrates utilizing the MIA pathway, understanding the capacity of the intermembrane space (IMS) to handle different types of stress is crucial. We used MS to identify additional proteins that interacted with the sulfhydryl oxidase Erv1 of the MIA pathway. Altered inheritance of mitochondria 32 (Aim32), a thioredoxin-like [2Fe-2S] ferredoxin protein, was identified as an Erv1-binding protein. Detailed localization studies showed that Aim32 resided in both the mitochondrial matrix and IMS. Aim32 interacted with additional proteins including redox protein Osm1 and protein import components Tim17, Tim23, and Tim22. Deletion of Aim32 or mutation of conserved cysteine residues that coordinate the Fe-S center in Aim32 resulted in an increased accumulation of proteins with aberrant disulfide linkages. In addition, the steady-state level of assembled TIM22, TIM23, and Oxa1 protein import complexes was decreased. Aim32 also bound to several mitochondrial proteins under nonreducing conditions, suggesting a function in maintaining the redox status of proteins by potentially targeting cysteine residues that may be sensitive to oxidation. Finally, Aim32 was essential for growth in conditions of stress such as elevated temperature and hydroxyurea, and under anaerobic conditions. These studies suggest that the Fe-S protein Aim32 has a potential role in general redox homeostasis in the matrix and IMS. Thus, Aim32 may be poised as a sensor or regulator in quality control for a broad range of mitochondrial proteins.
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http://dx.doi.org/10.1016/j.jbc.2021.101135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482512PMC
October 2021

Sensing Inflammation Biomarkers with Electrolyte-Gated Organic Electronic Transistors.

Adv Healthc Mater 2021 10 22;10(20):e2100955. Epub 2021 Aug 22.

Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 103, Modena, 41125, Italy.

An overview of cytokine biosensing is provided, with a focus on the opportunities provided by organic electronic platforms for monitoring these inflammation biomarkers which manifest at ultralow concentration levels in physiopathological conditions. Specifically, two of the field's state-of-the-art technologies-organic electrochemical transistors (OECTs) and electrolyte gated organic field effect transistors (EGOFETs)-and their use in sensing cytokines and other proteins associated with inflammation are a particular focus. The overview will include an introduction to current clinical and "gold standard" quantification techniques and their limitations in terms of cost, time, and required infrastructure. A critical review of recent progress with OECT- and EGOFET-based protein biosensors is presented, alongside a discussion onthe future of these technologies in the years and decades ahead. This is especially timely as the world grapples with limited healthcare diagnostics during the Coronavirus disease (COVID-19)pandemic where one of the worst-case scenarios for patients is the "cytokine storm." Clearly, low-cost point-of-care technologies provided by OECTs and EGOFETs can ease the global burden on healthcare systems and support professionals by providing unprecedented wealth of data that can help to monitor disease progression in real time.
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http://dx.doi.org/10.1002/adhm.202100955DOI Listing
October 2021

Masking Gender: The Impact of Facial Coverings on Gender Recognition.

Plast Reconstr Surg 2021 Sep;148(3):521e-522e

The Facialteam Group, HC Marbella International Hospital, Marbella, Málaga, Spain.

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http://dx.doi.org/10.1097/PRS.0000000000008273DOI Listing
September 2021

Effects of large gatherings on the COVID-19 epidemic: Evidence from professional and college sports.

Econ Hum Biol 2021 12 1;43:101033. Epub 2021 Jul 1.

O'Neill School, Indiana University, 1315 E 10th St, Bloomington, IN 47405, USA. Electronic address:

We compare COVID-19 case loads and mortality across counties that hosted more versus fewer NHL hockey games, NBA basketball games, and NCAA basketball games during the early months of 2020, before any large outbreaks were identified. We find that hosting one additional NHL/NBA game in March 2020 leads to an additional 7520 cases and 658 deaths. Similarly, we find that hosting an additional NCAA Division 1 men's basketball game in March 2020 results in an additional 34 deaths. Back-of-the-envelope calculations suggest that the per-game fatality costs were 200-300 times greater than per-game spending.
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http://dx.doi.org/10.1016/j.ehb.2021.101033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643424PMC
December 2021

Mild Therapeutic Hypothermia Alters Hemostasis in ST Elevation Myocardial Infarction Patients.

