bluuebunny/crossref_metadata_2025 huggingface dataset:
New Insights into the Role of Metals in Host–Pathogen Interactions
Authors: Ammendola Serena , Battistoni Andrea
Published: June 2022

Almost eighty years have passed since the publication of the studies by Arthur Schade and Leona Caroline, which we can consider as the first investigations that began to disclose the importance of metals in host–pathogen interactions [...]
Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model
Authors: Wang Peng , Yuan Peiqiang , Lin Sen , Zhong Heju , Zhang Xiaoling , Zhuo Yong , Li Jian , Che Lianqiang , Feng Bin , Lin Yan , Xu Shengyu , Wu De , Burrin Douglas G , Fang Zhengfeng
Published: June 2022

Abnormally elevated circulating bile acids (BA) during pregnancy endanger fetal survival and offspring health; however, the pathology and underlying mechanisms are poorly understood. A total of nineteen pregnant sows were randomly assigned to day 60 of gestation, day 90 of gestation (G60, G90), and the farrowing day (L0), to investigate the intercorrelation of reproductive hormone, including estradiol, progesterone and sulfated progesterone metabolites (PMSs), and BA in the peripheral blood of mother and fetuses during pregnancy. All data were analyzed by Student’s t-test or one-way ANOVA of GraphPad Prism and further compared by using the Student–Newman–Keuls test. Correlation analysis was also carried out using the CORR procedure of SAS to study the relationship between PMSs and BA levels in both maternal and fetal serum at G60, G90, and L0. Allopregnanolone sulphate (PM4S) and epiallopregnanolone sulphate (PM5S) were firstly identified in the maternal and fetal peripheral blood of pregnant sows by using newly developed ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) methods. Correlation analysis showed that pregnancy-associated maternal BA homeostasis was correlated with maternal serum PM4S levels, whereas fetal BA homeostasis was correlated with fetal serum PM5S levels. The antagonist activity role of PM5S on farnesoid X receptor (FXR)-mediated BA homeostasis and fibroblast growth factor 19 (FGF19) were confirmed in the PM5S and FXR activator co-treated pig primary hepatocytes model, and the antagonist role of PM4S on FXR-mediated BA homeostasis and FGF19 were also identified in the PM4S-treated pig primary hepatocytes model. Together with the high relative expression of FGF19 in pig hepatocytes, the pregnant sow is a promising animal model to investigate the pathogenesis of cholestasis during pregnancy.
Mathematical Modeling Reveals That Sucrose Regulates Leaf Senescence via Dynamic Sugar Signaling Pathways
Authors: Asim Muhammad , Hussain Quaid , Wang Xiaolin , Sun Yanguo , Liu Haiwei , Khan Rayyan , Du Shasha , Shi Yi , Zhang Yan
Published: June 2022

Sucrose (Suc) accumulation is one of the key indicators of leaf senescence onset, but little is known about its regulatory role. Here, we found that application of high (120–150 mM) and low levels (60 mM) of Suc to young leaf (YL) and fully expanded leaf (FEL) discs, respectively, decreased chlorophyll content and maximum photosynthetic efficiency. Electrolyte leakage and malondialdehyde levels increased at high Suc concentrations (90–120 mM in YL and 60 and 150 mM in FEL discs). In FEL discs, the senescence-associated gene NtSAG12 showed a gradual increase in expression with increased Suc application; in contrast, in YL discs, NtSAG12 was upregulated with low Suc treatment (60 mM) but downregulated at higher levels of Suc. In YL discs, trehalose-6-phosphate (T6P) accumulated at a low half-maximal effective concentration (EC50) of Suc (1.765 mM). However, T6P levels declined as trehalose 6 phosphate synthase (TPS) content decreased, resulting in the maximum velocity of sucrose non-fermenting-1-related protein kinase (SnRK) and hexokinase (HXK) occurring at higher level of Suc. We therefore speculated that senescence was induced by hexose accumulation. In FEL discs, the EC50 of T6P occurred at a low concentration of Suc (0.9488 mM); T6P levels progressively increased with higher TPS content, which inhibited SnRK activity with a dissociation constant (Kd) of 0.001475 U/g. This confirmed that the T6P–SnRK complex induced senescence in detached FEL discs.
Orlistat Resensitizes Sorafenib-Resistance in Hepatocellular Carcinoma Cells through Modulating Metabolism
Authors: Shueng Pei-Wei , Chan Hui-Wen , Lin Wei-Chan , Kuo Deng-Yu , Chuang Hui-Yen
Published: June 2022

Sorafenib is one of the options for advanced hepatocellular carcinoma treatment and has been shown to extend median overall survival. However, sorafenib resistance often develops a few months after treatment. Hence, developing various strategies to overcome sorafenib resistance and understand the possible mechanisms is urgently needed. We first established sorafenib-resistant hepatocellular carcinoma (HCC) cells. Then, we found that sorafenib-resistant Huh7 cells (Huh7/SR) exhibit higher glucose uptakes and express elevated fatty acid synthesis and glucose metabolism-related proteins than their parental counterparts (Huh7). The current study investigated whether sorafenib resistance could be reversed by suppressing fatty acid synthesis, using a fatty acid synthase (FASN) inhibitor, orlistat, in HCC cells. FASN inhibition-caused changes in protein expressions and cell cycle distribution were analyzed by Western blot and flow cytometry, and changes in glucose uptakes were also evaluated by 18F-FDG uptake. Orlistat remarkably enhanced the cytotoxicity of sorafenib in both Huh7 and Huh7/SR cells, and flow cytometry showed that combination treatment significantly increased the sub-G1 population in both cell lines. Western blot revealed that the combination treatment effectively increased the ratio of Bax/Bcl-2 and decreased expressions of pERK; additionally, the combination treatment also strongly suppressed fatty acid synthesis-related proteins (e.g., FASN and SCD) in both cell lines. Lastly, the 18F-FDG uptake was repressed by the combination treatment in both cell lines. Our results indicated that orlistat-mediated FASN inhibition could overcome sorafenib resistance and enhance cell killing in HCC by changing cell metabolism.
IL-31: State of the Art for an Inflammation-Oriented Interleukin
Authors: Borgia Francesco , Custurone Paolo , Li Pomi Federica , Cordiano Raffaele , Alessandrello Clara , Gangemi Sebastiano
Published: June 2022

