bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Chemical Stability, Membrane Permeability and Antiproliferative Activity of Cyclic Diarylheptanoids from European Hornbeam (Carpinus betulus L.)
Authors: Felegyi-Tóth Csenge Anna , Heilmann Tímea , Buda Eszter , Stipsicz Bence , Simon Alexandra , Boldizsár Imre , Bősze Szilvia , Riethmüller Eszter , Alberti Ágnes
Published: August 2023

Four cyclic diarylheptanoids—carpinontriols A (1) and B (2), giffonin X (3) and 3,12,17-trihydroxytricyclo [12.3.1.12,6]nonadeca-1(18),2(19),3,5,14,16-hexaene-8,11-dione (4)—were isolated from Carpinus betulus (Betulaceae). Chemical stability of the isolated diarylheptanoids was evaluated as a function of storage temperature (−15, 5, 22 °C) and time (12 and 23 weeks). The effect of the solvent and the pH (1.2, 6.8, 7.4) on the stability of these diarylheptanoids was also investigated. Compounds 2 and 4 showed good stability both in aqueous and methanolic solutions at all investigated temperatures. Only 2 was stable at all three studied biorelevant pH values. Degradation products of 1 and 3 were formed by the elimination of a water molecule from the parent compounds, as confirmed by ultrahigh-performance liquid chromatography–high-resolution tandem mass spectrometry (UHPLC-HR-MS). The permeability of the compounds across biological membranes was evaluated by the parallel artificial membrane permeability assay (PAMPA). Compound 3 possesses a logPe value of −5.92 ± 0.04 in the blood–brain barrier-specific PAMPA-BBB study, indicating that it may be able to cross the blood–brain barrier via passive diffusion. The in vitro antiproliferative activity of the compounds was investigated against five human cancer cell lines, confirming that 1 inhibits cell proliferation in A2058 human metastatic melanoma cells.
Impact of Developmental Changes of GABAA Receptors on Interneuron-NG2 Glia Transmission in the Hippocampus
Authors: Patt Linda , Tascio Dario , Domingos Catia , Timmermann Aline , Jabs Ronald , Henneberger Christian , Steinhäuser Christian , Seifert Gerald
Published: August 2023

NG2 glia receive synaptic input from neurons, but the functional impact of this glial innervation is not well understood. In the developing cerebellum and somatosensory cortex the GABAergic input might regulate NG2 glia differentiation and myelination, and a switch from synaptic to extrasynaptic neuron–glia signaling was reported in the latter region. Myelination in the hippocampus is sparse, and most NG2 glia retain their phenotype throughout adulthood, raising the question of the properties and function of neuron-NG2 glia synapses in that brain region. Here, we compared spontaneous and evoked GABAA receptor-mediated currents of NG2 glia in juvenile and adult hippocampi of mice of either sex and assessed the mode of interneuron–glial signaling changes during development. With patch-clamp and pharmacological analyses, we found a decrease in innervation of hippocampal NG2 glia between postnatal days 10 and 60. At the adult stage, enhanced activation of extrasynaptic receptors occurred, indicating a spillover of GABA. This switch from synaptic to extrasynaptic receptor activation was accompanied by downregulation of γ2 and upregulation of the α5 subunit. Molecular analyses and high-resolution expansion microscopy revealed mechanisms of glial GABAA receptor trafficking and clustering. We found that gephyrin and radixin are organized in separate clusters along glial processes. Surprisingly, the developmental loss of γ2 and postsynaptic receptors were not accompanied by altered glial expression of scaffolding proteins, auxiliary receptor subunits or postsynaptic interaction proteins. The GABAergic input to NG2 glia might contribute to the release of neurotrophic factors from these cells and influence neuronal synaptic plasticity.
Transcriptome Profiles Reveal the Promoting Effects of Exogenous Melatonin on Fruit Softening of Chinese Plum
Authors: Li Zhiyu , Zhang Lu , Xu Yaxin , Zhang Xuemei , Zhu Yanzhou , Wang Jin , Xia Hui , Liang Dong , Lv Xiulan , Lin Lijin
Published: August 2023

In this study, we investigated the effect of exogenous melatonin (MT) on cell wall metabolism leading to Chinese plum (Prunus salicina Lindl.) fruit softening. Exogenous MT treatment increased the endogenous MT content in plum fruits before fruit ripening. However, in mature plum fruits, exogenous MT treatment decreased the fruit hardness, pulp hardness, fruit elasticity, contents of ion-bound pectin, covalently-bound pectin, hemicellulose, and cellulose, and activities of xyloglucan endotransglycosylase/hydrolase and endo-β-1,4-glucanase, and increased the water-soluble pectin content, and activities of pectin methyl esterase, pectin lyase, polygalacturonase, β-galactopyranosidase, and α-L-arabinofuranosidase. Transcriptome analysis revealed that the differentially expressed genes (DEGs) associated with cell wall metabolism in the exogenous MT-treated plum fruits were mainly enriched in the pentose and glucuronate interconversions, phenylpropanoid biosynthesis, cyanoamino acid metabolism, and galactose metabolism pathways. Analysis of these DEGs revealed that exogenous MT treatment affected the expression of genes regulating the cell wall metabolism. Overall, exogenous MT treatment promotes the fruit softening of Chinese plum.
A Customized Human Mitochondrial DNA Database (hMITO DB v1.0) for Rapid Sequence Analysis, Haplotyping and Geo-Mapping
Authors: Shen-Gunther Jane , Gunther Rutger S. , Cai Hong , Wang Yufeng
Published: August 2023

