bluuebunny/crossref_metadata_2025 huggingface dataset:
Assays of CFTR Function In Vitro, Ex Vivo and In Vivo
Authors: Ramalho Anabela S. , Boon Mieke , Proesmans Marijke , Vermeulen François , Carlon Marianne S. , Boeck Kris
Published: January 2022

Cystic fibrosis, a multi-organ genetic disease, is characterized by abnormal function of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a chloride channel at the apical membrane of several epithelia. In recent years, therapeutic strategies have been developed to correct the CFTR defect. To evaluate CFTR function at baseline for diagnosis, or the efficacy of CFTR-restoring therapy, reliable tests are needed to measure CFTR function, in vitro, ex vivo and in vivo. In vitro techniques either directly or indirectly measure ion fluxes; direct measurement of ion fluxes and quenching of fluorescence in cell-based assays, change in transmembrane voltage or current in patch clamp or Ussing chamber, swelling of CFTR-containing organoids by secondary water influx upon CFTR activation. Several cell or tissue types can be used. Ex vivo and in vivo assays similarly evaluate current (intestinal current measurement) and membrane potential differences (nasal potential difference), on tissues from individual patients. In the sweat test, the most frequently used in vivo evaluation of CFTR function, chloride concentration or stimulated sweat rate can be directly measured. Here, we will describe the currently available bio-assays for quantitative evaluation of CFTR function, their indications, advantages and disadvantages, and correlation with clinical outcome measures.
Male Rat Offspring Are More Impacted by Maternal Obesity Induced by Cafeteria Diet than Females—Additive Effect of Postweaning Diet
Authors: Tajaddini Aynaz , Kendig Michael D. , Prates Kelly V. , Westbrook R. Frederick , Morris Margaret J.
Published: January 2022

Maternal obesity increases the risk of health complications in offspring, but whether these effects are exacerbated by offspring exposure to unhealthy diets warrants further investigation. Female Sprague-Dawley rats were fed either standard chow (n = 15) or ‘cafeteria’ (Caf, n = 21) diets across pre-pregnancy, gestation, and lactation. Male and female offspring were weaned onto chow or Caf diet (2–3/sex/litter), forming four groups; behavioural and metabolic parameters were assessed. At weaning, offspring from Caf dams were smaller and lighter, but had more retroperitoneal (RP) fat, with a larger effect in males. Maternal Caf diet significantly increased relative expression of ACACA and Fasn in male and female weanling liver, but not CPT-1, SREBP and PGC1; PPARα was increased in males from Caf dams. Maternal obesity enhanced the impact of postweaning Caf exposure on adult body weight, RP fat, liver mass, and plasma leptin in males but not females. Offspring from Caf dams appeared to exhibit reduced anxiety-like behaviour on the elevated plus maze. Hepatic CPT-1 expression was reduced only in adult males from Caf fed dams. Post weaning Caf diet consumption did not alter liver gene expression in the adult offspring. Maternal obesity exacerbated the obesogenic phenotype produced by postweaning Caf diet in male, but not female offspring. Thus, the impact of maternal obesity on adiposity and liver gene expression appeared more marked in males. Our data underline the sex-specific detrimental effects of maternal obesity on offspring.
Systemic Lectin-Glycan Interaction of Pathogenic Enteric Bacteria in the Gastrointestinal Tract
Authors: Cho Seung-Hak , Park Jun-young , Kim Cheorl-Ho
Published: January 2022

Microorganisms, such as bacteria, viruses, and fungi, and host cells, such as plants and animals, have carbohydrate chains and lectins that reciprocally recognize one another. In hosts, the defense system is activated upon non-self-pattern recognition of microbial pathogen-associated molecular patterns. These are present in Gram-negative and Gram-positive bacteria and fungi. Glycan-based PAMPs are bound to a class of lectins that are widely distributed among eukaryotes. The first step of bacterial infection in humans is the adhesion of the pathogen’s lectin-like proteins to the outer membrane surfaces of host cells, which are composed of glycans. Microbes and hosts binding to each other specifically is of critical importance. The adhesion factors used between pathogens and hosts remain unknown; therefore, research is needed to identify these factors to prevent intestinal infection or treat it in its early stages. This review aims to present a vision for the prevention and treatment of infectious diseases by identifying the role of the host glycans in the immune response against pathogenic intestinal bacteria through studies on the lectin-glycan interaction.
A Self-Standing Binder-Free Biomimetic Cathode Based on LMO/CNT Enhanced with Graphene and PANI for Aqueous Rechargeable Batteries
Authors: Bubulinca Constantin , Sapurina Irina , Kazantseva Natalia E. , Pechancova Viera , Saha Petr
Published: January 2022

The electrochemical parameters of a novel binder-free self-standing biomimetic cathode based on lithium manganese oxide (LMO) and carbon nanotubes (CNT) for rechargeable Lithium-ion aqueous batteries (ReLIAB) are improved using polyaniline (PANI) core-shell in situ polymerization and graphene (Gr). The fabricated cathode material exhibits the so-called “tectonic plate island bridge” biomimetic structure. This constitution is created by combining three components as shown by a SEM and a TEM analysis: the Gr substrates support an entangled matrix of conductive CNT which connect island of non-conductive inorganic material composed of LMO. The typical spinel structure of the LMO remains unchanged after modifying the basic structure with Gr and PANI due to a simplified hydrothermal method used for synthesis. The Gr and PANI core-shell coating improves the electric conductivity from 0.0025 S/cm up to 1 S/cm. The electrochemical performances of the LMO/CNT-Gr/PANI composite electrode are optimized up to 136 mA h g−1 compared to 111 mA h g−1 of the LMO/CNT. Besides that, the new electrode shows good cycling stability after 200 galvanostatic charging/discharging cycles, making this structure a future candidate for cathode materials for ReLIAB.
Current Knowledge about the New Drug Firibastat in Arterial Hypertension
Authors: Hansen Emma , Grimm Daniela , Wehland Markus
Published: January 2022