Interleukin 31 belongs to the IL-6 superfamily, and it is an itch mediator already studied in several diseases, comprising atopic dermatitis, allergic pathologies, and onco-hematological conditions. This research aims to assess the role of this cytokine in the pathogenesis of these conditions and its potential therapeutic role. The research has been conducted on articles, excluding reviews and meta-analysis, both on animals and humans. The results showed that IL-31 plays a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and itch severity. Traditional therapies target this interleukin indirectly, but monoclonal antibodies (Mab) directed against it have shown efficacy and safety profiles comparable with biological drugs that are already available. Future perspectives could include the development of new antibodies against IL-31 both for humans and animals, thus adding a new approach to the therapy, which often has proven to be prolonged and specific for each patient.
Integration of Adenylate Kinase 1 with Its Peptide Conformational Imprint
Authors: Wu Cheng-Hsin , Lin Chung-Yin , Lin Tzu-Chieh , Tai Dar-Fu
Published: June 2022

In the present study, molecularly imprinted polymers (MIPs) were used as a tool to grasp a targeted α-helix or β-sheet of protein. During the fabrication of the hinge-mediated MIPs, elegant cavities took shape in a special solvent on quartz crystal microbalance (QCM) chips. The cavities, which were complementary to the protein secondary structure, acted as a peptide conformational imprint (PCI) for adenylate kinase 1 (AK1). We established a promising strategy to examine the binding affinities of human AK1 in conformational dynamics using the peptide-imprinting method. Moreover, when bound to AK1, PCIs are able to gain stability and tend to maintain higher catalytic activities than free AK1. Such designed fixations not only act on hinges as accelerators; some are also inhibitors. One example of PCI inhibition of AK1 catalytic activity takes place when PCI integrates with an AK19-23 β-sheet. In addition, conformation ties, a general MIP method derived from random-coil AK1133-144 in buffer/acetonitrile, are also inhibitors. The inhibition may be due to the need for this peptide to execute conformational transition during catalysis.
Genome-Wide Identification of Switchgrass Laccases Involved in Lignin Biosynthesis and Heavy-Metal Responses
Authors: Li Rui , Zhao Yan , Sun Zhen , Wu Zhenying , Wang Honglun , Fu Chunxiang , Zhao Hongbo , He Feng
Published: June 2022

Plant laccase genes belong to a multigene family, play key roles in lignin polymerization, and participate in the resistance of plants to biotic and abiotic stresses. Switchgrass is an important resource for forage and bioenergy production, yet information about the switchgrass laccase gene family is scarce. Using bioinformatic approaches, a genome-wide analysis of the laccase multigene family in switchgrass was carried out in this study. In total, 49 laccase genes (PvLac1 to PvLac49) were identified; these can be divided into five subclades, and 20 of them were identified as targets of miR397. The tandem and segmental duplication of laccase genes on Chr05 and Chr08 contributed to the expansion of the laccase family. The laccase proteins shared conserved signature sequences but displayed relatively low sequence similarity, indicating the potential functional diversity of switchgrass laccases. Switchgrass laccases exhibited distinct tissue/organ expression patterns, revealing that some laccases might be involved in the lignification process during stem development. All five of the laccase isoforms selected from different subclades responded to heavy metal. The immediate response of lignin-related laccases, as well as the delayed response of low-abundance laccases, to heavy-metal treatment shed light on the multiple roles of laccase isoforms in response to heavy-metal stress.
The Impact of Ethnicity on Athlete ECG Interpretation: A Systematic Review
Authors: Davis Angus J. , Semsarian Christopher , Orchard John W. , La Gerche Andre , Orchard Jessica J.
Published: June 2022

Athlete ECG interpretation criteria have been developed and refined from research in athlete populations; however, current guidelines are based on available data primarily from Caucasian and Black athletes. This study aimed to assess the impact of ethnicity on ECG interpretation in athletes. A systematic review was conducted of the MEDLINE, EMBASE, Scopus, SPORTDiscus, and Web of Science databases, for papers that assessed athlete screening ECGs and compared findings on the basis of ethnicity. Fifty-one papers which compared ECGs from various ethnicities were included. Most studies assessed Black athletes against Caucasian athletes and found a greater prevalence of T-wave inversion (TWI) (2.6–22.8% vs. 0–5.0%) and anterior TWI (3.7–14.3% vs. 0.6–2.0%). Black athlete subgroups in Africa had TWI (20–40%) and anterior TWI (4.3–18.7%) at a higher prevalence than other Black athletes. Athletes who were defined as mixed-race, Asian, and Pacific Islander are potentially more like Black athletes than Caucasian athletes. Black ethnicity is known to have an impact on the accurate interpretation of athlete ECGs; however, there is nuance related to origin of both parents. Asian and Pacific Islander origin also may impact athlete ECG interpretation. Further research is required to assist in distinguishing abnormal and normal athlete ECGs in different ethnic populations.
When Does the Human Embryonic Heart Start Beating? A Review of Contemporary and Historical Sources of Knowledge about the Onset of Blood Circulation in Man
Authors: Männer Jörg
Published: June 2022

