bluuebunny/crossref_metadata_2025 huggingface dataset:
Ten-Year in-Hospital Mortality Trends among Paediatric Injured Patients in Japan: A Nationwide Observational Study
Authors: Toida Chiaki , Muguruma Takashi , Gakumazawa Masayasu , Shinohara Mafumi , Abe Takeru , Takeuchi Ichiro , Morimura Naoto
Published: October 2020

Injury is a major cause of worldwide child mortality. This retrospective nationwide study aimed to evaluate the characteristics of paediatric injured patients in Japan and their in-hospital mortality trends from 2009 to 2018. Injured patients aged <17 years were enrolled. Data were extracted from the Japan Trauma Data Bank. In the Cochran-Armitage test, in-hospital mortality significantly decreased during the study period (p < 0.001), except among patients <1 year old, and yearly reductions were observed among those with an Injury Severity Score ≥16 and survival rate ≥50% (p < 0.001). In regression analyses, patients who underwent urgent blood transfusion within 24 h after hospital admission (odds ratio (OR) = 3.24, 95% confidence interval (CI) = 2.38–4.41) had a higher in-hospital mortality risk. Higher survival probability as per the Trauma and Injury Severity Score was associated with lower in-hospital mortality (OR = 0.92, 95% CI = 0.91–0.92), a risk which decreased from 2009 to 2018 (OR = 6.16, 95% CI = 2.94–12.88). Based on our results, there is a need for improved injury surveillance systems for establishment of injury prevention strategies along with evaluation of the quality of injury care and outcome measures.
Indications and Outcome in Patients Undergoing Left Atrial Appendage Closure—The Austrian LAAC Registry
Authors: Zweiker David , Sieghartsleitner Raphael , Fiedler Lukas , Toth Gabor G. , Luha Olev , Stix Guenter , Gabriel Harald , Vock Paul , Lileg Brigitte , Strouhal Andreas , Delle-Karth Geort , Pfeffer Michael , Aichinger Josef , Tkalec Wolfgang , Steinwender Clemens , Sihorsch Kurt , Binder Ronald K. , Rammer Martin , Barbieri Fabian , Mueller Silvana , Verheyen Nicolas , Ablasser Klemens , Zirlik Andreas , Scherr Daniel
Published: October 2020

Background: Complete real-world data on the indications and outcomes of left atrial appendage closure (LAAC) outside of clinical trials are rare. In this study, we stratified patients undergoing LAAC by indication groups. Methods: This analysis of the national multicentre Austrian LAAC Registry comprised all patients that underwent LAAC up until 2018 at the currently active centres in Austria. The baseline characteristics, procedural details and outcomes between the following indication groups were compared: bleeding as an indication for LAAC (“bleeding” group) vs. thromboembolism despite oral anticoagulation (OAC; “thromboembolism” group) vs. an intolerance to OAC for reasons other than the above (“other” group). Results: The analysis included 186 patients, with 59.7% in the “bleeding” group, 8.1% in the “thromboembolism” group and 32.2% in the “other” group. The CHADS2 score was the highest in the “thromboembolism” group and the HAS-BLED score was the highest in the “bleeding” group. The procedural outcomes were similar between groups (implantation success, 97.3%), with major complications occurring in 7.0% of patients. One-year survival free from stroke, bleeding or LAAC-associated hospitalisation was 83.9%, 90.0% and 81.4% in the “bleeding”, “thromboembolism” and “other” groups, respectively (p = 0.891). Conclusions: In routine clinical practice, LAAC was used in a heterogeneous patient population with atrial fibrillation (AF) and contraindication, inefficacy or intolerance to OAC. The long-term outcome was favourable in all groups.
Transcutaneous Spinal Cord Stimulation Enhances Quadriceps Motor Evoked Potential in Healthy Participants: A Double-Blind Randomized Controlled Study
Authors: Megía-García Álvaro , Serrano-Muñoz Diego , Taylor Julian , Avendaño-Coy Juan , Comino-Suárez Natalia , Gómez-Soriano Julio
Published: October 2020

Transcutaneous electrical spinal cord stimulation (tSCS) is a non-invasive technique for neuromodulation and has therapeutic potential for motor rehabilitation following spinal cord injury. The main aim of the present study is to quantify the effect of a single session of tSCS on lower limb motor evoked potentials (MEPs) in healthy participants. A double-blind, sham-controlled, randomized, crossover, clinical trial was carried out in 15 participants. Two 10-min sessions of tSCS (active-tSCS and sham-tSCS) were applied at the T11-T12 vertebral level. Quadriceps (Q) and tibialis anterior (TA) muscle MEPs were recorded at baseline, during and after tSCS. Q and TA isometric maximal voluntary contraction was also recorded. A significant increase of the Q-MEP amplitude was observed during active-tSCS (1.96 ± 0.3 mV) when compared from baseline (1.40 ± 0.2 mV; p = 0.01) and when compared to sham-tSCS at the same time-point (1.13 ± 0.3 mV; p = 0.03). No significant modulation was identified for TA-MEP amplitude or for Q and TA isometric maximal voluntary isometric strength. In conclusion, tSCS applied over the T11-T12 vertebral level increased Q-MEP but not TA-MEP compared to sham stimulation. The specific neuromodulatory effect of tSCS on Q-MEP may reflect optimal excitation of this motor response at the interneuronal or motoneuronal level.
Delirium Superimposed on Dementia in Perioperative Period and Intensive Care
Authors: Krzych Łukasz J. , Rachfalska Natalia , Putowski Zbigniew
Published: October 2020