The field of mitochondrial genomics has advanced rapidly and has revolutionized disciplines such as molecular anthropology, population genetics, and medical genetics/oncogenetics. However, mtDNA next-generation sequencing (NGS) analysis for matrilineal haplotyping and phylogeographic inference remains hindered by the lack of a consolidated mitogenome database and an efficient bioinformatics pipeline. To address this, we developed a customized human mitogenome database (hMITO DB) embedded in a CLC Genomics workflow for read mapping, variant analysis, haplotyping, and geo-mapping. The database was constructed from 4286 mitogenomes. The macro-haplogroup (A to Z) distribution and representative phylogenetic tree were found to be consistent with published literature. The hMITO DB automated workflow was tested using mtDNA-NGS sequences derived from Pap smears and cervical cancer cell lines. The auto-generated read mapping, variants track, and table of haplotypes and geo-origins were completed in 15 min for 47 samples. The mtDNA workflow proved to be a rapid, efficient, and accurate means of sequence analysis for translational mitogenomics.
Assembling Spheroids of Rat Primary Neurons Using a Stress-Free 3D Culture System
Authors: Harley-Troxell Meaghan E. , Dhar Madhu
Published: August 2023

Neural injuries disrupt the normal functions of the nervous system, whose complexities limit current treatment options. Because of their enhanced therapeutic effects, neurospheres have the potential to advance the field of regenerative medicine and neural tissue engineering. Methodological steps can pose challenges for implementing neurosphere assemblies; for example, conventional static cultures hinder yield and throughput, while the presence of the necrotic core, time-consuming methodology, and high variability can slow their progression to clinical application. Here we demonstrate the optimization of primary neural cell-derived neurospheres, developed using a high-throughput, stress-free, 3D bioreactor. This process provides a necessary baseline for future studies that could develop co-cultured assemblies of stem cells combined with endothelial cells, and/or biomaterials and nanomaterials for clinical therapeutic use. Neurosphere size and neurite spreading were evaluated under various conditions using Image J software. Primary neural cells obtained from the hippocampi of three-day-old rat pups, when incubated for 24 h in a reactor coated with 2% Pluronic and seeded on Poly-D-Lysine-coated plates establish neurospheres suitable for therapeutic use within five days. Most notably, neurospheres maintained high cell viability of ≥84% and expressed the neural marker MAP2, neural marker β-Tubulin III, and glial marker GFAP at all time points when evaluated over seven days. Establishing these factors reduces the variability in developing neurospheres, while increasing the ease and output of the culture process and maintaining viable cellular constructs.
Reduced Expression of Septin7 Hinders Skeletal Muscle Regeneration
Authors: Szabó László , Telek Andrea , Fodor János , Dobrosi Nóra , Dócs Klaudia , Hegyi Zoltán , Gönczi Mónika , Csernoch László , Dienes Beatrix
Published: August 2023

Septins are considered the fourth component of the cytoskeleton with the septin7 isoform playing a critical role in the formation of diffusion barriers in phospholipid bilayers and intra- and extracellular scaffolds. While its importance has already been confirmed in different intracellular processes, very little is known about its role in skeletal muscle. Muscle regeneration was studied in a Sept7 conditional knock-down mouse model to prove the possible role of septin7 in this process. Sterile inflammation in skeletal muscle was induced which was followed by regeneration resulting in the upregulation of septin7 expression. Partial knock-down of Sept7 resulted in an increased number of inflammatory cells and myofibers containing central nuclei. Taken together, our data suggest that partial knock-down of Sept7 hinders the kinetics of muscle regeneration, indicating its crucial role in skeletal muscle functions.
Mucins 3A and 3B Are Expressed in the Epithelium of Human Large Airway
Authors: Merikallio Heta , Pincikova Terezia , Kotortsi Ioanna , Karimi Reza , Li Chuan-Xing , Forsslund Helena , Mikko Mikael , Nyrén Sven , Lappi-Blanco Elisa , Wheelock Åsa M. , Kaarteenaho Riitta , Sköld Magnus C.
Published: August 2023

Aberrant mucus secretion is a hallmark of chronic obstructive pulmonary disease (COPD). Expression of the membrane-tethered mucins 3A and 3B (MUC3A, MUC3B) in human lung is largely unknown. In this observational cross-sectional study, we recruited subjects 45–65 years old from the general population of Stockholm, Sweden, during the years 2007–2011. Bronchial mucosal biopsies, bronchial brushings, and bronchoalveolar lavage fluid (BALF) were retrieved from COPD patients (n = 38), healthy never-smokers (n = 40), and smokers with normal lung function (n = 40). Protein expression of MUC3A and MUC3B in bronchial mucosal biopsies was assessed by immunohistochemical staining. In a subgroup of subjects (n = 28), MUC3A and MUC3B mRNAs were quantified in bronchial brushings using microarray. Non-parametric tests were used to perform correlation and group comparison analyses. A value of p < 0.05 was considered statistically significant. MUC3A and MUC3B immunohistochemical expression was localized to ciliated cells. MUC3B was also expressed in basal cells. MUC3A and MUC3B immunohistochemical expression was equal in all study groups but subjects with emphysema had higher MUC3A expression, compared to those without emphysema. Smokers had higher mRNA levels of MUC3A and MUC3B than non-smokers. MUC3A and MUC3B mRNA were higher in male subjects and correlated negatively with expiratory air flows. MUC3B mRNA correlated positively with total cell concentration and macrophage percentage, and negatively with CD4/CD8 T cell ratio in BALF. We concluded that MUC3A and MUC3B in large airways may be a marker of disease or may play a role in the pathophysiology of airway obstruction.
Prompt Engineering in Medical Education
Authors: Heston Thomas , Khun Charya
Published: August 2023

