bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti-inflammatory Therapy for Coronary Atherosclerotic Heart Disease: Unanswered Questions Behind Existing Successes
Authors: Ma Jun , Chen Xiaoping
Published: February 2021

Coronary atherosclerotic heart disease is a serious threat to human health. The results of the Canakinumab Anti-Inflammatory Thrombosis Outcome Study published in 2017 put an end to the perennial debate about the anti-inflammatory treatment of coronary atherosclerotic heart disease. In addition to interleukin 1β monoclonal antibody, interleukin 6 receptor antagonists and colchicine have also shown exciting results in clinical trials within the last 3 years. However, behind these successes, questions remain that need to be addressed. In this review, we summarize the successes and existing doubts of interleukin 1β antibodies, interleukin 6 receptor antagonists, and colchicine in the anti-inflammatory treatment of coronary atherosclerotic heart disease.
Noninvasive Imaging in Interventional Cardiology: Hypoplastic Left Heart Syndrome
Authors: Bellsham-Revell Hannah
Published: February 2021

Hypoplastic left heart syndrome (HLHS) is a spectrum of left heart underdevelopment leaving the left side unable to support the systemic circulation. If active management is pursued, then the condition is managed with staged palliation to the Fontan circulation, leaving a systemic right ventricle. Through all surgical stages, and even after completion of Fontan, there are multiple areas that may require intervention, most frequently the branch pulmonary arteries which are essential to a successful Fontan circulation. Echocardiography is the mainstay of assessment, but there is an increasing use of magnetic resonance imaging (MRI) and computed tomography (CT) particularly in relation to extracardiac structures which can be more challenging with echocardiography. Both MRI and CT require set-up, experience and training, and usually sedation or anesthetic in smaller children, but can provide excellent imaging to guide interventions. Cardiac MRI is also able to quantify right ventricular (RV) function which can be challenging on echocardiography. This article describes the modalities available and their use in assessing patients with HLHS prior to catheter interventions.
Initial Ablation Ratio Predicts Volume Reduction and Retreatment After 5 Years From Radiofrequency Ablation of Benign Thyroid Nodules
Authors: Bernardi Stella , Cavallaro Marco , Colombin Giacomo , Giudici Fabiola , Zuolo Giulia , Zdjelar Adrian , Dobrinja Chiara , De Manzini Nicolò , Zanconati Fabrizio , Cova Maria Assunta , Stacul Fulvio , Fabris Bruno
Published: February 2021

Background

Radiofrequency ablation (RFA) has gained ground as an effective and well-tolerated technique to treat benign thyroid nodules. Most of the available studies have described the short-term outcomes of RFA, whereas there is a limited number of studies evaluating long-term issues, such as regrowth and the likelihood of retreatments. In addition, risk markers of regrowth and retreatment remain to be defined. The initial ablation ratio (IAR) is an index that measures the amount of ablation after RFA, which has been associated with technique efficacy (i.e. volume reduction >50% after 1 year from the procedure). This study aimed at evaluating i) IAR reproducibility and ii) IAR predictive value for RFA 5-year outcomes.

Materials and Methods

This is a retrospective single center study on patients with benign thyroid nodules treated with RFA and followed for 5 years after initial treatment. IAR interobserver reproducibility was evaluated with Bland-Altman method and Lin’s concordance correlation coefficient (ρc). IAR predictive value for RFA 5-year outcomes was evaluated with linear and logistic regression models, as well as with Cox models, while receiver operating characteristic (ROC) analyses were used for cut-offs.

Results

We selected 78 patients with 82 benign thyroid nodules. The procedure significantly reduced nodule volume and this reduction was generally maintained over time. Technique efficacy was achieved in 92% of patients, while 23% of nodules regrew and 12% of nodules were retreated. Median IAR was 83%. Lin’s concordance and Pearson’s correlation coefficients suggested a good interobserver reproducibility of this index, consistent with the limits of agreement of the Bland-Altman plot. IAR was significantly associated with technique efficacy, 1- and 5-year volume reduction ratio, and with the likelihood of a retreatment, but not with nodule regrowth. ROC analyses showed that IAR cut-off was 49% for technique efficacy and 73% for retreatment.

Conclusions

Our results show for the first time that IAR is reproducible and that it predicts the volume reduction and the likelihood of a retreatment after 5 years from RFA.
Switching From Immediate-Release to Fractionated Dual-Release Hydrocortisone May Improve Metabolic Control and QoL in Selected Primary Adrenal Insufficiency Patients
Authors: Delle Cese Francesca , Corsello Andrea , Cintoni Marco , Locantore Pietro , Pontecorvi Alfredo , Corsello Salvatore Maria , Paragliola Rosa Maria
Published: February 2021

Objective

The use of once-daily dual-release HC (DR-HC) in primary adrenal insufficiency (PAI) is often associated with benefits in metabolic parameters when compared to immediate-release HC (IR-HC). In this study, we evaluated the effects on clinical, biochemical and metabolic parameters of switching from IR-HC to lower-dose DR-HC given both in once and fractionated daily doses.

Methods

Twenty autoimmune-PAI subjects were included. Patients on 30 mg/day divided in three doses IR-HC regimen (group A) were switched to DR-HC 25 mg/day given in two daily doses (20 mg in the morning and 5 mg at 2.00 p.m.); patients on 25 mg/day divided in two doses IR-HC regimen (group B) were switched to DR-HC 20 mg once daily. Biochemical and metabolic parameters, BMI and quality of life (QoL) were evaluated at the baseline and six months after the switch.

