bluuebunny/crossref_metadata_2025 huggingface dataset:
Odontogenic Head and Neck Region Infections Requiring Hospitalization: An 18‐Month Retrospective Analysis
Authors: Zawiślak Ewa , Nowak Rafał
Published: January 2021

The aim of this study was to comprehensively review our experience with odontogenic infections in the head and neck region requiring treatment at a national referral center. We retrospectively reviewed 85 patients treated at the Chair and Clinic of Maxillofacial Surgery of the University Hospital in Wrocław between January 2018 and June 2019. We excluded patients with nonondontogenic infections or other than purulent clinical forms of dentivitis in the head and neck region. Several demographic, clinicopathological, and treatment variables were assessed. The majority of patients were men who were referred for inpatient treatment by a dentist or family doctor, presented to the Hospital Emergency Ward (SOR) by themselves, or transported to the SOR by paramedics SOR from their home or another hospital. All patients were treated in accordance with the current guidelines for head and neck region odontogenic infections. An incision was made and the abscess was drained. The odontogenic cause was removed followed by the collection of tissue for microbiological examination. The course of infection was monitored by means of laboratory parameters such as leukocyte counts and c‐reactive protein levels. Odontogenic infections in the head and neck region are a persistent and common problem. Rapid, accurate diagnosis and treatment minimizes the risk of life‐threatening complications, shortens the hospitalization period, and lowers treatment costs.
Double Auction-Based Two-Level Resource Allocation Mechanism for Computation Offloading in Mobile Blockchain Application
Authors: Li Li , Li Yue , Li Ruotong
Published: January 2021

It is increasingly popular that platforms integrate various services into mobile applications due to the high usage and convenience of mobile devices, many of which demand high computational capacities and energy, such as cryptocurrency services based on blockchain. However, it is hard for mobile devices to run these services due to the limited storage and computational capacity. In this paper, the problem of computation offloading that requires sufficient computing resources with high utilization in large-scale users and multiprovider MEC system was investigated. A mechanism based on the combinatorial double auction, G-TRAP, is proposed in this paper to solve the above problem. In the mechanism, resources are provided both in the cloud and at the edge of the network. Mobile users compete for these resources to offload computing tasks by the rule that the edge-level resources will be allocated at first while cloud-level resources could be the supplement for the edge level. Given that the proof-of-work (PoW), the core issue of blockchain application, is resource-expensive to implement in mobile devices, we provide resource allocation service to users of blockchain application as experimental subjects. Simulation results show that the proposed mechanism for serving large-scale users in a short execution time outperforms two existing algorithms in terms of social utility and resource utilization. Consequently, our proposed system can effectively solve the intensive computation offloading problem of mobile blockchain applications.
Simulation Research on Trapped Oil Pressure of Involute Internal Gear Pump
Authors: Guo Shanxin , Guan Xiangfeng
Published: January 2021

The main structure of an internal gear pump consisted of an internal gear pair, including an internal gear and an external gear. The internal gear pump had oil trapping phenomenon like other hydraulic gear pumps. In order to solve the oil trapping phenomenon of involute gear pump with internal meshing tooth profile, in this paper, the mathematical equation of gear outer contour is established according to the principle of generation method, and the variation law of the trapped oil area in meshing process is deduced by theoretical instantaneous flow rate obtained by scanning method. Then, the minimum trapped oil volume and unloading area are solved by the graphic method. Finally, based on fluid mechanics and dynamics, the trapped oil pressure model is obtained. The change of the trapped oil area and trapped oil pressure in a meshing cycle is simulated by MATLAB. The results show that the trapped oil area changes in a parabola, and the trapped pressure fluctuates in mountains and valleys. When the trapped area is the smallest, the trapped oil pressure reaches the peak at the corresponding corner. The research results can provide guidance for the development of high-performance internal gear pumps.
Mathematical Modelling of Lesser Date Moth Using Sex Pheromone Traps and Natural Enemies
Authors: El-Shahed Moustafa , Al-Dubiban Asmaa M.
Published: January 2021

In this paper, a mathematical model for lesser date moth is proposed and analyzed. The interaction between the date palm tree, lesser date moth, and natural enemy has been investigated. The impact of sex pheromone traps on lesser date moth is demonstrated. Some sufficient conditions are obtained to ensure the local and global stability of equilibrium points. The occurrence of local bifurcation near the equilibrium points is performed using Sotomayor’s theorem. Theoretical results are illustrated using numerical simulations.
Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture
Authors: Ritter Katharina , Jung Kirsten , Dolderer Christopher , Appel Dominik , Oswald Christine C. , Ritz Ulrike , Schäfer Michael K. E.
Published: January 2021