The onset of embryonic heart beating may be regarded as the defining feature for the beginning of personal human life. Clarifying the timing of the first human heartbeat, therefore, has religious, philosophical, ethical, and medicolegal implications. This article reviews the historical and contemporary sources of knowledge on the beginning of human heart activity. Special attention is given to the problem of the determination of the true age of human embryos and to the problem of visualization of the human embryonic heart activity. It is shown that historical and current textbook statements about the onset of blood circulation in man do not derive from observations on living human embryos but derive from the extrapolation of observations on animal embryos to the human species. This fact does not preclude the existence of documented observations on human embryonic heart activity: Modern diagnostic (ultrasound) and therapeutic (IVF) procedures facilitate the visualization of early embryonic heart activity in precisely dated pregnancies. Such studies showed that the human heart started its pumping action during the fourth post-fertilization week. A small number of direct observations on the heart activity of aborted human embryos were reported since the 19th century, but did not receive much recognition by embryologists.
Extracardiac Vagal Stimulation-Assisted Cardioneuroablation: Dynamically Evaluating the Impact of Sequential Ganglionated Plexus Ablation on Vagal Control of SAN and AVN in Patients with Sinoatrial Node Dysfunction
Authors: Chen Weijie , Liu Zengzhang , Xiao Peilin , Xu Yanping , Li Dan , Xiong Qingsong , Zou Lili , Qin Fang , Tao Xiexin , Chen Junan , Lan Xianbin , Du Huaan , Yin Yuehui , Ling Zhiyu
Published: June 2022

Cardioneuroablation (CNA) is proposed as a promising therapy for patients with sinoatrial node dysfunction (SND) that is mediated by excessive vagal tone. However, a series of urgent questions about CNA remain unanswered. From December 2020 to March 2022, six patients with symptomatic SND who underwent CNA were summarized in this report. Sequential CNA targeting Ao-SVC GP, PMLGP, RAGP, and LSGP was performed in patients, guided by fractionated intracardiac electrograms and dynamically evaluated by extracardiac vagal stimulation (ECVS). The results showed that Ao-SVC GP ablation led to a significant increase in heart rate (HR) and the elimination of sinus arrest evoked by ECVS, while the vagal responses of atrial ventricular block were eliminated by the ablation of PMLGP and LSGP. Post-procedure HR increased up to 64–86% of the maximum HR of an atropine test at baseline. The median HR from Holter monitoring increased from 52.8 ± 2.1 bpm at baseline to 73.0 ± 10.4 bpm after the procedure (p = 0.012) and to 71.3 ± 10.1 bpm at the six-month follow-up (p = 0.011). Bradycardia-related symptoms disappeared in all patients at the six-month follow-up. This case series reveals the feasibility of using the ECVS-assisted sequential CNA technique and indicates the critical role of ECVS in dynamically evaluating the impact of sequential CNA on the vagal control of SAN and AVN.
Structured Allocation of Transcatheter Aortic Valve Replacement Patients during Coronavirus Disease 2019 Pandemic: Impact on Patient Selection and Clinical Results
Authors: Berisha Nora , Klein Kathrin , Veulemans Verena , Maier Oliver , Piayda Kerstin , Binnebößel Stephan , Afzal Shazia , Polzin Amin , Westenfeld Ralf , Horn Patrick , Jung Christian , Kelm Malte , Quast Christine , Zeus Tobias
Published: June 2022

Due to shortages of medical resources during the Coronavirus Disease 2019 (COVID-19) pandemic, an allocation algorithm for Transcatheter Aortic Valve Replacement (TAVR) was established. We investigated the impact on patient selection and procedural results. In total, 456 TAVR patients before (pre-COVID-19 group) and 456 TAVR patients after (COVID-19 group) the implementation of our allocation algorithm were compared. Concerning patient characteristics, the COVID-19 group revealed a higher rate of cardiac decompensations/cardiogenic shocks (10.5% vs. 1.3%; p < 0.001), severe angina pectoris (Canadian Cardiovascular Society (CCS) II, III and IV: 18.7% vs. 11.8%; p = 0.004), troponin elevation (>14 ng/L: 84.9% vs. 77%; p = 0.003) and reduced left ventricular ejection fraction (LVEF) (<45%: 18.9% vs. 12%; p = 0.006). Referring to procedural characteristics, more predilatations (46.3% vs. 35.1%; p = 0.001) and a longer procedural time (80.2 min (+/−29.4) vs. 66.9 min (+/−17.5); p < 0.001) were observed. The success rate was evenly high; no differences in safety parameters were reported. Examining the utilization of hospital resources, the COVID-19 group showed a shorter in-hospital stay (8.4 days (+/−5.9) vs. 9.5 days (+/−9.33); p = 0.041) and fewer TAVR patients were treated per month (39 (+/−4.55) vs. 46.11 (+/−7.57); p = 0.03). Our allocation algorithm supported prioritization of sicker patients with similar efficient and safe TAVR procedures. In-hospital stay could be shortened.
Alexithymia, Phosphorus Levels, and Sleep Disorders in Patients on Hemodialysis
Authors: Pojatić Đorđe , Nikić Dajana , Tolj Ivana , Pezerović Davorin , Šantić Andrijana , Degmečić Dunja
Published: June 2022