Results

Our small non-randomized study with short follow up showed significant benefits in both group A and group B without any apparent side-effects. After the switch to DR-HC, a significant decrease in adrenocorticotropic hormone (ACTH), HbA1c, total cholesterol, triglycerides, LDL, cholesterol, BMI as well as a significant improvement in QoL, were observed in both groups. At 6 months, ACTH levels were lower in group A while HbA1C and total cholesterol were lower in group B.

Conclusion

The DR-HC is a valid and effective therapeutic strategy to improve the metabolic control and the QoL in PAI. The reduction of ACTH levels with DR-HC regimens reflects a better biochemical control of PAI, obtained by using a lower dose and more physiological HC formulation. Both once-daily and fractionated daily doses of DR-HC showed advantages compared with IR-HC formulation.
Anti-TIF-1γ Antibody Detection Using a Commercial Kit vs In-House Immunoblot: Usefulness in Clinical Practice
Authors: Mariscal Anaís , Milán Milena , Baucells Andrés , Martínez Maria Angeles , Guillen Andrea Garcia , Trallero-Araguás Ernesto , Alvarado-Cardenas Marcelo , Martínez-Martínez Laura , Alserawan Leticia , Franco-Leyva Teresa , Sanz-Martínez María Teresa , Viñas-Giménez Laura , Corominas Hector , Juárez Cándido , Castellví Iván , Selva-O’Callaghan Albert
Published: February 2021

Objectives

Anti-TIF-1γ autoantibody detection is important for cancer screening in patients with dermatomyositis. The gold standard for anti-TIF-1γ detection, immunoprecipitation, is only available from a few specialized laboratories worldwide, so commercial ELISA/immunoblot tests have emerged in recent years. To analyze their usefulness in diagnosing cancer-associated dermatomyositis, we compared Euroimmun Euroline profile with our previously validated in-house immunoblot assay with human recombinant TIF-1γ.

Methods

We included 308 adult patients from Hospital de la Santa Creu I Sant Pau and Vall Hebrón Hospital (Barcelona, Spain) tested for anti-TIF-1γ autoantibodies using the Euroline profile and an in-house immunoblot assay.

Results

A total of 27 anti-TIF-1γ were detected by the Euroline and 12 by the in-house assay. Fair agreement was observed between Euroline and the in-house immunoblot Cohen’s kappa 0.3163. Expected prevalence of anti-TIF-1γ autoantibodies was observed for the two methods for dermatomyositis and undifferentiated connective tissue diseases, but unexpectedly high prevalence of anti-TIF-1γ autoantibodies was detected by Euroline compared to the in-house immunoblot for other diseases (16.5% Euroline vs 0.8% in-house immunoblot, p<0.01). The in-house IB compared to Euroline more reliably detected cancer in patients with DM with anti-TIF-1γ antibodies (p=0.0014 vs p=0.0502 for in-house immunoblot vs Euroline).

Conclusion

We recommend using a second validated method to confirm Euroline-detected anti-TIF-1γ antibodies when the dermatomyositis diagnosis is not definitive. Furthermore, in the context of definite DM diagnosis with negative anti-TIF-1γ antibodies by Euroline and no other myositis specific antibody, is also recommendable to confirm by a second validated method.
Itch in Scabies—What Do We Know?
Authors: Ständer Sascha , Ständer Sonja
Published: February 2021

Scabies is a common parasitic skin infestation characterized by severe itch and a heterogenous clinical presentation. Itch, as the cardinal symptom of scabies, is imposing a high burden on affected patients and is often difficult to manage. Decreased life quality and secondary complications, caused by an itch-related disruption of the epidermal barrier and subsequent superinfections, illustrate the need to treat scabies and to understand the underlying mechanisms of itch in respective patients. This review summarizes available data on itch in scabies with a special focus on the clinical aspects and its underlying pathomechanisms.
A Bacterium Isolated From Soil in a Karst Rocky Desertification Region Has Efficient Phosphate-Solubilizing and Plant Growth-Promoting Ability
Authors: Xie Jinge , Yan Zongqiang , Wang Guifen , Xue Wenzhi , Li Cong , Chen Xiwen , Chen Defu
Published: February 2021

Phosphorus in the soil accessible to plants can easily be combined with calcium ion, the content of which is high in karst rocky desertification (KRD) regions, thereby resulting in a low utilization efficiency of phosphorus. The application of phosphate-solubilizing bacteria (PSB) from the KRD region would facilitate enhanced phosphate availability in the soil. In the present study, the strains belonging to Acinetobacter, Paraburkholderia, and Pseudomonas with efficient phosphate-solubilizing ability were isolated from fruit tree rhizosphere soils in KRD regions. Particularly, Acinetobacter sp. Ac-14 had a sustained and stable phosphate-solubilizing ability (439–448 mg/L, 48–120 h). Calcium carbonate decreased the phosphate-solubilizing ability in liquid medium; however, it did not affect the solubilization index in agar-solidified medium. When cocultivated with Arabidopsis thaliana seedling, Ac-14 increased the number of lateral roots, fresh weight, and chlorophyll content of the seedlings. Metabolomics analysis revealed that Ac-14 could produce 23 types of organic acids, majorly including gluconic acid and D-(-)-quinic acid. Expression of Ac-14 glucose dehydrogenase gene (gcd) conferred Pseudomonas sp. Ps-12 with a sustained and stable phosphate-solubilizing ability, suggesting that the production of gluconic acid is an important mechanism that confers phosphate solubilization in bacteria. Moreover, Ac-14 could also produce indole acetic acid and ammonia. Collectively, the isolated Ac-14 from KRD regions possess an efficient phosphate-solubilizing ability and plant growth-promoting effect which could be exploited for enhancing phosphorus availability in KRD regions. This study holds significance for the improvement of soil fertility and agricultural sustainable development in phosphorus-deficient KRD regions.
Distorted Optic Nerve Portends Neurological Complications in Infants With External Hydrocephalus
Authors: Serlin Yonatan , Ben-Arie Gal , Lublinsky Svetlana , Flusser Hagit , Friedman Alon , Shelef Ilan
Published: February 2021