Artificial intelligence-powered generative language models (GLMs), such as ChatGPT, Perplexity AI, and Google Bard, have the potential to provide personalized learning, unlimited practice opportunities, and interactive engagement 24/7, with immediate feedback. However, to fully utilize GLMs, properly formulated instructions are essential. Prompt engineering is a systematic approach to effectively communicating with GLMs to achieve the desired results. Well-crafted prompts yield good responses from the GLM, while poorly constructed prompts will lead to unsatisfactory responses. Besides the challenges of prompt engineering, significant concerns are associated with using GLMs in medical education, including ensuring accuracy, mitigating bias, maintaining privacy, and avoiding excessive reliance on technology. Future directions involve developing more sophisticated prompt engineering techniques, integrating GLMs with other technologies, creating personalized learning pathways, and researching the effectiveness of GLMs in medical education.
Social Media Mining and Analysis: A Brief Review of Recent Challenges
Authors: Thakur Nirmalya
Published: August 2023

Social media platforms are a type of web-based applications that are built on the conceptual and technical underpinnings of Web 2 [...]
Hepatic Involvement across the Metabolic Syndrome Spectrum: Non-Invasive Assessment and Risk Prediction Using Machine Learning
Authors: Solomon Adelaida , Cipăian Călin Remus , Negrea Mihai Octavian , Boicean Adrian , Mihaila Romeo , Beca Corina , Popa Mirela Livia , Grama Sebastian Mihai , Teodoru Minodora , Neamtu Bogdan
Published: August 2023

Metabolic-dysfunction-associated steatotic liver disease (MASLD) and metabolic syndrome (MetS) are inextricably linked conditions, both of which are experiencing an upward trend in prevalence, thereby exerting a substantial clinical and economic burden. The presence of MetS should prompt the search for metabolic-associated liver disease. Liver fibrosis is the main predictor of liver-related morbidity and mortality. Non-invasive tests (NIT) such as the Fibrosis-4 index (FIB4), aspartate aminotransferase-to-platelet ratio index (APRI), aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), hepatic steatosis index (HIS), transient elastography (TE), and combined scores (AGILE3+, AGILE4) facilitate the detection of liver fibrosis or steatosis. Our study enrolled 217 patients with suspected MASLD, 109 of whom were diagnosed with MetS. We implemented clinical and biological evaluations complemented by transient elastography (TE) to discern the most robust predictors for liver disease manifestation patterns. Patients with MetS had significantly higher values of FIB4, APRI, HSI, liver stiffness, and steatosis parameters measured by TE, as well as AGILE3+ and AGILE4 scores. Machine-learning algorithms enhanced our evaluation. A two-step cluster algorithm yielded three clusters with reliable model quality. Cluster 1 contained patients without significant fibrosis or steatosis, while clusters 2 and 3 showed a higher prevalence of significant liver fibrosis or at least moderate steatosis as measured by TE. A decision tree algorithm identified age, BMI, liver enzyme levels, and metabolic syndrome characteristics as significant factors in predicting cluster membership with an overall accuracy of 89.4%. Combining NITs improves the accuracy of detecting patterns of liver involvement in patients with suspected MASLD.
Body Dissatisfaction and Body-Related Attentional Bias: Is There a Causal Relationship?
Authors: Mendoza-Medialdea María Teresa , Meschberger-Annweiler Franck-Alexandre , Ascione Mariarca , Rueda-Pina Alejandra , Rabarbari Elisa , Porras-Garcia Bruno , Ferrer-Garcia Marta , Gutiérrez-Maldonado José
Published: August 2023

Previous research has shown an association between body dissatisfaction and attentional biases toward the body, but the nature of this relationship is not clear. It is possible that dissatisfaction causes attentional bias or that dissatisfaction is a result of such bias. To clarify the causal relationship between these two variables, this study manipulated dissatisfaction in a sample of healthy women by exposing them to images of “ideal” bodies and observed whether this manipulation increased attentional biases toward different body parts. Fifty-seven women took part in a pre–post experimental design in which they observed an avatar representing themselves in a virtual mirror before and after being exposed to “thin ideal” photographs. Eye-tracking technology was employed to quantify the frequency and duration of fixations on weight-related and weight-unrelated body parts. The outcomes revealed a successful induction of body dissatisfaction, leading participants to display a heightened number of fixations and prolonged fixation durations on unrelated-weight body parts. These findings remained significant after controlling for the effects of trait body dissatisfaction and body mass index. The results imply that heightened body dissatisfaction fosters the aversion of attention from weight-related body parts, which may function as a protective mechanism for preserving self-esteem and promoting psychological well-being.
Vincristine-Induced Neuropathy in Patients Diagnosed with Solid and Hematological Malignancies: The Role of Dose Rounding
Authors: Alwhaibi Abdulrahman M. , Alshamrani Ali A. , Alenazi Miteb A. , Altwalah Shroog F. , Alameel Nouf N. , Aljabali Noura N. , Alghamdi Sara B. , Bineid Abdulwahab I. , Alwhaibi Monira , Al Arifi Mohamed N.
Published: August 2023