Alexithymia, or the inability to distinguish between bodily feelings and emotions, has been linked to poor sleep quality in some studies. Rare studies examined the associations between electrolyte phosphorus in patients on hemodialysis and their sleep quality, daytime sleepiness, and alexithymia with inflammatory factors. Hemodialysis is a treatment method for terminal renal patients that involves the diffusion of unwanted metabolic products through the dialyzer membrane. Our study aimed to examine whether there was a difference in phosphorus levels, inflammatory factors, and daytime sleepiness according to the hemodialysis patients’ levels of alexithymia. The study involved 170 HD patients that had been treated with chronic dialysis for more than three months. Prior to the hemodialysis procedure, laboratory findings were sampled. Respondents completed the Pittsburgh Sleep Quality Index, the Toronto Alexithymia Scale 26, and the Epworth Sleepiness Scale, and were questioned about depression. The results showed that alexithymic HD patients exhibited significantly higher leukocyte counts, lower predialysis phosphorus values, and more pronounced daily sleepiness than the alexithymia-free group (Mann–Whitney U test, p = 0.02, p = 0.005, and p < 0.001, respectively). We concluded that alexithymia was an independent predictor of high daytime sleepiness in HD patients (OR = 1.05, 95% CI 1.02 to 1.09).
Potential of Hematologic Parameters in Predicting Mortality of Patients with Traumatic Brain Injury
Authors: Kim Sol Bi , Park Youngjoon , Ahn Ju Won , Sim Jeongmin , Park Jeongman , Kim Yu Jin , Hwang So Jung , Sung Kyoung Su , Lim Jaejoon
Published: June 2022

Traumatic brain injury (TBI) occurs frequently, and acute TBI requiring surgical treatment is closely related to patient survival. Models for predicting the prognosis of patients with TBI do not consider various factors of patient status; therefore, it is difficult to predict the prognosis more accurately. In this study, we created a model that can predict the survival of patients with TBI by adding hematologic parameters along with existing non-hematologic parameters. The best-fitting model was created using the Akaike information criterion (AIC), and hematologic factors including preoperative hematocrit, preoperative C-reactive protein (CRP), postoperative white blood cell (WBC) count, and postoperative hemoglobin were selected to predict the prognosis. Among several prediction models, the model that included age, Glasgow Coma Scale, Injury Severity Score, preoperative hematocrit, preoperative CRP, postoperative WBC count, postoperative hemoglobin, and postoperative CRP showed the highest area under the curve and the lowest corrected AIC for a finite sample size. Our study showed a new prediction model for mortality in patients with TBI using non-hematologic and hematologic parameters. This prediction model could be useful for the management of patients with TBI.
Chronic Pain and Emotional Stroop: A Systematic Review
Authors: Amaro-Díaz Lidia , Montoro Casandra I. , Fischer-Jbali Laura R. , Galvez-Sánchez Carmen M.
Published: June 2022

Chronic pain is an unpleasant sensory and emotional experience that persists for more than 3 months and is often accompanied by symptoms such as depression, fatigue, sleep disturbances, and cognitive impairment. Emotional dysregulation may also be involved in its etiology. Emotions are known to modulate the experience of pain by influencing cognition and behavior (emotional awareness, emotional expression and experience, and verbalizations). A useful task to explore emotional processing and emotional dysregulation is the emotional Stroop task. Despite the large number of studies using this task, their objectives are diverse; it is necessary to integrate them. The main objective of the present systematic review was to determine the extent of the abnormalities in behavioral performance (including attentional biases) and/or brain alterations in patients with chronic pain during the emotional Stroop task. This systematic review was conducted in accordance with the Cochrane Collaboration guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The protocol was previously registered in the Prospective Register of Systematic Reviews (PROSPERO) international database. The selected articles were extracted from the PubMed, Scopus, and Web of Science databases. Fifteen studies were identified as eligible for systematic review. The studies reported alterations in brain regions related to pain and emotional regulation, as well as attentional bias and higher response time latencies (related to the words’ emotional load) in patients with chronic pain. The results confirm the validity of the emotional Stroop task to measure emotions and selective attention. As attentional bias towards negative information is often seen in chronic pain patients, and given the relation between selective attention and greater activation of the brain areas associated with pain and emotional processing, this type of task plays a crucial role in research on emotional and attentional processes among chronic pain patients. Further, attentional bias towards negative information has been associated with higher levels of pain. Taken together, the results suggest the need for cognitive training and an emotional approach to chronic pain therapies, especially targeting attentional biases and negative mood.
Multiple Arterial Dissections and Connective Tissue Abnormalities
Authors: Erhart Philipp , Körfer Daniel , Dihlmann Susanne , Qiao Jia-Lu , Hausser Ingrid , Ringleb Peter , Männer Jörg , Dikow Nicola , Schaaf Christian P. , Grond-Ginsbach Caspar , Böckler Dittmar
Published: June 2022

Background: Although patients with multiple arterial dissections in distinct arterial regions rarely present with known connective tissue syndromes, we hypothesized that mild connective tissue abnormalities are common findings in these patients. Methods: From a consecutive register of 322 patients with cervical artery dissection (CeAD), we identified and analyzed 4 patients with a history of additional dissections in other vascular beds. In three patients, dermal connective tissue was examined by electron microscopy. DNA from all four patients was studied by whole-exome sequencing and copy number variation (CNV) analysis. Results: The collagen fibers of dermal biopsies were pathologic in all three analyzed patients. One patient carried a CNV disrupting the COL3A1 and COL5A2 genes (vascular or hypermobility type of Ehlers–Danlos syndrome), and another patient a CNV in MYH11 (familial thoracic aortic aneurysms and dissections). The third patient carried a missense substitution in COL5A2. Conclusion: Three patients showed morphologic alterations of the dermal connective tissue, and two patients carried pathogenic variants in genes associated with arterial connective tissue dysfunction. The findings suggest that genetic testing should be recommended after recurrent arterial dissections, independently of apparent phenotypical signs of connective tissue disorders.
Step Detection Accuracy and Energy Expenditure Estimation at Different Speeds by Three Accelerometers in a Controlled Environment in Overweight/Obese Subjects
Authors: Stenbäck Ville , Leppäluoto Juhani , Juustila Rosanna , Niiranen Laura , Gagnon Dominique , Tulppo Mikko , Herzig Karl-Heinz
Published: June 2022