Hypertension significantly increases the risk of cardiovascular disease. Currently, effective standard pharmacological treatment is available in the form of diuretics, ACE inhibitors, angiotensin II receptor blockers and calcium channel blockers. These all help to decrease blood pressure in hypertensive patients, each with their own mechanism. Recently, firibastat, a new first-in-class antihypertensive drug has been developed. Firibastat is a prodrug that when crossing the blood-brain barrier, is cleaved into two active EC33 molecules. EC33 is the active molecule that inhibits the enzyme aminopeptidase A. Aminopeptidase A converts angiotensin II to angiotensin III. Angiotensin III usually has three central mechanisms that increase blood pressure, so by inhibiting this enzyme activity, a decrease in blood pressure is seen. Firibastat is an antihypertensive drug that affects the brain renin angiotensin system by inhibiting aminopeptidase A. Clinical trials with firibastat have been performed in animals and humans. No severe adverse effects related to firibastat treatment have been reported. Results from studies show that firibastat is generally well tolerated and safe to use in hypertensive patients. The aim of this review is to investigate the current knowledge about firibastat in the treatment of hypertension.
Mitochondrial Genome Editing to Treat Human Osteoarthritis—A Narrative Review
Authors: Zhong Gang , Madry Henning , Cucchiarini Magali
Published: January 2022

Osteoarthritis (OA) is a severe, common chronic orthopaedic disorder characterised by a degradation of the articular cartilage with an incidence that increases over years. Despite the availability of various clinical options, none can stop the irreversible progression of the disease to definitely cure OA. Various mutations have been evidenced in the mitochondrial DNA (mtDNA) of cartilage cells (chondrocytes) in OA, leading to a dysfunction of the mitochondrial oxidative phosphorylation processes that significantly contributes to OA cartilage degeneration. The mitochondrial genome, therefore, represents a central, attractive target for therapy in OA, especially using genome editing procedures. In this narrative review article, we present and discuss the current advances and breakthroughs in mitochondrial genome editing as a potential, novel treatment to overcome mtDNA-related disorders such as OA. While still in its infancy and despite a number of challenges that need to be addressed (barriers to effective and site-specific mtDNA editing and repair), such a strategy has strong value to treat human OA in the future, especially using the groundbreaking clustered regularly interspaced short palindromic repeats (CRIPSR)/CRISPR-associated 9 (CRISPR/Cas9) technology and mitochondrial transplantation approaches.
Fine Mapping and Candidate Gene Prediction of Tuber Shape Controlling Ro Locus Based on Integrating Genetic and Transcriptomic Analyses in Potato
Authors: Fan Guiyan , Wang Qianru , Xu Jianfei , Chen Na , Zhu Wenwen , Duan Shaoguang , Yang Xiaohui , De Jong Walter S. , Guo Yangdong , Jin Liping , Li Guangcun
Published: January 2022

Tuber shape is one of the most important quality traits in potato appearance. Since poor or irregular shape results in higher costs for processing and influences the consumers’ willingness to purchase, breeding for shape uniformity and shallow eye depth is highly important. Previous studies showed that the major round tuber shape controlling locus, the Ro locus, is located on chromosome 10. However, fine mapping and cloning of tuber shape genes have not been reported. In this study, the analyses of tissue sectioning and transcriptome sequencing showed that the developmental differences between round and elongated tuber shapes begin as early as the hook stage of the stolon. To fine map tuber shape genes, a high-density genetic linkage map of the Ro region on chromosome 10 based on a diploid segregating population was constructed. The total length of the genetic linkage map was 25.8 cM and the average marker interval was 1.98 cM. Combined with phenotypic data collected from 2014 to 2017, one major quantitative trait locus (QTL) for tuber shape was identified, which explained 61.7–72.9% of the tuber shape variation. Through the results of genotyping and phenotypic investigation of recombinant individuals, Ro was fine mapped in a 193.43 kb interval, which contained 18 genes. Five candidate genes were preliminarily predicted based on tissue sections and transcriptome sequencing. This study provides an important basis for cloning Ro gene(s).
Transport Turnover Rates for Human OCT2 and MATE1 Expressed in Chinese Hamster Ovary Cells
Authors: Zhang Xiaohong , Wright Stephen H.
Published: January 2022