Delirium is a life-threatening condition, the causes of which are still not fully understood. It may develop in patients with pre-existing dementia. Delirium superimposed on dementia (DSD) can go completely unnoticed with routine examination. It may happen in the perioperative period and in the critical care setting, especially in the ageing population. Difficulties in diagnosing and lack of specific pharmacological and non-pharmacological treatment make DSD a seriously growing problem. Patient-oriented, multidirectional preventive measures should be applied to reduce the risk of DSD. For this reason, anesthesiologists and intensive care specialists should be aware of this interesting condition in their everyday clinical practice.
Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism—Results from the thrombEVAL Study
Authors: Keller Karsten , Göbel Sebastian , ten Cate Vincent , Panova-Noeva Marina , Eggebrecht Lisa , Nagler Markus , Coldewey Meike , Foebel Maike , Bickel Christoph , Lauterbach Michael , Espinola-Klein Christine , Lackner Karl J. , ten Cate Hugo , Münzel Thomas , S. Wild Philipp , H. Prochaska Jürgen
Published: October 2020

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011–March 2013). Patients were evaluated using clinical visits, computer-assisted personal interviews, self-reported data and laboratory measurements according to standard operating procedures. Overall, 360 patients with VTE from RMC and 254 from CS were included. Time in therapeutic range (TTR) was higher in CS compared to RMC (76.9% (interquartile range [IQR] 63.2–87.1%) vs. 69.5% (52.3–85.6%), p < 0.001). Crude rate of thromboembolic events (rate ratio [RR] 11.33 (95% confidence interval [CI] 1.85–465.26), p = 0.0015), clinically relevant bleeding (RR 6.80 (2.52–25.76), p < 0.001), hospitalizations (RR 2.54 (1.94–3.39), p < 0.001) and mortality under OAC (RR 5.89 (2.40–18.75), p < 0.001) were consistently higher in RMC compared with CS. Patients in RMC had higher risk for primary outcome (clinically relevant bleedings, thromboembolic events and mortality, hazard ratio [HR] 5.39 (95%CI 2.81–10.33), p < 0.0001), mortality (HR 5.54 (2.22–13.84), p = 0.00025), thromboembolic events (HR 6.41 (1.51–27.24), p = 0.012), clinically relevant bleeding (HR 5.31 (1.89–14.89), p = 0.0015) and hospitalization (HR 1.84 (1.34–2.55), p = 0.0002). Benefits of CS care were still observed after adjusting for comorbidities and TTR. In conclusion, anticoagulation quality and outcome of VTE patients undergoing VKA treatment was significantly better in CS than in RMC. Patients treated in CS had lower rates of adverse events, hospitalizations and lower mortality. CS was prognostically relevant, beyond providing advantages of improved international ratio (INR) monitoring.
Oxygenation before Endoscopic Sedation Reduces the Hypoxic Event during Endoscopy in Elderly Patients: A Randomized Controlled Trial
Authors: Kim Hyunil , Hyun Jeong Nam , Lee Kyong Joo , Kim Hyun-Soo , Park Hong Jun
Published: October 2020

Background: Sedation endoscopy increases patient and examiner satisfaction but involves complications. The most serious complication is hypoxia, the risk factors for which are old age, obesity, and American Society of Anesthesiologists physical status of 3 or greater. However, clear evidence of oxygenation during sedation endoscopy for elderly people is lacking in US, European, and Korean guidelines. Method: This study was conducted for 1 year starting in August 2018 to evaluate whether pre-oxygenation use 1 min before sedation endoscopy could reduce the incidence of hypoxia in patients older than 65 years of age. A total of 70 patients were divided into the non-oxygenated group (n = 35; control group) and oxygen-treated group (n = 35; experimental group) during endoscopy. Result: The incidence of hypoxia was 28 (80%) in the control group versus 0 (0%) in the pre-oxygenated group. Factors related to hypoxia in the non-oxygenated group were a relatively high dose of midazolam and concomitant injection with narcotic analgesics such as pethidine. Conclusion: The incidence of hypoxia during sedation endoscopy is high in patients over 65 years, but oxygenation during endoscopic sedation in elderly people can significantly reduce the incidence of intraprocedural hypoxic events.
Current Cognition Tests, Potential Virtual Reality Applications, and Serious Games in Cognitive Assessment and Non-Pharmacological Therapy for Neurocognitive Disorders
Authors: Jin Roger , Pilozzi Alexander , Huang Xudong
Published: October 2020

As the global population ages, the incidence of major neurocognitive disorders (major NCDs), such as the most common geriatric major NCD, Alzheimer’s disease (AD), has grown. Thus, the need for more definitive cognitive assessment or even effective non-pharmacological intervention for age-related NCDs is becoming more and more pressing given that no definitive diagnostics or efficacious therapeutics are currently unavailable for them. We evaluate the current state of the art of cognitive assessment for major NCDs, and then briefly glance ahead at potential application of virtual reality (VR) technologies in major NCD assessment and in cognition training of visuospatial reasoning in a 3D environment, as well as in the alleviation of depression and other symptoms of cognitive disorders. We believe that VR-based technologies have tremendous potentials in cognitive assessment and non-pharmacological therapy for major NCDs.
Photo-Optical Transcutaneous Oxygen Tension Measurement Is of Added Value to Predict Diabetic Foot Ulcer Healing: An Observational Study
Authors: Leenstra Bernard , de Kleijn Robert , Kuppens Geoffrey , Verhoeven Bart Arnoldus Nicolaas , Hinnen Jan Willem , de Borst Gert J.
Published: October 2020