Traumatic brain injury (TBI) represents a major cause of death and disability in early adulthood. Concomitant extracranial injury such as long bone fracture was reported to exacerbate TBI pathology. However, early reciprocal effects and mechanisms have been barely investigated. To address this issue, C57BL/6N mice were subjected to either the controlled cortical impact (CCI) model of TBI, fracture of the left femur (FF), combined injury (CCI+FF), or sham procedure. Behavioral alterations were monitored until 5 days post injury (dpi), followed by (immuno-)histology, gene and protein expression analyses using quantitative PCR, western blot, and ELISA. We found that CCI+FF mice exhibited increased neurological impairments, reduced recovery, and altered anxiety-related behavior compared to single injury groups. At 5 dpi, cerebral lesion size was not affected by combined injury but exaggerated hippocampal substance loss and increased perilesional astrogliosis were observed in CCI+FF mice compared to isolated CCI. Bone gene expression of the osteogenic markers Runx2, osteocalcin, alkaline phosphatase, and bone sialoprotein was induced by fracture injury but attenuated by concomitant TBI. Plasma concentrations of the biomarkers osteopontin and progranulin were elevated in CCI+FF mice compared to other experimental groups. Taken together, using a murine model of TBI and femoral fracture, we report early reciprocal impairments of brain tissue maintenance, behavioral recovery, and bone repair gene expression. Increased circulating levels of the biomarkers osteopontin and progranulin indicate ongoing tissue inflammation and repair. Our results may have implications for future therapeutic approaches to interfere with the pathological crosstalk between TBI and concomitant bone fracture.
Effects of Frozen Storage Temperature and Duration on Changes in Physicochemical Properties of Beef Myofibrillar Protein
Authors: Qian Shuyi , Li Xia , Wang Hang , Mehmood Waris , Zhang Chunhui , Blecker Christophe
Published: January 2021

This study aimed to address the effects of frozen storage temperature and duration on the changes in physicochemical properties of beef myofibrillar protein. The beef was stored at −1, −6, −9, −12, and −18°C for 28, 84, 126, 168, and 168 days, respectively. The myofibrillar protein of beef samples denatured gradually with the extention of storage period. Regarding the samples stored at temperature range of −12∼−1°C, higher storage temperature resulted in more severe denaturation (the myofibrillar protein exhibited lower sulfhydryl content, Ca2+-ATPase activity, ionic bonds, hydrogen bonds, and higher surface hydrophobicity). Particularly, difference in −12 and −18°C did not yield significant effects upon the protein properties throughout 168-day storage

P
>
0.05

. These results indicated that lowering freezing temperature may not minimize myofibrillar protein denaturation in a limited storage duration, which was also confirmed by the quality properties of beef.
Prevalence of Cryptococcal Antigenemia and Associated Factors among HIV/AIDS Patients at Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia
Authors: Jemal Mohabaw , Deress Teshiwal , Belachew Teshome , Adem Yesuf
Published: January 2021

Background. Cryptococcosis is the most common opportunistic fungal infection. High morbidity and mortality are frequently observed among hospitalized HIV/AIDS patients, particularly having CD4 count ≤100 cells/μl. Therefore, this study aimed to determine the prevalence of cryptococcal antigenemia and associated factors among HIV/AIDS patients. Methods. A hospital-based cross-sectional study was conducted among 140 HIV/AIDS patients. A cryptococcal antigen test was performed for all patients along with medical chart and laboratory registration book review. Cryptococcal antigen was detected from serum by using Remel Cryptococcal Antigen Test Kit. Data related to possible associated factors were extracted from patients’ charts and laboratory registration book. Data were coded, entered, and analyzed using SPSS version 20. Logistic regression analysis was done to see the association between dependent and independent variables. A

P

value <0.05 was considered statistically significant. Finally, data were presented in the form of texts, figures, and tables. Result. Among 140 serum cryptococcal antigenemia-tested study subjects, 16 (11.43%) were positive for serum cryptococcal antigen. Of them, 43.8% (7/16) were pulmonary tuberculosis coinfected, 31.2% (5/16) were extrapulmonary tuberculosis positive, and 25% (4/16) had bacterial bloodstream infections. In addition, 68.7% (11/16) had CD4 count less than 100 cells/μl, 18.7% (3/16) had CD4 count 100–150 cells/μl, 50% (8/16) were antiretroviral therapy defaulters, and 31.3% (5/16) were naïve. In this study, the majority, 75% (12/16), of the serum cryptococcal antigen-positive subjects were clinical stage IV. Of the assessed associated factors, tuberculosis coinfection (AOR: 0.04; 95% CI [0.005–0.25]) and antiretroviral therapy status (AOR: 0.02; 95% CI [0.001–0.5]) were significantly associated factors enhancing serum cryptococcal antigenemia. Conclusion. In this study, the high rate of cryptococcal antigenemia was observed among hospitalized HIV/AIDS patients, and it is alarming and highlights the need for improving CD4 status, expanding serum cryptococcal antigen screening, and strengthening regular cryptococcal antigenemia surveillance systems.
COVID-19 Coinfection with Mycobacterium abscessus in a Patient with Multiple Myeloma
Authors: Rodriguez Jose A. , Bonnano Charles , Khatiwada Pratik , Roa Alejandra A. , Mayer Daniel , Eckardt Paula A.
Published: January 2021