Background: Benign external hydrocephalus (BEH) is defined by rapid increase in head circumference in infancy, with neuroimaging evidence of enlarged cerebrospinal fluid (CSF) spaces. BEH was postulated to predispose to subdural hematoma, neurocognitive impairments, and autism. There is currently no consensus on BEH diagnostic criteria and no biomarkers to predict neurological sequalae.

Methods: MRI-based quantitative approach was used for measurement of potential imaging markers related to external hydrocephalus and their association with neurological outcomes. We scanned 23 infants diagnosed with BEH and 11 age-similar controls. Using anatomical measurements from a large sample of healthy infants (n = 150), Z-scores were calculated to classify subject's CSF spaces as enlarged (≥1.96SD of mean values) or normal.

Results: Subjects with abnormally enlarged CSF spaces had a significantly wider and longer ON (p = 0.017 and p = 0.020, respectively), and a significantly less tortuous ON (p = 0.006). ON deformity demonstrated a high diagnostic accuracy for abnormally enlarged frontal subarachnoid space (AUC = 0.826) and interhemispheric fissure (AUC = 0.833). No significant association found between enlarged CSF spaces and neurological complications (OR = 0.330, 95%CI 0.070–1.553, p = 0.161). However, cluster analysis identified a distinct subgroup of children (23/34, 67.6%) with enlarged CSF spaces and a wider, longer and less tortuous ON, to have an increased risk for neurological complications (RR = 7.28, 95%CI 1.07–49.40).

Discussion: This is the first report on the association between external hydrocephalus, ON deformity and neurological complications. Our findings challenge the current view of external hydrocephalus as a benign condition. ON deformity is a potential auxiliary marker for risk stratification in patients with enlarged CSF spaces.
PGC-1α Signaling Increases GABA(A) Receptor Subunit α2 Expression, GABAergic Neurotransmission and Anxiety-Like Behavior in Mice
Authors: Vanaveski Taavi , Molchanova Svetlana , Pham Dan Duc , Schäfer Annika , Pajanoja Ceren , Narvik Jane , Srinivasan Vignesh , Urb Mari , Koivisto Maria , Vasar Eero , Timmusk Tönis , Minkeviciene Rimante , Eriksson Ove , Lalowski Maciej , Taira Tomi , Korhonen Laura , Voikar Vootele , Lindholm Dan
Published: February 2021

Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is a master regulator of mitochondria biogenesis and cell stress playing a role in metabolic and degenerative diseases. In the brain PGC-1α expression has been localized mainly to GABAergic interneurons but its overall role is not fully understood. We observed here that the protein levels of γ-aminobutyric acid (GABA) type A receptor-α2 subunit (GABARα2) were increased in hippocampus and brain cortex in transgenic (Tg) mice overexpressing PGC-1α in neurons. Along with this, GABARα2 expression was enhanced in the hippocampus of the PGC-1α Tg mice, as shown by quantitative PCR. Double immunostaining revealed that GABARα2 co-localized with the synaptic protein gephyrin in higher amounts in the striatum radiatum layer of the hippocampal CA1 region in the Tg compared with Wt mice. Electrophysiology revealed that the frequency of spontaneous and miniature inhibitory postsynaptic currents (mIPSCs) was increased in the CA1 region in the Tg mice, indicative of an augmented GABAergic transmission. Behavioral tests revealed an increase for anxiety-like behavior in the PGC-1α Tg mice compared with controls. To study whether drugs acting on PPARγ can affect GABARα2, we employed pioglitazone that elevated GABARα2 expression in primary cultured neurons. Similar results were obtained using the specific PPARγ agonist, N-(2-benzoylphenyl)-O-[2-(methyl-2-pyridinylamino) ethyl]-L-tyrosine hydrate (GW1929). These results demonstrate that PGC-1α regulates GABARα2 subunits and GABAergic neurotransmission in the hippocampus with behavioral consequences. This indicates further that drugs like pioglitazone, widely used in the treatment of type 2 diabetes, can influence GABARα2 expression via the PPARγ/PGC-1α system.
Parsing Neurodynamic Information Streams to Estimate the Frequency, Magnitude and Duration of Team Uncertainty
Authors: Stevens Ronald H. , Galloway Trysha L.
Published: February 2021