MATE1 (multidrug and toxin extruder 1) and OCT2 (organic cation transporter 2) play critical roles in organic cation excretion by the human kidney. The transporter turnover rate (TOR) is relevant to understanding both their transport mechanisms and interpreting the in vitro–in vivo extrapolation (IVIVE) required for physiologically-based pharmacokinetic (PBPK) modeling. Here, we use a quantitative western blot method to determine TORs for MATE1 and OCT2 proteins expressed in CHO cells. MATE1 and OCT2, each with a C-terminal V-5 epitope tag, were cell surface biotinylated and the amount of cell surface MATE1 and OCT2 protein was quantified by western analysis, using standard curves for the V5 epitope. Cell surface MATE1 and OCT2 protein represented 25% and 24%, respectively, of the total expression of these proteins in CHO cells. The number of cell surface transporters was ~55 fmol cm−2 for MATE1 and ~510 fmol cm−2 for OCT2. Dividing these values into the different Jmax values for transport of MPP, metformin, and atenolol mediated by MATE1 and OCT2 resulted in calculated TOR values (±SE, n = 4) of 84.0 ± 22.0 s−1 and 2.9 ± 0.6 s−1; metformin, 461.0 ± 121.0 s−1 and 12.6 ± 2.4 s−1; atenolol, 118.0 ± 31.0 s−1, respectively. These values are consistent with the TOR values determined for a variety of exchangers (NHEs), cotransporters (SGLTs, Lac permease), and uniporters (GLUTs, ENTs).
BMP9-ID1 Signaling Activates HIF-1α and VEGFA Expression to Promote Tumor Angiogenesis in Hepatocellular Carcinoma
Authors: Chen Han , Nio Kouki , Tang Hong , Yamashita Taro , Okada Hikari , Li Yingyi , Doan Phuong Thi Bich , Li Ru , Lv Junyan , Sakai Yoshio , Yamashita Tatsuya , Mizukoshi Eishiro , Honda Masao , Kaneko Shuichi
Published: January 2022

Since hepatocellular carcinoma (HCC) is a typical hypervascular malignant tumor with poor prognosis, targeting angiogenesis is an important therapeutic strategy for advanced HCC. Involvement of bone morphologic protein 9 (BMP9), a transforming growth factor-beta superfamily member, has recently been reported in the development of liver diseases and angiogenesis. Here, we aimed to elucidate the role of BMP9 signaling in promoting HCC angiogenesis and to assess the antiangiogenic effect of BMP receptor inhibitors in HCC. By analyzing HCC tissue gene expression profiles, we found that BMP9 expression was significantly correlated with angiogenesis-associated genes, including HIF-1α and VEGFR2. In vitro, BMP9 induced HCC cell HIF-1α/VEGFA expression and VEGFA secretion. Silencing of the inhibitor of DNA-binding protein 1 (ID1), a transcription factor targeted by BMP9 signaling, suppressed BMP9-induced HIF-1α/VEGFA expression and VEGFA secretion, resulting in decreased human umbilical vein endothelial cell (HUVEC) lumen formation. BMP receptor inhibitors, which inhibit BMP9-ID1 signaling, suppressed BMP9-induced HIF-1α/VEGFA expression, VEGFA secretion, and HUVEC lumen formation. In vivo, the BMP receptor inhibitor LDN-212854 successfully inhibited HCC tumor growth and angiogenesis by inhibiting BMP9-ID1 signaling. In summary, BMP9-ID1 signaling promotes HCC angiogenesis by activating HIF-1α/VEGFA expression. Thus, targeting BMP9-ID1 signaling could be a pivotal therapeutic option for advanced HCC.
Organ-Specific Endothelial Cell Differentiation and Impact of Microenvironmental Cues on Endothelial Heterogeneity
Authors: Gifre-Renom Laia , Daems Margo , Luttun Aernout , Jones Elizabeth A. V.
Published: January 2022

Endothelial cells throughout the body are heterogeneous, and this is tightly linked to the specific functions of organs and tissues. Heterogeneity is already determined from development onwards and ranges from arterial/venous specification to microvascular fate determination in organ-specific differentiation. Acknowledging the different phenotypes of endothelial cells and the implications of this diversity is key for the development of more specialized tissue engineering and vascular repair approaches. However, although novel technologies in transcriptomics and proteomics are facilitating the unraveling of vascular bed-specific endothelial cell signatures, still much research is based on the use of insufficiently specialized endothelial cells. Endothelial cells are not only heterogeneous, but their specialized phenotypes are also dynamic and adapt to changes in their microenvironment. During the last decades, strong collaborations between molecular biology, mechanobiology, and computational disciplines have led to a better understanding of how endothelial cells are modulated by their mechanical and biochemical contexts. Yet, because of the use of insufficiently specialized endothelial cells, there is still a huge lack of knowledge in how tissue-specific biomechanical factors determine organ-specific phenotypes. With this review, we want to put the focus on how organ-specific endothelial cell signatures are determined from development onwards and conditioned by their microenvironments during adulthood. We discuss the latest research performed on endothelial cells, pointing out the important implications of mimicking tissue-specific biomechanical cues in culture.
Diabetic Retinopathy: From Animal Models to Cellular Signaling
Authors: Pitale Priyamvada M. , Gorbatyuk Marina S.
Published: January 2022

Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM), a metabolic disorder characterized by elevation in blood glucose level. The pathogenesis of DR includes vascular, neuronal, and inflammatory components leading to activation of complex cellular molecular signaling. If untreated, the disease can culminate in vision loss that eventually leads to blindness. Animal models mimicking different aspects of DM complications have been developed to study the development and progression of DR. Despite the significant contribution of the developed DR models to discovering the mechanisms of DR and the recent achievements in the research field, the sequence of cellular events in diabetic retinas is still under investigation. Partially, this is due to the complexity of molecular mechanisms, although the lack of availability of models that adequately mimic all the neurovascular pathobiological features observed in patients has also contributed to the delay in determining a precise molecular trigger. In this review, we provide an update on the status of animal models of DR to help investigators choose an appropriate system to validate their hypothesis. We also discuss the key cellular and physiological events of DR in these models.
An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability
Authors: Ou Keng-Liang , Huang Chiung-Fang , Lan Wen-Chien , Huang Bai-Hung , Pan Hsu-An , Shen Yung-Kang , Saito Takashi , Tsai Hsin-Yu , Cho Yung-Chieh , Hung Kuo-Sheng , Chou Hsin-Hua
Published: January 2022