Background: Vincristine is a vital constituent of chemotherapeutic regimens. Vincristine-induced neuropathy is a challenging adverse effect that impacts quality of life and treatment course. The dose rounding of chemotherapies is a strategy that is commonly used in clinical practice. Nevertheless, the frequency of developed neuropathy in vincristine first-time users and the potential association with dose rounding remains elusive. Methods: A retrospective analysis was conducted on patients administered vincristine for the first time between 2016 and 2022 using the King Saud University Medical City (KSUMC) database. Patients were stratified into pediatric and adult groups. Neuropathy frequency, its association with demographic and clinical parameters, and the Impact of dose rounding were assessed using SPSS software version 28. Results: Approximately 34.6% of patients were diagnosed with neuropathy after vincristine administration. Autonomic neuropathy was common among affected adults and pediatric patients (55.1% and 56.1%, respectively), while cranial neuropathy was more frequent in pediatric patients. Higher BSA (p = 0.038) and Scr (p = 0.044) in the pediatric group, the presence of respiratory comorbidities (p = 0.044), and the use of azole antifungals (p < 0.001) in the adult group were significantly associated with neuropathy episodes. The rounding-up of vincristine doses was significantly associated with increased neuropathy occurrence (p < 0.001), while dose rounding-down was significantly associated with a decrease in neuropathy in both groups of patients (p < 0.001). Conclusions: Our findings demonstrate that autonomic neuropathy is the most common vincristine-related neuropathy, regardless of the patient’s age. Dose rounding is a significant determinant of vincristine-induced neuropathy in both groups. Further studies are needed to evaluate the variables that exacerbate or prevent neuropathy associated with the first-time use of vincristine.
The Feasibility and Early Results of Multivessel Minimally Invasive Coronary Artery Bypass Grafting for All Comers
Authors: Demirsoy Ergun , Mavioglu Ilhan , Dogan Emre , Gulmez Harun , Dindar Ismet , Erol Mustafa Kemal
Published: August 2023

Objectives: Cardiovascular surgery advancements have emerged with various minimally invasive approaches for treating multivessel coronary disease to improve outcomes and minimize the burden associated with conventional cardiac surgery. We present our clinical experience and minimally invasive coronary bypass techniques through minithoracotomy, which we apply without selection to patients who have decided to have elective surgery for multivessel isolated coronary artery disease. Methods: It consists of 230 consecutive patients operated by the same team with this method between July 2020 and September 2022. The patients were assigned to one of the two methods preoperatively to their accompanying comorbidities and operated on either with blood cardioplegia via 5 to 7 cm left anterior minithoracotomy, with on-pump clamped technique or without pump via left anterolateral minithoracotomy. Results: Mortality was observed in two of our patients (0.9%), but myocardial infarction was not observed in our patients in the early postoperative period. None of our patients required conversion to sternotomy (0%). Five patients’ needed reoperation from the same incision due to postoperative bleeding (2.2%), and atrial fibrillation developed in 17 patients in the postoperative period (7.4%). The mean number of bypasses was found to be 3.0 ± 0.9. Conclusions: Minimally invasive coronary artery bypass surgery via minithoracotomy can be routinely reproduced safely. More long-term results and more multicenter studies are needed for more widespread acceptance of the technique.
Three-Dimensional Transesophageal Echocardiography in Percutaneous Catheter-Based Cardiac Interventions
Authors: Farina Juan M. , Barry Timothy , Arsanjani Reza , Ayoub Chadi , Naqvi Tasneem Z.
Published: August 2023

Cardiac structural and valve interventions have remained surgical procedures for several decades. The ability to directly visualize the region of interest during surgery made imaging of these structures pre- and postsurgery a secondary tool to compliment surgical visualization. The last two decades, however, have seen rapid advances in catheter-based percutaneous structural heart interventions (SHIs). Due to the “blind” nature of these interventions, imaging plays a crucial role in the success of these procedures. Fluoroscopy is used universally in all percutaneous cardiac SHIs and helps primarily in the visualization of catheters and devices. However, success of these procedures requires visualization of intracardiac soft tissue structures. Due to its portable nature and rapid ability to show cardiac structures online, transesophageal echocardiography (TEE) has become an integral tool for guidance for all percutaneous SHI. Transcatheter aortic valve replacement—one of the earliest catheter-based procedures—while initially dependent on TEE, has largely been replaced by preprocedural cardiac CT for accurate assessment of valve sizing. Developments in echocardiography now allow live three-dimensional (3D) visualization of cardiac structures mimicking surgical anatomy during TEE. Besides showing actual 3D intracardiac structures, 3D-TEE allows visualization of the interaction of intracardiac catheters and devices with soft tissue cardiac structures, thereby becoming a “second pair of eyes” for the operator. Real-time 3D-TEE now plays an important role complementing multiplane two dimensional and biplane TEE during such interventions. In this review, we discuss the incremental role of 3D-TEE during various SHIs performed today.
Self-Efficacy and Self-Care as Risk Factors for Ischemic Stroke: Development and Validation of a Nomogram
Authors: Rasyid Al , Pemila Uke , Aisah Siti , Harris Salim , Wiyarta Elvan , Fisher Marc
Published: August 2023

Background: This study addresses the knowledge gap on how self-efficacy and self-care affect stroke risk as factors and develops a valuable tool for clinicians to assess stroke risk. Methods: From January 2022 to January 2023, this nested-case control study was conducted. Medical data including gender, age, ethnicity, locality, education, marital status, employment, caregiver, social environment, blood viscosity, Barthel Index, modified Rankin Scale (mRS), stroke risk score, self-care score, and self-efficacy score were collected. Logistic regression was used to predict stroke risk, and a nomogram was developed and validated. Results: 240 patients were included in the analysis. Stroke risk score (OR: 3.513; p = 0.005), self-efficacy score (OR: 0.753; p = 0.048), and self-care score (OR: 0.817; p = 0.018) were predictors of ischemic stroke. Internal validation was carried out, with a C-index of 0.774, and the Hosmer–Lemeshow test indicated a good fit (p = 0.92). The calibration plot also shows that this nomogram model has good calibration abilities. The decision curve analysis (DCA) results show a threshold probability range of 10–95%. Conclusion: A nomogram has been developed with good validity, calibration, and clinical utility, including self-care and self-efficacy as risk factors for predicting ischemic stroke.
Human Papillomavirus-Associated Tumor Extracellular Vesicles in HPV+ Tumor Microenvironments
Authors: Gameiro Steven F. , Flondra Kaitlyn M.
Published: August 2023