Neurodynamic organizations are information-based abstractions, expressed in bits, of the structure of long duration EEG amplitude levels. Neurodynamic information (NI, the variable of neurodynamic organization) is thought to continually accumulate as EEG amplitudes cycle through periods of persistent activation and deactivation in response to the activities and uncertainties of teamwork. Here we show that (1) Neurodynamic information levels were a better predictor of uncertainty and novice and expert behaviors than were the EEG power levels from which NI was derived. (2) Spatial and temporal parsing of team NI from experienced submarine navigation and healthcare teams showed that it was composed of discrete peaks with durations up to 20–60 s, and identified the involvement of activated delta waves when precise motor control was needed. (3) The relationship between NI and EEG power was complex varying by brain regions, EEG frequencies, and global vs. local brain interactions. The presence of an organizational system of information that parallels the amplitude of EEG rhythms is important as it provides a greatly reduced data dimension while retaining the essential system features, i.e., linkages to higher scale behaviors that span temporal and spatial scales of teamwork. In this way the combinatorial explosion of EEG rhythmic variables at micro levels become compressed into an intermediate system of information and organization which links to macro-scale team and team member behaviors. These studies provide an avenue for understanding how complex organizations arise from the dynamics of underlying micro-scale variables. The study also has practical implications for how micro-scale variables might be better represented, both conceptually and in terms of parsimony, for training machines to recognize human behaviors that span scales of teams.
The Effects of Early Nutritional Intervention on Oral Mucositis and Nutritional Status of Patients With Head and Neck Cancer Treated With Radiotherapy
Authors: Zheng Zhuangzhuang , Zhao Xin , Zhao Qin , Zhang Yuyu , Liu Shiyu , Liu Zijing , Meng Lingbin , Xin Ying , Jiang Xin
Published: February 2021

Radiation-induced oral mucositis (RIOM) is a common side effect after radiotherapy (RT) in head and neck cancer (HNC) patients. RIOM patients with severe pain have difficulty in eating, which increases the incidence of malnutrition and affects patients’ quality of life and the process of RT. The mechanism of RIOM is not fully understood, and inflammatory response and oxidative stress appear to be important for RIOM occurrence and development. The nutritional status of patients is very important for their RT tolerance and recovery. Malnutrition, which can lead to anemia, low protein, decreased immunity and other problems, is an important clinical factor affecting tumor progression and treatment. Recent studies have shown that early nutritional intervention can ameliorate oral mucositis and nutritional status of patients with HNC. However, in clinical practice, early nutritional intervention for patients with HNC is not a conventional intervention strategy. Therefore, this review summarized the possible pathogenesis of RIOM, commonly used assessment tools for malnutrition in patients, and recent studies on the effects of early nutritional interventions on RIOM and nutritional status of patients with HNC. We hope to provide the basis and reference for the clinical application of early nutritional intervention models.
Application of Multimodal and Molecular Imaging Techniques in the Detection of Choroidal Melanomas
Authors: Li Xuying , Wang Lixiang , Zhang Li , Tang Fei , Wei Xin
Published: February 2021

Choroidal melanomas are the most common ocular malignant tumors worldwide. The onset of such tumors is insidious, such that affected patients often have no pain or obvious discomfort during early stages. Notably, enucleation is required for patients with a severe choroidal melanoma, which can seriously impact their quality of life. Moreover, choroidal melanomas metastasize early, often to the liver; this eventually causes affected patients to die of liver failure. Therefore, early diagnosis of choroidal melanomas is extremely important. Unfortunately, an early choroidal melanoma is easily confused with a choroidal nevus, which is the most common benign tumor of the eye and does not often require surgical treatment. This review discusses recent advances in the use of multimodal and molecular imaging to identify choroidal melanomas and choroidal nevi, detect early metastasis, and diagnose patients with choroidal melanomas.
Access to Essential Cardiovascular Medicines in Pakistan: A National Survey on the Availability, Price, and Affordability, Using WHO/HAI Methodology
Authors: Saeed Amna , Saeed Faria , Saeed Hamid , Saleem Zikria , Yang Caijun , Chang Jie , Jiang Minghuan , Zhao Mingyue , Saqlain Muhammad , Ji Wenjing , Aziz Muhammad Majid , Lambojon Krizzia , Gillani Ali Hassan , Hayat Khezar , Gul Sabiha , Fang Yu , Babar Zaheer-Ud-Din
Published: February 2021

Objective: This national survey was aimed at measuring the access to cardiovascular disease (CVD) medicines in terms of their availability, price, and affordability in Pakistan. This was done by using the standard WHO/Health Action International (HAI) methodology.

Methods: The price and availability data for 18 CVD medicines were collected from public sector hospitals (n = 40) and private sector retail pharmacies (n = 40) in eight cities of Pakistan. The outcome measures were availability (calculated as percentage of health facilities stocked with listed medicines), medicine price to the international reference price ratio (i.e., median price ratio (MPR)), and affordability (calculated as number of days’ wages (NDWs) of the lowest paid unskilled government worker required to afford one-month treatment of a chronic disease). The affordability of standard treatment in Pakistan with four CVD drugs was compared with data from six other low and middle income countries (LMICs) using HAI database.

Findings: The mean percent availability of CVD medicines was significantly low (p < 0.001) in the public sector as compared to the private sector, that is, 25.5% vs. 54.6% for originator brands (OBs) and 30.4% vs. 34.9% for lowest price generics (LPGs), respectively. For all OBs and LPGs, the inflation-adjusted mean MPR was 2.72 and 1, respectively. CVD medicines were found to be unaffordable with average NDWs of 6.4 and 2.2 for OBs and LPGs, respectively, that is, NDWs of more than 1. In international comparison with countries such as Sudan, Lebanon, Egypt, India, Afghanistan, and China, the affordability of standard treatment with selected CVD medicines (atenolol, amlodipine, captopril, and simvastatin) in Pakistan was found to be low. Overall, all four OBs and three out of four LPGs of selected CVD drugs were found unaffordable in Pakistan.