Currently, transcutaneous oxygen tension measurement (TCpO2) is the most favorable non-invasive test for diabetic foot ulcer (DFU) healing prognosis. Photo-optical TCpO2 is novel, less time-consuming and more practical in use compared to regular electro-chemical TCpO2. We prospectively investigated the clinical value of photo-optical TCpO2 to predict DFU healing. Patients with suspected DFU undergoing conservative treatment underwent an ankle pressure, toe-pressure and photo-optical TCpO2 test. The primary endpoint was DFU wound healing at 12 months. Based on their clinical outcome, patients were divided into a DFU healing and DFU non-healing group. Healing was defined as fully healed ulcers and non-healing as ulcers that deteriorated under conservative treatment or that required surgical amputation. Differences between groups were analyzed and an optimal TCpO2 cut-off value was determined. In total, 103 patients were included, of which 68 patients (66%) were classified as DFU healing. The remaining 35 patients (34%) had deteriorated ulcers, of which 29 (83%) eventually required surgical amputation. An optimal TCpO2 cut-off value of 43 mmHg provided a sensitivity, specificity and odds ratio of 0.78, 0.56 and 4.4, respectively. Photo-optical TCpO2 is an adequate alternative tool to validate the vascular status of the lower extremity indicating healing prognosis in patients with DFU. Therefore, we recommend that photo-optical TCpO2 can be safely coapplied in clinical practice to assist in DFU treatment strategy.
The Role of Ribonuclease 1 and Ribonuclease Inhibitor 1 in Acute Kidney Injury after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair
Authors: Zechendorf Elisabeth , Gombert Alexander , Bülow Tanja , Frank Nadine , Beckers Christian , Peine Arne , Kotelis Drosos , Jacobs Michael J. , Marx Gernot , Martin Lukas
Published: October 2020

Acute kidney injury (AKI) is one of the most common post-operative complications and is closely associated with increased mortality after open and endovascular thoracoabdominal aortic aneurysm (TAAA) repair. Ribonuclease (RNase) 1 belongs to the group of antimicrobial peptides elevated in septic patients and indicates the prediction of two or more organ failures. The role of RNase 1 and its antagonist RNase inhibitor 1 (RNH1) after TAAA repair is unknown. In this study, we analyzed RNase 1 and RNH1 serum levels in patients undergoing open (n = 14) or endovascular (n = 19) TAAA repair to determine their association with post-operative AKI and in-hospital mortality. Increased RNH1 serum levels after open TAAA repair as compared with endovascular TAAA repair immediately after surgery and 12, 48, and 72 h after surgery (all p < 0.05) were observed. Additionally, elevated RNase 1 and RNH1 serum levels 12, 24, and 48 h after surgery were shown to be significantly associated with AKI (all p < 0.05). RNH1 serum levels before and RNase 1 serum levels 12 h after TAAA repair were significantly correlated with in-hospital mortality (both p < 0.05). On the basis of these findings, RNase 1 and RNH1 may be therapeutically relevant and may represent biomarkers for post-operative AKI and in-hospital mortality.
Using the Thickness Map from Macular Ganglion Cell Analysis to Differentiate Retinal Vein Occlusion from Glaucoma
Authors: Lee Nam Ho , Park Kee Sup , Lee Han Min , Kim Jung Yeul , Kim Chang-sik , Kim Kyoung Nam
Published: October 2020

Purpose: We hypothesized that the thickness map from macular ganglion cell analysis (GCA) acquired from spectral-domain optical coherence tomography can be used to differentiate retinal vein occlusion (RVO) from glaucoma. Methods: In this retrospective case control study, 37 patients with resolved RVO and 74 patients with primary open-angle glaucoma (POAG) were enrolled. Two independent examiners diagnosed patients with RVO or POAG based on the topographic pattern in the GCA thickness map. Inter-observer agreement for a decision between RVO and POAG was assessed using kappa statistics. Diagnostic specificity and accuracy were calculated. Results: Inter-observer agreement was good, with a kappa value of 0.765 (95% confidence interval, 0.634–0.896, p < 0.001). The diagnostic specificity of RVO from POAG using the GCA thickness map was 93.2% and diagnosis accuracy was 80.4%. Conclusions: An irregular GCA thickness map represents a simple and convenient differential diagnostic clue to distinguish RVO from POAG.
Cystocele Repair by a Modified Surgical Technique of Bilateral Pubococcygeus Plication: Long-Term Surgical and Functional Results
Authors: Balzarro Matteo , Rubilotta Emanuele , Antonelli Alessandro
Published: October 2020

Here we describe our modified surgical technique of bilateral pubococcygeus plication (BPCP) for cystocele repair and assess its safety and long-term outcomes. This is a prospective study of 147 consecutive women who underwent BPCP for cystocele between January 2010 to January 2018. Inclusion criteria was naïve women with symptomatic cystocele ≥ POP-Q 2nd stage. Exclusion criteria: stress urinary incontinence (SUI), urgency urinary incontinence, other associated vaginal wall prolapses ≥ stage 2, neurological diseases, previous SUI surgeries, and previous radiation/surgery of the pelvic area. BPCP was performed by obtaining the medialization of the pubococcygeus muscle fibers of the right and left sides. Statistical analysis was performed. Objective cure was POP-Q < 2nd stage. Subjective cure and functional outcomes were evaluated by validated questionnaires. Patient’s satisfaction was assessed by a Likert-type scale. Mean operative time was 64 min. At a mean follow-up of 82.4 months, objective and subjective success rates were 89.8% and 92.2% respectively. De novo urgency was 3.2%. Surgery did not alter sexual function. Complications occurred in 4.8%, and were: wrong dissection plane, hematoma, and pain lasting between 24–72 h. BPCP for correction of cystocele is safe and effective, with limited risk of complication and good long-term results.
Diabetic Cardiovascular Autonomic Neuropathy, the Handgrip Test and Ambulatory Blood Pressure Monitoring Parameters: Are There Any Diagnostic Implications?
Authors: Kempler Miklós , Hajdú Noémi , Putz Zsuzsanna , Istenes Ildikó , Vági Orsolya , Békeffy Magdolna , Schnabel Karolina , Kempler Péter , Körei Anna E.
Published: October 2020