Background. Coronavirus disease (COVID-19) is a worldwide pandemic causing multiple fatalities and morbidities worldwide. We report a case of severe pneumonia causing acute respiratory distress syndrome due to a coinfection with SARS-CoV-2 and Mycobacterium abscessus in an elderly patient with multiple myeloma in Florida, USA. Case Presentation. An 84-year-old male with a medical history significant for multiple myeloma not in remission was sent to the emergency department to rule out COVID-19 infection prior to continuing his chemotherapy sessions. At presentation, he had nonspecific mild symptoms and an unremarkable physical examination. He had significant blood test findings including serum lactate dehydrogenase 373 U/L, high sensitive C-reactive protein 17.40 mg/l, and ferritin 415 ng/ml. Xpert-SARS-CoV-2 was positive. Chest radiograph revealed patchy areas of interstitial infiltrates in mid to lower lung zones. During his hospitalization course, his oxygenation deteriorated, requiring mechanical intubation. Repeat chest radiograph showed worsening bilateral infiltrates. He was started on broad-spectrum antibiotics and eventually weaned off mechanical intubation and extubated. On the 11th day of admission, he was found to be bradycardic and in shock, and he was reintubated. His labs showed worsening inflammatory markers along with kidney dysfunction to the point of requiring renal replacement therapy. He received both convalescent plasma and remdesivir for treatment of COVID-19 pneumonia. Eventually, repeat blood cultures came back positive for the growth of acid-fast beaded bacilli. While awaiting final culture and sensitivity reports, his antibiotics were upgraded to cover possible nocardia infection. Repeat blood and sputum cultures resulted in growth of AFB bacilli Mycobacterium abscessus 1 week after. Conclusions. This case report highlights the importance of keeping a broad differential and considering multiple coinfections, including atypical ones during this COVID-19 pandemic, such as the one that was discussed above, Mycobacterium abscessus, in order to provide goal-directed therapy.
Comparison of Mortality Risk Models in Patients with Postcardiac Arrest Cardiogenic Shock and Percutaneous Mechanical Circulatory Support
Authors: Chatzis Georgios , Markus Birgit , Syntila Styliani , Waechter Christian , Luesebrink Ulrich , Ahrens Holger , Divchev Dimitar , Schieffer Bernhard , Karatolios Konstantinos
Published: January 2021

Background. Although scoring systems are widely used to predict outcomes in postcardiac arrest cardiogenic shock (CS) after out-of-hospital cardiac arrest (OHCA) complicating acute myocardial infarction (AMI), data concerning the accuracy of these scores to predict mortality of patients treated with Impella in this setting are lacking. Thus, we aimed to evaluate as well as to compare the prognostic accuracy of acute physiology and chronic health II (APACHE II), simplified acute physiology score II (SAPS II), sepsis-related organ failure assessment (SOFA), the intra-aortic balloon pump (IABP), CardShock, the prediction of cardiogenic shock outcome for AMI patients salvaged by VA-ECMO (ENCOURAGE), and the survival after venoarterial extracorporeal membrane oxygenation (SAVE) score in patients with OHCA refractory CS due to an AMI treated with Impella 2.5 or CP. Methods. Retrospective study of 65 consecutive Impella 2.5 and 32 CP patients treated in our cardiac arrest center from September 2015 until June 2020. Results. Overall survival to discharge was 44.3%. The expected mortality according to scores was SOFA 70%, SAPS II 90%, IABP shock 55%, CardShock 80%, APACHE II 85%, ENCOURAGE 50%, and SAVE score 70% in the 2.5 group; SOFA 70%, SAPS II 85%, IABP shock 55%, CardShock 80%, APACHE II 85%, ENCOURAGE 75%, and SAVE score 70% in the CP group. The ENCOURAGE score was the most effective predictive model of mortality outcome presenting a moderate area under the curve (AUC) of 0.79, followed by the CardShock, APACHE II, IABP, and SAPS score. These derived an AUC between 0.71 and 0.78. The SOFA and the SAVE scores failed to predict the outcome in this particular setting of refractory CS after OHCA due to an AMI. Conclusion. The available intensive care and newly developed CS scores offered only a moderate prognostic accuracy for outcomes in OHCA patients with refractory CS due to an AMI treated with Impella. A new score is needed in order to guide the therapy in these patients.
Acetyl‐L‐Carnitine Induces Autophagy to Promote Mouse Spermatogonia Cell Recovery after Heat Stress Damage
Authors: Qiao Na , Chen Hanming , Du Peiquan , Kang Zhenlong , Pang Congying , Liu Bingxian , Zeng Qiwen , Pan Jiaqiang , Zhang Hui , Mehmood Khalid , Tang Zhaoxin , Li Ying
Published: January 2021

Acetyl‐L‐carnitine (ALC) is an effective substrate for mitochondrial energy metabolism and is known to prevent neurodegeneration and attenuate heavy metal‐induced injury. In this study, we investigated the function of ALC in the recovery of mouse spermatogonia cells (GC‐1 cells) after heat stress (HS). The cells were randomly divided into three groups: control group, HS group (incubated at 42°C for 90 min), and HS + ALC group (treatment of 150 μM ALC after incubated at 42°C for 90 min). After heat stress, all of the cells were recovered at 37°C for 6 h. In this study, the content of intracellular lactate dehydrogenase (LDH) in the cell supernatant and the malondialdehyde (MDA) levels, catalase (CAT) levels, and total antioxidant capacity (T‐AOC) were significantly increased in the HS group compared to the CON group. In addition, the mitochondrial membrane potential (MMP) was markedly decreased, while the apoptosis rate and the expression of apoptosis‐related genes (Bcl‐2, Bax, and caspase3) were significantly increased in the HS group compared to the CON group. Furthermore, the number of autophagosomes and the expression of autophagy‐related genes (Atg5, Beclin1, and LC3II) and protein levels of p62 were increased, but the expression of LAMP1 was decreased in the HS group compared to the CON group. However, treatment with ALC remarkably improved cell survival and decreased cell oxidative stress. It was unexpected that levels of autophagy were markedly increased in the HS + ALC group compared to the HS group. Taken together, our present study evidenced that ALC could alleviate oxidative stress and improve the level of autophagy to accelerate the recovery of GC‐1 cells after heat stress.
Determination of the Immunoglobulin G Spectrum by Surface-Enhanced Raman Spectroscopy Using Quasispherical Gold Nanoparticles
Authors: Ortiz-Dosal Alejandra , Loredo-García Elizabeth , Álvarez-Contreras Ana Gabriela , Núñez-Leyva Juan Manuel , Ortiz-Dosal Luis Carlos , Kolosovas-Machuca Eleazar Samuel
Published: January 2021