Front Cardiovasc Med 2021 6;8:707367. Epub 2021 Jul 6.

Division of Cardiology, Department of Internal Medicine II, Vienna General Hospital, Medical University of Vienna, Vienna, Austria.

Mild therapeutic hypothermia (MTH) is a concept to reduce infarct size and improve outcome after ST-segment elevation myocardial infarction (STEMI). In the STATIM trial, we investigated MTH as an additional therapy for STEMI patients. In the intention-to-treat set, 101 patients were included. No difference in primary and secondary endpoints measured by cardiac magnetic resonance imaging was found. Platelet activation and plasmatic coagulation are key in the pathophysiology of STEMI. In the present study, we investigated the effect of MTH on primary and secondary hemostasis in STEMI patients. Platelet function and morphology were assessed by routine blood count, aggregometry testing, and flow cytometry. Soluble platelet markers were determined by enzyme-linked immunosorbent assay (ELISA) testing. Plasmatic coagulation was measured throughout the study. Platelet count remained unchanged, irrespective of treatment, whereas platelet size decreased in both patient groups. Platelet aggregometry indicated increased platelet reactivity in the MTH group. Furthermore, higher adenosine diphosphate (ADP) plasma levels were found in MTH patients. Expression of glycoprotein IIb/IIIa was increased on platelets of STEMI patients treated with MTH. Lower patient temperatures correlated with longer clotting times and resulted in reduced pH. Lower pH values were positively correlated with longer clotting times. Present data indicate longer clotting times and higher platelet reactivity in STEMI patients treated with MTH. These changes did not correspond to clinical bleeding events or larger infarct size.
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http://dx.doi.org/10.3389/fcvm.2021.707367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290912PMC
July 2021

Synergistic Effect of PVDF-Coated PCL-TCP Scaffolds and Pulsed Electromagnetic Field on Osteogenesis.

Int J Mol Sci 2021 Jun 16;22(12). Epub 2021 Jun 16.

School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore 637459, Singapore.

Bone exhibits piezoelectric properties. Thus, electrical stimulations such as pulsed electromagnetic fields (PEMFs) and stimuli-responsive piezoelectric properties of scaffolds have been investigated separately to evaluate their efficacy in supporting osteogenesis. However, current understanding of cells responding under the combined influence of PEMF and piezoelectric properties in scaffolds is still lacking. Therefore, in this study, we fabricated piezoelectric scaffolds by functionalization of polycaprolactone-tricalcium phosphate (PCL-TCP) films with a polyvinylidene fluoride (PVDF) coating that is self-polarized by a modified breath-figure technique. The osteoinductive properties of these PVDF-coated PCL-TCP films on MC3T3-E1 cells were studied under the stimulation of PEMF. Piezoelectric and ferroelectric characterization demonstrated that scaffolds with piezoelectric coefficient = -1.2 pC/N were obtained at a powder dissolution temperature of 100 °C and coating relative humidity (RH) of 56%. DNA quantification showed that cell proliferation was significantly enhanced by PEMF as low as 0.6 mT and 50 Hz. Hydroxyapatite staining showed that cell mineralization was significantly enhanced by incorporation of PVDF coating. Gene expression study showed that the combination of PEMF and PVDF coating promoted late osteogenic gene expression marker most significantly. Collectively, our results suggest that the synergistic effects of PEMF and piezoelectric scaffolds on osteogenesis provide a promising alternative strategy for electrically augmented osteoinduction. The piezoelectric response of PVDF by PEMF, which could provide mechanical strain, is particularly interesting as it could deliver local mechanical stimulation to osteogenic cells using PEMF.
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http://dx.doi.org/10.3390/ijms22126438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234164PMC
June 2021

Targeted Chemotherapy of Glioblastoma Spheroids with an Iontronic Pump.

Adv Mater Technol 2021 May 12;6(5):2001302. Epub 2021 Apr 12.

Gottfried Schatz Research Center - Biophysics Medical University of Graz Graz 8010 Austria.