Most infections with human papillomaviruses (HPVs) are self-resolving and asymptomatic. However, some infections can lead to the development of cancer at different mucosal sites, such as the cervix and the head and neck. Head and neck cancers (HNCs) are dichotomized into HPV-positive (HPV+) or HPV-negative (HPV−) based on their respective etiologies. Notably, the tumor microenvironment (TME) of the HPV+ subtype has an immune landscape characterized with increased immune infiltration, higher levels of T cell activation, and higher levels of immunoregulatory stimuli compared to their HPV− counterparts. Both enveloped and nonenveloped viruses hijack the extracellular vesicle (EV) biogenesis pathway to deploy a “trojan horse” strategy with a pseudoviral envelope to enhance infectivity and evade inflammation. EVs derived from HPV-infected tumor cells could allow for the stealth transport of viral cargo to neighboring nonmalignant cellular populations or infiltrating immune cells within the TME. Furthermore, viral cargo or altered cellular cargo from HPV-associated tumor EVs (HPV-TEVs) could alter the functional state or biological responses of the recipient cellular populations, which could shape the distinctive HPV+ TME. This review will cover the impact of EVs released from HPV-infected cells on HPV-induced carcinogenesis, their role in shaping the distinctive HPV+ tumor microenvironment, and current efforts to develop a painless EV-based liquid biopsy for HPV+ cancers.
Delirium Screening and Pharmacotherapy in the ICU: The Patients Are Not the Only Ones Confused
Authors: Martinez F. Eduardo , Tee Rebecca , Poulter Amber-Louise , Jordan Leah , Bell Liam , Balogh Zsolt J.
Published: August 2023

Background: Delirium is difficult to measure in the Intensive Care Unit (ICU). It is possible that by considering the rate of screening, incidence, and rate of treatment with antipsychotic medications (APMs) for suspected delirium, a clearer picture can emerge. Methods: A retrospective, observational study was conducted at two ICUs in Australia, between April and June of 2020. All adult ICU patients were screened; those who spoke English and did not have previous neurocognitive pathology or intracranial pathology were included in the analysis. Data were collected from the hospitals’ electronic medical records. The primary outcome was incidence of delirium based on the use of the Confusion Assessment Method for ICU (CAM-ICU). Secondary outcomes included measures of screening for delirium, treatment of suspected delirium with APMs, and identifying clinical factors associated with both delirium and the use of APMs. Results: From 736 patients that were screened, 665 were included in the analysis. The incidence of delirium was 11.3% (75/665); on average, the Richmond Agitation and Sedation Scale (RASS) was performed every 2.9 h and CAM-ICU every 40 h. RASS was not performed in 8.4% (56/665) of patients and CAM-ICU was not performed in 40.6% (270/665) of patients. A total of 17% (113/665) of patients were prescribed an APM, with quetiapine being the most used. ICU length of stay (LOS), APACHE-III score, and the use of alpha-2 agonists were associated with the presence of delirium, while ICU LOS, the use of alpha-2 agonists, and the presence of delirium were associated with patients receiving APMs. Conclusions: The incidence of delirium was lower than previously reported, at 11.3%. The rate of screening for delirium was low, while the use of APMs for delirium was higher than the incidence of delirium. It is possible that the true incidence is higher than what was measured. Critical prospective assessment is required to optimize APM indications in the ICU.
Maternal SARS-CoV-2 Infection at Delivery Increases IL-6 Concentration in Umbilical Cord Blood
Authors: Kosińska-Kaczyńska Katarzyna , Rebizant Beata , Czeszko-Paprocka Hanna , Bojdo Agata , Przybylski Maciej , Chaberek Katarzyna , Lewandowska Agnieszka , Szymusik Iwona , Brawura-Biskupski-Samaha Robert
Published: August 2023

Background: SARS-CoV-2 infection in pregnant women may induce inflammation within the amniotic cavity and/or an increase in proinflammatory cytokines in fetal circulation. The aim was to investigate levels of IL-6 in maternal blood, umbilical cord blood, and amniotic fluid in pregnant women infected with SARS-CoV-2 at delivery. Methods: A single-center prospective observational case–control study of pregnant women diagnosed with SARS-CoV-2 infection at delivery was conducted. A total of 48 infected and 42 healthy women had IL-6 concentrations measured in their blood, amniotic fluid, and umbilical cord blood. Results: The concentrations of IL-6 in maternal blood and amniotic fluid were similar in the study and control groups, while umbilical cord blood concentrations were significantly higher in SARS-CoV-2-positive women. The umbilical cord blood IL-6 concentration was related to composite neonatal morbidity. Conclusions: Maternal SARS-CoV-2 infection in pregnant women at delivery increases umbilical cord blood IL-6 concentration. The correlation between maternal and umbilical blood concentrations indicates a possibility of passage of IL-6 through the placenta. Perinatal alterations resulting from maternal SARS-CoV-2 infection at delivery carry a risk of impacting the health of infants even in asymptomatic course of infection.
Myocardial Work in Middle-Aged Adults with Overweight and Obesity: Associations with Sex and Central Arterial Stiffness
Authors: Lindseth Katrine Tryti , Gerdts Eva , Midtbø Helga , Pristaj Nadia , Cramariuc Dana , Einarsen Eigir
Published: August 2023