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.
Translation Alignment with Ugarit
Authors: Yousef Tariq , Palladino Chiara , Shamsian Farnoosh , Foradi Maryam
Published: January 2022

Ugarit is a public web-based tool for manual annotation of parallel texts for generating word-level translation alignment. We aimed to develop a user-friendly interactive interface to visualize aligned texts and collect training data in the form of translation pairs to be used later, (i) for training an automatic translation alignment system for historical languages at the word/phrase level, (ii) as a gold standard to evaluate automatic alignment and machine translation systems. Ugarit is now widely used for learning new languages, especially historical languages, and as a reading environment for parallel texts. In the following sections, we present the related works and similar projects; then, we give an overview of the visualization techniques used to present the alignment results. Further, we explain how we could derive the translation graph from the aligned translation pairs. Finally, we discuss the usage limitations of Ugarit, possible improvements, and future development plans.
Effects of Wolf Spiders’ Captive Environment on Their Locomotor and Exploratory Behaviours
Authors: Trabalon Marie
Published: January 2022

Here I detail the effects of the abiotic/captive environment of an adult wandering spider, Pardosa saltans (Lycosidae) on its behaviour. These studies focused on spiders collected as adults in their natural environment and spiders developed in the laboratory under controlled conditions. Wild-caught spiders were tested either immediately after capture or after being housed for 15 days post-collection. Laboratory reared spiders were kept in different environments: small or large space combined with the presence or absence of litter. Two tests evaluated by sex show the influence of these rearing conditions: an open-field test and a radial-arm maze test. The results show that wild caught spiders of both sexes tested immediately after capture weighed significantly less and were significantly more active than spiders housed in the laboratory for 15 days and spiders reared in the laboratory. Laboratory conditions induced a positive impact on body mass and negative impact on behaviour activities. The locomotor and exploratory activities of spiders of both sexes kept in container without substrate showed lower. My results suggest that the physical enrichment of the environment can reduce these negative effects for females, but not for males that seem to be more affected by being reared under controlled conditions.
Adaptive Mechanisms of Renal Bile Acid Transporters in a Rat Model of Carbon Tetrachloride-Induced Liver Cirrhosis
Authors: Donadei Chiara , Angeletti Andrea , Cappuccilli Maria , Conti Massimiliano , Conte Diletta , Zappulo Fulvia , De Giovanni Alessio , Malvi Deborah , Aldini Rita , Roda Aldo , La Manna Gaetano
Published: January 2022

Background: Acute kidney injury (AKI) is common in advanced liver cirrhosis, a consequence of reduced kidney perfusion due to splanchnic arterial vasodilation and intrarenal vasoconstriction. It clinically manifests as hepatorenal syndrome type 1, type 2, or as acute tubular necrosis. Beyond hemodynamic factors, an additional mechanism may be hypothesized to explain the renal dysfunction during liver cirrhosis. Recent evidence suggest that such mechanisms may be closely related to obstructive jaundice. Methods: Given the not completely elucidated role of bile acids in kidney tissue damage, this study developed a rat model of AKI with liver cirrhosis induction by carbon tetrachloride (CCl4) inhalation for 12 weeks. Histological analyses of renal and liver biopsies were performed at sacrifice. Organic anion tubular transporter distribution and apoptosis in kidney cells were analyzed by immunohistochemistry. Circulating and urinary markers of inflammation and tubular injury were assayed in 21 treated rats over time (1, 2, 4, 8, and 12 weeks of CCl4 administration) and 5 controls. Results: No renal histopathological alterations were found at sacrifice. Comparing treated rats with controls, organic anion transporters were differentially expressed and localized. High serum bile acid values were detected in cirrhotic animals, while caspase-3 staining was negative in both groups. Increased levels of serum inflammatory and urinary tubular injury biomarkers were observed during cirrhosis progression, with a peak after 4 and 8 weeks of treatment. Conclusions: These findings suggest possible adaptive tubular mechanisms for bile acid transporters in response to cirrhosis-induced AKI.
Exhaled Nitric Oxide Level in Pharynx Angioedema
Authors: Moos Łukasz , Zajac Magdalena , Brzoza Zenon
Published: January 2022

Airway inflammation is related to increased nitric oxide production. It can be assessed noninvasively with exhaled nitric oxide measurement. As airway inflammation was supposed to be present in chronic urticaria and angioedema patients we hypothesized increased exhaled nitric oxide in this group. Twenty-six symptomatic chronic urticaria patients with an acute episode of pharynx angioedema (17 women and 9 men, median age 35) were included in the study group. None of the patients reported a history of asthma, allergic rhinitis or cigarette smoking. The control group consisted of 29 non-smoking healthy subjects (19 women and 10 men, median age 22) without any history of atopy. Exhaled nitric oxide measurement was performed in all subjects. Exhaled nitric oxide levels in the angioedema group did not differ statistically significantly from those detected in healthy subjects (15.5 ppb and 17.0 ppb respectively). Our results indicate the lack of airway inflammation in chronic urticaria patients with pharynx angioedema.
Genetic Factors of Idiopathic Gigantomastia: Clinical Implications of Aromatase and Progesterone Receptor Polymorphisms
Authors: Kasielska-Trojan Anna , Pietrusiński Michał , Bugaj-Tobiasz Magdalena , Strużyna Jerzy , Borowiec Maciej , Antoszewski Bogusław
Published: January 2022