Background. Immunoglobulins (Ig) are glycoprotein molecules produced by plasma cells in response to antigenic stimuli involved in various physiological and pathological conditions. Intravenous immunoglobulin (IVIG) is a compound whose composition corresponds to Ig concentrations in human plasma, predominantly IgG. It is used as a replacement treatment in immunodeficiencies and as an immunomodulator in inflammatory and autoimmune diseases. The determination of IgG concentrations is useful in the diagnosis of these immunodeficiencies. Surface-enhanced Raman spectroscopy (SERS) is a technique that allows protein quantification in a fast and straightforward way. Objective. This study is aimed at determining the Raman spectrum of IgG at physiological concentrations using quasispherical gold nanoparticles as a SERS substrate. Methods. We initially determined the Raman spectrum of IVIG at 5%. Subsequently, for SERS’ characterization, decreasing dilutions of the protein were made by adding deionized water and an equal volume of the 5 nm gold quasispherical nanoparticle colloid. For each protein concentration, the Raman spectrum was determined using a 10x objective; we focused the 532 and 785 nm laser on the sample surface, in a range of 500-1800 cm-1, with five acquisitions and an acquisition time of 30 seconds. Results. We obtained the IVIG spectrum using SERS up to a concentration of 75 mg/dl. The Raman bands correspond to aromatic amino acid side chains and the characteristic beta-sheet structure of IgG. Conclusion. The use of 5 nm quasispherical gold nanoparticles as a SERS substrate allows for detecting the Raman spectrum of IVIG at physiological concentrations.
Protective Effect of Capparis spinosa Extract against Potassium Bromate Induced Oxidative Stress and Genotoxicity in Mice
Authors: Al-Anazi Khalid Mashai , Al-Mareed Ali Abdullah , Farah Mohammed Abul , Ali M. Ajmal , Hailan Waleed A. Q. , Al-Hemaid Fahad M.
Published: January 2021

Despite the commercial value of potassium bromate (KBrO3), it has been linked to many diseases including cancer. Capparis spinosa possesses exceptional ethnobotanical, pharmaceutical, and economic prominence by virtue of its bioactive components. The present study was designed to explore the protective role and antioxidant potential of ethanolic leaves extract of C. spinosa against the oxidative stress, genotoxicity, and apoptosis induced by KBrO3 in an experimental animal model. The results of the study revealed remarkable diminution in the levels of oxidative stress in all the treatment groups. C. spinosa extract attenuated the toxic effects of KBrO3 significantly (

p

 < 0.05) in a time- and dose-dependent manner by restoring the normal levels of ROS and antioxidative enzymes in serum and liver tissues. The extract also abolished the oxidative DNA damage as it was evident in decreased frequency of micronuclei. A marked increase in viable cells was observed in annexin-V apoptosis assay. In conclusion, the findings of the present study demonstrate that ethanolic leaves extract of C. spinosa has considerable protective effects against KBrO3-induced toxicity in experimental mice which is attributed to its antioxidant activity. Therefore, leaves of C. spinosa could be used as a potential source of natural antioxidant and bioactive compounds.
Research on Damage Identification of Nonuniform Microcrack in Beam Structures
Authors: Guo Jia , Guan Deqing , Pan Yanran
Published: January 2021

Nonuniform microcrack identification is of great significance in mechanical, aerospace, and civil engineering. In this study, the nonuniform crack is simplified as a semielliptical crack, and simplified calculation methods are proposed for damage severity and damage identification of semielliptical cracks. The proposed methods are based on the calculation method for uniform cracks. The wavelet transform and the intelligent algorithm (IA) are used to identify the damage location and the damage severity of the structure, respectively. The singularity of the wavelet coefficient can be used to identify the signal singularity quickly and accurately, and IA efficiently and accurately calculates the structural damage severity. The particle swarm optimization (PSO) algorithm and the genetic algorithm (GA), widely used, are applied to identify the damage severity of the beam. Numerical simulations and experimental analyses of beams with transfixion and semielliptical cracks are carried out to evaluate the accuracy of the semielliptical crack calculation method and the method of wavelet analysis combined with PSO and GA for nonuniform crack identification. The results show that the wavelet‐particle swarm optimization (WPSO) and the wavelet‐genetic algorithm (WGA) can accurately and efficiently identify the structural semielliptical damage location and severity and that these methods are not easily influenced by noise. The damage severity calculation method for semielliptical cracks can accurately calculate the semielliptical size and can be used to identify damage in beams with semielliptical cracks.
MYC and TFEB Control DNA Methylation and Differentiation in AML
Authors: Wu Xiaoying , Eisenman Robert N.
Published: January 2021

Although the MYC transcription factor has been consistently implicated in acute myeloid leukemia (AML), its gene targets and precise role in leukemogenesis remain unknown. In this issue of Blood Cancer Discovery, Yun and colleagues provide evidence that MYC directly suppresses the expression of TFEB, an mTORC1-regulated transcription factor. They show that, in the context of the myelocytic/granulocytic lineage, TFEB acts as a tumor suppressor by inducing the IDH1/2–TET pathway, which in turn, leads to altered DNA methylation and increased expression of genes involved in myeloid differentiation and apoptosis. Therefore, high levels of MYC suppress an epigenetic pathway that should normally act to attenuate leukemic progression. Identification of the components of this pathway is likely to inform new therapeutic tactics for AML and possibly other cancers.