We explored global myocardial work index (GWI), a novel measure of myocardial function that integrates left ventricular (LV) hemodynamic load, in relation to sex and increased body mass index (BMI). We used data from 467 individuals (61% women, average age 47 ± 9 years and BMI 31.2 kg/m2) without known cardiac disease. Central arterial function was analysed by applanation tonometry. GWI was calculated from global longitudinal strain (GLS) and post-echocardiography supine blood pressure (BP). Covariables of GWI were identified in linear regression analyses. Women had higher BMI, aortic augmentation pressure (12 ± 7 vs. 8 ± 6 mmHg), LV GLS (20.0 ± 2.8 vs. 18.8 ± 2.8%), and GWI (2126 ± 385 vs. 2047 ± 389 mmHg%) than men (all p < 0.05). In univariable analyses, higher GWI was associated with female sex, higher age, systolic BP, LV wall stress, LV ejection fraction, left atrial size, LV ejection time, and with lower waist circumference (all p < 0.05). In multivariable analysis, adjusting for these correlates, female sex remained independently associated with higher GWI (β = 0.13, p = 0.007). After additional adjustment for aortic augmentation pressure or central pulse pressure, this association became non-significant. In conclusion, the higher GWI in women compared to men was mainly explained by increased LV workload due to higher aortic augmentation pressure in women.
Clinical Link between the BARD Score at Diagnosis and Mortality during Follow-Up in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis
Authors: Lee Tae-Geom , Park Pil-Gyu , Park Yong-Beom , Huh Ji-Hye , Lee Sang-Won
Published: August 2023

This study investigated whether the BARD score at diagnosis could predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study included 236 immunosuppressive drug-naïve patients without chronic liver diseases such as viral hepatitis, non-alcoholic fatty liver disease (NAFLD), and advanced liver diseases and their clinical data at diagnosis, such as age, sex, and the Birmingham Vasculitis Activity Score (BVAS). The BARD score was calculated by the sum of aspartate transaminase (AST)/alanine transaminase (ALT) ratio ≥ 0.8 (+2 points), body mass index (BMI) ≥ 28 kg/m2 (+1 point), and the presence of type 2 diabetes mellitus (T2DM) (+1 point). All-cause mortality was investigated as a poor outcome of AAV. The median age of AAV patients was 60.0 years, and 34.7% were men. Among AAV patients, 7, 50, and 187 scored 1, 1, and 2 points owing to having a BMI ≥ 28 kg/m2, T2DM, and an AST/ALT ratio ≥ 0.8, respectively. Patients with a BARD score ≥ 2 and those with a BARD score ≥ 3 exhibited significantly lower cumulative patient survival rates than those without (p = 0.038 and p = 0.003, respectively). In the multivariable Cox analysis, among the two cut-offs of the BARD scores, only a BARD score ≥ 3 (HR 2.866), along with age (HR 1.061), male sex (HR 2.327), and BVAS (HR 1.100), was independently associated with all-cause mortality during follow-up. In conclusion, this study was the first to demonstrate that the BARD score ≥ 3 at AAV diagnosis could predict all-cause mortality during follow-up in AAV patients.
Anxiety Symptoms, COVID-19-Related Stress Reactions in the Italian General Population, and Validation of the Italian COVID Stress Scales (CSS-I)
Authors: Del Casale Antonio , Modesti Martina Nicole , Lai Carlo , Carola Valeria , Mimun Simone , Bruzzese Alba , Speranza Anna Maria , Drakes Dalainey H. , Asmundson Gordon J. G. , Nicolais Giampaolo
Published: August 2023

Background. The COVID Stress Scales (CSS) assess COVID-related stress experienced in the past week related to danger and contamination fears, socioeconomic consequences, xenophobia, compulsive checking, and reassurance seeking, and traumatic stress symptoms. Our objective was to provide a translation into Italian, replication, and psychometric validation of the CSS in the general population. Moreover, we aimed to test the convergent and discriminant validity of the Italian CSS (CSS-I) with respect to anxiety, stress, and depressive symptoms in the general Italian population. Method. Adult participants (n = 935) over the age of 18 years were recruited from the general population in Italy. Psychological status was assessed using multiple validated measures, including the CSS, Depression, Anxiety and Stress Scales-21 (DASS-21), and the Prejudice Against Immigrants Scale (PAIS). Results. Our confirmatory factor analysis supported a 6-factor model, including danger fears (DAN), socioeconomic consequences (SEC), xenophobia (XEN), compulsive checking and reassurance seeking (CHE), contamination fears (CON), and traumatic stress symptoms (TSS). Strong reliability of the CSS-I (Cronbach’s α = 0.863–0.936) and convergent validity with the DASS-21 and PAI were established with positive correlations between total and scale scores across measures. Conclusions. The CSS-I is a valid and reliable instrument to measure COVID-19-related distress in the Italian population.
Hypertrophic Cardiomyopathy in a Latin American Center: A Single Center Observational Study
Authors: López-Ponce de Leon Juan David , Estacio Mayra , Giraldo Natalia , Escalante Manuela , Rodas Yorlany , Largo Jessica , Lores Juliana , Victoria María Camila , Argote Diana , Florez Noel , Carrillo Diana , Olaya Pastor , Mejia Mauricio , Gomez Juan Esteban
Published: August 2023