The role of estrogen, progesterone, their receptors and aromatase in the development of the breast is well documented. In this study we examined the association of genetic variants of progesterone receptor (PGR) and aromatase (CYP19A1) genes with gigantomastia risk. We conducted a case-control study among 124 women: 60 with gigantomastia and 64 controls. We examined the single nucleotide polymorphisms (SNPs) for CYP19A1 (rs749292 and rs7172156) and PGR (rs1042838). Our results showed that allele G in rs749292 (CYP19A1) increased the risk of gigantomastia, but not significantly (p = 0.09). There is a correlation between rs1042838 (PGR) and waist-to-hip ratio (WHR) in women with gigantomastia-AC genotype correlates with lower WHR and CC with higher WHR. There were no correlations between the onset of gigantomastia, the age of menarche and the length of the menstrual cycle, and rs1042838, rs749292 and rs7172156. We did not find differences in the SNP of PGR (rs1042838) between women with gigantomastia and controls. However, our findings showed more frequent G allele in CYP19A1 (rs749292) in women with gigantomastia.
Association between Duration of Deep Hypothermic Circulatory Arrest and Surgical Outcome in Patients with Acute Type A Aortic Dissection: A Large Retrospective Cohort Study
Authors: Salehi Ravesh Mona , Friedrich Christine , Schoettler Jan , Hummitzsch Lars , Elke Gunnar , Salem Mohamed , Lutter Georg , Puehler Thomas , Cremer Jochen , Haneya Assad
Published: January 2022

(1) Background: Deep hypothermic circulatory arrest (DHCA) with selective antegrade cerebral perfusion (ACP) is an established cerebral protection technique for the conduction of complex surgical procedures involving the aortic arch. It is controversial whether the duration of DHCA is associated with adverse outcome in patients with acute type A aortic dissection (AAAD). Our goal was to investigate whether DHCA time was associated with surgical outcome in patients undergoing a surgical treatment of AAAD. (2) Methods: A total of 410 patients were divided into two groups based on the DHCA time less than 60 min and equal to or longer than 60 min. (3) Results: Patients with longer DHCA times were significantly younger (p = 0.001). Intraoperatively, complex procedures with aortic arch surgery were more common in patients with longer DHCA times (p < 0.001). Accordingly, cardiopulmonary bypass (p < 0.001), cross-clamping (p < 0.001) and DHCA times (p < 0.001) were significantly longer in this group. Postoperatively, only the duration of mechanical ventilation (p < 0.001) and the rate of tracheotomy were significantly higher in these patients. Thirty-day mortality was satisfactory for both groups (p = 0.746). (4) Conclusions: Our results showed that improvements in perioperative management including ACP allow for the successful performance of surgical treatment of AAAD under DHCA with a duration of even longer than 60 min.
Urine Protein/Creatinine Ratio in Thrombotic Microangiopathies: A Simple Test to Facilitate Thrombotic Thrombocytopenic Purpura and Hemolytic and Uremic Syndrome Diagnosis
Authors: Burguet Laure , Taton Benjamin , Prezelin-Reydit Mathilde , Rubin Sébastien , Picard Walter , Gruson Didier , Ryman Anne , Contin-Bordes Cécile , Coppo Paul , Combe Christian , Delmas Yahsou
Published: January 2022

Background: Early diagnosis of thrombotic thrombocytopenic purpura (TTP) versus hemolytic and uremic syndrome (HUS) is critical for the prompt initiation of specific therapies. Objective: To evaluate the diagnostic performance of the proteinuria/creatininuria ratio (PU/CU) for TTP versus HUS. Patients/Methods: In a retrospective study, in association with the “French Score” (FS) (platelets < 30 G/L and serum creatinine level < 200 µmol/L), we assessed PU/CU for the diagnosis of TTP in patients above the age of 15 with thrombotic microangiopathy (TMA). Patients with a history of kidney disease or with on-going cancer, allograft or pregnancy were excluded from the analysis. Results: Between February 2011 and April 2019, we identified 124 TMA. Fifty-six TMA patients for whom PU/CU were available, including 35 TTP and 21 HUS cases, were considered. Using receiver–operating characteristic curves (ROC), those with a threshold of 1.5 g/g for the PU/CU had a 77% sensitivity (95% CI (63, 94)) and a 90% specificity (95% CI (71, 100)) for TTP diagnosis compared with those having an 80% sensitivity (95% CI (66, 92)) and a 90% specificity (95% CI (76, 100) with a FS of 2. In comparison, a composite score, defined as a FS of 2 or a PU/CU ≤ 1.5 g/g, improved sensitivity to 99.6% (95% CI (93, 100)) for TTP diagnosis and enabled us to reclassify seven false-negative TTP patients. Conclusions: The addition of urinary PU/CU upon admission of patients with TMA is a fast and readily available test that can aid in the differential diagnosis of TTP versus HUS alongside traditional scoring.
Magnetic Resonance for Differential Diagnosis of Left Ventricular Hypertrophy: Diagnostic and Prognostic Implications
Authors: Aquaro Giovanni Donato , Corsi Elisabetta , Todiere Giancarlo , Grigoratos Crysanthos , Barison Andrea , Barra Valerio , Di Bella Gianluca , Emdin Michele , Ricci Fabrizio , Pingitore Alessandro
Published: January 2022