See related article by Yun et al., p. 162.
Prenatal Nutritional Strategies to Reduce the Risk of Preterm Birth
Authors: Best Karen Patricia , Gomersall Judith , Makrides Maria
Published: January 2021

Worldwide, around 15 million preterm babies are born annually, and despite intensive research, the specific mechanisms triggering preterm birth (PTB) remain unclear. Cost-effective primary prevention strategies to reduce PTB are required, and nutritional interventions offer a promising alternative. Nutrients contribute to a variety of mechanisms that are potentially important to preterm delivery, such as infection, inflammation, oxidative stress, and muscle contractility. Several observational studies have explored the association between dietary nutrients and/or dietary patterns and PTB, often with contrasting results. Randomized trial evidence on the effects of supplementation with zinc, multiple micronutrients (iron and folic acid), and vitamin D is promising; however, results are inconsistent, and many studies are not adequately powered for outcomes of PTB. Large-scale clinical trials with PTB as the primary outcome are needed before any firm conclusions can be drawn for these nutrients. The strongest evidence to date for a nutritional solution exists for omega-3 long-chain polyunsaturated fatty acids (LCPUFAs), key nutrients in fish. In 2018, a Cochrane Review (including 70 studies) showed that prenatal supplementation with omega-3 LCPUFAs reduced the risk of PTB and early PTB (EPTB) compared with no omega-3 supplementation. However, the largest trial of omega-3 supplementation in pregnancy, the Omega-3 to Reduce the Incidence of Prematurity (ORIP) trial (n = 5,544), showed no reduction in EPTB and a reduction in PTB only in a prespecified analysis of singleton pregnancies. Exploratory analyses from the ORIP trial found that women with low baseline total omega-3 status were at higher risk of EPTB, and that this risk was substantially reduced with omega-3 supplementation. In contrast, women with replete or high baseline total omega-3 status were already at low risk of EPTB and additional omega-3 supplementation increased the risk of EPTB compared to control. These findings suggest that determining an individual woman’s PUFA status may be the most precise way to inform recommendations to reduce her risk of PTB.
Gestational Diabetes Mellitus and Developmental Programming
Authors: Chu Anne H.Y. , Godfrey Keith M.
Published: January 2021

During normal pregnancy, increased insulin resistance acts as an adaptation to enhance materno-foetal nutrient transfer and meet the nutritional needs of the developing foetus, particularly in relation to glucose requirements. However, about 1 in 6 pregnancies worldwide is affected by the inability of the mother’s metabolism to maintain normoglycaemia, with the combination of insulin resistance and insufficient insulin secretion resulting in gestational diabetes mellitus (GDM). A growing body of epidemiologic work demonstrates long-term implications for adverse offspring health resulting from exposure to GDM in utero. The effect of GDM on offspring obesity and cardiometabolic health may be partly influenced by maternal obesity; this suggests that improving glucose and weight control during early pregnancy, or better still before conception, has the potential to lessen the risk to the offspring. The consequences of GDM for microbiome modification in the offspring and the impact upon offspring immune dysregulation are actively developing research areas. Some studies have suggested that GDM impacts offspring neurodevelopmental and cognitive outcomes; confirmatory studies will need to separate the effect of GDM exposure from the complex interplay of social and environmental factors. Animal and human studies have demonstrated the role of epigenetic modifications in underpinning the predisposition to adverse health in offspring exposed to suboptimal hyperglycaemic in utero environment. To date, several epigenome-wide association studies in human have extended our knowledge on linking maternal diabetes-related DNA methylation marks with childhood adiposity-related outcomes. Identification of such epigenetic marks can help guide future research to develop candidate diagnostic biomarkers and preventive or therapeutic strategies. Longer-term interventions and longitudinal studies will be needed to better understand the causality, underlying mechanisms, or impact of GDM treatments to optimize the health of future generations.
Alpha-Synuclein: The Interplay of Pathology, Neuroinflammation, and Environmental Factors in Parkinson’s Disease
Authors: He Songzhe , Zhong Shan , Liu Gang , Yang Jun
Published: January 2021

Background: Parkinson’s disease (PD) is a multifactorial, chronic, and progressive neurodegenerative disease. α-Synuclein (α-syn), which is the main protein component of Lewy bodies, plays an important role in the pathological hallmarks of PD. However, the pathological function of α-syn and the molecular mechanisms responsible for the degeneration of dopaminergic neurons are still elusive. Summary: Cumulative evidence implicates that abnormal processing of α-syn will be predicted to lead to pathological changes in PD. Key Messages: In this review, we summarize the structure and physiological function of α-syn, and further discuss the interplay of pathology, neuroinflammation, and environmental factors in PD. Additionally, we suggest future directions for understanding the toxicity of α-syn to neurons, which may ultimately encourage us to better design disease-modifying therapeutic strategies for PD.
Delayed Arterial Occlusion Presenting as Foot Drop Following Primary Total Knee Arthroplasty in a Varus Knee: A Case Report and Review of the Literature
Authors: Del Prince Clayton , Matthews John Reza , Phillips Matthew
Published: January 2021

We present a 69-year-old male with osteoarthritis of a varus mechanically aligned left knee that developed delayed arterial thrombosis after primary total knee arthroplasty (TKA) requiring stenting and subsequent trans-metatarsal amputation. This case is unique since initial presentation involved neurologic instead of ischemic changes. We also performed a literature review of arterial injuries in primary TKA. This case highlights the importance of maintaining a high clinical suspicion for vascular insult in patients undergoing correction of varus malalignment with initial complaints of neurologic dysfunction.
Angiolipoma: A Unique Cause of Carpal Tunnel Syndrome
Authors: Deng Yi , Vrancic Sindy , Morey Adrienne
Published: January 2021