Our aim was to compare three research-grade accelerometers for their accuracy in step detection and energy expenditure (EE) estimation in a laboratory setting, at different speeds, especially in overweight/obese participants. Forty-eight overweight/obese subjects participated. Participants performed an exercise routine on a treadmill with six different speeds (1.5, 3, 4.5, 6, 7.5, and 9 km/h) for 4 min each. The exercise was recorded on video and subjects wore three accelerometers during the exercise: Sartorio Xelometer (SX, hip), activPAL (AP, thigh), and ActiGraph GT3X (AG, hip), and energy expenditure (EE) was estimated using indirect calorimetry for comparisons. For step detection, speed-wise mean absolute percentage errors for the SX ranged between 9.73–2.26, 6.39–0.95 for the AP, and 88.69–2.63 for the AG. The activPALs step detection was the most accurate. For EE estimation, the ranges were 21.41–15.15 for the SX, 57.38–12.36 for the AP, and 59.45–28.92 for the AG. All EE estimation errors were due to underestimation. All three devices were accurate in detecting steps when speed exceeded 4 km/h and inaccurate in EE estimation regardless of speed. Our results will guide users to recognize the differences, weaknesses, and strengths of the accelerometer devices and their algorithms.
Peritoneal Dialysis as a Renal Replacement Therapy Modality for Patients with Acute Kidney Injury
Authors: Khan Sana Farooq
Published: June 2022

Since the advent and predominant use of extracorporeal therapies for renal replacement therapies for acute kidney injury, the use of peritoneal dialysis has largely been limited to specific resource-limited settings. This review highlights the current data available for the utilization of peritoneal dialysis for acute kidney injury. Though the current randomized controlled trials have small patient numbers, they have demonstrated peritoneal dialysis to be an appropriate modality for dialysis therapy in acute kidney injury. Current outcomes do not show a difference in mortality, renal recovery rates, or infectious complications when compared to extracorporeal treatments. However, there is a marked heterogeneity in these trials, and more standardized reporting of trial design, techniques, complications, and outcomes is needed.
The Assessment of Myocardial Longitudinal Strain in a Paediatric Spanish Population Using a New Software Analysis
Authors: Aristizábal-Duque Cristhian , Fernández Cabeza Juan , Blancas Sánchez Isabel , Delgado Ortega Mónica , Aparicio Martinez Pilar , Romero-Saldaña Manuel , Fonseca del Pozo Francisco , Pan Manuel , Ruiz Ortiz Martin , Mesa-Rubio María
Published: June 2022

Background: Two-dimensional speckle-tracking echocardiography (2DSTE) has been present for years. However, it is underutilized due to the expertise and time requirements for its analysis. Our aims were to provide strain values in a paediatric Spanish population and to assess the feasibility and reproducibility of a new strain software analysis in our environment. Methods: A cross-sectional study of 156 healthy children aged 6 to 17 years. Longitudinal strain (LS) analysis of the left ventricle, right ventricle, and left atrium was performed. Feasibility and reproducibility were assessed. The associations of clinical and echocardiographic variables with strain values were investigated by multivariate analysis. Results: Mean age was 11 ± 3 years (50% female). Feasibility of LS measurement ranged from 94.2% for left ventricle global LS (LVGLS) to 98.1% for other chamber strain parameters. Strain values were 26.7 ± 2.3% for LVGLS; 30.5 ± 4.4% and 26.9 ± 4% for right ventricle free wall LS (RVFWLS) and four chambers view LS (RV4CLS) respectively; and 57.8 ± 10.5%, 44.9 ± 9.5%, and 12.9 ± 5.5% for left atrium LS reservoir phase (LALSr), conduct phase (LALScd) and contraction phase (LALSct), also respectively. Body surface area (BSA) and age presented a negative correlation with strain values. Higher values were found in females than in males, except for LALScd. Excellent intra- and inter-observer reproducibility were found for right and left ventricular strain measurement, with intraclass correlation coefficients (ICC) ranging from 0.88 to 0.98, respectively. In conclusion, we described strain values in a healthy Spanish paediatric population. LS assessment by this new strain analysis software by semi-automatic manner was highly feasible and reproducible.
Olfactory Training in Post-COVID-19 Persistent Olfactory Disorders: Value Normalization for Threshold but Not Identification
Authors: Vandersteen Clair , Payne Magali , Dumas Louise-Émilie , Cancian Élisa , Plonka Alexandra , D’Andréa Grégoire , Chirio David , Demonchy Élisa , Risso Karine , Askenazy-Gittard Florence , Savoldelli Charles , Guevara Nicolas , Robert Philippe , Castillo Laurent , Manera Valeria , Gros Auriane
Published: June 2022