Successful treatment of glioblastoma multiforme (GBM), the most lethal tumor of the brain, is presently hampered by (i) the limits of safe surgical resection and (ii) "shielding" of residual tumor cells from promising chemotherapeutic drugs such as Gemcitabine (Gem) by the blood brain barrier (BBB). Here, the vastly greater GBM cell-killing potency of Gem compared to the gold standard temozolomide is confirmed, moreover, it shows neuronal cells to be at least 10-fold less sensitive to Gem than GBM cells. The study also demonstrates the potential of an electronically-driven organic ion pump ("GemIP") to achieve controlled, targeted Gem delivery to GBM cells. Thus, GemIP-mediated Gem delivery is confirmed to be temporally and electrically controllable with pmol min precision and electric addressing is linked to the efficient killing of GBM cell monolayers. Most strikingly, GemIP-mediated GEM delivery leads to the overt disintegration of targeted GBM tumor spheroids. Electrically-driven chemotherapy, here exemplified, has the potential to radically improve the efficacy of GBM adjuvant chemotherapy by enabling exquisitely-targeted and controllable delivery of drugs irrespective of whether these can cross the BBB.
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http://dx.doi.org/10.1002/admt.202001302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218220PMC
May 2021

Reply by Authors.

J Urol 2021 09 16;206(3):732. Epub 2021 Jun 16.

Rush University Medical Center, Chicago, Illinois.

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http://dx.doi.org/10.1097/JU.0000000000001777.02DOI Listing
September 2021

Designing S100A9-Targeted Plant Virus Nanoparticles to Target Deep Vein Thrombosis.

Biomacromolecules 2021 06 1;22(6):2582-2594. Epub 2021 Jun 1.

Department of NanoEngineering, University of California, San Diego, La Jolla, California 92093, United States.

Thromboembolic conditions are a leading cause of death worldwide, and deep vein thrombosis (DVT), or occlusive venous clot formation, is a critical and rising problem that contributes to damage of vital organs, long-term complications, and life-threatening conditions such as pulmonary embolism. Early diagnosis and treatment are correlated to better prognosis. However, current technologies in these areas, such as ultrasonography for diagnostics and anticoagulants for treatment, are limited in terms of their accuracy and therapeutic windows. In this work, we investigated targeting myeloid related protein 14 (MRP-14, also known as S100A9) using plant virus-based nanoparticle carriers as a means to achieve tissue specificity aiding prognosis and therapeutic intervention. We used a combinatorial peptide library screen to identify peptide ligands that bind MRP-14. Candidates were selected and formulated as nanoparticles by using cowpea mosaic virus (CPMV) and tobacco mosaic virus (TMV). Intravascular delivery of our MRP-14-targeted nanoparticles in a murine model of DVT resulted in enhanced accumulation in the thrombi and reduced thrombus size, suggesting application of nanoparticles for molecular targeting of MRP-14 could be a promising direction for improving DVT diagnostics, therapeutics, and therefore prognosis.
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http://dx.doi.org/10.1021/acs.biomac.1c00303DOI Listing
June 2021

Hepatitis B virus genotypes in Brazil: Introduction and dissemination.

Infect Genet Evol 2021 09 21;93:104936. Epub 2021 May 21.

Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil; Laboratório de Diagnóstico Molecular, ULBRA, Canoas, RS, Brazil.

Hepatitis B is a viral infectious disease highly spread worldwide with a long evolutionary history associated with human migrations through the continents and countries. Hepatitis B virus (HBV) was disseminated probably from Africa and diverged into ten genotypes (HBV-A to HBV-J) distributed around the world. In Brazil, almost all HBV genotypes were already reported, with a predominance of three ones: A (52.1%), D (36.8%), and F (7.7%). This review aimed to evaluate the introduction and dissemination of the main HBV genotypes and subgenotypes in Brazil over the last centuries to explain the current epidemic scenario. The highest frequency of HBV-A is a consequence of the introduction and spreading of HBV-A1 in the 16th to 19th centuries due to the African slave trade, but the more recent introduction of HBV-A2 from Europe also contributed to the current situation. HBV-D is the second most frequent genotype because it was consecutively introduced by migrations from Europe (mainly subgenotype D3, but also D2) and the Middle East (D1) in the 19th to 20th centuries. On contrary, HBV-F (F1a, F1b, F2a, F2b, F3, and F4) was disseminated by the Amerindians in all South American countries, including Brazil, by migrations inside the continent for more than three centuries ago. Other HBV genotypes are rare and eventually frequent in some human groups because of the dissemination by very specific epidemiological routes. In conclusion, the current scenario of the HBV epidemics is a consequence of the introduction and dissemination of some subgenotypes from the three main genotypes A, D, and F over the last five centuries.
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http://dx.doi.org/10.1016/j.meegid.2021.104936DOI Listing
September 2021

The genetic influence of the brain-derived neurotrophic factor Val66Met polymorphism in chronic low back pain.