Carpal tunnel syndrome is one of the most common conditions affecting the hand. The majority of cases are idiopathic, with tumours causing less than 3% of cases. We present a unique case of an angiolipoma overlying the carpal tunnel as a cause of median nerve compression. A 54-year-old female presented with signs and symptoms consistent with carpal tunnel syndrome associated with an enlarging lump overlying the carpal tunnel on the palmar surface of her hand. Nerve conduction studies confirmed median neuropathy. The case was successfully treated by surgical excision of the tumour and open carpal tunnel release. Histopathology confirmed the presence of an angiolipoma. The patient had complete resolution of symptoms at the final 6-week follow-up. This case highlights the importance of considering tumours in the differential diagnosis of carpal tunnel syndrome.
Understanding Hormonal Therapies: Overview for the Dermatologist Focused on Hair
Authors: Desai Karishma , Almeida Bianca , Miteva Mariya
Published: January 2021

Hormones have an intimate relationship with hair growth. Hormonal replacement therapy is used to treat menopausal symptoms and to provide protection from chronic diseases for which postmenopausal women may be at risk. Additionally, hormonal therapies are prescribed for contraception and treatment of acne. Considering the widespread use of such therapies, there is a demand for further understanding of their implications in hair disorders. This article reviews the specific properties of current estrogen- and progesterone-containing hormonal treatments and their implications for the patient with hair loss. The complexity of the task comes from the paucity of data and discrepancy in the literature on the effect of the specific hormonal-receptor activities.
Reactivation of CNV after Discontinuation of Bevacizumab Treatment of Age-Related Macular Degeneration
Authors: Amarakoon Sankha , Martinez-Ciriano Jose P. , Baarsma Seerp , van den Born L. Ingeborgh , Missotten Tom
Published: January 2021

Introduction: Treatment of exudative age-related macular degeneration (ARMD) has shifted to pro re nata and treat-extend-stop strategies. However, a rational discontinuation strategy is lacking. To develop such a strategy, it is important to determine choroidal neovascularization (CNV) recurrence rates after anti-VEGF treatment is discontinued. Here we report prospective data on persistent and recurrent CNV activity after discontinuation of bevacizumab treatment. Methods: This prospective, single-center clinical trial enrolled 191 patients with exudative ARMD. Patients were randomly assigned to receiving intravitreal bevacizumab injections every 4, 6, or 8 weeks for 1 year. CNV activity was determined in the 157 patients who completed the 1-year treatment regimen. Patients with inactive CNV were then followed for signs of CNV reactivation. Results: After 1 year of treatment, 66 (42%) of the 157 patients still had signs of persistent active CNV. Of the remaining 91 (58%) patients, 61 (67%) needed retreatment for active CNV within the first year after discontinuation of treatment (mean 4.28 ± 0.29 months). CNV was reactivated in 50 (80%) of the 61 patients within 6 months after their final treatment for CNV. Conclusion: Based on quiescent disease, anti-VEGF therapy was discontinued in 58% of the patients after they received bevacizu­mab injections every 4, 6, or 8 weeks for 1 year; 67% showed reactivated CNV within a year after discontinuation. The high reactivation rate of CNV shown in this study should help clinicians to develop rational discontinuation protocols. Trial Registration: This study is registered as NTR1174 at http://www.trialregister.nl.
Automated E-Counseling for Chronic Heart Failure
Authors: Nolan Robert P. , Ross Heather J. , Farkouh Michael E. , Huszti Ella , Chan Sammy , Toma Mustafa , D’Antono Bianca , White Michel , Thomas Scott , Barr Susan I. , Perreault Sylvie , McDonald Michael , Zieroth Shelley , Isaac Debra , Wielgosz Andreas , Mielniczuk Lisa Marie
Published: January 2021

Background:

International task force statements advocate telehealth programs to promote health-related quality of life for patients with chronic heart failure (CHF). To that end, we evaluated the efficacy and usability of an automated e-counseling program.

Methods:

This Canadian multi-site double-blind randomized trial assessed whether usual care plus either internet-based e-counseling (motivational and cognitive-behavioral tools for CHF self-care) or e-based conventional CHF self-care education (e-UC) improved 12-month Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS). Secondary outcomes included program engagement (total logon weeks, logons, and logon hours), total CHF self-care behaviors, diet (fruit and vegetable servings), 6-minute walk test, and 4-day step count. The association between program engagement and health-related quality of life was assessed using KCCQ-OS tertiles.

Results:

We enrolled 231 patients, median age =59.5 years, 22% female, and elevated median KCCQ-OS=83.0 (interquartile range, 68–93). KCCQ-OS increase ≥5 points was not more prevalent for e-counseling, n=29 (29.6%) versus e-UC, n=32 (34.0%),
P
=0.51. E-Counseling versus e-UC increased total logon weeks (
P
=0.02), logon hours (
P
=0.001), and logons (
P
<0.001). Only e-counseling showed a positive association between 12-month KCCQ-OS tertile and logon weeks (
P
=0.04) and logon hours (
P
=0.004). E-Counseling increased CHF self-care behavior and diet but not 6-minute walk test or 4-day step count.