(1) Background: Persistent post-viral olfactory disorders (PPVOD) are estimated at 30% of patients one year after COVID-19 infection. No treatment is, to date, significantly effective on PPVOD with the exception of olfactory training (OT). The main objective of this work was to evaluate OT efficiency on post-COVID-19 PPVOD. (2) Methods: Consecutive patients consulting to the ENT department with post-COVID-19 PPVOD were included after completing clinical examination, the complete Sniffin’ Stick Test (TDI), the short version of the Questionnaire of olfactory disorders and the SF-36. Patients were trained to practice a self-olfactory training with a dedicated olfactory training kit twice a day for 6 months before returning to undergo the same assessments. (3) Results: Forty-three patients were included and performed 3.5 months of OT in average. We observed a significant TDI score improvement, increasing from 24.7 (±8.9) before the OT to 30.9 (±9.8) (p < 0.001). Based on normative data, a significant increase in the number of normosmic participants was observed only for the threshold values (p < 0.001). Specific and general olfaction-related quality of life improved after the OT. (4) Conclusions: Olfactory function appeared to improve only in peripheral aspects of post-COVID-19 PPVOD after OT. Future controlled studies must be performed to confirm the OT role and justify new therapeutic strategies that may focus on the central aspects of post-COVID-19 PPVOD.
Uterine Septum with or without Hysteroscopic Metroplasty: Impact on Fertility and Obstetrical Outcomes—A Systematic Review and Meta-Analysis of Observational Research
Authors: Noventa Marco , Spagnol Giulia , Marchetti Matteo , Saccardi Carlo , Bonaldo Giulio , Laganà Antonio Simone , Cavallin Francesco , Andrisani Alessandra , Ambrosini Guido , Vitale Salvatore Giovanni , Pacheco Luis Alonso , Haimovich Sergio , Di Spiezio Sardo Attilio , Carugno Jose , Scioscia Marco , Garzon Simone , Bettocchi Stefano , Buzzaccarini Giovanni , Tozzi Roberto , Vitagliano Amerigo
Published: June 2022

Objective: we performed a systematic review/meta-analysis to evaluate the impact of septate uterus and hysteroscopic metroplasty on pregnancy rate-(PR), live birth rate-(LBR), spontaneous abortion-(SA) and preterm labor (PL) in infertile/recurrent miscarriage-(RM) patients. Data sources: a literature search of relevant papers was conducted using electronic bibliographic databases (Medline, Scopus, Embase, Science direct). Study eligibility criteria: we included in this meta-analysis all types of observational studies that evaluated the clinical impact of the uterine septum and its resection (hysteroscopic metroplasty) on reproductive and obstetrics outcomes. The population included were patients with a diagnosis of infertility or recurrent pregnancy loss. Study appraisal and synthesis methods: outcomes were evaluated according to three subgroups: (i) Women with untreated uterine septum versus women without septum (controls); (ii) Women with treated uterine septum versus women with untreated septum (controls); (iii) Women before and after septum removal. Odds ratios (OR) with 95% confidence intervals (CI) were calculated for the outcome measures. A p-value < 0.05 was considered statistically significant. Subgroup analysis was performed according to the depth of the septum. Sources of heterogeneity were explored by meta-regression analysis according to specific features: assisted reproductive technology/spontaneous conception, study design and quality of papers included Results: data from 38 studies were extracted. (i) septum versus no septum: a lower PR and LBR were associated with septate uterus vs. controls (OR 0.45, 95% CI 0.27–0.76; p < 0.0001; and OR 0.21, 95% CI 0.12–0.39; p < 0.0001); a higher proportion of SA and PL was associated with septate uterus vs. controls (OR 4.29, 95% CI 2.90–6.36; p < 0.0001; OR 2.56, 95% CI 1.52–4.31; p = 0.0004). (ii) treated versus untreated septum: PR and PL were not different in removed vs. unremoved septum(OR 1.10, 95% CI 0.49–2.49; p = 0.82 and OR 0.81, 95% CI 0.35–1.86; p = 0.62); a lower proportion of SA was associated with removed vs. unremoved septum (OR 0.47, 95% CI 0.21–1.04; p = 0.001); (iii) before-after septum removal: the proportion of LBR was higher after the removal of septum (OR 49.58, 95% CI 29.93–82.13; p < 0.0001) and the proportion of SA and PL was lower after the removal of the septum (OR 0.02, 95% CI 0.02–0.04; p < 0.000 and OR 0.05, 95% CI 0.03–0.08; p < 0.0001) Conclusions: the results show the detrimental effect of the uterine septum on PR, LBR, SA and PL. Its treatment reduces the rate of SA.
Modernizing Total Hip Arthroplasty Perioperative Pathways: The Implementation of ERAS-Outpatient Protocol
Authors: Sivaloganathan Sivan , Blakeney William G. , Vendittoli Pascal-André
Published: June 2022

Pressure to reduce healthcare costs, limited hospital availability along with improvements in surgical technique and perioperative care motivated many centers to focus on outpatient pathway implementation. However, in many short-stay protocols, the focus has shifted away from aiming to reduce complications and improved rehabilitation, to using length of stay as the main factor of success. To improve patient outcomes and maintain safety, the best way to implement a successful outpatient program would be to combine it with the principles of enhanced recovery after surgery (ERAS), and to improve patient recovery to a level where the patient is able to leave the hospital sooner. This article delivers a case for modernizing total hip arthroplasty perioperative pathways by implementing ERAS-outpatient protocols.
Lower-Neck Sparing Using Proton Therapy in Patients with Uninvolved Neck Nasopharyngeal Carcinoma: Is It Safe?
Authors: De Felice Francesca , Vai Alessandro , Camarda Anna Maria , Iacovelli Nicola Alessandro , Orlandi Ester
Published: June 2022