Adv Rheumatol 2021 05 12;61(1):24. Epub 2021 May 12.

Molecular and Cellular Biology Applied to Health, Lutheran University of Brazil (ULBRA), Canoas, Brazil.

Background: The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is a potential biomarker of vulnerability to pain. Thus, the present study aimed to investigate the association of this polymorphism with clinical and biopsychosocial factors in patients with chronic low back pain (CLBP).

Methods: A total of 107 individuals with CLBP answered questionnaires that were validated and adapted for the Brazilian population, including the Brief Inventory of Pain, the Central Sensitization Inventory, the Roland Morris Disability Questionnaire, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, the Survey of Pain Attitude-Brief, and the Hospital Anxiety and Depression Scale. All of the subjects were genotyped for the BDNF Val66Met polymorphism.

Results: The sample showed moderate scores of disability, central sensitization, and kinesiophobia, in addition to mild anxiety, hopelessness, and ruminant thoughts. No significant association was observed between the Val66Met polymorphism and the variables analyzed. Besides, there was no relationship between the BDNF Val66Met polymorphism with CSI, catastrophization, or disabilities that were generated by CLBP.

Conclusion: The results showed that the Val66Met polymorphism of the BDNF gene was not associated with clinical and biopsychosocial characteristics of CLBP in the sample studied.
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http://dx.doi.org/10.1186/s42358-021-00183-7DOI Listing
May 2021

Sample Preparation Free Mass Spectrometry Using Laser-Assisted Rapid Evaporative Ionization Mass Spectrometry: Applications to Microbiology, Metabolic Biofluid Phenotyping, and Food Authenticity.

J Am Soc Mass Spectrom 2021 Jun 13;32(6):1393-1401. Epub 2021 May 13.

Department of Metabolism, Digestion, and Reproduction, Imperial College London, London SW7 2AZ, U.K.

Mass spectrometry has established itself as a powerful tool in the chemical, biological, medical, environmental, and agricultural fields. However, experimental approaches and potential application areas have been limited by a traditional reliance on sample preparation, extraction, and chromatographic separation. Ambient ionization mass spectrometry methods have addressed this challenge but are still somewhat restricted in requirements for sample manipulation to make it suitable for analysis. These limitations are particularly restrictive in view of the move toward high-throughput and automated analytical workflows. To address this, we present what we consider to be the first automated sample-preparation-free mass spectrometry platform utilizing a carbon dioxide (CO) laser for sample thermal desorption linked to the rapid evaporative ionization mass spectrometry (LA-REIMS) methodology. We show that the pulsatile operation of the CO laser is the primary factor in achieving high signal-to-noise ratios. We further show that the LA-REIMS automated platform is suited to the analysis of three diverse biological materials within different application areas. First, clinical microbiology isolates were classified to species level with an accuracy of 97.2%, the highest accuracy reported in current literature. Second, fecal samples from a type 2 diabetes mellitus cohort were analyzed with LA-REIMS, which allowed tentative identification of biomarkers which are potentially associated with disease pathogenesis and a disease classification accuracy of 94%. Finally, we showed the ability of the LA-REIMS system to detect instances of adulteration of cooking oil and determine the geographical area of production of three protected olive oil products with 100% classification accuracy.
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http://dx.doi.org/10.1021/jasms.0c00452DOI Listing
June 2021

Temporal and geographic spreading of hepatitis B virus genotype A (HBV-A) in Brazil and the Americas.

J Viral Hepat 2021 08 18;28(8):1130-1140. Epub 2021 May 18.

Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, ULBRA, Canoas, Brazil.