Background: Left ventricular hypertrophy (LVH) may be due to different causes, ranging from benign secondary forms to severe cardiomyopathies. Transthoracic Echocardiography (TTE) and ECG are the first-level examinations for LVH diagnosis. Cardiac magnetic resonance (CMR) accurately defines LVH type, extent and severity. Objectives: to evaluate the diagnostic and prognostic role of CMR in patients with TTE and/or ECG evidence of LVH. Methods: We performed CMR in 300 consecutive patients with echocardiographic and/or ECG signs of LVH. Results: Overall, 275 patients had TTE evidence of LVH, with initial suspicion of hypertrophic cardiomyopathy (HCM) in 132 (44%), cardiac amyloidosis in 41 (14%), hypertensive LVH in 48 (16%), aortic stenosis in 4 (1%), and undetermined LVH in 50 (16%). The initial echocardiographic diagnostic suspicion of LVH was confirmed in 172 patients (57.3%) and changed in 128 patients (42.7%, p < 0.0001): the diagnosis of HCM increased from 44% to 71% of patients; hypertensive and undetermined LVH decreased significantly (respectively to 4% and 5%). CMR allowed for a diagnosis in 41 out of 50 (82%) patients with undetermined LVH at TTE. CMR also identified HCM in 17 out of 25 patients with apparently normal echocardiography but with ECG criteria for LVH. Finally, the reclassification of the diagnosis by CMR was associated with a change in survival risk of patients: after CMR reclassification, no events occurred in patients with undetermined or hypertensive LVH. Conclusions: CMR changed echocardiographic suspicion in almost half of patients with LVH. In the subgroup of patients with abnormal ECG, CMR identified LVH (particularly HCM) in 80% of patients. This study highlights the indication of CMR to better characterize the type, extent and severity of LVH detected at echocardiography and suspected with ECG.
Assessment of the Effectiveness of the Sonofeedback Method in the Treatment of Stress Urinary Incontinence in Women—Preliminary Report
Authors: Kołodyńska Gabriela , Zalewski Maciej , Mucha Anna , Andrzejewski Waldemar
Published: January 2022

Urinary incontinence is a common problem that affects postmenopausal women. This ailment has a negative impact on many aspects of life, significantly limiting everyday functioning related to professional work, physical activity or the intimate sphere. The aim of the study was to assess the effectiveness of the sonofeedback method in reducing the severity of urinary incontinence in postmenopausal women with a urinary incontinence problem. A total of 60 patients aged 45–65 with stress urinary incontinence, confirmed by a gynecologist, were qualified for the study. All persons qualified for the study were randomly assigned to study group A (n = 20), comparative B (n = 20) and control C (n = 20). Patients from group A were treated with sonofeedback of the pelvic floor muscles. In group B, the combined electrostimulation method was used with biofeedback training. Group C was a control group in which only the measured parameters were measured at the same time interval as those carried out in groups A and B. In all patients, three times: before the therapy, after the fifth procedure and after the end of the therapy, the incidence and severity of stress urinary incontinence were assessed—Gaudenz questionnaire and the intensity of urinary incontinence—a modified 1 h pad test. The obtained results have an application value giving the possibility of using effective therapy with sonofeedback in women in whom the recommended electrostimulation method cannot be used due to health and behavioral reasons.
Recent Advances in Assessment and Treatment in Kienböck’s Disease
Authors: Chojnowski Karol , Opiełka Mikołaj , Piotrowicz Miłosz , Sobocki Bartosz Kamil , Napora Justyna , Dąbrowski Filip , Piotrowski Maciej , Mazurek Tomasz
Published: January 2022

Kienböck’s disease is a rare disease described as progressive avascular osteonecrosis of the lunate. The typical manifestations include a unilateral reduction in wrist motion with accompanying pain and swelling. Besides recent advances in treatment options, the etiology and pathophysiology of the disease remain poorly understood. Common risk factors include anatomical features including ulnar variance, differences in blood supply, increased intraosseous pressure along with direct trauma, and environmental influence. The staging of Kienböck’s disease depends mainly on radiographic characteristics assessed according to the modified Lichtman scale. The selection of treatment options is often challenging, as radiographic features may not correspond directly to initial clinical symptoms and differ among age groups. At the earliest stages of Kienböck disease, the nonoperative, unloading management is generally preferred. Patients with negative ulnar variance are usually treated with radial shortening osteotomy. For patients with positive or neutral ulnar variance, a capitate shortening osteotomy is a recommended option. One of the most recent surgical techniques used in Stage III Kienböck cases is vascularized bone grafting. One of the most promising procedures is a vascularized, pedicled, scaphoid graft combined with partial radioscaphoid arthrodesis. This technique provides excellent pain management and prevents carpal collapse. In stage IV, salvage procedures including total wrist fusion or total wrist arthroplasty are often required.
Loss of E-Cadherin Staining Continuity in the Trophoblastic Basal Membrane Correlates with Increased Resistance in Uterine Arteries and Proteinuria in Patients with Pregnancy-Induced Hypertension
Authors: Pęksa Marta , Kamieniecki Alexandra , Gabrych Anna , Lew-Tusk Anna , Preis Krzysztof , Świątkowska-Freund Małgorzata
Published: January 2022