Cardiovascular autonomic neuropathy (CAN) is a common complication of diabetes mellitus. Cardiovascular reflex tests (CARTs) are the gold standard in the diagnosis of CAN, but the handgrip test is no longer recommended to be performed. Previously, the inverse association between the presence of hypertension and handgrip test abnormality was demonstrated and hypertension as major cause for excessive diastolic blood pressure rise during handgrip testing in diabetic individuals proposed. The aim of the present study is to describe more precisely the association between handgrip test and hypertension by performing ambulatory blood pressure monitoring (ABPM) among diabetic patients. A more comprehensive evaluation of the relationship between cardiovascular autonomic function, hypertension and the handgrip test was targeted using heart rate variability (HRV) analysis. Our study involved 163 patients with diabetes. Cardiovascular autonomic neuropathy was assessed by the CARTs and sustained handgrip test was performed. All patients underwent ABPM and HRV analysis well. CAN was diagnosed in 69 patients. Significant associations were found between the diastolic blood pressure increase in response to handgrip exercise and the 24-h (rho = 0.245, p = 0.003), daytime (rho = 0.230, p = 0.005) and night-time (rho = 0.230, p = 0.006) mean systolic and 24-h diastolic (rho = 0.176, p = 0.034) blood pressure values, systolic blood pressure load (rho = 0.252, p = 0.003) and systolic (rho = 0.236, p = 0.005) and diastolic (rho = 0.165, p = 0.047) hyperbaric impacts. Higher values of ambulatory blood pressure monitoring parameters are associated with greater increases in diastolic blood pressure during isometric handgrip exercise. Diastolic blood pressure elevations during the handgrip test are also correlated, in order to diminished heart rate variability parameters attributable to parasympathetic dysfunction highlighting the pivotal role of sympathetic overactivity in evolving handgrip test results. Our study provides further evidence on the inverse association between handgrip test abnormality and hypertension in diabetic patients.
Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy
Authors: Motedayen Aval Leila , Pease James E. , Sharma Rohini , Pinato David J.
Published: October 2020

Immune checkpoint inhibitors (ICI) have revolutionised cancer therapy. However, they have been effective in only a small subset of patients and a principal mechanism underlying immune-refractoriness is a ‘cold’ tumour microenvironment, that is, lack of a T-cell-rich, spontaneously inflamed phenotype. As such, there is a demand to develop strategies to transform the tumour milieu of non-responsive patients to one supporting T-cell-based inflammation. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway is a fundamental regulator of innate immune sensing of cancer, with potential to enhance tumour rejection through the induction of a pro-inflammatory response dominated by Type I interferons. Recognition of these positive immune-modulatory properties has rapidly elevated the STING pathway as a putative target for immunotherapy, leading to a myriad of preclinical and clinical studies assessing natural and synthetic cyclic dinucleotides and non-nucleotidyl STING agonists. Despite pre-clinical evidence of efficacy, clinical translation has resulted into disappointingly modest efficacy. Poor pharmacokinetic and physiochemical properties of cyclic dinucleotides are key barriers to the development of STING agonists, most of which require intra-tumoral dosing. Development of systemically administered non-nucleotidyl STING agonists, or conjugation with liposomes, polymers and hydrogels may overcome pharmacokinetic limitations and improve drug delivery. In this review, we summarise the body of evidence supporting a synergistic role of STING agonists with currently approved ICI therapies and discuss whether, despite the numerous obstacles encountered to date, the clinical development of STING agonist as novel anti-cancer therapeutics may still hold the promise of broadening the reach of cancer immunotherapy.
Iridoschisis—A Systematic Review
Authors: Pieklarz Barbara , Grochowski Emil Tomasz , Saeed Emil , Sidorczuk Patryk , Mariak Zofia , Dmuchowska Diana Anna
Published: October 2020

Iridoschisis is a rare condition defined as a separation of the anterior iris stroma from the posterior stroma and muscle layers. In this paper, we review current data about the epidemiology, pathophysiology, clinical characteristics and differential diagnoses of this condition and discuss the specificity of surgical treatment of concomitant ocular diseases in iridoschisis patients. Iridoschisis may pose a challenge for both an ophthalmologist in an outpatient setting and an ophthalmic surgeon. Glaucoma, primarily angle-closure glaucoma, is the most often described condition concomitant to iridoschisis. Other ocular abnormalities found relatively often in iridoschisis patients include cataract, lens subluxation and corneal abnormalities. Special attention has been paid to potential complications of cataract surgery and prevention thereof. Beside addressing the practical aspects, we point to discrepancies and suggest topics for further investigation.
A Comparison of Case Fatality Risk of COVID-19 between Singapore and Japan
Authors: Kayano Taishi , Nishiura Hiroshi
Published: October 2020