Background: Hypertrophic cardiomyopathy (HCM) is a complex disorder that includes various phenotypes, leading to different manifestations. It also shares different disadvantages typical of rare diseases, including limited recognition, lack of prospective studies assessing treatment, and little or delayed access to advanced treatment options. Reliable data about the prevalence and natural history of cardiomyopathies in South America are lacking. This study summarizes the features and management of patients with HCM in a university hospital in Colombia. Methods: This was an observational retrospective cohort study of patients with HCM between January 2010 and December 2021. Patient data were analyzed from an institutional cardiomyopathy registry. Demographic, paraclinical, and outcome data were collected. Results: A total of 82 patients during the study period were enrolled. Of these, 67.1% were male, and the mean age at diagnosis was 49 years. Approximately 83% were in NYHA functional class I and II, and the most reported symptoms were dyspnea (38%), angina (20%), syncope (15%), and palpitations (11%). In addition, 89% had preserved left ventricular ejection fraction (LVEF) with an asymmetric septal pattern in 65%. Five patients (6%) had alcohol septal ablation and four (5%) had septal myectomy. One patient required heart transplantation during follow-up. Sudden cardiovascular death was observed in 2.6%. The overall mortality during follow-up was 7.3%. Conclusions: HCM is a complex and heterogeneous disorder that presents with significant morbidity and mortality. Our registry provides comprehensive data on disease courses and management in a developing country.
The Effects of Tissue Healing Factors in Wound Repair Involving Absorbable Meshes: A Narrative Review
Authors: Vasalou Varvara , Kotidis Efstathios , Tatsis Dimitris , Boulogeorgou Kassiani , Grivas Ioannis , Koliakos Georgios , Cheva Angeliki , Ioannidis Orestis , Tsingotjidou Anastasia , Angelopoulos Stamatis
Published: August 2023

Wound healing is a complex and meticulously orchestrated process involving multiple phases and cellular interactions. This narrative review explores the intricate mechanisms behind wound healing, emphasizing the significance of cellular processes and molecular factors. The phases of wound healing are discussed, focusing on the roles of immune cells, growth factors, and extracellular matrix components. Cellular shape alterations driven by cytoskeletal modulation and the influence of the ‘Formin’ protein family are highlighted for their impact on wound healing processes. This review delves into the use of absorbable meshes in wound repair, discussing their categories and applications in different surgical scenarios. Interleukins (IL-2 and IL-6), CD31, CD34, platelet rich plasma (PRP), and adipose tissue-derived mesenchymal stem cells (ADSCs) are discussed in their respective roles in wound healing. The interactions between these factors and their potential synergies with absorbable meshes are explored, shedding light on how these combinations might enhance the healing process. Recent advances and challenges in the field are also presented, including insights into mesh integration, biocompatibility, infection prevention, and postoperative complications. This review underscores the importance of patient-specific factors and surgical techniques in optimizing mesh placement and healing outcomes. As wound healing remains a dynamic field, this narrative review provides a comprehensive overview of the current understanding and potential avenues for future research and clinical applications.
Role of Absorbable Polysaccharide Hemostatic Powder in the Prevention of Bleeding and Wound Events after Thyroid Surgery
Authors: Docimo Giovanni , Filograna Pignatelli Marcello , Ferrandes Sonia , Monaco Alessandro , Calisti Francesco , Ruggiero Roberto , Tolone Salvatore , Lucido Francesco , Brusciano Luigi , Parisi Simona , Conzo Giovanni , Docimo Ludovico , Gambardella Claudio
Published: August 2023

Background: Bleeding is one of the most fearsome and life-threatening complications after thyroid surgery. Several medical devices and haemostatic agents have been proposed to improve haemostasis during total and hemi-thyroidectomy. Resorbable polysaccharide powder (HaemoCer™) is a plant-based polymer that is helpful in terms of the coagulation cascade becoming a gel and forming a barrier to prevent further bleeding, having tested for haemostasis in different districts. The aim of the current study was the evaluation of drain output, the presence of significant postoperative blood loss and complications in patients treated with or without resorbable polysaccharide powder during thyroid surgery. Methods: From January to December 2022, postoperative bleeding, drainage output and the postoperative wound events of patients undergoing thyroid surgery, in a tertiary centre, with haemostasis completion with resorbable polysaccharide powder (Group A) or not (Group B), were retrospectively analysed. Results: Eighty-one patients in Group A received a haemostasis improvement with the use of reabsorbable polysaccharide powder, and 96 patients in Group B received thyroid surgery alone. Patients in Group A presented lower drainage output (0.005), lower incidence of neck haematoma (0.005) and seroma (0.021), confirmed also by multivariate analysis. Conclusions: The resorbable polysaccharide powder, in the current series, appeared to be an effective agent in achieving haemostasis in thyroidectomies, reducing the postoperative drainage output, and also neck events such as neck haematoma and seroma, improving the postoperative comfort of the patients. Further larger comparative studies are needed to address this issue.
Missed Opportunities in Implementation and Optimization of Lipid-Lowering Therapies in Very-High-Risk Patients Presenting with ST-Segment Elevation Myocardial Infarction
Authors: Kopp Kristen , Motloch Lukas , Berezin Alexander , Maringgele Victoria , Ostapenko Halyna , Mirna Moritz , Schmutzler Lukas , Dieplinger Anna , Hoppe Uta C. , Lichtenauer Michael
Published: August 2023