Undifferentiated carcinoma of the nasopharynx (NPC) is a rare disease, which usually occurs in the Asian population. Due to its anatomic location, it is characterised by rich lymph node drainage and has a high incidence of cervical node metastasis. However, cervical nodal metastasis commonly involves retropharyngeal nodes and level II nodes, followed by level III nodes. In recent years, innovations in terms of systemic treatments and radiotherapy techniques have improved oncological outcome and treatment-related toxicities. Therefore, there is a growing interest in de-intensification strategies of reducing volumes and treatment-related side effects, especially in patients with NPC with N0–N1-stage disease. Proton therapy could represent a valid alternative to Intensity Modulated Radiotherapy (IMRT) in the management of NPC in this setting. With this Commentary, we aim to explore the feasibility of Intensity Modulated Proton Therapy (IMPT) in upper-neck irradiation of NPC N1-stage disease. We selected an NPC patient with N1 disease and compared the original IMRT plan with the IMPT plan in terms of dosimetric parameters. IMPT offers a minimal dosimetric advantage over IMRT in the bilateral lower-neck sparing. Clinical trials are needed to evaluate the significance of these proposed suggestions and their applicability in non-endemic areas.
Association of Thiazide Use in Patients with Hypertension with Overall Fracture Risk: A Population-Based Cohort Study
Authors: Chuang Cheng-Hsun , Yang Shun-Fa , Liao Pei-Lun , Huang Jing-Yang , Chan Man-Yee , Yeh Chao-Bin
Published: June 2022

Thiazide diuretics have long been widely used as antihypertensive agents. In addition to reducing blood pressure, thiazides also control calcium homeostasis and increase bone density. We hypothesized that the use of thiazides in patients with hypertension would reduce overall fracture risk. We used the Taiwan National Health Insurance Research Database to find patients with a hypertension diagnosis who accepted antihypertensive treatment from 2000 to 2017. The patients were further classified into thiazide users and nonthiazide users. Multivariable Cox regression analysis and Kaplan–Meier survival analysis were performed to estimate the adjusted hazard ratios (aHRs) and cumulative probability of fractures. After 1:1 propensity score matching by sex, age, urbanization level of place of residence, income, comorbidities, and medications, there were 18,483 paired thiazide users and non-users, respectively. The incidence densities of fractures (per 1000 person-months) were 1.82 (95% CI: 1.76–1.89) and 1.99 (95% CI: 1.92–2.06) in the thiazide and nonthiazide groups, respectively. The results indicated a lower hazard ratio for fractures in thiazide users (aHR = 0.93, 95% CI: 0.88–0.98). Kaplan–Meier survival analysis revealed a significantly lower cumulative incidence of fractures in the thiazide group (log-rank test; p = 0.0012). In conclusion, our results reveal that thiazide use can reduce fracture risk. When antihypertensive agents are being considered, thiazide may be a better choice if the patient is at heightened risk of fracture.
Assessment of Smell and Taste Disturbances among COVID-19 Convalescent Patients: A Cross-Sectional Study in Armenia
Authors: Melkumyan Karine , Shingala Darshan , Simonyan Syuzanna , Torossian Hrag , Mkrtumyan Karen , Dilbaryan Karen , Davtyan Garri , Vardumyan Erik , Yenkoyan Konstantin
Published: June 2022

Background and Objectives: Neurological manifestations of Coronavirus Disease 2019 (COVID-19) such as olfactory and gustatory disturbance have been reported among convalescent COVID-19 patients. However, scientific data on the prevalence of smell and taste disturbance are lacking. Therefore, we present findings on the degree of smell and taste disturbances among the Armenian population. Methods: Study participants were randomly recruited and then categorized into two groups based on their course of the disease. A cross-sectional study was performed to assess participants’ sensitivity to smell triggered by the olfactory and the trigeminal nerves; their ability to differentiate between various odors; and to evaluate their gustatory perception. Results: The smell test revealed that the degree of olfactory nerve disturbance was different by 30.7% in those participants of the early group as compared to those of the late group, and the degree of trigeminal nerve disturbance was different by 71.3% in the early group as compared to the late group. A variation of the differentiating ability among the participants of the early and late groups was detected. Gustatory disturbances for all flavors were also found to be different in both the groups. A moderate positive correlation (0.51) was found between the overall sensitivity of smell and the ability to differentiate between various odors as cumulatively stimulated by both the olfactory and trigeminal nerves. Also, a moderate positive correlation (0.33) was found between headache and smell sensitivity through the olfactory nerve and a high negative correlation (−0.71) was found between headache and smell sensitivity through the trigeminal nerve. Conclusion: Pathological changes in the olfactory and trigeminal perceptive abilities caused disturbances in smell sensation, with the trigeminal nerve being more affected. The capacity to differentiate fragrances did not improve with time and the disturbance severity of bitter taste perception was higher among the study participants.
Implant Sizing and Positioning in Anatomical Total Shoulder Arthroplasty Using a Rotator Cuff-Sparing Postero-Inferior Approach
Authors: Moroder Philipp , Lacheta Lucca , Minkus Marvin , Karpinski Katrin , Uhing Frank , De Souza Sheldon , van der Merwe Michael , Akgün Doruk
Published: June 2022