The crude case fatality risk (CFR) for coronavirus disease (COVID-19) in Singapore is remarkably small. We aimed to estimate the unbiased CFR by age for Singapore and Japan and compare these estimates by calculating the standardized mortality ratio (SMR). Age-specific CFRs for COVID-19 were estimated in real time, adjusting for the delay from illness onset to death. The SMR in Japan was estimated by using the age distribution of the Singapore population. Among cases aged 60–69 years and 70–79 years, the age-specific CFRs in Singapore were estimated as 1.84% (95% confidence interval: 0.46–4.72%) and 5.57% (1.41–13.97%), respectively, and those in Japan as 5.52% (4.55–6.62%) and 15.49% (13.81–17.27%), respectively. The SMR of COVID-19 in Japan, when compared with Singapore as the baseline, was estimated to be 1.46 (1.09–2.96). The overall CFR for Singapore is lower than that for Japan. It is possible that the circulating variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Singapore causes a milder clinical course of COVID-19 infection compared with other strains. If infection with a low-virulence SARS-CoV-2 variant provides protection against infection by high-virulence strains, the existence of such a strain is encouraging news for the many countries struggling to suppress this virus.
Surfactant Effects on the Synthesis of Redox Bifunctional V2O5 Photocatalysts
Authors: Ibrahim Islam , Belessiotis George V. , Arfanis Michalis K. , Athanasekou Chrysoula , Philippopoulos Athanassios I. , Mitsopoulou Christiana A. , Romanos George Em. , Falaras Polycarpos
Published: October 2020

Novel V2O5 bifunctional photocatalysts were prepared following a wet chemical process with the addition of anionic or non-ionic surfactants into the precursor solution and further heating under reflux. Detailed characterization and investigation of the relevant light-matter interactions proved that surfactants addition had a strong impact on the morphology, while also affecting the crystallinity, the optoelectronic properties, and the surface chemistry of the novel photocatalysts. The most efficient photocatalyst (T80) was based on tween 80, a surface-active agent employed for the first time in the synthesis of vanadium oxide materials. T80 presented crystalline nature without structural defects, which are usually centers of e− − h+ recombination. This material also exhibited small crystal size, high porosity, and short migration paths for the charge carriers, enabling their effective separation during photocatalysis. Under UV light illumination, T80 was capable to reduce hexavalent chromium to trivalent up to 70% and showed high yields in degrading methylene blue azo-dye and tetracycline antibiotic water pollutants. This remarkably high bifunctional performance defines T80 as a promising and capable photocatalytic material for both advanced oxidation and reduction processes (AOPs-ARPs).
Wetting Kinetics and Microstructure Analysis of BNi2 Filler Metal over Selective Laser Melted Ti-6Al-4V Substrate
Authors: Liu Jiankun , Liu Guanpeng , Ouyang Hua , Li Yulong , Yan Ming , Pecht Michael
Published: October 2020

The wetting kinetics of nickel-based filler metal (BNi2) over selective laser-melted Ti-6Al-4V (SLMed TC4) titanium alloy in a protective argon atmosphere is experimentally investigated using a real-time in situ hot stage equipped with an optical microscope. The spreading processes at different temperatures are similar, and the overall wetting/spreading process can be roughly divided into three stages: (i) an initial stage, (ii) a rapid spreading stage, and (iii) an asymptotic stage. Moreover, the wetting kinetics of the BNi2/SLMed TC4 system can be expressed by empirical power exponential function Rn~t with n = ~1. In the process of spreading, Ti-based solid solution (Ti(ss)) and intermetallic compound (Ti2Ni and TiB2) were formed at the interface within the reaction domain, and the phase transition of α’ martensitic to α-Ti and β-Ti also took place. The influence of elevated temperature on the spreading and wetting kinetics of the BNi2/SLMed TC4 system was studied, and the results show that the increase of temperature has a slightly promoting effect on the spreading, but a limited impact on the value of n. In addition, the spreading and wetting kinetics of BNi2/SLMed TC4 system are similar to those of BNi2 on conventional forged TC4 substrate.
Surface Activation of Polylactic Acid-Based Wood-Plastic Composite by Atmospheric Pressure Plasma Treatment
Authors: Sauerbier Philipp , Köhler Robert , Renner Gerrit , Militz Holger
Published: October 2020

Wood-plastic composite (WPC) based on a polylactic acid (PLA) matrix is a promising material since it is biobased, degradable, sustainable, and 3D printable. However, due to its coloring, visible layers after 3D-printing, and small build volumes of these printers, a coating or gluing of parts might be required. This study investigates the influence of a dielectric barrier discharge (DBD) plasma treatment of PLA-based WPC to activate the surface and improve, e.g., coating capabilities. X-ray photoelectron spectroscopy (XPS) measurements showed the oxidation of the surface due to the formation of carbonyl and carboxyl groups. Laser scanning microscopy revealed a surface roughening after the treatment. Contact angles of water and diiodomethane decreased significantly after the plasma treatment and the consecutively calculated surface free energy increased. Finally, two practical adhesion tests revealed an improvement of the applied acrylic dispersion coating’s adhesion to the WPC surface: The assigned cross-cut class improved, and the pull-off strength increased from 1.4 to 2.3 N/mm2.
Hand Injuries in the Polish Silesian Paediatric Population—An Exploratory Cross-Sectional Study of Post-Traumatic X-rays
Authors: Cebula Maciej , Modlińska Sandra , Machnikowska-Sokołowska Magdalena , Komenda Jacek , Cebula Agnieszka , Baron Jan , Gruszczyńska Katarzyna
Published: October 2020