Conclusion: This data indicated that the availability of selected CVD medicines was low in both public and private sector medicine outlets. Both OBs and LPGs were found unaffordable in the private sector, necessitating the redressal of pricing policies, structuring, and their implementation.
Antibacterial Activities of Echinops kebericho Mesfin Tuber Extracts and Isolation of the Most Active Compound, Dehydrocostus Lactone
Authors: Deyno Serawit , Mtewa Andrew G. , Hope Derick , Bazira Joel , Makonnen Eyasu , Alele Paul E.
Published: February 2021

Echinops keberichoMesfin is traditionally used for the treatment of various infectious diseases. This study investigated antibacterial activity of the essential oil (EO) and the different fractions of ethanol extract. The most active component was isolated and identified. Isolation and purification was accomplished using chromatographic techniques while identification was done by spectroscopic method. Minimum inhibitory concentration (MIC) was determined using the broth micro-dilution method. In bioactive-guided isolation, percent inhibition was determined using optical density (OD) measurement. The MICs of the essential oil ranged from 78.125 μg/ml to 625 μg/ml, and its activity was observed against methicillin-resistantStaphylococcus aureus(MRSA, NCTC 12493). Ethyl acetate fraction showed high activity against MRSA (NCTC 12493), MIC = 39.075 μg/ml followed byEnterococcus faecalis(ATCC 49532), MIC = 78.125 μg/ml and was least active againstKlebsiella pneumoniae(ATCC 700603), MIC = 1,250 μg/ml. MIC of hexane fraction ranged from 156.2 µg/ml toEscherichia coli(ATCC 49532) to 1,250 μg/ml toE. coli(NCTC 11954). The MICs of chloroform fraction ranged from 312.5 to 2500 μg/ml; while butanol fraction could be considered pharmacologically inactive as its MIC value was 2,500 μg/ml for all and no activity againstE. coli(NCTC 11954). Dehydrocostus lactone was successfully isolated and identified whose MIC was 19.53 μg/ml against MRSA. Dehydrocostus lactone isolated fromE. keberichoM. showed noteworthy antibacterial activity which lends support to ethnopharmacological use of the plant. Further optimization should be done to improve its antibacterial activities and pharmacokinetic profile.
Modeling Complex Orthopedic Trauma in Rodents: Bone, Muscle and Nerve Injury and Healing
Authors: Shen Huaishuang , Gardner Aysha M. , Vyas Juhee , Ishida Ryosuke , Tawfik Vivianne L.
Published: February 2021

Orthopedic injury can occur from a variety of causes including motor vehicle collision, battlefield injuries or even falls from standing. Persistent limb pain is common after orthopedic injury or surgery and presents a unique challenge, as the initiating event may result in polytrauma to bone, muscle, and peripheral nerves. It is imperative that we understand the tissue-specific and multicellular response to this unique type of injury in order to best develop targeted treatments that improve healing and regeneration. In this Mini Review we will first discuss current rodent models of orthopedic trauma/complex orthotrauma. In the second section, we will focus on bone-specific outcomes including imaging modalities, biomechanical testing and immunostaining for markers of bone healing/turnover. In the third section, we will discuss muscle-related pathology including outcome measures of fibrosis, muscle regeneration and tensile strength measurements. In the fourth section, we will discuss nervous system-related pathology including outcome measures of pain-like responses, both reflexive and non-reflexive. In all sections we will consider parallels between preclinical outcome measures and the functional and mechanistic findings of the human condition.
Potency, Safety, and Pharmacokinetic Profiles of Potential Inhibitors Targeting SARS-CoV-2 Main Protease
Authors: Mengist Hylemariam Mihiretie , Mekonnen Daniel , Mohammed Ahmed , Shi Ronghua , Jin Tengchuan
Published: February 2021

Effective, safe, and pharmacokinetically suitable drugs are urgently needed to curb the ongoing COVID-19 pandemic. The main protease or 3C-like protease (Mproor 3CLpro) of SARS-CoV-2 is considered an important target to formulate potent drugs corresponding to its crucial role in virus replication and maturation in addition to its relatively conserved active site. Promising baseline data on the potency and safety of drugs targeting SARS-CoV-2 Mproare currently available. However, preclinical and clinical data on the pharmacokinetic profiles of these drugs are very limited. This review discusses the potency, safety, and pharmacokinetic profiles of potential inhibitors of SARS-CoV-2 Mproand forward directions on the development of future studies focusing on COVID-19 therapeutics.
The Effect of An Emergency Evacuation on the Spread of COVID19
Authors: Butail Sachit , Porfiri Maurizio
Published: February 2021

In an emergency evacuation, people almost always come in close proximity as they quickly leave a built environment under a potential threat. With COVID19, this situation presents yet another challenge: that of getting unintentionally exposed to an infected individual. To assess the epidemiological consequences of an emergency evacuation, we expanded a popular pedestrian dynamic model to enable social distancing during a normal exit and analyze the effect of possible transmission through respiratory droplets and aerosol. Computer simulations point to a troubling outcome, whereby the benefits of a quick exit could be outweighed by the risk of infection.
Extracellular Vesicles and Exosomes: Insights From Exercise Science
Authors: Nederveen Joshua P. , Warnier Geoffrey , Di Carlo Alessia , Nilsson Mats I. , Tarnopolsky Mark A.
Published: February 2021