Background: The goal of this study was to compare the effectiveness of a rotator cuff-sparing postero-inferior (PI) approach with subdeltoidal access to the traditional subscapularis-takedown deltopectoral approach, in terms of implant sizing and positioning in anatomical total shoulder arthroplasty (aTSA). Methods: This study involved 18 human cadaveric shoulders with intact rotator cuffs and no evidence of head deforming osteoarthritis. An Eclipse stemless aTSA (Arthrex, Naples, FL, USA) was implanted in nine randomly selected specimens using a standard subscapularis-tenotomy deltopectoral approach, and in the other nine specimens using the cuff-sparing PI approach. Pre- and postoperative antero-posterior (AP) and axillary fluoroscopic radiographs were analyzed by two independent, blinded raters for the following parameters: (1) anatomic and prosthetic neck-shaft angle (NSA); (2) the shift between the anatomic and prosthetic center of rotation (COR); (3) anatomical size matching of the prosthetic humeral head; (4) the calculated Anatomic Reconstruction Score (ARS); (5) glenoid positioning; as well as (6) glenoid inclination and version. Results: While the COR was slightly but significantly positioned (p = 0.031) to be more medial in the PI approach group (3.7 ± 3.4%, range: −2.3% to 8.7%) than in the deltopectoral approach group (−0.2 ± 3.6%, range: −6.9% to 4.1%), on average, none of the remaining measured radiographic parameters significantly differed between both groups (PI approach group vs. deltopectoral group: NSA 130° vs. 127°, p = 0.57; COR supero-inferior, 2.6% vs. 1.0%, p = 0.35; COR antero-posterior, 0.9% vs. 1.7%, p = 0.57; head size supero-inferior, 97.3% vs. 98.5%, p = 0.15; head size antero-posterior, 101.1% vs. 100.6%, p = 0.54; ARS, 8.4 vs. 9.3, p = 0.13; glenoid positioning supero-inferior, 49.1% vs. 51.1%, p = 0.33; glenoid positioning antero-posterior, 49.3% vs. 50.4%, p = 0.23; glenoid inclination, 86° vs. 88°, p = 0.27; and glenoid retroversion, 91° vs. 89°, p = 0.27). Conclusions: A PI approach allows for sufficient exposure and orientation to perform rotator-cuff sparing aTSA with acceptable implant sizing and positioning in cadaveric specimens.
Association of Preoperative Basal Inflammatory State, Measured by Plasma suPAR Levels, with Intraoperative Sublingual Microvascular Perfusion in Patients Undergoing Major Non-Cardiac Surgery
Authors: Chalkias Athanasios , Papagiannakis Nikolaos , Saugel Bernd , Flick Moritz , Kolonia Konstantina , Angelopoulou Zacharoula , Ragias Dimitrios , Papaspyrou Dimitra , Bouzia Aikaterini , Ntalarizou Nicoletta , Stamoulis Konstantinos , Kyriakaki Aikaterini , Eugen-Olsen Jesper , Laou Eleni , Arnaoutoglou Eleni
Published: June 2022

It remains unknown whether chronic systemic inflammation is associated with impaired microvascular perfusion during surgery. We evaluated the association between the preoperative basal inflammatory state, measured by plasma soluble urokinase-type plasminogen activator receptor (suPAR) levels, and intraoperative sublingual microcirculatory variables in patients undergoing major non-cardiac surgery. Plasma suPAR levels were determined in 100 non-cardiac surgery patients using the suPARnostic® quick triage lateral flow assay. We assessed sublingual microcirculation before surgical incision and every 30 min during surgery using Sidestream Darkfield (SDF+) imaging and determined the De Backer score, the Consensus Proportion of Perfused Vessels (Consensus PPV), and the Consensus PPV (small). Elevated suPAR levels were associated with lower intraoperative De Backer score, Consensus PPV, and Consensus PPV (small). For each ng mL−1 increase in suPAR, De Backer score, Consensus PPV, and Consensus PPV (small) decreased by 0.7 mm−1, 2.5%, and 2.8%, respectively, compared to baseline. In contrast, CRP was not significantly correlated with De Backer score (r = −0.034, p = 0.36), Consensus PPV (r = −0.014, p = 0.72) or Consensus PPV Small (r = −0.037, p = 0.32). Postoperative De Backer score did not change significantly from baseline (5.95 ± 3.21 vs. 5.89 ± 3.36, p = 0.404), while postoperative Consensus PPV (83.49 ± 11.5 vs. 81.15 ± 11.8, p < 0.001) and Consensus PPV (small) (80.87 ± 13.4 vs. 78.72 ± 13, p < 0.001) decreased significantly from baseline. In conclusion, elevated preoperative suPAR levels were associated with intraoperative impairment of sublingual microvascular perfusion in patients undergoing elective major non-cardiac surgery.
Dupilumab Improves Skin Barrier Function in Adults with Atopic Dermatitis: A Prospective Observational Study
Authors: Montero-Vilchez Trinidad , Rodriguez-Pozo Juan-Angel , Diaz-Calvillo Pablo , Salazar-Nievas Maria , Tercedor-Sanchez Jesús , Molina-Leyva Alejandro , Arias-Santiago Salvador
Published: June 2022

Epidermal barrier dysfunction plays an important role in atopic dermatitis (AD). The difficulty of objectively assessing AD severity and the introduction of new biologicals into clinical practice highlight the need to find parameters to monitor clinical outcomes. The aim of this study is to evaluate the impact of dupilumab on skin barrier function and compare it with other treatments in patients with AD. A prospective observational study was conducted in adults with AD treated with topical corticosteroids (TCS), cyclosporine, or dupilumab. The main outcome measures after 16 weeks of treatment were Eczema Area and Severity (EASI)-50 (50% improvement in EASI), and transepidermal water loss (TEWL)-50 (50% improvement in TEWL). Forty-six patients with AD were included in the study. The proportion of patients who achieved EASI-50 at week 16 was significantly higher in patients receiving dupilumab (81.8% vs. 28.6% vs. 40%, p = 0.004). In eczematous lesions, TEWL decreased in patients receiving dupilumab (31.02 vs. 12.10 g·h−1·m−2, p < 0.001) and TCS (25.30 vs. 14.88 g·h−1·m−2, p = 0.047). The proportion of patients who achieved TEWL-50 at week 16 was higher for dupilumab than for cyclosporine or TCS. Temperature only decreased in the dupilumab group. Stratum corneum hydration increased in eczematous lesions and non-involved skin only in patients with dupilumab. In conclusion, dupilumab improves skin barrier function in patients with AD better than TCS or cyclosporine, both in eczematous lesions and in non-lesioned skin.