Background and objectives: In the paediatric population, hand injuries are one of the most frequent injuries and the second most frequent area of fracture. It is estimated that hand injuries account for up to 23% of the trauma-related causes of emergency department visits. Not only are they a significant factor in health care costs, but they may also lead to detrimental and long-term consequences for the patient. The discrepancy observed between the published studies suggests a geographical variation in their epidemiology. The aim of this study is to determine the localisation of injuries and fractures involving the hand in the paediatric population of the Polish Silesia region. This exploratory cross-sectional study involved 1441 post-traumatic hand X-ray examinations performed at the Department of Diagnostic Imaging of the John Paul II Upper Silesian Child Health Centre in Katowice between January and December 2014. Materials and Methods: The study group consisted of 656 girls and 785 boys who were 11.65 ± 3.50 and 11.51 ± 3.98 years old, respectively (range: 1–18 years). All examinations were evaluated for the location of the injury and presence of fracture(s). Results: Finger injuries were dominant (n = 1346), with the fifth finger being the most frequently injured (n = 381). The majority of injuries were observed among children who were 11 years old (n = 176), with a visible peak in the 11- to 13-year-old group. A total of 625 bone fractures were detected. Fractures of the proximal phalanges (n = 213) and middle phalanges (n = 159) were most common, and fifth finger (n = 189) predominance was again observed. A gender-independent positive correlation was found between patients’ age and finger injuries (p < 0.01) as well as metacarpal injuries (p < 0.01). There was no correlation between patients’ age and fractures in these locations (p > 0.05). Metacarpal injuries (p < 0.01), finger injuries (p < 0.01), fractures (p = 0.01), and fractures with displacement (p = 0.03) were more common among males regardless of age. Conclusions: The results indicate that 11-year-old boys are at an increased risk of hand injuries and fractures. The distal and middle phalanges of the right hand, especially of the fifth digit, were the most susceptible to fracture localisation. Thus, injuries in these areas should be perceived as most likely to cause fractures and therefore demand careful examination.
Role of the Mitochondrial Pyruvate Carrier in the Occurrence of Metabolic Inflexibility in Drosophila melanogaster Exposed to Dietary Sucrose
Authors: Simard Chloé J. , Touaibia Mohamed , Allain Eric Pierre , Hebert-Chatelain Etienne , Pichaud Nicolas
Published: October 2020

Excess dietary carbohydrates are linked to dysregulation of metabolic pathways converging to mitochondria and metabolic inflexibility. Here, we determined the role of the mitochondrial pyruvate carrier (MPC) in the occurrence of this metabolic inflexibility in wild-type (WT) and MPC1-deficient (MPC1def) flies that were exposed to diets with different sucrose concentrations for 15–25 days (Standard Diet: SD, Medium-Sucrose Diet: MSD, and High-Sucrose Diet: HSD). Our results showed that MPC1def flies had lower mitochondrial respiration rates than WT flies on the SD and MSD. However, when exposed to the HSD, WT flies displayed decreased mitochondrial respiration rates compared to MPC1def flies. WT flies exposed to the HSD also displayed increased proline contribution and slightly decreased MPC1 expression. Surprisingly, when fed the MSD and the HSD, few metabolites were altered in WT flies whereas MPC1def flies display significant accumulation of glycogen, glucose, fructose, lactate, and glycerol. Overall, this suggests that metabolic inflexibility starts to occur in WT flies after 15–25 days of exposure to the HSD whereas the MPC1def flies display metabolic inflexibility independently of the diet provided. This study thus highlights the involvement of MPC as an essential protein in Drosophila to maintain proper metabolic homeostasis during changes in dietary resources.
Temperate Propolis Has Anti-Inflammatory Effects and Is a Potent Inhibitor of Nitric Oxide Formation in Macrophages
Authors: Alanazi Samyah , Alenzi Naif , Fearnley James , Harnett William , Watson David G.
Published: October 2020

Previous research has shown that propolis has immunomodulatory activity. Extracts from two UK propolis samples were assessed for their anti-inflammatory activities by investigating their ability to alter the production of the cytokines: tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10 from mouse bone marrow-derived macrophages co-stimulated with lipopolysaccharide (LPS). The propolis extracts suppressed the secretion of IL-1β and IL-6 with less effect on TNFα. In addition, propolis reduced the levels of nitric oxide formed by LPS-stimulated macrophages. Metabolomic profiling was carried out by liquid chromatography (LC) coupled with mass spectrometry (MS) on a ZIC-pHILIC column. LPS increased the levels of intermediates involved in nitric oxide biosynthesis; propolis lowered many of these. In addition, LPS produced an increase in itaconate and citrate, and propolis treatment increased itaconate still further while greatly reducing citrate levels. Moreover, LPS treatment increased levels of glutathione (GSH) and intermediates in its biosynthesis, while propolis treatment boosted these still further. In addition, propolis treatment greatly increased levels of uridine diphosphate (UDP)–sugar conjugates. Overall, the results showed that propolis extracts exert an anti-inflammatory effect by the inhibition of pro-inflammatory cytokines and by the metabolic reprogramming of LPS activity in macrophages.
Predictive Model of Setting Times and Compressive Strengths for Low-Alkali, Ambient-Cured, Fly Ash/Slag-Based Geopolymers
Authors: Ukritnukun Supphatuch , Koshy Pramod , Rawal Aditya , Castel Arnaud , Sorrell Charles Christopher
Published: October 2020