Pregnancy-induced hypertension (PIH), especially when complicated with pre-eclampsia (PE), could be a life-threatening complication of pregnancy. Pre-eclampsia is one of the leading causes of perinatal morbidity and mortality in women. Pre-eclampsia is mainly characterized by hypertension and kidney damage with proteinuria. Abnormal placentation and altered structure of the placental barrier are believed to participate in the pathogenesis of pregnancy-induced hypertension, leading to PE. In the current study, we aimed to analyze the immunohistochemical expression pattern of E-cadherin and p120, two markers of epithelial–mesenchymal transition, in placental samples derived from a group of 55 patients with pregnancy-induced hypertension, including pre-eclampsia and 37 healthy pregnant controls. The results were correlated with the presence of an obtained early uterine artery flow notching during diastole on Doppler ultrasound. We observed a higher frequency of discontinuous E-cadherin staining in the basement membrane of syncytiotrophoblast in patients with PIH/PE compared to controls (p < 0.001, Fisher’s exact test). Moreover, the loss of continuity of E-cadherin expression correlated with the presence of a bilateral early diastolic notch on Doppler ultrasound (p < 0.001, Fisher’s exact test) and the presence of proteinuria (p = 0.013, Fisher’s exact test). These findings suggest that E-cadherin contributes to the integrity of the placental barrier, and its loss could be an immunohistochemical marker of PE.
Inter-Observer Agreement between Low-Dose and Standard-Dose CT with Soft and Sharp Convolution Kernels in COVID-19 Pneumonia
Authors: Blokhin Ivan , Gombolevskiy Victor , Chernina Valeria , Gusev Maxim , Gelezhe Pavel , Aleshina Olga , Nikolaev Alexander , Kulberg Nicholas , Morozov Sergey , Reshetnikov Roman
Published: January 2022

Computed tomography (CT) has been an essential diagnostic tool during the COVID-19 pandemic. The study aimed to develop an optimal CT protocol in terms of safety and reliability. For this, we assessed the inter-observer agreement between CT and low-dose CT (LDCT) with soft and sharp kernels using a semi-quantitative severity scale in a prospective study (Moscow, Russia). Two consecutive scans with CT and LDCT were performed in a single visit. Reading was performed by ten radiologists with 3–25 years’ experience. The study included 230 patients, and statistical analysis showed LDCT with a sharp kernel as the most reliable protocol (percentage agreement 74.35 ± 43.77%), but its advantage was marginal. There was no significant correlation between radiologists’ experience and average percentage agreement for all four evaluated protocols. Regarding the radiation exposure, CTDIvol was 3.6 ± 0.64 times lower for LDCT. In conclusion, CT and LDCT with soft and sharp reconstructions are equally reliable for COVID-19 reporting using the “CT 0-4” scale. The LDCT protocol allows for a significant decrease in radiation exposure but may be restricted by body mass index.
Codon Usage Bias in Phytoplankton
Authors: Krasovec Marc , Filatov Dmitry A.
Published: January 2022

Non-random usage of synonymous codons, known as “codon bias”, has been described in many organisms, from bacteria to Drosophila, but little is known about it in phytoplankton. This phenomenon is thought to be driven by selection for translational efficiency. As the efficacy of selection is proportional to the effective population size, species with large population sizes, such as phytoplankton, are expected to have strong codon bias. To test this, we measured codon bias in 215 strains from Haptophyta, Chlorophyta, Ochrophyta (except diatoms that were studied previously), Dinophyta, Cryptophyta, Ciliophora, unicellular Rhodophyta and Chlorarachniophyta. Codon bias is modest in most groups, despite the astronomically large population sizes of marine phytoplankton. The strength of the codon bias, measured with the effective number of codons, is the strongest in Haptophyta and the weakest in Chlorarachniophyta. The optimal codons are GC-ending in most cases, but several shifts to AT-ending codons were observed (mainly in Ochrophyta and Ciliophora). As it takes a long time to reach a new equilibrium after such shifts, species having AT-ending codons show a lower frequency of optimal codons compared to other species. Genetic diversity, calculated for species with more than three strains sequenced, is modest, indicating that the effective population sizes are many orders of magnitude lower than the astronomically large census population sizes, which helps to explain the modest codon bias in marine phytoplankton. This study represents the first comparative analysis of codon bias across multiple major phytoplankton groups.
Behavioral Pattern of Risso’s Dolphin (Grampus griseus) in the Gulf of Taranto (Northern Ionian Sea, Central-Eastern Mediterranean Sea)
Authors: Cipriano Giulia , Carlucci Roberto , Bellomo Stefano , Santacesaria Francesca Cornelia , Fanizza Carmelo , Ricci Pasquale , Maglietta Rosalia
Published: January 2022