Hepatitis B virus genotype A (HBV-A) is disseminated in different countries around the world. It presents a high genetic diversity and is classified into seven subgenotypes (A1-A7). HBV-A1 and HBV-A2 are the most frequent and spread in almost all American countries. This study aimed to evaluate the molecular epidemiology of these two subgenotypes, with a special focus on the temporal and geographic spreading in the Americas and Brazil. Bayesian coalescent analyses with HBV-A1 and HBV-A2 whole-genome sequences were performed to study viral phylodynamic and phylogeography. HBV-A1 evolutionary history demonstrated that it was initially disseminated from Africa to other continents probably after the 1400s and mainly in the 17th-18th centuries. The whole viral population grew between the 1700s-1900s and then reached a stationary phase. In Brazil, HBV-A1 common ancestors dated back to the 1600s with successive introductions between the 17th-18th centuries. In contrast, HBV-A2 spread from Europe to other continents after the 1800s, with an increase in the viral population over decades. It was introduced in the 20th century in America and between the 1950s-1970s in Brazil, presenting a high increase in the viral population from the 1970s to the 1980s. The circulation continents for HBV-A1 are Africa and America, while for HBV-A2 are Europe and America. HBV-A is one of the predominant genotypes in America (including Brazil) because of the early introduction by human migration processes of the subgenotypes A1 and A2 between the 16th and 20th centuries and the continuous spreading inside the continent over time.
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http://dx.doi.org/10.1111/jvh.13527DOI Listing
August 2021

Formation of Supported Lipid Bilayers Derived from Vesicles of Various Compositional Complexity on Conducting Polymer/Silica Substrates.

Langmuir 2021 05 30;37(18):5494-5505. Epub 2021 Apr 30.

Division of Nano and Biological Physics, Department of Physics, Chalmers University of Technology, 412 96 Gothenburg, Sweden.

Supported lipid bilayers (SLBs) serve important roles as minimalistic models of cellular membranes in multiple diagnostic and pharmaceutical applications as well as in the strive to gain fundamental insights about their complex biological function. To further expand the utility of SLBs, there is a need to go beyond simple lipid compositions to thereby better mimic the complexity of native cell membranes, while simultaneously retaining their compatibility with a versatile range of analytical platforms. To meet this demand, we have in this work explored SLB formation on PEDOT:PSS/silica nanoparticle composite films and mesoporous silica films, both capable of transporting ions to an underlying conducting PEDOT:PSS film. The SLB formation process was evaluated by using the quartz crystal microbalance with dissipation (QCM-D) monitoring, total internal reflection fluorescence (TIRF) microscopy, and fluorescence recovery after photobleaching (FRAP) for membranes made of pure synthetic lipids with or without the reconstituted membrane protein β-secretase 1 (BACE1) as well as cell-derived native lipid vesicles containing overexpressed BACE1. The mesoporous silica thin film was superior to the PEDOT:PSS/silica nanoparticle composite, providing successful formation of bilayers with high lateral mobility and low defect density even for the most complex native cell membranes.
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http://dx.doi.org/10.1021/acs.langmuir.1c00175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8280725PMC
May 2021

Spermatic Cord Block Series as a Minimally Invasive Therapy for Chronic Scrotal Content Pain.

J Urol 2021 Sep 19;206(3):725-732. Epub 2021 Apr 19.

Rush University Medical Center, Chicago, Illinois.

Purpose: The primary aim of our study was to evaluate relief of chronic scrotal content pain after a series of spermatic cord blocks with a combination of local anesthetic and a steroid. Secondary aims were to assess factors associated with a positive response and complications.

Materials And Methods: We performed a retrospective chart review of patients who underwent spermatic cord block series for chronic scrotal content pain at our practice between 2012 and 2019. Pain scores were compared before and after treatment using an 11-point numerical pain rating scale. We performed univariate analysis to assess differences between responders and nonresponders, and the relationship between symptom duration and response was analyzed by rank-order correlation.

Results: We included 44 men with chronic scrotal content pain present for a median duration of 24 months who underwent a spermatic cord block series. At a median followup of 16 months, 31 patients (70.5%) experienced sustained relief, including 9 patients (20.5%) with complete resolution of pain. There were no differences between responders and nonresponders in terms of symptom duration, perceived etiology, or previous treatments, and there was no association between response and duration of pain. Minor complications occurred in 5 cases (11.4%).

Conclusions: Spermatic cord block series is a safe, minimally invasive treatment for men with refractory chronic scrotal content pain. Response to cord block series appears to be independent of symptom duration, perceived etiology or prior medical and surgical treatments. Future studies should be conducted to evaluate long-term durability and predictors of success.
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http://dx.doi.org/10.1097/JU.0000000000001777DOI Listing
September 2021

A digital nervous system aiming toward personalized IoT healthcare.