The effects of curing temperature, blast furnace slag content, and Ms on the initial and final setting times, and compressive strengths of geopolymer paste and mortars are examined. The present work demonstrates that ambient-cured geopolymer pastes and mortars can be fabricated without requiring high alkalinity activators or thermal curing, provided that the ratios of Class F fly ash (40–90 wt%), blast furnace slag (10–60 wt%), and low alkalinity sodium silicate (Ms = 1.5, 1.7, 2.0) are appropriately balanced. Eighteen mix designs were assessed against the criteria for setting time and compressive strength according to ASTM C150 and AS 3972. Using these data, flexible and reproducible mix designs in terms of the fly ash/slag ratio and Ms were mapped and categorised. The optimal mix designs are 30–40 wt% slag with silicate modulus (Ms) = 1.5–1.7. These data were used to generate predictive models for initial and final setting times and for ultimate curing times and ultimate compressive strengths. These projected data indicate that compressive strengths >100 MPa can be achieved after ambient curing for >56 days of mixes of ≥40 wt% slag.
NMR as a “Gold Standard” Method in Drug Design and Discovery
Authors: Emwas Abdul-Hamid , Szczepski Kacper , Poulson Benjamin Gabriel , Chandra Kousik , McKay Ryan T. , Dhahri Manel , Alahmari Fatimah , Jaremko Lukasz , Lachowicz Joanna Izabela , Jaremko Mariusz
Published: October 2020

Studying disease models at the molecular level is vital for drug development in order to improve treatment and prevent a wide range of human pathologies. Microbial infections are still a major challenge because pathogens rapidly and continually evolve developing drug resistance. Cancer cells also change genetically, and current therapeutic techniques may be (or may become) ineffective in many cases. The pathology of many neurological diseases remains an enigma, and the exact etiology and underlying mechanisms are still largely unknown. Viral infections spread and develop much more quickly than does the corresponding research needed to prevent and combat these infections; the present and most relevant outbreak of SARS-CoV-2, which originated in Wuhan, China, illustrates the critical and immediate need to improve drug design and development techniques. Modern day drug discovery is a time-consuming, expensive process. Each new drug takes in excess of 10 years to develop and costs on average more than a billion US dollars. This demonstrates the need of a complete redesign or novel strategies. Nuclear Magnetic Resonance (NMR) has played a critical role in drug discovery ever since its introduction several decades ago. In just three decades, NMR has become a “gold standard” platform technology in medical and pharmacology studies. In this review, we present the major applications of NMR spectroscopy in medical drug discovery and development. The basic concepts, theories, and applications of the most commonly used NMR techniques are presented. We also summarize the advantages and limitations of the primary NMR methods in drug development.
Morphology, Surface Structure and Water Adsorption Properties of TiO2 Nanoparticles: A Comparison of Different Commercial Samples
Authors: Mino Lorenzo , Negri Chiara , Santalucia Rosangela , Cerrato Giuseppina , Spoto Giuseppe , Martra Gianmario
Published: October 2020

Water is a molecule always present in the reaction environment in photocatalytic and biomedical applications of TiO2 and a better understanding of its interaction with the surface of TiO2 nanoparticles is crucial to develop materials with improved performance. In this contribution, we first studied the nature and the surface structure of the exposed facets of three commercial TiO2 samples (i.e., TiO2 P25, SX001, and PC105) by electron microscopy and IR spectroscopy of adsorbed CO. The morphological information was then correlated with the water adsorption properties, investigated at the molecular level, moving from multilayers of adsorbed H2O to the monolayer, combining medium- and near-IR spectroscopies. Finally, we assessed in a quantitative way the surface hydration state at different water equilibrium pressures by microgravimetric measurements.
Extract Derived from Cedrus atlantica Acts as an Antitumor Agent on Hepatocellular Carcinoma Growth In Vitro and In Vivo
Authors: Huang Xiao-Fan , Chang Kai-Fu , Lee Shan-Chih , Sheu Gwo-Tarng , Li Chia-Yu , Weng Jun-Cheng , Hsiao Chih-Yen , Tsai Nu-Man
Published: October 2020

Cedrus atlantica is widely used in herbal medicine. However, the anti-cancer activity of C. atlantica extract (CAt extract) has not been clarified in hepatocellular carcinoma. In the study, we elucidated the anti-hepatoma capacity of CAt extract on HCC in vitro and in vivo. To explore the anti-hepatoma mechanisms of the CAt extract in vitro, HCC and normal cells were treated with the CAt extract, which showed marked inhibitory effects on HCC cells in a dose-dependent manner; in contrast, the CAt extract treatment was less cytotoxic to normal cells. In addition, our results indicate that the CAt extract induced apoptosis via caspase-dependent and independent apoptosis pathways. Furthermore, the CAt extract inhibited HCC tumor cell growth by restraining cell cycle progression, and it reduced the signaling of the AKT, ERK1/2, and p38 pathways. In the xenograft model, the CAt extract suppressed HCC tumor cell growth and prolonged lifespan by inhibiting PCNA protein expression, repressing part of the VEGF-induced autocrine pathway, and triggering strong expression of cleaved caspase-3, which contributed to cell apoptosis. Moreover, the CAt extract did not induce any obvious changes in pathological morphology or body weight, suggesting it had no toxicity. CAt extract exerted anti-tumor effects on HCC in vitro and in vivo. Thus, CAt extract could be used as a potential anti-cancer therapeutic agent against HCC.
Validated Reversed-Phase Liquid Chromatographic Method with Gradient Elution for Simultaneous Determination of the Antiviral Agents: Sofosbuvir, Ledipasvir, Daclatasvir, and Simeprevir in Their Dosage Forms
Authors: Ezzeldin Essam , Abo-Talib Nisreen F. , Tammam Marwa H. , Asiri Yousif A. , Amr Abd El-Galil E. , Almehizia Abdulrahman A.
Published: October 2020