Conclusions:

The primary KCCQ-OS end point was negative for this trial. Only e-counseling showed a positive association between program engagement and 12-month KCCQ-OS tertile, and it improved CHF self-care behavior and diet.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT01864369.
Extracardiac Abnormalities of Preload Reserve
Authors: Fudim Marat , Sobotka Paul A. , Dunlap Mark E.
Published: January 2021

While many of the cardiac limitations to exercise performance are now well-characterized, extracardiac limitations to exercise performance have been less well recognized but are nevertheless important. We propose that abnormalities of cardiac preload reserve represents an under-recognized but common cause of exercise limitations. We further propose that mechanistic links exist between conditions as seemingly disparate as heart failure with preserved ejection fraction, nonalcoholic fatty liver disease, and pelvic venous compression/obstruction syndromes (eg, May-Thurner). We conclude that extracardiac abnormalities of preload reserve serve as a major pathophysiologic mechanism underlying these and other disease states.
Impairments in Blood Pressure Regulation and Cardiac Baroreceptor Sensitivity Among Patients With Heart Failure Supported With Continuous-Flow Left Ventricular Assist Devices
Authors: Sailer Christine , Edelmann Hannah , Buchanan Cullen , Giro Pedro , Babcock Matthew , Swanson Christine , Spotts Melanie , Schulte Margaret , Pratt-Cordova Ashley , Coe Greg , Beindorff Mark , Page Robert L. , Ambardekar Amrut V. , Pal Jay D. , Kohrt Wendy , Wolfel Eugene , Lawley Justin S. , Tarumi Takashi , Cornwell William K.
Published: January 2021

Background:

Continuous-flow (CF) left ventricular assist devices (LVADs) improve outcomes for patients with advanced heart failure (HF). However, the lack of a physiological pulse predisposes to side-effects including uncontrolled blood pressure (BP), and there are little data regarding the impact of CF-LVADs on BP regulation.

Methods:

Twelve patients (10 males, 60±11 years) with advanced heart failure completed hemodynamic assessment 2.7±4.1 months before, and 4.3±1.3 months following CF-LVAD implantation. Heart rate and systolic BP via arterial catheterization were monitored during Valsalva maneuver, spontaneous breathing, and a 0.05 Hz repetitive squat-stand maneuver to characterize cardiac baroreceptor sensitivity. Plasma norepinephrine levels were assessed during head-up tilt at supine, 30
o
and 60
o
. Heart rate and BP were monitored during cardiopulmonary exercise testing.

Results:

Cardiac baroreceptor sensitivity, determined by Valsalva as well as Fourier transformation and transfer function gain of Heart rate and systolic BP during spontaneous breathing and squat-stand maneuver, was impaired before and following LVAD implantation. Norepinephrine levels were markedly elevated pre-LVAD and improved—but remained elevated post-LVAD (supine norepinephrine pre-LVAD versus post-LVAD: 654±437 versus 323±164 pg/mL). BP increased during cardiopulmonary exercise testing post-LVAD, but the magnitude of change was modest and comparable to the changes observed during the pre-LVAD cardiopulmonary exercise testing.

Conclusions:

Among patients with advanced heart failure with reduced ejection fraction, CF-LVAD implantation is associated with modest improvements in autonomic tone, but persistent reductions in cardiac baroreceptor sensitivity. Exercise-induced increases in BP are blunted. These findings shed new light on mechanisms for adverse events such as stroke, and persistent reductions in functional capacity, among patients supported by CF-LVADs.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03078972.
Prognostic Value of Pulmonary Transit Time by Cardiac Magnetic Resonance on Mortality and Heart Failure Hospitalization in Patients With Advanced Heart Failure and Reduced Ejection Fraction
Authors: Houard Laura , Amzulescu Mihaela S. , Colin Geoffrey , Langet Helene , Militaru Sebastian , Rousseau Michel F. , Ahn Sylvie A. , Vanoverschelde Jean-Louis J. , Pouleur Anne-Catherine , Gerber Bernhard L.
Published: January 2021

Background:

Pulmonary transit time (PTT) from first-pass perfusion imaging is a novel parameter to evaluate hemodynamic congestion by cardiac magnetic resonance (cMR). We sought to evaluate the additional prognostic value of PTT in heart failure with reduced ejection fraction over other well-validated predictors of risk including the Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause.

Methods:

We prospectively followed 410 patients with chronic heart failure with reduced ejection fraction (61±13 years, left ventricular (LV) ejection fraction 24±7%) who underwent a clinical cMR to assess the prognostic value of PTT for a primary endpoint of overall mortality and secondary composite endpoint of cardiovascular death and heart failure hospitalization. Normal reference values of PTT were evaluated in a population of 40 asymptomatic volunteers free of cardiovascular disease.

Results

PTT was significantly increased in patients with heart failure with reduced ejection fraction as compared to controls (9±6 beats and 7±2 beats, respectively,
P
<0.001), and correlated not only with New York Heart Association class, cMR–LV and cMR–right ventricular (RV) volumes, cMR-RV and cMR-LV ejection fraction, and feature tracking global longitudinal strain, but also with cardiac output. Over 6-year median follow-up, 182 patients died and 200 reached the secondary endpoint. By multivariate Cox analysis, PTT was an independent and significant predictor of both endpoints after adjustment for Meta-Analysis Global Group in Chronic Heart Failure risk score and ischemic cause. Importantly in multivariable analysis, PTT in beats had significantly higher additional prognostic value to predict not only overall mortality (χ
2
to improve, 12.3; hazard ratio, 1.35 [95% CI, 1.16–1.58];
P
<0.001) but also the secondary composite endpoints (χ
2
to improve=20.1; hazard ratio, 1.23 [95% CI, 1.21–1.60];
P
<0.001) than cMR-LV ejection fraction, cMR-RV ejection fraction, LV–feature tracking global longitudinal strain, or RV–feature tracking global longitudinal strain. Importantly, PTT was independent and complementary to both pulmonary artery pressure and reduced RV ejection fraction<42% to predict overall mortality and secondary combined endpoints.