Sci Rep 2021 04 8;11(1):7757. Epub 2021 Apr 8.

Laboratory of Organic Electronics, Department of Science and Technology, Linköping University, 601 74, Norrköping, Sweden.

Body area networks (BANs), cloud computing, and machine learning are platforms that can potentially enable advanced healthcare outside the hospital. By applying distributed sensors and drug delivery devices on/in our body and connecting to such communication and decision-making technology, a system for remote diagnostics and therapy is achieved with additional autoregulation capabilities. Challenges with such autarchic on-body healthcare schemes relate to integrity and safety, and interfacing and transduction of electronic signals into biochemical signals, and vice versa. Here, we report a BAN, comprising flexible on-body organic bioelectronic sensors and actuators utilizing two parallel pathways for communication and decision-making. Data, recorded from strain sensors detecting body motion, are both securely transferred to the cloud for machine learning and improved decision-making, and sent through the body using a secure body-coupled communication protocol to auto-actuate delivery of neurotransmitters, all within seconds. We conclude that both highly stable and accurate sensing-from multiple sensors-are needed to enable robust decision making and limit the frequency of retraining. The holistic platform resembles the self-regulatory properties of the nervous system, i.e., the ability to sense, communicate, decide, and react accordingly, thus operating as a digital nervous system.
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http://dx.doi.org/10.1038/s41598-021-87177-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032817PMC
April 2021

Trends in "Deaths of Despair" Among Working-Aged White and Black Americans, 1990-2017.

Am J Epidemiol 2021 09;190(9):1751-1759

Life expectancy for US White men and women declined between 2013 and 2017. Initial explanations for the decline focused on increases in "deaths of despair" (i.e., deaths from suicide, drug use, and alcohol use), which have been interpreted as a cohort-based phenomenon afflicting middle-aged White Americans. There has been less attention on Black mortality trends from these same causes, and whether the trends are similar or different by cohort and period. We complement existing research and contend that recent mortality trends in both the US Black and White populations most likely reflect period-based exposures to 1) the US opioid epidemic and 2) the Great Recession. We analyzed cause-specific mortality trends in the United States for deaths from suicide, drug use, and alcohol use among non-Hispanic Black and non-Hispanic White Americans, aged 20-64 years, over 1990-2017. We employed sex-, race-, and cause-of-death-stratified Poisson rate models and age-period-cohort models to compare mortality trends. Results indicate that rising "deaths of despair" for both Black and White Americans are overwhelmingly driven by period-based increases in drug-related deaths since the late 1990s. Further, deaths related to alcohol use and suicide among both White and Black Americans changed during the Great Recession, despite some racial differences across cohorts.
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http://dx.doi.org/10.1093/aje/kwab088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8579049PMC
September 2021

Dissemination and evolution of SARS-CoV-2 in the early pandemic phase in South America.

J Med Virol 2021 07 8;93(7):4496-4507. Epub 2021 Apr 8.

Programa de Pós-Graduação em Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, ULBRA, Canoas, Rio Grande do Sul, Brazil.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning in South America, mainly in Brazil with more than seven million cases of infection. Three major pandemic lineages/clades could be identified along with SARS-CoV-2 dissemination (G, GR, and GH) in the Americas. These clades differ according to their genomic characteristics, virulence, and spreading times. The present study describes the main clades and the respective temporal spreading analyses based on SARS-CoV-2 whole-genome sequences (WGS) from South America, obtained in the early pandemic phase (from March 1 to May 31 in 2020). SARS-CoV-2 WGSs with available information from country and year of sampling were obtained from different countries and the main clades were identified and analyzed independently with a Bayesian approach. The results demonstrated the prevalence of clades GR (n = 842; 54.6%), G (n = 529; 34.3%), and GH (n = 171; 11.1%). The frequencies of the clades were significantly different between South American countries. Clade G was the most prevalent in Ecuador, Suriname, and Uruguay, clade GR in Argentina, Brazil, and Peru, and clade GH in Colombia. The phylodynamic analysis indicated that all these main lineages increased viral spreading from February to early March and after an evolutionary stationary phase was observed. The decrease observed in the virus dissemination was directly associated to the reduction of social movement after March. In conclusion, these data demonstrated the current predominance of clades G, GR, and GH in South America because of the early dissemination of them in the first pandemic phase in South America.
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http://dx.doi.org/10.1002/jmv.26967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250755PMC
July 2021

Machine Learning Algorithms for Prediction of Permanent Pacemaker Implantation After Transcatheter Aortic Valve Replacement.