A simple, rapid, sensitive, and precise reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of four direct-acting antivirals, sofosbuvir (SF), ledipasvir (LD), declatasvir (DC), and simeprevir (SM), in their respective pharmaceutical formulations. Effective chromatographic separation was achieved on an Agilent Eclipse plus C8 column (250 mm × 4.6 mm, 5 µm) at 40 °C with gradient elution using a mobile phase composed of acetonitrile:phosphate buffer (pH 6.5). The quantification of SF and DC was based on peak area measurements at 260 nm, while the quantification of LD and SM was achieved at 330 nm. The linearity was acceptable from 1.0 to 20.0 μg/mL for the studied drugs, with correlation coefficients >0.999. The analytical performance of the newly proposed HPLC procedure was thoroughly validated according to ICH guidelines in terms of linearity, precision (RSD%, 0.39–1.57), accuracy (98.05–101.90%), specificity, limit of detection (LOD) (0.022–0.039 μg/mL), limit of quantification (LOQ) (0.067–0.118 μg/mL), and robustness. The validated HPLC method was successfully used to analyze the abovementioned drugs in their pure and dosage forms without interference from common excipients present in commercial formulations.
The Chemical Composition of Brazilian Green Propolis and Its Protective Effects on Mouse Aortic Endothelial Cells against Inflammatory Injury
Authors: Xu Xiaolan , Yang Bo , Wang Danfeng , Zhu Yuxuan , Miao Xiaoqing , Yang Wenchao
Published: October 2020

Propolis has a very complex composition, with antibacterial, anti-inflammatory and other properties. To determine the composition of ethanol extracts of Brazilian green propolis (EEP-B) and their protective effect on mouse aortic endothelial cells (MAECs), the chemical composition of EEP-B was analysed by UPLC/Q-TOF-MS/MS, and the protective effect of EEP-B on the proliferation of lipopolysaccharide (LPS)-induced MAECs was determined by Cell Counting Kit-8 (CCK-8) assays. The protein levels of inflammatory cytokines tumour necrosis factor-α (TNF-α) and interleukin- 6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA), and ICAM-1, VCAM-1 and MCP-1 expressions were analysed by western blotting. The results showed that a total of 24 compounds belonging to cinnamic acids and flavonoids, including 3,5-diisopentenyl-4-hydroxycinnamic acid (artepillin C), kaempferide, 3-isoprenyl p-coumaric acid, pinocembrin and 4′-methoxy pinobanksin, were identified in EEP-B. Among them, a new component, suggested to be 5-isoprenyl caffeic acid p-coumaric acid ester, was reported for the first time. The LPS-induced levels of TNF-α, IL-6, ICAM-1, VCAM-1 and MCP-1 were downregulated in response to 5, 10 and 20 μg/mL EEP-B. This study revealed that EEP-B could reduce LPS-induced inflammatory reactions, improve cell survival, and protect MAECs by regulating ICAM-1, VCAM-1 and MCP-1 expression. These findings could provide a theoretical basis for MAEC treatment using EEP-B.
Synthesis, Docking, 3-D-Qsar, and Biological Assays of Novel Indole Derivatives Targeting Serotonin Transporter, Dopamine D2 Receptor, and Mao-A Enzyme: In the Pursuit for Potential Multitarget Directed Ligands
Authors: Cerda-Cavieres Christopher , Quiroz Gabriel , Iturriaga-Vásquez Patricio , Rodríguez-Lavado Julio , Alarcón-Espósito Jazmín , Saitz Claudio , Pessoa-Mahana Carlos D. , Chung Hery , Araya-Maturana Ramiro , Mella-Raipán Jaime , Cabezas David , Ojeda-Gómez Claudia , Reyes-Parada Miguel , Pessoa-Mahana Hernán
Published: October 2020

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1H-3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7(a–o) and (2-{4-[3-(1H-3-indolyl)-propyl]-1-piperazinyl}-acetylamine)-N-(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13(a–l) were synthesized and evaluated as novel multitarget ligands towards dopamine D2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying Ki values from 5 to 10 nM. Compounds 7k, Ki = 5.63 ± 0.82 nM, and 13c, Ki = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D2 receptor in the nanomolar range (7n: Ki = 307 ± 6 nM and 7m: Ki = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D2 receptor (D2/SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure–activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q2 = 0.625, 0.523 for CoMFA and CoMSIA and r2ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).
Photoprotective Role of Neoxanthin in Plants and Algae
Authors: Giossi Chiara , Cartaxana Paulo , Cruz Sónia
Published: October 2020

Light is a paramount parameter driving photosynthesis. However, excessive irradiance leads to the formation of reactive oxygen species that cause cell damage and hamper the growth of photosynthetic organisms. Xanthophylls are key pigments involved in the photoprotective response of plants and algae to excessive light. Of particular relevance is the operation of xanthophyll cycles (XC) leading to the formation of de-epoxidized molecules with energy dissipating capacities. Neoxanthin, found in plants and algae in two different isomeric forms, is involved in the light stress response at different levels. This xanthophyll is not directly involved in XCs and the molecular mechanisms behind its photoprotective activity are yet to be fully resolved. This review comprehensively addresses the photoprotective role of 9′-cis-neoxanthin, the most abundant neoxanthin isomer, and one of the major xanthophyll components in plants’ photosystems. The light-dependent accumulation of all-trans-neoxanthin in photosynthetic cells was identified exclusively in algae of the order Bryopsidales (Chlorophyta), that lack a functional XC. A putative photoprotective model involving all-trans-neoxanthin is discussed.