The benefits of exercise on health and longevity are well-established, and evidence suggests that these effects are partially driven by a spectrum of bioactive molecules released into circulation during exercise (e.g., exercise factors or ‘exerkines’). Recently, extracellular vesicles (EVs), including microvesicles (MVs) and exosomes or exosome-like vesicles (ELVs), were shown to be secreted concomitantly with exerkines. These EVs have therefore been proposed to act as cargo carriers or ‘mediators’ of intercellular communication. Given these findings, there has been a rapidly growing interest in the role of EVs in the multi-systemic, adaptive response to exercise. This review aims to summarize our current understanding of the effects of exercise on MVs and ELVs, examine their role in the exercise response and long-term adaptations, and highlight the main methodological hurdles related to blood collection, purification, and characterization of ELVs.
Role of 25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 in Chicken Embryo Osteogenesis, Adipogenesis, Myogenesis, and Vitamin D3 Metabolism
Authors: Chen Chongxiao , White Dima Lynn , Marshall Brett , Kim Woo Kyun
Published: February 2021

A study was conducted to understand the effects of 25-hydroxyvitamin D3 (25OHD) and 1,25-dihydroxyvitamin D3 (1,25OHD) administration on the expression of key genes related to osteogenesis, adipogenesis, myogenesis, and vitamin D3 metabolism in the chicken embryo. A total of 120 fertilized Cobb 500 eggs were used in the current study and were reared under standard incubation conditions. On embryonic day 3 (ED 3), PBS (C), PBS with 40ng 1,25OHD (1,25D-L), 200ng 1,25OHD (1,25D-H), 40ng 25OHD (25D-L), or 200ng 25OHD (25D-H) were injected into the dorsal vein of developing embryos. Whole embryos were harvested at 1, 3, and 6h post-injection for gene expression analyses (n=8). Gene expression for key osteogenesis markers (RUNX2: runt-related transcription factor 2; BMP2: bone morphogenetic protein 2; COL1A2: collagen type I alpha 2 chain; BGLAP: bone gamma-carboxyglutamate protein; SPP1: secreted phosphoprotein 1; and ALP: alkaline phosphatese), adipogenesis markers (PPAR-γ: peroxisome proliferator-activated receptor gamma; FASN: fatty acid synthase; and FABP4: fatty acid binding protein 4), myogenesis markers (MYOG: myogenin; MYOD1: myogenic differentiation 1; and MYF5: myogenic factor 5), and the enzyme responsible for vitamin D3 inactivation (CYP24A1: cytochrome P450 family 24 subfamily A member 1) were measured using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Data were normalized by the ΔΔCT method and analyzed using a one-way ANOVA. Results indicated that at 1h post-injection, no differences were found among treatments. At 3h, the early osteogenesis differentiation marker, ALP, was increased by 1,25D-H and 25D-H, and 25D-H also stimulated the expression of adipogenesis markers (FAPB4 and FASN). In contrast, the expression of myogenesis markers (MYOD1 and MYF5) was suppressed by 25OHD or 1,25OHD treatments, respectively. At 6h, a late osteogenic differentiation marker, SPP1, was increased by 25D-H. MYOD1 and MYF5 were continuously suppressed by 25OHD treatments or 1,25D-H. The evidence of vitamin D3 metabolite retention was assessed by measuring CYP24A1 expression. At 1h, there were no differences in CYP24A1 expression. At 3h, all treatments upregulated CYP24A1 expression relative to control (PBS) embryos. However, at 6h, only the 25D-H group retained higher CYP24A1 expression compared to the other treatments. In conclusion, the results suggested both 1,25OHD and 25OHD induced chicken embryo osteogenesis and adipogenesis, but inhibited myogenesis during early chicken embryo development. The higher dosage of 25OHD showed a possibility of a longer retention time in the embryos.
Signaling Toward Reactive Oxygen Species-Scavenging Enzymes in Plants
Authors: Dvořák Petr , Krasylenko Yuliya , Zeiner Adam , Šamaj Jozef , Takáč Tomáš
Published: February 2021

Reactive oxygen species (ROS) are signaling molecules essential for plant responses to abiotic and biotic stimuli as well as for multiple developmental processes. They are produced as byproducts of aerobic metabolism and are affected by adverse environmental conditions. The ROS content is controlled on the side of their production but also by scavenging machinery. Antioxidant enzymes represent a major ROS-scavenging force and are crucial for stress tolerance in plants. Enzymatic antioxidant defense occurs as a series of redox reactions for ROS elimination. Therefore, the deregulation of the antioxidant machinery may lead to the overaccumulation of ROS in plants, with negative consequences both in terms of plant development and resistance to environmental challenges. The transcriptional activation of antioxidant enzymes accompanies the long-term exposure of plants to unfavorable environmental conditions. Fast ROS production requires the immediate mobilization of the antioxidant defense system, which may occur via retrograde signaling, redox-based modifications, and the phosphorylation of ROS detoxifying enzymes. This review aimed to summarize the current knowledge on signaling processes regulating the enzymatic antioxidant capacity of plants.
On the Relationship of Interoceptive Accuracy and Attention: A Controlled Study With Depressed Inpatients and a Healthy Cohort
Authors: Schultchen Dana , Schneider Carolin , Berberich Götz , Zaudig Michael , Erle Thorsten M. , Pollatos Olga
Published: February 2021

Objective

Previous research has shown reduced interoceptive accuracy (IAcc) in depression. Attention deficit represents a key symptom of depression. Moreover, IAcc is positively correlated with attention. There is no study that investigates the effect of depression on IAcc and attention. The aim of this study is to examine the mediating effect of IAcc on depression and attention.