Circ Arrhythm Electrophysiol 2021 03 9;14(3):e008941. Epub 2021 Mar 9.

Division of Cardiology, Department of Medicine (S.A.-K., F.N., G.F.A., M.A.C., D.I.S., M.S.A., J.A.M., S.G.T.), Case Western Reserve University, Harrington Heart and Vascular Institute, and University Hospitals Cleveland Medical Center, OH.

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http://dx.doi.org/10.1161/CIRCEP.120.008941DOI Listing
March 2021

Association of interferon lambda-4 rs12979860 polymorphism with hepatocellular carcinoma in patients with chronic hepatitis C infection.

World J Hepatol 2021 Jan;13(1):109-119

PPG Biologia Celular e Molecular Aplicada à Saúde, Universidade Luterana do Brasil, Canoas 92425-900, Rio Grande do Sul, Brazil.

Background: Hepatitis C virus (HCV) infection is a public health concern worldwide. Several factors, including genetic polymorphisms, may be evolved in the progression of HCV infection to liver diseases. Interferon lambdas (IFNLs) modulate the immune response during viral infections. IFNLs induce antiviral activity, interfering in the viral replication by promoting the expression of several genes that regulate immunological functions. The interferon lambda-4 () rs12979860 polymorphism, which is characterized by a C to T transition in intron 1, is associated with spontaneous and treatment-induced clearance of HCV infection and may play a role in the development of HCV-associated liver diseases, including hepatocellular carcinoma (HCC).

Aim: To investigate the association of rs12979860 polymorphism with fibrosis, cirrhosis, and HCC in patients with chronic HCV infection.

Methods: This study was comprised of 305 chronic HCV-infected patients (53 fibrosis, 154 cirrhosis, and 98 HCC cases). The control group was comprised of 260 HCV-negative healthy individuals. The rs12979860 polymorphism was genotyped using the TaqMan assay. Fibrosis was diagnosed based on liver biopsy findings, while cirrhosis was diagnosed through clinical, laboratory, anatomopathological, and/or imaging data. HCC was diagnosed through imaging tests, tumor, and/or anatomopathological markers.

Results: The T allele was observed in the three groups of patients (fibrosis, cirrhosis, and HCC) at a significantly higher frequency when compared with the control group ( = 0.047, < 0.001, and = 0.01, respectively). Also, genotype frequencies presented significant differences between the control group and cirrhosis patients ( < 0.001) as well as HCC patients ( = 0.002). The risk analysis was performed using the codominant and dominant T allele models. In the codominant model, it was observed that the CT genotype showed an increased risk of developing cirrhosis in comparison with the CC genotype [odds ratio (OR) = 2.53; 95% confidence interval (CI): 1.55-4.15; < 0.001] as well as with HCC (OR = 2.54; 95%CI: 1.44-4.56; = 0.001). A similar result was observed in the comparison of the TT CC genotype between the control group and cirrhosis group (OR = 2.88; 95%CI: 1.44-5.77; = 0.001) but not for HCC patients. In the dominant T allele model, the CT + TT genotypes were associated with an increased risk for progression to cirrhosis (OR = 2.60; 95%CI: 1.63-4.19; < 0.001) and HCC (OR = 2.45; 95%CI: 1.42-4.31; = 0.001).

Conclusion: These findings suggest that the T allele of rs12979860 polymorphism is associated with the development of cirrhosis and HCC in chronic HCV-infected patients.
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http://dx.doi.org/10.4254/wjh.v13.i1.109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856861PMC
January 2021

DO DEATHS OF DESPAIR MOVE TOGETHER? COUNTY-LEVEL MORTALITY CHANGES BY SEX AND URBANIZATION, 1990-2017.

Am J Epidemiol 2021 06;190(6):1169-1171

Department of Sociology, University of Colorado Boulder, Boulder, Colorado, United States.

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http://dx.doi.org/10.1093/aje/kwab015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316609PMC
June 2021
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