Relatively scant information is available on the Risso’s dolphin in comparison to the other species regularly present in the Mediterranean Sea. Recently, its conservation status has been updated to Endangered by the International Union for Conservation of Nature (IUCN) in this Sea. Therefore, the need to increase information on its biology and ecology is even more urgent. This study reports the first preliminary information on the behavioral traits of the species occurring in the Gulf of Taranto (Northern Ionian Sea). Data on predominant behavioral activity states and on a set of group composition variables (group formation, cruising speed, dive duration and interaction between individuals) were collected from April 2019 to September 2021, applying the focal-group protocol with instantaneous scan sampling. Group size, depth and group composition variables were compared between activity states. Results highlight that both the group size and the several variables considered varied significantly depending on activity state. The group size was significantly smaller during feeding than resting and traveling and a characterization in terms of group formation, cruise speed, dive duration and interaction between animals is provided for the different activity states. Moreover, a list of behavioral events which occurred, as well as their relative frequency of distribution among activity states, is reported. Finally, details on the sympatric occurrences between Risso’s and striped dolphins, as well as the repetitive interaction observed between adult individuals and plastic bags floating on the sea surface, are reported and discussed.
Improved In Vitro Anti-Mucorales Activity and Cytotoxicity of Amphotericin B with a Pegylated Surfactant
Authors: Brunet Kévin , Diop Cheikh A. B. , Chauzy Alexia , Prébonnaud Noémie , Marchand Sandrine , Rammaert Blandine , Tewes Frédéric
Published: January 2022

The aim of this study was to evaluate the effect of the combination of amphotericin B (AmB) and various non-ionic surfactants on the anti-Mucorales activity of AmB, the toxicity of the combination on eukaryotic cells and the modification of AmB aggregation states. Checkerboards were performed on five genera of Mucorales (12 strains) using several combinations of different surfactants and AmB. These data were analyzed by an Emax model. The effect of surfactants on the cytotoxic activity of AmB was then evaluated for red blood cells and two eukaryotic cell lines by absorbance and propidium iodide internalization. Finally, the effect of polyethylene glycol (15)-hydroxystearate (PEG15HS) on the aggregation states of AmB was evaluated by UV-visible spectrometry. PEG15HS increased the efficacy of AmB on four of the five Mucorales genera, and MICs of AmB were decreased up to 68-fold for L. ramosa. PEG15HS was the only surfactant to not increase the cytotoxic activity of AmB. Finally, the analysis of AmB aggregation states showed that the increased efficacy of AmB and the absence of toxicity are related to an increase in monomeric and polyaggregated forms of AmB at the detriment of the dimeric form. In conclusion, PEG15HS increases the in vitro efficacy of AmB against Mucorales at low concentration, without increasing its toxicity; this combination could therefore be evaluated in the treatment of mucormycosis.
Frequency and Clinical Features of Candida Bloodstream Infection Originating in the Urinary Tract
Authors: Elbaz Meital , Chikly Amanda , Meilik Ronnie , Ben-Ami Ronen
Published: January 2022

The urinary tract is considered an uncommon source of Candida bloodstream infection (CBSI). We aimed to determine the source of CBSI in hospitalized patients, and to compare clinical and microbiological features of CBSI originating in the urinary tract (U-CBSI) and non-urinary CBSI (NU-CBSI). Of 134 patients with CBSI, 28 (20.8%) met criteria for U-CBSI, 34 (25.3%) had vascular catheter-related CBSI and 21 (15.6%) had a gastrointestinal origin. Compared to NU-CBSI patients, patients with U-CBSI were older with higher rates of dementia. Bladder catheterization for urinary retention and insertion of ureteral stents or nephrostomies were risk factors for U-CBSI. Fifty percent of U-CBSI cases occurred within 48 h of hospital admission, versus 16.9% of NU-CBSI (p < 0.0001). The mortality rate was lowest for CBSI originating in the urinary tract and highest for CBSI of undetermined origin. CBSI of undetermined origin remained associated with higher mortality in a Cox regression model that included age, Candida species, Pitt bacteremia score and neutropenia as explanatory variables. U-CBSI may be increasing in frequency, reflecting extensive use of bladder catheters and urologic procedures in elderly debilitated patients. Distinct clinical features are relevant to the diagnosis, treatment and prevention of U-CBSI.
Lactate and Lactate-to-Pyruvate Ratio in Critically Ill COVID-19 Patients: A Pilot Study
Authors: Vassiliou Alice G. , Tsipilis Stamatios , Keskinidou Chrysi , Vrettou Charikleia S. , Jahaj Edison , Gallos Parisis , Routsi Christina , Orfanos Stylianos E. , Kotanidou Anastasia , Dimopoulou Ioanna
Published: January 2022

A limited number of coronavirus disease-19 (COVID-19) cases may require treatment in an intensive care unit (ICU). Arterial blood lactate levels are routinely measured in the ICU to estimate disease severity, predict poor outcomes, and monitor therapeutic handlings. A number of studies have suggested that, simultaneously with lactate, pyruvate should also be measured, providing augmented prognostic ability, and a better understanding of the underlying metabolic alterations in ICU patients. Hence, the aim of the present study was to elucidate the relationship between lactate levels and the lactate-to-pyruvate (LP) ratio with the clinical outcome in mechanically ventilated COVID-19 patients. Lactate and pyruvate were serially measured during the first 24 h of ICU stay. A group of ICU non-COVID-19 patients was used as a comparison group. The majority of COVID-19 patients (82.5%) had normal lactate levels and a normal LP ratio on ICU admission (normal metabolic pattern). A small, yet significant, percentage of patients had either elevated lactate levels or a high LP ratio (abnormal metabolic pattern); these patients exhibited a significantly higher risk of ICU mortality compared to the patients with a normal metabolic pattern (72.7% vs. 34.6%, p = 0.04). In our critically ill COVID-19 patients, elevated lactate levels or high LP ratios on admission to the ICU could be associated with poor clinical outcome.