Methods

Thirty-six depressed patients from the Psychosomatic Clinic in Windach were matched with 36 healthy controls according to age and sex and were assessed at Ulm University. All participants completed the Beck Depression Inventory-II, the heartbeat perception task to examine IAcc, and the d2 test assessing selective attention.

Results

Depressed patients showed attention deficits—both for general visual attention and IAcc—compared to healthy controls. The mediation analyses revealed that the relationship between depression and attention is not mediated via IAcc. Furthermore, depression predicts IAcc and attention, but these effects are direct and largely unaffected by the respective other variable.

Discussion

The results of the present study highlight both interoceptive as well as attention deficits in depressed patients. No clear mediation between these variables could be shown in this study. More elaborative research is needed to clarify whether different approaches to improve IAcc are effective for these deficits in depressed patients and could therefore be of importance as an additional aspect of therapy in depression.
Effect of Modulating Activity in the Right DLPFC on Revenge Behavior: Evidence From a Noninvasive Brain Stimulation Investigation
Authors: Zheng Wanjun , Tao Yuanping , Li Yuzhen , Ye Hang , Luo Jun
Published: February 2021

Revenge is common in our daily lives, and people feel good when engaging in revenge behavior. However, revenge behavior is a complex process and remains somewhat of a puzzle of human behavior. Neuroimaging studies have revealed that revenge behaviors are associated with activation of a neural network containing the anterior cingulate cortex, ventral striatum, inferior frontal gyrus, and dorsolateral prefrontal cortex (DLPFC). Recent brain stimulation research using transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation has shown a causal relationship between brain regions and revenge behaviors, but the findings have been mixed. In the present study, we aimed to study whether stimulation in the DLPFC can change participants’ revenge behavior in conditions where participants’ wealth was taken away in different ways. We adapted the moonlighting game and designed a new paradigm. Our study revealed that revenge behavior increased following activation in the right DLPFC, suggesting that the right DLPFC plays an important role in overriding self-interest and retaliation. In addition, our results revealed that the right DLPFC is crucial in revenge behavior related to the motivation of invasion.
Co-developing a Mental Health and Wellbeing Chatbot With and for Young People
Authors: Grové Christine
Published: February 2021

There are many young people who experience mental health and wellbeing challenges. A potential negative mental health trigger for some youth is a struggle to cope with stress at school, feelings of depression and anxiety and availability of adequate help for these stressors. In response to youth needs a mental health and wellbeing Chatbot has been co-developed with youth, technology partners and expert stakeholders. An element of the Chatbot is powered by artificial intelligence and rules based AI using natural language processing. It is created to communicate evidence based resources, wellbeing support, educational mental health information and adaptive coping strategies. This paper will discuss how the Chatbot has been developed, highlighting its participatory, co-design process with youth who are the key stakeholders to benefit from this digital tool. Research from interviews and surveys informed the creation of the Chabots personality and its character design. Examples of the conversation design and content development are provided. The paper finishes with how, if at all, digital tools such as Chatbot applications could support the mental health of young people in secondary schools or health care settings in conjunction with the wellbeing or health care team, concluding with lessons learned and cautions.
Less Social Support for Patients With COVID-19: Comparison With the Experience of Nurses
Authors: Li Zhenyu , Ge Jingwu , Feng Jianping , Jiang Riyue , Zhou Qin , Xu Xiaolin , Pan Yinbing , Liu Shijiang , Gui Bo , Wang Zhongyun , Zhu Bin , Hu Yimin , Yang Jianjun , Wang Rong , Su Dongan , Hashimoto Kenji , Yang Meiling , Yang Chun , Liu Cunming
Published: February 2021

Context: Since December 2019, more than 80,000 patients have been diagnosed with coronavirus disease 2019 (COVID-19) in China. Social support status of COVID-19 patients, especially the impact of social support on their psychological status and quality of life, needs to be addressed with increasing concern.

Objectives: In this study, we used social support rating scale (SSRS) to investigate the social support in COVID-19 patients and nurses.

Methods: The present study included 186 COVID-19 patients at a Wuhan mobile cabin hospital and 234 nurses at a Wuhan COVID-19 control center. Responses to a mobile phone app-based questionnaire about social support, anxiety, depression, and quality of life were recorded and evaluated.

Results: COVID-19 patients scored significantly lower than nurses did on the Social Support Rating Scale (SSRS). Among these patients, 33.9% had anxiety symptoms, while 23.7% had depression symptoms. Overall SSRS, subjective social support scores and objective support scores of patients with anxiety were lower than those of patients without anxiety. This result was also found in depression. In addition, all dimensions of social support were positively correlated with quality of life. Interestingly, in all dimensions of social support, subjective support was found to be an independent predictive factor for anxiety, depression, and quality of life, whereas objective support was a predictive factor for quality of life, but not for anxiety and depression via regression analysis.