The aim of this retrospective study was to provide real-world data on lipid-lowering therapy (LLT) implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in an ST-segment elevation myocardial infarction (STEMI) population, with a focus on very-high-risk patients according to European guidelines criteria. Methods: Included were all STEMI patients with available LDL-C and total cholesterol treated at a large tertiary center in Salzburg, Austria, 2018–2020 (n = 910), with stratification into very-high-risk cohorts. Analysis was descriptive, with variables reported as number, percentages, median, and interquartile range. Results: Among patients with prior LLT use, statin monotherapy predominated, 5.3% were using high-intensity statins, 1.2% were using combined ezetimibe therapy, and none were taking PCSK9 inhibitors at the time of STEMI. In very-high-risk secondary prevention cohorts, LLT optimization was alarmingly low: 8–22% of patients were taking high-intensity statins, just 0–6% combined with ezetimibe. Depending on the very-high-risk cohort, 27–45% of secondary prevention patients and 58–73% of primary prevention patients were not taking any LLTs, although 19–60% were actively taking/prescribed medications for hypertension and/or diabetes mellitus. Corresponding LDL-C target achievement in all very-high-risk cohorts was poor: <22% of patients had LDL-C values < 55 mg/dL at the time of STEMI. Conclusion: Severe shortcomings in LLT implementation and optimization, and LDL-C target achievement, were observed in the total STEMI population and across all very-high-risk cohorts, attributable in part to deficits in care delivery.
Performance of Prognostic Scoring Systems in MINOCA: A Comparison among GRACE, TIMI, HEART, and ACEF Scores
Authors: Fedele Damiano , Canton Lisa , Bodega Francesca , Suma Nicole , Tattilo Francesco , Impellizzeri Andrea , Amicone Sara , Di Iuorio Ornella , Ryabenko Khrystyna , Armillotta Matteo , Sansonetti Angelo , Stefanizzi Andrea , Cavallo Daniele , Casuso Marcello , Bertolini Davide , Lovato Luigi , Gallinoro Emanuele , Belmonte Marta , Rinaldi Andrea , Angeli Francesco , Casella Gianni , Foà Alberto , Bergamaschi Luca , Paolisso Pasquale , Pizzi Carmine
Published: August 2023

Background: the prognosis of patients with myocardial infarction with non-obstructive coronary arteries (MINOCA) is not benign; thus, prompting the need to validate prognostic scoring systems for this population. Aim: to evaluate and compare the prognostic performance of GRACE, TIMI, HEART, and ACEF scores in MINOCA patients. Methods: A total of 250 MINOCA patients from January 2017 to September 2021 were included. For each patient, the four scores at admission were retrospectively calculated. The primary outcome was a composite of all-cause death and acute myocardial infarction (AMI) at 1-year follow-up. The ability to predict 1-year all-cause death was also tested. Results: Overall, the tested scores presented a sub-optimal performance in predicting the composite major adverse event in MINOCA patients, showing an AUC ranging between 0.7 and 0.8. Among them, the GRACE score appeared to be the best in predicting all-cause death, reaching high specificity with low sensitivity. The best cut-off identified for the GRACE score was 171, higher compared to the cut-off of 140 generally applied to identify high-risk patients with obstructive AMI. When the scores were tested for prediction of 1-year all-cause death, the GRACE and the ACEF score showed very good accuracy (AUC = 0.932 and 0.828, respectively). Conclusion: the prognostic scoring tools, validated in AMI cohorts, could be useful even in MINOCA patients, although their performance appeared sub-optimal, prompting the need for risk assessment tools specific to MINOCA patients.
Factors Influencing Postoperative Complications Following Minimally Invasive Ivor Lewis Esophagectomy: A Retrospective Cohort Study
Authors: Peters Antje K. , Juratli Mazen A. , Roy Dhruvajyoti , Merten Jennifer , Fortmann Lukas , Pascher Andreas , Hoelzen Jens Peter
Published: August 2023

Background: Complications arising following minimally invasive Ivor Lewis esophagectomy often result from inadequate enteral nutrition, highlighting the need for proactive measures to prevent such issues. One approach involves identifying high-risk cases prone to complications and implementing percutaneous endoscopic jejunostomy (PEJ) tube placement during esophageal resection to ensure timely enteral nutrition. Methods: In this single-center, retrospective cohort study, we examined patients who underwent minimally invasive esophagectomy for esophageal cancer at a high-volume center. The dataset encompassed demographic information, comorbidities, laboratory parameters, and intraoperative details. Our center utilized the EndoVac system pre-emptively to safeguard the anastomosis from harmful secretions and to enhance local oxygen partial pressure. All patients received pre-emptive EndoVac therapy and underwent esophagogastroduodenoscopy in the early postoperative days. The need for multiple postoperative EndoVac cycles indicated complications, including anastomotic insufficiency and subsequent requirement for a PEJ. The primary objectives were identifying predictive factors for anastomotic insufficiency and the need for multi-cycle EndoVac therapy, quantifying their effects, and assessing the likelihood of postoperative complications. Results: 149 patients who underwent minimally invasive or hybrid Ivor Lewis esophagectomy were analyzed and 21 perioperative and demographic features were evaluated. Postoperative complications were associated with the body mass index (BMI) category, the use of blood pressure medication, and surgery duration. Anastomotic insufficiency as a specific complication was correlated with BMI and the Charlson comorbidity index. The odds ratio of being in the high-risk group significantly increased with higher BMI (OR = 1.074, p = 0.048) and longer surgery duration (OR = 1.005, p = 0.004). Conclusions: Based on our findings, high BMI and longer surgery duration are potential risk factors for postoperative complications following minimally invasive esophagectomy. Identifying such factors can aid in pre-emptively addressing nutritional challenges and reducing the incidence of complications in high-risk patients.