Conclusions:

Despite limitations in temporal resolution, PTT derived from first-pass perfusion imaging provides higher and independent prognostic information in heart failure with reduced ejection fraction than clinical and other cMR parameters, including LV and RV ejection fraction or feature tracking global longitudinal strain.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03969394.
Myocardial Inflammation and Dysfunction in COVID-19–Associated Myocardial Injury
Authors: Weckbach Ludwig T. , Curta Adrian , Bieber Stephanie , Kraechan Angelina , Brado Johannes , Hellmuth Johannes C. , Muenchhoff Maximilian , Scherer Clemens , Schroeder Ines , Irlbeck Michael , Maurus Stefan , Ricke Jens , Klingel Karin , Kääb Stefan , Orban Mathias , Massberg Steffen , Hausleiter Jörg , Grabmaier Ulrich
Published: January 2021

Background:

Myocardial injury, defined by elevated troponin levels, is associated with adverse outcome in patients with coronavirus disease 2019 (COVID-19). The frequency of cardiac injury remains highly uncertain and confounded in current publications; myocarditis is one of several mechanisms that have been proposed.

Methods:

We prospectively assessed patients with myocardial injury hospitalized for COVID-19 using transthoracic echocardiography, cardiac magnetic resonance imaging, and endomyocardial biopsy.

Results:

Eighteen patients with COVID-19 and myocardial injury were included in this study. Echocardiography revealed normal to mildly reduced left ventricular ejection fraction of 52.5% (46.5%–60.5%) but moderately to severely reduced left ventricular global longitudinal strain of −11.2% (−7.6% to −15.1%). Cardiac magnetic resonance showed any myocardial tissue injury defined by elevated T1, extracellular volume, or late gadolinium enhancement with a nonischemic pattern in 16 patients (83.3%). Seven patients (38.9%) demonstrated myocardial edema in addition to tissue injury fulfilling the Lake-Louise criteria for myocarditis. Combining cardiac magnetic resonance with speckle tracking echocardiography demonstrated functional or morphological cardiac changes in 100% of investigated patients. Endomyocardial biopsy was conducted in 5 patients and revealed enhanced macrophage numbers in all 5 patients in addition to lymphocytic myocarditis in 1 patient. SARS-CoV-2 RNA was not detected in any biopsy by quantitative real-time polymerase chain reaction. Finally, follow-up measurements of left ventricular global longitudinal strain revealed significant improvement after a median of 52.0 days (−11.2% [−9.2% to −14.7%] versus −15.6% [−12.5% to −19.6%] at follow-up;
P
=0.041).

Conclusions:

In this small cohort of COVID-19 patients with elevated troponin levels, myocardial injury was evidenced by reduced echocardiographic left ventricular strain, myocarditis patterns on cardiac magnetic resonance, and enhanced macrophage numbers but not predominantly lymphocytic myocarditis in endomyocardial biopsies.
Spatially Weighted Coronary Artery Calcium Score and Coronary Heart Disease Events in the Multi-Ethnic Study of Atherosclerosis
Authors: Shea Steven , Navas-Acien Ana , Shimbo Daichi , Brown Elizabeth R. , Budoff Matthew , Bancks Michael P. , Barr R. Graham , Kronmal Richard
Published: January 2021

Background:

A limitation of the Agatston coronary artery calcium (CAC) score is that it does not use all of the calcium density information in the computed tomography scan such that many individuals have a score of zero. We examined the predictive validity for incident coronary heart disease (CHD) events of the spatially weighted coronary calcium score (SWCS), an alternative scoring method for CAC that assigns scores to individuals with Agatston CAC=0.

Methods:

The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study that conducted a baseline exam from 2000 to 2002 in 6814 participants including computed tomography scanning for CAC. Subsequent exams and systematic follow-up of the cohort for outcomes were performed. Statistical models were adjusted using the MESA risk score based on age, sex, race/ethnicity, systolic blood pressure, use of hypertension medications, diabetes, total and HDL (high-density lipoprotein) cholesterol, use of lipid-lowering medications, smoking status, and family history of heart attack.

Results:

In the 3286 participants with Agatston CAC=0 at baseline and for whom SWCS was computed, 98 incident CHD events defined as definite or probably myocardial infarction or definite CHD death occurred during a median follow-up of 15.1 years. In this group, SWCS predicted incident CHD events after multivariable adjustment (hazard ratio=1.30 per SD of natural logarithm [SWCS] [95% CI, 1.04–1.60];
P
=0.005); and progression from Agatston CAC=0 at baseline to CAC>0 at subsequent exams (multivariable-adjusted incidence rate difference per SD of natural logarithm [SWCS] per 100 person-years 1.68 [95% CI, 1.03–2.33];
P
<0.0001).

Conclusions:

SWCS predicts incident CHD events in individuals with Agatston CAC score=0 as well as conversion to Agatston CAC>0 at repeat computed tomography scanning at later exams. SWCS has predictive validity as a subclinical phenotype and marker of CHD risk in individuals with Agatston CAC=0.