Conclusion: Medical staffs should pay attention to the subjective feelings of patients and make COVID-19 patients feel respected, supported, and understood from the perspective of subjective support, which may greatly benefit patients, alleviate their anxiety and depression, and improve their quality of life.
Managing Multimorbidity (Multiple Chronic Diseases) Amid COVID-19 Pandemic: A Community Based Study From Odisha, India
Authors: Pati Sanghamitra , Mahapatra Pranab , Kanungo Srikanta , Uddin Azhar , Sahoo Krushna Chandra
Published: February 2021

While most of the studies to date demonstrate the deleterious effect of multiple chronic diseases on COVID-19 risk and outcome, there is sparse information available on the effect of the pandemic on multimorbidity management, with no reports yet from India. We sought to explore the effect of COVID-19 pandemic on routine and emergency care for multimorbidity among community-dwelling adults in Odisha, India. A community-based cross-sectional study was undertaken pandemic lockdown, in Khurda district of Odisha, India. Around 600 individuals having at least one chronic disease residing in rural, urban residential and slums were interviewed using a specifically developed questionnaire MAQ COVID-19. The association of socio-demographic characteristics and multimorbidity with pandemic-related care challenges was examined by multiple logistic regression. Principal Component Analysis was employed to minimize the dimensionality of factors related to multimorbidity care. Multimorbidity was highly prevalent in younger age group (46–60 years) with cardio-metabolic clusters being dominant. Individuals with multimorbidity experienced significantly higher care challenges than those with single condition (AOR = 1.48, 95% CI = 1.01–2.05) with notable disruption in treatment and routine check-up. Most frequently cited concerns were—physician consultation (43%), diagnostic-services (26%), transport (33%), and mobility restrictions (21%). Multivariate analysis revealed older adults living alone in urban residence to have higher challenges than their rural counterparts. Patient activation for self-care, multimorbidity literacy, and technology-enabled tele-consultation could be explored as potential interventions. Future studies should qualitatively explore the challenges of physicians as well as garner an in-depth understanding of multimorbidity management in the vulnerable subgroups.
Eccentric Exercise Is Powerful but Can Be Painful
Authors: Clos Pierre , Garnier Yoann M. , Lepers Romuald
Published: February 2021

Your muscles can contract in different ways: when you walk upstairs, the muscles at the fronts of your thighs shorten (concentric contraction), whereas when you walk downstairs, they lengthen (eccentric contraction). Concentric contractions require more oxygen and thus make you burn more calories. Eccentric contractions are easier but break parts of the muscle and make you feel sore for several days. If you repeat eccentric exercises, however, your muscles will probably get bigger and stronger than they would by repeating concentric contractions. Most physical activities (like running and jumping) include both concentric and eccentric phases. Scientists have designed tools to study each type of muscle contraction, such as eccentric cycling, which uses a bike on which you must resist the pedals as they are driven backward by an engine.
Summary of the Experience in the Diagnosis and Treatment of Complex Preauricular Fistulas in 78 Children
Authors: Xu Ying , Seng Dongjie , Jiang Lan , Wang Shengcai , Ni Xin , Zhang Jie , Han Fugen
Published: February 2021

Objective: This study aimed to investigate the application of mini-incisions in complex preauricular fistula resection in children.

Methods: A total of 78 children who were diagnosed with preauricular fistula infection between January 2017 and December 2019 were included in the study. Their clinical data were analyzed retrospectively, and surgical treatment with mini-incisions based on plastic surgery principles and techniques was provided.

Results: All the patients achieved healing following the first application of the treatment. The patients were followed up for 6–42 months, and no recurrence or local auricular deformation occurred.

Conclusion: The application of mini-incisions and plastic surgery techniques in complex preauricular fistula resection in children can achieve a good effect and improve the satisfaction of the children and their parents.
Reduced Performance Due to Adenoviral Gizzard Erosion in 16-Day-Old Commercial Broiler Chickens in Iran, Confirmed Experimentally
Authors: Mirzazadeh Amin , Grafl Beatrice , Abbasnia Mohammad , Emadi-Jamali Sobhan , Abdi-Hachesoo Bahman , Schachner Anna , Hess Michael
Published: February 2021

Adenoviral gizzard erosion (AGE) in broilers is an emerging infectious disease with negative impact on flock productivity. Despite of known primary etiological role of fowl adenovirus serotype 1 (FAdV-1) in AGE, there are a limited number of field reports worldwide, possibly because the disease is less noticeable and clinically difficult to assess. The present study documents an outbreak of AGE in 16-day-old broiler chickens on a farm in the north of Iran and the reproduction of the disease in an experimental setting. In the field, a sudden onset of mortality was noticed in affected broilers resulting in 6% total mortality and decreased weight gain leading to approximately 1-week delay to reach the target slaughter weight. Necropsy findings in dead broilers revealed black colored content in crop, proventriculus and gizzard together with severe gizzard erosions characterized by multiple black-brown areas of variable size in the koilin layer and mucosal inflammation. Microscopic examination revealed necrotizing ventriculitis marked with severe dissociation of koilin layer and degeneration of glandular epithelium with infiltration of mononuclear inflammatory cells. FAdV-1 was isolated from affected gizzards. Phylogenetic analysis of the hexon loop-1 (L1) sequence of the isolated virus showed 100% identity with pathogenic FAdV-1 strains previously reported from broiler chickens with AGE. Subsequently, an in vivo study infecting day-old commercial layer chickens with the field isolate demonstrated characteristic lesions and histopathological changes of AGE together with decreased weight gain in the infected birds. For the first time, the progress of a natural outbreak of AGE in Iran is described and experimental reproduction of the disease is demonstrated. The findings highlight the economic impact of the disease for regional poultry production due to mortality and impaired weight gain of the affected broilers.